{"id": "converted_2261", "sentence1": "Has ruxolitinib received FDA approval?", "sentence2": "Testing for JAK2 mutations is now included in the World Health Organization (WHO) criteria for the diagnosis of MPN, and in 2011 the oral JAK2 kinase inhibitor ruxolitinib became the first Food and Drug Administration (FDA)-approved drug for the treatment of myelofibrosis.[SEP]Relations: Ruxolitinib has relations: drug_drug with Rutin, drug_drug with Rutin, drug_drug with Orlistat, drug_drug with Orlistat, drug_drug with Medical Cannabis, drug_drug with Medical Cannabis, drug_drug with Lapatinib, drug_drug with Lapatinib, drug_drug with Dovitinib, drug_drug with Dovitinib.", "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_4463", "sentence1": "Is EuroQol 5-Dimension Health Assessment (EQ-5D) [a widely used, simple instrument that monitors the general health-related quality of life (HRQoL) in chronic disease] a 5 question assessment?", "sentence2": "The 6-question EuroQol 5-Dimension Health Assessment (EQ-5D) is a widely used, simple instrument that monitors general health-related quality of life (HRQoL) in chronic disease. , OBJECTIVE: The 6-question EuroQol 5-Dimension Health Assessment (EQ-5D) is a widely used, simple instrument that monitors general health-related quality of life (HRQoL) in chronic disease., OBJECTIVE: The 6-question EuroQol 5-Dimension Health Assessment (EQ-5D) is a widely used, simple instrument that monitors general health-related quality of life (HRQoL) in chronic d, OBJECTIVE: The 6-question EuroQol 5-Dimension Health Assessment (EQ-5D) is a widely used, simple instrument that monitors general health-related quality of life (HRQoL) in chron[SEP]Relations: Chronic lung disease has relations: disease_phenotype_positive with severe acute respiratory syndrome, disease_phenotype_positive with severe acute respiratory syndrome, disease_phenotype_positive with alobar holoprosencephaly, disease_phenotype_positive with alobar holoprosencephaly, disease_phenotype_positive with cognitive impairment - coarse facies - heart defects - obesity - pulmonary involvement - short stature - skeletal dysplasia syndrome, disease_phenotype_positive with cognitive impairment - coarse facies - heart defects - obesity - pulmonary involvement - short stature - skeletal dysplasia syndrome, disease_phenotype_positive with combined immunodeficiency due to LRBA deficiency, disease_phenotype_positive with combined immunodeficiency due to LRBA deficiency, disease_phenotype_positive with toxic epidermal necrolysis, disease_phenotype_positive with toxic epidermal necrolysis.", "label": "no"}
{"id": "converted_2522", "sentence1": "Does Uc.160 promote cancer?", "sentence2": "We previously discovered the downregulation of T-UCR expression in gastric cancer (GC), indicating that T-UCRs could play an important role in GC biology. Uc.160+, a T-UCR reported to be downregulated in human cancer, has not been examined in GC.METHODS: We analyzed the expression pattern of Uc.160+ in nonneoplastic and tumor tissues of the stomach by using uantitative reverse transcription polymerase chain reaction (qRT-PCR) and in situ hybridization (ISH), specifically focusing on the mechanism of transcriptional regulation and target genes that are regulated by T-UCRs. We also attempted to determine the effect of Uc.160+ expression on biological features of GC cell lines by Western blotting.RESULTS: On the basis of the qRT-PCR and ISH results, Uc.160+ expression in adenoma and GC tissues was clearly downregulated compared with that in nonneoplastic mucosa tissues of the stomach. Cancer-specific DNA methylation in the promoter region of Uc.160 was observed by bisulfite genomic DNA sequencing analysis. The effect of DNA methylation on Uc.160+ expression was further confirmed by reporter gene assay. We also revealed that Uc.160+ inhibited the phosphorylation of Akt by regulating phosphatase and tensin homolog (PTEN) expression.CONCLUSIONS: These results indicate that Uc.160+ could possibly have a tumor suppressive role in GC., Uc.160+, a T-UCR reported to be downregulated in human cancer, has not been examined in GC.<br><b>METHODS</b>: We analyzed the expression pattern of Uc.160+ in nonneoplastic and tumor tissues of the stomach by using uantitative reverse transcription polymerase chain reaction (qRT-PCR) and in situ hybridization (ISH), specifically focusing on the mechanism of transcriptional regulation and target genes that are regulated by T-UCRs., We also revealed that Uc.160+ inhibited the phosphorylation of Akt by regulating phosphatase and tensin homolog (PTEN) expression.<br><b>CONCLUSIONS</b>: These results indicate that Uc.160+ could possibly have a tumor suppressive role in GC.<br>, We also attempted to determine the effect of Uc.160+ expression on biological features of GC cell lines by Western blotting.<br><b>RESULTS</b>: On the basis of the qRT-PCR and ISH results, Uc.160+ expression in adenoma and GC tissues was clearly downregulated compared with that in nonneoplastic mucosa tissues of the stomach., CONCLUSIONS These results indicate that Uc.160+ could possibly have a tumor suppressive role in GC., Uc.160+, a T-UCR reported to be downregulated in human cancer, has not been examined in GC., Among the T-UCRs that were reactivated upon drug treatment, Uc.160+, Uc283+A and Uc.346+ were found to undergo specific CpG island hypermethylation-associated silencing in cancer cells compared with normal tissues., Uc.160+, a T-UCR reported to be downregulated in human cancer, has not been examined in GC., These results indicate that Uc.160+ could possibly have a tumor suppressive role in GC..[SEP]Relations: malignant giant cell tumor has relations: disease_disease with cancer, disease_disease with cancer. tumor of adipose tissue has relations: disease_disease with lipomatous cancer, disease_disease with lipomatous cancer, disease_disease with benign lipomatous neoplasm, disease_disease with benign lipomatous neoplasm, disease_disease with mesenchymal cell neoplasm, disease_disease with mesenchymal cell neoplasm. adenoma has relations: disease_protein with SUZ12, disease_protein with SUZ12.", "label": "no"}
{"id": "converted_2451", "sentence1": "Can multiple myeloma patients develop hyperviscosity syndrome?", "sentence2": "Multiple myeloma (MM) is an immedicable malignancy of the human plasma cells producing abnormal antibodies (also referred to as paraproteins) leading to kidney problems and hyperviscosity syndrome. , This skin condition may be observed in patients with the following condtions, such as primary polycythemic hyperviscosity (polycythemia, thrombocytemia) treated with hydroxyurea, primary plasma hyperviscosity (multiple myeloma, cryoglobulinemia, cryofibrinogenemia, dysfibrinogenemia, and connective tissue diseases), primary sclerocythemic hyperviscosity (hereditary spherocytosis, thalassemia, and sickle cell disease). ,  A 73-year-old woman with known MM who received little treatment for several years, presented secondary to dysarthria and at first was thought to have hyperviscosity syndrome. ,  After a comprehensive evaluation ruled out common causes of acute renal failure, the patient underwent testing with a bone survey, urine protein electrophoresis (UPEP), serum protein electrophoresis (SPEP), and immunoelectrophoresis for suspected plasma cell dyscrasia and received plasmapheresis for hyperviscosity syndrome and nephrotoxicity, which resulted in improved renal function. Lab results showed monoclonal gammopathy, elevated serum free light chains, and Bence Jones protein in the urine with a follow-up bone marrow biopsy indicating plasma cell dyscrasia. The patient received a diagnosis of multiple myeloma (MM) and was started on chemotherapy and immunosuppression. , Plasmapheresis (PE) is recommended for patients with hyperviscosity syndrome or cast nephropathy presented with AKI, which may help to increase the dialysis-independency., Multiple myeloma is a neoplastic plasma-cell disorder resulting from malignant plasma cells in the bone marrow. It can cause a hyperviscosity syndrome secondary to the paraproteinaemia associated with the disease. The increased hyperviscosity can lead to retinal vein occlusions and other ocular problems that may challenge clinicians. , Etiologies are various but symptomatic hyperviscosity is more common in Waldenström's macroglobulinemia and multiple myeloma. , Double filtration plasmapheresis in a dog with multiple myeloma and hyperviscosity syndrome., A 12 year old, 38 kg, mix-breed, intact male dog presented with a 20 day history of clinical signs consistent with hyperviscosity syndrome secondary to multiple myeloma. , The present study reported for the first time the use of double filtration plasmapheresis to reduce clinical signs of hyperviscosity syndrome in a dog with multiple myeloma., An otherwise healthy young man presents with bilateral CRVO as the first sign of hyperviscosity syndrome in the setting of new multiple myeloma.,  In haematology the most common indication for plasmapheresis is the supportive treatment of multiple myeloma. The procedure is performed in patients with high protein levels endangered with hyperviscosity syndrome., Five to 10 percent of patients with multiple myeloma are suffered from the hyperviscosity syndrome because of increased serum viscosity due to the presence of myeloma protein., Plasmapheresis is known as an efficient method for rapid improvement of the hyperviscosity syndrome, and double filtration plasmapheresis is most commonly used for plasma exchange of multiple myeloma patients in our country., PE is the most effective method in the treatment of hyperviscosity syndrome often seen with multiple myeloma and Waldenström's macroglobulinemia, and it is therapy of choice for this complication., Patients with multiple myeloma who have complications secondary to hyperviscosity are treated by chemotherapy and/or plasmapheresis.[SEP]Relations: polyclonal hyperviscosity syndrome has relations: disease_disease with hematologic disease, disease_disease with hematologic disease. Multiple myeloma has relations: drug_effect with Bortezomib, drug_effect with Bortezomib, disease_phenotype_positive with insulin-resistance syndrome, disease_phenotype_positive with insulin-resistance syndrome, disease_phenotype_positive with capillary leak syndrome, disease_phenotype_positive with capillary leak syndrome, disease_phenotype_positive with scleromyxedema, disease_phenotype_positive with scleromyxedema.", "label": "yes"}
{"id": "converted_2105", "sentence1": "Does the word ovine refers to goats?", "sentence2": "Jaagsiekte sheep retrovirus (JSRV) is the causative agent of ovine pulmonary adenocarcinoma (OPA), a transmissible lung cancer of sheep that has rarely been found in goats. , In sheep, a bronchiolo-alveolar carcinoma, known as ovine pulmonary carcinoma (OPC), is caused by jaagsiekte sheep retrovirus (JSRV), an exogenous type D retrovirus. [SEP]Relations: protein complex oligomerization has relations: bioprocess_protein with OPA1, bioprocess_protein with OPA1, bioprocess_protein with BOK, bioprocess_protein with BOK, bioprocess_protein with MCU, bioprocess_protein with MCU, bioprocess_protein with ADCY8, bioprocess_protein with ADCY8, bioprocess_protein with NOL3, bioprocess_protein with NOL3.", "label": "no"}
{"id": "converted_3399", "sentence1": "Does CXorf21 escape X chromosome inactivation?", "sentence2": "This revealed a 637-kb tandem duplication that in addition to DAX1 includes the four MAGEB genes, the hypothetical gene CXorf21, GK, and part of the MAP3K7IP3 gene, Among statin users, diabetes cases had marginal but insignificantly different expression of ZNF532 (up-regulated 15%, Q-value=0.0584), CXORF21 (up-regulated 11%, Q-value=0.0584), and ZNHIT3 (up-regulated 19%, Q-value=0.0959), compared with controls.,  For this, we selected five SNPs (rs1801274 in FCGR2A and rs2286672 in PLD2, rs887369 in CXorf21, rs9782955 in LYST, and rs3794060 in NADSYN1), Examination of X-linked DEGs, such as GTPBP6, TAF9L, and CXORF21, that show verbal cognition-gene expression correlations may establish a causal link between these genes, neurodevelopment, and language function.[SEP]Relations: ZNHIT3 has relations: protein_protein with XRCC3, protein_protein with XRCC3, bioprocess_protein with box C/D snoRNP assembly, bioprocess_protein with box C/D snoRNP assembly. NADSYN1 has relations: protein_protein with NOXA1, protein_protein with NOXA1, anatomy_protein_absent with cerebellar vermis, anatomy_protein_absent with cerebellar vermis. Protein S human has relations: drug_drug with Coagulation Factor IX (Recombinant), drug_drug with Coagulation Factor IX (Recombinant).", "label": "yes"}
{"id": "converted_285", "sentence1": "Is ospemifene effective for treatment of dyspareunia?", "sentence2": "Ospemifene, a novel selective estrogen receptor modulator, has been developed for the treatment of vulvovaginal atrophy and dyspareunia in postmenopausal women. , For the comparison of short-term ospemifene with placebo, parabasal cells (the standardized mean difference [SMD] = -37.5, 95% confidence interval [CI] = -41.83 to -33.17, P < 0.00001), superficial cells (SMD = 9.24, 95% CI = 7.70 to 10.79, P < 0.00001), vaginal PH (SMD = -0.89, 95% CI = -0.98 to -0.80, P = 0.00001), and dyspareunia (SMD = -0.37, 95% CI = -0.43 to -0.30, P = 0.00001) indicated that ospemifene was more effective than the placebo. , This meta-analysis indicates that ospemifene to be an effective and safe treatment for dyspareunia associated with postmenopausal vulvar and vaginal atrophy., Ospemifene is a selective estrogen receptor modulator (SERM), or estrogen receptor agonist/antagonist, that was recently approved by the US Food and Drug Administration for the treatment of dyspareunia associated with vulvar and vaginal atrophy, a chronic condition that affects up to 60% of postmenopausal women., In conclusion, ospemifene is a SERM with a unique estrogen agonist/antagonist tissue profile that was recently approved in the US for the treatment of dyspareunia associated with vulvar and vaginal atrophy in postmenopausal women. , To characterize the pharmacokinetics of the oral, non-estrogen agent ospemifene, an estrogen agonist/antagonist with tissue-selective effects (also called a selective estrogen receptor modulator) that was recently approved for the treatment of dyspareunia associated with vulvar and vaginal atrophy in postmenopausal women., Here, we review the estrogen agonist/antagonist profile of ospemifene, a novel triphenylethylene derivative recently approved to treat dyspareunia, a symptom of vulvar and vaginal atrophy (VVA) due to menopause, both preclinically and clinically.,  Long-term studies on the endometrial safety of local estrogen and ospemifene are lacking. , Ospemifene is a tissue-selective estrogen agonist/antagonist (a selective estrogen receptor modulator) recently approved by the US Food and Drug Administration for treatment of dyspareunia, a symptom of VVA, due to menopause., SERMs with positive vaginal effects (such as improvement in the vaginal maturation index, reduced vaginal pH, and improvement in the signs and symptoms of VVA) on postmenopausal symptomatic women include lasofoxifene (clinical development on hold) and ospemifene, which was recently approved for the treatment of VVA-related dyspareunia, with a class effect warning of potential venous thrombosis risk. , Ospemifene is the first non-estrogen treatment approved for moderate to severe dyspareunia in women with menopause-related vulvar and vaginal atrophy. , This article summarizes the milestones in the development of ospemifene leading to this first approval for moderate to severe dyspareunia, a symptom of postmenopausal vulvar and vaginal atrophy., The aim of this work was to study the role of ospemifene, a novel selective estrogen receptor modulator, in the treatment of vulvar and vaginal atrophy in postmenopausal women with moderate to severe dyspareunia and physiological vaginal changes. , In this study, once-daily oral ospemifene 60 mg was effective for the treatment of vulvar and vaginal atrophy in postmenopausal women with dyspareunia., Clinical trials have confirmed that daily doses are well-tolerated and that it is effective in normalizing vaginal maturation index and pH as well as improving the symptoms associated with VVA including dyspareunia., Ospemifene was shown to be effective and well tolerated for the treatment of the symptoms of vaginal dryness and dyspareunia associated with vulvovaginal atrophy over and above the use of provided lubricants.[SEP]Relations: Ospemifene has relations: drug_drug with Antipyrine, drug_drug with Antipyrine, drug_drug with Orphenadrine, drug_drug with Orphenadrine, drug_drug with Amodiaquine, drug_drug with Amodiaquine. Dyspareunia has relations: drug_effect with Progesterone, drug_effect with Progesterone, drug_effect with Fluoxetine, drug_effect with Fluoxetine.", "label": "yes"}
{"id": "converted_2270", "sentence1": "Are there ultraconserved genomic regions in the budding yeast?", "sentence2": "Here, we present a systematic study of ultraconserved genomic regions in the budding yeast based on the publicly available genome sequences, in order to reveal their relationship with the adaptability or fitness advantages of the budding yeast.Results: Our results indicate that, in addition to some fundamental biological functions, the UCSs play an important role in the adaptation of S. cerevisiae to the acidic environment, which is backed up by the previous observation. Besides that, we also find the highly unchanged genes (HUGs) are enriched in some other pathways, such as the nutrient-sensitive signaling pathway. To facilitate the investigation of unique UCSs, the UCSC Genome Browser was utilized to visualize the chromosomal position and related annotations of UCSs in S. cerevisiae genome., Here, we present a systematic study of ultraconserved genomic regions in the budding yeast based on the publicly available genome sequences, in order to reveal their relationship with the adaptability or fitness advantages of the budding yeast.[SEP]Relations: anatomical entity has relations: anatomy_anatomy with insect mouthpart, anatomy_anatomy with insect mouthpart, anatomy_anatomy with anatomical cluster, anatomy_anatomy with anatomical cluster, anatomy_anatomy with immaterial anatomical entity, anatomy_anatomy with immaterial anatomical entity, anatomy_anatomy with material anatomical entity, anatomy_anatomy with material anatomical entity.", "label": "yes"}
{"id": "converted_1962", "sentence1": "Do normal cells express the protein TERT?", "sentence2": "Since telomerase has been recognized as a relevant factor distinguishing cancer cells from normal cells, it has become a very promising target for anti-cancer therapy, Telomerase plays a pivotal role in cellular immortality and tumorigenesis. Its activity is normally not detectable in most somatic cells while it is reactivated in the vast majority of cancer cells. Therefore, inhibition of telomerase has been viewed as a promising anticancer approach due to its specificity for cancer cells., Telomerase activity is found in 85%-90% of all human cancers but not in their adjacent normal cells. Human telomerase reverse transcriptase (hTERT) is an essential component in the telomerase complex that plays an important role in telomerase activity., elomerase activation is considered to be a critical step in carcinogenesis and its activity correlates closely with human telomerase reverse transcriptase (hTERT) expression. Since only tumor cells that express telomerase activity would activate this promoter, the hTERT proximal promoter allows for preferential expression of viral genes in tumor cells, leading to selective viral replication[SEP]Relations: Protein S human has relations: drug_drug with Platelet Activating Factor, drug_drug with Platelet Activating Factor, drug_protein with PROC, drug_protein with PROC, drug_drug with Iloprost, drug_drug with Iloprost, drug_drug with Dienogest, drug_drug with Dienogest, drug_drug with Sarpogrelate, drug_drug with Sarpogrelate.", "label": "no"}
{"id": "converted_296", "sentence1": "is intense physical activity associated with longevity ?", "sentence2": "We found a very significant increase in average longevity (17%) of the cyclists when compared with the general population. The age at which 50% of the general population died was 73.5 vs. 81.5 years in Tour de France participants. Our major finding is that repeated very intense exercise prolongs life span in well trained practitioners., Competitive exercise does not induce cardiac damage in individuals with healthy hearts, but does induce physiological functional and structural cardiac adaptations which have positive effects on life expectancy., Medallists lived an average of 2.8 years longer than controls. Medallists in eight of the nine country groups had a significant survival advantage compared with controls. Gold, silver, and bronze medallists each enjoyed similar sized survival advantages. Medallists in endurance sports and mixed sports had a larger survival advantage over controls at 30 years (1.13, 1.09 to 1.17; 1.11, 1.09 to 1.13) than that of medallists in power sports (1.05, 1.01 to 1.08). CONCLUSIONS: Olympic medallists live longer than the general population, irrespective of country, medal, or sport. This study was not designed to explain this effect, but possible explanations include genetic factors, physical activity, healthy lifestyle, and the wealth and status that come with international sporting glory., Long-term endurance training induces in elderly subjects an increased HRV and a higher exercise working capacity, which are well-established predictors of cardiovascular and overall mortality., Sports activity in adolescents and young adults was associated with an increased risk of SD, both in males and females. Sports, per se, was not a cause of the enhanced mortality, but it triggered SD in those athletes who were affected by cardiovascular conditions predisposing to life-threatening ventricular arrhythmias during physical exercise.[SEP]Relations: SLC17A5 has relations: molfunc_protein with transmembrane transporter activity, molfunc_protein with transmembrane transporter activity, molfunc_protein with carbohydrate:proton symporter activity, molfunc_protein with carbohydrate:proton symporter activity. Ventricular arrhythmia has relations: drug_effect with Ganciclovir, drug_effect with Ganciclovir, drug_effect with Sildenafil, drug_effect with Sildenafil. Silver has relations: drug_effect with Inflammatory abnormality of the skin, drug_effect with Inflammatory abnormality of the skin.", "label": "yes"}
{"id": "converted_3810", "sentence1": "Can AGY be used as antidiuretic replacement therapy?", "sentence2": "AGY, a Novel Egg Yolk-Derived Anti-gliadin Antibody, Is Safe for Patients with Celiac Disease., Oral egg yolk anti-gliadin antibody (AGY) is a novel treatment to neutralize gluten and may improve the efficacy of the GFD., To determine the safety, tolerability, and potential efficacy of AGY in patients with CD., Most patients had fewer celiac symptoms (especially tiredness, headache, and bloating), improved quality of life, lowered antibodies, and lowered LMER when taking AGY compared to the run-in period., In our cohort, AGY was safe and potentially associated with improved CD-related outcome measures in patients on a GFD. [SEP]Relations: Headache has relations: drug_effect with Acyclovir, drug_effect with Acyclovir, drug_effect with Azithromycin, drug_effect with Azithromycin, drug_effect with Oxybutynin, drug_effect with Oxybutynin. Fatigue has relations: drug_effect with Acyclovir, drug_effect with Acyclovir, drug_effect with Oxybutynin, drug_effect with Oxybutynin.", "label": "no"}
{"id": "converted_2848", "sentence1": "Is inositol effective for trichotillomania?", "sentence2": "Patients assigned to inositol failed to show significantly greater reductions on primary or secondary outcomes measures compared with placebo (all P>0.05)., This is the first study assessing the efficacy of inositol in the treatment of trichotillomania, but found no differences in symptom reductions between inositol and placebo., At study endpoint, 42.1% of patients were 'much or very much improved' on inositol compared with 35.3% on placebo., Conclusions • The review indicates that yoga, aerobic exercise, acupuncture, biofeedback, hypnosis, and inositol and N-acetylcysteine all show promise in the treatment of excoriation disorder and other body-focused repetitive behaviors, such as trichotillomania., Future studies should examine whether inositol may be beneficial in controlling pulling behavior in a subgroup of individuals with trichotillomania.[SEP]Relations: Inositol has relations: drug_drug with Triazolam, drug_drug with Triazolam, drug_drug with Triethylenetetramine, drug_drug with Triethylenetetramine, drug_drug with Trifluridine, drug_drug with Trifluridine, drug_drug with Triamterene, drug_drug with Triamterene, drug_drug with Trichlormethiazide, drug_drug with Trichlormethiazide.", "label": "no"}
{"id": "converted_1843", "sentence1": "Are deletions of chromosomal regulatory boundaries associated with congenital disease?", "sentence2": "Deletions of chromosomal regulatory boundaries are associated with congenital disease., Our results suggest that enhancer adoption caused by deletions of regulatory boundaries may contribute to a substantial minority of copy-number variation phenotypes and should thus be taken into account in their medical interpretation, Deletions of chromosomal regulatory boundaries are associated with congenital disease, Deletions of chromosomal regulatory boundaries are associated with congenital disease.[SEP]Relations: congenital nervous system disorder has relations: disease_disease with chromosome 18q deletion syndrome, disease_disease with chromosome 18q deletion syndrome, disease_disease with chromosome 1p36 deletion syndrome, disease_disease with chromosome 1p36 deletion syndrome, disease_disease with chromosome 5q12 deletion syndrome, disease_disease with chromosome 5q12 deletion syndrome, disease_disease with chromosome 19p13.13 deletion syndrome, disease_disease with chromosome 19p13.13 deletion syndrome, disease_disease with chromosome 19q13.11 deletion syndrome, disease_disease with chromosome 19q13.11 deletion syndrome.", "label": "yes"}
{"id": "converted_3498", "sentence1": "Has ProSavin undergone phase IV clinical trials by 2018?", "sentence2": "Long-term safety and tolerability of ProSavin, a lentiviral vector-based gene therapy for Parkinson's disease: a dose escalation, open-label, phase 1/2 trial., We undertook a phase 1/2 open-label trial with 12-month follow-up at two study sites (France and UK) to assess the safety and efficacy of ProSavin after bilateral injection into the putamen of patients with Parkinson's disease. [SEP]Relations: Parkinson disease has relations: contraindication with Prochlorperazine, contraindication with Prochlorperazine, contraindication with Indomethacin, contraindication with Indomethacin, contraindication with Amikacin, contraindication with Amikacin, contraindication with Rivastigmine, contraindication with Rivastigmine, contraindication with Perphenazine, contraindication with Perphenazine.", "label": "no"}
{"id": "converted_1099", "sentence1": "Are there any HCV replication inhibitors available?", "sentence2": "We report here the discovery of the first small-molecule HCV infectivity inhibitor, GS-563253, also called HCV infectivity inhibitor 1 (HCV II-1). , Resistance to mericitabine (prodrug of HCV NS5B polymerase inhibitor PSI-6130) is rare and conferred by the NS5B S282T mutation., We tested the ability of NA808 to inhibit SPT's enzymatic activity in FLR3-1 replicon cells, The SPT inhibitor NA808 prevents replication of HCV genotypes 1a, 1b, 2a, 3a, and 4a in cultured hepatocytes and in mice with humanized livers., Vaniprevir (phase III clinical trials) and MK-5172 (phase II clinical trials) are two potent antiviral compounds that target NS3/4A protease, treatment for hepatitis C virus (HCV) infection has been significantly improved with the approval of the first two HCV NS3/4A protease inhibitors, telaprevir (Incivek) and boceprevir (Victrelis). , Combination therapy with telaprevir and BMS-788329 (NS5A inhibitor) reduced serum HCV RNA to undetectable levels. The presence of an NS3-V36A telaprevir resistance mutation resulted in poor response to telaprevir monotherapy but showed significant HCV reduction when telaprevir was combined with BMS-788329. However, a BMS-788329-resistant strain emerged at low frequency. Infection with a BMS-788329-resistant NS5A-L31V mutation rapidly resulted in gain of an additional NS5A-Y93A mutation that conferred telaprevir resistance during combination therapy, HCV NS5A replication complex inhibitors, exemplified by Daclatasvir (BMS-790052), represent a new class of DAA, ACH-806 (or GS-9132) is a novel, small-molecule inhibitor specific for hepatitis C virus (HCV). , Telaprevir and boceprevir are the first two protease inhibitor (PI) DAAs to be approved for combination therapy with pegylated interferon (PEG-IFN) and ribavirin (RBV). , symmetrical bidentate structure of the NS5A inhibitor BMS-790052, a series of new monodentate molecules were designed, In vitro, boceprevir is more active than telaprevir against the HCV G3 NS3/4A enzyme in cell-based and biochemical assays and against G3 isolates in replicon assays, Alisporivir is the most advanced host-targeting antiviral in clinical development. Alisporivir blocks HCV replication by neutralizing the peptidyl-prolyl isomerase activity of the abundant host cytosolic protein, cyclophilin A, Interestingly, the NS5A inhibitor daclatasvir (BMS-790052) caused a decrease in serum HCV RNA levels by about two orders of magnitude within 6 h of administration[SEP]Relations: hepatitis C virus infection has relations: contraindication with Tipranavir, contraindication with Tipranavir, contraindication with Lopinavir, contraindication with Lopinavir, contraindication with Nevirapine, contraindication with Nevirapine, contraindication with Tenofovir, contraindication with Tenofovir, contraindication with Amprenavir, contraindication with Amprenavir.", "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]Relations: myocardial infarction has relations: contraindication with Nylidrin, contraindication with Nylidrin, contraindication with Fosamprenavir, contraindication with Fosamprenavir, contraindication with Lansoprazole, contraindication with Lansoprazole, contraindication with Drospirenone, contraindication with Drospirenone, contraindication with Modafinil, contraindication with Modafinil.", "label": "yes"}
{"id": "converted_381", "sentence1": "Is cadasil syndrome a hereditary disease?", "sentence2": " CADASIL is the most frequent hereditary small-vessel disease of the brain. The clinical impact of various MR imaging markers has been repeatedly studied in this disorder, but alterations of contrast between gray matter and normal-appearing white matter remain unknown. The aim of this study was to evaluate the contrast alterations between gray matter and normal-appearing white matter on T1-weighted images in patients with CADASIL compared with healthy subjects,  (CADASIL) is the most common form of hereditary cerebral angiopathy, Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited cerebral small vessel disease, clinically characterized by migraine, recurrent transient ischemic attacks or strokes, psychiatric disorders and cognitive decline. Strokes are typically ischemic, while hemorrhagic events have been only sporadically described, Mutations in the TREX1 and NOTCH3 genes cause retinal vasculopathy with cerebral leukodystrophy (RVCL) and cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), respectively, We used immunohistochemistry and immunogold electron microscopy (EM) to examine the distribution of GOM and NOTCH3 ectodomain (N3ECD) protein in microvasculature of brain gray matter and white matter in patients with CADASIL, non-CADASIL hereditary small-vessel disease and sporadic age-related degenerative disease, and comparable-age controls[SEP]Relations: CARASIL syndrome has relations: disease_phenotype_positive with Autosomal recessive inheritance, disease_phenotype_positive with Autosomal recessive inheritance, disease_disease with cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy,, disease_disease with cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy,, disease_protein with HTRA1, disease_protein with HTRA1. genetic cerebral small vessel disease has relations: disease_disease with genetic central nervous system and retinal vascular disease, disease_disease with genetic central nervous system and retinal vascular disease, disease_disease with Coats plus syndrome, disease_disease with Coats plus syndrome.", "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_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_2670", "sentence1": "The TRPM2 gene is associated with development of spontaneous thromboembolism?", "sentence2": "TheTransientReceptorPotentialMelastatin 2 (TRPM2) is a member of G protein coupled receptor superfamily and a novel dual-function protein that possesses both ion channel andAdenosine 5'-DiphosPhataseRibose (ADPR) hydrolase function. TRPM2 is involved in Ca2+signaling in various cells as an endogenous redox sensor for oxidative stress and reactive oxygen species, and contributes to cytokine production, insulin release, motility, Ca2+entry and Ca2+-dependent cellular reactions such as endothelial hyper-permeability and apoptosis., We show here that the redox-sensitive transient receptor potential (TRP) cation channel TRPM2 is expressed in the phagosomal membrane and regulates macrophage bactericidal activity through the activation of phagosomal acidification, The transient receptor potential melastatin-2 (TRPM2) is an oxidative stress sensing channel that is expressed in a number of inflammatory cells and therefore it has been suggested that inhibition of TRPM2 could lead to a beneficial effect in COPD patients., TRPM2 is a recently identified TRPM family cation channel which is unique among known ion channels in that it contains a C-terminal domain which is homologous to the NUDT9 ADP-ribose hydrolase and possesses intrinsic ADP-ribose hydrolase activity, These results suggest that TRPM2 may participate in antigen-induced extracellular Ca(2+) influx and subsequent degranulation. In addition, TRPM2 inhibitors were shown to improve food allergic reactions in a mouse model. Together, these results suggest that TRPM2 inhibitors suppress MMC degranulation via regulation of the increase in [Ca(2+)]cyt. Thus, TRPM2 may play a key role in degranulation by modulating intracellular Ca(2+) in MMCs., he Na+ and Ca(2+)-permeable melastatin related transient receptor potential 2 (TRPM2) channels can be gated either by ADP-ribose (ADPR) in concert with Ca(2+) or by hydrogen peroxide (H(2)O(2)), an experimental model for oxidative stress, binding to the channel's enzymatic Nudix domain, hese alterations of the extracellular milieu change the activity of transient receptor potential melastatin subfamily member 2 (TRPM2), a nonselective cation channel expressed in the central nervous system and the immune system. , TRPM2 (Transient Receptor Potential Melastatin 2) is a Ca2+-permeable ion channel that is activated under conditions of oxidative stress. , Transient receptor potential melastatin 2 (TRPM2) is a thermosensitive, Ca2+-permeable cation channel. TRPM2 contributes to the pathogenesis of inflammatory bowel disease, and inflammatory and neuropathic pain. We hypothesized that TRPM2 is important for visceral nociception and the development of visceral hypersensitivity., Here, we describe the computational identification of a melanoma-enriched antisense transcript, TRPM2-AS, mapped within the locus of TRPM2, an ion channel capable of mediating susceptibility to cell death, The transient receptor potential melastatin 2 (TRPM2) channel, a Ca(2+)-permeable nonselective cation channel activated by oxidative stress, has been implicated in neurodegenerative diseases, and more recently in amyloid-induced toxicity, Transient receptor potential melastatin 2 (TRPM2) is a calcium-permeable cation channel activated by ADP-ribose or reactive oxygen species.,  Transient receptor potential melastatin type 2 (TRPM2) is a Ca2+ permeable non-selective cation channel expressed in several cell types including hippocampal pyramidal neurons. Moreover, activation of TRPM2 during oxidative stress has been linked to cell death. [SEP]Relations: TRPM2-AS has relations: anatomy_protein_present with blood, anatomy_protein_present with blood, anatomy_protein_present with brain, anatomy_protein_present with brain, anatomy_protein_present with lymph node, anatomy_protein_present with lymph node, anatomy_protein_present with spleen, anatomy_protein_present with spleen, anatomy_protein_present with neocortex, anatomy_protein_present with neocortex.", "label": "no"}
{"id": "converted_1959", "sentence1": "Are Ultra-conserved elements (UCEs) enriched in segmental duplications?", "sentence2": "Here we address the process by which CNVs become depleted of UCEs., 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., Alternatively, lack of depletion for UCEs from cancer CNVs may reflect the diseased state. , ULEs are located in intergenic or intronic regions and are depleted from segmental duplications., Interestingly, human UCEs have been reported to be strongly depleted among segmental duplications and benign copy number variants (CNVs)., In addition, here we show that these elements are preferentially found in pathogenic deletions (enrichment ratio 3.6 vs. 0.5 in duplications), and that this association is not related with a higher content of genes., In contrast, pathogenic CNVs lacking UCEs showed almost a threefold higher content in genes, We have demonstrated that nonexonic UCEs are depleted among segmental duplications (SDs) and copy number variants (CNVs) and proposed that their ultraconservation may reflect a mechanism of copy counting via comparison., Mammalian ultraconserved elements are strongly depleted among segmental duplications and copy number variants., Here, we show that UCEs are significantly depleted among segmental duplications and copy number variants. Notably, of the UCEs that are found in segmental duplications or copy number variants, the majority overlap exons, indicating, along with other findings presented, that UCEs overlapping exons represent a distinct subset., Ultraconserved elements (UCEs) are strongly depleted from segmental duplications and copy number variations (CNVs) in the human genome, suggesting that deletion or duplication of a UCE can be deleterious to the mammalian cell., Here, we show that UCEs are significantly depleted among segmental duplications and copy number variants., We have demonstrated that nonexonic UCEs are depleted among segmental duplications (SDs) and copy number variants (CNVs) and proposed that their ultraconservation may reflect a mechanism of copy counting via comparison., Here, we show that UCEs are significantly depleted among segmental duplications and copy number variants., Ultraconserved elements (UCEs) are strongly depleted from segmental duplications and copy number variations (CNVs) in the human genome, suggesting that deletion or duplication of a UCE can be deleterious to the mammalian cell, melanogaster genome revealed depletion of the P-element and piggyBac insertions in and around the Sophophora UCEs., Mammalian ultraconserved elements are strongly depleted among segmental duplications and copy number variants., Here, we show that UCEs are significantly depleted among segmental duplications and copy number variants., Interestingly, human UCEs have been reported to be strongly depleted among segmental duplications and benign copy number variants (CNVs).[SEP]Relations: mammalian vulva has relations: anatomy_protein_present with CCS, anatomy_protein_present with CCS, anatomy_protein_absent with UCN3, anatomy_protein_absent with UCN3, anatomy_protein_present with UCHL5, anatomy_protein_present with UCHL5, anatomy_protein_present with UCP2, anatomy_protein_present with UCP2, anatomy_protein_present with EFS, anatomy_protein_present with EFS.", "label": "no"}
{"id": "converted_1948", "sentence1": "Do IEG create a ripple effect of transcription?", "sentence2": "Rapid induction of immediate-early genes (IEGs) in response to growth factor stimulations is accompanied by co-upregulation of their neighbouring genes., Even in surrounding intergenic regions, transcriptional activation took place at the same time. , Here we show that intensive transcription at one locus frequently spills over into its physical neighbouring loci., Ripples from neighbouring transcription., Ripples from neighbouring transcription.[SEP]Relations: insect neurogenic region has relations: anatomy_anatomy with embryonic structure, anatomy_anatomy with embryonic structure.", "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_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_2264", "sentence1": "Does deflazacort have more side effects than prednisone?", "sentence2": "Though Deflazacort and prednisone improve clinical endpoints in Duchenne muscular dystrophy (DMD) patients, Deflazacort produces fewer side effects.[SEP]Relations: Deflazacort has relations: drug_drug with Prednisone, drug_drug with Prednisone, drug_drug with Prednisolone, drug_drug with Prednisolone, drug_drug with Meprednisone, drug_drug with Meprednisone, drug_drug with Prednylidene, drug_drug with Prednylidene, drug_drug with Methylprednisone, drug_drug with Methylprednisone.", "label": "no"}
{"id": "converted_4148", "sentence1": "Is the glucocorticoid receptor a transcription factor?", "sentence2": "GR and KLF4, both pioneer transcription factors,, The glucocorticoid receptor (GR) is a ligand-binding dependent transcription factor that ultimately regulates vital biological processes and inflammation response through specific gene expression control, thus representing a notable drug target to explore. , The glucocorticoid receptor (GR) is a ligand-activated transcription factor that translocates to the nucleus upon hormone stimulation and distributes between the nucleoplasm and membraneless compartments named nuclear foci.[SEP]Relations: glucocorticoid receptor activity has relations: molfunc_protein with NR3C1, molfunc_protein with NR3C1. Protein S human has relations: drug_drug with Antihemophilic factor, human recombinant, drug_drug with Antihemophilic factor, human recombinant, drug_drug with Antihemophilic factor human, drug_drug with Antihemophilic factor human, drug_drug with Platelet Activating Factor, drug_drug with Platelet Activating Factor, drug_drug with Factor IX Complex (Human), drug_drug with Factor IX Complex (Human).", "label": "yes"}
{"id": "converted_218", "sentence1": "Has vitamin D has been shown to reduce incidence of falls in older people in clinical trials?", "sentence2": "However, apart from the beneficial effects of 800 IU/d of vitamin D3 for reduction of falls in the elderly, causality remains yet unproven in randomized controlled trials (RCTs). , The rate of falls and the number of fallers was significantly reduced in two studies evaluating the effect of medication on preventing falls; one study (85 participants) compared vitamin D versus placebo in institutionalised women after stroke with low vitamin D levels, and the other study (79 participants) evaluated alendronate versus alphacalcidol in hospitalised people after stroke., Two studies testing vitamin D versus placebo and alendronate versus alphacalcidol found a significant reduction in falls and the number of people falling, .Overall, vitamin D supplementation does not appear to reduce falls but may be effective in people who have lower vitamin D levels before treatment., Overall, vitamin D did not reduce rate of falls (RaR 1.00, 95% CI 0.90 to 1.11; seven trials; 9324 participants) or risk of falling (RR 0.96, 95% CI 0.89 to 1.03; 13 trials; 26,747 participants), but may do so in people with lower vitamin D levels before treatment., Vitamin D affects bone and muscle health and likely reduces the risk of falls in the elderly., We found 26 eligible trials of moderate quality that enrolled 45,782 participants, the majority of which were elderly and female. Vitamin D use was associated with statistically significant reduction in the risk of falls (odds ratio for suffering at least one fall, 0.86; 95% confidence interval, 0.77-0.96), This effect was more prominent in patients who were vitamin D deficient at baseline and in studies in which calcium was coadministered with vitamin D., Vitamin D combined with calcium reduces the risk of falls., The majority of the evidence is derived from trials enrolling elderly women., Studies of vitamin D and calcium for fracture prevention have produced inconsistent results, as a result of different vitamin D status and calcium intake at baseline, different doses and poor to adequate compliance., Despite significant increases in the provision of hip protectors and use of vitamin D supplementation in both intervention and control facilities, there was no difference in the number of falls or falls injuries between the intervention and control groups, nor a reduction in falls overall., Beyond fall and fracture prevention, vitamin D may also reduce overall morbidity by multiple mechanisms. , There is evidence to suggest that these agents may reduce the incidence of nonvertebral fractures and falls; however, their benefit on vertebral fracture reduction may depend on the type of active vitamin D. [SEP]Relations: Cholecalciferol has relations: drug_drug with Vitamin D, drug_drug with Vitamin D, contraindication with familial isolated deficiency of vitamin E, contraindication with familial isolated deficiency of vitamin E. Ergocalciferol has relations: drug_drug with Vitamin D, drug_drug with Vitamin D, contraindication with familial isolated deficiency of vitamin E, contraindication with familial isolated deficiency of vitamin E. Alfacalcidol has relations: drug_drug with Vitamin D, drug_drug with Vitamin D.", "label": "yes"}
{"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]Relations: response to rhamnose has relations: bioprocess_bioprocess with response to hexose, bioprocess_bioprocess with response to hexose, bioprocess_bioprocess with cellular response to rhamnose stimulus, bioprocess_bioprocess with cellular response to rhamnose stimulus. Increased groin pigmentation with raindrop depigmentation has relations: phenotype_phenotype with Mixed hypo- and hyperpigmentation of the skin, phenotype_phenotype with Mixed hypo- and hyperpigmentation of the skin, phenotype_phenotype with Irregular hyperpigmentation, phenotype_phenotype with Irregular hyperpigmentation, disease_phenotype_positive with thumb deformity-alopecia-pigmentation anomaly syndrome, disease_phenotype_positive with thumb deformity-alopecia-pigmentation anomaly syndrome.", "label": "yes"}
{"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_3856", "sentence1": "Does an antiphlogistic promotes inflammation?", "sentence2": "The therapeutic effect of olipiphate was demonstrated for chronic inflammation of advanced arthritis and concanavalin A-related acute edema. The best systemic effect was obtained with 50 mg/kg, symptomatic--100 mg/kg. Skin wounds treated with 5% olipiphate (26 + 2) healed faster than those treated with 2% solcoseryl (30 + 0.8) or in control (33 + 0.6). It was shown histologically that the proliferative and antiphlogistic effect of olipiphate involved no scars., Moreover, we observed an in vitro-inhibition of human neutrophil elastase, a protease involved in the inflammatory process, by extracts and fractions from yarrow, which suggests additional mechanisms of antiphlogistic action., Blood 5-HT in adrenalectomized rats with inflammationadrenalectomized rats 42 days and 3 months old with inflammation after injection of phenylbutazone an increase of 5-HT was observed, but in 18-month-old animals in which antiphlogistic action is highest a decrease of 5-HT was observed., These results indicate that methotrexate is a nonsteroidal antiinflammatory agent, the antiphlogistic action of which is due to increased adenosine release at inflamed sites., The antiphlogistic Ibuprofen incorporated in liposomes caused a decrease of the inflammatory edema induced by Carrageenan in the distal part of the rat's hind leg after both the intramuscular and percutaneous administration., Enhancement of the immunoreactivity inhibition caused by the drugs was not proportional to the increase in their antiphlogistic effects determined by the Selye model of inflammation., Antiinflammatory agents: new series of N-substituted amino acids with complex pyrimidine structures endowed with antiphlogistic activity.,  investigate whether the antiphlogistic ingredient may suppress the inflammatory response to ultraviolet (UV) irradiation, the SPF was determined in vivo. F, Antiphlogistics were found to enhance the membrane viscosity both in control and under inflammation., e in vivo determination of the SPF. Evidence of anti-inflammatory activity of the sunscreen antiphlogistics bisabolol and panthenol was also not apparent in the UV model over a time course of 48 h. Conlusion: The antiphlogistic ingredients panthenol and bisabolol incorporated in the tested sunscreen formula do not interfere with erythema reddening and thus , nts was analyzed in vitro. To investigate whether the antiphlogistic ingredient may suppress the inflammatory response to ultraviolet (UV) irradiation, the , The aim of this study was to analyze the formation of the most relevant inflammation mediators including proteins and lipids in human fibroblasts upon inflammatory stimulation and subsequent treatment with dexamethasone, a powerful antiphlogistic drug.[SEP]Relations: Ibuprofen has relations: contraindication with inflammatory bowel disease, contraindication with inflammatory bowel disease, drug_effect with Nephrotic syndrome, drug_effect with Nephrotic syndrome, drug_effect with Inflammatory abnormality of the skin, drug_effect with Inflammatory abnormality of the skin. Methotrexate has relations: contraindication with inflammatory bowel disease, contraindication with inflammatory bowel disease. Adenosine has relations: drug_effect with Inflammatory abnormality of the skin, drug_effect with Inflammatory abnormality of the skin.", "label": "no"}
{"id": "converted_3068", "sentence1": "Has the protein SIRT2 been associated to cervical cancer?", "sentence2": " A progressive increase in the expression of both SIRT2 and SIRT7 was noted during cancer progression in the following order: normal < preneoplasia < cancer.,  We demonstrate that treatment of cervical cancer cells with a RhoGDIα-derived K52-trifluoroacetylated, substrate-derived peptidic sirtuin inhibitor severely impairs cell proliferation. [SEP]Relations: PPP1R1A has relations: disease_protein with liver cancer, disease_protein with liver cancer, protein_protein with ACTA2, protein_protein with ACTA2, protein_protein with ZPBP2, protein_protein with ZPBP2, anatomy_protein_present with spinal cord, anatomy_protein_present with spinal cord. NAD-dependent protein deacetylase activity has relations: molfunc_protein with SIRT2, molfunc_protein with SIRT2.", "label": "yes"}
{"id": "converted_402", "sentence1": "Is paroxetine effective for treatment of premenstrual dysphoric disorder?", "sentence2": "To evaluate the cost effectiveness of the four medications with a US FDA-approved indication for PMDD: fluoxetine, sertraline, paroxetine and drospirenone plus ethinyl estradiol (DRSP/EE)., All SSRIs (fluoxetine, paroxetine, sertraline, fluvoxamine, citalopram, and clomipramine) were effective in reducing premenstrual symptoms., Paroxetine has been approved for the treatment of major depressive disorder (MDD), obsessive-compulsive disorder, panic disorder (PD), generalised anxiety disorder, post traumatic stress disorder (PTSD), and social anxiety disorder (SAD) in adults, whereas paroxetine CR is approved for the treatment of MDD, SAD, PD and premenstrual dysphoric disorder in adults., Selective serotonin-reuptake inhibitors (SSRIs) have been proven safe and effective for the treatment of PMDD and are recommended as first-line agents when pharmacotherapy is warranted. Currently fluoxetine, controlled-release paroxetine, and sertraline are the only Food and Drug Administration-approved agents for this indication., When compared with placebo, patients treated with paroxetine 20 mg attained a significant reduction in irritability (difference in median percent change: -23.9, 95% CI = -51.3 to -6.2, p = .014; difference in mean absolute change: -18.6, 95% CI = -32.5 to -4.6, p = .007). A statistically significant difference was not observed when the patients treated with the lower dose of paroxetine (10 mg) were compared with placebo. Treatment was well tolerated with no unexpected side effects., Intermittent administration of paroxetine 20 mg significantly reduced irritability symptoms in patients with PMDD., All these women had significant improvements in the HAMA, HAMD, CGI, and PRISM calendar. The rate of response to paroxetine treatment lay between 50% and 78.6% in the continuous-treatment group, and 37.5-93.8% in the intermittent-treatment group, as determined at the study end-point., The present results indicate that paroxetine is effective in both continuous and intermittent treatment of oriental PMDD women, and that the effects of active treatment lasted for six consecutive treatment menstrual cycles., Paroxetine CR is approved for the treatment of major depression, social anxiety disorder, panic disorder and premenstrual dysphoric disorder in adults., Continuous treatment with paroxetine reduced premenstrual symptoms effectively with a response rate of 85%., Intermittent treatment was as effective as continuous treatment in reducing irritability, affect lability, and mood swings, but had a somewhat weaker effect on depressed mood and somatic symptoms., Daily Record of Severity of Problems scores were lower in the paroxetine group compared with the placebo group, although the differences were not statistically significant., However, the mean on-treatment Inventory of Depressive Symptomatology (clinician-rated) score for the paroxetine group was 17.9 +/- 8.3 compared with 31.5 +/- 11.2 in the placebo group (adjusted mean difference = 13.6, P = 0.009)., Response (Clinical Global Impressions Scale score of 1 or 2) occurred in 70% of subjects randomized to paroxetine CR and 10% of those assigned to placebo (chi2(1) = 7.5, P = 0.006)., The US Food and Drug Administration and Health Canada recently approved paroxetine for the treatment of premenstrual dysphoric disorder., Patients treated with either dose of paroxetine CR demonstrated significantly greater improvements on the primary efficacy measure (change from baseline in mean luteal phase VAS-Mood scores) and on the majority of secondary efficacy measures compared with patients randomly assigned to placebo., For the treatment of PMDD, luteal phase dosing with 12.5 mg and 25 mg of paroxetine CR is effective and generally well tolerated., A statistically significant difference was observed in favor of paroxetine CR 25 mg versus placebo on the VAS-Mood (adjusted mean difference = -12.58 mm, 95% CI = -18.40 to -6.76; p < .001) and for paroxetine CR 12.5 mg versus placebo (adjusted mean difference = -7.51 mm, 95% CI = -13.40 to -1.62; p = .013)., Paroxetine CR doses of 12.5 mg/day and 25 mg/day are effective in treating PMDD and are well tolerated., At end point, subjects treated with paroxetine CR (12.5 mg and 25 mg) demonstrated significant improvement in VAS-Mood scores compared with those who received placebo (paroxetine CR 12.5 mg mean treatment difference vs. placebo, -8.7 mm; 95% CI, -15.7, -1.7; p =.015; paroxetine CR 25 mg mean treatment difference vs. placebo, -12.1 mm; 95% CI, -18.9, -5.3; p <.001)., Both doses of paroxetine CR 12.5 mg and 25 mg daily are effective and well tolerated in patients who suffer from PMDD., Of these agents, sertraline, fluoxetine and paroxetine (as an extended-release formulation) are approved by the US FDA for luteal phase, as well as continuous, administration., In well designed placebo-controlled trials in patients with major depressive disorder (including a study in the elderly), social anxiety disorder or premenstrual dysphoric disorder (PMDD), paroxetine CR was consistently superior to placebo with regards to primary endpoints (i.e. mean Hamilton Rating Scale for Depression total score [major depressive disorder], Liebowitz social anxiety scale total score and Clinical Global Impressions-Global Improvement score [social anxiety disorder] and Visual Analogue Scale-Mood score [PMDD])., Paroxetine is a potent selective serotonin reuptake inhibitor (SSRI) with indications for the treatment of depression, obsessive- compulsive disorder, panic disorder and social phobia. It is also used in the treatment of generalized anxiety disorder, post-traumatic stress disorder, premenstrual dysphoric disorder and chronic headache., Studies having compared the efficiency of antidepressants according to their serotonin activity (paroxetine or sertraline versus maprotiline, that is a selective noradrenaline re-uptake inhibitor), showed that serotonin re-uptake inhibitors were significantly more efficient on all symptoms than maprotiline, that was not more efficient than placebo., Paroxetine is a potent and selective serotonin reuptake inhibitor (SSRI) with currently approved indications for the treatment of depression, obsessive-compulsive disorder, panic disorder and social phobia. It is also used in the treatment of generalized anxiety disorder, post traumatic stress disorder, premenstrual dysphoric disorder and chronic headache., Preliminary data suggest that paroxetine has potential in the treatment of social phobia, premenstrual dysphoric disorder and chronic headache., The effects of active treatment were marked by the first active cycle with luteal phase 17-item Hamilton Rating Scale for Depression scores decreasing from 14.9 (+/- 5.3) to 8.2 (+/- 4.9) in the first, 7.8 (+/- 5.1) in the second, and 7.8 (+/- 6.8) in the third active treatment cycles (F[1,13] = 17.6; p < 0.0001)., The most conservative measure, the Clinical Global Impression (CGI), revealed that 7 of 14 patients had a complete response (CGI = 1 or 2) whereas 4 patients had a partial response (CGI = 3)., These open trial findings are consistent with the notion that paroxetine is effective in the acute phase for the treatment of PDD., The rating of premenstrual irritability, depressed mood, increase in appetite, and anxiety/tension was markedly lower during treatment with paroxetine than before, and this reduction in symptomatology appeared unabated for the entire treatment period.[SEP]Relations: Paroxetine has relations: drug_effect with Dyspnea, drug_effect with Dyspnea, contraindication with bipolar disorder, contraindication with bipolar disorder, drug_effect with Dysphagia, drug_effect with Dysphagia, drug_effect with Dysuria, drug_effect with Dysuria, drug_effect with Dyssynergia, drug_effect with Dyssynergia.", "label": "yes"}
{"id": "converted_2799", "sentence1": "Can simvastatin alleviate depressive symptoms?", "sentence2": "Simvastatin-treated patients experienced significantly more reductions in HDRS scores compared to the placebo group by the end of the trial (p=0.02). Early improvement and response rates were significantly greater in the simvastatin group than the placebo group (p=0.02 and p=0.01, respectively) but remission rate was not significantly different between the two groups (p=0.36)., In conclusion, simvastatin seems to be a safe and effective adjuvant therapy for patients suffering from major depressive disorder.[SEP]Relations: Simvastatin has relations: drug_effect with Anxiety, drug_effect with Anxiety, drug_effect with Pain, drug_effect with Pain, drug_effect with Headache, drug_effect with Headache, drug_effect with Arthritis, drug_effect with Arthritis, drug_effect with Dyspnea, drug_effect with Dyspnea.", "label": "yes"}
{"id": "converted_150", "sentence1": "Is PTEN involved in follicular thyroid carcinoma?", "sentence2": "Two of the 259 patients (0.8%), with both follicular thyroid carcinoma and macrocephaly, were found to carry a germline mutation in the PTEN gene. The PTEN mutation frequency in unselected cases of follicular thyroid carcinoma was 4.8%, The frequency of germline pathogenic PTEN mutations in an unselected series of patients with DTC is relatively low, but it is enriched by considering follicular histology and macrocephaly, Similarly, there is increasing evidence demonstrating that mutations leading to activation of the phosphatidylinositol 3- kinase (PI3K)/AKT effectors -PTEN and PI3KCa- are essential for the pathogenesis of follicular thyroid carcinoma (FTC), A single male with follicular thyroid carcinoma from one of these 64 (2%) CS-like families harboured a germline point mutation, c.209T-->C, Similarly, there is increasing evidence demonstrating that mutations leading to activation of the phosphatidylinositol 3- kinase (PI3K)/AKT effectors -PTEN and PI3KCa- are essential for the pathogenesis of follicular thyroid carcinoma (FTC)., The transcriptional silencing of PTEN was significantly associated with the anaplastic subtype, suggesting that PTEN is involved in the carcinogenesis of highly malignant or late-stage thyroid cancers, whereas this particular mechanism appears to be of minor importance in differentiated follicular thyroid tumors., These results show a high frequency of PTEN promoter hypermethylation, especially in follicular tumors, suggesting its possible role in thyroid tumorigenesis, Our findings suggest that the PTEN tumor suppressor gene is occasionally inactivated in sporadic follicular thyroid tumors, Germline mutations in the tumor suppressor gene PTEN, which encodes a dual-specificity phosphatase, have been found in up to 80% of patients with Cowden syndrome suggesting a role of PTEN in the pathogenesis of follicular thyroid tumors, The most common neoplasms in Cowden disease patients arise in the breast, skin, and thyroid (follicular subtype), The transcriptional silencing of PTEN was significantly associated with the anaplastic subtype, suggesting that PTEN is involved in the carcinogenesis of highly malignant or late-stage thyroid cancers, whereas this particular mechanism appears to be of minor importance in differentiated follicular thyroid tumors[SEP]Relations: PTEN has relations: disease_protein with thyroid gland carcinoma, disease_protein with thyroid gland carcinoma, disease_protein with thyroid cancer, disease_protein with thyroid cancer, anatomy_protein_present with thyroid gland, anatomy_protein_present with thyroid gland, disease_protein with carcinoma, disease_protein with carcinoma, disease_protein with prostate carcinoma, disease_protein with prostate carcinoma.", "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_1826", "sentence1": "Is the protein lefty an inhibitor of nodal?", "sentence2": "The expression of lefty, an inhibitor of nodal is often reduced in tumor cells.,  Nodal, and an inhibitor, Lefty., as well as the expression of Lefty, an inhibitor of nodal signaling,, he Nodal inhibitor lefty, The morphogen Nodal was proposed to form a long-range signaling gradient via a reaction-diffusion system, on the basis of differential diffusion rates of Nodal and its antagonist Lefty.[SEP]Relations: malignancy in giant cell tumor of bone has relations: disease_disease with bone sarcoma, disease_disease with bone sarcoma, disease_disease with malignant giant cell tumor, disease_disease with malignant giant cell tumor.", "label": "yes"}
{"id": "converted_1057", "sentence1": "Are there clinical trials on stem cells in multiple sclerosis", "sentence2": "Cells are generally given intravenously. Multiple sclerosis, rheumatoid arthritis and lupus have been successfully treated in human clinical trials, Human multipotent mesenchymal stem cell (MSC) therapies are currently being tested in clinical trials for Crohn's disease, multiple sclerosis, graft-versus-host disease, type 1 diabetes, bone fractures, cartilage damage, and cardiac diseases., Based on these results, several small pilot clinical trials in subjects with advanced MS have demonstrated that MSC administration is safe and provided an early signal of clinical effectiveness. The current aim of clinicians and scientists interested in the development of MSC-based strategies for the treatment of MS is to have the ultimate demonstration in large clinical trials that MSC can inhibit CNS inflammation and foster tissue repair, Mesenchymal stem cells (MSC) promote functional recovery in experimental models of central nervous system (CNS) pathology and are currently being tested in clinical trials for stroke, multiple sclerosis and CNS injury., Autologous bone marrow stromal cells (BMSCs) offer significant practical advantages for potential clinical applications in multiple sclerosis (MS). Based on recent experimental data, a number of clinical trials have been designed for the intravenous (IV) and/or intrathecal (ITH) administration of BMSCs in MS patients., Fingolimod is a S1P receptor modulator in MS clinical trials due to systemic anti-inflammatory properties, yet may impact cells within the CNS by crossing the blood-brain barrier., Their development in vitro and their use in vivo in animal models of degenerative neurological disease and recent first efforts in human clinical trials were the topics of a recent international meeting sponsored by the Multiple Sclerosis International Federation and the National Multiple Sclerosis Society on \"Stem Cells & MS: Prospects and Strategies\", Here we discuss key observations and questions emerging from clinical trials of hematopoietic stem cell transplantation for MS, Another possibility to achieve remyelination is the transplantation of myelinating cells into the central nervous system. Proof of principle and demonstration of the functionality were shown in numerous experiments, and a first clinical trial in patients with MS has started, This first trial will show if cell transplantation is a feasible concept in MS and whether the transplanted cells will survive and form new myelin.[SEP]Relations: multiple sclerosis has relations: disease_disease with brain disease, disease_disease with brain disease, disease_disease with multiple sclerosis, susceptibility to, disease_disease with multiple sclerosis, susceptibility to, disease_protein with IL12A, disease_protein with IL12A, disease_protein with SELE, disease_protein with SELE, disease_protein with IL1RN, disease_protein with IL1RN.", "label": "yes"}
{"id": "converted_142", "sentence1": "Is amiodarone a class I anti-arrhythmic drug?", "sentence2": "Common class I agents are excluded due to the inherent abnormal cardiac structure and function in the setting of cardiogenic shock. Class III drug options include dofetilide and amiodarone., Amiodarone has been used as an anti-arrhythmic drug since the 1970s and has an established role in the treatment of ventricular tachyarrhythmias. Although considered to be a class III anti-arrhythmic, amiodarone also has class I, II and IV actions, which gives it a unique pharmacological and anti-arrhythmic profile. , Amiodarone, an iodinated benzofuran derivative, introduced in 1960's as an anti-anginal agent, emerged as a potent anti-arrhythmic agent by 1970's and is currently one of the most commonly prescribed drugs in US for ventricular and atrial arrhythmias. Although amiodarone is considered a class III anti-arrhythmic agent, it also has class I, II, IV actions, making it a unique and effective anti-arrhythmic agent., Amiodarone, a representative class III agent, exerts negative dromotropism by suppressing the fast sodium current responsible for conduction in acute administration (class I effects). Chronic amiodarone causes prolongation of ERP (class III effects), which is sometimes associated with negative dromotropism based on the alteration of passive or active membrane properties., Amiodarone, an iodinated benzofuran derivative with predominantly class III anti-arrhythmic effects, is used to treat supraventricular and ventricular arrhythmias., Although amiodarone is considered a class III anti-arrhythmic agent, it also has class I, II, IV actions, making it a unique and effective anti-arrhythmic agent, Amiodarone, a class III antiarrhythmic drug, is one of the most effective drugs used in the treatment of ventricular and paroxysmal supraventricular tachyarrhythmia, Although amiodarone is considered a class III anti-arrhythmic agent, it also has class I, II, IV actions, making it a unique and effective anti-arrhythmic agent, Although considered to be a class III anti-arrhythmic, amiodarone also has class I, II and IV actions, which gives it a unique pharmacological and anti-arrhythmic profile, Amiodarone is a potent class III anti-arrhythmic drug that also possesses beta-blocking properties[SEP]Relations: Amiodarone has relations: drug_effect with Arrhythmia, drug_effect with Arrhythmia, drug_drug with Antipyrine, drug_drug with Antipyrine, drug_drug with Erythromycin, drug_drug with Erythromycin, drug_drug with Arformoterol, drug_drug with Arformoterol, drug_drug with Estrone, drug_drug with Estrone.", "label": "no"}
{"id": "converted_4400", "sentence1": "Does the royal jelly contain proteins?", "sentence2": " We observed differences in the metabolome, proteome, and phytosterol compositions of royal jelly synthesized by nurse bees from multi-pesticide exposed colonies, including significant reductions of key nutrients such as 24-methylenecholesterol, major royal jelly proteins, and 10-hydroxy-2-decenoic acid. ,  Two-dimensional electrophoresis was used for the fractionation of royal jelly proteins, the main bioactive compounds of RJ, such as proteins, peptides, fatty acids, and phenolic,  the expression of four of the major royal jelly proteins (MRJP1, MRJP2, MRJP4, and MRJP5) and also several proteins associated with carbohydrate metabolism and energy synthesis, the antioxidant system, detoxification, biosynthesis, amino acid metabolism, transcription and translation, protein folding and binding, olfaction, and learning and memory.[SEP]Relations: 12-Hydroxydodecanoic Acid has relations: drug_protein with ADH5, drug_protein with ADH5.", "label": "yes"}
{"id": "converted_963", "sentence1": "Is STAT3 involved in EIF2AK2-dependent suppression of autophagy?", "sentence2": "STAT3 may act as a competitive inhibitor of EIF2AK2. Indeed, pharmacological or genetic inhibition of STAT3 stimulates EIF2AK2-dependent EIF2S1 phosphorylation and autophagy. Conversely, the overexpression of wild-type STAT3 as well as of STAT3 mutants that cannot be phosphorylated by JAK2 or are excluded from the nucleus inhibits autophagy. However, STAT3 mutants that fail to interact with EIF2AK2 are unable to suppress autophagy, Both STAT3-targeting agents (i.e., Stattic, JSI-124 and WP1066) and EIF2AK2 activators (such as the double-strand RNA mimetic polyinosinic:polycytidylic acid) are capable of disrupting the inhibitory interaction between STAT3 and EIF2AK2 in cellula, A further screen designed to identify EIF2AK2-dependent autophagy inducers revealed that several fatty acids including palmitate trigger autophagy via a pathway that involves the disruption of the STAT3-EIF2AK2 complex, These results reveal an unsuspected crosstalk between cellular metabolism (fatty acids), pro-inflammatory signaling (STAT3), innate immunity (EIF2AK2), and translational control (EIF2S1) that regulates autophagy, Cytoplasmic STAT3 represses autophagy by inhibiting PKR activity, The SH2 domain of STAT3 was found to interact with the catalytic domain of the eIF2α kinase 2 EIF2AK2, best known as protein kinase R (PKR). Pharmacological and genetic inhibition of STAT3 stimulated the activating phosphorylation of PKR and consequent eIF2α hyperphosphorylation. Moreover, PKR depletion inhibited autophagy as initiated by chemical STAT3 inhibitors or free fatty acids like palmitate, STAT3-targeting chemicals and palmitate caused the disruption of inhibitory STAT3-PKR interactions, followed by PKR-dependent eIF2α phosphorylation, which facilitates autophagy induction, Indeed, pharmacological or genetic inhibition of STAT3 stimulates EIF2AK2-dependent EIF2S1 phosphorylation and autophagy., A further screen designed to identify EIF2AK2-dependent autophagy inducers revealed that several fatty acids including palmitate trigger autophagy via a pathway that involves the disruption of the STAT3-EIF2AK2 complex as well as the phosphorylation of mitogen-activated protein kinase 8/c-Jun N-terminal kinase 1 (MAPK8/JNK1) and EIF2S1., A further screen designed to identify EIF2AK2-dependent autophagy inducers revealed that several fatty acids including palmitate trigger autophagy via a pathway that involves the disruption of the STAT3-EIF2AK2 complex as well as the phosphorylation of mitogen-activated protein kinase 8/c-Jun N-terminal kinase 1 (MAPK8/JNK1) and EIF2S1, Indeed, pharmacological or genetic inhibition of STAT3 stimulates EIF2AK2-dependent EIF2S1 phosphorylation and autophagy, However, STAT3 mutants that fail to interact with EIF2AK2 are unable to suppress autophagy, Direct interaction between STAT3 and EIF2AK2 controls fatty acid-induced autophagy, A further screen designed to identify EIF2AK2-dependent autophagy inducers revealed that several fatty acids including palmitate trigger autophagy via a pathway that involves the disruption of the STAT3-EIF2AK2 complex as well as the phosphorylation of mitogen-activated protein kinase 8/c-Jun N-terminal kinase 1 (MAPK8/JNK1) and EIF2S1. , Indeed, pharmacological or genetic inhibition of STAT3 stimulates EIF2AK2-dependent EIF2S1 phosphorylation and autophagy. , Direct interaction between STAT3 and EIF2AK2 controls fatty acid-induced autophagy., These results unravel an unsuspected mechanism of autophagy control that involves STAT3 and PKR as interacting partners., Both STAT3-targeting agents (i.e., Stattic, JSI-124 and WP1066) and EIF2AK2 activators (such as the double-strand RNA mimetic polyinosinic:polycytidylic acid) are capable of disrupting the inhibitory interaction between STAT3 and EIF2AK2 in cellula, yet only the latter does so in cell-free systems in vitro. A further screen designed to identify EIF2AK2-dependent autophagy inducers revealed that several fatty acids including palmitate trigger autophagy via a pathway that involves the disruption of the STAT3-EIF2AK2 complex as well as the phosphorylation of mitogen-activated protein kinase 8/c-Jun N-terminal kinase 1 (MAPK8/JNK1) and EIF2S1., A further screen designed to identify EIF2AK2-dependent autophagy inducers revealed that several fatty acids including palmitate trigger autophagy via a pathway that involves the disruption of the STAT3-EIF2AK2 complex as well as the phosphorylation of mitogen-activated protein kinase 8/c-Jun N-terminal kinase 1 (MAPK8/JNK1) and EIF2S1. These results reveal an unsuspected crosstalk between cellular metabolism (fatty acids), pro-inflammatory signaling (STAT3), innate immunity (EIF2AK2), and translational control (EIF2S1) that regulates autophagy., Thus, STAT3 may act as a competitive inhibitor of EIF2AK2. Indeed, pharmacological or genetic inhibition of STAT3 stimulates EIF2AK2-dependent EIF2S1 phosphorylation and autophagy., Indeed, pharmacological or genetic inhibition of STAT3 stimulates EIF2AK2-dependent EIF2S1 phosphorylation and autophagy. Conversely, the overexpression of wild-type STAT3 as well as of STAT3 mutants that cannot be phosphorylated by JAK2 or are excluded from the nucleus inhibits autophagy., , Stattic, JSI-124 and WP1066) and EIF2AK2 activators (such as the double-strand RNA mimetic polyinosinic:polycytidylic acid) are capable of disrupting the inhibitory interaction between STAT3 and EIF2AK2 in cellula, yet only the latter does so in cell-free systems in vitro. A further screen designed to identify EIF2AK2-dependent autophagy inducers revealed that several fatty acids including palmitate trigger autophagy via a pathway that involves the disruption of the STAT3-EIF2AK2 complex as well as the phosphorylation of mitogen-activated protein kinase 8/c-Jun N-terminal kinase 1 (MAPK8/JNK1) and EIF2S1.[SEP]Relations: EIF2AK2 has relations: protein_protein with STAT3, protein_protein with STAT3, protein_protein with STAT2, protein_protein with STAT2, protein_protein with STAT1, protein_protein with STAT1, pathway_protein with Inhibition of PKR, pathway_protein with Inhibition of PKR, molfunc_protein with protein phosphatase regulator activity, molfunc_protein with protein phosphatase regulator activity.", "label": "yes"}
{"id": "converted_3444", "sentence1": "Does ProSavin use an adenoviral vector?", "sentence2": "Long-Term Follow-Up of a Phase I/II Study of ProSavin, a Lentiviral Vector Gene Therapy for Parkinson's Disease., ProSavin, a lentiviral vector based gene therapy that delivers local and continuous dopamine, was previously shown to be well tolerated in a Phase I/II first-in-human study, with significant improvements in motor behavior from baseline at 1 year. [SEP]Relations: Dopamine has relations: drug_drug with Saquinavir, drug_drug with Saquinavir, drug_drug with Adefovir dipivoxil, drug_drug with Adefovir dipivoxil, drug_drug with Protirelin, drug_drug with Protirelin, drug_drug with Adefovir, drug_drug with Adefovir, drug_drug with Procaine benzylpenicillin, drug_drug with Procaine benzylpenicillin.", "label": "no"}
{"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_3269", "sentence1": "Is Li–Fraumeni syndrome a rare, autosomal recessive, hereditary disorder that predisposes carriers to cancer development?", "sentence2": "Li-Fraumeni syndrome (LFS) is a rare cancer predisposition syndrome inherited in an autosomal dominant fashion that involves a germline mutation of tumor protein 53 (TP53). , Li-Fraumeni syndrome (LFS), a multiorgan cancer predisposition caused by germline TP53 mutations, confers significant cancer risks for young people (15-39 years). Yet evidence of how individuals experience this condition and the psychosocial implications are lacking. Therefore, this systematic review assessed the psychosocial implications of living with, or at risk of, an autosomal dominant condition as a young person, to, Li-Fraumeni syndrome (LFS) is a rare autosomal dominant disorder caused by a mutation in the p53 gene., Li-Fraumeni syndrome (LFS) is an autosomal dominant disorder occurring at a young age that predisposes individuals to multiple forms of cancer and to a heterogeneous spectrum of malignancies., Li-Fraumeni syndrome (LFS) is a rare hereditary autosomal dominant cancer disorder., Li-Fraumeni syndrome (LFS) is an autosomal dominant hereditary cancer disorder., Li-Fraumeni syndrome (LFS) is a rare, autosomal dominant, hereditary cancer predisposition disorder., Li-Fraumeni syndrome is a rare autosomal dominant cancer predisposition syndrome., Li-Fraumeni syndrome is an autosomal dominant disorder that is characterized by various types of cancer in childhood and adult cases., Li-Fraumeni syndrome (LFS) is a rare hereditary cancer syndrome associated with an autosomal dominant mutation inheritance in the TP53 tumor suppressor gene and a wide spectrum of cancer diagnoses., The Li-Fraumeni syndrome is an autosomal dominant disorder characterized by a high risk of developing osteosarcoma and has been found in up to 3% of children with osteosarcoma., Li-Fraumeni syndrome (LFS) is a rare, autosomal dominant, hereditary cancer predisposition disorder., Li-Fraumeni syndrome (LFS) is an inherited, autosomal-dominant condition that predisposes individuals to a wide-spectrum of tumors at an early age., The Li-Fraumeni syndrome (LFS) is an autosomal dominant hereditary disorder associated with different tumor types in childhood and young adults.[SEP]Relations: Li-Fraumeni syndrome has relations: disease_disease with autosomal dominant disease, disease_disease with autosomal dominant disease, disease_disease with autosomal dominant disease, disease_disease with autosomal dominant disease, 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. autosomal dominant disease has relations: disease_disease with Li-Fraumeni syndrome, disease_disease with Li-Fraumeni syndrome.", "label": "no"}
{"id": "converted_705", "sentence1": "Is Bladder training an effective method to treat  urge incontinence ?", "sentence2": "Mindfulness-based stress reduction appears to be a treatment worthy of further study, as in the short term, it is as effective as historical studies of drug treatment and bladder training in reducing urge incontinence and incontinence-related quality of life., All patients, irrespective of the results of cystometry were subsequently treated with oxybutynin 2.5 mg twice daily along with bladder training., Of the 29 patients with stable bladder and symptoms of OAB, 100% cure rate was achieved in 20 (68.9%) and 06 (20.6%) patients respectively. While in 3 patients in both groups, decrease of symptoms upto 75% after 6 months of treatment was observed., Both urodynamically proven unstable and stable bladder showed nearly equal improvement with treatment, There are 3 types of urine incontinence (urge-, stress-, and overflow-incontinence). Another standardization of urinary incontinence follows dysfunctions of the pelvic floor: detrusor muscle-dependent, due to sphincter spasm, prostate gland dependent. Urge incontinence with a dysfunction of the detrusor muscle is the most common type. Mixed types are frequent. Non-drug measures (e.g. pelvic muscle training, bladder training, toilet training are first choice treatments., Treatment of stress, urge and mixed incontinence can usually be commenced in primary care; pelvic floor exercises and bladder training are preferred. If bladder training is not effective for urge incontinence, anticholinergic drugs should be considered., Sixty patients (age 8 to 12 years) with urge incontinence or dysfunctional voiding were evaluated. After a no-treatment control period (average 6 months), patients underwent a 6-day bladder training course, Six months after training completion, 64.1% and 64.7% of the inpatient and outpatient groups with daytime wetting and 51.5% and 17.7% of the inpatient and outpatient groups with nighttime wetting were cured or had improved, Of the inpatient group with urge incontinence, the functional bladder capacity increased by 15%., To compare the efficacy of tolterodine plus simplified bladder training (BT) with tolterodine alone in patients with an overactive bladder., CONCLUSIONS: Tolterodine 2 mg twice daily is an effective and well tolerated treatment for an overactive bladder, the effectiveness of which can be augmented by a simplified BT regimen., Bladder training is a modification of bladder drill that is conducted more gradually on an outpatient basis and has resulted in significant reduction of incontinence in older, community-dwelling women., OBJECTIVE: To evaluate the long-term effect of treatment of female incontinence by the general practitioner (pelvic floor exercises, and bladder training) in female urinary incontinence., Stress incontinence and urge incontinence were treated by means of pelvic floor exercises and bladder training respectively, while a mixed incontinence was treated by bladder training followed by pelvic floor exercises. T, The treatment consisted of training of pelvic muscles in stress incontinence and bladder training in urge incontinence, RESULTS: After 3 months the mean frequency of urine loss per week diminished from 21 to 8, and after 12 months to 6 times., Some elders suffering from urge incontinence prefer pelvic muscle exercises to bladder training as the behavioral intervention of choice, for eight out of nine women their continence had improved, both subjectively and objectively., Bladder training is a simple, safe, and effective treatment in the management of mild to moderate forms of urinary incontinence in outpatient populations. It can be used as a first-line treatment or in combination with such other interventions as pelvic muscle exercises, bladder pressure biofeedback, electrical stimulation, and drug therapy, Treatment consisted of pelvic floor exercises in the case of stress incontinence and bladder training in the case of urge incontinence., After 3 months about 60% of the patients were either dry or only mildly incontinent, terodiline group shows this drug to be a valuable adjunct to a bladder regimen in children with urge incontinence, Basing on our experience with 39 patients with severe urge incontinence (in one-quarter of the cases pure urge incontinence, in one-half of the cases mixed incontinence and in a further quarter of the cases neurogenic bladder disorders) a supervised programme (mictiogram) and a well-tried therapy (especially in the Anglo-Saxon countries) consisting of the triad hospitalisation/bladder training/medication therapy are presented. After an average hospitalisation period of 14 days, we were able to achieve a symptom-free state in 94% of the patients., Anamnestic and urodynamical results are evaluated before and after bladder retraining drill (BRD) in women suffering from urge incontinence., We could state that the BRD is a good possibility to realize multistep-therapy of female incontinence., Twenty consecutive female patients with urge incontinence and stable detrusor function on provocative rapid fill CO2-cystometry were treated as out-patients with a bladder training programme and with terodiline/placebo in a double-blind cross-over design., In conclusion, female patients with idiopathic urge incontinence and stable detrusor function did respond to treatment as do female patients with urge incontinence and proven instability., The results of in-patient bladder training in 65 women with frequency, urgency and urge incontinence are reported. There was a good initial response in 88%. By 6 months the response rate had fallen to 38%., Patients with sensory urgency appeared to do better than those with detrusor instability and it is suggested that bladder training may be indicated as primary treatment in sensory urgency., Bladder training and/or biofeedback techniques were used to treat 75 patients with frequency, urgency, nocturia and urge incontinence. Significant improvement or cure was obtained in 70 per cent of enuretic children, and 66 per cent of men and 74 per cent of women with unstable detrusor function.[SEP]Relations: Urinary incontinence has relations: drug_effect with Ibuprofen, drug_effect with Ibuprofen, drug_effect with Acamprosate, drug_effect with Acamprosate, drug_effect with Urofollitropin, drug_effect with Urofollitropin, drug_effect with Naproxen, drug_effect with Naproxen, drug_effect with Levonorgestrel, drug_effect with Levonorgestrel.", "label": "yes"}
{"id": "converted_1145", "sentence1": "Could RG7112 be used as cancer therapy?", "sentence2": "RG7112 is a potent and selective member of the nutlin family of MDM2 antagonists currently in phase I clinical studies., Our findings offer a preclinical proof-of-concept that RG7112 is effective in treatment of solid tumors expressing wild-type p53., On the other hand, JNJ-26854165, a novel tryptamine derivative and RG7112, a cis-imidazoline representative have shown promising results in early phases of trials in cancer patients., MDM2 small-molecule antagonist RG7112 activates p53 signaling and regresses human tumors in preclinical cancer models., On the other hand, JNJ-26854165, a novel tryptamine derivative and RG7112, a cis-imidazoline representative have shown promising results in early phases of trials in cancer patients., RG7112 is a selective inhibitor of p53-MDM2 binding that frees p53 from negative control, activating the p53 pathway in cancer cells leading to cell cycle arrest and apoptosis., In cancer cells expressing wild-type p53, RG7112 stabilizes p53 and activates the p53 pathway, leading to cell cycle arrest, apoptosis, and inhibition or regression of human tumor xenografts., Treatment of cancer cells expressing wild-type p53 with RG7112 activated the p53 pathway, leading to cell-cycle arrest and apoptosis., RG7112 was selected for evaluation by the Pediatric Preclinical Testing Program (PPTP) due to the relatively low incidence of p53 mutations in pediatric cancers compared with adult malignancies., Treatment of cancer cells expressing wild-type p53 with RG7112 activated the p53 pathway, leading to cell-cycle arrest and apoptosis, On the other hand, JNJ-26854165, a novel tryptamine derivative and RG7112, a cis-imidazoline representative have shown promising results in early phases of trials in cancer patients, RG7112 is a selective inhibitor of p53-MDM2 binding that frees p53 from negative control, activating the p53 pathway in cancer cells leading to cell cycle arrest and apoptosis, MDM2 small-molecule antagonist RG7112 activates p53 signaling and regresses human tumors in preclinical cancer models, In cancer cells expressing wild-type p53, RG7112 stabilizes p53 and activates the p53 pathway, leading to cell cycle arrest, apoptosis, and inhibition or regression of human tumor xenografts, RG7112 was selected for evaluation by the Pediatric Preclinical Testing Program (PPTP) due to the relatively low incidence of p53 mutations in pediatric cancers compared with adult malignancies, We report a proof-of-mechanism study of RG7112, a small-molecule MDM2 antagonist, in patients with chemotherapy-naive primary or relapsed well-differentiated or dedifferentiated MDM2-amplified liposarcoma who were eligible for resection, BACKGROUND: RG7112 is a selective inhibitor of p53-MDM2 binding that frees p53 from negative control, activating the p53 pathway in cancer cells leading to cell cycle arrest and apoptosis. RG7112 was selected for evaluation by the Pediatric Preclinical Testing Program (PPTP) due to the relatively low incidence of p53 mutations in pediatric cancers compared with adult malignancies. , Treatment of cancer cells expressing wild-type p53 with RG7112 activated the p53 pathway, leading to cell-cycle arrest and apoptosis. , Effect of the MDM2 antagonist RG7112 on the P53 pathway in patients with MDM2-amplified, well-differentiated or dedifferentiated liposarcoma: an exploratory proof-of-mechanism study., RG7112 was selected for evaluation by the Pediatric Preclinical Testing Program (PPTP) due to the relatively low incidence of p53 mutations in pediatric cancers compared with adult malignancies. , Thus, inhibitors of p53-MDM2 binding that can reactivate p53 in cancer cells may offer an effective approach for cancer therapy., Treatment of cancer cells expressing wild-type p53 with RG7112 activated the p53 pathway, leading to cell-cycle arrest and apoptosis. RG7112 showed potent antitumor activity against a panel of solid tumor cell lines., A crystal structure of the RG7112-MDM2 complex revealed that the small molecule binds in the p53 pocket of MDM2, mimicking the interactions of critical p53 amino acid residues. Treatment of cancer cells expressing wild-type p53 with RG7112 activated the p53 pathway, leading to cell-cycle arrest and apoptosis., RG7112 (2g) is the first clinical small-molecule MDM2 inhibitor designed to occupy the p53-binding pocket of MDM2. In cancer cells expressing wild-type p53, RG7112 stabilizes p53 and activates the p53 pathway, leading to cell cycle arrest, apoptosis, and inhibition or regression of human tumor xenografts., RG7112 was selected for evaluation by the Pediatric Preclinical Testing Program (PPTP) due to the relatively low incidence of p53 mutations in pediatric cancers compared with adult malignancies. RG7112 and its inactive enantiomer RG7112i were evaluated against the 23 cell lines of the PPTP in vitro panel using 96 hours exposure (1 nM to 10 µM)., Thus, inhibitors of p53-MDM2 binding that can reactivate p53 in cancer cells may offer an effective approach for cancer therapy. RG7112 is a potent and selective member of the nutlin family of MDM2 antagonists currently in phase I clinical studies., In cancer cells expressing wild-type p53, RG7112 stabilizes p53 and activates the p53 pathway, leading to cell cycle arrest, apoptosis, and inhibition or regression of human tumor xenografts.  ., Restoration of p53 activity by inhibiting the p53-MDM2 interaction may represent a novel approach to cancer treatment. RG7112 (2g) is the first clinical small-molecule MDM2 inhibitor designed to occupy the p53-binding pocket of MDM2., RG7112 was selected for evaluation by the Pediatric Preclinical Testing Program (PPTP) due to the relatively low incidence of p53 mutations in pediatric cancers compared with adult malignancies.RG7112 and its inactive enantiomer RG7112i were evaluated against the 23 cell lines of the PPTP in vitro panel using 96 hours exposure (1 nM to 10 µM)., Notably, RG7112 was highly synergistic with androgen deprivation in LNCaP xenograft tumors. Our findings offer a preclinical proof-of-concept that RG7112 is effective in treatment of solid tumors expressing wild-type p53., RG7112 induced tumor regressions in solid tumors from different histotype panels, and exhibited consistent high-level activity against ALL xenografts. This high level of activity supports prioritization of RG7112 for further evaluation., RG7112 is a selective inhibitor of p53-MDM2 binding that frees p53 from negative control, activating the p53 pathway in cancer cells leading to cell cycle arrest and apoptosis. RG7112 was selected for evaluation by the Pediatric Preclinical Testing Program (PPTP) due to the relatively low incidence of p53 mutations in pediatric cancers compared with adult malignancies.[SEP]Relations: Protein S human has relations: drug_drug with Rituximab, drug_drug with Rituximab, drug_drug with Bamet-UD2, drug_drug with Bamet-UD2, drug_drug with Methotrexate, drug_drug with Methotrexate, drug_drug with Bortezomib, drug_drug with Bortezomib, drug_drug with NS-398, drug_drug with NS-398.", "label": "yes"}
{"id": "converted_3706", "sentence1": "Do genes with monoallelic expression contribute proportionally to genetic diversity in humans?", "sentence2": "Genes with monoallelic expression contribute disproportionately to genetic diversity in humans., An unexpectedly large number of human autosomal genes are subject to monoallelic expression (MAE). Our analysis of 4,227 such genes uncovers surprisingly high genetic variation across human populations. This increased diversity is unlikely to reflect relaxed purifying selection. Remarkably, MAE genes exhibit an elevated recombination rate and an increased density of hypermutable sequence contexts. However, these factors do not fully account for the increased diversity. We find that the elevated nucleotide diversity of MAE genes is also associated with greater allelic age: variants in these genes tend to be older and are enriched in polymorphisms shared by Neanderthals and chimpanzees. Both synonymous and nonsynonymous alleles of MAE genes have elevated average population frequencies. We also observed strong enrichment of the MAE signature among genes reported to evolve under balancing selection. We propose that an important biological function of widespread MAE might be the generation of cell-to-cell heterogeneity; the increased genetic variation contributes to this heterogeneity., Genes with monoallelic expression contribute disproportionately to genetic diversity in humans[SEP]Relations: myoclonic-astastic epilepsy has relations: disease_protein with RAPGEF2, disease_protein with RAPGEF2, disease_protein with SLC6A1, disease_protein with SLC6A1, disease_phenotype_positive with Developmental regression, disease_phenotype_positive with Developmental regression, disease_protein with AP2M1, disease_protein with AP2M1, disease_phenotype_positive with Global developmental delay, disease_phenotype_positive with Global developmental delay.", "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]Relations: LADD syndrome has relations: disease_disease with EEC syndrome and related syndrome, disease_disease with EEC syndrome and related syndrome, disease_disease with autosomal dominant disease, disease_disease with autosomal dominant disease, disease_disease with genetic otorhinolaryngological malformation, disease_disease with genetic otorhinolaryngological malformation, disease_disease with genetic multiple congenital anomalies/dysmorphic syndrome without intellectual disability, disease_disease with genetic multiple congenital anomalies/dysmorphic syndrome without intellectual disability, disease_phenotype_positive with Autosomal dominant inheritance, disease_phenotype_positive with Autosomal dominant inheritance.", "label": "no"}
{"id": "converted_1216", "sentence1": "Can desvenlafaxine be used at a dose of 50mg/day?", "sentence2": "Long-term use of desvenlafaxine was safe and well tolerated, with a clinical benefit/risk profile similar to that in other populations., e objective of this study was to evaluate the long-term safety of desvenlafaxine for continuation treatment of major depressive disorder (MDD) in Japanese patients. This was a phase 3, multicenter, 10-month, open-label study with flexible dosing of desvenlafaxine (25, 50, 100 mg/day), n an effort to establish the lowest effective dose of desvenlafaxine (administered as desvenlafaxine succinate), we assessed the efficacy, safety, and tolerability of 10- and 50-mg/day desvenlafaxine vs placebo for the treatment of major depressive disorder, Change from baseline to final evaluation in adjusted HAM-D(17) total scores was not significantly different comparing desvenlafaxine 10 mg/day (-9.28) and desvenlafaxine 50 mg/day (-8.92) with placebo (-8.42), Overall rates of treatment-emergent adverse events with both doses were similar to placebo, However, in a companion study reported separately, desvenlafaxine 50 mg, but not 25 mg, separated from placebo. Taken together, these studies suggest that 50 mg is the minimum effective dose of desvenlafaxine for the treatment of major depressive disorder. , Desvenlafaxine XR was dosed at 50 mg/day for 10 days., Desvenlafaxine therapy is initiated at the therapeutic dose (50 mg/day) without a need for dose titration., Clinical studies have investigated the efficacy of DVS in doses ranging from 50 to 400 mg/day for the treatment of MDD in adult outpatients. The effects of DVS 50 mg/day have been clearly distinguished from placebo in the reduction of MDD symptoms in such clinical trials. No additional therapeutic benefits were found at doses > 50 mg/day. The recommended dose of DVS ranges from 50 to 100 mg., Adult outpatients with major depressive disorder received desvenlafaxine doses ranging from 50-400 mg/day or placebo for 8 weeks,  At the recommended therapeutic dose of 50 mg/day, discontinuation due to adverse events was similar to placebo, atients received fixed (50, 100, 200, or 400 mg/day; n=1,342) or flexible doses (100-400 mg/day; n=463) of desvenlafaxine or placebo (n=1,108), Desvenlafaxine demonstrated short-term efficacy for treating major depressive disorder across the range of doses studied. No evidence of greater efficacy was observed with doses >50 mg/day; a strong dose-response effect on tolerability was observed., To assess the efficacy, safety, and tolerability of 50- and 100-mg/day doses of desvenlafaxine (administered as desvenlafaxine succinate), a serotonin-norepinephrine reuptake inhibitor, for the treatment of major depressive disorder (MDD), Patients with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) MDD and 17-item Hamilton Rating Scale for Depression (HAM-D(17)) scores > or =20 were randomly assigned to double-blind placebo or desvenlafaxine treatment (fixed dose of 50 mg/day or 100 mg/day) for 8 weeks., Desvenlafaxine 50 mg was associated with a significantly greater adjusted mean change from baseline on the HAM-D(17) (-11.5) compared with placebo (-9.5, p=0.018),  These results demonstrate efficacy, safety, and tolerability of desvenlafaxine 50 mg/day for treating MDD. , CONCLUSIONS: Desvenlafaxine at the recommended dose of 50 mg/d was effective in relapse prevention of depression during a 6-month period in patients who demonstrated stable response after 20 weeks of open-label desvenlafaxine treatment.[SEP]Relations: Desvenlafaxine has relations: drug_drug with Dosulepin, drug_drug with Dosulepin, drug_drug with Colistimethate, drug_drug with Colistimethate, drug_drug with Etonogestrel, drug_drug with Etonogestrel, drug_drug with Nomifensine, drug_drug with Nomifensine, drug_drug with Pemetrexed, drug_drug with Pemetrexed.", "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]Relations: regulation of neural retina development has relations: bioprocess_protein with PTF1A, bioprocess_protein with PTF1A, bioprocess_protein with SIX3, bioprocess_protein with SIX3, bioprocess_protein with DLL4, bioprocess_protein with DLL4, bioprocess_bioprocess with negative regulation of neural retina development, bioprocess_bioprocess with negative regulation of neural retina development, bioprocess_bioprocess with positive regulation of neural retina development, bioprocess_bioprocess with positive regulation of neural retina development.", "label": "yes"}
{"id": "converted_3639", "sentence1": "Is poliosis circumscripta another term for a white or unpigmented patch of hair or skin?", "sentence2": "\"white forelock,\" poliosis circumscripta, defined as a localized patch of white hair in a group of hair follicle, Although traditionally known as \"white forelock,\" poliosis circumscripta, defined as a localized patch of white hair in a group of hair follicles, can involve any hairy area on the body including the scalp, eyebrows, and eyelashes., Although traditionally known as \" white forelock , \" poliosis circumscripta , defined as a localized patch of white hair in a group of hair follicles , can involve any hairy area on the body including the scalp , eyebrows , and eyelashes, Although traditionally known as \"white forelock,\" poliosis circumscripta, defined as a localized patch of white hair in a group of hair follicles, can involve any hairy area on the body including the scalp, eyebrows, and eyelashes.[SEP]Relations: eyelash has relations: anatomy_anatomy with strand of hair, anatomy_anatomy with strand of hair. muscle structure has relations: anatomy_anatomy with insect adult somatic muscle, anatomy_anatomy with insect adult somatic muscle, anatomy_anatomy with somatic muscle, anatomy_anatomy with somatic muscle, anatomy_anatomy with urethra muscle tissue, anatomy_anatomy with urethra muscle tissue, anatomy_anatomy with anatomical structure, anatomy_anatomy with anatomical structure.", "label": "yes"}
{"id": "converted_1468", "sentence1": "Is it possible to determine the proteome of a formalin fixed and paraffin embedded  (FFPE) tissue?", "sentence2": "ver the last few years, advances in methodology have made it possible to recover peptides from FFPE tissues that yield a reasonable representation of the proteins recovered from identical fresh or frozen specimens., Thus, laser capture microdissection of FFPE tissue coupled with downstream proteomic analysis is a valid approach, Qualitative proteome profiling of formalin-fixed, paraffin-embedded (FFPE) tissue is advancing the field of clinical proteomics., Recent improvements in proteomics technologies, from the 2D gel analysis of intact proteins to the \"shotgun\" quantification of peptides and the use of isobaric tags for absolute and relative quantification (iTRAQ) method, have made the analysis of FFPE tissues possible., The ability to investigate the proteome of formalin-fixed, paraffin-embedded (FFPE) tissues can be considered a major recent achievement in the field of clinical proteomics., The label-free approach enables the quantitative measurement of radiation-induced alterations in FFPE tissue and facilitates retrospective biomarker identification using clinical archives., Proteomic analysis of formalin-fixed paraffin-embedded pancreatic tissue using liquid chromatography tandem mass spectrometry., We report that differentially expressed proteins can be identified among FFPE tissue specimens originating from individuals with different pancreatic histologic findings., Formalin-fixed paraffin-embedded (FFPE) proteome analysis using gel-free and gel-based proteomics., This study will facilitate the development of future proteomic analysis of FFPE tissue and provide a tool for the validation in archival samples of biomarkers of exposure, prognosis and disease., The CAAR method presented here complements previously described antigen-retrieval protocols and is an important step in being able to fully analyze the proteome of archived FFPE tissue., Proteome, phosphoproteome, and N-glycoproteome are quantitatively preserved in formalin-fixed paraffin-embedded tissue and analyzable by high-resolution mass spectrometry., It has only recently been shown that proteins in FFPE tissues can be identified by mass spectrometry-based proteomics but analysis of post-translational modifications is thought to be difficult or impossible, Results from the FFPE-FASP procedure do not indicate any discernible changes due to storage time, hematoxylin staining or laser capture microdissection., Thus, FFPE biobank material can be analyzed by quantitative proteomics at the level of proteins and post-translational modifications., A novel tissue microdissection technique has been developed and combined with a method to extract soluble peptides directly from FFPE tissue for mass spectral analysis of prostate cancer (PCa) and benign prostate hyperplasia (BPH). Hundreds of proteins from PCa and BPH tissue were identified,, espite using tissue blocks stored for as many as 28 years, high confidence and comparative proteome analysis between the leiomyomas and the sarcoma is achieved., These findings demonstrate that formalin fixation, paraffin processing, and LCM do not negatively impact protein quality and quantity as determined by MS and that FFPE samples are amenable to global proteomic analysis., Protein extraction of formalin-fixed, paraffin-embedded tissue enables robust proteomic profiles by mass spectrometry.[SEP]Relations: benign prostatic hyperplasia (disease) has relations: disease_protein with FGF7, disease_protein with FGF7, contraindication with Pentoxyverine, contraindication with Pentoxyverine, contraindication with Methylene blue, contraindication with Methylene blue. specialized connective tissue has relations: anatomy_anatomy with connective tissue, anatomy_anatomy with connective tissue. benign neoplasm of prostate has relations: disease_disease with prostatic adenoma, disease_disease with prostatic adenoma.", "label": "yes"}
{"id": "converted_2067", "sentence1": "Can glyburide reduce cerebral edema?", "sentence2": "Preclinical studies have shown that a continuous infusion of glyburide blocks edema formation and improves outcome. We hypothesize that treatment with RP-1127 (Glyburide for Injection) reduces formation of brain edema in patients after large anterior circulation infarction., CONCLUSIONS: GAMES-RP was designed to provide critical information regarding glyburide for injection in patients with large hemispheric stroke and will inform the design of future studies., Glyburide is associated with attenuated vasogenic edema in stroke patients., Glyburide is reported to prevent brain swelling in preclinical rodent models of ischemic stroke through inhibition of a non-selective channel composed of sulfonylurea receptor 1 and transient receptor potential cation channel subfamily M member 4. , RESULTS: We report that IV glyburide was associated with T2 fluid-attenuated inversion recovery signal intensity ratio on brain MRI, diminished the lesional water diffusivity between days 1 and 2 (pseudo-normalization), and reduced blood MMP-9 level.CONCLUSIONS: Several surrogate markers of vasogenic edema appear to be reduced in the setting of IV glyburide treatment in human stroke. , Pilot study of intravenous glyburide in patients with a large ischemic stroke., BACKGROUND AND PURPOSE: Preclinical and retrospective clinical data indicate that glyburide, a selective inhibitor of sulfonylurea receptor 1-transient receptor potential melastatin 4, is effective in preventing edema and improving outcome after focal ischemia. , Preclinical data suggest that glyburide, an inhibitor of SUR1-TRPM4, is effective in preventing edema., Glyburide in Treating Malignant Cerebral Edema. , Glyburide in Treating Malignant Cerebral Edema. Blocking Sulfonyl Urea One (SUR1) Receptors., The sulfonylurea receptor 1-regulated NC(Ca-ATP) channel is upregulated in rodent models of stroke with block of the channel by the sulfonylurea, glibenclamide (glyburide), significantly reducing mortality, cerebral edema, and infarct volume., Glyburide is a safe, inexpensive, and efficacious alternative to dexamethasone for the treatment of cerebral metastasis-related vasogenic edema., In this focused review, we explore preclinical data linking Sur1 channel formation to development of edema and reference evidence suggesting that the antidiabetic sulfonylurea drug glyburide (a Sur1 inhibitor) is an inexpensive and well-tolerated agent that can be clinically tested to reduce or prevent malignancy and/or treatment-associated edema., Potential of glyburide to reduce intracerebral edema in brain metastases., Glyburide Advantage in Malignant Edema and Stroke (GAMES-RP) Trial: Rationale and Design., Preclinical data suggest that glyburide, an inhibitor of SUR1-TRPM4, is effective in preventing edema., Inhibition of sulfonylurea receptor 1 (SUR1) by glyburide has been shown to decrease edema after subarachnoid hemorrhage., Glyburide is a safe, inexpensive, and efficacious alternative to dexamethasone for the treatment of cerebral metastasis-related vasogenic edema, RESULTS: We report that IV glyburide was associated with T2 fluid-attenuated inversion recovery signal intensity ratio on brain MRI, diminished the lesional water diffusivity between days 1 and 2 (pseudo-normalization), and reduced blood MMP-9 level. , Preclinical data suggest that glyburide, an inhibitor of SUR1-TRPM4, is effective in preventing edema. , Exploratory analysis of glyburide as a novel therapy for preventing brain swelling., Inhibition of sulfonylurea receptor 1 (SUR1) by glyburide has been shown to decrease edema after subarachnoid hemorrhage. , In this focused review, we explore preclinical data linking Sur1 channel formation to development of edema and reference evidence suggesting that the antidiabetic sulfonylurea drug glyburide (a Sur1 inhibitor) is an inexpensive and well-tolerated agent that can be clinically tested to reduce or prevent malignancy and/or treatment-associated edema., Glyburide is a safe, inexpensive, and efficacious alternative to dexamethasone for the treatment of cerebral metastasis-related vasogenic edema., Glyburide is reported to prevent brain swelling in preclinical rodent models of ischemic stroke through inhibition of a non-selective channel composed of sulfonylurea receptor 1 and transient receptor potential cation channel subfamily M member 4., Several surrogate markers of vasogenic edema appear to be reduced in the setting of IV glyburide treatment in human stroke., We hypothesize that treatment with RP-1127 (Glyburide for Injection) reduces formation of brain edema in patients after large anterior circulation infarction., Glyburide is a safe, inexpensive, and efficacious alternative to dexamethasone for the treatment of cerebral metastasis-related vasogenic edema.., Glyburide is associated with attenuated vasogenic edema in stroke patients.[SEP]Relations: Glyburide has relations: drug_effect with Edema, drug_effect with Edema, drug_effect with Hypoglycemia, drug_effect with Hypoglycemia. Cerebral edema has relations: drug_effect with Glycine betaine, drug_effect with Glycine betaine, drug_effect with Glatiramer, drug_effect with Glatiramer, drug_effect with Carmustine, drug_effect with Carmustine.", "label": "yes"}
{"id": "converted_317", "sentence1": "Have mutations in the Polycomb group been found in human diseases?", "sentence2": "We identify a novel mutation in PHC1, a human orthologue of the Drosophila polyhomeotic member of polycomb group (PcG), which significantly decreases PHC1 protein expression, increases Geminin protein level and markedly abolishes the capacity to ubiquitinate histone H2A in patient cells., In clinical specimens of head and neck cancer, we found that coamplification of BMI1 and AURKA correlated with poorer prognosis., Mutations of EZH2, RUNX1, TP53, and ASXL1 were associated with shorter overall survival independent of the LR-PSS., In this study, we show the high frequency of spontaneous γδ T-cell leukemia (T-ALL) occurrence in mice with biallelic deletion of enhancer of zeste homolog 2 (Ezh2)., Subsequently, analysis of deletion profiles of other PRC2 members revealed frequent losses of genes such as EZH2, AEBP2, and SUZ12; however, the deletions targeting these genes were large. We also identified two patients with homozygous losses of JARID2 and AEBP2. We observed frequent codeletion of AEBP2 and ETV6, and similarly, SUZ12 and NF1., A total of 25 different EZH2 mutations were detected in 5.9% of PMF, 1.2% of PPV-MF, and 9.4% of PET-MF patients; most were exonic heterozygous missense changes., In the present investigation we have focused on the candidate region in 6p23, a region that have been found linked to CL/P in several investigations, in the attempt to find out the susceptibility gene provisionally named OFC1. Gene expression experiments in mice embryo of positional candidate genes revealed that JARID2 was highly and specifically expressed in epithelial cells in merging palatal shelves., High expression of EZH2 and amplification of EZH2 was found in 54.1% and 12.0% of ESCCs, respectively., We also observed that HOXA9 levels were significantly inversely correlated with survival and that BMI-1 was overexpressed in cases with 11q23 rearrangements, suggesting that p19(ARF) suppression may be involved in MLL-associated leukemia., We demonstrate that in multiple experimental models of metastatic prostate cancer both BMI1 and Ezh2 genes are amplified and gene amplification is associated with increased expression of corresponding mRNAs and proteins., he EZH2 gene amplification was significantly (P < 0.05) associated with increased EZH2 protein expression., The third tumor showed a t(6p;10q;10p) as the sole karyotypic abnormality, leading to the fusion of PHF1 with another partner, the enhancer of polycomb (EPC1) gene from 10p11; EPC1 has hitherto not been associated with neoplasia.[SEP]Relations: Protein S human has relations: drug_drug with Polythiazide, drug_drug with Polythiazide, drug_drug with Polythiazide, drug_drug with Polythiazide, drug_drug with Polythiazide, drug_drug with Polythiazide, drug_drug with Polythiazide, drug_drug with Polythiazide, drug_drug with Polythiazide, drug_drug with Polythiazide.", "label": "yes"}
{"id": "converted_745", "sentence1": "Is rivaroxaban metabolized in kidneys?", "sentence2": "The novel oral anticoagulants (i.e., dabigatran, apixaban, rivaroxaban) all undergo renal metabolism to varying degrees, and hence dosing, efficacy, and safety require special consideration in CKD patients., The new oral anticoagulants have relatively little data in patients with severe renal impairment, and all have an element of renal excretion., Now new anticoagulant drugs(dabigatran and rivaroxaban) can become available. Therefore, we have to learn how to use those drugs. They have to carefully be used because they discharge from kidney and old aged patients have potential renal dysfunction. , In the everyday practice it will be necessary to be very cautious in patients with impaired renal function, as all these drugs are eliminated by kidneys., Dabigatran etexilate and rivaroxaban carry the highest risk due to a high degree of renal excretion, whereas the risk for apixaban, edoxaban and betrixaban seems lower., However, all these agents undergo renal clearance to varying degrees, and hence dosing, efficacy, and safety require special consideration in patients with CKD. , Rivaroxaban being excreted via kidney and liver, some precautions should apply in case of liver insufficiency. , Rivaroxaban elimination is mainly renal, but also through faecal matter and by hepatic metabolism. [SEP]Relations: Rivaroxaban has relations: contraindication with kidney disease, contraindication with kidney disease, drug_drug with Carboplatin, drug_drug with Carboplatin, drug_drug with Conjugated estrogens, drug_drug with Conjugated estrogens, drug_drug with Colistin, drug_drug with Colistin, drug_drug with Metaxalone, drug_drug with Metaxalone.", "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_3130", "sentence1": "Are apoE mimetics being considered as a treatment against Alzheimer's disease?", "sentence2": "The apolipoprotein-E-mimetic COG112 protects amyloid precursor protein intracellular domain-overexpressing animals from Alzheimer's disease-like pathological features., Studies show that administration of apolipoprotein E (apoE) and apoE-derived small peptide mimetics protect AD mouse models against these AD-like features.[SEP]Relations: amyloid precursor protein metabolic process has relations: bioprocess_protein with APOE, bioprocess_protein with APOE, bioprocess_protein with APH1A, bioprocess_protein with APH1A, bioprocess_protein with PSENEN, bioprocess_protein with PSENEN, bioprocess_bioprocess with amyloid precursor protein catabolic process, bioprocess_bioprocess with amyloid precursor protein catabolic process. apolipoprotein E recycling has relations: bioprocess_bioprocess with protein transport, bioprocess_bioprocess with protein transport.", "label": "yes"}
{"id": "converted_741", "sentence1": "Is the circadian clock involved in ribosome biogenesis?", "sentence2": "The circadian clock coordinates ribosome biogenesis., Here we show that the circadian clock exerts its function also through the regulation of mRNA translation. Namely, the circadian clock influences the temporal translation of a subset of mRNAs involved in ribosome biogenesis by controlling the transcription of translation initiation factors as well as the clock-dependent rhythmic activation of signaling pathways involved in their regulation. Moreover, the circadian oscillator directly regulates the transcription of ribosomal protein mRNAs and ribosomal RNAs. Thus the circadian clock exerts a major role in coordinating transcription and translation steps underlying ribosome biogenesis., Namely, the circadian clock influences the temporal translation of a subset of mRNAs involved in ribosome biogenesis by controlling the transcription of translation initiation factors as well as the clock-dependent rhythmic activation of signaling pathways involved in their regulation, The circadian clock coordinates ribosome biogenesis, Here we show that the circadian clock exerts its function also through the regulation of mRNA translation, Here we show that the circadian clock exerts its function also through the regulation of mRNA translation. Namely, the circadian clock influences the temporal translation of a subset of mRNAs involved in ribosome biogenesis by controlling the transcription of translation initiation factors as well as the clock-dependent rhythmic activation of signaling pathways involved in their regulation.[SEP]Relations: ribosome has relations: cellcomp_protein with AURKAIP1, cellcomp_protein with AURKAIP1, cellcomp_protein with SNCA, cellcomp_protein with SNCA, cellcomp_protein with RNA28SN5, cellcomp_protein with RNA28SN5, cellcomp_protein with RPS17, cellcomp_protein with RPS17, cellcomp_protein with RNA28SN4, cellcomp_protein with RNA28SN4.", "label": "yes"}
{"id": "converted_3431", "sentence1": "Is ozanezumab effective for amyotrophic lateral sclerosis?", "sentence2": "The adjusted mean of the joint-rank score was -14·9 (SE 13·5) for the ozanezumab group and 15·0 (13·6) for the placebo group, with a least squares mean difference of -30·0 (95% CI -67·9 to 7·9; p=0·12). , INTERPRETATION: Ozanezumab did not show efficacy compared with placebo in patients with ALS. Therefore, Nogo-A does not seem to be an effective therapeutic target in ALS., INTERPRETATION\n\nOzanezumab did not show efficacy compared with placebo in patients with ALS., The adjusted mean of the joint-rank score was -14·9 (SE 13·5) for the ozanezumab group and 15·0 (13·6) for the placebo group, with a least squares mean difference of -30·0 (95% CI -67·9 to 7·9; p=0·12)., INTERPRETATION Ozanezumab did not show efficacy compared with placebo in patients with ALS., The adjusted mean of the joint-rank score was -14·9 (SE 13·5) for the ozanezumab group and 15·0 (13·6) for the placebo group, with a least squares mean difference of -30·0 (95% CI -67·9 to 7·9; p=0·12).[SEP]Relations: amyotrophic lateral sclerosis has relations: disease_protein with TIAM1, disease_protein with TIAM1, disease_protein with WNT7A, disease_protein with WNT7A, disease_protein with SLC6A1, disease_protein with SLC6A1, disease_protein with CHMP2B, disease_protein with CHMP2B, disease_protein with TMSB4X, disease_protein with TMSB4X.", "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]Relations: cytoplasmic microtubule has relations: cellcomp_protein with SPACA9, cellcomp_protein with SPACA9, cellcomp_protein with TOGARAM1, cellcomp_protein with TOGARAM1, cellcomp_protein with C4orf47, cellcomp_protein with C4orf47, cellcomp_protein with ARHGAP18, cellcomp_protein with ARHGAP18, cellcomp_protein with SYBU, cellcomp_protein with SYBU.", "label": "yes"}
{"id": "converted_3501", "sentence1": "Do MAIT cells have a role in multiple myeloma?", "sentence2": "hus, MAIT cells are reduced in MM patients, which may contribute to disease in these individuals, and moreover, MAIT cells may represent new immunotherapeutic targets for treatment of MM and other malignancies., Here we have analysed the frequency and function of MAIT cells in multiple myeloma (MM) patients. We show that MAIT cell frequency in blood is reduced compared to healthy adult donors, but comparable to elderly healthy control donors, Newly diagnosed MM patient MAIT cells had reduced IFNγ production and CD27 expression, suggesting an exhausted phenotype, although IFNγ-producing capacity is restored in relapsed/refractory patient samples. , We describe recent observations with regard to functional exhaustion of iNKT and MAIT cells in MM pathology and discuss the potential application of checkpoint inhibition as an attractive target for prolonged activation of these immunomodulatory T cells in the treatment of MM., Enumeration, functional responses and cytotoxic capacity of MAIT cells in newly diagnosed and relapsed multiple myeloma., Thus, MAIT cells are reduced in MM patients, which may contribute to disease in these individuals, and moreover, MAIT cells may represent new immunotherapeutic targets for treatment of MM and other malignancies.[SEP]Relations: Multiple myeloma has relations: disease_phenotype_positive with plasma cell myeloma, disease_phenotype_positive with plasma cell myeloma, drug_effect with Bortezomib, drug_effect with Bortezomib, drug_effect with Muromonab, drug_effect with Muromonab, drug_effect with Lenalidomide, drug_effect with Lenalidomide, drug_effect with Zoledronic acid, drug_effect with Zoledronic acid.", "label": "yes"}
{"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_1981", "sentence1": "Does the hERG gene code for a protein which is part of a sodium channel?", "sentence2": " The human ether-à-go-go-related gene (hERG 1a) potassium channel is critical for cardiac repolarization, Human ether-a-go-go-related gene (hERG) channels conduct delayed rectifier K(+) current. , The KvLQT1 and minK genes code the slowly activating, delayed rectifier (Iks) potassium channel, the HERG gene code the rapidly activating, delayed rectifier (Ikr) potassium channel of the heart, while the SCN5A gene codes a cardiac sodium channel., The molecular basis of inherited disorders caused by a mutation in either the gene coding for a particular potassium channel called HERG-or another gene, SCN5A, which codes for the sodium channel and disruption of which results in a loss of inactivation of the Na+ current., The aim of this study was to test whether a recently reported polymorphism in the HERG gene coding for the rapidly activating delayed rectifier K+ channel has influence on myocardial repolarization., Mutations in KvLQT1, minK and HERG genes affects repolarising, rectifier potassium currents, while SCN5A mutations cause delayed inactivation and reopening of the cardiac sodium channel, which initiates the depolarisation of cardiac cells., A human genetic defect associated with 'long Q-T syndrome', an abnormality of cardiac rhythm involving the repolarization of the action potential, was recently found to lie in the HERG gene, which codes for a potassium channel., Therefore, matrine and oxymatrine may have the potential to cure LQT2 as a potassium channel activator by promoting hERG channel activation and increasing hERG channel expression., The human delta1261 mutation of the HERG potassium channel results in a truncated protein that contains a subunit interaction domain and decreases the channel expression., HERG (human eag-related gene) encodes an inward-rectifier potassium channel formed by the assembly of four subunits., The human ether-?-go-go-related gene (HERG) encodes the pore-forming subunit of the rapidly activating delayed rectifier potassium channel in the heart., The human ether-a-go-go-related gene (hERG) encodes the rapidly activating, delayed rectifier potassium channel (IKr) important for cardiac repolarization., Role of glycosylation in cell surface expression and stability of HERG potassium channels., The human ERG protein (HERG or Kv 11.1) encoded by the human ether-a-go-go-related gene (herg) is the pore-forming subunit of the cardiac delayed rectifier potassium current (IKr) responsible for action potential (AP) repolarization, Human ether-a-go-go related gene (herg) encoding HERG K(+) channel has been demonstrated in many previous studies with its association to cell cycle progression and growth in tumor cells, A human genetic defect associated with 'long Q-T syndrome', an abnormality of cardiac rhythm involving the repolarization of the action potential, was recently found to lie in the HERG gene, which codes for a potassium channel. , Drug-induced long QT syndrome: hERG K+ channel block and disruption of protein trafficking by fluoxetine and norfluoxetine., OBJECTIVES: The aim of this study was to test whether a recently reported polymorphism in the HERG gene coding for the rapidly activating delayed rectifier K+ channel has influence on myocardial repolarization. , The aim of this study was to test whether the K897T polymorphism of the KCNH2 (HERG) gene coding for the rapidly activating delayed rectifier K+ channel influences cardiac repolarization assessed by principal component analysis (PCA) of T-wave morphology. , The KvLQT1 and minK genes code the slowly activating, delayed rectifier (Iks) potassium channel, the HERG gene code the rapidly activating, delayed rectifier (Ikr) potassium channel of the heart, while the SCN5A gene codes a cardiac sodium channel., All code for subunits of sodium or potassium channels: two a subunits of the potassium channels (QVLQT1 for LQT1, HERG for LQT2), the a subunit of the sodium channel INa (SCN5A for LQT3), and two regulatory subunits of potassium channels (KCNE1 for LQT5 regulating the KvLQT1 channel and MiRP1 regulating HERG)., The corresponding genes code for potassium channels KVLQT1 (LQT1) and HERG (LQT2) and the sodium channel SCN5A (LQT3)., The molecular basis of inherited disorders caused by a mutation in either the gene coding for a particular potassium channel called HERG-or another gene, SCN5A, which codes for the sodium channel and disruption of which results in a loss of inactivation of the Na+ current., There may also be correlation between the strength of binding of the medicinal substance to the potassium channel coded by the HERG gene and prolongation of the QT interval., We demonstrate that the mRNA 3'UTR of ppk29 affects neuronal firing rates and associated heat-induced seizures by acting as a natural antisense transcript (NAT) that regulates the neuronal mRNA levels of seizure (sei), the Drosophila homolog of the human Ether-à-go-go Related Gene (hERG) potassium channel., Mutations in KvLQT1, minK and HERG genes affects repolarising, rectifier potassium currents, while SCN5A mutations cause delayed inactivation and reopening of the cardiac sodium channel, which initiates the depolarisation of cardiac cells., Among the congenital forms, particularly interest is focused on the potassium channel coded by the HERG gene located on chromosome 7 and with a key role in the normal electric cardiac activity., By employing heterologous expression and making comparisons to cells expressing wild-type human-ether-a-go-go-related protein (HERG), a potassium channel that contributes to I(Kr) current in ventricular cardiomyocytes, we demonstrate activation of an elevated endoplasmic reticulum (ER) stress response by the mutant I593R HERG potassium channel implicated in long QT syndrome type 2., Correction of defective protein trafficking of a mutant HERG potassium channel in human long QT syndrome., Mutations in the human ether-à-go-go-related gene (HERG), which encodes a delayed-rectifier potassium channel,, s HERG and KvLQT1 potassium channel genes, HERG encodes the cardiac I(Kr) potassium channel., block of the cardiac potassium channel human ether-à-go-go-related gene (hERG) , The human ether-a-go-go-related gene (hERG) encodes the pore-forming α-subunit of the rapidly activating delayed rectifier K(+) channel in the heart, which plays a critical role in cardiac action potential repolarization. , Effects of donepezil on hERG potassium channels., Human ether-a-go-go related-gene K⁺ channels (hERG) participate in the regulation of tumor cell proliferation and apoptosis. HERG channel activity is up-regulated by growth factors,  hERG potassium channels, HERG, a K+ channel gene.[SEP]Relations: sodium channel complex has relations: cellcomp_protein with SCNN1G, cellcomp_protein with SCNN1G, cellcomp_protein with SCNN1B, cellcomp_protein with SCNN1B, cellcomp_protein with SCNN1D, cellcomp_protein with SCNN1D, cellcomp_protein with SCNN1A, cellcomp_protein with SCNN1A, cellcomp_protein with TRPM4, cellcomp_protein with TRPM4.", "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]Relations: Protein C has relations: drug_drug with Nonacog beta pegol, drug_drug with Nonacog beta pegol, drug_drug with Vatreptacog alfa, drug_drug with Vatreptacog alfa, drug_drug with Anagrelide, drug_drug with Anagrelide, drug_drug with Damoctocog alfa pegol, drug_drug with Damoctocog alfa pegol, drug_drug with Sarpogrelate, drug_drug with Sarpogrelate.", "label": "yes"}
{"id": "converted_1281", "sentence1": "Is TNNI3K a cardiac-specific protein?", "sentence2": "cardiomyocyte-specific kinase TNNI3K , We report that cardiac troponin I-interacting kinase (TNNI3K), a cardiomyocyte-specific kinase,, TNNI3K, a cardiac-specific kinase, ,  The cardiac troponin I-interacting kinase (TNNI3K), a novel cardiac specific kinase, is associated with cardiomyocyte hypertrophy, Human cardiac troponin I-interacting kinase (TNNI3K) is a novel cardiac-specific functional kinase that can bind to cTnI in a yeast two-hybrid screen. , Overexpression of TNNI3K, a cardiac-specific MAPKKK, promotes cardiac dysfunctio, Cardiac troponin I-interacting kinase (TNNI3K) is a cardiac-specific kinase whose biological function remains largely unknown,  Cardiac troponin I-interacting kinase (TNNI3K) is a novel cardiac-specific kinase gene,  a novel cardiac-specific kinase gene (TNNI3K),,  TNNI3K is a novel cardiac troponin I-interacting kinase gene and its overexpression may promote cardiac myogenesis, , TNNI3K is a new cardiac-specific MAP kinase whose gene is localized to 1p31.1 and that belongs to a tyrosine kinase-like branch in the kinase tree of the human genome., The cardiac ankyrin repeat kinase (CARK) gene, also named TNNI3K for its interaction with cardiac troponin I, is both a unique expression and heart-enriched gene, Molecular cloning of cardiac troponin I-interacting kinase (TNNI3K), a novel cardiac-specific protein kinase containing seven N-terminal ankyrin (ANK) repeats followed by a protein kinase domain and a C-terminal Ser-rich domain, has previously been reported.,  TNNI3K is highly expressed in heart, but is undetectable in other tissues. Immunohistochemical analysis predominantly localized TNNI3K in the nucleus of cardiac myocytes. [SEP]Relations: TNNI3K has relations: protein_protein with TNNI3, protein_protein with TNNI3, anatomy_protein_present with heart, anatomy_protein_present with heart, protein_protein with NFATC3, protein_protein with NFATC3, protein_protein with ACTC1, protein_protein with ACTC1, protein_protein with HADHB, protein_protein with HADHB.", "label": "yes"}
{"id": "converted_665", "sentence1": "Has overexpression of sirtuins been reported to increase lifespan in budding yeast (Saccharomyces cerevisiae)?", "sentence2": "In addition, Sir2 overexpression prevents Rif1 deletion from disrupting Sir2 at IGS1 and shortening lifespan. , Roles for sirtuin proteins at telomeres are thought to promote lifespan in yeast and mammals., Overexpression of sirtuins (NAD(+)-dependent protein deacetylases) has been reported to increase lifespan in budding yeast (Saccharomyces cerevisiae), When overexpressed, the NAD-dependent protein deacetylase Sir2 extends the lifespan of both budding yeast , When overexpressed in primary mouse embryo fibroblasts (MEFs), SIRT1 antagonizes PML-induced acetylation of p53 and rescues PML-mediated premature cellular senescence. [SEP]Relations: megaloblastic anemia (disease) has relations: contraindication with Phenytoin, contraindication with Phenytoin, contraindication with Primidone, contraindication with Primidone. NAD-dependent histone deacetylase activity has relations: molfunc_protein with SIRT1, molfunc_protein with SIRT1, molfunc_protein with SIRT2, molfunc_protein with SIRT2, molfunc_protein with SIRT3, molfunc_protein with SIRT3.", "label": "yes"}
{"id": "converted_3712", "sentence1": "Are stem cell transplants used to treat acute kidney injury?", "sentence2": "Animal studies have shown that mesenchymal stromal cell (MSC) infusions improve acute kidney injury (AKI) outcomes when administered early after ischemic/reperfusion injury or within 24 hours after cisplatin administration., Early Diagnostic Markers for Detection of Acute Kidney Injury in Allogeneic Hematopoietic Stem Cell Transplant Recipients., Risk assessment for acute kidney injury after allogeneic hematopoietic stem cell transplantation based on Acute Kidney Injury Network criteria.[SEP]Relations: acute kidney failure has relations: disease_disease with acute disease, disease_disease with acute disease, disease_disease with kidney failure, disease_disease with kidney failure, disease_disease with acute kidney tubular necrosis, disease_disease with acute kidney tubular necrosis, disease_protein with INS, disease_protein with INS. Cisplatin has relations: drug_effect with Acute kidney injury, drug_effect with Acute kidney injury.", "label": "yes"}
{"id": "converted_4416", "sentence1": "Is periampullary carcinoma (PAC) a relatively rare genitourinary malignancy", "sentence2": "Pancreaticobiliary subtype of Periampullary carcinoma (PAC) has a poor prognosis in comparison to the intestinal subtype., MUC1, CK20, and CDX2 immunohistochemical markers can sub-classify periampullary carcinomas into pancreaticobiliary, intestinal, and mixed subtypes., Pancreaticoduodenectomy (PD) is a complex surgical procedure involving resection of the duodenum, the pancreatic head and uncinate process, and the distal common bile duct. It is most commonly performed for periampullary malignancy but may also be indicated in select cases of chronic pancreatitis or benign periampullary tumors., In patients suspected of pancreatic or periampullary cancer, abdominal contrast-enhanced computed tomography (CT) is the standard diagnostic modality., The pre-operative neutrophil-to-lymphocyte ratio (NLR), when ≥5 has been associated with reduced survival for patients with various gastrointestinal tract cancers, however, it's prognostic value in patients with periampullary tumour has not been reported to date., Comparison Of Biliary Stenting And Surgical Bypass In Palliative Management Of Irresectable Periampullary Carcinoma.,  Some 20-40% of the periampullary carcinoma is irresectable at the time of diagnosis. Biliary stenting and surgical bypass are commonly used palliative procedure., Whereas Periampulary AdenoCarcinoma (PAC) having four anatomic subtypes, pancreatic, Common Bile Duct (CBD), ampullary and duodenum shows relative better prognosis, DEFINITION: Periampullary carcinomas are rare and constitute a special entity, as diagnosed earlier and having a better prognosis than other duodenal tumors.METHODS: In the present study, we retrospectively reviewed the medical records of 16 patients with periampullary carcinomas over 10 years.RESULTS: 16 patients, 10 men and 6 women (median age 66.7 years, range 42-80) had a , Periampullary carcinomas: a special entity of duodenal tumors., Periampullary adenocarcinomas are rare neoplasm that originates from the pancreatic head, the ampulla of vater, the distal bile duct or the duodenum.[SEP]Relations: periampullary adenocarcinoma has relations: disease_disease with ampulla of vater adenocarcinoma, disease_disease with ampulla of vater adenocarcinoma. intestine has relations: anatomy_protein_present with PACS2, anatomy_protein_present with PACS2, anatomy_protein_present with PACS1, anatomy_protein_present with PACS1, anatomy_protein_present with PACSIN2, anatomy_protein_present with PACSIN2. duodenum has relations: anatomy_protein_present with PACS1, anatomy_protein_present with PACS1.", "label": "no"}
{"id": "converted_2889", "sentence1": "Does Panitumumab prolong survival of biliary tract cancer patients?", "sentence2": "Panitumumab in combination with gemcitabine and oxaliplatin does not prolong survival in wild-type KRAS advanced biliary tract cancer: A randomized phase 2 trial (Vecti-BIL study)., CONCLUSIONS: Panitumumab in combination with chemotherapy does not improve ORR, PFS and OS in patients with KRAS wild-type, advanced biliary cancer. , No survival differences were observed: the median overall survival was 9.9 months in arm A and 10.2 months in arm B (P = .42). In a subgroup analysis, no differences in PFS according to the site of the primary tumor were observed; patients with intrahepatic cholangiocarcinoma treated with panitumumab may have had a survival benefit in comparison with the control group (15.1 vs 11.8 months, P = .13). , CONCLUSIONS\nPanitumumab in combination with chemotherapy does not improve ORR, PFS and OS in patients with KRAS wild-type, advanced biliary cancer., CONCLUSIONS Panitumumab in combination with chemotherapy does not improve ORR, PFS and OS in patients with KRAS wild-type, advanced biliary cancer., Despite many clinical trials being conducted with molecular targeted agents including erlotinib, cetuximab, panitumumab, bevacizumab, sorafenib, cediranib, trametinib and vandetanib, no agent has shown to be effective for advanced biliary tract cancer., Adding panitumumab to standard protocols does not prolong survival but provokes additional adverse effects.[SEP]Relations: biliary tract cancer has relations: disease_disease with liver cancer, disease_disease with liver cancer, disease_protein with PRKACB, disease_protein with PRKACB, disease_disease with bile duct cancer, disease_disease with bile duct cancer. Panitumumab has relations: drug_drug with Bimagrumab, drug_drug with Bimagrumab, drug_drug with Afelimomab, drug_drug with Afelimomab.", "label": "no"}
{"id": "converted_1550", "sentence1": "Is macitentan an ET agonist?", "sentence2": "Administration of an ET receptor antagonist, either bosentan or macitentan, markedly attenuated PD-induced MMT, fibrosis, angiogenesis, and peritoneal functional decline. , Macitentan is an oral, once-daily, dual endothelin (ET)A and ETB receptor antagonist with high affinity and sustained receptor binding that was approved in the USA, Europe, Canada, and Switzerland for the treatment of PAH., Macitentan (Opsumit®) is a novel dual endothelin receptor antagonist (ERA) with sustained receptor binding properties developed by Actelion Pharmaceuticals Ltd., Macitentan, also called Actelion-1 or ACT-064992 [N-[5-(4-bromophenyl)-6-(2-(5-bromopyrimidin-2-yloxy)ethoxy)-pyrimidin-4-yl]-N'-propylaminosulfonamide], is a new dual ET(A)/ET(B) endothelin (ET) receptor antagonist designed for tissue targeting. Selection of macitentan was based on inhibitory potency on both ET receptors and optimization of physicochemical properties to achieve high affinity for lipophilic milieu. In vivo, macitentan is metabolized into a major and pharmacologically active metabolite, ACT-132577. , Macitentan and its metabolite antagonized the specific binding of ET-1 on membranes of cells overexpressing ET(A) and ET(B) receptors and blunted ET-1-induced calcium mobilization in various natural cell lines, with inhibitory constants within the nanomolar range. In functional assays, macitentan and ACT-132577 inhibited ET-1-induced contractions in isolated endothelium-denuded rat aorta (ET(A) receptors) and sarafotoxin S6c-induced contractions in isolated rat trachea (ET(B) receptors). In rats with pulmonary hypertension, macitentan prevented both the increase of pulmonary pressure and the right ventricle hypertrophy, and it markedly improved survival. , In conclusion, macitentan, by its tissue-targeting properties and dual antagonism of ET receptors, protects against end-organ damage in diabetes and improves survival in pulmonary hypertensive rats. This profile makes macitentan a new agent to treat cardiovascular disorders associated with chronic tissue ET system activation., Pharmacology of macitentan, an orally active tissue-targeting dual endothelin receptor antagonist., Renal, retinal and cardiac changes in type 2 diabetes are attenuated by macitentan, a dual endothelin receptor antagonist., Here we investigated the effects of macitentan, an orally-active, tissue-targeting dual ET receptor antagonist on chronic complications in type 2 diabetes.MAIN METHODS: db/db mice and their age- and sex-matched controls were examined after 2 and 4 months of diabetes. , Macitentan is a novel dual ETA/ETB receptor antagonist with enhanced tissue distribution and sustained receptor binding properties designed to achieve a more efficacious ET receptor blockade. , Recently oral prostacyclin receptor agonists have shown encouraging results. Many clinical studies targeting the vasoconstrictor ET-1 pathway with receptor antagonists like bosentan and ambrisentan have shown strong results, even more optimism coming from macitentan, the newest drug.[SEP]Relations: Macitentan has relations: drug_drug with Etomidate, drug_drug with Etomidate, drug_drug with Inotersen, drug_drug with Inotersen, drug_drug with Pitolisant, drug_drug with Pitolisant, drug_drug with Antipyrine, drug_drug with Antipyrine, drug_drug with Etoperidone, drug_drug with Etoperidone.", "label": "no"}
{"id": "converted_1478", "sentence1": "Is Titin the largest single protein molecule found in Nature?", "sentence2": "Titin, the largest protein in the human body, is well known as a molecular spring in muscle cells and scaffold protein aiding myofibrillar assembly., Titin is the largest protein in mammals; it forms an elastic filament along the myofibril of cardiac and skeletal muscles., Titin is recently known as the largest protein which exists in the striated muscle sarcomere and is dynamic both in biomechanics properties and biochemical functions. , Titin, the largest protein known to date, has been linked to sarcomere assembly and function through its elastic adaptor and signaling domains., The giant sarcomere protein titin/connectin is the largest protein known to date., Titin is the largest protein known to date and acts as a mechanosensor that regulates muscle protein expression in a sarcomere strain-dependent fashion., Titin is the largest protein known, and is essential for organising muscle sarcomeres., It has many domains with a variety of functions, and stretches from the Z-line to the M-line in the muscle sarcomere. , Titin, is definitely the largest protein in the body, with a molecular weight of 3 million Dalton and composed of 27,000 amino acids., Titin, the largest protein identified to date (over 1 micron long, almost 3 million daltons in mass) is the third most abundant component of the sarcomere., Titin is the largest polypeptide yet described (relative molecular mass approximately 3 x 10(6); refs 1, 2) and an abundant protein of striated muscle., Titin is at present the largest known protein (M(r) 3000 kDa) and its expression is restricted to vertebrate striated muscle., Titin is the largest protein known, and is essential for organising muscle sarcomeres, Titin is at present the largest known protein (M(r) 3000 kDa) and its expression is restricted to vertebrate striated muscle, Titin is the largest polypeptide yet described (relative molecular mass approximately 3 x 10(6); refs 1, 2) and an abundant protein of striated muscle, Titin is recently known as the largest protein which exists in the striated muscle sarcomere and is dynamic both in biomechanics properties and biochemical functions, Titin, the biggest single (poly) peptide found in humans, and throughout nature so far, was long considered as a good candidate for inherited muscle diseases[SEP]Relations: Protein C has relations: drug_drug with Ticlopidine, drug_drug with Ticlopidine, drug_drug with Tirofiban, drug_drug with Tirofiban, drug_drug with Tibolone, drug_drug with Tibolone, drug_drug with Ticagrelor, drug_drug with Ticagrelor, drug_drug with Tioguanine, drug_drug with Tioguanine.", "label": "yes"}
{"id": "converted_1758", "sentence1": "Has Glucose-6-phosphate dehydrogenase (G6PD) deficiency an X-linked inheritance?", "sentence2": "Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the commonest red cell enzymopathy in humans and has an X-linked inheritance. , This genetic defect shows sex linked inheritance and a marked heterogeneity., G6PD deficiency is the most common enzymopathy in the world. , Study of the deficiency pattern amongst family members of the enzyme deficient subjects confirmed the X-linked inheritance of G-6-PD deficiency., This was caused by Glucose-6-Phosphate-Dehydrogenase-Deficiency, which could be demonstrated by a red-cell-enzyme analysis. The investigation of the patient's whole family showed the typical recessive X-linked inheritance of this enzyme-defect. Frequency and clinical manifestations of this defect are discussed., After having described in detail the pathophysiology, symptomatology, X-chromosomal inheritance and some laboratory methods in detecting G-6-PD-deficiency by demonstrating a case of favism (Schulz et al. 1977), the authors now discuss the particularities of the enzyme deficiency in the newborn. , Severe red cell glucose-6-phosphate dehydrogenase (G-6-PD) deficiency has been found in an 'aboriginal' Finnish family. 2 male and 9 female carriers of the variant G-6-PD were studied. The genetic pattern is consistent with x-linked recessive inheritance and the defect is associated with drug (primaquine) induced haemolysis., Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the commonest red cell enzymopathy in humans and has an X-linked inheritance., X-linked glucose-6-phosphate dehydrogenase deficiency in Mus musculus., Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a common X-linked enzyme defect., Glucose-6-phosphate dehydrogenase deficiency is an X-linked recessive hereditary disease characterised by abnormally low levels of G6PD., UNLABELLED: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked recessive disorder in which haemolytic anaemia is the major symptom., Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most frequent enzyme deficiency., Glucose-6-phosphate dehydrogenase (G6PD) deficiency is transmitted as an X-linked recessive disorder, and thus female infants are expected to be only rarely affected., Erythrocytic glucose-6-phosphate dehydrogenase (G6PD) of a mutant mouse strain with X-linked G6PD-deficiency was purified and compared with the wildtype G6PD by biochemical and physiological characteristics., A mouse with X-linked glucose-6-phosphate dehydrogenase (G6PD) deficiency has been recovered in offspring of 1-ethyl-1-nitrosourea-treated male mice., Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the commonest red cell enzymopathy in humans and has an X-linked inheritance, Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked recessive hemolytic anemia caused by a mutation in the G6PD gene on Xq28, Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked recessive genetic defect that can cause hemolytic crisis, Glucose-6-phosphate-dehydrogenase (G6PD) deficiency is an X-linked genetic defect, affecting around 400 million people worldwide and is characterized by considerable biochemical and molecular heterogeneity, Glucose-6-phosphate dehydrogenase deficiency (G6PD) is an X-linked genetic disorder with a relatively high frequency in malaria-endemic regions, Glucose-6-phosphate dehydrogenase deficiency (G6PD) is the most common enzyme pathology in humans; it is X-linked inherited and causes neonatal hyperbilirubinaemia, chronic nonspherocytic haemolytic anaemia and drug-induced acute haemolytic anaemia, Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked hereditary disease that predisposes red blood cells to oxidative damage, Glucose-6-phosphate dehydrogenase (G6PD) deficiency is one of the most common human genetic abnormalities, and it has a significant prevalence in the male population (X chromosome linked), Glucose-6-phosphate dehydrogenase (G6PD) deficiency, a common X-linked enzymopathy can lead to severe hyperbilirubinemia, acute bilirubin encephalopathy and kernicterus in the United States, Glucose-6-phosphate dehydrogenase deficiency (G6PD), an x-linked inherited enzymopathy, is a barrier to malaria control because primaquine cannot be readily applied for radical cure in individuals with the condition, G6PD deficiency has an x-linked pattern of inheritance in which hemizygous males are deficient, while females may or may not be deficient depending on the number of affected alleles., Phenotype frequencies and family data verified the X-linked inheritance of the G6PD polymorphism., BACKGROUND: Glucose-6-phosphate dehydrogenase (G6PD) is a metabolic enzyme involved in the pentose phosphate pathway, its especially important in red blood cell metabolism. Glucose-6-phosphate dehydrogenase deficiency is an X-linked recessive hereditary disease characterised by abnormally low levels of G6PD., BACKGROUND: Glucose-6-phosphate dehydrogenase (G6PD) is a metabolic enzyme involved in the pentose phosphate pathway, its especially important in red blood cell metabolism. Glucose-6-phosphate dehydrogenase deficiency is an X-linked recessive hereditary disease characterised by abnormally low levels of G6PD. About 400 million people worldwide have a deficiency of this enzyme., Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a common X-linked enzyme defect. We report a new variant, G6PD Durham713G, that is associated with chronic nonspherocytic hemolytic anemia., Glucose-6-phosphate dehydrogenase (G6PD) deficiency is one of the most common human genetic abnormalities, and it has a significant prevalence in the male population (X chromosome linked)., The human X-linked gene encoding glucose 6-phosphate dehydrogenase (G6PD) is highly polymorphic; more than 300 G6PD variants have been identified., Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked incompletely dominant enzyme deficiency that results from G6PD gene mutations., Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked recessive genetic defect that can cause hemolytic crisis., Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked recessive hemolytic anemia caused by a mutation in the G6PD gene on Xq28., Glucose-6-phosphate dehydrogenase deficiency is an X-linked recessive hereditary disease characterised by abnormally low levels of G6PD., X-linked glucose-6-phosphate dehydrogenase (G6PD) and autosomal 6-phosphogluconate dehydrogenase (6PGD) polymorphisms in baboons., X-linked glucose-6-phosphate dehydrogenase deficiency in Mus musculus., Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked recessive disorder in which haemolytic anaemia is the major symptom.[SEP]Relations: G6PD has relations: molfunc_protein with glucose-6-phosphate dehydrogenase activity, molfunc_protein with glucose-6-phosphate dehydrogenase activity, disease_protein with G6PD deficiency, disease_protein with G6PD deficiency, disease_protein with galactosemia, disease_protein with galactosemia, disease_protein with malaria, disease_protein with malaria. glucose-6-phosphate dehydrogenase-like has relations: disease_disease with Mendelian disease, disease_disease with Mendelian disease.", "label": "yes"}
{"id": "converted_4261", "sentence1": "Is Lysozyme abundant in human tears?", "sentence2": "lysozyme present in the natural tear, Lysozyme (Lyz) is a naturally occurring enzyme that operates against Gram-positive bacteria and leads to cell death. This antimicrobial enzyme forms the part of the innate defense system of nearly all animals and exists in their somatic discharges such as milk, tears, saliva and urine., tear lysozyme, lysozyme in tears, saliva, sweat, and other body fluids, , In this study we quantify lysozyme, the most prevalent protein in tear fluid, , Lysozyme (LZM) is a natural anti-bacterial protein that is found in the saliva, tears and milk of all mammals including humans. [SEP]Relations: Protein C has relations: drug_drug with Factor IX Complex (Human), drug_drug with Factor IX Complex (Human), drug_drug with Factor XIII (human), drug_drug with Factor XIII (human), drug_drug with Antihemophilic factor human, drug_drug with Antihemophilic factor human, drug_drug with Von Willebrand Factor Human, drug_drug with Von Willebrand Factor Human, drug_drug with Chlorotrianisene, drug_drug with Chlorotrianisene.", "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_1370", "sentence1": "Are nucleosomes positioned at DNA replication origins?", "sentence2": "yeast origins are characterized by an asymmetric pattern of positioned nucleosomes flanking the ACS. The origin sequences are sufficient to maintain a nucleosome-free origin; however, ORC is required for the precise positioning of nucleosomes flanking the origin., Here, we identify nucleosome occupancy as a likely candidate to set up ORI distribution, we demonstrate that open chromatin domains, characterized by nucleosome depletion, are preferentially permissive for replication, Nucleosome assembly of the template prevented DNA replication. Replication of chromosomes was severely inhibited at more than two-thirds of physiological nucleosome density[SEP]Relations: nucleosome assembly has relations: bioprocess_bioprocess with DNA replication-dependent nucleosome assembly, bioprocess_bioprocess with DNA replication-dependent nucleosome assembly, bioprocess_protein with SET, bioprocess_protein with SET, bioprocess_bioprocess with DNA replication-independent nucleosome assembly, bioprocess_bioprocess with DNA replication-independent nucleosome assembly, bioprocess_protein with SETSIP, bioprocess_protein with SETSIP, bioprocess_protein with NPM1, bioprocess_protein with NPM1.", "label": "no"}
{"id": "converted_4483", "sentence1": "Is resistance training usually associated with increasing muscle hypertrophy?", "sentence2": "While traditional resistance exercises have been widely used to promote muscle strength and hypertrophy in the elderly, ,  These findings suggest that in young untrained men, progressing from a training frequency of once per week to a training frequency of 5 times per week with equated volume produces similar gains in LBM and muscle strength as a constant training frequency of once per week, over an 8-week training period., Resistance training is one of the effective methods to overcome a decline in muscle mass,, Therefore, in RT prescription for elbow flexors hypertrophy, single-joint exercises such as BC should be emphasized, Our studies establish that resistance training in older adults with type 2 diabetes results in muscle fiber hypertrophy, despite a greater accumulation of inflammatory cytokine transcripts in muscle., Resistance training results in muscle hypertrophy and improves glycemic control in patients with type 2 diabetes., Resistance training (RT) is a popular method of conditioning to enhance sport performance as well as an effective form of exercise to attenuate the age-mediated decline in muscle strength and mass., Enzyme activities, reflecting oxidative potential; decrease during long-term heavy resistance training, resulting in muscle hypertrophy., Optimal adaptations to resistance training (muscle hypertrophy and strength increases) also seem to occur in the late afternoon, which is interesting, since cortisol and, particularly, testosterone (T) concentrations are higher in the morning., Heavy resistance training is associated with increased body weight, lean body mass, and muscle cross-sectional area., The implications for this are (a) athletes are advised to coincide training times with performance times, and (b) individuals may experience greater hypertrophy and strength gains when resistance training protocols are designed dependent on individual T response., Therefore, the combination of resistance training and overexpression of IGF-I induced greater hypertrophy than either treatment alone., The intake of protein after resistance training increases plasma amino acids, which results in the activation of signaling molecules leading to increased muscle protein synthesis (MPS) and muscle hypertrophy., The rate and amount of muscle hypertrophy associated with resistance training is influenced by a wide array of variables including the training program, plus training experience, gender, genetic predisposition, and nutritional status of the individual., Resistance training is commonly prescribed to enhance strength/power qualities and is achieved via improved neuromuscular recruitment, fiber type transition, and/ or skeletal muscle hypertrophy., The mechanisms responsible for the changes in basal post-absorptive protein turnover and its impact on muscle hypertrophy following resistance exercise training are unknown., It has been proposed that protein supplementation during resistance exercise training enhances muscle hypertrophy., BACKGROUND: Effects of resistance training on muscle strength and hypertrophy are well established in adults and younger elderly., Chronic resistance training induces increases in muscle fibre cross-sectional area (CSA), otherwise known as hypertrophy. , Resistance training of healthy young men typically results in muscle hypertrophy and a shift in vastus lateralis composition away from type IIx fibers to an increase in IIa fiber content, In resistance training, it has been empirically accepted that muscle hypertrophy is developed by low intensity and high volume training, while muscle strength and power are developed by high intensity and low volume training. , gh intensity resistance training (HIRT) has led to increased protein synthesis, along with muscle hypertrophy measured at the whole body, whole muscle, and muscle fibre levels, in older adults. Typica, t has been well documented that the increase in strength over the first few weeks of resistance training (i.e. acute) has a strong underlying neural component and further enhancement in strength with long-term (i.e. chronic) resistance training is due to muscle hypertrophy. For, Low-intensity blood flow restricted (LI-BFR) resistance training has been shown to produce comparable increases in muscle hypertrophy to traditional high-intensity (HI) resistance training. Ho, r adaptations caused by resistance training include increased cross-sectional area of the muscle (hypertrophy, hyperplasia, or both), selective hypertrophy of fast twitch fibers, decreased or maintained mitochondrial number and capillary density of muscle, and possible changes in energy sources. Changes in nerv, Skeletal muscle hypertrophy following resistance training is accompanied by a fiber type-specific increase in satellite cell content in elderly men, High-intensity resistance (HIR) training has been associated with muscle hypertrophy and decreased microvascular density that might produce a blood flow limitation. , The rate and amount of muscle hypertrophy associated with resistance training is influenced by a wide array of variables including the training program, plus training experience, gender, genetic predisposition, and nutritional status of the individual, CONCLUSION: The results of this study suggest that pBFR can stimulate muscle hypertrophy to the same degree to that of high-intensity resistance trainin, It is universally accepted that resistance training promotes increases in muscle strength and hypertrophy in younger and older populations, Resistance training (RT) is a popular method of conditioning to enhance sport performance as well as an effective form of exercise to attenuate the age-mediated decline in muscle strength and mass, Resistance training of healthy young men typically results in muscle hypertrophy and a shift in vastus lateralis composition away from type IIx fibers to an increase in IIa fiber content., Resistance training increases muscle size (i.e., causes hypertrophy) and muscle strength, particularly in untrained individuals., Hypertrophy is widely believed to be one of the mechanisms (i.e., a mediator) by which resistance training increases strength., Chronic resistance training induces increases in muscle fibre cross-sectional area (CSA), otherwise known as hypertrophy., The aim of the study was to determine whether it is possible to improve both maximum and rapid force production using resistance training that is typically used to induce muscle hypertrophy in previously untrained older men., Is an Energy Surplus Required to Maximize Skeletal Muscle Hypertrophy Associated With Resistance Training., We conclude that resistance training of prediabetic obese subjects is effective at changing muscle, resulting in fiber hypertrophy and increased type IIx fiber content, and these changes continue up to 16 wk of training.NEW & NOTEWORTHY Obese, insulin-resistant men responded to 16 wk of progressive resistance training with muscle hypertrophy and increased strength and a shift in muscle fiber composition toward fast-twitch, type IIx fibers., BACKGROUND: Effects of resistance training on muscle strength and hypertrophy are well established in adults and youn, Increments in the cross-sectional area of muscle after resistance training can be primarily attributed to fibre hypertrophy., However, no data are reported in the literature to describe and compare the efficacy of the different hypertrophic resistance training strategies in hypoxia.Moreover, improvements in sprinting, jumping, or throwing performance have also been described at terrestrial altitude, encouraging research into the speed of explosive movements at altitude., We conclude that a program of resistance exercise can be safely carried out by elderly women, such a program significantly increases muscle strength, and such gains are due, at least in part, to muscle hypertrophy.[SEP]Relations: Skeletal muscle hypertrophy has relations: phenotype_phenotype with Generalized muscle hypertrophy, phenotype_phenotype with Generalized muscle hypertrophy, phenotype_phenotype with Muscle hypertrophy of the lower extremities, phenotype_phenotype with Muscle hypertrophy of the lower extremities, disease_phenotype_positive with rippling muscle disease, disease_phenotype_positive with rippling muscle disease, disease_phenotype_positive with myostatin-related muscle hypertrophy, disease_phenotype_positive with myostatin-related muscle hypertrophy, phenotype_phenotype with Marked muscular hypertrophy, phenotype_phenotype with Marked muscular hypertrophy.", "label": "yes"}
{"id": "converted_4655", "sentence1": "Is Erythropoietin effective for neuroprotection of Preterm Infants.", "sentence2": "BACKGROUND: High-dose erythropoietin has been shown to have a neuroprotective effect in preclinical models of neonatal brain injury, and phase 2 trials have suggested possible efficacy; however, the benefits and safety of this therapy in extremely preterm infants have not been established., There was no significant difference between the erythropoietin group and the placebo group in the incidence of death or severe neurodevelopmental impairment at 2 years of age (97 children [26%] vs. 94 children [26%]; relative risk, 1.03; 95% confidence interval, 0.81 to 1.32; P = 0.80). There were no significant differences between the groups in the rates of retinopathy of prematurity, intracranial hemorrhage, sepsis, necrotizing enterocolitis, bronchopulmonary dysplasia, or death or in the frequency of serious adverse events.CONCLUSIONS: High-dose erythropoietin treatment administered to extremely preterm infants from 24 hours after birth through 32 weeks of postmenstrual age did not result in a lower risk of severe neurodevelopmental impairment or death at 2 years of age., Based on existing evidence, it is still too early to recommend Epo as the standard treatment for preterm brain injury., Erythropoietin treatment of preterm infants did not result in neuroprotection at 2 years of age in two out of three published large randomized controlled trials; however, long-term follow-up of these infants is needed to come to definite conclusions.[SEP]Relations: Erythropoietin has relations: drug_effect with Pruritus, drug_effect with Pruritus, drug_effect with Pruritus, drug_effect with Pruritus, drug_drug with Prednimustine, drug_drug with Prednimustine, drug_drug with Prednimustine, drug_drug with Prednimustine, drug_drug with Transcrocetinate, drug_drug with Transcrocetinate.", "label": "no"}
{"id": "converted_3928", "sentence1": "Is the Apis mellifera genome available?", "sentence2": " Mining Apis mellifera sequences made it possible to identify the honey bee subspecies both at the mitochondrial and nuclear genome levels., Honey bee research is believed to be influenced dramatically by colony collapse disorder (CCD) and the sequenced genome release in 2006, but this assertion has never been tested.,  The genome release and CCD had quantitively only minor effects, mainly on honey bee health-related topics post-2006. , We show that the honeybee genome is structured with respect to plasticity; genes that respond to an environmental trigger are colocated in the honeybee genome in a series of gene clusters, many of which have been assembled in the last 80 My during the evolution of the Apidae. , we have mined histone methyltransferases and demethylases from the whole genome sequence of Aedes aegypti (Diptera), the pea aphid Acyrthosiphon pisum, the triatomid bug Rhodnius prolixus (Hemiptera), the honeybee Apis mellifera (Hymenoptera),[SEP]Relations: mitochondrion has relations: cellcomp_protein with MSRA, cellcomp_protein with MSRA, cellcomp_protein with IBA57, cellcomp_protein with IBA57, cellcomp_protein with RXRA, cellcomp_protein with RXRA, cellcomp_protein with DIP2A, cellcomp_protein with DIP2A, cellcomp_protein with TEX10, cellcomp_protein with TEX10.", "label": "yes"}
{"id": "converted_297", "sentence1": "Are cyclophilins proteins that bind to prolines?", "sentence2": "Cyclophilins are ubiquitously expressed proteins that bind to prolines and can catalyse cis/trans isomerization of proline residues., a characteristic of the cyclophilin family of proteins that bind prolines and often act as cis-trans peptidyl-prolyl isomerases. , The cyclophilins are widely expressed enzymes that catalyze the interconversion of the cis and trans peptide bonds of prolines. ,  an immunophilin on the isomerization of critical prolines that are found in the tCHT1 sequence.[SEP]Relations: Protein S human has relations: drug_protein with PROC, drug_protein with PROC, drug_drug with Proglumetacin, drug_drug with Proglumetacin, drug_drug with Procarbazine, drug_drug with Procarbazine, drug_drug with Doxycycline, drug_drug with Doxycycline, drug_drug with Progesterone, drug_drug with Progesterone.", "label": "yes"}
{"id": "converted_1272", "sentence1": "Is curcumin a phytochemical?", "sentence2": "we analyzed turmeric from different agroclimatic regions for influence of various factors on its growth and yield of important phytochemicals, The phytochemical, curcumin, has been reported to play many beneficial roles., Curcumin (CUR), the major component in Curcuma longa, has been shown as a potent chemopreventive phytochemical that modulates various signaling pathways. , Curcumin (CUR) is a phytochemical that inhibits the xenobiotic ABC efflux transporters implicated in cancer multidrug resistance (MDR), such as P-glycoprotein (P-gp), breast cancer resistance protein (BCRP) and multidrug resistance-associated proteins 1 and 5 (MRP1 and MRP5). , In this study, we tested the efficacy of combining temozolomide with curcumin, a phytochemical known to inhibit glioblastoma growth, and investigated the mechanisms involved.,  In the present study, we investigate whether curcumin (cur), a phytochemical compound with potent anti-inflammatory effect, the Phytochemicals Curcumin , in combination with the phytochemicals curcumin and quercetin, Curcumin is a phytochemical derived from rhizome of turmeric Curcuma longa, present in the curry spice. , Curcumin, a naturally occurring polyphenolic phytochemical isolated from the medicinal plant Curcuma longa, has anti-inflammatory activities, In the present study curcumin (CUR), a known anticancer phytochemical, ,  Curcumin, a natural phytochemical, exhibits potent anticancer activities., hat curcumin, a phytochemical compound with potent anti-inflammatory properties , curcumin, a phytochemical[SEP]Relations: Curcumin has relations: drug_drug with Colchicine, drug_drug with Colchicine, drug_drug with Pemigatinib, drug_drug with Pemigatinib, drug_drug with Pretomanid, drug_drug with Pretomanid, drug_drug with Lumateperone, drug_drug with Lumateperone, drug_drug with Lefamulin, drug_drug with Lefamulin.", "label": "yes"}
{"id": "converted_1491", "sentence1": "Is there any research that relates the function of Notch Signaling with Alzheimer Disease?", "sentence2": "RIP regulates signaling pathways by abrogating or releasing signaling molecules. Since the discovery, already >15 years ago, of its catalytic component, presenilin, and even much earlier with the identification of amyloid precursor protein as its first substrate, γ-secretase has been commonly associated with Alzheimer's disease. However, starting with Notch and thereafter a continuously increasing number of novel substrates, γ-secretase is becoming linked to an equally broader range of biological processes., In the last decade, increasing evidence has pointed out an important role of this pathway beyond embryonic development, indicating that Notch also displays a critical function in the mature brain of vertebrates and invertebrates. This pathway appears to be involved in neural progenitor regulation, neuronal connectivity, synaptic plasticity and learning/memory. In addition, Notch appears to be aberrantly regulated in neurodegenerative diseases, including Alzheimer's disease and ischemic injury, Along with β-secretase, this enzyme produces the amyloid β-protein of Alzheimer's disease (AD) from the amyloid β-protein precursor. Because of its key role in the pathogenesis of AD, γ-secretase has been a prime target for drug discovery, and many inhibitors of this protease have been developed. The therapeutic potential of these inhibitors is virtually negated by the fact that γ-secretase is an essential part of the Notch signaling pathway, rendering the compounds unacceptably toxic upon chronic exposure, High physiological concentrations of Aβ monomer induced angiogenesis by a conserved mechanism that blocks γ-secretase processing of a Notch intermediate, NEXT, and reduces the expression of downstream Notch target genes. Our findings allude to an integration of signaling pathways that utilize γ-secretase activity, which may have significant implications for our understanding of Alzheimer's pathogenesis vis-à-vis vascular changes that set the stage for ensuing neurodegeneration., Aggregated forms of Aβ have a pathogenic role in Alzheimer disease and, thus, reducing the Aβ levels by inhibiting γ-secretase is a possible treatment strategy for Alzheimer disease. Regrettably, clinical trials have shown that inhibition of γ-secretase results in Notch-related side effects. Therefore, it is of great importance to find ways to inhibit amyloid precursor protein (APP) processing without disturbing vital signaling pathways such as Notch. Nicastrin (Nct) is part of the γ-secretase complex and has been proposed to be involved in substrate recognition and selection[SEP]Relations: Alzheimer disease has relations: disease_disease with genetic dementia, disease_disease with genetic dementia, disease_disease with dementia (disease), disease_disease with dementia (disease), disease_protein with GAPDHS, disease_protein with GAPDHS, disease_disease with familial Alzheimer disease, disease_disease with familial Alzheimer disease, disease_protein with ARC, disease_protein with ARC.", "label": "yes"}
{"id": "converted_44", "sentence1": "Does BNP increase after intensive exercise in athletes?", "sentence2": "NT-pro-BNP was significantly elevated postexercise in both adults and adolescents and remained above baseline at 24 h in both groups., NT-pro-BNP concentrations increased significantly (28 +/- 17.1 vs 795 +/- 823 ng x L, P < 0.05), whereas postrace cTnT were elevated in just five athletes (20%)., [NT-pro-BNP] was observed immediately after the marathon (median [NT-pro-BNP] before: 39.6 pg ml(-1), after: 138.6 pg ml(-1), p=0.003) with a further increase on day one. [BNP] did not increase immediately after the marathon but increased on day one (median [BNP] before: 15 pg ml(-1), day one: 27.35 pg ml(-1), p=0.006)., Pro-BNP was significantly increased immediately post-race (27+/-21 vs 7+/-2 pmol/L pre-race, P < or = 0.007), which 12-24 h later, decreased to 19+/-14 pmol/L (P = 0.07 vs pre-race)., The relatively high NT-proBNP levels after active recovery when psychophysical stress is higher, because of cycling and cold water immersion, suggest that not only endurance exercise, but also strenuous, stressful short exercise can induce an increase in NT-proBNP concentrations., Running a marathon significantly increases NT-pro-BNP levels in healthy adults. This increase could be partially attributed to cardiac stress., Increases in NT-proBNP can be found in a major part of obviously healthy athletes after prolonged strenuous exercise. The release of BNP during and after exercise may not result from myocardial damage but may have cytoprotective and growth-regulating effects. The different nature of exercise-induced increases in BNP and cardiac troponins has to be elucidated in the future., In healthy cyclists, transient increases in NT-pro-BNP and cTnT are more likely to reflect cardiac fatigue than injury., The rise in BNP in older athletes may reflect a reversible, mainly diastolic left ventricular dysfunction. , Plasma BNP concentrations were higher in both the judo and marathon groups than in controls, and positively correlated with LV mass as well as with deceleration time., Such exercise significantly increased ANP and BNP levels in healthy men, and the increases could be partially attributed to myocardial damage during the race.[SEP]Relations: Nesiritide has relations: drug_effect with Ventricular extrasystoles, drug_effect with Ventricular extrasystoles, contraindication with hypertrophic cardiomyopathy, contraindication with hypertrophic cardiomyopathy, drug_effect with Renal insufficiency, drug_effect with Renal insufficiency, drug_effect with Ventricular arrhythmia, drug_effect with Ventricular arrhythmia. Abnormal A-type atrial natriuretic peptide level has relations: phenotype_phenotype with Increased circulating A-type natriuretic peptide level, phenotype_phenotype with Increased circulating A-type natriuretic peptide level.", "label": "yes"}
{"id": "converted_1652", "sentence1": "Is cardiac magnetic resonance imaging indicated in the pre-participation screening of athletes?", "sentence2": "As modern imaging further enhances our understanding of the spectrum of athlete's heart, its role may expand from the assessment of athletes with suspected disease to being part of comprehensive pre-participation screening in apparently healthy athletes., Finally we will address the role of CMR in pre-participation screening.[SEP]", "label": "no"}
{"id": "converted_4283", "sentence1": "Is AZD9668 a VEGF mRNA drug?", "sentence2": "AZD9668, a neutrophil elastase inhibitor, plus ongoing budesonide/formoterol in patients with COPD., AZD9668 is a reversible and selective inhibitor of NE, well tolerated at doses of 60 mg bid during Phase I/IIa development.[SEP]Relations: ELANE has relations: protein_protein with AZU1, protein_protein with AZU1, drug_protein with Pegfilgrastim, drug_protein with Pegfilgrastim, protein_protein with NOTCH2NLA, protein_protein with NOTCH2NLA, drug_protein with Mdl 101,146, drug_protein with Mdl 101,146. chronic obstructive pulmonary disease has relations: disease_protein with MIR218-2, disease_protein with MIR218-2.", "label": "no"}
{"id": "converted_3047", "sentence1": "Is there any approved treatment for NAFLD?", "sentence2": "Non-alcoholic fatty liver disease (NAFLD) is the leading chronic hepatic condition worldwide and new approaches to management and treatment are limited., Non-alcoholic fatty liver disease (NAFLD) has become one of the most prominent forms of chronic liver disease worldwide, reflecting the epidemic of global obesity. Those with the progressive variant of NAFLD, non-alcoholic steatohepatitis (NASH), are at significantly increased risk of multisystem morbidity and mortality. However, there are currently no approved pharmacologic therapies for NASH., Although much progress has been made in enhancing our understanding of NAFLD pathogenesis, development of pharmacologic treatments has been hindered by challenges in clinical trial enrollment and complexities in clinical trial design. , Nonalcoholic fatty liver disease (NAFLD) is the most prevalent liver disease worldwide, and there is no approved pharmacotherapy., Nonalcoholic fatty liver disease (NAFLD) has an increasing prevalence worldwide. At present, no specific pharmacotherapy is approved for NAFLD. [SEP]Relations: non-alcoholic steatohepatitis has relations: contraindication with Efavirenz, contraindication with Efavirenz, contraindication with Zidovudine, contraindication with Zidovudine, contraindication with Entecavir, contraindication with Entecavir, contraindication with Tenofovir disoproxil, contraindication with Tenofovir disoproxil, contraindication with Abacavir, contraindication with Abacavir.", "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]Relations: Vorinostat has relations: drug_effect with Cholecystitis, drug_effect with Cholecystitis, drug_effect with Erythroderma, drug_effect with Erythroderma, drug_effect with T-cell lymphoma, drug_effect with T-cell lymphoma, drug_drug with Entinostat, drug_drug with Entinostat, drug_effect with Xerostomia, drug_effect with Xerostomia.", "label": "no"}
{"id": "converted_1604", "sentence1": "Are pseudogenes enriched with housekeeping protein families?", "sentence2": "housekeeping families tend to be enriched with a large number of pseudogenes[SEP]", "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_3357", "sentence1": "Is SARS virus interacting with ACE2 encoded protein?", "sentence2": "The trimeric SARS coronavirus (SARS-CoV) surface spike (S) glycoprotein consisting of three S1-S2 heterodimers binds the cellular receptor angiotensin-converting enzyme 2 (ACE2) and mediates fusion of the viral and cellular membranes through a pre- to postfusion conformation transition, The viral spike glycoprotein (S) utilizes angiotensin-converting enzyme 2 (ACE2) as a host protein receptor and mediates fusion of the viral and host membranes, making S essential to viral entry into host cells and host species tropism., Cell entry studies demonstrated that three newly identified SARSr-CoVs with different S protein sequences are all able to use human ACE2 as the receptor, Angiotensin-converting enzyme 2 (ACE2), a relatively new member of the RAS, has drawn extensive attention since 2003, because of the findings that ACE2 is the receptor for SARS Corona virus and that maintenance of normal ACE2 levels in the lung is beneficial for the host to combat inflammatory lung disease., The infection of target cells by the SARS CoV is mediated through the interaction of the viral Spike (S) protein (1255 amino acids) and its cellular receptor, angiotensin-converting enzyme 2 (ACE2).[SEP]Relations: severe acute respiratory syndrome has relations: disease_protein with ACE, disease_protein with ACE. Protein S human has relations: drug_drug with Saruplase, drug_drug with Saruplase, drug_drug with Sarpogrelate, drug_drug with Sarpogrelate. peptidyl-dipeptidase activity has relations: molfunc_protein with ACE2, molfunc_protein with ACE2, molfunc_protein with ACE, molfunc_protein with ACE.", "label": "yes"}
{"id": "converted_3580", "sentence1": "Can discharge destinations be accurately predicted using the Risk Assessment and Prediction Tool (RAPT)?", "sentence2": "CONCLUSION: Our analysis identified age, lower lumbar/lumbosacral surgery, and RAPT walk score as independent predictors of discharge to SNF, and demonstrated superior predictive power compared with the total RAPT Score when combined in a novel grading scale. , PURPOSE: The aim of this study was to evaluate the value of conventional factors, the Risk Assessment and Predictor Tool (RAPT) and performance-based functional tests as predictors of delayed recovery after total hip arthroplasty (THA)., CONCLUSIONS: The RAPT accurately predicted discharge disposition for high- and low-risk patients in our cohort. , The RAPT allows for identification of patients who are likely to be discharged home or to rehabilitation, which may facilitate preoperative planning of postoperative care. Additionally, it identifies intermediate-risk patients and could be used to implement targeted interventions to facilitate discharge home in this group of patients., RESULTS: Overall predictive accuracy was 78%. , OBJECTIVE: To assess the relevance of the RAPT (Risk Assessment and Prediction Tool), among a cohort of patients undergoing total hip arthroplasty (THA)., CONCLUSION: This study confirmed the usefulness of the RAPT to help in patient orientation decision after total hip arthroplasty. , CONCLUSIONS\n\nThe RAPT accurately predicted discharge disposition for high- and low-risk patients in our cohort., RAPT scores<6 and >10 (of 12) predicted with >90% accuracy discharge to inpatient rehabilitation and home, respectively., The RAPT allows for identification of patients who are likely to be discharged home or to rehabilitation, which may facilitate preoperative planning of postoperative care., The Risk Assessment and Prediction Tool (RAPT) is a preoperative survey constructed to predict discharge disposition after total joint arthroplasty (TJA)., CONCLUSIONS The RAPT accurately predicted discharge disposition for high- and low-risk patients in our cohort., The Risk Assessment and Prediction Tool (RAPT) is a preoperative survey constructed to predict discharge disposition after total joint arthroplasty (TJA)., A low RAPT score is reported to indicate a high risk of needing any form of inpatient rehabilitation after TJA, including short-term nursing facilities., CONCLUSIONS\nThe RAPT accurately predicted discharge disposition for high- and low-risk patients in our cohort., CONCLUSIONS: The RAPT accurately predicted discharge disposition for high- and low-risk patients in our cohort., BACKGROUND: The Risk Assessment and Prediction Tool (RAPT) is used to predict patient discharge disposition after total joint arthroplasty., CONCLUSIONS: The RAPT accurately predicted discharge disposition for high- and low-risk patients in our cohort.[SEP]", "label": "yes"}
{"id": "converted_687", "sentence1": "Is the Miller-Fisher syndrome considered to be a variant of Guillain-Barré?", "sentence2": "Miller Fisher syndrome is a variant of Guillain-Barre syndrome characterized by the classic triad of ophthalmoplegia, ataxia, and areflexia, We are reporting a rare case of Miller-Fisher (MFS) variant of Guillain-Barré syndrome (GBS) as the first manifestation of SLE in a 41-year-old female, Miller-Fisher syndrome is defined as ophthalmoplegia, ataxia and areflexia. Considered as a variant of Guillain-Barré syndrome, it differs in its clinical presentation and by anti-GQ1b antibody positivity, Guillain-Barré syndrome (GBS) and its variant, Miller Fisher syndrome (MFS), exist as several clinical subtypes with different neurological features and presentations, Using in vitro and in vivo models of the Guillain-Barré syndrome variant, Miller Fisher syndrome, we have shown previously that anti-GQ1b ganglioside antibodies target the presynaptic motor nerve terminal axon and surrounding perisynaptic Schwann cells, thereby mediating destructive injury through deposition of membrane attack complex., Miller Fisher syndrome is a variant of Guillain-Barré syndrome, characterized by ophthalmoplegia, ataxia and areflexia., Miller Fisher syndrome is a localized variant of Guillain-Barré syndrome, characterized by ophthalmoplegia, areflexia and ataxia., Miller Fisher syndrome, a variant of Guillain-Barré syndrome, is associated with IgG antibody to GQ1b ganglioside., Miller Fisher syndrome (MFS), a variant of Guillain-Barré syndrome, is a rare disorder typically characterized by a triad of ataxia, areflexia, and ophthalmoplegia, which may have a highly variable clinical presentation., Miller Fisher syndrome is an acute inflammatory polyradiculoneuropathy that is generally considered a variant of Guillain-Barré syndrome and is characterized by the clinical triad of ataxia, areflexia, and ophthalmoplegia., The objective of this study was to review the occurrence and clinical features of Guillain-Barré syndrome and its variant, the Miller Fisher syndrome, during TNFalpha antagonist therapy., Miller Fisher variant of Guillain-Barré syndrome masquerading as acute sphenoid sinusitis with orbital apex syndrome., Controversy exists concerning whether Miller Fisher syndrome (MFS) is the result of a predominantly axonal or demyelinating polyneuropathy and whether the Guillain-Barré syndrome variant of acute ataxia and areflexia without ophthalmoplegia, ataxic Guillain-Barré syndrome (atxGBS), has a distinct pathophysiology., Miller Fisher syndrome is characterised by the triad ophthalmoparesis, ataxia and areflexia and is considered to be a variant of Guillain-Barré syndrome; its differential diagnosis includes Wernicke&apos;s encephalopathy, Miller Fisher syndrome is an acute inflammatory polyradiculoneuropathy that is generally considered a variant of Guillain-Barré syndrome and is characterized by the clinical triad of ataxia, areflexia, and ophthalmoplegia, Miller-Fisher syndrome is characterised by the clinical triad of ophthalmoplegia, ataxia and areflexia and is considered a variant form of Guillain-Barré syndrome, The syndrome of ataxia, areflexia and ophthalmoplegia, or Miller-Fisher syndrome, has been considered to be a variant of Guillain-Barré syndrome with pathology restricted to the peripheral nervous system, Miller-Fisher syndrome (MFS) is considered the most common variant of Guillain-Barré syndrome (GBS) and is characterized by the clinical triad of ophthalmoplegia, ataxia and areflexia, Miller Fisher syndrome (MFS), characterized as ataxia, areflexia and ophthalmoplegia, is generally considered as a variant of Guillain-Barré syndrome (GBS), Miller Fisher Syndrome (MFS), which is characterized by ophthalmoplegia, ataxia and tendon areflexia, is generally considered as a clinical variant of Guillain-Barré Syndrome, Miller-Fisher syndrome (MFS), a variant of Guillain-Barré syndrome (GBS) is a self-limiting demyelinating disease of the peripheral nervous system, BACKGROUND: Miller-Fisher syndrome is characterised by the clinical triad of ophthalmoplegia, ataxia and areflexia and is considered a variant form of Guillain-Barré syndrome. , BACKGROUND AND OBJECTIVE: Miller-Fisher syndrome (MFS) is considered the most common variant of Guillain-Barré syndrome (GBS) and is characterized by the clinical triad of ophthalmoplegia, ataxia and areflexia. , Miller Fisher syndrome is characterised by the triad ophthalmoparesis, ataxia and areflexia and is considered to be a variant of Guillain-Barré syndrome; its differential diagnosis includes Wernicke's encephalopathy. , A recent report described serum anti-GQ1b ganglioside antibodies in Miller Fisher syndrome (MFS), a clinical variant of Guillain-Barré syndrome (GBS)., The syndrome of ataxia, areflexia and ophthalmoplegia, or Miller-Fisher syndrome, has been considered to be a variant of Guillain-Barré syndrome with pathology restricted to the peripheral nervous system., Guillain-Barré syndrome (GBS), an acute inflammatory polyneuropathy, is preceded in most cases by an infectious illness, and Campylobacter jejuni, a leading cause of acute gastroenteritis, is the most common antecedent to GBS and its ocular variant, Miller Fisher syndrome (MFS)., Miller-Fisher syndrome is characterised by the clinical triad of ophthalmoplegia, ataxia and areflexia and is considered a variant form of Guillain-Barré syndrome., Miller-Fisher syndrome is characterised by the clinical triad of ophthalmoplegia, ataxia and areflexia and is considered a variant form of Guillain-Barré syndrome.,  The syndrome of ataxia, areflexia and ophthalmoplegia, or Miller-Fisher syndrome, has been considered to be a variant of Guillain-Barré syndrome with pathology restricted to the peripheral nervous system. A patient with Miller-Fisher syndrome and bilateral demyelinating optic neuropathy suggesting associated central nervous system pathology is presented., Miller Fisher syndrome is an acute inflammatory polyradiculoneuropathy that is generally considered a variant of Guillain-Barré syndrome and is characterized by the clinical triad of ataxia,,  Miller Fisher syndrome is an uncommon disease and it is a variant of Guillain-Barre syndrome. Miller Fisher syndrome also has rarer variants., Miller Fisher syndrome is characterised by the triad ophthalmoparesis, ataxia and areflexia and is considered to be a variant of Guillain-Barré syndrome; its differential diagnosis includes Wernicke's encephalopathy., Miller Fisher syndrome is an acute inflammatory polyradiculoneuropathy that is generally considered a variant of Guillain-Barré syndrome and is characterized by the clinical triad of ataxia, areflexia, and ophthalmoplegia., Data were separately analysed for Miller Fisher syndrome and other Guillain-Barré syndrome variants., Guillain-Barré syndrome variants alone (excluding Miller Fisher syndrome) accounted for 10.5% of total cases., The syndrome of ataxia, areflexia and ophthalmoplegia, or Miller-Fisher syndrome, has been considered to be a variant of Guillain-Barré syndrome with pathology restricted to the peripheral nervous system.[SEP]Relations: Miller Fisher syndrome has relations: disease_disease with regional variant of Guillain-Barre syndrome, disease_disease with regional variant of Guillain-Barre syndrome, disease_disease with cerebellar disease, disease_disease with cerebellar disease. Guillain-Barre syndrome has relations: disease_disease with variant of Guillain-Barre syndrome, disease_disease with variant of Guillain-Barre syndrome, disease_protein with PMP22, disease_protein with PMP22, disease_disease with syndromic disease, disease_disease with syndromic disease.", "label": "yes"}
{"id": "converted_404", "sentence1": "Is endostatin a proangiogenic factor?", "sentence2": "endostatin (antiangiogenic factor, antiangiogenic factors include thrombospondin-1, angiostatin, and endostatin,  human endostatin (rh-endostatin), a potential antiangiogenic agent, , antiangiogenic PF4 and endostatin, Angiostatin and endostatin are endogenous inhibitors of angiogenesis with anticancer effects, the antiangiogenic factors, cystatin C and endostatin, were measured, accumulation of endostatin and Abeta peptides which have been shown to be antiangiogenic, antioangiogenic factors such as pigment epithelial derived factor (PEDF), angiostatin, endostatin, Endostatin is an antiangiogenic growth factor., angiogenesis inhibitor endostatin, Circulating and cellular proangiogenic and antiangiogenic proteins such as vascular endothelial growth factor (VEGF) and endostatin contribute to the local angiogenic balance, Thrombospondin-1 (Tsp1), endostatin, and tumstatin are extracellular matrix-associated proteins that inhibit angiogenesis, specific inhibitors of angiogenesis such as platelet factor, angiostatin, endostatin, endostatin, an endogenous inhibitor of angiogenesis., antiangiogenic factors (pigment epithelium-derived factor [PEDF]; angiostatin; restin; and endostatin, endostatin peptide, a potent inhibitor of angiogenesis derived from type XVIII collagen,, endogenous angiogenesis inhibitors endostatin , ndostatin is a potent inhibitor of angiogenesis and tumor growth., endogenous angiogenesis inhibitor - endostatin , Endostatin (ES), a fragment of collagen XVIII, is an endogenous inhibitor of angiogenesis, antiangiogenic protein endostatin, A number of endogenous inhibitors of angiogenesis are found in the body. Some of these are synthesized by specific cells in different organs, and others are created by extracellular proteolytic cleavage of plasma-derived or extracellular matrix-localized proteins. In this review, we focus on angiostatin, endostatin,, endostatin (a direct inhibitor of angiogenesis) , endogenous angiogenesis inhibitor endostatin, Endostatin, a peptide derived from proteolysis of collagen XVIII, is an endogenous inhibitor of angiogenesis and tumor growth. , anti-angiogenic factor endostatin, Endostatin is the first endogenous angiogenesis inhibitor to enter clinical trials, angiogenic inhibitors such as endostatin, endostatin inhibits the angiogenic switch, antiangiogenic endostatin , direct acting antiangiogenic agents (e.g., endostatin) , Endostatin is an antiangiogenic fragment of the basement membrane protein, collagen XVIII., specific inhibitors of angiogenesis such as platelet factor-4, angiostatin, endostatin, Endostatin, which is a natural inhibitor of angiogenesis, Angiostatin and endostatin are two powerful inhibitors of angiogenesis in experimental models[SEP]Relations: Platelet Activating Factor has relations: drug_drug with Enoxaparin, drug_drug with Enoxaparin, drug_drug with Argatroban, drug_drug with Argatroban, drug_drug with Menadione, drug_drug with Menadione, drug_drug with Epoprostenol, drug_drug with Epoprostenol, drug_drug with Apixaban, drug_drug with Apixaban.", "label": "no"}
{"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_1765", "sentence1": "Is the toxin produced by Clostridium botulinum always deadly?", "sentence2": "Animals treated with trace elements recovered. It appears that intestinal microbiota dysbiosis and trace element deficiency could explain the extensive emergence of chronic Botulism., The patient was treated with human botulism immune globulin and had rapid recovery in weakness. A stool sample from the patient was positive for Type A Clostridium botulinum toxin eventually confirming the diagnosis of infant botulism, The botulism immunoglobulin was administered, and a diagnosis was confirmed with positive botulinum toxin in the stool samples. Full recovery was made by the infant, Botulinum neurotoxin (BoNT) serotype B (BoNT/B) is one of the serotypes of BoNT that causes deadly human botulism, though it is used clinically for treatment of many neuromuscular diseases., Foodborne botulism is a rare and sometimes fatal illness caused by consuming foods containing botulinum neurotoxin, To assess the effectiveness and safety of botulinum toxin in treating MPS, excluding MPS in neck and head muscles., Botulinum toxin (BTX) is one of the most potent bacterial toxins known and its effectiveness in the treatment of some pain syndromes is well known.,  An emerging treatment option to address these issues is the use of a paralyzing material such as botulinum toxin A (Botox) to decrease the appearance of the wrinkles, which yields a more esthetic and youthful facial appearanc, lthough BoNT is an extremely toxic molecule, it is now increasingly used for the treatment of disorders related to muscle hyperactivity and glandular hyperactivity.[SEP]Relations: Botulinum toxin type A has relations: drug_drug with Clorgiline, drug_drug with Clorgiline, drug_drug with Clidinium, drug_drug with Clidinium, drug_drug with Clobazam, drug_drug with Clobazam. Botulinum Toxin Type B has relations: drug_drug with Clorgiline, drug_drug with Clorgiline, drug_drug with Clorgiline, drug_drug with Clorgiline.", "label": "no"}
{"id": "converted_3703", "sentence1": "Does radiotherapy for Hodgkin disease increases risk for lung cancer?", "sentence2": "Risks of lung, breast, and gastrointestinal (GI) cancers increase with higher radiation dose. , CONCLUSIONS: RT treatment, especially with doses higher than 42 Gy, and smoking increase the risk of SN after HL. In this series, LC patients with early stages had a shorter elapsed time from HL diagnosis and longer OS, therefore the role of LC screening in HL survivors should be prospectively evaluated and smoking cessation counseling ought to be a key aspect during follow-up., BACKGROUND: Long-term Hodgkin lymphoma (HL) survivors have an increased risk of late cardiac morbidity and secondary lung cancer after chemotherapy and mediastinal radiotherapy. , PURPOSE: Hodgkin lymphoma (HL) survivors have an increased risk of cardiovascular disease (CD), lung cancer, and breast cancer., Lung cancer (LC) represents the most common solid tumor in survivors of Hodgkin's disease (HD), and the assessment of the mutational status of oncogenic driver mutations in LC is now standard. , PURPOSE: Hodgkin lymphoma (HL) survivors face an increased risk of treatment-related lung cancer. , Increased risk of second lung cancer in Hodgkin's lymphoma survivors: a meta-analysis., BACKGROUND: Patients treated for Hodgkin's lymphoma (HL) have a higher risk of developing second lung cancer (SLC) compared with the general population. , The pooled relative risk (RR) of SLC was 4.62 (95 % confidence interval [CI], 3.18-6.70], I (2) = 98 %), with a median absolute excess rate of 10.4 per 10,000 person-years. , CONCLUSIONS: The current meta-analysis provided a detailed estimate of the risk of SLC among HL survivors. , CONCLUSIONS\n\nThe excess risk of lung cancer in Hodgkin's disease patients treated with radiotherapy is related to the radiation dose received by the affected area of the lung., BACKGROUND\n\nLung cancer is a frequent cause of death in patients cured of Hodgkin's disease, but the contributions of chemotherapy, radiotherapy, and smoking are not well described., CONCLUSIONS\n\nPast treatments with alkylating agents and radiation therapy for Hodgkin's disease were associated with an increased risk of lung cancer in a dose-dependent and additive fashion., BACKGROUND\n\nSeveral studies have shown that survivors of Hodgkin's disease have increased risk of lung cancer, but the factors responsible for this excess risk are not well known., PURPOSE\n\nThis study was undertaken to investigate the effects of radiation dose, chemotherapy, and smoking on the risk of lung cancer following treatment of Hodgkin's disease., Increased risk of lung cancer, non-Hodgkin's lymphoma, and leukemia following Hodgkin's disease., It is recognized that survivors of Hodgkin's disease are at a substantially increased risk of lung cancer., The risk of lung and breast cancer is significantly increased after therapy for Hodgkin 's disease ( HD) , but there are few data that describe the molecular profiles of these tumors . , Hodgkin lymphoma ( HL ) survivors have an increased risk of cardiovascular disease ( CD) , lung cancer , and breast cancer . , BACKGROUND\nLung cancer is a frequent cause of death in patients cured of Hodgkin's disease, but the contributions of chemotherapy, radiotherapy, and smoking are not well described., CONCLUSIONS\nPast treatments with alkylating agents and radiation therapy for Hodgkin's disease were associated with an increased risk of lung cancer in a dose-dependent and additive fashion., Lung cancer in Hodgkin's disease: association with previous radiotherapy., Twenty-eight (94%) of 30 patients developing metachronous lung cancer received supradiaphragmatic irradiation as primary therapy for HD., The risk ratio for the development of lung cancer among HD patients was 5.6 times that expected in the general population., Seven cases of lung cancer were observed in patients with Hodgkin's disease (HD) since 1970., BACKGROUND\nSeveral studies have shown that survivors of Hodgkin's disease have increased risk of lung cancer, but the factors responsible for this excess risk are not well known., The excess risk of lung cancer in Hodgkin's disease patients treated with radiotherapy is related to the radiation dose received by the affected area of the lung., Lung cancer is a frequent cause of death in patients cured of Hodgkin's disease, but the contributions of chemotherapy, radiotherapy, and smoking are not well described., Past treatments with alkylating agents and radiation therapy for Hodgkin's disease were associated with an increased risk of lung cancer in a dose-dependent and additive fashion., Several studies have shown that survivors of Hodgkin's disease have increased risk of lung cancer, but the factors responsible for this excess risk are not well known.[SEP]Relations: Non-Hodgkin lymphoma has relations: drug_effect with Bortezomib, drug_effect with Bortezomib, drug_effect with Bortezomib, drug_effect with Bortezomib, drug_effect with Fluoxetine, drug_effect with Fluoxetine, drug_effect with Fluoxetine, drug_effect with Fluoxetine, drug_effect with Raltegravir, drug_effect with Raltegravir.", "label": "yes"}
{"id": "converted_1427", "sentence1": "Can cffDNA be used for non-invasive testing?", "sentence2": "Non-invasive prenatal testing using cell-free fetal DNA in maternal circulation, The identification of cell-free fetal DNA (cffDNA) in maternal circulation has made non-invasive prenatal testing (NIPT) possible., 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. This review briefly summarizes the technical aspects of the NIPT and application of NIPT in clinical practice., 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, To determine how adults in the United States view non-invasive prenatal testing using cell-free fetal DNA (cffDNA testing) in order to help estimate uptake, Non-invasive prenatal testing of cell-free fetal DNA (cffDNA) in maternal plasma can predict the fetal RhD type in D negative pregnant women, The identification of cell-free fetal DNA (cffDNA) in maternal circulation has made non-invasive prenatal testing (NIPT) possible, The effectiveness and clinical utility of non-invasive prenatal diagnosis (NIPD) for fetal sex determination using cell-free fetal DNA (cffDNA) was assessed by undertaking a prospective national audit of UK testing, 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 aneuploidy testing that utilizes cell-free fetal DNA (cffDNA) circulating in maternal blood is one example of an innovative technology that promises significant benefits for its intended end users; however, it is currently uncertain whether it will achieve widespread clinical implementation, Analysis of cell free fetal (cff) DNA in maternal plasma is used routinely for non invasive prenatal diagnosis (NIPD) of fetal sex determination, fetal rhesus D status and some single gene disorders, Non-invasive prenatal diagnosis (NIPD) using cell-free fetal DNA (cffDNA) in maternal plasma is an alternative to invasive prenatal diagnosis (IPD), which carries a 1% risk of miscarriage. , 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. , The effectiveness and clinical utility of non-invasive prenatal diagnosis (NIPD) for fetal sex determination using cell-free fetal DNA (cffDNA) was assessed by undertaking a prospective national audit of UK testing. , NIFTY (Non-invasive Fetal Trisomy Test) is a non-invasive prenatal test which is used for diagnosing fetal trisomy. The test is based on the analysis of cell free fetal DNA (cffDNA) present in the plasma and serum of a pregnant woman., Using non-invasive method of cffDNAs in the shortest time possible, as well as avoiding invasive tests for early determination of fetal gender, provides the opportunity of deciding and employing early treatment for fetuses at risk of genetic diseases., The identification of cell-free fetal DNA (cffDNA) in maternal circulation has made non-invasive prenatal testing (NIPT) possible., To determine how adults in the United States view non-invasive prenatal testing using cell-free fetal DNA (cffDNA testing) in order to help estimate uptake., Nowadays, new advances in the use of cell free fetal DNA (cffDNA) in maternal plasma of pregnant women has provided the possibility of applying cffDNA in prenatal diagnosis as a non-invasive method., Non-invasive prenatal testing of cell-free fetal DNA (cffDNA) in maternal plasma can predict the fetal RhD type in D negative pregnant women., Prevention of contamination following our anti-contamination criteria is a good practice for certain non-invasive sex determination, using cffDNA.[SEP]Relations: infantile dystonia-parkinsonism has relations: disease_phenotype_positive with Ocular flutter, disease_phenotype_positive with Ocular flutter, disease_phenotype_positive with Absent speech, disease_phenotype_positive with Absent speech, disease_phenotype_positive with Autosomal recessive inheritance, disease_phenotype_positive with Autosomal recessive inheritance, disease_phenotype_positive with Rigidity, disease_phenotype_positive with Rigidity, disease_phenotype_positive with Incoordination, disease_phenotype_positive with Incoordination.", "label": "yes"}
{"id": "converted_4421", "sentence1": "Is the 22-item sino-nasal outcome test (SNOT-22) a widely used measure for Health-Related Quality-of-Life (HRQOL) associated with chronic rhinosinusitis (CRS)?", "sentence2": "The Sino-Nasal-Outcome-Test-22 (SNOT-22) represents the reference questionnaire to assess symptoms, health-related quality-of-life (HRQOL) and treatment-response in patients with chronic rhinosinusitis (CRS). , Assessment of health-related quality-of-life in patients with chronic Rhinosinusitis - Validation of the German Sino-Nasal Outcome Test-22 (German-SNOT-22).,  Patients meeting diagnostic criteria for CRS were prospectively enrolled in a cross-sectional study. Responses from the Sinonasal Outcomes Test-22 (SNOT-22), a measure of patient HRQOL, as well as the Lund-Kennedy and Lund-Mackay scores were recorded at enrollment, Three groups of 12 participants each were examined: patients with CRS without polyposis (CRS group), patients with symptoms of CRS but radiologically normal sinuses (symptoms-only), and healthy controls. Measurements of nNO were carried out using aspiration method and humming maneuver. All participants completed the Sino-Nasal Outcome Test (SNOT-22)., PURPOSE: The Sino-Nasal-Outcome-Test-22 (SNOT-22) represents the reference questionnaire to assess symptoms, health-related quality-of-life (HRQOL) and treatment-response in patients with chronic rhinosinusitis (CRS)., tcomes included scores on the CRS disease severity visual analog scale (VAS), 22-item Sino-Nasal Outcome Test (SNOT-22), 5-dimension EuroQoL (EQ-5D) general health status VAS, and 36-item Short-Form Health Survey (SF-36) for HRQoL and nasal polyp-related healthcare resource use questionnaires.RE, BACKGROUND: The 22-item Sino-Nasal Outcome Test (SNOT-22) is a commonly utilized outcome measure for chronic rhinosinus, BACKGROUND: The 22-item sino-nasal outcome test (SNOT-22) is a widely used and powerful patient-reported outcomes measure for chronic rhinosinus, BACKGROUND: Prior study demonstrated that baseline 22-item Sino-Nasal Outcome Test (SNOT-22) aggregate scores accurately predict selection of surgical intervention in patients with chronic rhinosinus, OBJECTIVES/HYPOTHESIS: Sinonasal Outcomes Test-22 (SNOT-22) is used widely as a patient-reported sinonasal quality-of-life (QOL) instrument for endoscopic endonasa, Is sino-nasal outcome test-22 reliable for guiding chronic rhinosinusitis patients for endoscopic sinus surgery, The Sino-Nasal Outcome Test-22 as a tool to identify chronic rhinosinusitis in adults with cystic fibrosis, rden. Our objective was to investigate the utility of the 22-item Sino-Nasal Outcome Test (SNOT-22) as a tool to identify CRS in adults wit, OBJECTIVES/HYPOTHESIS: The 22-item Sinonasal Outcome Test (SNOT-22) is a validated chronic rhinosinusitis health-related quality-of-life outcome (HRQoL) measure; however, SNOT-22 domains have not been validated specifically for chronic rhinosinusitis with nas, OBJECTIVE: The SNOT-22 (22-item Sinonasal Outcome Test) is a high-quality outcome measure that assesses chronic rhinosinusitis-specific quality of lif, BACKGROUND: The 22-item sino-nasal outcome test (SNOT-22) is a widely used and powerful patient-reported outcomes measure for chronic rhinosinusitis (CRS, OBJECTIVES/HYPOTHESIS: The 22-item Sinonasal Outcome Test (SNOT-22) is a validated chronic rhinosinusitis health-related quality-of-life outcome (HRQoL) measure; however, SNOT-22 domains have not been validated specifically for chronic rhinosinusitis with nasal polyps (CRSwNP, BACKGROUND: The 22-item Sino-Nasal Outcome Test (SNOT-22) is a commonly utilized outcome measure for chronic rhinosinusitis (CRS, OBJECTIVES/HYPOTHESIS: The 22-item Sinonasal Outcome Test (SNOT-22) is a validated chronic rhinosinusitis health-related quality-of-life outcome (HRQoL) measure; however, SNOT-22 domains have not been validated specifically for chronic rhinosinusitis with nasal polyps (CRSwNP).STUDY DESIGN: Validation of SNOT-22 domain structure, using data from 3 randomized, placebo-controlled, double-blinded, multicenter clinical trials of dupilumab in adults with moderate-to-severe CRSwNP.METHODS: Preliminary dimensional structure was derived by exploratory factor analyses of SNOT-22 data from a phase 2 trial (NCT01920, OBJECTIVES: We set out to determine the psychometric validation of a disease-specific health related quality of life instrument for use in chronic rhinosinusitis, the 22 item Sinonasal Outcome Test (SNOT-22), a modification of a pre-existing instrument, the SNOT-20.DESIGN, SETTING AND PARTICIPANTS: The National Comparative Audit of Surgery for Nasal Polyposis and Chronic Rhinosinusitis was a prospective cohort study collecting data on 3128 adult patients undergoing sinonasal sur, OBJECTIVE: The SNOT-22 (22-item Sinonasal Outcome Test) is a high-quality outcome measure that assesses chronic rhinosinusitis-specific quali, act of CRS. We sought to determine if 22-item Sino-Nasal Outcome Test (SNOT-22) score is predictive of patient-perceived CRS symptom control.METHODS: Prospective cross-sectional study of 2, The Sinonasal Outcome Test (SNOT-22) Is a Poor Diagnostic Tool for Chronic Rhinosinusitis., The 22-item Sino-Nasal Outcome Test accurately reflects patient-reported control of chronic rhinosinusitis symptomatology., Development of Sinonasal Outcome Test (SNOT-22) Domains in Chronic Rhinosinusitis With Nasal Polyps., cture with strong Cronbach's alpha values (all >0.80). Moderate-to-high correlations were observed between change in SNOT-22 domain scores and other study patient-reported outcome measures, along with large effect-size estimates (≥0.7), demonstrating re[SEP]Relations: Chronic sinusitis has relations: disease_phenotype_positive with Keutel syndrome, disease_phenotype_positive with Keutel syndrome, disease_phenotype_positive with familial nasal acilia, disease_phenotype_positive with familial nasal acilia. Nasal polyposis has relations: drug_effect with Pramipexole, drug_effect with Pramipexole, drug_effect with Human calcitonin, drug_effect with Human calcitonin, drug_effect with Ropinirole, drug_effect with Ropinirole.", "label": "yes"}
{"id": "converted_432", "sentence1": "Is it possible to detect survivin protein expression in normal human adult tissues?", "sentence2": "Survivin (BIRC5) is one of the members of IAP-family apoptosis inhibitors. The BIRCS gene is expressed in most human embryonic tissues and malignant tumors but not in normal differentiated tissues of adult human., Survivin is an inhibitor of apoptosis that is undetectable in most terminally differentiated normal human tissues, strongly expressed in embryonic and fetal organs and is strongly expressed in many different human cancers., Survivin is a member of the inhibitor apoptosis family that is overexpressed in many malignancies. It has five known alternative splice forms, some of which differ in their antiapoptotic properties and expression levels in human cancers., survivin is usually not expressed in normal adult tissues,, AZD1152-hQPA induced caspase-dependent apoptosis of some cell lines, demonstrated by loss of mitochondrial membrane potential, activation of caspase-9, followed by activation of caspase-3. This effect was accompanied by the inhibition of survivin expression. In vivo efficacy was determined in NOD/SCID/γc(null) mice implanted with the Ramos human BL cell line. AZD1152 had anti-tumour effects in this murine xenograft model. There preclinical data suggest that the inhibition of Aurora B kinase is a potentially useful therapeutic strategy in BL and HL., a novel antiapoptosis gene, i.e., survivin, was identified as a structurally unique member of the inhibitor of apoptosis protein family. Survivin expression is turned off during fetal development and not found in non-neoplastic adult human tissues but is again turned on in the most common human cancers. The antiapoptotic properties of survivin might provide a significant growth advantage in tumors and possibly also contribute to chemoresistance of cancer., Further comparison of the distribution of PDEF with other widely recognized cancer-associated molecules showed that PDEF has more restricted distributions than Her-2/neu, Bcl-2, survivin or telomerase in cDNA libraries from normal human tissues and more increased distribution than Her-2/neu, CA-125, Bcl-2, survivin and telomerase in cDNA libraries from brain (except survivin), breast, lung and ovarian tumors. These data together show a better tumor-association for PDEF and suggest that PDEF is a more suitable target for developing specific cancer therapies., we identified decreased FHIT expression resulting in apoptosis inhibition and decreasing apoptosis associated with abnormal levels of some pro- and anti-apoptotic proteins (Bax, Bcl-2 and Survivin) by TUNEL and TMA. Our results demonstrated that the mutation in the FHIT gene significantly reduced FHIT expression in human CRC. Both TUNEL and TMA experiments demonstrated significantly inhibited apoptosis by down-regulation of Bax and up-regulation of Survivin and Bcl-2. Collectively, these studies identify the mechanism by which an important tumor suppressor gene, FHIT, inactivated specifically in human CRC, and contributes to our understanding of the mechanism of colorectal carcinogenesis.[SEP]Relations: PPP1R1A has relations: anatomy_protein_present with adult mammalian kidney, anatomy_protein_present with adult mammalian kidney, anatomy_protein_present with adipose tissue, anatomy_protein_present with adipose tissue, anatomy_protein_present with muscle tissue, anatomy_protein_present with muscle tissue, anatomy_protein_present with blood, anatomy_protein_present with blood. breast has relations: anatomy_protein_present with VIM, anatomy_protein_present with VIM.", "label": "no"}
{"id": "converted_1173", "sentence1": "Do Parkinson's disease patients experience stridor?", "sentence2": "The authors describe a patient experiencing stridor and dysphagia with confirmed pulmonary restriction and aspiration following subthalamic nucleus deep brain stimulator adjustment, with a resolution of symptoms and signs when the stimulator was switched off., Stridor was not noted during sleep at night. Endoscopic examination of the larynx revealed insufficient abduction of the bilateral vocal cords, although the glottis was not so small as to cause stridor during inspiration. , The stridor was specific to MSA. , Patients with MSA can present other clinical features, such as inspiratory stridor and rapid eye movement (REM) sleep behaviour disorder (RBD). We report a patient with pathologically confirmed MSA who presented with a longstanding history of stridor, RBD and autonomic disturbances but did not develop overt parkinsonism or cerebellar signs. This case illustrates that MSA may present clinically without its cardinal motor symptoms, and that stridor and RBD may be clues to recognise the disease in a patient with autonomic failure., Patients with PD did not display sleep hypoventilation, stridor and abnormal central sleep apnea. , DEVELOPMENT: Autonomic disorders such as seborrhoeic dermatitis and disorders involving sweating, fatigue, weight loss or respiratory problems (dyspnea, inspiratory stridor) are highly prevalent and very disabling symptoms. In addition, they may be the main problem in a particular phase of PD (fatigue, stridor) and condition the quality of life of patients with Parkinson. , . Her dyspneic attacks consisting of inspiratory stridor and cyanosis occurred mainly during the wearing-off time and continued for less than 30 min, The most commonly reported sleep disorders were sleep fragmentation (52.5%), vocalisation (60%), REM sleep behaviour disorder (47.5%), and nocturnal stridor (19%). Except for sleep fragmentation, the incidence of these disorders was significantly higher than in PD, Six days after admission, dyspnea and inspiratory stridor were noted, and the respiratory distress worsened. , A patient is described with idiopathic Parkinson's disease and severe laryngeal stridor., The laryngeal stridor responded to levodopa therapy, and we are not aware that this has been reported previously., The subsequent clinical course of the former eight patients has been typical of idiopathic Parkinson's disease, whilst the ninth patient has developed postural hypotension, urinary incontinence and respiratory stridor typical of multiple system atrophy. , Although each of five autonomic domains was affected in variable numbers of IPD patients, AD in MSA generally involved more autonomic domains than in IPD, and to a more severe degree, in particular with regard to inspiratory stridor., However, the presence of severe AD, of AD preceding parkinsonism, or of inspiratory stridor, are all individually suggestive of MSA., Apart from dysautonomia, the principal discriminant clinical features that distinguished SND from PD were the early appearance of the following symptoms and signs: (a) severe and atypical progressive parkinsonism characterized by bilateral bradykinesia and rigidity, slowness of gait, postural instability, and falls, and poor or absent response to adequate levodopa treatment; (b) increased tendon reflexes associated or not with frank pyramidal signs, severe dysarthria, and less consistently, dysphagia, stridor, antecollis, and stimulus-sensitive myoclonus, which, when present, are highly suggestive of the disease., OBJECTIVES: (1) To present a rare case of stridor secondary to prolonged laryngospasm in a patient with Parkinson's disease, and (2) to review the literature on stridor in Parkinson's disease. METHODS: We report a 73-year-old Parkinson's disease patient who developed acute stridor due to prolonged laryngospasm triggered by overspill of excessive secretions. , RESULT: Only 12 previously reported cases of stridor in Parkinson's disease patients were identified. , This case emphasises the importance of recognising different causes of stridor in Parkinson's disease patients, as this affects management., RESULT: Only 12 previously reported cases of stridor in Parkinsons disease patients were identified., This case emphasises the importance of recognising different causes of stridor in Parkinsons disease patients, as this affects management., OBJECTIVES: (1) To present a rare case of stridor secondary to prolonged laryngospasm in a patient with Parkinsons disease, and (2) to review the literature on stridor in Parkinsons disease., METHODS: We report a 73-year-old Parkinsons disease patient who developed acute stridor due to prolonged laryngospasm triggered by overspill of excessive secretions., (1) To present a rare case of stridor secondary to prolonged laryngospasm in a patient with Parkinson's disease, and (2) to review the literature on stridor in Parkinson's disease.[SEP]Relations: Stridor has relations: disease_phenotype_positive with infantile dystonia-parkinsonism, disease_phenotype_positive with infantile dystonia-parkinsonism, disease_phenotype_positive with multiple system atrophy, parkinsonian type, disease_phenotype_positive with multiple system atrophy, parkinsonian type. Parkinson disease has relations: disease_disease with parkinsonian disorder, disease_disease with parkinsonian disorder, contraindication with Streptomycin, contraindication with Streptomycin. parkinsonian disorder has relations: disease_disease with Parkinson disease, disease_disease with Parkinson disease.", "label": "yes"}
{"id": "converted_2236", "sentence1": "Is sonidegib effective for basal cell carcinoma?", "sentence2": "This review of the literature aims to describe previous and current treatment options for oral therapy in locally advanced and metastatic NMSC otherwise unamenable to standard treatment. Oral Smoothened (Smo) inhibitors Vismodegib, Sonidegib, and Taladegib have shown to be effective in several trials. , Sonidegib is a new smoothened inhibitor currently under investigation for treatment of laBCC, which demonstrates a comparable safety profile to vismodegib. , The recent development of novel hedgehog pathway inhibitors for high-risk BCC (including oral vismodegib and sonidegib) may represent a paradigm shift towards medical management of NMSC., Sonidegib (Odomzo®), an oral smoothened (SMO) antagonist, is indicated for the treatment of adults with locally advanced basal cell carcinoma (laBCC) who are not candidates for surgery or radiation therapy, or adults with recurrent laBCC following surgery or radiation therapy. , The acceptable benefit-risk profile of sonidegib, along with a paucity of treatment options and the seriousness of the condition, makes sonidegib an emerging option for the treatment of adults with laBCC that has recurred following surgery or radiation therapy, or in those who are not candidates for surgery or radiation therapy., Sonidegib phosphate: new approval for basal cell carcinoma., Sonidegib, a novel smoothened inhibitor for the treatment of advanced basal cell carcinoma., Serious adverse events occurred in 11 (14%) of 79 patients in the 200 mg group and 45 (30%) of 150 patients in the 800 mg group.The benefit-to-risk profile of 200 mg sonidegib might offer a new treatment option for patients with advanced basal cell carcinoma, a population that is difficult to treat.Novartis Pharmaceuticals Corporation.<CopyrightInformation>Copyright © 2015 Elsevier Ltd. All rights reserved.</, However, to date, Hh inhibitors, specifically those targeting Smoothened [such as vismodegib, BMS-833923, saridegib (IPI-926), sonidegib/erismodegib (LDE225), PF-04449913, LY2940680, LEQ 506, and TAK-441], have demonstrated good efficacy as monotherapy in patients with basal cell carcinoma and medulloblastoma, but have shown limited activity in other tumor types., The hedgehog pathway inhibitor sonidegib demonstrated meaningful tumor shrinkage in more than 90% of patients with locally advanced basal cell carcinoma (BCC) or metastatic BCC in the BCC Outcomes with LDE225 Treatment study.This report provides long-term follow-up data collected up to 12 months after the last patient was randomized.In this multicenter, randomized, double-blind phase II study, patients were randomized 1:2 to sonidegib 200 or 800 mg. The primary end point was objective response rate assessed by central review.Objective response rates in the 200- and 800-mg arms were 57.6% and 43.8% in locally advanced B, Serious adverse events occurred in 11 (14%) of 79 patients in the 200 mg group and 45 (30%) of 150 patients in the 800 mg group.The benefit-to-risk profile of 200 mg sonidegib might offer a new treatment option for patients with advanced basal cell carcinoma, a population that is difficult to treat.Novartis Pharmaceuticals Corporation.<CopyrightInformation>Copyright © 2015 Elsevier Ltd. All rights reserved.</C, Oral sonidegib is approved in Switzerland for the treatment of adult patients with advanced basal cell carcinoma (BCC) and in the US and EU for the treatment of adult patients with locally advanced BCC that has recurred following surgery or radiation therapy, or those who are not candidates for surgery or radiation therapy., Sonidegib phosphate: new approval for basal cell carcinoma.[SEP]Relations: Sonidegib has relations: drug_drug with Carbamazepine, drug_drug with Carbamazepine, drug_drug with Carbomycin, drug_drug with Carbomycin, drug_drug with Afelimomab, drug_drug with Afelimomab. basal cell carcinoma has relations: contraindication with Methoxsalen, contraindication with Methoxsalen, disease_disease with carcinoma, disease_disease with carcinoma.", "label": "yes"}
{"id": "converted_61", "sentence1": "Is c-met involved in the activation of the Akt pathway?", "sentence2": "Amplification of MET has been reported in approximately 5%-22% of lung tumors with acquired resistance to small-molecule inhibitors of the epidermal growth factor receptor (EGFR). Resistance to EGFR inhibitors is likely mediated through downstream activation of the phosphoinositide 3-kinase /AKT pathway., Simultaneous treatment of resistant tumors with a MET inhibitor plus an EGFR inhibitor can abrogate activation of downstream effectors of cell growth, proliferation, and survival, thereby overcoming acquired resistance to EGFR inhibitors., HGF mediated both ERK and Akt phosphorylation., ERK/Akt signaling, but not the Smad pathway, may be one of the main processes in HGF-induced EMT,, The MAPK/Akt pathway is indispensable in HGF/c-Met signaling., Inhibition of c-Met activation sensitizes osteosarcoma cells to cisplatin via suppression of the PI3K-Akt signaling, Specifically, we demonstrated that inhibition of c-Met activity led to suppression of the PI3K-Akt pathway, thus enhancing cisplatin chemosensitivity., Our study clearly suggests that inhibition of c-Met activity can effectively sensitize osteosarcoma cells to cisplatin via suppression of the PI3K-Akt signaling., We found that a dual Met/VEGF receptor 2 kinase inhibitor, E7050, circumvented HGF-induced EGFR-TKI resistance in EGFR mutant lung cancer cell lines by inhibiting the Met/Gab1/PI3K/Akt pathway in vitro., Here, we report that i) treatment of RL95-2 cells with HGF resulted in phosphorylation of the HGF receptor c-Met, activation of Akt and IκB, translocation of NF-κB into the nucleus, and up-regulation of COX-2 mRNA;, Our data suggest that HGF possesses chemotactic ability, has anti-apoptosis action, and induces cellular infiltration via the PI3K/Akt pathway;, Hepatocyte growth factor-induced c-Src-phosphatidylinositol 3-kinase-AKT-mammalian target of rapamycin pathway inhibits dendritic cell activation by blocking IκB kinase activity, Activation of c-Src in turn establishes a complex consisting of phosphatidylinositol 3-kinase and c-MET, and promotes downstream activation of the phosphatidylinositol 3-kinase/AKT pathway and mammalian target of rapamycin., Notably, hepatocyte growth factor-stimulated c-Src activation results in induction of phosphatidylinositol 3-kinase complexes p85α/p110α and p85α/p110δ, which is required for activation of mammalian target of rapamycin, and consequent inhibition of IκB kinase and nuclear factor-κB activation., Our findings, for the first time, have identified the c-Src-phosphatidylinositol 3-kinase-AKT-mammalian target of rapamycin pathway that plays a pivotal role in mediating the inhibitory effects of hepatocyte growth factor on dendritic cell activation by blocking nuclear factor-κB signaling., Cyr61 siRNA inhibited a second phase of Akt phosphorylation measured 12 hours after cell stimulation with HGF and also inhibited HGF-induced phosphorylation of the Akt target glycogen synthase kinase 3alpha., HGF+EGF treatment increased the duration of ERK1/2 and AKT activation compared to HGF or EGF alone. All these data indicate that a crosstalk between the EGF and HGF pathways in mammary epithelial cells may modulate the development of the mammary gland., Hepatocyte growth factor and c-Met promote dendritic maturation during hippocampal neuron differentiation via the Akt pathway, Consistent with these results, HGF activated Akt, which phosphorylates glycogen synthase kinase-3beta (GSK-3beta) to inactivate it, and reduced phosphorylation of microtubule-associated protein 2 (MAP2), which can promote microtubule polymerization and dendrite elongation when dephosphorylated., Conversely, pharmacological inhibition of c-Met with its specific inhibitor, PHA-665752, or genetic knock-down of c-Met with short hairpin RNAs (shRNAs) suppressed HGF-induced phosphorylation of Akt and GSK-3beta, increased phosphorylation of MAP2, and reduced dendrite number and length in cultured hippocampal neurons., Inhibiting Akt activity with the phosphoinositide-3-kinase inhibitor LY294002 or Akt inhibitor X suppressed HGF-induced phosphorylation of GSK-3beta, increased MAP2 phosphorylation, and blocked the ability of HGF to enhance dendritic length., These observations indicate that HGF and c-Met can regulate the early stages of dendrite maturation via activation of the Akt/GSK-3beta pathway., Involvement of PI3K/Akt signaling pathway in hepatocyte growth factor-induced migration of uveal melanoma cells, HGF was found to enhance cell migration, and that HGF-induced migration depends on PI3K/Akt pathway. The activation of PI3K/Akt pathway induced by the HGF/c-Met axis is involved in the downregulation of cell adhesion molecules E-cadherin and beta-catenin, contributing to the attenuation of cell-cell adhesion and promoting the enhanced motility and migration of uveal melanoma cells., HGF protects cultured cortical neurons against hypoxia/reoxygenation induced cell injury via ERK1/2 and PI-3K/Akt pathways, HGF stimulated both ERK1/2 and Akt activities in cortical neurons., Inhibition of ERK activation completely abolished the protective effects of HGF, and inhibition of Akt activation reduced, but did not completely eliminate the HGF mediated neuroprotection., It is suggested that the neuroprotection of HGF depend on ERK1/2 pathway, and, to a lesser extent, PI-3K/Akt pathway. , Met signals hepatocyte survival by preventing Fas-triggered FLIP degradation in a PI3k-Akt-dependent manner, Thus, Met acting on PI3K and Akt ensures high levels of FLIPL, and disruption of this pathway contributes to hepatic apoptosis and possibly to Fas-related liver diseases., The HGF-induced increase in Nkx 2.5 expression was inhibited by co-treatment with the PI3 kinase inhibitors Wortmannin and LY294002, but not by its inactive homolog LY303511, suggesting an involvement of the PI3 kinase/Akt pathway in this effect., X-Linked inhibitor of apoptosis protein expression level in colorectal cancer is regulated by hepatocyte growth factor/C-met pathway via Akt signaling, Activation of XIAP expression by HGF was inhibited by siRNA targeting Akt1 and Akt2., Activation of C-MET enhances XIAP through the Akt pathway., Hepatocyte growth factor prevents ventricular remodeling and dysfunction in mice via Akt pathway and angiogenesis, A significant reduction in apoptosis in the HGF-treated hearts was observed compared with control hearts, and was strongly associated with increased Akt activation., The antiapoptotic effect of HGF was mediated by activation of PI3-kinase/Akt pathway., The protective effect of HGF/SF against the ADR-induced apoptosis was abolished in the presence of either LY294002, an inhibitor of phosphatidylinositol-3'-OH kinase (PI3-K) or 1L-6-hydroxymethyl-chiro-inositol 2-(R)-2-O-methyl-3-O-octadecylcarbonate, an inhibitor of Akt, thus implicating the activation of PI3-K-Akt signaling in the antiapoptotic action of HGF/SF., Immunoblotting analysis revealed that HGF/SF stimulated the sustained phosphorylation of Akt for several hours, Furthermore, ADR-induced activation of caspase-9, a downstream molecule of Akt, was inhibited for at least 24 h after HGF/SF stimulation,, These results indicate that HGF/SF, but not EGF, transmitted protective signals against ADR-induced apoptosis by causing sustained activation of the PI3-K-Akt signaling pathway., Hepatocyte growth factor/scatter factor inhibits UVB-induced apoptosis of human keratinocytes but not of keratinocyte-derived cell lines via the phosphatidylinositol 3-kinase/AKT pathway, When we analyzed the signaling pathways initiated by the HGF/SF receptor c-met, we found that the phosphatidylinositol (PI) 3-kinase and its downstream-element AKT and the mitogen-activated protein (MAP) kinase were activated., Inhibition of PI 3-kinase led to a complete abrogation of the anti-apoptotic effect of HGF/SF, whereas blockade of the MAP kinase pathway had no effect., We now show in detached cells a cooperative effect of HGF and FN in the activation of PI 3-kinase and on the phosphorylation of PKB/Akt at serine 473., PI 3-kinase activity is also required for the HGF- and fibronectin-induced survival responses, as well as anchorage-independent colony growth., Together, these results demonstrate that the PI 3-kinase/Akt pathway is a key effector of the HGF- and fibronectin-induced survival response of breast carcinoma cells under detached conditions and corroborate an interaction between integrin and HGF/ Met signalling pathways in the development of invasive breast cancer.[SEP]Relations: CTNNB1 has relations: protein_protein with AKT1, protein_protein with AKT1, protein_protein with AKT2, protein_protein with AKT2, pathway_protein with RHO GTPases activate IQGAPs, pathway_protein with RHO GTPases activate IQGAPs, pathway_protein with Deactivation of the beta-catenin transactivating complex, pathway_protein with Deactivation of the beta-catenin transactivating complex. phosphatidylinositol 3-kinase signaling has relations: bioprocess_protein with AKT1, bioprocess_protein with AKT1.", "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]Relations: Afatinib has relations: drug_drug with Sirolimus, drug_drug with Sirolimus, drug_drug with Cannabidiol, drug_drug with Cannabidiol, drug_drug with Lapatinib, drug_drug with Lapatinib, drug_drug with Binimetinib, drug_drug with Binimetinib, drug_drug with Dovitinib, drug_drug with Dovitinib.", "label": "yes"}
{"id": "converted_2429", "sentence1": "Is Apremilast effective for Behcet’s syndrome?", "sentence2": "Apremilast is an immunomodulatory agent that works through phosphodiesterase 4 inhibition. A randomized controlled trial has shown that it is effective for the management of oral and genital ulcers and is generally well tolerated., AREAS COVERED: This review provides a digest of all current experience and evidence about pharmacological agents recently described as having a role in the treatment of BS, including interleukin (IL)-1 inhibitors, tocilizumab, rituximab, alemtuzumab, ustekinumab, interferon-alpha-2a, and apremilast., CONCLUSIONS: Apremilast was effective in treating oral ulcers, which are the cardinal manifestation of Behçet's syndrome.,  Apremilast, an inhibitor of phosphodiesterase-4, was effective in a phase 2, double blind, placebo-controlled study., Apremilast (Otezla(®)), an oral small molecule inhibitor of type-4 cyclic nucleotide phosphodiesterase (PDE-4), is under development with Celgene Corporation for the treatment of psoriatic arthritis, psoriasis, ankylosing spondylitis, Behçet's syndrome, atopic dermatitis, and rheumatoid arthritis., There were two serious adverse events in patients receiving apremilast.<br><b>CONCLUSIONS</b>: Apremilast was effective in treating oral ulcers, which are the cardinal manifestation of Behçet's syndrome., Apremilast (Otezla(®)), an oral small molecule inhibitor of type-4 cyclic nucleotide phosphodiesterase (PDE-4), is under development with Celgene Corporation for the treatment of psoriatic arthritis, psoriasis, ankylosing spondylitis, Behçet's syndrome, atopic dermatitis, and rheumatoid arthritis., CONCLUSIONS Apremilast was effective in treating oral ulcers, which are the cardinal manifestation of Behçet's syndrome., Apremilast, an oral small molecule inhibitor of phosphodiesterase 4 (PDE4), is in development for chronic inflammatory disorders, and has shown efficacy in psoriasis, psoriatic arthropathies, and Behçet's syndrome., oral ulcers the hallmark of behçet s syndrome can be resistant to conventional treatment therefore alternative agents are needed apremilast is an oral phosphodiesterase 4 inhibitor that modulates several inflammatory pathways we conducted a phase 2 multicenter placebo controlled study in which 111 patients with behçet s syndrome who had two or more oral ulcers were randomly assigned to receive 30 mg of apremilast twice daily or placebo for 12 weeks this regimen was followed by a 12 week extension phase in which the placebo group was switched to apremilast and a 28 day post treatment observational follow up phase the patients and clinicians were unaware of the study assignments throughout the trial the primary end point was the number of oral ulcers at week 12 secondary outcomes included pain from these ulcers measured on a 100 mm visual analogue scale with higher scores indicating worse pain the number of genital ulcers overall disease activity and quality of life the mean sd number of oral ulcers per patient at week 12 was significantly lower in the apremilast group than in the placebo group 0 5 1 0 vs 2 1 2 6 p 0 001 the mean decline in pain from oral ulcers from baseline to week 12 was greater with apremilast than with placebo 44 7 24 3 mm vs 16 0 32 5 mm p 0 001 nausea vomiting and diarrhea were more common in the apremilast group with 22 9 and 12 incidents respectively among 55 patients than in the placebo group with 10 1 and 2 incidents respectively among 56 patients findings that were similar to those in previous studies of apremilast there were two serious adverse events in patients receiving apremilast apremilast was effective in treating oral ulcers which are the cardinal manifestation of behçet s syndrome this preliminary study was neither large enough nor long enough to assess long term efficacy the effect on other manifestations of behçet s syndrome or the risk of uncommon serious adverse events funded by celgene clinicaltrials gov number nct00866359., current trends in the management of behçet s syndrome will be reviewed in this article biologic agents have gained increasing importance over the years in the management of behçet s syndrome long term results of observational studies have shown that anti tumor necrosis factor agents may be effective in behçet s syndrome patients with refractory eye involvement case series reporting about use of anti tumor necrosis factor agents in vascular and gastrointestinal involvement have also shown good results caution is required for infectious complications with these agents apremilast is an immunomodulatory agent that works through phosphodiesterase 4 inhibition a randomized controlled trial has shown that it is effective for the management of oral and genital ulcers and is generally well tolerated the outcome of behçet s syndrome with major organ involvement has improved with more effective management strategies especially with the use of biologic agents in severe cases controlled trials are needed to guide physicians in making treatment decisions.[SEP]Relations: Apremilast has relations: drug_drug with Bepotastine, drug_drug with Bepotastine, drug_drug with Bevacizumab, drug_drug with Bevacizumab, drug_drug with Aprepitant, drug_drug with Aprepitant, drug_drug with Bexarotene, drug_drug with Bexarotene, drug_drug with Cefetamet, drug_drug with Cefetamet.", "label": "yes"}
{"id": "converted_2229", "sentence1": "Does PCSK9 (Proprotein convertase subtilisin/kexin type 9) binds with HDL-receptor (HDL-R)?", "sentence2": "Recently it was revealed that the secreted Proprotein Convertase Subtilisin Kexin 9 (PCSK9) binds with LDL-receptor (LDL-R) causing its degradation in the lysosome with the result of LDL-C accumulating in the blood., The major goal of this study is to identify peptide/s from the catalytic domain of hPCSK9 that can block the binding of hPCSK9 and LDL-R and therefore can reduce LDL-R degradation leading to the clearance of LDL-C from the plasma., In vitro administration of SRT3025 to cultured AML12 hepatocytes attenuated Pcsk9 secretion and its binding to Ldlr, thereby reducing Pcsk9-mediated Ldlr degradation and increasing Ldlr expression and LDL uptake., Proprotein convertase subtilisin/kexin type 9 (PCSK9), which involves in low-density lipoprotein cholesterol (LDL-C) metabolism by interacting with the LDL receptor, is considered as a potent therapeutic target for treating hypercholesterolemia. , Taken together, these results suggested that the IgG1-PA4 can be served as a potential candidate for the treatment of hypercholesterolemia by inhibiting PCSK9-mediated degradation of cell surface LDLRs., Proprotein convertase subtilisin/kexin type 9 (PCSK9) binds to the low-density lipoprotein receptor, escorting it to its destruction in the lysosome and thereby preventing the recirculation of the low-density lipoprotein receptor to the hepatocyte cell surface. , However, statins have low efficiency because they also increase PCSK9 which targets LDLR for degradation., Inhibition of the enzyme PCSK9 (proprotein convertase subtilisin/kexin type 9), which is involved in depletion of the LDL-receptor, is a new pharmacologic approach. , Proprotein convertase subtilisin kexin type 9 (PCSK9) modulates LDL-c through post-translational degradation of the LDLR., Mechanistically, hepatic S1P KD was shown to decrease the liver and plasma levels of the protein proprotein convertase subtilisin/kexin type 9 (PCSK9), which degrades LDLR protein. , We report here the development of sdAbs targeting human PCSK9 (proprotein convertase subtilisin/kexin type 9) as an alternative to anti-PCSK9 mAbs., PCSK9 proprotein convertase subtilisin/kexin type (PCSK9) protein plays an important role in LDL cholesterol (LDL-C) metabolism, due to its role in the degradation of the LDL receptor., Proprotein convertase subtilisin/kexin type 9 (PCSK9) binds to LDL receptors, leading to their degradation, Low density lipoprotein binds to proprotein convertase subtilisin/kexin type-9 (PCSK9) in human plasma and inhibits PCSK9-mediated low density lipoprotein receptor degradation, Proprotein convertase subtilisin/kexin type-9 (PCSK9) is a secreted protein that binds to the epidermal growth factor-like-A domain of the low density lipoprotein receptor (LDLR) and mediates LDLR degradation in liver, Proprotein convertase subtilisin/kexin type 9 (PCSK9) binds LDL receptors, targeting them for degradation, Proprotein convertase subtilisin/kexin type 9 (PCSK9), which binds the low-density lipoprotein receptor and targets it for degradation, has emerged as an important regulator of serum cholesterol levels and cardiovascular disease risk, Secreted proprotein convertase subtilisin/kexin type 9 (PCSK9) binds to the low-density lipoprotein receptor (LDLR) at the cell surface and disrupts the normal recycling of the LDLR, Proprotein convertase, subtilisin/kexin type 9 (PCSK9), a key regulator of plasma LDL-cholesterol (LDL-c) and cardiovascular risk, is produced in liver and secreted into plasma where it binds hepatic LDL receptors (LDLR), leading to their degradation, Proprotein convertase subtilisin/kexin type 9 (PCSK9) promotes the degradation of the hepatic low-density lipoprotein receptor (LDL-R) and is therefore a prominent therapeutic target for reducing LDL-cholesterol, In the present study we scanned the related gene of a clinically diagnosed autosomal genetic hypercholesterolemia family for the possible mutations and established eukaryotic expression vector of mutation of proprotein convertase subtilisin/kexin type 9 (PCSK9) gene with gene recombination technique to investigate the contributions of the variation on low density lipoprotein receptor (LDL-R) metabolism and function alternation.Mutation detection was conducted for LDL-R, apolipoprotein B(100) (apoB(100)) and PCSK9 gene with nucleotide sequencing in a Chinese FH family, Proprotein convertase subtilisin-kexin type 9 (PCSK9) provides a key step in LDL metabolism by stimulating LDL receptor degradation., The proprotein convertase subtilisin-kexin type 9 (PCSK9) pathway plays a key role in lipoprotein metabolism by promoting LDL-receptor degradation., Proprotein convertase subtilisin-kexin type 9 (PCSK9) plays a key role in LDL receptor processing., Proprotein convertase subtilisin/kexin type 9 (PCSK9) promotes the degradation of the LDL receptor (LDLr) in hepatocytes, and its expression in mouse liver has been shown to decrease with fenofibrate treatment.We developed a sandwich ELISA using recombinant human PCSK9 protein and 2 affinity-purified polyclonal antibodies directed against human PCSK9., Proprotein convertase subtilisin kexin type 9 (PCSK9) enhances the degradation of the LDLR and modulates liver CD81 levels., Low-density lipoprotein (LDL) metabolism is governed by proprotein convertase subtilisin-kexin type 9 (PCSK9), which down-regulates LDL receptor expression, resulting in higher LDL cholesterol (LDL-C)., Proprotein convertase subtilisin kexin type 9 (PCSK9) is gaining attention as a key regulator of serum LDL-cholesterol (LDLC)., The proprotein convertase subtilisin/kexin type 9 (PCSK9) gene regulates cholesterol homoeostasis by accelerating low-density lipoprotein receptor (LDLR) degradation resulting in the decreased catabolism of low-density lipoprotein (LDL) leading to hypercholesterolaemia., Low density lipoprotein binds to proprotein convertase subtilisin/kexin type-9 (PCSK9) in human plasma and inhibits PCSK9-mediated low density lipoprotein receptor degradation., Proprotein convertase subtilisin/kexin type-9 (PCSK9) is a secreted protein that binds to the epidermal growth factor-like-A domain of the low density lipoprotein receptor (LDLR) and mediates LDLR degradation in liver., Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a regulator of LDL-cholesterol receptor homeostasis and emerges as a therapeutic target in the prevention of cardiovascular (CV) disease., The present study was conducted to investigate the role of plasma proprotein convertase subtilisin kexin type 9 (PCSK9) levels, a regulator of LDL-receptor expression, in the occurrence of diabetic dyslipidemia.[SEP]Relations: cell surface has relations: cellcomp_protein with PCSK9, cellcomp_protein with PCSK9, cellcomp_protein with PCSK6, cellcomp_protein with PCSK6, cellcomp_protein with KLRC4-KLRK1, cellcomp_protein with KLRC4-KLRK1. lysosome has relations: cellcomp_protein with PCSK9, cellcomp_protein with PCSK9. low-density lipoprotein particle has relations: cellcomp_protein with LDLR, cellcomp_protein with LDLR.", "label": "no"}
{"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]Relations: SETD1A has relations: disease_protein with schizophrenia, disease_protein with schizophrenia, disease_protein with epilepsy, disease_protein with epilepsy, protein_protein with SETD1B, protein_protein with SETD1B, protein_protein with BOD1L1, protein_protein with BOD1L1, protein_protein with E2F1, protein_protein with E2F1.", "label": "yes"}
{"id": "converted_1658", "sentence1": "Does cucumber lower blood sugar in diabetics?", "sentence2": "The ethanolic extract of Cucumis sativus Linn, Cucumis melo utilissimum Roxb, Cucumis melo Linn, Benincasa hispida Thunb Cogn and Tricosanthes anguina Nees, when administered in 250 mg/kg dose, orally to rats failed to lower blood sugar or to depress the peak value, after glucose load., Ethanolic extract of Tricosanthes dioica Roxb plant caused a significant lowering of blood sugar in fasted rats and depressed the peak value in glucose loaded single and longterm fed groups of rats. The ethanolic extract of the aerial part of T. dioica also induced significant depression in the peak values in the glucose loaded models., The amount of sucrose in ordinary marinated foods, such as herring, cucumber, and common beet was negligible, Dietary saponins of sea cucumber ameliorate obesity, hepatic steatosis, and glucose intolerance in high-fat diet-fed mice., In this study, we investigated the effects of saponins of sea cucumber (SSC) on high-fat diet-induced obesity, insulin resistance, and fatty liver in mice., Mice administrated with 0.1% SSC had significantly decreased serum glucose and insulin levels, lower homeostatic model assessment for insulin resistance index, and area under the blood glucose curve, suggesting that insulin sensitivity is enhanced by dietary SSC., [Effects of sea cucumber cerebroside and its long-chain base on lipid and glucose metabolism in obese mice]., OBJECTIVE: To investigate the effect of sea cucumber cerebroside(SCC) and its long-chain base(LCB) on lipid and glucose metabolism in obese mice., CONCLUSIONS: Sea cucumber cerebroside and its long-chain base can improve the glucose and lipid metabolism in obese mice., The hitherto unknown glucose regulating role of three vegetable peels from cucurbitaceae family was evaluated. In a preliminary study, effects of ethanolic extracts of Cucurbita pepo, Cucumis sativus and Praecitrullus fistulosus peels were studied at 250 and 500 mg kg(-1) d(-1) for 15 days in the alterations in serum glucose and in hepatic lipid peroxidation (LPO) in male mice., All the three peel extracts nearly reversed most of these changes induced by alloxan suggesting their possible role in ameliorating diabetes mellitus and related changes in serum lipids., Antidiabetic activity of aqueous fruit extract of Cucumis trigonus Roxb. in streptozotocin-induced-diabetic rats., Cucumis trigonus Roxb. (Cucurbitaceae) fruit is used in the Indian traditional medicine for the treatment of diabetes. Based on a number of reports on the blood glucose level reduction and the other complications of diabetes associated with some Cucurbitaceae plants, the antidiabetic effect of Cucumis trigonus fruit was investigated., The antidiabetic activity of aqueous extract of Cucumis trigonus fruit was evaluated by using normal and streptozotocin-induced-diabetic rats., The aqueous fruit extract of Cucumis trigonus has had beneficial effects in reducing the elevated blood glucose level and lipid profile of STZ-induced-diabetic rats., Possible amelioration of atherogenic diet induced dyslipidemia, hypothyroidism and hyperglycemia by the peel extracts of Mangifera indica, Cucumis melo and Citrullus vulgaris fruits in rats., Hitherto unknown efficacy of the peel extracts of Mangifera indica (MI), Cucumis melo (CM) and Citrullus vulgaris (CV) fruits in ameliorating the diet-induced alterations in dyslipidemia, thyroid dysfunction and diabetes mellitus have been investigated in rats., Rats, treated simultaneously with either of the peel extracts reversed the CCT-diet induced increase in the levels of tissue LPO, serum lipids, glucose, creatinine kinase-MB and decrease in the levels of thyroid hormones and insulin indicating their potential to ameliorate the diet induced alterations in serum lipids, thyroid dysfunctions and hyperglycemia/diabetes mellitus., Role of pectin from cucumber (Cucumis sativus) in modulation of protein kinase C activity and regulation of glycogen metabolism in rats., The regulatory role of protein kinase C (PKC) in glycogen metabolism in pectin fed rats was investigated. Administration of pectin (5 g/kg body wt/day) from cucumber (Cucumis sativius L.) led to inhibitory effects on PKC activity in the liver of rats. In the brain and pancreas, PKC activity was significantly higher in pectin-treated rats as compared to the control group. Level of blood glucose was significantly lowered and the level of glycogen in the liver was significantly increased in pectin-administered rats., Addition of fermented milk (yogurt) and pickled cucumber to a breakfast with a high-glycemic index bread significantly lowered postprandial glycemia and insulinemia compared with the reference meal. In contrast, addition of regular milk and fresh cucumber had no favorable effect on the metabolic responses., Tolbutamide, Cucurbita ficifolia, Phaseolus vulgaris, Opuntia streptacantha, Spinacea oleracea, Cucumis sativus and Cuminum cyminum decrease significantly the area under the glucose tolerance curve and the hyperglycemic peak., Two unsaturated fatty acids with potent α-glucosidase inhibitory activity purified from the body wall of sea cucumber (Stichopus japonicus)., In this study, 2 fatty acids with strong α-glucosidase-inhibitory activity, 7(Z)-octadecenoic acid and 7(Z),10(Z)-octadecadienoic acid, were purified and identified from sea cucumber. Therefore, sea cucumber fatty acids can potentially be developed as a novel natural nutraceutical for the management of type-2 diabetes.[SEP]Relations: Glucose intolerance has relations: disease_phenotype_positive with Cushing disease due to pituitary adenoma, disease_phenotype_positive with Cushing disease due to pituitary adenoma, disease_phenotype_positive with diabetes mellitus (disease), disease_phenotype_positive with diabetes mellitus (disease), disease_phenotype_positive with obesity due to SIM1 deficiency, disease_phenotype_positive with obesity due to SIM1 deficiency. Tolbutamide has relations: drug_drug with Invert sugar, drug_drug with Invert sugar, drug_effect with Hypoglycemia, drug_effect with Hypoglycemia.", "label": "yes"}
{"id": "converted_3527", "sentence1": "Does metformin alleviate atherosclerosis?", "sentence2": "Metformin and rosiglitazone both improve glycemic control in type 2 diabetes mellitus, however may possess different anti-inflammatory and anti-atherosclerotic properties. , Demonstrating antiatherothrombotic properties of dipeptidyl peptidase-4 inhibitors on proven markers is of substantial clinical significance. Coupled with their proven good safety profile these findings could translate into a significant clinical benefit., pleiotropic benefits of metformin in attenuation of atherosclerosis., Pleiotropic effects of metformin ameliorate atherosclerosis and vascular senescence., Metformin inhibits monocyte-to-macrophage differentiation via AMPK-mediated inhibition of STAT3 activation: potential role in atherosclerosis., Metformin attenuated Ang-II-induced atheromatous plaque formation and aortic aneurysm in ApoE(-/-) mice partly by reducing monocyte infiltration., Metformin, an anti-diabetic drug, was reported to possess anti-atherosclerotic effects. , Combined use of metformin and atorvastatin attenuates atherosclerosis in rabbits fed a high-cholesterol diet.,  In cultured macrophages, co-treatment with metformin and atorvastatin promoted cholesterol efflux and up-regulated expression of ATP-binding cassette transporters A1 and G1. Taken together, our results suggest that atorvastatin/metformin combination therapy may achieve additional anti-atherosclerotic benefits likely through increasing cholesterol efflux in macrophages., Metformin Suppresses Diabetes-Accelerated Atherosclerosis via the Inhibition of Drp1-Mediated Mitochondrial Fission., metformin abated the progression of diabetes-accelerated atherosclerosis by inhibiting mitochondrial fission in endothelial cells., metformin attenuated the development of atherosclerosis by reducing Drp1-mediated mitochondrial fission in an AMPK-dependent manner. , metformin's effects on lipids and atherosclerotic vascular disease and/or provide insights into the drug's mechanisms of action on the heart and vasculature., Several recently completed randomized clinical trials have reported effects of metformin on surrogate measures of atherosclerotic vascular disease, Metformin treatment prevents SREBP2-mediated cholesterol uptake and improves lipid homeostasis during oxidative stress-induced atherosclerosis, Metformin ameliorates the progression of atherosclerosis via suppressing macrophage infiltration and inflammatory responses, Our results suggest that metformin impeded the progression of atherosclerosis, possibly by suppressing macrophage infiltration and inflammatory responses.[SEP]Relations: Metformin has relations: drug_effect with Hyperhidrosis, drug_effect with Hyperhidrosis, drug_drug with Ifosfamide, drug_drug with Ifosfamide, drug_effect with Erythema, drug_effect with Erythema, drug_drug with Cyclosporine, drug_drug with Cyclosporine, drug_effect with Lethargy, drug_effect with Lethargy.", "label": "yes"}
{"id": "converted_3151", "sentence1": "Can oleuropein aglycone interfere with amyloid aggregation?", "sentence2": "Oleuropein, a phenolic secoiroid glycoside, is the main polyphenol in the olive oil. It has been reported that the aglycone form of Oleuropein (OleA) interferes in vitro and in vivo with amyloid aggregation of a number of proteins/peptides involved in amyloid, particularly neurodegenerative, diseases avoiding the growth of toxic oligomers and displaying protection against cognitive deterioration.[SEP]Relations: Abnormality of immune serum protein physiology has relations: phenotype_phenotype with Abnormal cytokine signaling, phenotype_phenotype with Abnormal cytokine signaling. Motor deterioration has relations: disease_phenotype_positive with PRKAR1B-related neurodegenerative dementia with intermediate filaments, disease_phenotype_positive with PRKAR1B-related neurodegenerative dementia with intermediate filaments, disease_phenotype_positive with neuronal ceroid lipofuscinosis, disease_phenotype_positive with neuronal ceroid lipofuscinosis, disease_phenotype_positive with infantile neuronal ceroid lipofuscinosis, disease_phenotype_positive with infantile neuronal ceroid lipofuscinosis, disease_phenotype_positive with spinocerebellar ataxia, disease_phenotype_positive with spinocerebellar ataxia.", "label": "yes"}
{"id": "converted_4098", "sentence1": "Is Nanog repressed in pluripotent stem cells?", "sentence2": "Aggregation of embryonic stem cells induces Nanog repression and primitive endoderm differentiation, Interestingly, cell aggregation by itself induced Nanog repression at the outer layer, which was essential for aggregation-induced primitive endoderm formation, early embryonic development, when downregulation of Nanog plays a crucial role., The homeobox gene Nanog is a key intrinsic determinant of self renewal in embryonic stem (ES) cells, and its repression leads ES cells to selectively differentiate into primitive endoderm., These data indicate that the Grb2/Mek pathway primarily mediates Nanog gene repression upon ES cell differentiation into primitive endoderm., Nanog and Oct4 associate with unique transcriptional repression complexes in embryonic stem cells, Nanog and Oct4 are essential transcription factors that regulate self-renewal and pluripotency of ES cells. , the mechanisms by which Nanog and Oct4 modulate ES cell fate remain unknown. , Nanog, Oct4 and repressor proteins co-occupy Nanog-target genes in mouse ES cells, suggesting that Nanog and Oct4 together may communicate with distinct repression complexes to control gene transcription., Nanog and Oct4 associate with unique repressor complexes on their target genes to control ES cell fate., he main finding of this study is that knockdown of Trp53 and Pten independently resulted in significantly higher expression levels of the pluripotency-associated gene Nanog, and we hypothesize that TRP53 and PTEN mediated repression is important for the insulation of male germ cells from pluripotency., The homeodomain transcription factor NANOG plays a central role in maintaining hESC pluripotency, The newly derived NANOG reporter hESC lines present novel tools to visualize NANOG expression in viable hESCs. , Loss of Pten causes tumor initiation following differentiation of murine pluripotent stem cells due to failed repression of Nanog., Furthermore, our data show that the mechanism by which Pten null ECCs emerge in vitro and cause tumors in vivo is through increased survival and self-renewal, due to failed repression of the transcription factor Nanog., We report here that Nanog and Oct4 are reexpressed in two mouse embryonic stem cell (mESC) lines following exposure to the differentiating agent DETA/NO., Furthermore, Nanog binding to the promoter of Brachyury leads to repression of this gene, thus disrupting mesendoderm transition., Maintaining pluripotency and indefinite self-renewal of embryonic stem cells requires a tight control of the expression of several key stemness factors, particularly Nanog and Oct4 transcription factors., Current evidence suggests that ES cells maintain their pluripotent state by expressing a battery of transcription factors including Oct4 and Nanog., Embryonic stem (ES) cell pluripotency is dependent upon sustained expression of the key transcriptional regulators Oct4, Nanog, and Sox2., The expression of Oct4 is activated by FoxD3 and Nanog but repressed by Oct4 itself, thus, exerting an important negative feedback loop to limit its own activity., Nanog, Oct4, and Sox2 form the core of a transcription factor network that maintains embryonic stem cells in the pluripotent state in both humans and mice., w that Bmi1 is enriched in the extraembryonic (endoderm [XEN] and trophectodermal stem [TS]) compartment and repressed by Nanog in pluripotent embryonic stem (ES) cells. In vivo, Bm, Nanog is a newly identified transcriptional factor bearing a homeodomain and expressed in pluripotential cells of preimplantation and early postimplantation embryos, and embryonic stem (ES) and embryonic germ (EG) cells., Knockout experiments indicate that Nanog functions as a key player in maintaining the pluripotency of stem cells., Thus, in germ cell development, NANOG is expressed in proliferating germ cells, in which nuclear reprogramming is progressing., Nanog maintains pluripotency of mouse embryonic stem cells by inhibiting NFkappaB and cooperating with Stat3., We performed a genome-wide screen that combined full-length mESC transcriptome genomic mapping data with chromatin immunoprecipitation genomic location maps of the key mESC transcription factors Oct4 and Nanog., Nanog safeguards pluripotency in mouse embryonic stem cells (mESCs)., Notably, the expression of Nanog, a key pluripotency regulator and repressor of extraembryonic endoderm specification in ES cells, was significantly reduced in Zic3 knockdown cells.[SEP]Relations: NANOG has relations: pathway_protein with Transcriptional regulation of pluripotent stem cells, pathway_protein with Transcriptional regulation of pluripotent stem cells, bioprocess_protein with positive regulation of stem cell proliferation, bioprocess_protein with positive regulation of stem cell proliferation, bioprocess_protein with stem cell population maintenance, bioprocess_protein with stem cell population maintenance, bioprocess_protein with somatic stem cell population maintenance, bioprocess_protein with somatic stem cell population maintenance, pathway_protein with POU5F1 (OCT4), SOX2, NANOG repress genes related to differentiation, pathway_protein with POU5F1 (OCT4), SOX2, NANOG repress genes related to differentiation.", "label": "no"}
{"id": "converted_2390", "sentence1": "Is Loss of function one of the cardinal signs of inflammation?", "sentence2": "The concept of the four cardinal signs of acute inflammation comes from antiquity as rubor et tumor cum calore et dolore, (redness and swelling with heat and pain) extended later by functio laesa (loss of function)., As early as 2000 years ago, the Roman encyclopaedist Aulus Cornelius Celsus recognised four cardinal signs of this response-redness, heat, swelling and pain; a fifth sign is loss of function.[..., It was Galen who added the disturbance of function (functio laesa) as the fifth cardinal sign of inflammation to the four well-known cardinal signs of Celsus (rubor, calor, tumor, dolor)., Tumor, calor, rubor, and dolor describe four cardinal signs of inflammation. The fifth-functio laesa, or loss of function-was promulgated by Rudolf Virchow, who, in the 19th century, also noted an intricate link between inflammation and cancer. [SEP]Relations: Impaired temperature sensation has relations: disease_phenotype_positive with superficial siderosis, disease_phenotype_positive with superficial siderosis, disease_phenotype_positive with pachydermoperiostosis, disease_phenotype_positive with pachydermoperiostosis, disease_phenotype_positive with Charcot-Marie-Tooth disease, disease_phenotype_positive with Charcot-Marie-Tooth disease. Portal inflammation has relations: phenotype_phenotype with Abnormality of the biliary system, phenotype_phenotype with Abnormality of the biliary system. Erythema has relations: disease_phenotype_positive with neonatal inflammatory skin and bowel disease, disease_phenotype_positive with neonatal inflammatory skin and bowel disease.", "label": "yes"}
{"id": "converted_2071", "sentence1": "Has the gorilla genome been determined?", "sentence2": "Starting with human, chimpanzee, gorilla, and orangutan genomes, our software generated an exhaustive data set of 292 ALs (∼1 kb each) in ∼3 h. , We generated a high-quality assembly of the gorilla genome using single-molecule, real-time sequence technology and a string graph de novo assembly algorithm, Here we present the assembly and analysis of a genome sequence for the western lowland gorilla, and compare the whole genomes of all extant great ape genera., DNA sequencing reveals that the genomes of the human, gorilla and chimpanzee share more than 98% homology.[SEP]", "label": "yes"}
{"id": "converted_3736", "sentence1": "Is αCGRP a member of the CGRP family?", "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., These efforts unravel a novel amyloidogenic member of the CGRP family and provide insights into the mechanism underlying the αCGRP polymerization., These efforts unravel a novel amyloidogenic member of the CGRP family and provide insights into the mechanism underlying the αCGRP polymerization.[SEP]Relations: neuropeptide hormone activity has relations: molfunc_protein with GRP, molfunc_protein with GRP, molfunc_protein with AGRP, molfunc_protein with AGRP, molfunc_protein with CCK, molfunc_protein with CCK, molfunc_protein with QRFP, molfunc_protein with QRFP, molfunc_protein with PRLH, molfunc_protein with PRLH.", "label": "yes"}
{"id": "converted_905", "sentence1": "Are viruses involved in the etiology of human subacute thyroiditis?", "sentence2": "he etiology of subacute (de Quervain's) thyroiditis (SAT) is uncertain, although it probably represents a nonspecific inflammatory response by the thyroid to a variety of viruses., Subacute thyroiditis is an inflammatory disorder of the thyroid caused probably by viruses. I, We believe that the etiologic agent was the Epstein-Barr virus because heterophile and Epstein-Barr virus-specific antibodies were positive., ltogether, these results indicate that the mechanism of inhibition of Spumavirinae infection by interferon differs from that described for the other Retroviridae, and particularly for types B, C and D viruses. Our data is of therapeutic interest since Spumavirinae have been linked to pathological processes such as de Quervain thyroiditis.[SEP]Relations: subacute thyroiditis has relations: disease_disease with thyroiditis (disease), disease_disease with thyroiditis (disease). regulation of excitatory postsynaptic membrane potential involved in skeletal muscle contraction has relations: bioprocess_bioprocess with modulation of excitatory postsynaptic potential, bioprocess_bioprocess with modulation of excitatory postsynaptic potential.", "label": "yes"}
{"id": "converted_3806", "sentence1": "Does head ct increase brain tumor risk?", "sentence2": "Excess relative risk of new brain tumor averaged 1.29 (95% confidence interval, 0.66-1.93) for pediatric patients exposed to one or more head CTs. Tumor incidence increased with number of pediatric head CTs in a dose-dependent manner, with measurable excess incidence even after a single scan. Converging evidence from epidemiological studies supported a small excess risk of brain tumor incidence after even a single CT exam in pediatric patients. , Recent epidemiologic evidence from a national registry of children who underwent CT scans suggests a higher-than-expected incidence of secondary tumors. , However, we found 1) a statistically significant correlation between radiation dose and age at procedure, as well as number and type of procedures, and 2) a substantial increase in lifetime predicted risk of tumor above baseline in the cohort of young children who undergo neurointerventions.CONCLUSIONS: Although neurointerventional procedures have dramatically improved the prognosis of children facing serious cerebrovascular conditions, the predicted risk of secondary tumors, particularly in the youngest patients and those undergoing multiple procedures, is sobering., Conclusion When prevalent cases of meningioma at first exposure to CT of the head are excluded, no statistically significant increase in risk of meningioma was found among exposed subjects compared with unexposed control subjects.,  data suggest that 1 excess brain malignancy occurred after 4000 brain CTs (40 mSv per scan) and that the estimated risk in the 10 years following CT exposure was 1 brain tumor per 10,000 patients exposed to a 10 mGy scan at less than 10 years of age.CONCLU, SIONS: The model predicts that the effective radiation dose from a single head CT is capable of inducing a thyroid or brain tumor in an infant or child. These, Neither whole head CT nor cumulative brain dose to the brain increased the risk of glioma or of all brain tumours., rison of exposed and unexposed cohorts showed that there was no statistically significant increase in the risk of meningioma after exposure to CT of the head (HR: 1.49; 95% confidence interval: 0.97, 2.30; P = .07). If incident c, from epidemiological studies supported a small excess risk of brain tumor incidence after even a single CT exam in pediatric patients. However, refined e, ve risk of new brain tumor averaged 1.29 (95% confidence interval, 0.66-1.93) for pediatric patients exposed to one or more head CTs. Tumor incidence,  CT nor cumulative brain dose to the brain increased the risk of glioma or of all brain tumours. Although this st, o for developing a brain tumour from having a brain CT was 0.93 (95% confidence interval: 0.38-1.82). This was har, Tumor incidence increased with number of pediatric head CTs in a dose-dependent manner, with measurable excess incidence even after a single scan., Converging evidence from epidemiological studies supported a small excess risk of brain tumor incidence after even a single CT exam in pediatric patients., Excess relative risk of new brain tumor averaged 1.29 (95% confidence interval, 0.66-1.93) for pediatric patients exposed to one or more head CTs., Epidemiological studies consistently cited increased tumor incidence in pediatric patients (ages 0-18) exposed to head CTs., RESULTS: A positive correlation between exposure to CT scans and developing central nervous system tumors was evident in all cohorts. The strength of the association varied across the studies. Exclusion of patients with predisposing factors to central nervous system tumors was examined in four studies with a decreased risk to develop central nervous system tumors noted in three studies. Two studies reported nonsignificant reduction in the excess relative risk per milliGray of brain dose after adjusting for predisposing factors, whereas the reduction was significant in one study. The frequency of CT exposure was proportional to the risk of developing tumors in two studies although not significantly maintained in two other studies. , RESULTS: The overall risk was not significantly different in the two cohorts (incidence rate=36.72 per 100 000 person-years in the exposed cohort, 28.48 per 100 000 person-years in the unexposed cohort, hazard ratio (HR)=1.29, 95% confidence interval (CI)=0.90-1.85). The risk of benign brain tumour was significantly higher in the exposed cohort than in the unexposed cohort (HR=2.97, 95% CI=1.49-5.93). The frequency of CT examination showed strong correlation with the subsequent overall risk of malignancy and benign brain tumour.CONCLUSIONS: We found that paediatric head CT examination was associated with an increased incidence of benign brain tumour., CONCLUSIONS: We found evidence that CT-related radiation exposure increases brain tumor risk. , Compared with the general population, incidence of brain tumors was higher in the cohort of children with CT scans, requiring cautious interpretation of the findings., BACKGROUND: Recent studies linking radiation exposure from pediatric computed tomography (CT) to increased risks of leukemia and brain tumors lacked data to control for cancer susceptibility syndromes (CSS). , IMPACT: Future studies should identify TSC patients in order to avoid overestimation of brain tumor risks due to radiation exposure from CT scans., The radiation-induced occurrence of meningiomas and other brain tumours most probably contributes to the continuously increasing incidence of these diseases which is observed in several industrial nations, as well as the exposure of the bone marrow by CT to the increase of childhood leukaemia., 1,000 annual paediatric CT investigations of the skull will lead to about 3 excess neoplasms in the head region, i.e., the probability of an induced late effect must be suspected in the range of some thousandths. [SEP]Relations: malignant ear neoplasm has relations: disease_disease with head and neck cancer, disease_disease with head and neck cancer. tuberous sclerosis has relations: disease_disease with polymalformative genetic syndrome with increased risk of developing cancer, disease_disease with polymalformative genetic syndrome with increased risk of developing cancer. Brain neoplasm has relations: drug_effect with Carmustine, drug_effect with Carmustine. benign neoplasm of brain has relations: disease_disease with intracranial hemangioma, disease_disease with intracranial hemangioma, disease_protein with PTCH1, disease_protein with PTCH1.", "label": "yes"}
{"id": "converted_4647", "sentence1": "Is telomestatin, a novel statin drug used to treat high cholesterol?", "sentence2": "Telomestatin is a natural product isolated from Streptomyces anulatus 3533-SV4 and has been shown to be a very potent telomerase inhibitor., Telomestatin, a potent telomerase inhibitor that interacts quite specifically with the human telomeric intramolecular g-quadruplex., Activity of a novel G-quadruplex-interactive telomerase inhibitor, telomestatin (SOT-095), ,  G-quadruplex-interactive telomerase inhibitor, telomestatin (SOT-095),,  We found that treatment with telomestatin reproducibly inhibited telomerase activity in the BCR-ABL-positive leukemic cell lines, A novel telomerase inhibitor, telomestatin, isolated from Streptomyces anulatus is the most potent telomerase inhibitor so far., Telomerase inhibitor, telomestatin, a specific mechanism to interact with telomere structure, Telomestatin specifically inhibited telomerase without affecting reverse transcriptases and polymerases., In addition, telomestatin induced telomere shortening, but its ratio was extremely faster than that observed in physiological telomere shortening., A novel telomerase inhibitor, telomestatin, isolated from Streptomyces anulatus is the most potent telomerase inhibitor so far. , ructure has been yet resolved for the complex with telomestatin, one of the most promising G-quadruplex-targeting anticancer drug candidates. Here, Telomestatin, a strong telomerase inhibitor with G-quadruplex stabilizing activity, is a potential therapeutic agent for treating cancers., Thus, telomestatin provide the novel therapeutic molecular target for cancer chemotherapy., Telomerase inhibition with a novel G-quadruplex-interactive agent, telomestatin: in vitro and in vivo studies in acute leukemia., Activity of a novel G-quadruplex-interactive telomerase inhibitor, telomestatin (SOT-095), against human leukemia cells: involvement of ATM-dependent DNA damage response pathways.[SEP]Relations: telomerase inhibitor activity has relations: molfunc_protein with POT1, molfunc_protein with POT1, molfunc_protein with TEN1, molfunc_protein with TEN1, molfunc_protein with PINX1, molfunc_protein with PINX1, molfunc_protein with PIF1, molfunc_protein with PIF1. Telomere Extension By Telomerase has relations: pathway_protein with TERT, pathway_protein with TERT.", "label": "no"}
{"id": "converted_4677", "sentence1": "Is Ameloblastoma (AB) a benign tumor that never metastasizes?", "sentence2": "Ameloblastic carcinoma (AC) is defined as a rare primary epithelial odontogenic malignant neoplasm and the malignant counterpart of benign epithelial odontogenic tumor of ameloblastoma (AB) by the WHO classification, AC develops pulmonary metastasis in about one third of the patients and reveals a poor prognosis, Ameloblastomas are benign but locally invasive neoplasms which may grow to massive proportions and cause significant morbidity. Although some types of ameloblastoma can be treated predictably with aggressive surgical treatment, recurrent ameloblastoma and metastasising ameloblastoma are still difficult to treat., Ameloblastoma of the maxilla is a rare odontogenic tumor that rarely metastasizes., Ameloblastoma is an odontogenic tumor, usually benign, which rarely metastasizes to distant organs., Although ameloblastomas rarely metastasise, recurrences together with radical surgery often result in facial deformity and significant morbidity., The World Health Organization (WHO) has defined malignant ameloblastoma (MA) as a histologically benign-appearing ameloblastoma that has metastasized., Distant metastasis is a very rare condition and is designated as metastasizing (malignant) ameloblastoma despite its benign histological appearance., Ameloblastoma is a locally invasive, histologically nonmalignant tumor that may on very rare occasions give rise to metastases.[SEP]Relations: ameloblastoma has relations: disease_disease with musculoskeletal system benign neoplasm, disease_disease with musculoskeletal system benign neoplasm, disease_disease with musculoskeletal system benign neoplasm, disease_disease with musculoskeletal system benign neoplasm, disease_disease with benign epithelial neoplasm, disease_disease with benign epithelial neoplasm, disease_disease with benign epithelial neoplasm, disease_disease with benign epithelial neoplasm, disease_disease with bone ameloblastoma, disease_disease with bone ameloblastoma.", "label": "no"}
{"id": "converted_882", "sentence1": "Is nivolumab used for treatment of Non–Small-Cell Lung Cancer?", "sentence2": "BACKGROUND: Patients with advanced squamous-cell non-small-cell lung cancer (NSCLC) who have disease progression during or after first-line chemotherapy have limited treatment options. This randomized, open-label, international, phase 3 study evaluated the efficacy and safety of nivolumab, a fully human IgG4 programmed death 1 (PD-1) immune-checkpoint-inhibitor antibody, as compared with docetaxel in this patient population., CONCLUSIONS: Among patients with advanced, previously treated squamous-cell NSCLC, overall survival, response rate, and progression-free survival were significantly better with nivolumab than with docetaxel, regardless of PD-L1 expression level., Agents currently in active clinical development for lung cancer include ipilimumab, which modulates the cytotoxic T-lymphocyte-associated antigen 4 pathway, and multiple agents targeting the programmed death protein 1 (PD-1) pathway, both anti-PD-1 compounds (nivolumab, pembrolizumab [MK-3475]) and those that target programmed death ligand 1 (PD-L1), a key ligand for PD-1 (BMS-936559, MPDL3280A)., Overall Survival and Long-Term Safety of Nivolumab (Anti-Programmed Death 1 Antibody, BMS-936558, ONO-4538) in Patients With Previously Treated Advanced Non-Small-Cell Lung Cancer., We report overall survival (OS), response durability, and long-term safety in patients with non-small-cell lung cancer (NSCLC) receiving nivolumab in this trial.PATIENTS AND METHODS: Patients (N = 129) with heavily pretreated advanced NSCLC received nivolumab 1, 3, or 10 mg/kg intravenously once every 2 weeks in 8-week cycles for up to 96 weeks. , CONCLUSION: Nivolumab monotherapy produced durable responses and encouraging survival rates in patients with heavily pretreated NSCLC. Randomized clinical trials with nivolumab in advanced NSCLC are ongoing., Two PD-1 inhibitors, Bristol-Myers Squibb's nivolumab and Merck's MK-3475, both demonstrated positive results in phase I trials of previously treated patients with non-small cell lung cancer, reported at the World Conference on Lung Cancer in Sydney, Australia., Recently, many trials addressed the role of such therapies for metastatic NSCLC treatment: ipilimumab, tremelimumab, nivolumab and lambrolizumab are immunotherapeutic agents of main interest in this field., Two PD-1 inhibitors, Bristol-Myers Squibb&apos;s nivolumab and Merck&apos;s MK-3475, both demonstrated positive results in phase I trials of previously treated patients with non-small cell lung cancer, reported at the World Conference on Lung Cancer in Sydney, Australia, Nivolumab, pembrolizumab (formerly known as MK-3475 and lambrolizumab), and pidilizumab are anti-PD-1 antibodies in clinical development for melanoma, non-small cell lung cancer, renal cell carcinoma, head and neck cancers, lymphoma, and several other cancers, Nivolumab versus Docetaxel in Advanced Squamous-Cell Non-Small-Cell Lung Cancer., Activity and safety of nivolumab, an anti-PD-1 immune checkpoint inhibitor, for patients with advanced, refractory squamous non-small-cell lung cancer (CheckMate 063): a phase 2, single-arm trial.,  Patients with squamous non-small-cell lung cancer that is refractory to multiple treatments have poor outcomes. We assessed the activity of nivolumab, a fully human IgG4 PD-1 immune checkpoint inhibitor antibody, for patients with advanced, refractory, squamous non-small-cell lung cancer.,  Nivolumab has clinically meaningful activity and a manageable safety profile in previously treated patients with advanced, refractory, squamous non-small cell lung cancer. These data support the assessment of nivolumab in randomised, controlled, phase 3 studies of first-line and second-line treatment.[SEP]Relations: Nivolumab has relations: drug_drug with Blosozumab, drug_drug with Blosozumab, drug_drug with Sifalimumab, drug_drug with Sifalimumab, drug_drug with Nimotuzumab, drug_drug with Nimotuzumab, drug_drug with Tositumomab, drug_drug with Tositumomab, drug_drug with Afelimomab, drug_drug with Afelimomab.", "label": "yes"}
{"id": "converted_4409", "sentence1": "Does addition of valproic acid improve survival of patients with diffuse intrinsic pontine glioma?", "sentence2": "Median event-free survival (EFS) and overall survival (OS) for DIPG were 7.8 (95% CI 5.6-8.2) and 10.3 (7.4-13.4) months, and estimated one-year EFS was 12% (2%-31%). Median EFS and OS for HGG were 9.1 (6.4-11) and 12.1 (10-22.1) months, and estimated one-year EFS was 24% (7%-45%). , CONCLUSION: Addition of VPA and bevacizumab to radiation was well tolerated but did not appear to improve EFS or OS in children with DIPG or HGG., Event-free survival and overall survival of patients not treated with valproic acid were 6.5 and 7.8 months. Accelerated failure time model (a parametric multivariate regression test for time-to-failure data) showed a statistically significant superiority of the median event-free survival of treated patients (6.5 vs. 9.5 months in treated patients; HR 0.54-95 % CI 0.33-0.87; p < 0.05) and also of overall survival (7.8 vs. 13.4 months in treated patients; HR 0.60-95 % CI 0.37-0.98; p = 0.05).[SEP]Relations: diffuse intrinsic pontine glioma has relations: disease_disease with childhood brain stem glioma, disease_disease with childhood brain stem glioma. Valproic acid has relations: contraindication with inherited porphyria, contraindication with inherited porphyria, contraindication with hyperargininemia, contraindication with hyperargininemia, contraindication with porphyrin metabolism disease, contraindication with porphyrin metabolism disease, contraindication with pancreatitis, contraindication with pancreatitis.", "label": "no"}
{"id": "converted_930", "sentence1": "Is the length of the poly(A) tail involved in human disease?", "sentence2": "In human mitochondria, polyadenylation of mRNA, undertaken by the nuclear-encoded mitochondrial poly(A) RNA polymerase, is essential for maintaining mitochondrial gene expression. Our molecular investigation of an autosomal-recessive spastic ataxia with optic atrophy, present among the Old Order Amish, identified a mutation of MTPAP associated with the disease phenotype. When subjected to poly(A) tail-length assays, mitochondrial mRNAs from affected individuals were shown to have severely truncated poly(A) tails.[SEP]Relations: Mitochondrial inheritance has relations: disease_phenotype_positive with cyclic vomiting syndrome, disease_phenotype_positive with cyclic vomiting syndrome, disease_phenotype_positive with MELAS syndrome, disease_phenotype_positive with MELAS syndrome. Optic atrophy has relations: disease_phenotype_positive with distal monosomy 17q, disease_phenotype_positive with distal monosomy 17q, disease_phenotype_positive with distal monosomy 13q, disease_phenotype_positive with distal monosomy 13q, disease_phenotype_positive with Cockayne syndrome, disease_phenotype_positive with Cockayne syndrome.", "label": "yes"}
{"id": "converted_4586", "sentence1": "Is Mediator present at super enhancers?", "sentence2": "BRD4 and Mediator were found to co-occupy thousands of enhancers associated with active genes., Master transcription factors and mediator establish super-enhancers at key cell identity genes, Master transcription factors Oct4, Sox2, and Nanog bind enhancer elements and recruit Mediator to activate much of the gene expression program of pluripotent embryonic stem cells (ESCs)., These domains, which we call super-enhancers, consist of clusters of enhancers that are densely occupied by the master regulators and Mediator, BRD4 maintains transcription of core stem cell genes such as OCT4 and PRDM14 by occupying their super-enhancers (SEs), large clusters of regulatory elements, and recruiting to them Mediator and CDK9, the catalytic subunit of the positive transcription elongation factor b (P-TEFb), to allow Pol-II-dependent productive elongation., The term 'super-enhancer' has been used to describe groups of putative enhancers in close genomic proximity with unusually high levels of Mediator binding, as measured by chromatin immunoprecipitation and sequencing (ChIP-seq)., Mediator kinase inhibition further activates super-enhancer-associated genes in AML., Furthermore, the binding of SIM2 marks a particular sub-category of enhancers known as super-enhancers. These regions are characterized by typical DNA modifications and Mediator co-occupancy (MED1 and MED12). , Many genes determining cell identity are regulated by clusters of Mediator-bound enhancer elements collectively referred to as super-enhancers. , A number of studies have recently demonstrated that super-enhancers, which are large cluster of enhancers typically marked by a high level of acetylation of histone H3 lysine 27 and mediator bindings, are frequently associated with genes that control and define cell identity during normal development. , Super-enhancers are characterized by high levels of Mediator binding and are major contributors to the expression of their associated genes. [SEP]Relations: Protein S human has relations: drug_drug with Resveratrol, drug_drug with Resveratrol, drug_drug with Resveratrol, drug_drug with Resveratrol, drug_drug with Resveratrol, drug_drug with Resveratrol, drug_drug with Platelet Activating Factor, drug_drug with Platelet Activating Factor, drug_drug with Platelet Activating Factor, drug_drug with Platelet Activating Factor.", "label": "yes"}
{"id": "converted_4540", "sentence1": "Do only changes in coding regions of MEF2C cause developmental disorders?", "sentence2": "Non-coding region variants upstream of MEF2C cause severe developmental disorder through three distinct loss-of-function mechanisms., Clinical genetic testing of protein-coding regions identifies a likely causative variant in only around half of developmental disorder (DD) cases. The contribution of regulatory variation in non-coding regions to rare disease, including DD, remains very poorly understood. We screened 9,858 probands from the Deciphering Developmental Disorders (DDD) study for de novo mutations in the 5' untranslated regions (5' UTRs) of genes within which variants have previously been shown to cause DD through a dominant haploinsufficient mechanism. We identified four single-nucleotide variants and two copy-number variants upstream of MEF2C in a total of ten individual probands. We developed multiple bespoke and orthogonal experimental approaches to demonstrate that these variants cause DD through three distinct loss-of-function mechanisms, disrupting transcription, translation, and/or protein function. These non-coding region variants represent 23% of likely diagnoses identified in MEF2C in the DDD cohort, but these would all be missed in standard clinical genetics approaches. Nonetheless, these variants are readily detectable in exome sequence data, with 30.7% of 5' UTR bases across all genes well covered in the DDD dataset. Our analyses show that non-coding variants upstream of genes within which coding variants are known to cause DD are an important cause of severe disease and demonstrate that analyzing 5' UTRs can increase diagnostic yield. We also show how non-coding variants can help inform both the disease-causing mechanism underlying protein-coding variants and dosage tolerance of the gene.[SEP]Relations: developmental disability has relations: disease_protein with MECP2, disease_protein with MECP2. MEF2C has relations: disease_protein with intellectual disability, disease_protein with intellectual disability, disease_protein with autism spectrum disorder, disease_protein with autism spectrum disorder, disease_protein with autism (disease), disease_protein with autism (disease), disease_protein with autism susceptibility 1, disease_protein with autism susceptibility 1.", "label": "no"}
{"id": "converted_1486", "sentence1": "Does ventriculoperitoneal shunt improve normal pressure hydrocephalus?", "sentence2": "Clinical improvement depends not only on the capability to restore the cerebrospinal fluid dynamic, but also on the ability of cerebral parenchyma to recover the metabolic function.,  After shunting, the global CMRglu significantly increased (2.95 ± 0.44 vs 4.38 ± 0.68, p = 10(-7)) in all INPH patients with a mean percentage value of 48.7%. , Our preliminary data show that changes in the CMRglu are promptly reversible after surgery and that there is a relationship between the early metabolic changes and clinical symptoms, independently from the simultaneous changes in the ventricular size. The remarkable and prompt improvement in the global CMRglu and in symptoms may also have important implications for the current concept of \"neuronal plasticity\" and for the cells' reactivity in order to recover their metabolic function., Outcome of shunting in INPH is most often successful when patients are accurately diagnosed, suitably evaluated for surgical candidacy, and managed carefully throughout the preoperative, surgical, and postoperative periods., The decision to perform the only efficient procedure, i.e., a ventricular shunt operation, depends upon a number of established arguments in favor of that procedure. Clinical improvement, which is often spectacular, can then confirm the diagnosis. , During the 1st postoperative year, there was improvement in the condition of 22 patients (96%) who had received a ventricular shunt; 21 of these patients (91%) remained improved until death or for at least 5 years., Shunt treatment showed an effect on cognitive functions of distractibility of attention and motor speed, but not on intelligence of memory. Three patients deteriorated, eleven remained stable and sixteen showed significant improvement on psychological tests, mainly those for attention, motor speed and memory, but rarely did any improvement of intelligence occur.[SEP]Relations: Cessation of head growth has relations: phenotype_phenotype with Secondary microcephaly, phenotype_phenotype with Secondary microcephaly, disease_phenotype_positive with Angelman syndrome due to a point mutation, disease_phenotype_positive with Angelman syndrome due to a point mutation, disease_phenotype_positive with leukoencephalopathy with vanishing white matter, disease_phenotype_positive with leukoencephalopathy with vanishing white matter, disease_phenotype_positive with neurodevelopmental disorder with progressive microcephaly, spasticity, and brain anomalies, disease_phenotype_positive with neurodevelopmental disorder with progressive microcephaly, spasticity, and brain anomalies. cerebrospinal fluid has relations: anatomy_anatomy with transudate, anatomy_anatomy with transudate.", "label": "yes"}
{"id": "converted_480", "sentence1": "Are epigenetic modifications implicated in cardiovascular development and disease?", "sentence2": "Gene expression regulation through the interplay of DNA methylation and histone modifications is well-established, although the knowledge about the function of epigenetic signatures in cardiovascular disease is still largely unexplored., The study of epigenetic markers is, therefore, a very promising frontier of science which may aid in a deeper understanding of molecular mechanisms underlying the modulation of gene expression in the biomolecule pathways linked to cardiovascular diseases., This review highlights our current knowledge of epigenetic gene regulation and the evidence that chromatin remodeling and histone modifications play key roles in the pathogenesis of cardiovascular disease through (re)programming of cardiovascular (stem) cells commitment, identity and function., Notably, multiple subunits of switching defective/sucrose non-fermenting (SWI/SNF) chromatin-remodeling complexes have been identified as strong candidates underlying these defects because they physically and functionally interact with cardiogenic transcription factors critical to cardiac development, such as TBX5, GATA-4, and NKX2-5. While these studies indicate a critical role of SWI/SNF complexes in cardiac development and congenital heart disease, many exciting new discoveries have identified their critical role in the adult heart in both physiological and pathological conditions involving multiple cell types in the heart, including cardiomyocytes, vascular endothelial cells, pericytes, and neural crest cells., Recent studies have greatly expanded our understanding of the regulation of cardiovascular development at the chromatin level, including the remodeling of chromatin and the modification of histones. Chromatin-level regulation integrates multiple inputs and coordinates broad gene expression programs. Thus, understanding chromatin-level regulation will allow for a better appreciation of gene regulation as a whole and may set a fundamental basis for cardiovascular disease., Genetic and epigenetic factors are of great importance in cardiovascular biology and disease. Tobacco-smoking, one of the most important cardiovascular risk factors, is itself partially determined by genetic background and is associated with altered epigenetic patterns., Epigenetic modifications, including DNA methylation, histone modification (acetylation, methylation and phosphorylation) and miRNA, are critical for regulating developmental events. However, aberrant epigenetic mechanisms may lead to pathological consequences such as cardiovascular disease (CAD), neurodegenerative disease, obesity, metabolic disorder, bone and skeletal diseases and various cancers., Cardiovascular disease pathways are now being approached from the epigenetic perspective, including those associated with atherosclerosis, angiogenesis, ischemia-reperfusion damage, and the cardiovascular response to hypoxia and shear stress, among many others. With increasing interest and expanding partnerships in the field, we can expect new insights to emerge from epigenetic perspectives of cardiovascular health., Epigenetic modifications are heritable alterations of the genome, which can govern gene expression without altering the DNA sequence. The purpose of this review is to render an overview of the possible mechanisms of epigenetic regulation of gene expression in response to environmental pollutants leading to cardiovascular diseases (CVD)., From varied study approaches directed either toward the general understanding of the key pathway regulatory genes, or sampling population cohorts for global and gene-specific changes, it has been possible to identify several epigenetic signatures of environmental exposure relevant to CVD., An understanding of chromatin remodelling in response to environmental stimuli conducive to CVD is emerging, with the promise of novel diagnostic and therapeutic candidates., Consolidated knowledge is accumulating as to the role of epigenetic regulatory mechanisms in the physiology of vascular development and vascular tone as well as in the pathogenesis of cardiovascular disease. The modulation of gene expression through modification of the epigenome by structural changes of the chromatin architecture without alterations of the associated genomic DNA sequence is part of the cellular response to environmental changes. Such environmental conditions, which are finally being translated into adaptations of the cardiovascular system, also comprise pathological conditions such as atherosclerosis or myocardial infarction. , Emerging data suggest that these epigenetic modifications also impact on the development of cardiovascular disease. Histone modifications lead to the modulation of the expression of genetic information through modification of DNA accessibility. In addition, RNA-based mechanisms (e.g., microRNAs and long non-coding RNAs) influence the development of disease., We here outline the recent work pertaining to epigenetic changes in a cardiovascular disease setting., Epigenetics may represent one of the possible scientific explanations of the impact of such intrauterine risk factors for the subsequent development of cardiovascular disease (CVD) during adulthood., Epigenetic mechanisms include DNA methylation, histone modification, and microRNA alterations, which collectively enable the cell to respond quickly to environmental changes. A number of CVD risk factors, such as nutrition, smoking, pollution, stress, and the circadian rhythm, have been associated with modification of epigenetic marks. Further examination of these mechanisms may lead to earlier prevention and novel therapy for CVD.,  Emerging data suggest that these epigenetic modifications also impact on the development of cardiovascular disease., Emerging data suggest that these epigenetic modifications also impact on the development of cardiovascular disease., Epigenetic alterations are associated with inflammation and cardiovascular disease in patients with chronic kidney disease., Emerging data suggest that these epigenetic modifications also impact on the development of cardiovascular disease, Epigenetic mechanisms that underpin metabolic and cardiovascular diseases., Epigenetic regulation of cardiovascular differentiation., Epigenetic control mechanisms play a key role in the regulation of embryonic development and tissue homeostasis and modulate cardiovascular diseases.[SEP]Relations: cardiovascular disease has relations: disease_disease with autoimmune disease of cardiovascular system, disease_disease with autoimmune disease of cardiovascular system, contraindication with Epinephrine, contraindication with Epinephrine, contraindication with Ephedrine, contraindication with Ephedrine, disease_disease with disease by anatomical system, disease_disease with disease by anatomical system, disease_disease with congenital anomaly of cardiovascular system, disease_disease with congenital anomaly of cardiovascular system.", "label": "yes"}
{"id": "converted_1871", "sentence1": "Can NEECHAM Confusion Scale be used for evaluation of postoperative delirium?", "sentence2": "Sampling was achieved in a nonrandomized targeted manner and delirium was assessed using NeeCham questionnaire. , Delirium in older patients: a diagnostic study of NEECHAM Confusion Scale in surgical intensive care unit., AIMS AND OBJECTIVES: To estimate the diagnostic value and determine the feasibility of the NEECHAM Confusion Scale on critically ill older patients., CONCLUSIONS: Findings from this study confirm the good diagnostic value and ease of application of the NEECHAM scale with nonventilated intensive care patients.RELEVANCE TO CLINICAL PRACTICE: The NEECHAM scale can be used to detect delirium during the routine nursing assessment of nonintubated older patients as it requires minimal demand and stress on the patient as well as on the bedside nurse., The NEECHAM Confusion Scale and the validated chart review instrument were used for diagnosis of delirium. , Among the various screening instruments, NEECHAM confusion scale and delirium observation scale appear to be most suitable screening instrument for patients' in general medical and surgical wards, depending on the type of rater (physician or nurse). , Use of NEECHAM scaling enabled medical staff to identify cases of possible confusion early, indicating that the NEECHAM confusion scale should be useful for the detection of postoperative delirium and confusion in the surgical ward., Early detection of postoperative delirium and confusion in a surgical ward using the NEECHAM confusion scale., In this study, we investigated whether the early detection of postoperative delirium in elderly patients is possible using a simple, useful behavior-assessing scale, the NEECHAM Confusion Scale, and a method for comprehensively evaluating elderly persons' stress related to surgery, E-PASS., Assessment of the risk of postoperative delirium in elderly patients using E-PASS and the NEECHAM Confusion Scale., The aim of this study was to determine which of the two delirium observation screening scales, the NEECHAM Confusion Scale or the Delirium Observation Screening (DOS) scale, has the best discriminative capacity for diagnosing delirium and which is more practical for daily use by nurses., For delirium diagnosis and severity assessment, we used the NEECHAM Confusion Scale., Use of NEECHAM scaling enabled medical staff to identify cases of possible confusion early, indicating that the NEECHAM confusion scale should be useful for the detection of postoperative delirium and confusion in the surgical ward., The NEECHAM Confusion Scale was performed upon admission and prior to discharge.RESULTS: The incidence of DSM-IV related delirium was 24%., A comparison of the CAM-ICU and the NEECHAM Confusion Scale in intensive care delirium assessment: an observational study in non-intubated patients., Predictive value and validation of the NEECHAM Confusion Scale using DSM-IV criteria for delirium as gold standard., Early detection of postoperative delirium and confusion in a surgical ward using the NEECHAM confusion scale, The aim of this study was to determine which of the two delirium observation screening scales, the NEECHAM Confusion Scale or the Delirium Observation Screening (DOS) scale, has the best discriminative capacity for diagnosing delirium and which is more practical for daily use by nurses.The project was conducted on four wards of a university hospital; 87 patients were included, In addition, we scored the participants on the NEECHAM Scale and evaluated their postoperative delirium and postoperative arrhythmia.On the nights of Days 4 and 5, the amount of activity of the exposure group was significantly lower and The sympathetic nervous index was significantly lower on the night of Day 5, In this study, we investigated whether the early detection of postoperative delirium in elderly patients is possible using a simple, useful behavior-assessing scale, the NEECHAM Confusion Scale, and a method for comprehensively evaluating elderly persons' stress related to surgery, E-PASS. , The cut-off value of the NEECHAM score was established as 20 points, and patients showing values less than this after surgery were regarded as having postoperative delirium. , Identification of delirium was based on evaluation of the level of consciousness with the NEECHAM Confusion Scale and/or a chart-based instrument for delirium., For delirium diagnosis and severity assessment, we used the NEECHAM Confusion Scale., In this study, we investigated whether the early detection of postoperative delirium in elderly patients is possible using a simple, useful behavior-assessing scale, the NEECHAM Confusion Scale, and a method for comprehensively evaluating elderly persons' stress related to surgery, E-PASS.The subjects were 160 patients aged more than 75 years who underwent surgery., In this study a nursing screening instrument, the NEECHAM confusion scale, was studied for early recognition of delirium ICU patients., The psychometric characteristics and the ease of use of the NEECHAM confusion scale enables ICU nurses to early recognize delirium., The trends of the NEECHAM scores in the 3 groups were compared, and the relationship between the NEECHAM scores and suspected clinical risk factors for delirium was investigated., In groups showing an MMSE score of less than 25 or a preoperative NEECHAM score of less than 27, the incidence of postoperative delirium was 76%.CONCLUSION: The results suggest that E-PASS and the NEECHAM score facilitate assessment of the risk of postoperative delirium in elderly patients, contributing to early prevention/treatment., In this study, we investigated whether the early detection of postoperative delirium in elderly patients is possible using a simple, useful behavior-assessing scale, the NEECHAM Confusion Scale, and a method for comprehensively evaluating elderly persons' stress related to surgery, E-PASS., Use of NEECHAM scaling enabled medical staff to identify cases of possible confusion early, indicating that the NEECHAM confusion scale should be useful for the detection of postoperative delirium and confusion in the surgical ward.., Early detection of postoperative delirium and confusion in a surgical ward using the NEECHAM confusion scale., Assessment of the risk of postoperative delirium in elderly patients using E-PASS and the NEECHAM Confusion Scale., For delirium diagnosis and severity assessment, we used the NEECHAM Confusion Scale., The Neecham Confusion Scale and the Delirium Observation Screening Scale: capacity to discriminate and ease of use in clinical practice., The aim of this study was to determine which of the two delirium observation screening scales, the NEECHAM Confusion Scale or the Delirium Observation Screening (DOS) scale, has the best discriminative capacity for diagnosing delirium and which is more practical for daily use by nurses.[SEP]Relations: delirium has relations: contraindication with Trolnitrate, contraindication with Trolnitrate, disease_disease with cognitive disorder, disease_disease with cognitive disorder, disease_disease with subacute delirium, disease_disease with subacute delirium, contraindication with Tacrolimus, contraindication with Tacrolimus, contraindication with Olanzapine, contraindication with Olanzapine.", "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_2786", "sentence1": "Do yeast LTR give rise to circular DNA?", "sentence2": "Circular retrotransposition products generated by a LINE retrotransposon, Formation of Extrachromosomal Circular DNA from Long Terminal Repeats of Retrotransposons in Saccharomyces cerevisiae, Ty eccDNA can arise from the circularization of extrachromosomal linear DNA during the transpositional life cycle of retrotransposons, or from circularization of genomic Ty DNA, Circularization may happen through nonhomologous end-joining (NHEJ) of long terminal repeats (LTRs) flanking Ty elements, by Ty autointegration, or by LTR-LTR recombination, We have recently shown that yeast LTR elements generate circular DNAs through recombination events between their flanking long terminal repeats (LTRs)., Similarly, circular DNAs can be generated by recombination between LTRs residing at different genomic loci, in which case the circular DNA will contain the intervening sequence., A recent study on circular DNAs in yeast found that transposable element sequence residing in circular structures mostly corresponded to full-length transposable elements.[SEP]Relations: Nonhomologous End-Joining (NHEJ) has relations: pathway_protein with XRCC6, pathway_protein with XRCC6, pathway_protein with XRCC5, pathway_protein with XRCC5, pathway_protein with RAD50, pathway_protein with RAD50, pathway_protein with XRCC4, pathway_protein with XRCC4, pathway_protein with TDP2, pathway_protein with TDP2.", "label": "yes"}
{"id": "converted_3216", "sentence1": "Is collagen matrix of human articular cartilage changing with disease?", "sentence2": "The collagen matrix of human articular cartilage is an essentially permanent structure that has no significant turnover in adults, even with the occurrence of disease., the chondrocytes in ageing articular cartilage have limited capacity to turnover the interterritorial matrix., Type II collagen is a major component of articular cartilage and its breakdown is a key feature of osteoarthritis. [SEP]Relations: articular cartilage of joint has relations: anatomy_anatomy with hyaline cartilage tissue, anatomy_anatomy with hyaline cartilage tissue. negative rheumatoid factor polyarthritis has relations: disease_disease with arthritic joint disease, disease_disease with arthritic joint disease. collagen type II trimer has relations: cellcomp_protein with COL2A1, cellcomp_protein with COL2A1. chondrocyte hypertrophy has relations: bioprocess_bioprocess with growth plate cartilage chondrocyte growth, bioprocess_bioprocess with growth plate cartilage chondrocyte growth, bioprocess_protein with MEX3C, bioprocess_protein with MEX3C.", "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]Relations: escherichia coli infection has relations: disease_disease with infectious disease, disease_disease with infectious disease, disease_disease with infectious disease, disease_disease with infectious disease, disease_phenotype_positive with Recurrent gram-negative bacterial infections, disease_phenotype_positive with Recurrent gram-negative bacterial infections, disease_phenotype_positive with Recurrent gram-negative bacterial infections, disease_phenotype_positive with Recurrent gram-negative bacterial infections.", "label": "yes"}
{"id": "converted_3889", "sentence1": "Is Hunter's disease is associated with the X Chromosome?", "sentence2": "Segregation analysis on five samples of families with Hunter's syndrome (158 cases overall) shows that the mutant allele segregates in agreement with Mendelian expectations for an X linked recessive, The utility of polymerase chain reaction (PCR) amplification of amelogenin gene as a reliable and rapid means of determination of sex chromosomes was tested in 20 patients of X-linked disorders (Duchenne muscular dystrophy, haemophilia and Wiscott-Aldrich and Hunter's syndromes), , We describe a 3 year old girl with the typical clinical features of the X linked recessive condition, Hunter's disease, We describe a 3 year old girl with the typical clinical features of the X linked recessive condition, Hunter's disease., Hunter's disease in a girl: association with X:5 chromosomal translocation disrupting the Hunter gene., Further evidence localising the gene for Hunter's syndrome to the distal region of the X chromosome long arm., Full expression of Hunter's disease in a female with an X-chromosome deletion leading to non-random inactivation., Hunter disease in a girl caused by R468Q mutation in the iduronate-2-sulfatase gene and skewed inactivation of the X chromosome carrying the normal allele., These findings strongly suggest that the severe form of Hunter disease in this girl was the result of selective expression of the maternal allele carrying the missense mutation R468Q, which in turn resulted from skewed X inactivation of the paternal nonmutant X chromosome., LUSIONS: This is a report of a female with a 10.6 Mb Xq27-28 deletion with skewed inactivation of the deleted X chromosome. Con, Brother/sister siblings affected with Hunter disease: evidence for skewed X chromosome inactivation., The normal X chromosome was preferentially inactivated, supporting the view that the translocation had disrupted the Hunter gene., Hunter disease (mucopolysaccharidosis type II) associated with unbalanced inactivation of the X chromosomes in a karyotypically normal girl., INTRODUCTION: Hunter syndrome, or mucopolysaccharidosis type II, is an inherited disease linked to the X chromosome that is caused by a deficit of the enzyme iduronate-2-sulfatase and its main symptoms affect the bones, neurological system and the viscera., INTRODUCTION: Hunter syndrome, or mucopolysaccharidosis type II, is an inherited disease linked to the X chromosome that is caused by a deficit of the enzyme iduronate-2-sulfatase and its main symptoms affect the bones, neurological system and the, Mucopolysaccharidosis type II (MPS II, Hunter disease) is an X chromosome-linked inherited metabolic disease caused by mutations resulting in deficiency of activity of iduronate-2-sulfatase (IDS) and accumulation of undegraded glycosaminoglycans (GAGs), heparan sulfate, and dermatan sulfate. Previous, Mucopolysaccharidosis type II (MPS-II, Hunter disease) is a X-linked recessive disorder. Affe, Mucopolysaccharidosis type II (MPS II or Hunter syndrome) is a rare X-linked disorder caused by deficient activity of the lysosomal enzyme, iduronate-2-sulfatase (IDS). Pheno, Hunter disease or mucopolysaccharidosis type II is an X-linked disease caused by the deficiency of the lysosomal enzyme iduronate-2-sulfatase (IDS). Th, Mucopolysaccharidosis type II (MPS II, Hunter syndrome) is an X-linked lysosomal storage disease caused by a deficiency of iduronate-2-sulfatase (IDS). Two a, We report the results of studies on the characterization of the mutation associated with marked unbalanced expression of the mutant X chromosome in a karyotypically normal girl with Hunter disease (mucopolysaccharidosis type II). So, BACKGROUND: Hunter syndrome (mucopolysaccharidosis type II) is a recessive X-linked disorder due to mutations in the iduronate 2-sulfatase (IDS, Familial X-chromosome inactivation (XCI) skewing was investigated in a family in which a female mucopolysaccharidosis type II (MPS II) (Hunter syndrome, an X-linked genetic disease) occurred. Among e, Studies using BrdU indicated that the deleted X chromosome was consistently late replicating, and as a result the Hunter gene was fully expressed on the other X chromosome., All mucopolysaccharidosis are autosomal recessive disorders, except for Hunter's syndrome that is X-linked and recessive., Female twin with Hunter disease due to nonrandom inactivation of the X-chromosome: a consequence of twinning., Hunter syndrome (mucopolysaccharidosis type II) is a recessive X-linked disorder due to mutations in the iduronate 2-sulfatase (IDS) gene., Hunter disease is an X-linked recessive mucopolysaccharide storage disorder caused by iduronate-2-sulfatase deficiency and is rare in females., Hunter disease is an X-linked recessive disorder caused by a deficiency of iduronate-2-sulfatase activity.[SEP]Relations: X-linked disease has relations: disease_disease with sex-linked disease, disease_disease with sex-linked disease, disease_disease with X-linked dominant disease, disease_disease with X-linked dominant disease, disease_disease with X-linked immunoneurologic disorder, disease_disease with X-linked immunoneurologic disorder, disease_disease with X-linked intellectual disability, disease_disease with X-linked intellectual disability, disease_disease with choroideremia, disease_disease with choroideremia.", "label": "yes"}
{"id": "converted_3536", "sentence1": "Is there an increased risk of meningiomas in atomic bomb survivors?", "sentence2": "RESULTS: Meningioma was the most common tumor among clinically diagnosed tumors, followed by neuroepithelial tumor, schwannoma, and pituitary tumor. , The predominance of meningiomas over neuroepithelial tumors in the Japanese population was noteworthy and warrants further investigation. , Risk increases, although not statistically significant, were seen for meningiomas (ERR(Sv) = 0.6, 95% CI = -0.01 to 1.8), gliomas (ERR(Sv) = 0.6, 95% CI = -0.2 to 2.0), other nervous system tumors (ERR(Sv) = 0.5, 95% CI = <-0.2 to 2.2), and pituitary tumors (ERR(Sv) = 1.0, 95% CI = <-0.2 to 3.5)., High incidence of meningioma among Hiroshima atomic bomb survivors., The incidence of meningioma among Hiroshima atomic bomb survivors has increased since 1975. There was a significant correlation between the incidence and the dose of radiation to the brain. The present findings strongly suggest that meningioma is one of the tumors induced by atomic bombing in Hiroshima., Incidence of intracranial meningiomas in Nagasaki atomic-bomb survivors., The analysis showed a high correlation between incidence of meningiomas and distance from the hypocenter. The incidence among Nagasaki atomic-bomb survivors over 40 years of age, especially in those proximally exposed, appears to be increasing, in inverse proportion to the exposure distance, since 1981, 36 years after the explosion of the atomic bomb., The incidence of meningioma among Hiroshima atomic bomb survivors has increased since 1975., The present findings strongly suggest that meningioma is one of the tumors induced by atomic bombing in Hiroshima., The incidences of meningioma among the survivors of Hiroshima in 5-year intervals since 1975 were 5.3, 7.4, 10.1, and 14.9, respectively., The analysis showed a high correlation between incidence of meningiomas and distance from the hypocenter.[SEP]Relations: skin meningioma has relations: disease_disease with meningioma (disease), disease_disease with meningioma (disease), disease_disease with malignant tumor of meninges, disease_disease with malignant tumor of meninges. benign meningioma has relations: disease_disease with meningioma (disease), disease_disease with meningioma (disease). Intracranial meningioma has relations: disease_phenotype_positive with meningioma (disease), disease_phenotype_positive with meningioma (disease), disease_phenotype_positive with neurofibromatosis, disease_phenotype_positive with neurofibromatosis.", "label": "yes"}
{"id": "converted_3660", "sentence1": "Is Impetigo a viral infection that affects the skin?", "sentence2": "Importance: Ozenoxacin, a novel topical antibacterial agent with potent bactericidal activity against gram-positive bacteria, has been developed as a cream with 1% active drug for the treatment of impetigo, a highly contagious bacterial skin infection, : To compare the in vitro activity of the anti-impetigo agent, ozenoxacin, and other antimicrobial agents against Gram-positive clinical isolates from skin and soft tissue infections, Streptococcus pyogenes is responsible for a wide variety of cutaneous infections ranging from superficial impetigo to fulminant invasive necrotizing fasciitis., Impetigo is a highly contagious bacterial skin infection and is one of the most common skin infections in children, Impetigo is a superficial bacterial infection that most commonly affects the face and extremities of children., Impetigo is the most common bacterial skin infection of children., Impetigo is the most common bacterial skin infection in children two to five years of age., BACKGROUND Impetigo can result from Staphylococcus aureus (S. aureus)., Impetigo , cellulitis , and abscess comprise the majority of childhood bacterial skin infections and are treated with topical or systemic antibiotics that cover group A Streptococcus and Staphylococcus aureus . , BACKGROUND\nImpetigo can result from Staphylococcus aureus (S. aureus)., Impetigo is a superficial bacterial infection that most commonly affects the face and extremities of children., Impetigo is a superficial, but contagious, bacterial infection of the skin that predominantly affects children and is common in primary care., Impetigo is a common, superficial, bacterial infection of the skin characterized by an inflamed and infected epidermis., Impetigo, a bacterial skin infection that involves the superficial layers of the skin, is one of the most common skin infections in children ages 2 to 5 but can occur in individuals across the lifespan., Impetigo contagiosa is a common, superficial, bacterial infection of the skin characterised by an inflamed and infected epidermis caused by Staphylococcus aureus, Streptococcus pyogenes or both.[SEP]Relations: impetigo has relations: disease_disease with skin infection, disease_disease with skin infection, disease_disease with skin disease caused by infection, disease_disease with skin disease caused by infection, disease_disease with streptococcal infection, disease_disease with streptococcal infection, disease_disease with staphylococcus aureus infection, disease_disease with staphylococcus aureus infection, disease_disease with ecthyma, disease_disease with ecthyma.", "label": "no"}
{"id": "converted_1656", "sentence1": "Is the microRNA 132 (miR-132) involved in brain pathologies?", "sentence2": "miR-132 dysregulation and subsequent abnormal expression of miR-132 target genes contribute to the neurodevelopmental and neuromorphological pathologies present in schizophrenia., micro-RNAs encoding miR-9, miR-124a, miR-125b, miR-128, miR-132 and miR-219 are abundantly represented in fetal hippocampus, are differentially regulated in aged brain, and an alteration in specific micro-RNA complexity occurs in Alzheimer hippocampus. These data are consistent with the idea that altered micro-RNA-mediated processing of messenger RNA populations may contribute to atypical mRNA abundance and neural dysfunction in Alzheimer's disease brain., Levels of several microRNA (miR-10a, -10b, -212, -132, -495) were significantly altered. One of them (miR-132) has been reported to be highly inducible by growth factors and to be a key regulator of neurite outgrowth. Moreover, miR-132-recognition sequences were detected in the mRNA transcripts of two differentially expressed proteins. MicroRNA may thus represent novel biomarkers for neuronal malfunction and potential therapeutic targets for human neurodegenerative diseases., Expression of key neuronal microRNAs-including mir-9/9*, mir-124 and mir-132-is repressed in the brains of human HD patients and mouse models., To determine if production of miR-132 is regulated by neuronal activity its expression in mouse brain was monitored by quantitative RT-PCR (RT-qPCR), Expression levels of primary and mature-miR-132 increased significantly between postnatal Days 10 and 24. We conclude that miR-132 is an activity-dependent microRNA in vivo, and may contribute to the long-lasting proteomic changes required for experience-dependent neuronal plasticity., We investigated how prior seizure preconditioning affects the miRNA response to status epilepticus evoked by intra-amygdalar kainic acid in mice., Increased miR-132 levels were matched with increased binding to Argonaute-2, a constituent of the RNA-induced silencing complex. In tolerant animals, expression responses of >40% of the injury-group-detected miRNAs differed, being either unchanged relative to control or down-regulated, and this included miR-132. In vivo microinjection of locked nucleic acid-modified oligonucleotides (antagomirs) against miR-132 depleted hippocampal miR-132 levels and reduced seizure-induced neuronal death. Thus, our data strongly suggest that miRNAs are important regulators of seizure-induced neuronal death., Preconditioning describes the ischemic stimulus that triggers an endogenous, neuroprotective response that protects the brain during a subsequent severe ischemic injury, a phenomenon known as 'tolerance'., Downregulation of miR-132 is consistent with our finding that preconditioning ischemia induces a rapid increase in MeCP2 protein, but not mRNA, in mouse cortex. These studies reveal that ischemic preconditioning regulates expression of miRNAs and their predicted targets in mouse brain cortex, and further suggest that miRNAs and MeCP2 could serve as effectors of ischemic preconditioning-induced tolerance., Huntington's disease (HD) is a genetic neurodegenerative disease caused by abnormal CAG expansion. MicroRNAs (miRNAs) are short RNA molecules regulating gene expression, and are implicated in a variety of diseases including HD., Nine miRNAs (miR-22, miR-29c, miR-128, miR-132, miR-138, miR-218, miR-222, miR-344, and miR-674*) were commonly down-regulated in both the 12-month-old YAC128 and 10-week-old R6/2 mice., transgenic HD mice have abnormal miRNA biogenesis. This information should aid in future studies on therapeutic application of miRNAs in HD., miR-132 directly targets the neuronal splicing factor polypyrimidine tract-binding protein 2 (PTBP2), which protein levels were increased in PSP patients. miR-132 overexpression or PTBP2 knockdown similarly affected endogenous 4R:3R-tau ratios in neuronal cells. Finally, we provide evidence that miR-132 is inversely correlated with PTBP2 during post-natal brain development at the time when 4R-tau becomes expressed. Taken together, these results suggest that changes in the miR-132/PTBP2 pathway could contribute to the abnormal splicing of tau exon 10 in the brain, and sheds light into the potential role played by miRNAs in a subset of tauopathies., reports of microRNA (miR) modulators of both neuronal and immune processes (here termed NeurimmiRs) predict therapeutic potential for manipulating NeurimmiR levels in diseases affecting both the immune system and higher brain functions, such as Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS) and anxiety-related disorders. In our opinion, NeurimmiRs that function within both the nervous and the immune systems, such as miR-132 and miR-124, may act as 'negotiators' between these two interacting compartments.[SEP]Relations: Parkinson disease has relations: disease_protein with MIR181C, disease_protein with MIR181C. Viral Messenger RNA Synthesis has relations: pathway_protein with NUP133, pathway_protein with NUP133, pathway_protein with NUP214, pathway_protein with NUP214, pathway_protein with NUP188, pathway_protein with NUP188, pathway_protein with NUP107, pathway_protein with NUP107.", "label": "yes"}
{"id": "converted_1701", "sentence1": "Is the protein KCNQ2 associated with idiopathic epilepsy?", "sentence2": "Juvenile idiopathic epilepsy (JIE) in Arabian foals resembles benign-familial neonatal convulsion (BFNC) syndrome, a rare idiopathic epilepsy of new-born humans. BFNC syndrome exhibits genetic heterogeneity, as has been hypothesised to occur in Arabian foals, and is known to be caused by mutations in the voltage-gated potassium channel subunit KCNQ2 and KCNQ3 genes., They also demonstrate that sequence variations of the KCNQ2 and KCNQ3 genes may contribute to the etiology of common IE syndromes., The underlying genetic abnormalities of rare familial idiopathic epilepsy have been identified, such as mutation in KCNQ2, a K(+) channel gene., Sequence variations of the KCNQ2 and KCNQ3 genes may contribute to the etiology of common idiopathic epilepsy syndromes., This paper summarizes recent findings concerning sodium (SCN1A) and potassium channel (KCNQ2 and KCNQ3) dysfunctions in the pathogenesis of rare and common idiopathic epilepsies (IE). , Mutations in the SCN1A gene are found in up to 80% of individuals with severe myoclonic epilepsy of infancy (SMEI), and mutations in KCNQ2 and KCNQ3 were identified in benign familial neonatal convulsions (BFNC) as well as in single families with Rolandic epilepsy (RE) and idiopathic generalized epilepsies (IGE)., The involvement of KCNQ2 (Kv7.2) and KCNQ3 (Kv7.3) in a benign idiopathic neonatal epilepsy, KCNQ4 (Kv7.4) in a form of congenital deafness, and the discovery that neuronal KCNQ heteromultimers were among the molecular substrates of M-channels, resulted in a high level of interest for potential drug development strategies, Mutations in the SCN1A gene are found in up to 80% of individuals with severe myoclonic epilepsy of infancy (SMEI), and mutations in KCNQ2 and KCNQ3 were identified in benign familial neonatal convulsions (BFNC) as well as in single families with Rolandic epilepsy (RE) and idiopathic generalized epilepsies (IGE), The functional interaction between KCNQ2 and KCNQ3 provides a framework for understanding how mutations in either channel can cause a form of idiopathic generalized epilepsy, Mutations in KCNQ2- or KCNQ3-encoding genes cause benign familiar neonatal convulsions (BFNCs), a rare autosomal-dominant idiopathic epilepsy of the newborn, Mutations in KCNQ2 or KCNQ3 that reduce the M-current are responsible for benign familial neonatal seizures, a rare autosomal dominant idiopathic epilepsy of the newborn, These include benign familial neonatal convulsions due to mutations in KCNQ2 or KCNQ3, generalized epilepsy with febrile seizures plus due to mutations in SCN1A, SCN2A, SCN1B, and GABRG2, autosomal-dominant juvenile myoclonic epilepsy (JME) due to a mutation in GABRA1 and mutations in CLCN2 associated with several IGE sub-types, KCNQ2 and KCNQ3 mutations contribute to different idiopathic epilepsy syndromes, Role of KCNQ2 and KCNQ3 genes in juvenile idiopathic epilepsy in Arabian foals, Mutations in the voltage gated potassium channel gene KCNQ2 and the homologous gene KCNQ3 have been found to cause a rare monogenic subtype of idiopathic generalized epilepsy, the benign familial neonatal convulsions, Role of KCNQ2 and KCNQ3 genes in juvenile idiopathic epilepsy in Arabian foals., KCNQ2 and KCNQ3 mutations contribute to different idiopathic epilepsy syndromes.[SEP]Relations: epilepsy has relations: disease_protein with KCNQ2, disease_protein with KCNQ2, disease_protein with KCNA2, disease_protein with KCNA2, disease_protein with KCNAB2, disease_protein with KCNAB2, disease_protein with KCNT2, disease_protein with KCNT2, disease_protein with KCND2, disease_protein with KCND2.", "label": "yes"}
{"id": "converted_4701", "sentence1": "Is ASF1 phopshorylated by  the Tousled-like kinases?", "sentence2": "Asf1, a key histone H3-H4 chaperone required for this process, is phosphorylated by Tousled-like kinases (TLKs). , The Tousled-like kinases 1 and 2 (TLK1/2) control histone deposition through the ASF1 histone chaperone, The Tousled-like kinases (TLKs) are involved in chromatin assembly, DNA repair, and transcription. Two TLK genes exist in humans, and their expression is often dysregulated in cancer. TLKs phosphorylate Asf1 , TLKs interact specifically (and phosphorylate) with the chromatin assembly factor Asf1, a histone H3-H4 chaperone, TLK1 substrates were identified as the histone H3 and Asf1 (a histone H3/H4 chaperone)[SEP]Relations: histone H3 acetylation has relations: bioprocess_protein with TAF5L, bioprocess_protein with TAF5L, bioprocess_protein with TAF6L, bioprocess_protein with TAF6L, bioprocess_protein with LEF1, bioprocess_protein with LEF1, bioprocess_protein with TAF5, bioprocess_protein with TAF5, bioprocess_protein with IRF4, bioprocess_protein with IRF4.", "label": "yes"}
{"id": "converted_109", "sentence1": "Does TGF-beta play a role in cardiac regeneration after myocardial infarction?", "sentence2": "We then performed a chemical screen and identified several small molecules that increase or reduce cardiomyocyte proliferation during heart development. These compounds act via Hedgehog, Insulin-like growth factor or Transforming growth factor β signaling pathways. , Here, we report that the balance between the reparative and regenerative processes is achieved through Smad3-dependent TGFβ signaling. , Thus, TGFβ signaling orchestrates the beneficial interplay between scar-based repair and cardiomyocyte-based regeneration to achieve complete heart regeneration., As expected, transforming growth factor (TGF)-beta, a profibrotic cytokine, was dramatically upregulated in MI hearts, but its phosphorylated comediator (pSmad) was significantly downregulated in the nuclei of Cx43-deficient hearts post-MI, suggesting that downstream signaling of TGF-beta is diminished substantially in Cx43-deficient hearts. This diminution in profibrotic TGF-beta signaling resulted in the attenuation of adverse structural remodeling as assessed by echocardiography., Potentially beneficial changes include increases in the HSMP secretory-leucocyte-protease-inhibitor (SLPI) and cytokine transforming growth factor (TGF)-beta(1). Targeting these proteins may mitigate enhanced LV remodeling and dysfunction with aging., After injury, the presence of macrophages, which secreted high levels of transforming growth factor-beta and vascular endothelial growth factor-A, led to rapid removal of cell debris and replacement by granulation tissue containing inflammatory cells and blood vessels, followed by myofibroblast infiltration and collagen deposition., Secretion of transforming growth factor-beta and vascular endothelial growth factor-A as well as neovascularization, myofibroblast infiltration, and collagen deposition decreased. , Repression of proinflammatory cytokine and chemokine synthesis, mediated in part through Transforming Growth Factor (TGF)-beta and Interleukin (IL)-10, is critical for resolution of the inflammatory infiltrate and transition to fibrous tissue deposition., TGF-beta conducted the myogenic differentiation of CD117+ stem cells by upregulating GATA-4 and NKx-2.5 expression. Therefore, the intramyocardial implantation of TGF-beta-preprogrammed CD117+ cells effectively assisted the myocardial regeneration and induced therapeutic angiogenesis, contributing to functional cardiac regeneration., These results indicate that TGF-beta/Smad signaling may be involved in the remodeling of the infarct scar after the completion of wound healing per se, via ongoing stimulation of matrix deposition.[SEP]Relations: transforming growth factor beta receptor binding has relations: molfunc_protein with TGFB2, molfunc_protein with TGFB2, molfunc_protein with TGFBR3, molfunc_protein with TGFBR3, molfunc_protein with TGFBRAP1, molfunc_protein with TGFBRAP1, molfunc_protein with INHBC, molfunc_protein with INHBC, molfunc_protein with RASL11B, molfunc_protein with RASL11B.", "label": "yes"}
{"id": "converted_813", "sentence1": "Does a selective sweep increase genetic variation?", "sentence2": "An East African population that gave rise to non-Africans underwent a selective sweep affecting the subcentromeric region where MTMR8 is located. This and similar sweeps in four other regions of the X chromosome, documented in the literature, effectively reduced genetic diversity of non-African chromosomes, a selective sweep that has removed genetic variation from much of the drive X chromosome., evidence of reduced diversity and an excess of fixed replacement sites, consistent with a species-wide selective sweep., recent independent selective sweeps in AGO2 have reduced genetic variation, episodes of natural selection (likely a selective sweep) predating the coalescent of human lineages, within the last 25 million years, account for the observed reduced diversity, reduced variation or deviations from neutrality that might indicate a recent selective sweep, Consider a genetic locus carrying a strongly beneficial allele which has recently fixed in a large population. As strongly beneficial alleles fix quickly, sequence diversity at partially linked neutral loci is reduced. This phenomenon is known as a selective sweep., a local selective sweep or demographic process that reduced variability, reduced variation (a selective sweep), the mtDNA diversity, but not the nuclear DNA diversity, has been reduced relative to the neutral expectation of molecular evolution, suggesting the action of a selective sweep, Furthermore, the amount of genetic variation after a selective sweep is expected to be unequal over demes: a greater reduction in expected heterozygosity occurs in the subpopulation from which the beneficial mutation originates than in its neighboring subpopulations., Our observation of reduction in variation at both intragenic and flanking loci of mutant pfcrt gene confirmed the selective sweep model of natural selection in chloroquine resistant P., A selective sweep describes the reduction of linked genetic variation due to strong positive selection., In these situations, adaptation should commonly produce 'soft' selective sweeps, where multiple adaptive alleles sweep through the population at the same time, either because the alleles were already present as standing genetic variation or arose independently by recurrent de novo mutations., CONCLUSIONS: The severe reduction in nucleotide variation at OsAMT1;1 in rice was caused by a selective sweep around OsAMT1;1, which may reflect the nitrogen uptake system under strong selection by the paddy soil during the domestication of rice., A selective sweep describes the reduction of linked genetic variation due to strong positive selection[SEP]Relations: adaptation to pheromone regulating conjugation with mutual genetic exchange has relations: bioprocess_bioprocess with response to pheromone regulating conjugation with mutual genetic exchange, bioprocess_bioprocess with response to pheromone regulating conjugation with mutual genetic exchange, bioprocess_bioprocess with regulation of conjugation, bioprocess_bioprocess with regulation of conjugation, bioprocess_bioprocess with negative adaptation of signaling pathway, bioprocess_bioprocess with negative adaptation of signaling pathway. Lacrimation abnormality has relations: phenotype_phenotype with Decreased lacrimation, phenotype_phenotype with Decreased lacrimation, phenotype_phenotype with Gustatory lacrimation, phenotype_phenotype with Gustatory lacrimation.", "label": "no"}
{"id": "converted_3482", "sentence1": "Is PF-05190457 an inverse agonist of the ghrelin receptor?", "sentence2": "Pharmacokinetics and pharmacodynamics of PF-05190457: The first oral ghrelin receptor inverse agonist to be profiled in healthy subjects., To evaluate safety, tolerability and pharmacokinetics of oral PF-05190457, an oral ghrelin receptor inverse agonist, in healthy adults.,  PF-05190457 is a well-tolerated first-in-class ghrelin receptor inverse agonist with acceptable pharmacokinetics for oral daily dosing.[SEP]Relations: growth hormone secretagogue receptor activity has relations: molfunc_protein with GHSR, molfunc_protein with GHSR.", "label": "yes"}
{"id": "converted_462", "sentence1": "Does melanoma  occur in people of African origin ?", "sentence2": "ALM is the most common type of melanoma amongst Asians, Africans,, ALM develops on palmar, plantar, and subungual skin, and its biology is different from that of other cutaneous melanomas, where sunlight is the major known environmental determinant, We present four albinos with histologic diagnoses of skin cancer, Four Nigerian albinos (two men and two women) with skin cancer, The sites of the lesions included the head [squamous cell carcinoma (SCC) in two patients and basal cell carcinoma (BCC) in one patient] and the upper limb (melanoma, wenty-nine patients (18 males and 11 females) with skin cancer were identified, Kaposi sarcoma associated with HIV represented 81.8 percent of KS cases found. Squamous cell carcinoma (SCC) ranked second and malignant melanoma third, Earlier studies have shown frequent mutations in the BRAF and NRAS genes in cutaneous melanoma, but these alterations have not been examined in the rare category of melanoma from black Africans., In a series of melanomas from black Africans (n=26), only two BRAF mutations (8%) were found, both being different from the common T1799A substitution. Moreover, melanomas from black Africans exhibited mutations in NRAS exon 1 only (12%), whereas NRAS exon 2 mutations were predominant in melanomas from Caucasians. Thus, the frequencies of BRAF and NRAS mutations were particularly low in melanomas from black Africans, supporting a different pathogenesis of these tumors., Malignant melanoma (MM) remains a pediatric rarity world-wide, but perhaps more so in black Africans. To the best of our knowledge, the current report of MM in a two-and-a-half-year-old Nigerian who had a pre-existing congenital giant hairy nevus is probably the first (in an accessible literature) in a black African child., Malignant melanomas in black Africans are predominantly located on the lower extremities, Thus, our findings indicate that melanomas located on the lower extremities in black Africans show several features of aggressiveness; in particular, the proliferative activity was high, and p16 alterations was frequent as evidenced by loss of protein staining. Our findings also indicated that the diagnosis is delayed among black Africans., Africans with dark skin have a reduced risk of getting all types of skin cancer as compared with Caucasians, but the ratio of their incidence rates of cutaneous malignant melanoma to that of squamous cell carcinoma is larger than the corresponding ratio for Caucasians. (, Albino Africans, as compared with normally pigmented Africans, seem to have a relatively small risk of getting cutaneous malignant melanomas compared to nonmelanomas. This is probably also true for albino and normally pigmented Caucasians., Scant data exists on melanoma in blacks from Africa, The mean age at presentation of the 39 women and 24 men was 60.5 years (range of 30 to 85 years), with a peak incidence in the sixth decade. The foot was the most common site of disease (45 patients). Seven patients had subungual melanoma, seven had primary mucosal lesions, and in six, the primary lesion could not be found., The poor prognosis in black patients in South Africa is the result of delayed presentation with thick primary lesions and advanced disease, The outcome of treatment in 40 black patients (27 women, 13 men; mean age 62.9 years) with plantar melanoma over a 13-year period was analysed, Delay in presentation and locally advanced disease may explain the poor prognosis of plantar melanoma in black South Africans., Eighteen cases of malignant skin tumors seen at the University of Port Harcourt Teaching Hospital over 3 years (1984 to 1987) were analyzed for diagnoses, site of tumors, sex, and age. Seven patients (39%) had malignant melanomas affecting only the soles of the feet, while the same number had squamous cell carcinomas widely distributed in various parts of the body, Non-white populations experienced in general a much lower incidence of melanoma although there was some overlap of white and non-white rates., Populations of African descent were found to have a higher incidence than those of Asiatic origin, but it was concluded that this was due largely to the high frequency of tumours among Africans on the sole of the foot., Pathological features of twenty-one cases of malignant melanoma studied in the University of Nigeria Teaching Hospital, Enugu during the period January, 1974 to December, 1975 are presented. Malignant melanoma accounted for 2.4% of all tumours and 4.5% of all malignant tumours, greatest age incidence being in the fifth to seventh decades., 81% melanomas occurred on the sole of feet validating the hypothesis that the pigmented skin in Africans is resistant to malignant melanoma., This paper reports the incidence of this lesion in association with invasive malignant melanomas of the feet and hands of Black Africans., Follow-up data (over a 3-year period) and the histological appearances of primary lesion were studied and related in 40 Black patients with malignant melanoma., Malignant melanoma of the skin in Blacks in formidable and sinister tumour., The incidence of malignant melanoma in Johannesburg Black was 1,2 per 100 000 and accounted for 2% of all cancers. The largest number of cases occurred in the 50- 70-year age group and there was a female preponderance. As in previous studies, the sites predominantly affected were the foot and the hand, mainly on the plantar and palmar surfaces., Twenty-one cases of malignant melanoma occurring in the Igbos of Nigeria have been analysed. The site of predilection is the sole of the foot. This result supports the conclusion that Negroes tend to have the disease in the non-pigmented parts., A case of leptomeningeal melanoma in an African child of 7 years is presented together with a survey of pigmentation in the normal African brain.[SEP]Relations: melanoma has relations: disease_disease with melanomatosis, disease_disease with melanomatosis, disease_disease with familial melanoma, disease_disease with familial melanoma, disease_disease with childhood malignant melanoma, disease_disease with childhood malignant 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_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]Relations: Histamine receptors has relations: pathway_protein with HRH3, pathway_protein with HRH3, pathway_protein with HRH1, pathway_protein with HRH1, pathway_protein with HRH4, pathway_protein with HRH4. cognitive disorder has relations: contraindication with Lithium citrate, contraindication with Lithium citrate, contraindication with Lithium carbonate, contraindication with Lithium carbonate.", "label": "yes"}
{"id": "converted_2858", "sentence1": "Has Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) been reported to be a plasminogen receptor in pathogenic bacteria?", "sentence2": " binding of plasminogen (Plg) to bacterial surfaces, as it has been shown that this interaction contributes to bacterial adhesion to host cells, invasion of host tissues, and evasion of the immune system. Several bacterial proteins are known to serve as receptors for Plg including glyceraldehyde-3-phosphate dehydrogenase (GAPDH),, Moreover, several isoforms of the glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and galectin (GAL) were identified in both antigenic extracts as plasminogen-binding proteins., Purified GAPDH was found to bind human plasminogen and fibrinogen in Far-Western blot and ELISA-based assays., GAPDH exhibits a high affinity for plasmin and a significantly lower affinity for plasminogen., Moreover, several isoforms of the glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and galectin (GAL) were identified in both antigenic extracts as plasminogen-binding proteins. [SEP]Relations: Protein S human has relations: drug_drug with Tedizolid phosphate, drug_drug with Tedizolid phosphate, drug_drug with Tedizolid phosphate, drug_drug with Tedizolid phosphate, drug_drug with Protocatechualdehyde, drug_drug with Protocatechualdehyde, drug_drug with Protocatechualdehyde, drug_drug with Protocatechualdehyde, drug_drug with Dehydrochloromethyltestosterone, drug_drug with Dehydrochloromethyltestosterone.", "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]Relations: cohesin complex has relations: cellcomp_protein with STAG2, cellcomp_protein with STAG2, cellcomp_protein with RAD21, cellcomp_protein with RAD21, cellcomp_protein with STAG1, cellcomp_protein with STAG1, cellcomp_protein with SMC1A, cellcomp_protein with SMC1A, cellcomp_protein with SMC1B, cellcomp_protein with SMC1B.", "label": "no"}
{"id": "converted_1671", "sentence1": "Is LPS a microbial product?", "sentence2": "and microbial translocation [lipopolysaccaride (LPS), microbial 16S rDNA and sCD14] , Lipopolysaccharide sensing an important factor in the innate immune response to Gram-negative bacterial infections, bacterial lipopolysaccharide (LPS), sterile bacterial wall lipopolysaccharide (LPS) to investigate the changes in innate lung microbiota[SEP]Relations: Recurrent bacterial infections has relations: disease_phenotype_positive with immunodeficiency, partial combined, with absence of HLA Determinants and beta-2-microglobulin from lymphocytes, disease_phenotype_positive with immunodeficiency, partial combined, with absence of HLA Determinants and beta-2-microglobulin from lymphocytes, disease_phenotype_positive with SLC35A1-CDG, disease_phenotype_positive with SLC35A1-CDG, disease_phenotype_positive with agammaglobulinemia, disease_phenotype_positive with agammaglobulinemia. bacterial arthritis has relations: disease_protein with TNF, disease_protein with TNF, disease_disease with infectious disease, disease_disease with infectious disease.", "label": "yes"}
{"id": "converted_1225", "sentence1": "Is the regulation of Vsr endonuclease independent of the growth phase of bacteria?", "sentence2": "Growth phase-dependent regulation of Vsr endonuclease, Vsr endonuclease levels are growth phase dependent., Growth phase-dependent regulation of Vsr endonuclease may contribute to 5-methylcytosine mutational hot spots in Escherichia coli., Using rabbit polyclonal antibodies, we have shown that the Dcm cytosine methylase of Escherichia coli is maintained at a constant level during cell growth, while Vsr endonuclease levels are growth phase dependent., Vsr endonuclease, which initiates very short patch repair, has been hypothesized to regulate mutation in stationary-phase cells., The efficiency of the two pathways changes during the bacterial life cycle; MMR is more efficient during exponential growth and VSP repair is more efficient during the stationary phase., Overexpression of Vsr does dramatically increase the stationary-phase reversion of a Lac- frameshift allele, but the absence of Vsr has no effect., Using rabbit polyclonal antibodies, we have shown that the Dcm cytosine methylase of Escherichia coli is maintained at a constant level during cell growth, while Vsr endonuclease levels are growth phase dependent, The efficiency of the two pathways changes during the bacterial life cycle; MMR is more efficient during exponential growth and VSP repair is more efficient during the stationary phase, Vsr endonuclease, which initiates very short patch repair, has been hypothesized to regulate mutation in stationary-phase cells[SEP]Relations: escherichia coli infection has relations: disease_phenotype_positive with Recurrent gram-negative bacterial infections, disease_phenotype_positive with Recurrent gram-negative bacterial infections. mismatch repair has relations: bioprocess_protein with RNASEH2A, bioprocess_protein with RNASEH2A, bioprocess_protein with MLH1, bioprocess_protein with MLH1, bioprocess_protein with POLD2, bioprocess_protein with POLD2, bioprocess_protein with EXO1, bioprocess_protein with EXO1.", "label": "no"}
{"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]Relations: collagen type IV trimer has relations: cellcomp_protein with OTOL1, cellcomp_protein with OTOL1, cellcomp_protein with COL4A1, cellcomp_protein with COL4A1, cellcomp_protein with COL4A5, cellcomp_protein with COL4A5, cellcomp_protein with COL4A3, cellcomp_protein with COL4A3, cellcomp_protein with COL4A2, cellcomp_protein with COL4A2.", "label": "yes"}
{"id": "converted_443", "sentence1": "Can we detect DNA strand asymmetries using dinucleotide relative abundance \"genomic signatures\"?", "sentence2": "comparing the heterogeneities of bacterial genomes with respect to strand-independent first- and second-order features, (i) G + C content and (ii) dinucleotide relative abundance,, the concept of a genomic signature was introduced with the observation of species-type specific Dinucleotide Relative Abundance Profiles (DRAPs); dinucleotides were identified as the subsequences with the greatest bias in representation in a majority of genomes., dinucleotide relative abundance values (the genomic signature), The dinucleotide relative abundance profile can be regarded as a genomic signature because, despite diversity between species, it varies little between 50 kilobase or longer windows on a given genome., The profile is computed from the base step \"odds ratios\" that compare dinucleotide frequencies to those expected under the assumption of stochastic equilibrium (thorough shuffling). , The genome signatures (dinucleotide relative abundance values), Early biochemical experiments measuring nearest neighbor frequencies established that the set of dinucleotide relative abundance values (dinucleotide biases) is a remarkably stable property of the DNA of an organism., the set of dinucleotide biases constitutes a 'genomic signature' that can discriminate sequences from different organisms., the set of dinucleotide odds ratio (relative abundance) values constitute a signature of each DNA genome, Dinucleotide relative abundance extremes: a genomic signature., The dinucleotide relative abundance profile can be regarded as a genomic signature because, despite diversity between species, it varies little between 50 kilobase or longer windows on a given genome., Previously, the concept of a genomic signature was introduced with the observation of species-type specific Dinucleotide Relative Abundance Profiles (DRAPs); dinucleotides were identified as the subsequences with the greatest bias in representation in a majority of genomes., Comparisons within and between species sample sequences are based on the profile of dinucleotide relative abundance values (The profile is rho*XY = f*XY/f*Xf*Y for all XY, where f*X denotes the frequency of the nucleotide X and f*XY denotes the frequency of the dinucleotide XY, both computed from the sequence concatenated with its inverted complement)., Dinucleotide relative abundances (i.e., dinucleotide representations normalized by the component nucleotide frequencies) are consonant with respect to the leading and lagging strands[SEP]Relations: anatomical entity has relations: anatomy_anatomy with immaterial anatomical entity, anatomy_anatomy with immaterial anatomical entity, anatomy_anatomy with anatomical cluster, anatomy_anatomy with anatomical cluster, anatomy_anatomy with insect mouthpart, anatomy_anatomy with insect mouthpart, anatomy_anatomy with material anatomical entity, anatomy_anatomy with material anatomical entity. male organism has relations: anatomy_anatomy with multicellular organism, anatomy_anatomy with multicellular organism.", "label": "no"}
{"id": "converted_4565", "sentence1": "Is Sotrovimab effective for COVID-19?", "sentence2": "It seems that monoclonal antibodies (e.g., low dosage bamlanivimab, baricitinib, imatinib, and sotrovimab) are a better choice for treating severe or non-severe COVID-19 patients. , The Food and Drug Administration has granted emergency use authorization to sotrovimab for the treatment of mild to moderate COVID-19 in patients at increased risk for progression to severe illness., Early Treatment for Covid-19 with SARS-CoV-2 Neutralizing Antibody Sotrovimab., Sotrovimab is a pan-sarbecovirus monoclonal antibody that was designed to prevent progression of Covid-19 in high-risk patients early in the course of disease, CONCLUSIONS: Among high-risk patients with mild-to-moderate Covid-19, sotrovimab reduced the risk of disease progression., The Food and Drug Administration has granted emergency use authorization to sotrovimab for the treatment of mild to moderate COVID-19 in patients at increased risk for progression to severe illness.Sotrovimab is a monoclonal antibody that works directly against the spike protein of SARS-CoV-2 to block its attachment and entry into a human cell., In patients with non-severe covid-19, casirivimab-imdevimab probably reduces hospitalisation; bamlanivimab-etesevimab, bamlanivimab, and sotrovimab may reduce hospitalisation. Convalescen, ms that monoclonal antibodies (e.g., low dosage bamlanivimab, baricitinib, imatinib, and sotrovimab) are a better choice for treating severe or non-severe COVID-19 patients. Clini, Early Treatment for Covid-19 with SARS-CoV-2 Neutralizing Antibody Sotrovimab, The Food and Drug Administration has granted emergency use authorization to sotrovimab for the treatment of mild to moderate COVID-19 in patients at increased risk for progression to severe illness[SEP]Relations: Baricitinib has relations: drug_drug with Sofosbuvir, drug_drug with Sofosbuvir, drug_drug with Cortivazol, drug_drug with Cortivazol, drug_drug with Somatostatin, drug_drug with Somatostatin, drug_drug with Efalizumab, drug_drug with Efalizumab. Imatinib has relations: drug_drug with Sofosbuvir, drug_drug with Sofosbuvir.", "label": "yes"}
{"id": "converted_4300", "sentence1": "Is istiratumab effective for pancreatic cancer?", "sentence2": "CONCLUSIONS: Istiratumab failed to improve the efficacy of SOC chemotherapy in this patient setting. [SEP]", "label": "no"}
{"id": "converted_903", "sentence1": "Does Rad9 interact with Aft1 in S.cerevisiae?", "sentence2": "Rad9 interacts with Aft1 to facilitate genome surveillance in fragile genomic sites under non-DNA damage-inducing conditions in S. cerevisiae., Here we show that Rad9 checkpoint protein, known to mediate the damage signal from upstream to downstream essential kinases, interacts with Aft1 transcription factor in the budding yeast. Aft1 regulates iron homeostasis and is also involved in genome integrity having additional iron-independent functions. Using genome-wide expression and chromatin immunoprecipitation approaches, we found Rad9 to be recruited to 16% of the yeast genes, often related to cellular growth and metabolism, while affecting the transcription of ∼2% of the coding genome in the absence of exogenously induced DNA damage. Importantly, Rad9 is recruited to fragile genomic regions (transcriptionally active, GC rich, centromeres, meiotic recombination hotspots and retrotransposons) non-randomly and in an Aft1-dependent manner. Further analyses revealed substantial genome-wide parallels between Rad9 binding patterns to the genome and major activating histone marks, such as H3K36me, H3K79me and H3K4me. Thus, our findings suggest that Rad9 functions together with Aft1 on DNA damage-prone chromatin to facilitate genome surveillance, thereby ensuring rapid and effective response to possible DNA damage events., Here we show that Rad9 checkpoint protein, known to mediate the damage signal from upstream to downstream essential kinases, interacts with Aft1 transcription factor in the budding yeast, Rad9 interacts with Aft1 to facilitate genome surveillance in fragile genomic sites under non-DNA damage-inducing conditions in S. cerevisiae, Here we show that Rad9 checkpoint protein, known to mediate the damage signal from upstream to downstream essential kinases, interacts with Aft1 transcription factor in the budding yeast. Aft1 regulates iron homeostasis and is also involved in genome integrity having additional iron-independent functions. Using genome-wide expression and chromatin immunoprecipitation approaches, we found Rad9 to be recruited to 16% of the yeast genes, often related to cellular growth and metabolism, while affecting the transcription of ?2% of the coding genome in the absence of exogenously induced DNA damage. , Importantly, Rad9 is recruited to fragile genomic regions (transcriptionally active, GC rich, centromeres, meiotic recombination hotspots and retrotransposons) non-randomly and in an Aft1-dependent manner. Further analyses revealed substantial genome-wide parallels between Rad9 binding patterns to the genome and major activating histone marks, such as H3K36me, H3K79me and H3K4me. Thus, our findings suggest that Rad9 functions together with Aft1 on DNA damage-prone chromatin to facilitate genome surveillance, thereby ensuring rapid and effective response to possible DNA damage events.[SEP]Relations: centromere clustering has relations: bioprocess_bioprocess with chromosome localization, bioprocess_bioprocess with chromosome localization, bioprocess_bioprocess with centromere clustering at the mitotic interphase nuclear envelope, bioprocess_bioprocess with centromere clustering at the mitotic interphase nuclear envelope, bioprocess_bioprocess with centromere localization, bioprocess_bioprocess with centromere localization, bioprocess_bioprocess with meiotic centromere clustering, bioprocess_bioprocess with meiotic centromere clustering. anatomical entity has relations: anatomy_anatomy with insect mouthpart, anatomy_anatomy with insect mouthpart.", "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]Relations: hippocampus fimbria has relations: anatomy_anatomy with central nervous system cell part cluster, anatomy_anatomy with central nervous system cell part cluster. frontal cortex has relations: anatomy_protein_present with HIPK3, anatomy_protein_present with HIPK3, anatomy_protein_present with HIPK4, anatomy_protein_present with HIPK4, anatomy_protein_present with HIPK2, anatomy_protein_present with HIPK2, anatomy_protein_present with HIPK1, anatomy_protein_present with HIPK1.", "label": "yes"}
{"id": "converted_2111", "sentence1": "Does the TOP2B/TOP2A expression ratio affect the response to AML chemotherapy?", "sentence2": "High TOP2B/TOP2A expression ratio at diagnosis correlates with favourable outcome for standard chemotherapy in acute myeloid leukaemia, Genes with distinct expression profiles such as TOP2B/TOP2A expression ratio at diagnosis can be employed for outcome prediction after the treatment with standard regimens in AML patients with M2 subtype., Another interesting finding is that high ratios of TOP2B/RRM2 and TOP2B/TOP2 alpha (TOP2A) in a combined analysis were also shown to have a prognostic impact for longer survival with improved accuracy., Among the four markers, when adjusted for the influence of other clinical factors in multivariate analysis, the TOP2B/TOP2A ratio was significantly correlated with treatment outcomes; patients with high ratios trended toward longer disease-free survival (HR, 0.24; P=0.002) and overall survival (HR, 0.29; P=0.005), High TOP2B/TOP2A expression ratio at diagnosis correlates with favourable outcome for standard chemotherapy in acute myeloid leukaemia., Among the four markers, when adjusted for the influence of other clinical factors in multivariate analysis, the TOP2B/TOP2A ratio was significantly correlated with treatment outcomes; patients with high ratios trended toward longer disease-free survival (HR, 0.24; P=0.002) and overall survival (HR, 0.29; P=0.005).Genes with distinct expression profiles such as TOP2B/TOP2A expression ratio at diagnosis can be employed for outcome prediction after the treatment with standard regimens in AML patients with M2 subtype, CONCLUSION: Genes with distinct expression profiles such as TOP2B/TOP2A expression ratio at diagnosis can be employed for outcome prediction after the treatment with standard regimens in AML patients with M2 subtype., Genes with distinct expression profiles such as TOP2B/TOP2A expression ratio at diagnosis can be employed for outcome prediction after the treatment with standard regimens in AML patients with M2 subtype.., High TOP2B/TOP2A expression ratio at diagnosis correlates with favourable outcome for standard chemotherapy in acute myeloid leukaemia., Among the four markers, when adjusted for the influence of other clinical factors in multivariate analysis, the TOP2B/TOP2A ratio was significantly correlated with treatment outcomes; patients with high ratios trended toward longer disease-free survival (HR, 0.24; P=0.002) and overall survival (HR, 0.29; P=0.005)., Another interesting finding is that high ratios of TOP2B/RRM2 and TOP2B/TOP2 alpha (TOP2A) in a combined analysis were also shown to have a prognostic impact for longer survival with improved accuracy.[SEP]Relations: acute promyelocytic leukemia has relations: disease_protein with IRF2BP2, disease_protein with IRF2BP2, disease_protein with DAPK2, disease_protein with DAPK2, disease_protein with TET2, disease_protein with TET2, disease_protein with PML, disease_protein with PML, disease_protein with ITGB2, disease_protein with ITGB2.", "label": "yes"}
{"id": "converted_649", "sentence1": "Is low T3 syndrome related with high BNP in cardiac patients?", "sentence2": "BNP and fT3 are independently associated with exercise capacity in severely compromised HF patients., fter adjustment for known confounders, NT-pro-BNP was significantly associated with fT3 and low-T3 syndrome. fT3 (HR 0.58, 95%CI 0.34-0.98) and low-T3 syndrome (HR 3.0, 95%CI 1.4-6.3) were predictive for mortality after adjustment for NT-pro-BNP levels and other cardiovascular prognostic variables., fT3 and low-T3 syndrome are significantly related to NT-pro-BNP in patients with cardiovascular disease, but are predictors of mortality independently of NT-pro-BNP and other known cardiovascular risk parameters., Higher NT-pro BNP concentrations were related to lower total T3 concentrations (r = -0.294, p = 0.011) and to higher reverse T3 concentrations (r = 0.353, p = 0.002)[SEP]Relations: cardiovascular disease has relations: contraindication with Dipotassium phosphate, contraindication with Dipotassium phosphate, contraindication with Polyethylene glycol 300, contraindication with Polyethylene glycol 300, contraindication with Zinc sulfate, contraindication with Zinc sulfate, contraindication with Succinylcholine, contraindication with Succinylcholine. hydrops fetalis has relations: disease_protein with FOXP3, disease_protein with FOXP3.", "label": "yes"}
{"id": "converted_1294", "sentence1": "Are optogenetics tools used in the study and treatment of epilepsy?", "sentence2": "The emerging revolutionary technique of optogenetics enables manipulation of the activity of specific neuronal populations in vivo with exquisite spatiotemporal resolution using light. We used optogenetic approaches to test the role of hippocampal excitatory neurons in the lithium-pilocarpine model of acute elicited seizures in awake behaving rats., This chapter focuses on the development of optogenetics and on-demand technologies for the study of epilepsy and the control of seizures., We then turn to the use of optogenetics, including on-demand optogenetics in the study of epilepsies, which highlights the powerful potential of optogenetics for epilepsy research., Optogenetic techniques provide powerful tools for bidirectional control of neuronal activity and investigating alterations occurring in excitability disorders, such as epilepsy.,  Therefore, one could optogenetically activate specific or a mixed population of interneurons and dissect their selective or concerted inhibitory action on principal cells. We chose to explore a conceptually novel strategy involving simultaneous activation of mixed populations of interneurons by optogenetics and study their impact on ongoing epileptiform activity in mouse acute hippocampal slices., Our data suggest that global optogenetic activation of mixed interneuron populations is a more effective approach for development of novel therapeutic strategies for epilepsy, but the initial action potential generation in principal neurons needs to be taken in consideration., Recently, a number of experiments have explored the treatments for epilepsy with optogenetic control of neurons. Here, we discuss the possibility that an optogenetic approach could be used to control the release of gliotransmitters and improve astrocyte function such as glutamate and K(+) uptake, and thereby offer a potential strategy to investigate and treat astrocyte-related epilepsy., Optogenetic and designer receptor technologies provide unprecedented and much needed specificity, allowing for spatial, temporal and cell type-selective modulation of neuronal circuits. Using such tools, it is now possible to begin to address some of the fundamental unanswered questions in epilepsy, to dissect epileptic neuronal circuits and to develop new intervention strategies. , We then turn to the use of optogenetics, including on-demand optogenetics in the study of epilepsies, which highlights the powerful potential of optogenetics for epilepsy research., Moreover, optogenetics may be considered for developing potential treatment strategies for brain diseases, particularly for excitability disorders such as epilepsy., This chapter focuses on the development of optogenetics and on-demand technologies for the study of epilepsy and the control of seizures., How might novel technologies such as optogenetics lead to better treatments in epilepsy?, WONOEP appraisal: optogenetic tools to suppress seizures and explore the mechanisms of epileptogenesis., Finally, optogenetic tools allow rapid and reversible suppression of epileptic electroencephalography (EEG) activity upon photoactivation., Our data suggest that epileptiform activity in the hippocampus caused by impaired inhibition may be controlled by optogenetic silencing of principal neurons and potentially can be developed as an alternative treatment for epilepsy., Seizure suppression by high frequency optogenetic stimulation using in vitro and in vivo animal models of epilepsy., Optogenetic techniques provide powerful tools for bidirectional control of neuronal activity and investigating alterations occurring in excitability disorders, such as epilepsy. , We first discuss the benefits and caveats to using optogenetic approaches and recent advances in optogenetics related tools. We then turn to the use of optogenetics, including on-demand optogenetics in the study of epilepsies, which highlights the powerful potential of optogenetics for epilepsy research.[SEP]Relations: epilepsy has relations: contraindication with Edetic acid, contraindication with Edetic acid, contraindication with Olanzapine, contraindication with Olanzapine, contraindication with Ergometrine, contraindication with Ergometrine, contraindication with Atomoxetine, contraindication with Atomoxetine, contraindication with Physostigmine, contraindication with Physostigmine.", "label": "yes"}
{"id": "converted_1013", "sentence1": "Is  farnesoid X receptor (FXR) a nuclear receptor?", "sentence2": "Farnesoid X receptor (FXR) belongs to the ligand-activated nuclear receptor superfamily, and functions as a transcription factor regulating the transcription of numerous genes involved in bile acid homeostasis, lipoprotein and glucose metabolism,  Farnesoid X receptor (FXR) is an ascending target for metabolic and inflammatory diseases. As a nuclear receptor, FXR exhibits many physiological effects in transcription control of several genes.,  FXR is a member of the nuclear receptor superfamily which is also highly expressed in the liver. , Farnesoid X receptor (FXR) is a bile acid nuclear receptor described through mouse knockout studies as a tumor suppressor for the development of colon adenocarcinomas, Farnesoid X receptor (FXR, Nr1h4) is a ligand-activated transcription factor belonging to the nuclear receptor superfamily., the nuclear receptor farnesoid X receptor ,  farnesoid X receptor (FXR), a nuclear receptor activated by bile acid ligands. , T-β-MCA is an farnesoid X receptor (FXR) nuclear receptor antagonist,,  Farnesoid X receptor (FXR), a nuclear receptor (NR) and originally considered as a bile acid-activated transcriptional factor, ,  The nuclear receptor farnesoid X receptor (FXR) plays a major role in the enterohepatic cycling of bile acids, Liver X receptors, LXRs, are ligand-activated transcription factors that belong to the group H nuclear receptor (NR) superfamily. , The intracellular nuclear receptor farnesoid X receptor and the transmembrane G protein-coupled receptor TGR5 respond to bile acids by activating transcriptional networks and/or signalling cascades., ncluding those of nuclear receptors, primarily farnesoid X receptor (FXR), , ile acids and their cognate nuclear receptor, FXR,, Farnesoid X receptor (FXR, Nr1h4) and small heterodimer partner (SHP, Nr0b2) are nuclear receptors that are critical to liver homeostasis., he activation of the nuclear receptor farnesoid X receptor (FXRα), bile acid-activated nuclear receptor farnesoid X receptor (FXR),  nuclear receptor signaling, notably by the farnesoid X receptor (FXR, FXR (farnesoid X receptor, NRIH4), a nuclear receptor, plays a major role in the control of cholesterol metabolism., The role of the nuclear receptor FXR is unclear., nuclear receptor FXR , a member of the nuclear receptor superfamily of ligand-activated transcription factors,, Farnesoid X receptor (FXR) is a nuclear receptor that functions as a bile acid sensor controlling bile acid homeostasis.[SEP]Relations: nuclear receptor activity has relations: molfunc_protein with RXRA, molfunc_protein with RXRA, molfunc_protein with RXRG, molfunc_protein with RXRG, molfunc_protein with RXRB, molfunc_protein with RXRB, molfunc_protein with NKX3-1, molfunc_protein with NKX3-1, molfunc_protein with ESR1, molfunc_protein with ESR1.", "label": "yes"}
{"id": "converted_1733", "sentence1": "Is mitofusin 2 a receptor for parkin?", "sentence2": "Recent work demonstrates that a phosphorylated form of the mitochondrial fusion protein Mitofusin 2 serves as a receptor for Parkin translocation to damaged mitochondria., We show that the mitochondrial outer membrane guanosine triphosphatase mitofusin (Mfn) 2 mediates Parkin recruitment to damaged mitochondria. , Mfn2 functions as a mitochondrial receptor for Parkin and is required for quality control of cardiac mitochondria., Mitofusin 1 and mitofusin 2 are ubiquitinated in a PINK1/parkin-dependent manner upon induction of mitophagy[SEP]Relations: mitochondrion has relations: cellcomp_protein with AZIN2, cellcomp_protein with AZIN2, cellcomp_protein with REXO2, cellcomp_protein with REXO2, cellcomp_protein with ACO2, cellcomp_protein with ACO2, cellcomp_protein with YARS2, cellcomp_protein with YARS2, cellcomp_protein with PARK7, cellcomp_protein with PARK7.", "label": "yes"}
{"id": "converted_22", "sentence1": "Are transcription and splicing connected?", "sentence2": ", as splicing is often cotranscriptional, a complex picture emerges in which splicing regulation not only depends on the balance of splicing factor binding to their pre-mRNA target sites but also on transcription-associated features such as protein recruitment to the transcribing machinery and elongation kinetics., recent evidence shows that chromatin structure is another layer of regulation that may act through various mechanisms, hese span from regulation of RNA polymerase II elongation, which ultimately determines splicing decisions, to splicing factor recruitment by specific histone marks., Chromatin may not only be involved in alternative splicing regulation but in constitutive exon recognition as well, Moreover, splicing was found to be necessary for the proper 'writing' of particular chromatin signatures, giving further mechanistic support to functional interconnections between splicing, transcription and chromatin structure., These links between chromatin configuration and splicing raise the intriguing possibility of the existence of a memory for splicing patterns to be inherited through epigenetic modifications., Spliceosome assembly occurs co-transcriptionally, raising the possibility that DNA structure may directly influence alternative splicing., upporting such an association, recent reports have identified distinct histone methylation patterns, elevated nucleosome occupancy and enriched DNA methylation at exons relative to introns, Moreover, the rate of transcription elongation has been linked to alternative splicing., ere we provide the first evidence that a DNA-binding protein, CCCTC-binding factor (CTCF), can promote inclusion of weak upstream exons by mediating local RNA polymerase II pausing both in a mammalian model system for alternative splicing, CD45, and genome-wide, We recently showed that cotranscriptional splicing occurs efficiently in Drosophila,, In recent years it became apparent that splicing is predominantly cotranscriptional, To determine the prevalence of cotranscriptional splicing in Drosophila, we sequenced nascent RNA transcripts from Drosophila S2 cells as well as from Drosophila heads. Eighty-seven percent of the introns assayed manifest >50% cotranscriptional splicing. The remaining 13% are cotranscriptionally spliced poorly or slowly, with ∼3% being almost completely retained in nascent pre-mRNA., We estimate that > or =90% of endogenous yeast splicing is posttranscriptional, consistent with an analysis of posttranscriptional snRNP-associated pre-mRNA., Notably, the topoisomerase I inhibitor camptothecin, which stalls elongating Pol II, increased cotranscriptional splicing factor accumulation and splicing in parallel. This provides direct evidence for a kinetic link between transcription, splicing factor recruitment and splicing catalysis., Recent evidence indicates that transcriptional elongation and splicing can be influenced reciprocally: Elongation rates control alternative splicing and splicing factors can, in turn, modulate pol II elongation., The presence of transcription factors in the spliceosome and the existence of proteins, such as the coactivator PGC-1, with dual activities in splicing and transcription can explain the links between both processes and add a new level of complexity to the regulation of gene expression in eukaryotes.[SEP]Relations: RNA splicing has relations: bioprocess_protein with SYNCRIP, bioprocess_protein with SYNCRIP, bioprocess_protein with SON, bioprocess_protein with SON, bioprocess_protein with USB1, bioprocess_protein with USB1, bioprocess_protein with SNRPG, bioprocess_protein with SNRPG. transcription factor binding has relations: molfunc_protein with SP1, molfunc_protein with SP1.", "label": "yes"}
{"id": "converted_3143", "sentence1": "Velocardial facial syndrome, otherwise known as Di George syndrome  is caused by a deletion in chromosome 21, yes or no?", "sentence2": "The deletion of chromosome 22q11.2 is involved in the majority of DiGeorge or velo-cardiofacial syndrome., deletions of chromosome 7q11.23 (Williams syndrome), 15q11-q13 (Angelman syndrome, Prader-Willi syndrome) and 22q11 (Di George syndrome), Submicroscopic deletions of chromosome 22q11 have been reported in a multiple anomaly syndrome variously labelled as velocardiofacial syndrome, conotruncal anomaly face syndrome, and Di George syndrome, The 22q11.2 deletion syndrome (di George syndrome) is one of the most prevalent genetic disorders., UNLABELLED\nMost of the children with Di George syndrome and 60% of patients with velocardiofacial syndrome exhibit a microdeletion within chromosome 22q11., Submicroscopic deletions of chromosome 22q11 have been reported in a multiple anomaly syndrome variously labelled as velocardiofacial syndrome, conotruncal anomaly face syndrome, and Di George syndrome., 22q11.2DS has several presentations including Di George's syndrome, velo-cardio-facial syndrome or Shprintzen's syndrome and it is the most frequent microdeletion syndrome in the general population (prevalence estimated at 1/4000 births, de novo: 90%)., Di George syndrome due to mutation on 22q or 10q) and can also result from microdeletion or point mutation (in the Shprintzen syndrome 70% represent microdeletion and 30% point mutation at 22q11, in Rubinstein-Taybi syndrome 10% cases result from microdeletions and 90% from point mutations); 7) Population incidence of microdeletions is high (1:4000 to 1:30,000) because their etiologic mechanism is related to the common unequal crossing over; 8) Imprinting plays a role in some cases, e.g., [Microdeletion of the chromosome 22q11 in children: apropos of a series of 49 patients].<AbstractText Label=\"UNLABELLED\">Most of the children with Di George syndrome and 60% of patients with velocardiofacial syndrome exhibit a microdeletion within chromosome 22q11. , 22q11.2DS has several presentations including Di George's syndrome, velo-cardio-facial syndrome or Shprintzen's syndrome and it is the most frequent microdeletion syndrome in the general population (prevalence estimated at 1/4000 births, de novo: 90%). , <b>UNLABELLED</b>: Most of the children with Di George syndrome and 60% of patients with velocardiofacial syndrome exhibit a microdeletion within chromosome 22q11., Most of the children with Di George syndrome and 60% of patients with velocardiofacial syndrome exhibit a microdeletion within chromosome 22q11.[SEP]Relations: Williams syndrome has relations: disease_disease with syndrome caused by partial chromosomal deletion, disease_disease with syndrome caused by partial chromosomal deletion, disease_disease with partial deletion of the long arm of chromosome 7, disease_disease with partial deletion of the long arm of chromosome 7. DiGeorge syndrome has relations: disease_disease with syndrome caused by partial chromosomal deletion, disease_disease with syndrome caused by partial chromosomal deletion. Abnormality of the dentition has relations: disease_phenotype_positive with chromosome 15q24 deletion syndrome, disease_phenotype_positive with chromosome 15q24 deletion syndrome, disease_phenotype_positive with chromosome 9p deletion syndrome, disease_phenotype_positive with chromosome 9p deletion syndrome.", "label": "no"}
{"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]Relations: cerebral malaria has relations: disease_disease with malaria, disease_disease with malaria, contraindication with Betamethasone, contraindication with Betamethasone, contraindication with Methylprednisolone, contraindication with Methylprednisolone, contraindication with Prednisone, contraindication with Prednisone. Plasmodium falciparum malaria has relations: disease_disease with malaria, disease_disease with malaria.", "label": "yes"}
{"id": "converted_2279", "sentence1": "Is there increased recombination rate in human regulatory domains?", "sentence2": "Evidence of reduced recombination rate in human regulatory domains., We study the relationship between recombination rate and gene regulatory domains, defined by a gene and its linked control elements. We define these links using expression quantitative trait loci (eQTLs), methylation quantitative trait loci (meQTLs), chromatin conformation from publicly available datasets (Hi-C and ChIA-PET), and correlated activity links that we infer across cell types. Each link type shows a \"recombination rate valley\" of significantly reduced recombination rate compared to matched control regions. This recombination rate valley is most pronounced for gene regulatory domains of early embryonic development genes, housekeeping genes, and constitutive regulatory elements, which are known to show increased evolutionary constraint across species. Recombination rate valleys show increased DNA methylation, reduced doublestranded break initiation, and increased repair efficiency, specifically in the lineage leading to the germ line. Moreover, by using only the overlap of functional links and DNA methylation in germ cells, we are able to predict the recombination rate with high accuracy.CONCLUSIONS: Our results suggest the existence of a recombination rate valley at regulatory domains and provide a potential molecular mechanism to interpret the interplay between genetic and epigenetic variations.[SEP]Relations: Geneticin has relations: drug_drug with Antihemophilic Factor (Recombinant), PEGylated, drug_drug with Antihemophilic Factor (Recombinant), PEGylated, drug_drug with Antithrombin III human, drug_drug with Antithrombin III human, drug_drug with Botulinum Toxin Type B, drug_drug with Botulinum Toxin Type B, drug_drug with Certolizumab pegol, drug_drug with Certolizumab pegol, drug_drug with Tubocurarine, drug_drug with Tubocurarine.", "label": "no"}
{"id": "converted_3744", "sentence1": "Has tocilizumab been assessed against Covid-19?", "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.[SEP]Relations: interleukin-6 receptor activity has relations: molfunc_protein with IL6ST, molfunc_protein with IL6ST, molfunc_protein with IL6R, molfunc_protein with IL6R. interleukin-6 receptor complex has relations: cellcomp_protein with IL6ST, cellcomp_protein with IL6ST, cellcomp_protein with IL6R, cellcomp_protein with IL6R, cellcomp_protein with IL6, cellcomp_protein with IL6.", "label": "yes"}
{"id": "converted_2517", "sentence1": "Does wheat belongs to the genus Avena, yes or no?", "sentence2": "oat seedlings (Avena sativa), wild green-oat (Avena sativa) ,  Oat (Avena sativa L.), Oat (Avena sativa L.), Avena (Oats), wild oats (Avena fatua L.), oats (genus Avena), Avena sativa L. and A. byzantina C. Koch) ,  oat (Avena sativa L.)., oat (Avena sativa L.) and wheat (Triticum aestivum[SEP]Relations: ornithine-oxo-acid transaminase activity has relations: molfunc_protein with OAT, molfunc_protein with OAT.", "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]Relations: 3,5-diiodothyropropionic acid has relations: drug_drug with Ethionamide, drug_drug with Ethionamide, drug_drug with Motesanib, drug_drug with Motesanib, drug_drug with Ritonavir, drug_drug with Ritonavir, drug_drug with Escitalopram, drug_drug with Escitalopram, drug_drug with Flumatinib, drug_drug with Flumatinib.", "label": "yes"}
{"id": "converted_3543", "sentence1": "Does an interferon (IFN) signature exist for SLE patients?", "sentence2": "Interferon regulatory factor 7 activation correlates with the IFN signature and recurrent disease., In SLE post-transplant, recurrent disease activity and induction of IRF7 protein expression correlated with activation of the IFN signature., JAK inhibitor has the amelioration effect in lupus-prone mice: the involvement of IFN signature gene downregulation., We also detected decreased expression of several IFN-signature genes Ifit3 and Isg15 in CD4+ from SLE-prone mice following TOFA and DEXA treatment, and IFIT3 in CD3+ T cells from human patients following immunosuppressant therapy including steroid, respectively, We found that cDCs from prediseased TCSle male mice express the IFN signature as female TCSle cDCs do. Estrogens are necessary but not sufficient to express this IFN signature, but high doses of E2 can compensate for other steroidal components., Conventional DCs from Male and Female Lupus-Prone B6.NZM Sle1/Sle2/Sle3 Mice Express an IFN Signature and Have a Higher Immunometabolism That Are Enhanced by Estrogen., Type I IFN signature in childhood-onset systemic lupus erythematosus,  Interferon type I (IFN-I) plays a pivotal role in the pathogenesis of SLE. , The IFN-I score (positive or negative), as a measure of IFN-I activation, was assessed using real-time quantitative PCR (RT-PCR) expression values of IFN-I signature genes (IFI44, IFI44L, IFIT1, Ly6e, MxA, IFITM1) in CD14+ monocytes of cSLE patients and healthy controls (HCs)[SEP]Relations: Human interferon beta has relations: drug_protein with IFNAR1, drug_protein with IFNAR1, drug_drug with Aminophylline, drug_drug with Aminophylline, drug_drug with Fenethylline, drug_drug with Fenethylline, drug_drug with Proxyphylline, drug_drug with Proxyphylline, drug_drug with 8-chlorotheophylline, drug_drug with 8-chlorotheophylline.", "label": "yes"}
{"id": "converted_4708", "sentence1": "Can whole genome sequencing be used for diagnosis of mitochondrial disease?", "sentence2": "Whole genome sequencing is a useful diagnostic test in patients with suspected mitochondrial disorders, yielding a diagnosis in a further 31% after exclusion of common causes. Most diagnoses were non-mitochondrial disorders and included developmental disorders with intellectual disability, epileptic encephalopathies, other metabolic disorders, cardiomyopathies, and leukodystrophies. These would have been missed if a targeted approach was taken, and some have specific treatments.[SEP]Relations: mitochondrial disease has relations: disease_disease with inborn mitochondrial metabolism disorder, disease_disease with inborn mitochondrial metabolism disorder, disease_disease with disease of membrane bound organelle, disease_disease with disease of membrane bound organelle. metabolic disease has relations: disease_disease with DNA repair disease, disease_disease with DNA repair disease. Intellectual disability has relations: disease_phenotype_positive with multiple mitochondrial dysfunctions syndrome, disease_phenotype_positive with multiple mitochondrial dysfunctions syndrome, disease_phenotype_positive with HSD10 mitochondrial disease, disease_phenotype_positive with HSD10 mitochondrial disease.", "label": "yes"}
{"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_2342", "sentence1": "Does DDX54 play a role in DNA damage response?", "sentence2": "DDX54 regulates transcriptome dynamics during DNA damage response., The contribution of post-transcriptional gene regulatory networks to the DNA damage response (DDR) has not been extensively studied. Here, we systematically identified RNA-binding proteins differentially interacting with polyadenylated transcripts upon exposure of human breast carcinoma cells to ionizing radiation (IR). Interestingly, more than 260 proteins, including many nucleolar proteins, showed increased binding to poly(A)+RNA in IR-exposed cells. The functional analysis of DDX54, a candidate genotoxic stress responsive RNA helicase, revealed that this protein is an immediate-to-early DDR regulator required for the splicing efficacy of its target IR-induced pre-mRNAs. Upon IR exposure, DDX54 acts by increased interaction with a well-defined class of pre-mRNAs that harbor introns with weak acceptor splice sites, as well as by protein-protein contacts within components of U2 snRNP and spliceosomal B complex, resulting in lower intron retention and higher processing rates of its target transcripts. Because DDX54 promotes survival after exposure to IR, its expression and/or mutation rate may impact DDR-related pathologies. Our work indicates the relevance of many uncharacterized RBPs potentially involved in the DDR., The functional analysis of DDX54, a candidate genotoxic stress responsive RNA helicase, revealed that this protein is an immediate-to-early DDR regulator required for the splicing efficacy of its target IR-induced pre-mRNAs.[SEP]Relations: protein binding has relations: molfunc_protein with DDX55, molfunc_protein with DDX55, molfunc_protein with DDX5, molfunc_protein with DDX5, molfunc_protein with DDX6, molfunc_protein with DDX6, molfunc_protein with DDX60, molfunc_protein with DDX60, molfunc_protein with DDX42, molfunc_protein with DDX42.", "label": "yes"}
{"id": "converted_2877", "sentence1": "Can enasidenib be used for the treatment of acute myeloid leukemia?", "sentence2": "In August 2017, the United States Federal Drug Administration (FDA) approved enasidenib (Idhifa, Celgene/Agios) for adults with relapsed and refractory acute myelogenous leukemia (AML) with an IDH2 mutation. [SEP]Relations: acute promyelocytic leukemia has relations: disease_disease with bilineal acute myeloid leukemia, disease_disease with bilineal acute myeloid leukemia, disease_disease with acute myeloid leukemia with recurrent genetic anomaly, disease_disease with acute myeloid leukemia with recurrent genetic anomaly, disease_protein with KIT, disease_protein with KIT, disease_protein with CEBPA, disease_protein with CEBPA, disease_protein with ITGAM, disease_protein with ITGAM.", "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_3904", "sentence1": "Is Ixodes a species of tick?", "sentence2": "ixodid ticks, ixodid ticks ,  ixodid ticks, tick, Ixodes ricinus, hard ticks (family Ixodidae), The two enzootic tick vectors, Ixodes affinis and Ixodes minor, rarely bite humans but are more important than the human biting \"bridge\" vector, Ixodes scapularis, in maintaining the enzootic spirochete cycle in nature., is more common in coastal habitats, where a greater diversity of Ixodes species ticks are found feeding on small mammal hosts (four species when compared with only I. pacificus in other sampled habitats)., We found three of five previously reported tick species as well as a tick resembling the eastern North American tick Ixodes minor Neumann (which we here designate Ixodes \"Mojave morphotype\") on isolated Amargosa voles and Owens Valley voles (Microtus californicus vallicola Bailey) in Inyo County in 2012 and 2014., THODS: We focused on the well-studied tick genus Ixodes from which many species are known to transmit zoonotic diseases to humans. W, Ectoparasites of Microtus californicus and Possible Emergence of an Exotic Ixodes Species Tick in California., Since 2007, non-native tick species have been documented in the state every year, including Amblyomma americanum, Dermacentor andersoni, Dermacentor occidentalis, Dermacentor variabilis, Ixodes pacificus, Ixodes ricinus, Ixodes scapularis, Ixodes texanus, and Rhipicephalus sanguineus sensu lato (s.l.)., in 1.5% of Ixodes species ticks and 3.6% of small mammals., Data-driven predictions and novel hypotheses about zoonotic tick vectors from the genus Ixodes., spirochetes and transmitted by Ixodes species ticks., In this study, cutaneous bite-site lesions were analyzed using Affymetrix mouse genome 430A 2.0 arrays and histopathology at 1, 3, 6, and 12 hours after uninfected Ixodes scapularis nymphal tick attachment., The minimally vegetated, extremely arid desert surrounding the pools is essentially uninhabitable for Ixodes species ticks., Biology of Ixodes species ticks in relation to tick-borne zoonoses., Borrelia miyamotoi is a newly described emerging pathogen transmitted to people by Ixodes species ticks and found in temperate regions of North America, Europe, and Asia., Rickettsia conorii was found in virtually all non- Ixodes tick species from Albania and Turkey., Ixodes anatis is a species of endophilic (nidicolous) tick species parasitizing brown kiwi (Apteryx mantelli). Even, Ixodes ariadnae is a tick species of bats so far reported only in Central Europe, with its description based on the female and nymph. Th, BACKGROUND: Ixodes collaris Hornok, 2016 is a recently discovered tick species associated with bats, Ixodes holocyclus (Acarina: Ixodidae) and Ixodes cornuatus (Acarina: Ixodidae) are two tick species found in the more densely populated areas of Australia and are known to be the cause of the neurotoxic disease tick paralysis in humans and mammals. Borre, Ixodes affinis Neumann (Acari: Ixodidae) is a hard-bodied tick species distributed throughout much of the southeastern United States. Alt, ixodid tick fauna consists of 241 species in the genus Ixodes and 442 species in the genera Amblyomma, Anomalohimalaya, Bothriocroton, Cosmiomma, Dermacentor, Haemaphysalis, Hyalomma, Margaropus, Nosomma, Rhipicentor and Rhipicephalus in the family Ixodidae, with the genus Boophilus becoming a subgenus of the genus Rhipicephalus. The family Nutt, e following 16 ixodid tick species were identified: Ixodes fuscipes, Amblyomma auricularium, Amblyomma coelebs, Amblyomma dubitatum, Amblyomma geayi, Amblyomma humerale, Amblyomma latepunctatum, Amblyomma longirostre, Amblyomma naponense, Amblyomma nodosum, Amblyomma oblongoguttatum, Amblyomma ovale, Amblyomma romitii, Amblyomma rotundatum, Amblyomma scalpturatum, and Amblyomma varium. From these, A. aur, In 2014, a new tick species, Ixodes inopinatus, was described, which is closely related to Ixodes ricinus. So fa, ontinent. Zoonotic Babesia is vectored by Ixodes ticks and is commonly transmitted in North America by Ixodes scapularis, the tick species responsible for transmitting the pathogens that also cause Lyme disease, Powassan virus, and anaplasmosis in hu, In addition to identifying novel, testable hypotheses about intrinsic features driving vectorial capacity across Ixodes tick species, our model identifies particular Ixodes species with the highest probability of carrying zoonotic diseases, offering specific targets for increased zoonotic investigation and surveillance., To date, the tick fauna of this area consists of 117 species in the following families: Argasidae-Argas (7 species), Carios (4 species) and Ornithodoros (2 species); Ixodidae-Amblyomma (8 species), Anomalohimalaya (2 species), Dermacentor (12 species), Haemaphysalis (44 species), Hyalomma (6 species), Ixodes (24 species) and Rhipicephalus (8 species)., During a 3-yr comprehensive study, 196 ixodid ticks (9 species) were collected from 89 passerine birds (32 species) from 25 localities across Canada to determine the distribution of avian-associated tick species and endogenous Lyme disease spirochetes, Borrelia burgdorferi Johnson, Schmid, Hyde, Steigerwalt, and Brenner., In the Polish fauna there are 19 species of ticks (Ixodida) recognized as existing permanently in our country: Argas reflexus, Argas polonicus, Carios vespertilionis, Ixodes trianguliceps, Ixodes arboricola, Ixodes crenulatus, Ixodes hexagonus, Ixodes lividus, Ixodes rugicollis, Ixodes caledonicus, Ixodes frontalis, Ixodes simplex, Ixodes vespertilionis, Ixodes apronophorus, Ixodes persulcatus, Ixodes ricinus, Haemaphysalis punctata, Haemaphysalis concinna, Dermacentor reticulatus., Occasionally, alien species of ticks transferred to the territory of Poland are recorded: Amblyomma sphenodonti, Amblyomma exornatum, Amblyomma flavomaculatum, Amblyomma latum, Amblyomma nuttalli, Amblyomma quadricavum, Amblyomma transversale, Amblyomma varanensis, Amblyomma spp., Dermacentor marginatus, Hyalomma aegyptium, Hyalomma marginatum, Ixodes eldaricus, Ixodes festai, Rhipicephalus rossicus, Rhipicephalus sanguineus., Haemaphysalis leporispalustris (Packard) (one nymph, 14 larvae); the bird tick Ixodes brunneus Koch (two larvae); the American dog tick, Dermacentor variabilis (Say) (one nymph); and Ixodes affinis Neumann (one larva)., Four members of the Ixodes ricinus species complex, Ixodes pacificus, Ixodes persulcatus, Ixodes ricinus and Ixodes scapularis, have, between them, a worldwide distribution within the northern hemisphere., Diapause in ticks of the medically important Ixodes ricinus species complex., Herein, we report these ticks to represent three different species: Ixodes catarinensis n. sp., We found that 430 endemic ticks were from 3 Ixodes species: Ixodes pacificus, Ixodes spinipalpis, and Ixodes angustus, whereas Ixodes scapularis (n = 111) was the most common species among the 119 nonendemic ticks., In total, 549 human-biting Ixodes ticks were submitted comprising both endemic and nonendemic species., Human-Biting Ixodes Ticks and Pathogen Prevalence from California, Oregon, and Washington., In this study, we show that many nonendemic Ixodes ticks (119/549) are most likely acquired from travel to a different geographic region., The Ixodes ricinus species complex is a group of ticks distributed in almost all geographic regions of the world., We report a tick associated with the enhancement of mammalian meat anaphylaxis after tick bite which is novel for both Australia and the world and establishes Ixodes (Endopalpiger) australiensis as a second tick species associated with mammalian meat allergy in Australia., Among the various species of hard ticks, Ixodes ricinus is the most frequently found tick throughout Europe.,  in humans. We aimed to identify intrinsic traits that predict which Ixodes tick species are confirmed or strongly suspected to be vectors of zoonotic pathogens.METHODS: We focused on the well-studied tick genus Ixodes from which many species are known to transmit zoonoti, A list of the 70 species of Australian ticks; diagnostic guides to and species accounts of Ixodes holocyclus (paralysis tick), Ixodes cornuatus (southern paralysis tick) and Rhipicephalus australis (Australian cattle tick); and consideration of the place of Australia in the evolution of ticks with comments on four controversial ideas., Differentiation of medically important Euro-Asian tick species Ixodes ricinus, Ixodes persulcatus, Ixodes hexagonus, and Dermacentor reticulatus by polymerase chain reaction., All these I. granulatus ticks collected from Taiwan and Japan were genetically affiliated to a monophyletic group with highly homogeneous sequences (95.8-99.5% similarity), and can be discriminated from other species and subgenera of Ixodes ticks with a sequence divergence ranging from 13.6% to 62.9%., The phylogenetic relationships were analyzed by comparing the sequences of mitochondrial 16S ribosomal DNA gene obtained from 19 strains of ticks representing seven species of Ixodes and two outgroup species (Rhipicephalus sanguineus and Haemaphysalis inermis)., e, I. woyliei n. sp. was only found on two I. o. fusciventer.CONCLUSIONS: Morphological and molecular data have confirmed the first new Australian Ixodes tick species described in ov, More than 800 tick species have been reported world-wide however only about 30 tick species feed on humans, among them Ixodes ricinus, which is the most frequent tick species biting humans in Europe., Description of a new tick species, Ixodes collaris n. sp. (Acari: Ixodidae), from bats (Chiroptera: Hipposideridae, Rhinolophidae) in Vietnam.[SEP]Relations: Lyme disease has relations: disease_disease with tick-borne infectious disease, disease_disease with tick-borne infectious disease, disease_disease with spirochaetales infections, disease_disease with spirochaetales infections. anaplasmosis has relations: disease_disease with tick-borne infectious disease, disease_disease with tick-borne infectious disease. Rickettsiosis has relations: disease_disease with tick-borne relapsing fever, disease_disease with tick-borne relapsing fever. Dental malocclusion has relations: disease_phenotype_positive with enthesitis-related juvenile idiopathic arthritis, disease_phenotype_positive with enthesitis-related juvenile idiopathic arthritis.", "label": "yes"}
{"id": "converted_1804", "sentence1": "Is RASA2 involved in melanoma?", "sentence2": "Analysis of 501 melanoma exomes identified RASA2, encoding a RasGAP, as a tumor-suppressor gene mutated in 5% of melanomas. Recurrent loss-of-function mutations in RASA2 were found to increase RAS activation, melanoma cell growth and migration. RASA2 expression was lost in ≥30% of human melanomas and was associated with reduced patient survival. These findings identify RASA2 inactivation as a melanoma driver and highlight the importance of RasGAPs in cancer., Analysis of 501 melanoma exomes identified RASA2, encoding a RasGAP, as a tumor-suppressor gene mutated in 5% of melanomas, These findings identify RASA2 inactivation as a melanoma driver and highlight the importance of RasGAPs in cancer., Recurrent loss-of-function mutations in RASA2 were found to increase RAS activation, melanoma cell growth and migration., Analysis of 501 melanoma exomes identified RASA2, encoding a RasGAP, as a tumor-suppressor gene mutated in 5% of melanomas.[SEP]Relations: melanoma has relations: disease_protein with RASA2, disease_protein with RASA2, disease_protein with RAC2, disease_protein with RAC2, disease_protein with ARL2, disease_protein with ARL2, disease_protein with MDM2, disease_protein with MDM2, disease_protein with GPHA2, disease_protein with GPHA2.", "label": "yes"}
{"id": "converted_1432", "sentence1": "Do U6-associated proteins Lsm4 and Lsm6 interact with SMN?", "sentence2": "SMN also interacts with at least two of the U6-associated Sm-like (Lsm) proteins, Lsm4 and Lsm6. , Interestingly, SMN also interacts with at least two of the U6-associated Sm-like (Lsm) proteins, Lsm4 and Lsm6, Furthermore, we present evidence for two separate binding sites in SMN for Sm/Lsm proteins., Interestingly, SMN also interacts with at least two of the U6-associated Sm-like (Lsm) proteins, Lsm4 and Lsm6. , Symmetrical dimethylation of arginine residues in spliceosomal Sm protein B/B' and the Sm-like protein LSm4, and their interaction with the SMN protein., Interestingly, SMN also interacts with at least two of the U6-associated Sm-like (Lsm) proteins, Lsm4 and Lsm6. Furthermore, the carboxyl-terminal arginine- and glycine-rich domain of Lsm4 directly interacts with SMN., This entity promotes the binding of a set of factors, termed LSm/Sm proteins, onto snRNA to form the core structure of these particles. , Toward an assembly line for U7 snRNPs: interactions of U7-specific Lsm proteins with PRMT5 and SMN complexes., In this report, we demonstrate that the coilin C-terminal domain binds directly to various Sm and Lsm proteins via their Sm motifs. We show that the region of coilin responsible for this binding activity is separable from that which binds to SMN., Thus, the ability to interact with free Sm (and Lsm) proteins as well as with intact snRNPs, indicates that coilin and CBs may facilitate the modification of newly formed snRNPs, the regeneration of 'mature' snRNPs, or the reclamation of unassembled snRNP components., Moreover this structure has important consequences for snRNP assembly that is mediated by two complexes containing the PRMT5 methyltransferase and the SMN (survival of motor neurons) protein, respectively., Arginine/glycine (RG)-rich domains in components of the SMN complex interact with Sm, like-Sm (LSm), fibrillarin, RNA helicase A (Gu), and coilin proteins, all of which are antigen targets in a variety of diseases. [SEP]Relations: SMN complex has relations: cellcomp_protein with GEMIN6, cellcomp_protein with GEMIN6, cellcomp_protein with SMN2, cellcomp_protein with SMN2, cellcomp_protein with SMN1, cellcomp_protein with SMN1. small nuclear ribonucleoprotein complex has relations: cellcomp_protein with LSM6, cellcomp_protein with LSM6, cellcomp_protein with LSM6, cellcomp_protein with LSM6.", "label": "yes"}
{"id": "converted_4543", "sentence1": "Is CircRNA produced by back splicing of exon, intron or both, forming exon or intron circRNA?", "sentence2": "CircRNAs are a subclass of lncRNAs that have been found to be abundantly present in a wide range of species, including humans. CircRNAs are generally produced by a noncanonical splicing event called backsplicing that is dependent on the canonical splicing machinery, giving rise to circRNAs classified into three main categories: exonic circRNA, circular intronic RNA, and exon-intron circular RNA. , Circular RNA (circRNA) is a large class of covalently closed circRNA., Human transcriptome contains a large number of circular RNAs (circRNAs) that are mainly produced by back splicing of pre-mRNA., Analyses of the other reads revealed two origins for non-canonical circRNAs: (1) Intronic sequences for lariat-derived intronic circRNAs and intron circles, (2) Mono-exonic genes (mostly non-coding) for either a new type of circRNA (including only part of the exon: sub-exonic circRNAs) or, even more rarely, mono-exonic canonical circRNAs., Our objective was to characterize non-canonical circRNAs, namely not originating from back splicing and circRNA produced by non-coding genes., Recent studies have identified a new class of ncRNAs called circular RNAs (circRNAs), which are produced by back-splicing and fusion of either exons, introns, or both exon-intron into covalently closed loops., CircRNA is produced by the reverse splicing of exon, intron or both, forming exon or intron circRNA., Circular RNAs (circRNAs) belong to a recently re-discovered species of RNA that emerge during RNA maturation through a process called back-splicing. , Exonic circular RNAs (circRNAs) are RNA molecules that are covalently closed by back-splicing via canonical splicing machinery. , Human transcriptome contains a large number of circular RNAs (circRNAs) that are mainly produced by back splicing of pre-mRNA. , Circular RNAs (circRNAs) are a class of non‑coding RNAs formed by covalently closed loops through back‑splicing and exon‑skipping. , Here, we review the emerging understanding that both, circRNAs produced by co- and posttranscriptional head-to-tail \"backsplicing\" of a downstream splice donor to a more upstream splice acceptor, as well as circRNAs generated from intronic lariats during colinear splicing, may exhibit physiologically relevant regulatory functions in eukaryotes., Compared to the linear RNA, circRNAs are produced differentially by backsplicing exons or lariat introns from a pre-messenger RNA (mRNA) forming a covalently closed loop structure missing 3' poly-(A) tail or 5' cap, rendering them immune to exonuclease-mediated degradation., CircRNAs are a large class of endogenous single-stranded RNA that is different from other linear RNA, which are produced by back-splicing and fusion of either exons, introns, or both exon-intron into covalently closed loops., Circular RNAs (circRNAs) derived from back-spliced exons have been widely identified as being co-expressed with their linear counterparts.[SEP]Relations: Viral Messenger RNA Synthesis has relations: pathway_protein with POLR2C, pathway_protein with POLR2C, pathway_protein with POLR2B, pathway_protein with POLR2B, pathway_protein with POLR2K, pathway_protein with POLR2K, pathway_protein with POLR2E, pathway_protein with POLR2E, pathway_protein with POLR2L, pathway_protein with POLR2L.", "label": "yes"}
{"id": "converted_4240", "sentence1": "Is Cabotegravir effective for HIV prevention?", "sentence2": "A new paradigm for antiretroviral delivery: long-acting cabotegravir and rilpivirine for the treatment and prevention of HIV., PURPOSE OF REVIEW: Cabotegravir (CAB) and rilpivirine (RPV) is the first long-acting injectable antiretroviral therapy (ART) option approved for virologically suppressed adults with HIV-1. In addition, long-acting CAB is a promising agent for HIV preexposure prophylaxis (PrEP). , SUMMARY: Clinical trial results support the use of long-acting CAB for HIV PrEP and long-acting CAB and RPV as a switch strategy for adults with HIV-1 who are first virologically suppressed with oral ART. , OBJECTIVE: We had previously shown that long-acting cabotegravir (CAB-LA) injections fully protected macaques from vaginal simian HIV (SHIV) infection., The Potential Impact of Long-Acting Cabotegravir for HIV Prevention in South Africa: A Mathematical Modeling Study.,  Long-acting cabotegravir (CAB LA) is a potential new injectable formulation for human immunodeficiency virus (HIV) PrEP being tested in phase III trials., Design and Testing of a Cabotegravir Implant for HIV Prevention., Cabotegravir and rilpivirine long-acting injectable antiretroviral therapy for the treatment of HIV-1 infection brings promise of a new mode of delivery and potential solutions to some problems of oral therapy, but also new challenges and unanswered questions., Cabotegravir is an investigational integrase inhibitor in development for the treatment and pre-exposure prophylaxis of HIV-1 infection., Bictegravir, cabotegravir, dolutegravir, elvitegravir, and raltegravir are members of the latest class of antiretrovirals available to treat human immunodeficiency virus (HIV) infection, the integrase strand transfer inhibitors., PURPOSE OF REVIEW: Long-acting cabotegravir may provide a novel therapeutic option for both the treatment and prevention of HIV-1 infection that does not necessitate adherence, Long-acting injectable cabotegravir for the prevention of HIV infection, BACKGROUND: The HIV Prevention Trials Network (HPTN) 083 trial demonstrated that long-acting cabotegravir (CAB-LA) was more effective than tenofovir disoproxil fumarate-emtricitabine (TDF/FTC) in preventing human immunodeficiency virus (HIV) in cisgender men and transgender women who have sex with, Areas covered: Here, we review trials of cabotegravir (CAB) as treatment of HIV-1 infection and its potential use as pre-exposure prophylaxis (PrEP) in high risk individuals, including issues around oral lead in and potential resistance emergence. Exper, frequent dosing. This review focuses on the potential benefits and considerations for the study and use of 2 long-acting injectable agents, cabotegravir (GSK1265744LA, CAB LA) and rilpivirine (TMC278LA, RPV LA), for use as chemoprophylaxis for HIV , An evaluation of cabotegravir for HIV treatment and prevention., Cabotegravir long-acting for HIV-1 prevention., Our findings suggest that cabotegravir should be evaluated in clinical trials as a potential option for antiretroviral therapy and preexposure prophylaxis in HIV-2-prevalent settings., Profile of cabotegravir and its potential in the treatment and prevention of HIV-1 infection: evidence to date., Long-Acting Cabotegravir for HIV/AIDS Prophylaxis., Cabotegravir for HIV Prevention in Cisgender Men and Transgender Women., Cabotegravir is a novel human immunodeficiency virus integrase enzyme inhibitor used for prevention and treatment of HIV infection., PURPOSE OF REVIEW: Long-acting cabotegravir may provide a novel therapeutic option for both the treatment and prevention of HIV-1 infection that does not necessitate adherence , Cabotegravir in the treatment and prevention of Human Immunodeficiency Virus-1., Cabotegravir: its potential for antiretroviral therapy and preexposure prophylaxis., Satisfaction and acceptability of cabotegravir long-acting injectable suspension for prevention of HIV: Patient perspectives from the ECLAIR trial.[SEP]Relations: Rilpivirine has relations: contraindication with chronic hepatitis B virus infection, contraindication with chronic hepatitis B virus infection, drug_drug with Cabazitaxel, drug_drug with Cabazitaxel, drug_drug with Paritaprevir, drug_drug with Paritaprevir. Raltegravir has relations: drug_drug with Pibrentasvir, drug_drug with Pibrentasvir, drug_drug with Paritaprevir, drug_drug with Paritaprevir.", "label": "yes"}
{"id": "converted_1854", "sentence1": "Is vortioxetine effective for treatment of depression?", "sentence2": "Vortioxetine is the most recently approved medication for the treatment of major depressive disorder (MDD). , [Vortioxetine: a new antidepressant to treat depressive episodes]., Vortioxetine is a new antidepressant, which mechanism of action is multimodal, targeting the 5-HT1A, 5-HT1B, 5-HT1D, 5-HT3, 5-HT7 receptors and the serotonin transporter (5-HTT). , In short-term studies (8 weeks), vortioxetine is more efficacious than placebo in decreasing depressive symptoms as measured by the MADRS total score, response rate (vortioxetine: 53.2% vs placebo: 35.2%) and remission rate (vortioxetine: 29.2% vs placebo: 19.3%). In a long-term study (52 weeks), vortioxetine is also superior to placebo in preventing relapses and recurrences. Moreover, in second line treatment, after failure of a first line selective serotonin reuptake inhibitor (SSRI) or serotonin norepinephrin reuptake inhibitor (SNRI), vortioxetine is superior to agomelatine in improving depressive symptoms and achieving response and remission. , Against this background, we feature the novel antidepressants vortioxetine, vilazodone and milnacipran/levomilnacipran with regard to their serotonin receptor targets such as the 5-HT1A, 5-HT3 and 5-HT7 which may account for their specific effects on certain symptoms of depression (e.g. cognition and anxiety) as well as a characteristic side-effect profile., CONCLUSION: Vortioxetine dominated venlafaxine XR in South Korea and is a relevant treatment option for MDD patients initiating or switching therapy., Vortioxetine: a New Treatment for Major Depressive Disorder., INTRODUCTION: Vortioxetine is a structurally novel medication that has recently been approved for treatment of major depressive disorder (MDD)., EXPERT OPINION: Results of placebo-controlled trials suggest efficacy and an overall safety profile comparable to existing first-line antidepressants. , The authors suggest that vortioxetine is currently a good second-line antidepressant option and shows promise, pending additional long-term data, to become a first-line antidepressant option., Clinical studies indicate that vortioxetine is effective in the treatment of major depression, though there is no suggestion of superiority over active comparators., Vortioxetine has been effective in various animal models of depression and anxiety and clinical studies have shown the antidepressant and antianxiety properties of vortioxetine in a dose range of 5-20 mg/day., Vortioxetine was significantly more effective than was placebo, with a standardized mean difference (SMD) of -0.118 (95% CIs, -0.203 to -0.033, P = 0.007)., Vortioxetine for the treatment of depression., Vortioxetine for the treatment of major depression., Vortioxetine (Lu-AA-21004; 1-[2-(2,4-dimethylphenylsulfanyl)phenyl]piperazine hydrobromide) is a novel orally active molecule that is being investigated by Lundbeck and Takeda for the treatment of major depression and generalized anxiety disorders., Vortioxetine (Lu AA21004) is a multi-modal antidepressant in clinical development for the treatment of major depressive disorder (MDD)., A randomized, double-blind, fixed-dose study comparing the efficacy and tolerability of vortioxetine 2.5 and 10 mg in acute treatment of adults with generalized anxiety disorder., Vortioxetine has been effective in various animal models of depression and anxiety and clinical studies have shown the antidepressant and antianxiety properties of vortioxetine in a dose range of 5-20 mg/day., Secondary endpoints included response and remission rates, anxiety symptoms(Hamilton Anxiety Rating Scale), Clinical Global Impression, overall functioning (Sheehan Disability Scale), health-related quality of life(EuroQol 5 Dimensions), productivity (work limitation questionnaire) and family functioning (Depression and Family Functioning Scale).RESULTS: Primary endpoint noninferiority was established and vortioxetine (n = 252) was superior to agomelatine (n = 241) by 2.2 MADRS points (p<0.01)., Vortioxetine (Lu AA21004) is an antidepressant with a mechanism of action thought to be related to a combination of 2 pharmacologic actions: direct modulation of several receptors and inhibition of the serotonin transporter.To evaluate the efficacy of vortioxetine 10 and 20 mg once daily in outpatients with major depressive disorder.This 8-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group study was conducted from July 2010 to January 2012 among adults with a primary diagnosis of recurrent major depressive disorder (DSM-IV-TR).Eligible subjects were randomized in 1:1:1 ratio to 1 of 3 treatment arms: vortioxetine 10 mg, vortioxetine 20 mg, or placebo once daily for 8 weeks., Vortioxetine (Lu AA21004) is a new antidepressant that combines a number of neurotransmitter reuptake and receptor effects that have been thought to predict efficacy as a treatment for depressive and anxiety disorders.This review summarizes the pharmacology and neurobiology of vortioxetine, In the study of elderly patients, vortioxetine 5 mg (n = 136) improved 12-item Health Status Questionnaire scores significantly more than placebo (n = 148) for the domains of health perception (10.4, P &lt; 0.0001, SES of 0.54), mental health (7.9, P &lt; 0.001, SES of 0.44), and energy (6.4, P &lt; 0.05, SES of 0.28) (FAS, mixed model for repeated measures).Vortioxetine yielded significant, meaningful HRQoL improvements in 6 MDD studies of 6 to 8 weeks duration., All references included were published between 1999 and 2014.All studies that included humans and were published in English, with data describing vortioxetine for the treatment of MDD, were reviewed.Vortioxetine is a novel multimodal antidepressant agent, which inhibits the 5-HT transporter protein, acts as a 5-HT3 antagonist, 5-HT1A receptor agonist, 5-HT7 receptor antagonist, and a partial agonist of the 5-HT1B receptor, Vortioxetine has been effective in various animal models of depression and anxiety and clinical studies have shown the antidepressant and antianxiety properties of vortioxetine in a dose range of 5-20 mg/day, Vortioxetine is an antidepressant with multimodal activity which has shown efficacy in major depressive disorder (MDD) patients in six of ten short-term, randomized, placebo-controlled trials (completed end 2012).We performed meta-regression analyses to indirectly compare vortioxetine to seven marketed antidepressants with different mechanisms of action, Data were available from 51 human trials involving vortioxetine, and included a total of 7,666 healthy volunteers and patients with a diagnosis of major depressive disorder (MDD) or generalized anxiety disorder who were exposed to at least 1 dose of vortioxetine for a total of 2,743 patient-years.Vortioxetine was effective in treating MDD in the United States at a dose of 20 mg/d, Vortioxetine is a recently approved multimodal antidepressant with anxiolytic properties in preclinical studies.This double-blind, placebo-controlled study assessed the efficacy and tolerability of vortioxetine in subjects with a primary diagnosis of generalized anxiety disorder.Subjects (n = 457) were randomized 1:1:1 to treatment with placebo or vortioxetine 2.5 or 10 mg once daily, There was a significant difference for nausea between the two groups (OR=3.01, 95 % CI=2.22-4.09, Z=7.08, P=0.00001), but no significant differences were observed for the other four adverse effects.CONCLUSIONS: For the treatment of major depressive disorder, our results show that a dose of 5 mg/day vortioxetine was more effective, but more easily induced nausea, compared to placebo., The efficacy and safety of 5 mg/d Vortioxetine compared to placebo for major depressive disorder: A meta-analysis., Vortioxetine: a meta-analysis of 12 short-term, randomized, placebo-controlled clinical trials for the treatment of major depressive disorder., Vortioxetine in the treatment of adult patients with major depressive disorder: a meta-analysis of randomized double-blind controlled trials., Vortioxetine has been effective in various animal models of depression and anxiety and clinical studies have shown the antidepressant and antianxiety properties of vortioxetine in a dose range of 5-20 mg/day. , Clinical studies indicate that vortioxetine is effective in the treatment of major depression, though there is no suggestion of superiority over active comparators., The incidence of treatment-emergent adverse events was significantly higher in the duloxetine group than in the vortioxetine group.Duloxetine was more effective but less well-tolerated than vortioxetine in MDD., There was no significant difference in discontinuation rates between vortioxetine and comparators owing to inefficacy (OR 0.983, 95% CI 0.585 to 1.650), whereas discontinuation owing to AEs was significantly less common in the vortioxetine than in the comparator group (OR 0.728, 95% CI 0.554 to 0.957).Studies examining the role of vortioxetine in the treatment of MDD are limited.Although our results suggest that vortioxetine may be an effective treatment option for MDD, they should be interpreted and translated into clinical practice with caution, as the meta-analysis was based on a l, We performed a meta-analysis to increase the statistical power of these studies and enhance our current understanding of the role of vortioxetine in the treatment of MDD.We performed an extensive search of databases and the clinical trial registry., BACKGROUND: Vortioxetine is a recently approved multimodal antidepressant with anxiolytic properties in preclinical studies.OBJECTIVE: This double-blind, placebo-controlled study assessed the efficacy and tolerability of vortioxetine in subjects with a primary diagnosis of generalized anxiety disorder.METHODS: Subjects (n = 457) were randomized 1:1:1 to treatment with placebo or vortioxetine 2.5 or 10 mg once daily., Vortioxetine significantly improved objective and subjective measures of cognitive function in adults with recurrent MDD and these effects were largely independent of its effect on improving depressive symptoms., Furthermore, a statistically significant number of patients with MDD who were on vortioxetine have achieved a greater than or equal to 50% reduction in depression symptoms from baseline., BACKGROUND: Vortioxetine is a novel multimodal compound that has recently been approved by the FDA for the treatment of major depressive disorder (MDD)., Although our results suggest that vortioxetine may be an effective treatment option for MDD, they should be interpreted and translated into clinical practice with caution, as the meta-analysis was based on a limited number of heterogeneous RCTs.., Vortioxetine is an effective agent for the treatment of MDD, but it does not have any clear advantages over other available treatment options.., Vortioxetine was significantly more effective than placebo for acute treatment of major depressive disorder (MDD)., Duloxetine was more effective but less well-tolerated than vortioxetine in MDD., Vortioxetine is an orally administered small molecule developed by Lundbeck A/S for the once-daily treatment of major depressive disorder (MDD) and generalized anxiety disorder (GAD). Vortioxetine received its first global approval for MDD in the USA in September 2013 and regulatory approval for its use in this indication in the EU (where it has received a positive opinion) and Canada is awaited. , This article summarizes the milestones in the development of vortioxetine leading to this first approval for MDD., Vortioxetine was efficacious and well tolerated in the treatment of patients with major depressive disorder., On the primary efficacy endpoint, both vortioxetine doses were statistically significantly superior to placebo, with a mean difference to placebo (n=158) of -5.5 (vortioxetine 15 mg, P<0.0001, n=149) and -7.1 MADRS points (vortioxetine 20 mg, P<0.0001, n=151)., The change in the severity of depressive and anxiety symptoms was maintained throughout the study as reflected by a 24-item Hamilton Depression Scale total score of 8.2 at week 52 (from 17.6 at open-label baseline) in the observed case data set., Vortioxetine is a multi-modal antidepressant that functions as a human 5-HT3A and 5-HT7 receptor antagonist, 5-HT1B receptor partial agonist, 5-HT1A receptor agonist, and inhibitor of the serotonin transporter. , Approval for the treatment of MDD was based on a clinical development programme that included six positive 6-8 week studies, including one study in elderly people, and one positive maintenance study in adults., Vortioxetine represents another option for the treatment of MDD. , The multimodal compounds vortioxetine and vilazodone are examples of this approach with diverse mechanisms, and their different clinical effects will provide valuable insights into serotonergic modulation of glutamate transmission for the potential treatment of depression and associated cognitive dysfunction., Two new antidepressant drugs, vilazodone (marketed in the USA) and vortioxetine (in development) incorporate partial 5-HT1A-R agonist properties with SERT blockade., Novel drugs in development include those that combine multiple simultaneous pharmacologic mechanisms in addition to SERT inhibition within the same molecule, such as vilazodone (combining 5HT1A partial agonism with SERT inhibition), triple reuptake inhibitors (combining norepinephrine and dopamine reuptake inhibition with SERT inhibition), and vortioxetine, a multimodal antidepressant combining actions at the G protein receptor mode (5HT1A and 5HT1B partial agonism and 5HT7 antagonism), at the ion channel mode (5HT3 antagonism) as well as the neurotransmitter transporter mode (SERT inhibition). , In this study of adults with MDD treated for 8 weeks with vortioxetine 2.5 mg or 5 mg per day, reductions in depression symptoms were not statistically significant compared with placebo. , However, on the basis of these findings, vortioxetine (2.5, 5, 10 mg/day) demonstrated a favourable safety and tolerability profile and maintained effectiveness over 12 months of treatment. , In this study of adults with MDD, 5 mg vortioxetine did not differ significantly from placebo in reducing depression symptoms after 6 wk of treatment., After 8 weeks of treatment with Lu AA21004 10 mg, there was a significant reduction in HDRS-24 total score compared with placebo in adults with MDD., In conclusion, Lu AA21004 was efficacious and well tolerated in the treatment of elderly patients with recurrent major depressive disorder., Thus, Lu AA21004 was effective in preventing relapse of MDD and was well tolerated as maintenance treatment.,  Findings on secondary outcome measures, using MMRM instead of LOCF, were supportive of likely efficacy for Lu AA21004 5mg and 10mg and duloxetine. , In this study, treatment with 5 mg and 10 mg Lu AA21004 for 6 wk was efficacious and well tolerated in patients with MDD., Results from phase II clinical trials have reported improvement in depression and anxiety symptoms after 6 weeks of treatment. [SEP]Relations: Vortioxetine has relations: drug_drug with Antipyrine, drug_drug with Antipyrine, drug_drug with Paroxetine, drug_drug with Paroxetine, drug_drug with Harmaline, drug_drug with Harmaline, drug_drug with Methadone, drug_drug with Methadone, drug_drug with Cocaine, drug_drug with Cocaine.", "label": "yes"}
{"id": "converted_3697", "sentence1": "Is SATB1 necessary for T-cell maturation?", "sentence2": "Special AT-rich binding protein 1 (SATB1) nuclear protein, expressed predominantly in T cells, regulates genes through targeting chromatin remodeling during T-cell maturation., the transcription factor SATB1 that regulates the T-cell maturation, SATB1 is a transcriptional regulator controlling the gene expression that is essential in the maturation of the immune T-cell. , Special AT-rich sequence binding protein 1 (SATB1) regulates gene expression essential in immune T-cell maturation and switching of fetal globin species, by binding to matrix attachment regions (MARs) of DNA and inducing a local chromatin remodeling. [SEP]Relations: Tat protein binding has relations: molfunc_protein with GABARAPL1, molfunc_protein with GABARAPL1, molfunc_protein with NPM1, molfunc_protein with NPM1, molfunc_protein with SMARCB1, molfunc_protein with SMARCB1, molfunc_protein with DLL1, molfunc_protein with DLL1, molfunc_protein with DNAJA1, molfunc_protein with DNAJA1.", "label": "yes"}
{"id": "converted_2571", "sentence1": "Can gas vesicles be detected by ultrasound?", "sentence2": "Gas vesicles-genetically encoded protein nanostructures isolated from buoyant photosynthetic microbes-have recently been identified as nanoscale reporters for ultrasound., Here, we demonstrate that genetic engineering of gas vesicles results in nanostructures with new mechanical, acoustic, surface, and functional properties to enable harmonic, multiplexed, and multimodal ultrasound imaging as well as cell-specific molecular targeting. [SEP]Relations: cell surface has relations: cellcomp_protein with VASN, cellcomp_protein with VASN, cellcomp_protein with CTSZ, cellcomp_protein with CTSZ, cellcomp_protein with VWDE, cellcomp_protein with VWDE, cellcomp_protein with VEGFA, cellcomp_protein with VEGFA, cellcomp_protein with EPCAM, cellcomp_protein with EPCAM.", "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_1901", "sentence1": "Is there any role for Pds5b in cohesion establishment?", "sentence2": "Pds5B is required for cohesion establishment and Aurora B accumulation at centromeres., Here, we demonstrate that Pds5 proteins are essential for cohesion establishment by allowing Smc3 acetylation by the cohesin acetyl transferases (CoATs) Esco1/2 and binding of Sororin. While both proteins contribute to telomere and arm cohesion, Pds5B is specifically required for centromeric cohesion. Furthermore, reduced accumulation of Aurora B at the inner centromere region in cells lacking Pds5B impairs its error correction function, promoting chromosome mis-segregation and aneuploidy. Our work supports a model in which the composition and function of cohesin complexes differs between different chromosomal regions., Pds5B is required for cohesion establishment and Aurora B accumulation at centromeres., Here, we demonstrate that Pds5 proteins are essential for cohesion establishment by allowing Smc3 acetylation by the cohesin acetyl transferases (CoATs) Esco1/2 and binding of Sororin.[SEP]Relations: Protein S human has relations: drug_drug with Coagulation Factor IX (Recombinant), drug_drug with Coagulation Factor IX (Recombinant), drug_drug with Platelet Activating Factor, drug_drug with Platelet Activating Factor, drug_drug with p-Coumaric acid, drug_drug with p-Coumaric acid, drug_drug with Peginterferon alfa-2b, drug_drug with Peginterferon alfa-2b. centromere clustering has relations: bioprocess_bioprocess with chromosome localization, bioprocess_bioprocess with chromosome localization.", "label": "yes"}
{"id": "converted_274", "sentence1": "Is single-cell analysis (SCA) possible in proteomics?", "sentence2": "Toward Single Cell Analysis by Plume Collimation in Laser Ablation Electrospray Ionization Mass Spectrometry., he advent of proteomics and genomics at a single-cell level has set the basis for an outstanding improvement in analytical technology and data acquisition., The new-generation technology of single-cell analysis is able to better characterize a cell's population, identifying and differentiating outlier cells, in order to provide both a single-cell experiment and a corresponding bulk measurement, through the identification, quantification and characterization of all system biology aspects (genomics, transcriptomics, proteomics, metabolomics, degradomics and fluxomics). The movement of omics into single-cell analysis represents a significant and outstanding shift., Laser ablation electrospray ionization (LAESI) is a novel method for the direct imaging of biological tissues by mass spectrometry. By performing ionization in the ambient environment, this technique enables in vivo studies with potential for single-cell analysis., Other approaches for MS-based chemical imaging and profiling include those based on near-field laser ablation and inductively-coupled plasma MS analysis, which offer complementary capabilities for subcellular chemical imaging and profiling., Mass spectrometry imaging and profiling of single cells., his is rapidly changing with the recent examples of single cell genomics, transcriptomics, proteomics and metabolomics. The rate of change is expected to accelerate owing to emerging technologies that range from micro/nanofluidics to microfabricated interfaces for mass spectrometry to third- and fourth-generation automated DNA sequencers, Single-cell analysis (SCA) has been increasingly recognized as the key technology for the elucidation of cellular functions, which are not accessible from bulk measurements on the population level. Thus far, SCA has been achieved by miniaturization of established engineering concepts to match the dimensions of a single cell, Single-cell proteomic chip for profiling intracellular signaling pathways in single tumor cells., The amount of single proteins in single cells can be as low as one copy per cell and is for most proteins in the attomole range or below; usually considered as insufficient for proteomic analysis., n Arabidopsis thaliana, we have successfully identified nine unique proteins in a single-cell sample and 56 proteins from a pool of 15 single-cell samples from glucosinolate-rich S-cells by nanoLC-MS/MS proteomic analysis, thus establishing the proof-of-concept for true single-cell proteomic analysis, A first step towards practical single cell proteomics: a microfluidic antibody capture chip with TIRF detection.[SEP]Relations: Bite cells has relations: disease_phenotype_positive with hereditary stomatocytosis, disease_phenotype_positive with hereditary stomatocytosis, phenotype_phenotype with Poikilocytosis, phenotype_phenotype with Poikilocytosis. superior cerebellar artery has relations: anatomy_anatomy with branch of basilar artery, anatomy_anatomy with branch of basilar artery.", "label": "no"}
{"id": "converted_1242", "sentence1": "Is nimodipine recommended for prevention of vasospasm in aneurysmal subarachnoid hemorrhage patients?", "sentence2": "This article discusses some of these unresolved issues, including the use of medications such as nimodipine, antifibrinolytics, statins, and magnesium; coiling or clipping for aneurysm securement; and the prevention and treatment of potential complications., The results of this study were as follows: nimodipine demonstrated benefit following aneurysmal SAH; other calcium channel blockers, including nicardipine, do not provide unequivocal benefit; triple-H therapy, fasudil, transluminal balloon angioplasty, thrombolytics, endothelin receptor antagonists, magnesium, statins, and miscellaneous therapies such as free radical scavengers and antifibrinolytics require additional study., The present results suggest that fasudil is equally or more effective than nimodipine for the prevention of cerebral vasospasm and subsequent ischemic injury in patients undergoing surgery for SAH., Three studies (2 meta-analyses and 1 randomized controlled trial) demonstrated that nimodipine use confers benefits (reduced morbidity and mortality) for patients with aneurysmatic subarachnoid hemorrhage., Nimodipine is the only preventative treatment that can be recommended., Nimodipine (Nimotop), HMG Co-A reductase inhibitor (statins) and enoxaparin (Lovenox) were the only drugs with level-1 evidence available for the treatment of vasospasm from aneurysmal subarachnoid hemorrhage as defined by the US Preventative Services Task Force., The calcium antagonist nimodipine has been shown to reduce the incidence of ischemic complications following aneurysmal subarachnoid hemorrhage (SAH)., There was no significant difference in the incidence of DINDs (28 vs 30% in the peroral and intravenous groups, respectively) or middle cerebral artery blood flow velocities (> 120 cm/second, 50 vs 45%, respectively)., Clinical outcome according to the Glasgow Outcome Scale was the same in both groups, and there was no difference in the number of patients with new infarctions on MR imaging., The results suggest that there is no clinically relevant difference in efficacy between peroral and intravenous administration of nimodipine in preventing DINDs or cerebral vasospasm following SAH., the risk of delayed cerebral ischemia is reduced with nimodipine and avoiding hypovolemia, A recommendations (standard) for the prophylaxis and treatment of cerebral vasospasm with oral Nimodipine in good grade patients., Of the 75 patients initially considered for active treatment, 83% underwent surgery within 48 hours of rupture, all received nimodipine, 16% received tissue plasminogen activator to lyse subarachnoid or intraventricular clots, 40% underwent hypertensive treatment, and 7% underwent transluminal balloon angioplasty for vasospasm., All patients with aneurysmal SAH should be treated with the calcium antagonist nimodipine, and in certain circumstances patients should receive anticonvulsants., The following review gives an account of pathophysiological mechanisms; the importance of treatment with calcium antagonists, hypervolaemic haemodilution, and induced arterial hypertension is discussed in light of the current literature., Seven placebo-controlled clinical studies have shown that nimodipine improves the outcome of patients with severe neurological damage due to cerebral vasospasm., In a series of 100 individuals with a ruptured supratentorial aneurysm, who were subjected to aneurysm operation in the acute stage and who subsequently received intravenous treatment with the calcium channel blocker nimodipine, the occurrence of DID with FND was reduced to 5%., There are many possible successful treatment options for preventing vasospasm, delayed ischemic neurologic deficits, and poor neurologic outcome following aneurysmal subarachnoid hemorrhage; however, further multicenter RCTs need to be performed to determine if there is a significant benefit from their use. Nimodipine is the only treatment that provided a significant benefit across multiple studies., Absence of symptomatic vasospasm, occurrence of low density areas associated with vasospasm on CT, and occurrence of adverse events were similar between the two groups. The clinical outcomes were more favorable in the fasudil group than in the nimodipine group (p = 0.040). The proportion of patients with good clinical outcome was 74.5% (41/55) in the fasudil group and 61.7% (37/60) in the nimodipine group., Cerebral vasospasm is the classic cause of delayed neurological deterioration leading to cerebral ischemia and infarction, and thus, poor outcome and occasionally death, after aneurysmal subarachnoid hemorrhage (SAH). Advances in diagnosis and treatment, principally nimodipine, intensive care management, hemodynamic manipulations, and endovascular neuroradiology procedures, have improved the prospects for these patients, but outcomes remain disappointing., Cerebral vasospasm is the classic cause of delayed neurological deterioration after aneurysmal subarachnoid hemorrhage, leading to cerebral ischemia and infarction, and thus to poor outcome and occasionally death. Advances in diagnosis and treatment-principally the use of nimodipine, intensive care management, hemodynamic manipulations and endovascular neuroradiology procedures-have improved the prospects for these patients, but outcomes remain disappointing., Cerebral vasospasm and delayed cerebral ischemia remain common complications of aneurysmal subarachnoid hemorrhage (SAH), and yet therapies for cerebral vasospasm are limited. Despite a large number of clinical trials, only calcium antagonists have strong evidence supporting their effectiveness., The only proven therapy for vasospasm is nimodipine., nimodipine is indicated after SAH and tirilazad is not effective., Fasudil hydrochloride and nimodipine both showed inhibitory effects on cerebral vasospasm. The incidence of symptomatic vasospasm was five of 33 patients in the fasudil group and nine of 32 patients in the nimodipine group. Good recovery evaluated by the Glasgow Outcome Scale was achieved by 23 of 33 patients in the fasudil group and 19 of 34 patients in the nimodipine group. Both drugs significantly improved consciousness levels and neurological deficits such as aphasia. However, fasudil hydrochloride improved motor disturbance more than nimodipine.[SEP]Relations: Nimodipine has relations: drug_effect with Gastrointestinal hemorrhage, drug_effect with Gastrointestinal hemorrhage, drug_drug with Nitroprusside, drug_drug with Nitroprusside, drug_effect with Erythema, drug_effect with Erythema, drug_drug with Nitroaspirin, drug_drug with Nitroaspirin, drug_drug with Chlorpropamide, drug_drug with Chlorpropamide.", "label": "yes"}
{"id": "converted_2130", "sentence1": "Have studies shown that there is no link between DNA methylation patterns and Post Traumatic Stress Disorder?", "sentence2": "Using pre-deployment SKA2 methylation levels and childhood trauma exposure, we found that the previously published suicide prediction rule significantly predicted post-deployment PTSD symptoms (AUC=0.66, 95% CI: 0.53-0.79) with an optimal sensitivity of 0.81 and specificity of 0.91. Permutation analysis using random methylation loci supported these findings. Together, these data establish the importance of SKA2 for cortisol stress responsivity and the development of PTSD and provide further evidence that SKA2 is a promising biomarker for stress-related disorders including PTSD.,  Results provide novel support for PTSD-related accelerated aging in DNAm and extend the evidence base of known DNAm age correlates to the domains of neural integrity and cognition., We investigated serum DNA methylation patterns in genomic repetitive elements, LINE-1 and Alu, for post-traumatic stress disorder (PTSD) cases and controls who were US military service members recently deployed to Afghanistan or Iraq., In light of its role in glucocorticoid receptor transactivation, we investigated whether SKA2 DNA methylation influences cortisol stress reactivity and is involved in the development of post-traumatic stress disorder (PTSD)., These results suggest that alterations in global methylation pattern are involved in behavioural adaptation to environmental stress and pinpoint Dlgap2 as a possible target in PTSD., Here we examined whether there was a link between an established rat model of post-traumatic stress disorder (PTSD) and Bdnf DNA methylation, We investigated serum DNA methylation patterns in genomic repetitive elements, LINE-1 and Alu, for post-traumatic stress disorder (PTSD) cases and controls who were US military service members recently deployed to Afghanistan or Iraq.Cases (n = 75) had a postdeployment diagnosis of PTSD, DNA methylation in repetitive elements and post-traumatic stress disorder: a case-control study of US military service members, Here we examined whether there was a link between an established rat model of post-traumatic stress disorder (PTSD) and Bdnf DNA methylation. , DNA methylation in repetitive elements and post-traumatic stress disorder: a case-control study of US military service members., AIM: We investigated serum DNA methylation patterns in genomic repetitive elements, LINE-1 and Alu, for post-traumatic stress disorder (PTSD) cases and controls who were US military service members recently deployed to Afghanistan or Iraq. , Together, these results suggest that psychosocial stress may alter global and gene-specific DNA methylation patterns potentially associated with peripheral immune dysregulation., DNA methylation in vulnerability to post-traumatic stress in rats: evidence for the role of the post-synaptic density protein Dlgap2., Subjects with PTSD showed a higher DNA methylation of four CpG sites at the BDNF promoter compared with those without PTSD, Cumulatively, the data suggest that epigenetic variation at SKA2 mediates vulnerability to suicidal behaviors and PTSD through dysregulation of the HPA axis in response to stress.[SEP]Relations: post-traumatic stress disorder has relations: disease_disease with neurotic disorder, disease_disease with neurotic disorder. DLGAP2 has relations: anatomy_protein_absent with decidua, anatomy_protein_absent with decidua, anatomy_protein_present with hypothalamus, anatomy_protein_present with hypothalamus, anatomy_protein_present with substantia nigra, anatomy_protein_present with substantia nigra, anatomy_protein_present with prefrontal cortex, anatomy_protein_present with prefrontal cortex.", "label": "no"}
{"id": "converted_3925", "sentence1": "Are the major royal jelly proteins similar to the yellow proteins?", "sentence2": "Major royal jelly proteins (named MRJP1-5) of honeybee (Apis mellifera), yellow proteins of Drosophila, together with putative proteins found in several bacteria, form a protein family termed the MRJP/yellow family., Analysis of Drosophila yellow-B cDNA reveals a new family of proteins related to the royal jelly proteins in the honeybee, he Yellow proteins are related to the Royal Jelly proteins and have no relatives in other non-insect metazoan species. [SEP]Relations: Bacteremia has relations: disease_phenotype_positive with listeriosis, disease_phenotype_positive with listeriosis, disease_phenotype_positive with cyclic hematopoiesis, disease_phenotype_positive with cyclic hematopoiesis, disease_phenotype_positive with toxic shock syndrome, disease_phenotype_positive with toxic shock syndrome, disease_phenotype_positive with nocardiosis, disease_phenotype_positive with nocardiosis, disease_phenotype_positive with shigellosis, disease_phenotype_positive with shigellosis.", "label": "yes"}
{"id": "converted_4359", "sentence1": "Is proton beam therapy used for treatment of craniopharyngioma?", "sentence2": " The majority of children had adjuvant therapy comprising proton beam therapy (18/59; 30.5%) or conventional radiotherapy (16/59; 27.1%)., Proton Therapy for Craniopharyngioma - An Early Report from a Single European Centre., AIMS: Proton beam therapy (PBT) is being increasingly used for craniopharyngioma. , MATERIALS AND METHODS: Between August 2013 and July 2016, 18 patients with craniopharyngiomas were treated with 54 Cobalt Gray Equivalent (CGE) in 30 fractions over 6 weeks at our centre., CONCLUSIONS: Our early results are encouraging and comparable with the limited literature on PBT for craniopharyngioma., All of the other patients underwent proton-beam radiotherapy with no documented tumor growth (median follow-up: 20 months; range 5.1-29.9 months)., Where aggressive subtotal resection is achieved, patients should be closely followed, with radiation initiated at the time of progression or recurrence-ideally via proton beam therapy, although three-dimensional conformal radiotherapy, intensity-modulated radiotherapy, and stereotactic radiosurgery are very appropriate in a range of circumstances, governed by access, patient age, disease architecture, and character of the recurrence.,  This study examined parental distress in a sample of families of patients with Cp treated with proton beam therapy to identify factors for targeting psychological intervention.PROCEDURE: Prior to (n = 96) and 1 year after (n = 73) proton therapy, parents of children diagnosed with Cp (9.81 ± 4.42 years at baseline; 49% male) completed a self-report measure of distress, the Brief Symptom Inventory (BSI)., Diagnoses included medulloblastoma, craniopharyngioma, ependymoma, glial tumors, germ cell tumors, and others., Initial experience with proton beam therapy in childhood-onset craniopharyngioma patients shows promising results in terms of more protective radiological treatment. , Monte Carlo simulations were used to assess secondary neutron doses received by patients treated with proton therapy for ocular melanoma and craniopharyngioma., Secondary neutron doses in proton therapy treatments of ocular melanoma and craniopharyngioma., AIMS: Proton beam therapy (PBT) is being increasingly used for craniopharyngioma., LTS: Published reports suggest a benefit to proton beam therapy for use in tumors of the skull base, including craniopharyngiomas, chordomas, skull-base sarcomas, and unresectable meningiomas.CONC, In recent years, proton therapy (PT), with its physical properties of heavy ion beam, that is, Prague peak phenomenon, has been more frequently used in patients with craniopharyngioma., Proton beam therapy versus conformal photon radiation therapy for childhood craniopharyngioma: multi-institutional analysis of outcomes, cyst dynamics, and toxicity., PURPOSE: We compared proton beam therapy (PBT) with intensity modulated radiation therapy (IMRT) for pediatric craniopharyngioma in terms of disease control, cyst dynamics, and toxicity., Proton therapy for craniopharyngioma in adults: a protocol for systematic review and meta-analysis., We hereby report a case of a 7-year-old boy with a craniopharyngioma which had been subtotally resected and was subsequently treated with modern pencil beam proton therapy under high-precision image guidance., Pencil beam scanning proton therapy for the treatment of craniopharyngioma complicated with radiation-induced cerebral vasculopathies: A dosimetric and linear energy transfer (LET) evaluation., tial experience with proton beam therapy in childhood-onset craniopharyngioma patients shows promising results in terms of more protective radiological treatment. R, PURPOSE: We compared proton beam therapy (PBT) with intensity modulated radiation therapy (IMRT) for pediatric craniopharyngioma in terms of disease control, cyst dynamics, and toxic, BACKGROUND AND PURPOSE: This study analyses the dosimetric and dose averaged Linear Energy transfer (LETd) correlation in paediatric craniopharyngioma (CP) patients with and without radiation-induced cerebral vasculopathies (RICVs) treated with pencil beam scanning (PBS) pro, OBJECTIVE: The authors compared survival and multiple comorbidities in children diagnosed with craniopharyngioma who underwent gross-total resection (GTR) versus subtotal resection (STR) with radiation therapy (RT), either intensity-modulated radiation therapy (IMRT) or proton beam therapy (P, Proton Therapy for Craniopharyngioma - An Early Report from a Single European Centre, s. Some studies have shown that PT has advantages in the treatment of craniopharyngioma in adu, Postoperative cerebral glucose metabolism in pediatric patients receiving proton therapy for craniopharyngioma, Clinical equipoise: Protons and the child with craniopharyngioma., skull base. More public attention has been given to proton beam therapy due to the increasing number of centers now in operation or in the planning stages for offering this treatment option.METHODS: We reviewed the physical properties of protons and the clinical studies performed to justify their use in the management of skull-base tumors and determine the benefits of proton beam therapy.RESULTS: Published reports suggest a benefit to proton beam therapy for use in tumors of the skull base, including craniopharyngiomas, chordomas, skull-base sarcomas, and unresectable meningiomas.CONCLUSIONS: Use of proton beam th, PURPOSE: We report the results of the early cohort of patients treated for craniopharyngioma with combined proton-photon irradiation at the Massachusetts General Hospital and the Harvard Cyclotron Laboratory.METHODS AND MATERIALS: Between 1981 and 1988, 15 patients with craniopharyngioma were treated in part or entirely with fractiona, UNLABELLED: This retrospective preliminary review evaluated the efficacy and toxicity of fractionated proton radiotherapy in the management of pediatric craniopharyngioma.METHODS: Sixteen patients, aged 7-34 years, were treated with p, population. We evaluated the outcomes of all adult craniopharyngioma patients treated at our institution using proton therapy to report outcomes for disease control, treatment-related toxicity, and tumor response.METHODS: We analyzed 14 adult patie, Proton radiation has been used safely and effectively for medulloblastoma, primitive neuro-ectodermal tumors, craniopharyngioma, ependymoma, germ cell intracranial tumors, low-grade glioma, retinoblastoma, rhabdomyosarcoma and other soft tissue sarcomas, Ewing's sarcoma and other bone sarcomas., ontroversial. The purpose of this study was to evaluate the efficacy and safety of PT for craniopharyngioma in adults.METHODS AND ANALYSIS: We will search six databases (MEDLINE, EMBASE, Web of Science, the Cochrane Library, Amed, Scopus), clinical research registration websites and grey literature, aiming to identify randomised controlled trials (RCTs) on PT for craniopharyngioma in adults between 1[SEP]Relations: craniopharyngioma has relations: disease_protein with CTNNB1, disease_protein with CTNNB1, disease_phenotype_positive with Headache, disease_phenotype_positive with Headache, disease_disease with disease of facial skeleton, disease_disease with disease of facial skeleton, disease_phenotype_positive with Bitemporal hemianopia, disease_phenotype_positive with Bitemporal hemianopia, disease_disease with bone benign neoplasm, disease_disease with bone benign neoplasm.", "label": "yes"}
{"id": "converted_2246", "sentence1": "Is NEMO a zinc finger protein?", "sentence2": "To better understand the thermodynamics and dynamics of the zinc finger of NEMO (NF-κB essential modulator), an alteration in the zinc finger domain of NEMO (K392R) , CYLD and the NEMO Zinc Finger Regulate Tumor Necrosis Factor Signaling and Early Embryogenesis., our simulations of the zinc finger NEMO, An important regulatory domain of NF-[Formula: see text]B Essential Modulator (NEMO) is a ubiquitin-binding zinc finger, with a tetrahedral CYS3HIS1 zinc-coordinating binding site., NEMO function is mediated by two distal ubiquitin binding domains located in the regulatory C-terminal domain of the protein: the coiled-coil 2-leucine zipper (CC2-LZ) domain and the zinc finger (ZF) domain. ,  We show here that the NEMO C terminus, comprising the ubiquitin binding region and a zinc finger,[SEP]Relations: C2H2 zinc finger domain binding has relations: molfunc_protein with EHMT1, molfunc_protein with EHMT1, molfunc_protein with EHMT2, molfunc_protein with EHMT2, molfunc_protein with GATA1, molfunc_protein with GATA1, molfunc_protein with LEF1, molfunc_protein with LEF1, molfunc_protein with THAP7, molfunc_protein with THAP7.", "label": "yes"}
{"id": "converted_3897", "sentence1": "Can Freund's complete adjuvant induce arthritis?", "sentence2": "complete Freund's adjuvant (CFA) induced RA, The RA model was established using Freund's complete adjuvant, ,  Rheumatoid arthritis (RA) was induced by Freund's Complete Adjuvant (FCA; 1 mg/0.1 ml paraffin oil), injected subcutaneously on days 0, 30 and 40, The rats were made arthritic using a subcutaneous injection with 0.1 ml complete Freund's adjuvant (CFA) into the footpad of the left hind paw.[SEP]Relations: Rheumatoid arthritis has relations: drug_effect with Fluvoxamine, drug_effect with Fluvoxamine, drug_effect with Fluoxetine, drug_effect with Fluoxetine, drug_effect with Pregabalin, drug_effect with Pregabalin, drug_effect with Sibutramine, drug_effect with Sibutramine, drug_effect with Paroxetine, drug_effect with Paroxetine.", "label": "yes"}
{"id": "converted_543", "sentence1": "Is the gene DUX4 epigenetically regulated in somatic cells?", "sentence2": "There are several genes on chromosome 4q35 region including DUX4 within D4Z4 repeats. Transcription of these genes is usually repressed by epigenetic modifications of this chromosomal region and also accumulation of transcriptional repressors to the repeat array., Recent studies provide compelling evidence that a retrotransposed gene in the D4Z4 repeat, DUX4, is expressed in the human germline and then epigenetically silenced in somatic tissues. , The human double-homeodomain retrogene DUX4 is expressed in the testis and epigenetically repressed in somatic tissues., Facioscapulohumeral dystrophy (FSHD) is a progressive muscular dystrophy caused by decreased epigenetic repression of the D4Z4 macrosatellite repeats and ectopic expression of DUX4, a retrogene encoding a germline transcription factor encoded in each repeat.,  These mice recapitulate important epigenetic and DUX4 expression attributes seen in patients and controls, respectively, including high DUX4 expression levels in the germline, (incomplete) epigenetic repression in somatic tissue, and FSHD-specific variegated DUX4 expression in sporadic muscle nuclei associated with D4Z4 chromatin relaxation., DUX4, a retrogene contained in the D4Z4 repeats, is normally epigenetically silenced in somatic cells., In contrast to control skeletal muscle and most other somatic tissues, full-length DUX4 transcript and protein is expressed at relatively abundant levels in human testis, most likely in the germ-line cells. Induced pluripotent (iPS) cells also express full-length DUX4 and differentiation of control iPS cells to embryoid bodies suppresses expression of full-length DUX4, whereas expression of full-length DUX4 persists in differentiated FSHD iPS cells. Together, these findings indicate that full-length DUX4 is normally expressed at specific developmental stages and is suppressed in most somatic tissues., Recent studies provide compelling evidence that a retrotransposed gene in the D4Z4 repeat, DUX4, is expressed in the human germline and then epigenetically silenced in somatic tissues., DUX4, a retrogene contained in the D4Z4 repeats, is normally epigenetically silenced in somatic cells. , DUX4, a retrogene contained in the D4Z4 repeats, is normally epigenetically silenced in somatic cells., Recent studies provide compelling evidence that a retrotransposed gene in the D4Z4 repeat, DUX4, is expressed in the human germline and then epigenetically silenced in somatic tissues., Normally expressed in the testis and epigenetically repressed in somatic tissues, DUX4 expression in skeletal muscle induces expression of many germline, stem cell, and other genes that might account for the pathophysiology of FSHD., Recent studies provide compelling evidence that a retrotransposed gene in the D4Z4 repeat, DUX4, is expressed in the human germline and then epigenetically silenced in somatic tissues, The human double-homeodomain retrogene DUX4 is expressed in the testis and epigenetically repressed in somatic tissues, Normally expressed in the testis and epigenetically repressed in somatic tissues, DUX4 expression in skeletal muscle induces expression of many germline, stem cell, and other genes that might account for the pathophysiology of FSHD, DUX4, a retrogene contained in the D4Z4 repeats, is normally epigenetically silenced in somatic cells, Recent studies provide compelling evidence that a retrotransposed gene in the D4Z4 repeat, DUX4, is expressed in the human germline and then epigenetically silenced in somatic tissues, The identification of the gene(s) and the exact epigenetic pathway underlining this disease will be mandatory to increase the rate of diagnosis for FSHD2 patients and to confirm the hypothesis of a common FSHD1 and FSHD2 pathophysiological pathway involving DUX4 gene, This deletion induces epigenetic modifications that affect the expression of several genes located in the vicinity. In each D4Z4 element, we identified the double homeobox 4 (DUX4) gene. DUX4 expresses a transcription factor that plays a major role in the development of FSHD through the initiation of a large gene dysregulation cascade that causes myogenic differentiation defects, atrophy and reduced response to oxidative stress. , decreased epigenetic repression and variegated expression of DUX4 in skeletal muscle, (incomplete) epigenetic repression in somatic tissue,, Facioscapulohumeral dystrophy (FSHD) is characterized by chromatin relaxation of the D4Z4 macrosatellite array on chromosome 4 and expression of the D4Z4-encoded DUX4 gene in skeletal muscle., derepression of the DUX4 retrogene, The aim of our study was to identify relationships between epigenetic parameters correlating with a relaxed chromatin state of the DUX4 promoter region and clinical severity as measured by a clinical severity score or muscle pathologic changes in D4Z4 contraction-dependent (FSHD1) and -independent (FSHD2) facioscapulohumeral muscular dystrophy patients. , Specifically, abundance of RNA transcripts encoded by the DUX4 locus correlated to differential DNA methylation and H3K36me3 enrichment., Together, these findings indicate that full-length DUX4 is normally expressed at specific developmental stages and is suppressed in most somatic tissue[SEP]Relations: Transcriptional regulation of pluripotent stem cells has relations: pathway_protein with PBX1, pathway_protein with PBX1, pathway_protein with SMAD4, pathway_protein with SMAD4, pathway_protein with KLF4, pathway_protein with KLF4, pathway_protein with SALL4, pathway_protein with SALL4, pathway_protein with SMAD2, pathway_protein with SMAD2.", "label": "yes"}
{"id": "converted_4717", "sentence1": "Can parasite infections by Schistosoma japonicum prevent or improve asthma?", "sentence2": "Helminths and their products can shape immune responses by modulating immune cells, which are dysfunctional in inflammatory diseases such as asthm, Schistosoma japonicum peptide SJMHE1 suppresses airway inflammation of allergic asthma in mice., Schistosoma japonicum infection downregulates house dust mite-induced allergic airway inflammation in mice., To our knowledge, it is the first study to reveal the impact of S. japonicum infection on house dust mite induced severe asthma. More in depth investigation is need to elucidate the underlying mechanisms, Novel T-cell epitopes on Schistosoma japonicum SjP40 protein and their preventive effect on allergic asthma in mice., hese results reveal a novel form of immune protective mechanism, which may play an important role in the modulating effect of helminth infection on allergic asthmatic reactions., Using a panel of overlapping peptides, we identified T-cell epitopes on SjP40 protein of Schistosoma japonicum, which can induce Th1 cytokine and inhibit the production of Th2 cytokines and airway inflammation in a mouse model of allergic asthma., Helminths and their products can regulate immune response and offer new strategies to control and alleviate inflammation, including asthma., SJMHE1 Peptide from Schistosoma japonicum Inhibits Asthma in Mice by Regulating Th17/Treg Cell Balance via miR-155., We previously found that a peptide named as SJMHE1 from Schistosoma japonicum can suppress asthma in mice, el of overlapping peptides, we identified T-cell epitopes on SjP40 protein of Schistosoma japonicum, which can induce Th1 cytokine and inhibit the production of Th2 cytokines and airway inflammation in a mouse model of allergic asthma. These resul, has been shown that helminth infections including Schistosoma mansoni may modulate atopic diseases including asthma. I, Schistosoma japonicum infection downregulates house dust mite-induced allergic airway inflammation in mice, it is the first study to reveal the impact of S. japonicum infection on house dust mite induced severe asthma. More in depth inv, s study, we investigated the impact of Schistosoma japonicum infection on the allergic airway inflammation induced by repeated intracheal inoculations of house dust mites (HDM), which is a Th17 and neutrophils dominant murine asthma model, mimicking severe asthma. We found, Schistosoma japonicum infection showed protective effects against allergic airway inflammation (AAI)., Therefore, we hypothesize that Schistosoma japonicum egg antigens, a type of native antigen, can induce production of CD4(+) CD25(+) T cells with regulatory activity, modulating airway inflammation and inhibiting asthma development., Schistosoma japonicum infection modulates the development of allergen-induced airway inflammation in mice., It has been shown that helminth infections including Schistosoma mansoni may modulate atopic diseases including asthma., Schistosoma japonicum egg antigens stimulate CD4 CD25 T cells and modulate airway inflammation in a murine model of asthma., Most previous studies focused on understanding the preventive effect of S. japonicum infection on asthma (infection before allergen sensitization), whereas the protective effects of S. japonicum infection (allergen sensitization before infection) on asthma were rarely investigated., In conclusion, our data showed that lung-stage S. japonicum infection could relieve OVA-induced asthma in a mouse model., In this study, we investigated the protective effects of S. japonicum infection on AAI using a mouse model of OVA-induced asthma.,  prior to OVA immunization. These results suggest that both bisexual and male S. japonicum infections may modulate the development of allergic asthma., aponicum, which can induce Th1 cytokine and inhibit the production of Th2 cytokines and airway inflammation in a mouse model of allergic asthma. These, ve found that Schistosoma infection or Schistosoma related products can improve or prevent some immune and inflammatory diseases, such as severe asthm, Our findings indicated that S. japonicum infection was able to effectively inhibit host's allergic airway inflammation, which may be related to the upregulated Treg cells upon infection., These results suggest that both bisexual and male S. japonicum infections may modulate the development of allergic asthma., We found that lung-stage S. japonicum infection significantly ameliorated OVA-induced AAI, whereas post-lung-stage infection did not., In a murine model of asthma, S. japonicum egg antigens decreased the expression of Th2 cytokines, relieved antigen-induced airway inflammation, and inhibited asthma development., We found that S. japonicum infection downregulated airway hyperresponsiveness., However, in recent years, studies have found that Schistosoma infection or Schistosoma related products can improve or prevent some immune and inflammatory diseases, such as severe asthma, inflammatory bowel disease, diabetes and so on., In areas where schistosomiasis is endemic, a negative correlation is observed between atopy and helminth infection, associated with a low prevalence of asthma.[SEP]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_828", "sentence1": "Is muscle lim protein (MLP) involved in cardiomyopathies?", "sentence2": "Muscle LIM protein (MLP) has been proposed to be a central player in the pathogenesis of heart muscle disease. In line with this notion, the homozygous loss of MLP results in cardiac hypertrophy and dilated cardiomyopathy. Moreover, MLP is induced in several models of cardiac hypertrophy such as aortic banding and myocardial infarction. , Muscle LIM protein (MLP) null mice are often used as a model for human dilated cardiomyopathy., A lack of MLP leads to an age-dependent impairment of excitation-contraction coupling with resulting contractile dysfunction and secondary fibrosis., Loss of murine MLP results in dilated cardiomyopathy, and mutations in human MLP lead to cardiac hypertrophy, indicating a critical role for MLP in maintaining normal cardiac function., Our data indicate that MLP contributes to muscle stiffness and is necessary for maximum work and power generation., Interestingly, MLP was also found to be down-regulated in humans with heart failure (Zolk et al. Circulation 101:2674-2677, 2000) and MLP mutations are able to cause hypertrophic and dilated forms of cardiomyopathy in humans (Bos et al. Mol Genet Metab 88:78-85, 2006; Geier et al. Circulation 107:1390-1395, 2003; Hershberger et al. Clin Transl Sci 1:21-26, 2008; Knöll et al. Cell 111:943-955, 2002; Knöll et al. Circ Res 106:695-704, 2010; Mohapatra et al. Mol Genet Metab 80:207-215, 2003)., MLP soon became an important model for experimental cardiology when it was first demonstrated that MLP deficiency leads to myocardial hypertrophy followed by a dilated cardiomyopathy and heart failure phenotype (Arber et al. Cell 88:393-403, 1997). , Previous studies have shown an association between CSRP3 missense mutations and either dilated cardiomyopathy (DCM) or HCM, but all these studies were unable to provide comprehensive genetic evidence for a causative role of CSRP3 mutations. , We used a newly designed monoclonal antibody to show that muscle LIM protein (MLP), the protein encoded by CSRP3, is mainly a cytosolic component of cardiomyocytes and not tightly anchored to sarcomeric structures. Our functional data from both in vitro and in vivo analyses suggest that at least one of MLP's mutated forms seems to be destabilized in the heart of HCM patients harbouring a CSRP3 missense mutation., Muscle LIM protein (MLP) is a cytoskeletal protein located at the Z-disc of sarcomeres. Mutations in the human MLP gene are associated with hypertrophic and dilated cardiomyopathy., Our data demonstrate that Mlp84B is essential for normal cardiac function and establish the Drosophila model for the investigation of the mechanisms connecting defective cardiac Z-disc components to the development of cardiomyopathy., Muscle LIM protein (MLP) is a cytoskeletal LIM-only protein expressed in striated muscle. Mutations in human MLP are associated with cardiomyopathy;, TTN-encoded titin, CSRP3-encoded muscle LIM protein, and TCAP-encoded telethonin are Z-disc proteins essential for the structural organization of the cardiac sarcomere and the cardiomyocyte's stretch sensor. All three genes have been established as cardiomyopathy-associated genes for both dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM). , Approximately 4.1% of unrelated patients had HCM-associated MLP or TCAP mutations. MLP/TCAP-HCM phenotypically mirrors myofilament-HCM and is more severe than the subset of patients who still remain without a disease-causing mutation. The precise role of W4R-MLP in the pathogenesis of either DCM or HCM warrants further investigation., MLP (muscle-LIM-protein) deficient mice develop DCM and changes in the mechanical coupling of cardiomyocytes result in alterations at the intercalated disks and enhanced accumulation of adherens junction proteins., Targeted deletion of cytoskeletal muscle LIM protein (MLP) in mice consistently leads to dilated cardiomyopathy (DCM) after one or more months. , In summary, young MLPKO mice revealed substantial alterations in passive myocardial properties and relaxation time, but not in most systolic characteristics. These results indicate that the progression to heart failure in the MLPKO model may be driven by diastolic myocardial dysfunction and abnormal passive properties rather than systolic dysfunction., Mice lacking the muscle LIM protein (MLP) develop morphological and clinical signs resembling human dilated cardiomyopathy and heart failure., Our results show that the absence of MLP causes a local loss of mitochondria. We hypothesize that this is caused by a disturbed interaction between cytoskeleton and mitochondria, which interferes with energy sensing and energy transfer. Recovery of energy depletion by stimulating mitochondrial biogenesis might be a useful therapeutic strategy for improving the energy imbalance in heart failure., Previous work has shown that mutations in muscle LIM protein (MLP) can cause hypertrophic cardiomyopathy (HCM). In order to gain an insight into the molecular basis of the disease phenotype, we analysed the binding characteristics of wild-type MLP and of the (C58G) mutant MLP that causes hypertrophic cardiomyopathy., The molecular basis for HCM-causing mutations in the MLP gene might therefore be an alteration in the equilibrium of interactions of the ternary complex MLP-N-RAP-alpha-actinin., Muscle LIM protein (MLP) is a member of the cysteine-rich protein (CRP) family and has been implicated in both myogenesis and sarcomere assembly. In the latter role, it binds zyxin and alpha-actinin, both of which are involved in actin organization. An MLP-deficient mouse has been described; these mice develop dilated cardiomyopathy and heart failure., We identified a patient with DCM and EFE, having a mutation in MLP with the residue lysine 69 substituted by arginine (K69R). , MLP-knockout mice develop a marked cardiac hypertrophy reaction and dilated cardiomyopathy (DCM). MLP is therefore a candidate gene for heritable forms of hypertrophic cardiomyopathy (HCM) and DCM in humans., Family studies revealed cosegregation of clinically affected individuals with the respective mutations in MLP. CONCLUSION: Here, we present evidence that mutations in the CRP3/MLP gene can cause HCM., The skeletal muscle LIM protein 1 (SLIM1) is highly expressed in skeletal and cardiac muscle, and its expression is downregulated significantly in dilated human cardiomyopathy. , Targeted disruption of muscle LIM protein (MLP) has previously been shown to result in dilated cardiomyopathy with many of the clinical signs of heart failure, although the effects of MLP disruption on passive ventricular mechanics and myocyte architecture are not known., These results suggest that the disruption of the cytoskeletal protein MLP results in less compliant passive tissue and concomitant structural alterations in the three-dimensional myocyte architecture that may in part explain the ventricular dysfunction in the dilated heart.,  Mutations in cysteine and glycine-rich protein 3 (CSRP3), the gene encoding MLP, have been directly associated with human cardiomyopathies, whereas aberrant expression patterns are reported in human cardiac and skeletal muscle diseases., Muscle LIM protein (MLP) has been proposed to be a central player in the pathogenesis of heart muscle disease., Previous work has shown that mutations in muscle LIM protein (MLP) can cause hypertrophic cardiomyopathy (HCM)[SEP]Relations: muscle tissue has relations: anatomy_protein_present with MLXIP, anatomy_protein_present with MLXIP, anatomy_protein_present with LIMS1, anatomy_protein_present with LIMS1, anatomy_protein_present with MLIP, anatomy_protein_present with MLIP, anatomy_protein_present with LIMS3, anatomy_protein_present with LIMS3, anatomy_protein_present with MLPH, anatomy_protein_present with MLPH.", "label": "yes"}
{"id": "converted_2347", "sentence1": "Do bacteria from the genus Morexella cause respiratory infections?", "sentence2": "gainst pathogens associated with respiratory tract ailments [Staphylococcus aureus (ATCC 25923), Klebsiella pneumoniae (ATCC 13883) and Morexella cattarhalis (ATCC 14468)] , The efficacy and safety of oral ofloxacin, 400 mg once daily, for the treatment of patients with lower respiratory tract infections were studied. The most common species recovered from the sputum specimens of these patients were Haemophilus influenzae, followed by Streptococcus pneumoniae (S. pneumoniae), Staphylococcus aureus (S. aureus), Gram positive cocci unidentified, Pseudomonas aeruginosa (P. aeruginosa), Morexella catarrhalis,, the efficacy and safety of oral ofloxacin 400 mg once daily for the treatment of patients with lower respiratory tract infections were studied the most common species recovered from the sputum specimens of these patients were haemophilus influenzae followed by streptococcus pneumoniae s pneumoniae staphylococcus aureus s aureus gram positive cocci unidentified pseudomonas aeruginosa p aeruginosa morexella catarrhalis streptococcus epidermidis and another haemophilus species in this order all these bacteria were susceptible to ofloxacin except for one strain of methicillin resistant s aureus a satisfactory clinical outcome was achieved in 34 of 40 patients 85 it is concluded that ofloxacin 400 mg once daily is useful for patients with respiratory tract infections.[SEP]Relations: Respiratory tract infection has relations: phenotype_phenotype with Pneumonia, phenotype_phenotype with Pneumonia, phenotype_phenotype with Acute infectious pneumonia, phenotype_phenotype with Acute infectious pneumonia, drug_effect with Deferasirox, drug_effect with Deferasirox, phenotype_phenotype with Recurrent respiratory infections, phenotype_phenotype with Recurrent respiratory infections. Ofloxacin has relations: drug_effect with Respiratory tract infection, drug_effect with Respiratory tract infection.", "label": "yes"}
{"id": "converted_3255", "sentence1": "Can Daptacel be used instead of IPOL?", "sentence2": "Our goal was to compare the safety and immunogenicity of a combination vaccine (DTaP(5)-IPV-Hib; Pentacel) with that of its separately administered, US-licensed equivalent vaccines (diphtheria, tetanus, 5-component acellular pertussis vaccine [DTaP(5); Daptacel], inactivated poliovirus vaccine [IPV; IPOL], and Haemophilus influenzae type b [Hib] vaccine [ActHIB]), when administered to infants and toddlers concomitantly with other routinely recommended vaccines and to assess antibody persistence from the fourth dose in toddlers to the fifth (preschool) DTaP(5) dose., DTaP(5)-IPV-Hib is a suitable replacement for separately administered DTaP, IPV, and Hib vaccines.,  In this randomized, multicenter study, 1939 healthy infants were immunized at 2, 4, and 6 months of age with 1 of 3 lots of DTaP(5) coadministered with IPV and Hib vaccines or 1 lot of DTaP(5)-IPV-Hib combination vaccine., DTaP(5)-IPV-Hib elicited similar or fewer solicited injection-site and systemic reactions as compared with the separate administration of US-licensed DTaP(5), IPV, and Hib vaccines. [SEP]Relations: Corynebacterium diphtheriae toxoid antigen (formaldehyde inactivated) has relations: drug_drug with Certolizumab pegol, drug_drug with Certolizumab pegol, drug_drug with Dactinomycin, drug_drug with Dactinomycin, drug_drug with Dacarbazine, drug_drug with Dacarbazine, drug_drug with Clobetasol, drug_drug with Clobetasol. Clostridium tetani toxoid antigen (formaldehyde inactivated) has relations: drug_drug with Dactinomycin, drug_drug with Dactinomycin.", "label": "no"}
{"id": "converted_2660", "sentence1": "Can GDF15 be a biomarker for metformin treatment?", "sentence2": "Growth Differentiation Factor 15 as a Novel Biomarker for Metformin., GDF15 levels are a biomarker for the use of metformin in people with dysglycemia, and its concentration reflects the dose of metformin.[SEP]Relations: Metformin has relations: drug_protein with GPD1, drug_protein with GPD1, drug_drug with Glymidine, drug_drug with Glymidine, drug_drug with GLPG-0492, drug_drug with GLPG-0492, drug_drug with Glimepiride, drug_drug with Glimepiride, drug_protein with ETFDH, drug_protein with ETFDH.", "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]Relations: Chronic lung disease has relations: disease_phenotype_positive with midline interhemispheric variant of holoprosencephaly, disease_phenotype_positive with midline interhemispheric variant of holoprosencephaly, disease_phenotype_positive with primary ciliary dyskinesia, disease_phenotype_positive with primary ciliary dyskinesia, disease_phenotype_positive with neonatal acute respiratory distress due to SP-B deficiency, disease_phenotype_positive with neonatal acute respiratory distress due to SP-B deficiency, disease_phenotype_positive with combined immunodeficiency due to LRBA deficiency, disease_phenotype_positive with combined immunodeficiency due to LRBA deficiency, disease_phenotype_positive with familial papillary or follicular thyroid carcinoma, disease_phenotype_positive with familial papillary or follicular thyroid carcinoma.", "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]Relations: Kabuki syndrome has relations: disease_protein with KMT2D, disease_protein with KMT2D, disease_protein with KDM6A, disease_protein with KDM6A, disease_phenotype_positive with Generalized hypotonia, disease_phenotype_positive with Generalized hypotonia, disease_protein with RAP1B, disease_protein with RAP1B, disease_protein with RAP1A, disease_protein with RAP1A.", "label": "no"}
{"id": "converted_2587", "sentence1": "Are sleep apnea and snoring associated with cardiac arrhythmias?", "sentence2": "Atrial fibrillation (AF) is the commonest arrhythmia in clinical practice and is associated with increased cardiovascular morbidity and mortality. Obstructive sleep apnea (OSA), a common breathing disorder, is an independent risk factor for AF., There is a growing consensus in the scientific community that suggests a strong association between obstructive sleep apnea (OSA) and cardiovascular (CVD) conditions and events, including coronary artery disease, hypertension, arrhythmia, heart failure, and sudden cardiac death. , part from well-established risk factors that increase the odds for the development of AF, e.g. age or arterial hypertension, recent analyses indicate that obstructive sleep apnoea (OSA) may independently, negatively modify the arrhythmia occur-rence profile. , Evidence supports a causal association of sleep apnea with the incidence and morbidity of hypertension, coronary heart disease, arrhythmia, heart failure, and stroke., Severe snoring may be associated with pulmonary and systemic hypertension, secondary polycythemia, and cardiac arrhythmias.<br>, Severe snoring may be associated with pulmonary and systemic hypertension, secondary polycythemia, and cardiac arrhythmias., BACKGROUND AND PURPOSE Nocturnal cardiac arrhythmias occur in patients with obstructive sleep apnea (OSA), reportedly as a consequence of the autonomic effects of recurrent apnea with subsequent oxygen desaturation., Obstructive apnea is associated with myocardial ischemia (silent or symptomatic), acute coronary events, stroke and transient ischemic attacks, cardiac arrhythmia, pulmonary hypertension and heart failure., Obstructive sleep apnea (OSA) is the most common form of sleep-disordered breathing, affecting 5-15% of the population. It is characterized by intermittent episodes of partial or complete obstruction of the upper airway during sleep that disrupts normal ventilation and sleep architecture, and is typically associated with excessive daytime sleepiness, snoring, and witnessed apneas. Patients with obstructive sleep apnea present risk to the general public safety by causing 8-fold increase in vehicle accidents, and they may themselves also suffer from the physiologic consequences of OSA; these include hypertension, coronary artery disease, stroke, congestive heart failure, pulmonary hypertension, and cardiac arrhythmias, Obstructive sleep apnea and central sleep apnea with Cheyne-Stokes respiration                     are associated with an increased risk of cardiac arrhythmia. , Obstructive sleep apnea (OSA) affects approximately 4% of middle-aged men and 2% of middle-aged women. Cardiac arrhythmias are common problems in patients with OSA, even though the true prevalence and clinical relevance of cardiac arrhythmias remains to be determined. , Cardiac arrhythmias during wakefulness and sleep in 15 patients with sleep-induced obstructive apnea, and the effect of atropine and tracheostomy on these arrhythmias were studied by continuous overnight Holter electrocardiographic, respiratory and electroencephalographic recordings., obstructive sleep apnea (OSA) as its most extreme variant, is characterized by intermittent episodes of partial or complete obstruction of the upper airway, leading to cessation of breathing while asleep. Cardiac arrhythmias are common problems in OSA patients, although the true prevalence and clinical relevance of cardiac arrhythmias remains to be determined, The mechanisms associated with the cardiovascular consequences of obstructive sleep apnea include abrupt changes in autonomic tone, which can trigger cardiac arrhythmias. ,  Recent studies have shown that cardiac arrhythmias and conduction disorders are common in patients with SA. Sleep apnea, Severity of nocturnal cardiac arrhythmias correlates with intensity of sleep apnea in men, Patients affected with OSA are frequently hypertensive and can have dangerous cardiac arrhythmias., Patients with stable cardiac failure who snore may present sleep hypopnea and cardiac arrhythmias. ,  Obstructive sleep apnea (OSA) is associated with increased cardiovascular morbidity and mortality. Cardiac arrhythmias are common in patients with OSA. , Nocturnal hypoxia has been associated with serious ventricular tachyarrhythmias as well as life-threatening bradyarrhythmias. Obesity and snoring, both of which increase with age, have been identified as risk factors for sleep-related breathing disorders, as have hypertension and heart disease., Obstructive sleep apnea syndrome is associated with excess daytime sleepiness, depression, and an increased incidence of ischemic cardiopathy, cardiac arrhythmias, systemic hypertension and brain infarction., We found 58 percent prevalence of arrhythmias in patients with sleep apnea (apnea/hypopnea index = AHI>10), vs 42 percent in nonapneic controls (chi 2 = 16.7, p<0.0001)[SEP]Relations: obstructive sleep apnea syndrome has relations: disease_phenotype_positive with Snoring, disease_phenotype_positive with Snoring. sleep apnea syndrome has relations: disease_disease with sleep-wake disorder, disease_disease with sleep-wake disorder, disease_disease with obstructive sleep apnea syndrome, disease_disease with obstructive sleep apnea syndrome, disease_disease with central sleep apnea syndrome, disease_disease with central sleep apnea syndrome, disease_disease with respiratory system disease, disease_disease with respiratory system disease.", "label": "yes"}
{"id": "converted_3222", "sentence1": "Is Pim-1 a protein phosphatase?", "sentence2": "Pim-1 proto-oncogene, serine/threonine kinase (PIM-1) phosphorylates a series of substrates to exert its oncogenic function in numerous malignancies., The Pim1 serine/threonine kinase is associated with multiple cellular functions including proliferation, survival, differentiation, apoptosis, tumorigenesis, immune regulation and inflammation in vertebrates.[SEP]Relations: Portal inflammation has relations: disease_phenotype_positive with FADD-related immunodeficiency, disease_phenotype_positive with FADD-related immunodeficiency, phenotype_phenotype with Abnormality of the biliary system, phenotype_phenotype with Abnormality of the biliary system. malignant ear neoplasm has relations: disease_disease with sensory system cancer, disease_disease with sensory system cancer, disease_disease with ear neoplasm, disease_disease with ear neoplasm, disease_disease with head and neck cancer, disease_disease with head and neck cancer.", "label": "no"}
{"id": "converted_4258", "sentence1": "Can FTO promote pancreatic cancer development?", "sentence2": "m6A demethylase FTO suppresses pancreatic cancer tumorigenesis by demethylating PJA2 and inhibiting Wnt signaling., Moreover, FTO demethylated the m6A modification of praja ring finger ubiquitin ligase 2 (PJA2), thereby reducing its mRNA decay, suppressing Wnt signaling, and ultimately restraining the proliferation, invasion, and metastasis of pancreatic cancer cells.[SEP]Relations: malignant exocrine pancreas neoplasm has relations: disease_disease with exocrine pancreatic carcinoma, disease_disease with exocrine pancreatic carcinoma, disease_disease with pancreatoblastoma, disease_disease with pancreatoblastoma, disease_disease with pancreatic exocrine neoplasm, disease_disease with pancreatic exocrine neoplasm, disease_disease with malignant pancreatic neoplasm, disease_disease with malignant pancreatic neoplasm, disease_disease with pancreatic intraductal papillary-mucinous neoplasm, disease_disease with pancreatic intraductal papillary-mucinous neoplasm.", "label": "no"}
{"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_2846", "sentence1": "Is phospholipid hydroperoxide glutathione peroxidase a selenoprotein?", "sentence2": "Glutathione peroxidase (Gpx1) is the major selenoprotein in most tissues in animals., The selenoenzyme Gpx4 is essential for early embryogenesis and cell viability for its unique function to prevent phospholipid oxidation., the major selenoprotein expressed by germ cells in the testis, the phospholipid hydroperoxide glutathione peroxidase (PHGPx/GPx4) [SEP]Relations: GPX1 has relations: molfunc_protein with phospholipid-hydroperoxide glutathione peroxidase activity, molfunc_protein with phospholipid-hydroperoxide glutathione peroxidase activity. GPX4 has relations: molfunc_protein with phospholipid-hydroperoxide glutathione peroxidase activity, molfunc_protein with phospholipid-hydroperoxide glutathione peroxidase activity. glutathione peroxidase activity has relations: molfunc_protein with ALOX5AP, molfunc_protein with ALOX5AP, molfunc_protein with GSTP1, molfunc_protein with GSTP1, molfunc_protein with PTGES, molfunc_protein with PTGES.", "label": "yes"}
{"id": "converted_3480", "sentence1": "Does nintedanib hold promise for lung disease associated with systemic sclerosis?", "sentence2": "The patient developed progressive lung fibrosis under several immunosuppressants and was started on nintedanib, with clinical and functional stabilization. Nintedanib is a tyrosine-kinase inhibitor that blocks several profibrotic pathways, inhibiting proliferation and migration of fibroblasts and decreasing the synthesis of extracellular matrix proteins. It is approved for idiopathic lung fibrosis and has demonstrated good results in inhibiting migration and proliferation of systemic sclerosis dermal fibroblasts, constituting a promising agent for systemic sclerosis-associated lung fibrosis., BACKGROUND: Nintedanib is an inhibitor targeting platelet-derived growth factor receptor, fibroblast growth factor receptor and vascular endothelial growth factor receptor tyrosine kinases that has recently been approved for the treatment of idiopathic pulmonary fibrosis. , CONCLUSION: Nintedanib targets core features of SSc in Fra2-transgenic mice and ameliorates histological features of pulmonary arterial hypertension, destructive microangiopathy and pulmonary and dermal fibrosis. These data might have direct implications for the ongoing phase III clinical trial with nintedanib in SSc-associated interstitial lung disease., In light of the ongoing advances in our understanding of the pathogenic mechanisms underlying interstitial lung disease in systemic sclerosis, this review also summarizes novel treatment approaches, presenting clinical and preclinical evidence for rituximab, tocilizumab, pirfenidone, and nintedanib, as well as hematopoietic stem cell transplantation and lung transplantation., Pirfenidone and nintedanib are emerging agents that exert pleiotropic effects, reflective of the multiple mechanistic pathways of IPF. , Design of a randomised, placebo-controlled clinical trial of nintedanib in patients with systemic sclerosis-associated interstitial lung disease (SENSCIS™)., The SENSCIS™ trial is a randomised, placebo-controlled Phase III trial that will evaluate the efficacy and safety of nintedanib in patients with SSc-ILD (NCT02597933)., CONCLUSIONS: This trial will assess the efficacy and safety of nintedanib in patients with SSc-ILD., Nintedanib for Systemic Sclerosis-Associated Interstitial Lung Disease., Nintedanib, a tyrosine kinase inhibitor, has been shown to have antifibrotic and antiinflammatory effects in preclinical models of systemic sclerosis and ILD., METHODS\n\nWe conducted a randomized, double-blind, placebo-controlled trial to investigate the efficacy and safety of nintedanib in patients with ILD associated with systemic sclerosis., CONCLUSIONS\n\nAmong patients with ILD associated with systemic sclerosis, the annual rate of decline in FVC was lower with nintedanib than with placebo; no clinical benefit of nintedanib was observed for other manifestations of systemic sclerosis., Potential of Nintedanib in Treatment of Progressive Fibrosing Interstitial Lung Diseases., Anti-fibrotic nintedanib-a new opportunity for systemic sclerosis patients?, Newer agents with anti-fibrotic properties, such as pirfenidone or nintedanib, might hold promise also for the pulmonary fibrosis seen in sarcoidosis., This suggests that nintedanib inhibits fundamental processes in the pathogenesis of fibrosis., This suggests that nintedanib and pirfenidone , drugs known to slow disease progression in patients with idiopathic pulmonary fibrosis , may also slow the progression of ILD associated with systemic autoimmune diseases, In the SENSCIS® trial , nintedanib reduced the rate of ILD progression in patients with systemic sclerosis-associated ILD, Nintedanib, a tyrosine kinase inhibitor, has been shown to have antifibrotic and antiinflammatory effects in preclinical models of systemic sclerosis and ILD., The goal of the present study was to determine the effects of nintedanib on a cellular model of SSc-associated interstitial lung disease (ILD)., OBJECTIVES\nNintedanib is approved for the treatment of idiopathic pulmonary fibrosis (IPF) and was demonstrated to slow disease progression in patients with IPF by reducing decline in forced vital capacity by 50%., Nintedanib: new indication for systemic sclerosis-associated interstitial lung disease., Nintedanib (Ofev™), an oral triple kinase inhibitor targeting pro-fibrotic pathways, has been used for treatment of idiopathic pulmonary fibrosis (IPF)., These data might have direct implications for the ongoing phase III clinical trial with nintedanib in SSc-associated interstitial lung disease., Based on positive results from phase III, placebo-controlled, randomized comparative clinical trial conducted in patients with systemic sclerosis-associated interstitial lung disease (SSc-ILD), nintedanib received marketing approval in the United States and Japan for the treatment of SSc-ILD., Nintedanib is an intracellular inhibitor of tyrosine kinases that has been approved for treatment of IPF and has recently been shown to reduce the rate of lung function decline in patients with ILD associated with systemic sclerosis (SSc-ILD).[SEP]Relations: systemic sclerosis has relations: disease_disease with pulmonary systemic sclerosis, disease_disease with pulmonary systemic sclerosis, disease_disease with limited scleroderma, disease_disease with limited scleroderma, disease_protein with KIAA0319L, disease_protein with KIAA0319L, disease_disease with limited systemic sclerosis, disease_disease with limited systemic sclerosis, disease_protein with NECTIN2, disease_protein with NECTIN2.", "label": "yes"}
{"id": "converted_529", "sentence1": "Is TALEN being used on stem cells?", "sentence2": "Precise correction of the dystrophin gene in duchenne muscular dystrophy patient induced pluripotent stem cells by TALEN and CRISPR-Cas9., Genetic correction of patient-derived induced pluripotent stem cells (iPSCs) by TALENs or CRISPR-Cas9 holds promise for DMD gene therapy; however, the safety of such nuclease treatment must be determined., We generated helper-dependent, capsid-modified adenovirus (HD-Ad5/35) vectors for zinc-finger nuclease (ZFN)- or transcription activator-like effector nuclease (TALEN)-mediated genome editing in human CD34+ hematopoietic stem cells (HSCs) from mobilized adult donors. , We used transcription activator-like effector nuclease (TALEN)-mediated gene editing in mouse embryonic stem cells (mESCs) to produce mice with targeted gene disruptions and insertions in two Y-linked genes--Sry and Uty., Transcription activator-like effector nuclease (TALEN)-mediated gene correction in integration-free β-thalassemia induced pluripotent stem cells., A TALEN genome-editing system for generating human stem cell-based disease models., Low incidence of off-target mutations in individual CRISPR-Cas9 and TALEN targeted human stem cell clones detected by whole-genome sequencing., Using CRISPR-Cas9 and TALEN targeted human pluripotent stem cell clones, we performed whole-genome sequencing at high coverage in order to assess the degree of mutagenesis across the entire genome., A modified TALEN-based system for robust generation of knock-out human pluripotent stem cell lines and disease models., In this study, we utilized a cell-penetrating peptide-based system for ZFN and TALEN delivery., At all loci tested we obtained human embryonic stem cell (ESC) and induced pluripotent stem cell (iPSC) clones carrying transgenic cassettes solely at the TALEN-specified location., We report here the use of TALENs to rapidly and efficiently generate mutant alleles of 15 genes in cultured somatic cells or human pluripotent stem cells, the latter for which we differentiated both the targeted lines and isogenic control lines into various metabolic cell types., Zinc-finger nucleases (ZFNs) and transcription activator-like effector nucleases (TALENs) have been successfully used to knock out endogenous genes in stem cell research., Here we report different methods to efficiently perform TALEN-mediated gene integration and inactivation in different mammalian cell systems including induced pluripotent stem cells and delineate experimental examples associated with these approaches, Together, our results demonstrate that TALE-based transcriptional repressor and TALENs are two promising approaches for loss-of-function studies of microRNA clusters in somatic cells and pluripotent stem cells, We report here the use of TALENs to rapidly and efficiently generate mutant alleles of 15 genes in cultured somatic cells or human pluripotent stem cells, the latter for which we differentiated both the targeted lines and isogenic control lines into various metabolic cell types, TALEN-mediated generation and genetic correction of disease-specific human induced pluripotent stem cells., Baculoviral transduction facilitates TALEN-mediated targeted transgene integration and Cre/LoxP cassette exchange in human-induced pluripotent stem cells., We used transcription activator-like effector nuclease (TALEN)-mediated gene editing in mouse embryonic stem cells (mESCs) to produce mice with targeted gene disruptions and insertions in two Y-linked genes--Sry and Uty. , Using CRISPR-Cas9 and TALEN targeted human pluripotent stem cell clones, we performed whole-genome sequencing at high coverage in order to assess the degree of mutagenesis across the entire genome. , A 5% modification rate was observed in human induced pluripotent stem cells (hiPSCs) treated with TAT-TALEN as measured by the Surveyor assay.  TAT-TALEN protein-mediated gene disruption was applicable in hiPSCs and represents a promising technique for gene knockout in stem cells., Here we engineered transcription activator-like effector nucleases (TALENs) for five distinct genomic loci. At all loci tested we obtained human embryonic stem cell (ESC) and induced pluripotent stem cell (iPSC) clones carrying transgenic cassettes solely at the TALEN-specified location., Seamless correction of the sickle cell disease mutation of the HBB gene in human induced pluripotent stem cells using TALENs., At all loci tested we obtained human embryonic stem cell (ESC) and induced pluripotent stem cell (iPSC) clones carrying transgenic cassettes solely at the TALEN-specified location. Our data suggest that TALENs employing the specific architectures described here mediate site-specific genome modification in human pluripotent cells with similar efficiency and precision as do zinc-finger nucleases (ZFNs).[SEP]Relations: hematopoietic stem cell homeostasis has relations: bioprocess_protein with EMCN, bioprocess_protein with EMCN, bioprocess_protein with ADAR, bioprocess_protein with ADAR, bioprocess_protein with NLE1, bioprocess_protein with NLE1, bioprocess_protein with CCN3, bioprocess_protein with CCN3, bioprocess_protein with EXT1, bioprocess_protein with EXT1.", "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]Relations: Type I diabetes mellitus has relations: disease_phenotype_positive with vasculitis due to ADA2 deficiency, disease_phenotype_positive with vasculitis due to ADA2 deficiency, disease_phenotype_positive with late-onset isolated ACTH deficiency, disease_phenotype_positive with late-onset isolated ACTH deficiency, disease_phenotype_positive with Wolcott-Rallison syndrome, disease_phenotype_positive with Wolcott-Rallison syndrome. diabetes mellitus, noninsulin-dependent has relations: disease_disease with type 2 diabetes mellitus, disease_disease with type 2 diabetes mellitus, disease_disease with inborn errors of metabolism, disease_disease with inborn errors of metabolism.", "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_1594", "sentence1": "Is Tuberous Sclerosis a genetic disease?", "sentence2": "Tuberous sclerosis complex (TSC) is a genetic disease, Tuberous sclerosis is a rare genetic disease, Tuberous sclerosis complex (TSC) is a multisystem genetic disease, Tuberous sclerosis complex (TSC) is a genetic disease, The disease is caused by mutational inactivation of the tumor suppressor gene tuberous sclerosis complex 1 (TSC1) or TSC2., mTOR inhibitors have antiepileptogenic and antiseizure effects in animal models of the genetic disease, tuberous sclerosis complex., Tuberous sclerosis (TSC) is an autosomal-dominant genetic disease, Tuberous sclerosis is a rare genetic disease, Tuberous Sclerosis Complex (TSC) is a genetic disease, Tuberous sclerosis complex (TSC) is a multiorgan genetic disease, Tuberous sclerosis complex (TSC) is a genetic disease, Tuberous Sclerosis Complex (TSC) is a multiorgan genetic disease, Tuberous sclerosis complex (TSC) is a genetic disease, Tuberous sclerosis complex (TSC) is a multiorgan genetic disease, In all these lesions, genetic alterations related to the tuberous sclerosis complex (TSC) have been demonstrated., Although epilepsy affects most patients with tuberous sclerosis complex (TSC), little is known about the natural history of epilepsy in this genetic disease., The tuberous sclerosis gene 2 product tuberin is an important regulator of the mammalian target of rapamycin (mTOR)., Tuberous sclerosis complex (TSC) is a genetic disease, Tuberous Sclerosis Complex (TSC) is a multiorgan genetic disease, Tuberous sclerosis complex (TSC) is a relatively rare autosomal dominant disorder, Tuberous sclerosis is a genetic disease with autosomal dominant inheritance,, PEComas are related to the genetic alterations of tuberous sclerosis complex (TSC), an autosomal dominant genetic disease due to losses of TSC1 (9q34) or TSC2 (16p13.3) genes which seem to have a role in the regulation of the Rheb/mTOR/p70S6K pathway., Tuberous sclerosis complex (TSC) is a multiorgan genetic disease, Tuberous sclerosis complex (TSC) is a genetic disease, Tuberous sclerosis is a rare genetic disease, Tuberous sclerosis complex (TSC) is a genetic disease, Tuberous sclerosis complex (TSC) is a genetic disease caused by mutation in either TSC1 or TSC2., Tuberous sclerosis complex (TSC) is a genetic disease caused by mutations in either TSC1 or TSC2 tumor suppressor genes., Mutation in either the TSC1 or TSC2 tumor suppressor gene is responsible for the inherited genetic disease of tuberous sclerosis complex., Tuberous sclerosis (TSC) is a frequent autosomal-dominant condition (affecting 1 in 6000 individuals) caused by various mutations in either the hamartin (TSC1) or the tuberin gene (TSC2)., Tuberous sclerosis is a rare genetic disease, Tuberous sclerosis (TS) is a genetic disease with prominent cutaneous and brain involvement , TSC was recognized to be a genetic disease with autosomal dominant inheritance, On average TSC families are very small; in most cases there are fewer than two informative meioses. The size distribution of chromosome 9 linked families was similar to that of non-linked families., The effects of missense changes and small in-frame deletions and insertions on protein function are not easy to predict, and the identification of such variants in individuals at risk of a genetic disease can complicate genetic counselling. One option is to perform functional tests to assess whether the variants affect protein function. We have used this strategy to characterize variants identified in the TSC1 and TSC2 genes in individuals with, or suspected of having, Tuberous Sclerosis Complex (TSC)., Tuberous sclerosis is a dominant hereditary disease, Many of these advances originated from studies of the genetic disease tuberous sclerosis complex (TSC)[SEP]Relations: tuberous sclerosis has relations: disease_disease with genetic nervous system disorder, disease_disease with genetic nervous system disorder, disease_disease with genetic nervous system disorder, disease_disease with genetic nervous system disorder, disease_disease with genetic nervous system disorder, disease_disease with genetic nervous system disorder, disease_disease with genetic nervous system disorder, disease_disease with genetic nervous system disorder, disease_disease with inherited neurodegenerative disorder, disease_disease with inherited neurodegenerative disorder.", "label": "yes"}
{"id": "converted_3241", "sentence1": "Can Enlimomab improve stroke outcomes?", "sentence2": "Treatment with a murine anti-ICAM-1 antibody (enlimomab) has been investigated in patients with acute ischemic stroke in the Enlimomab Acute Stroke Trial (EAST). Unfortunately, the case fatality rate in this trial was significantly higher in the enlimomab patient group than in the placebo group., The two clinical trials of therapy aimed at limiting the inflammatory response in acute stroke that have been carried out to date, however, have not shown a benefit to such therapy. , en classes of neuroprotective agents have reached phase III efficacy trials but have shown mixed results. They included calcium channel antagonists, NMDA receptor antagonists, lubeluzole, CDP-choline, the free radical scavenger tirilazad and ebselen, enlimomab, GABA agonist clomethiazole, the sodium channel antagonist fosphenytoin, magnesium, glycine site antagonist GV150526 and piracetam. , 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. , 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., ESULTS: At day 90, the Modified Rankin Scale score was worse in patients treated with enlimomab than with placebo (p = 0.004). 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., CONCLUSIONS\n\nThe 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., There were significantly more adverse events with enlimomab treatment than placebo, primarily infections and fever., RESULTS\n\nAt day 90, the Modified Rankin Scale score was worse in patients treated with enlimomab than with placebo (p = 0.004)., The negative effect of enlimomab was apparent on days 5, 30, and 90 of treatment (p = 0.005)., However, this treatment failed to show benefit in the Enlimomab Acute Stroke Trial., There were significantly more adverse events with enlimomab treatment than placebo, primarily infections and fever., These observations provide several possible mechanisms for central nervous system-related clinical deterioration that occurred when Enlimomab was given in acute ischemic stroke., RESULTS\nAt day 90, the Modified Rankin Scale score was worse in patients treated with enlimomab than with placebo (p = 0.004)., Unfortunately, the case fatality rate in this trial was significantly higher in the enlimomab patient group than in the placebo group., CONCLUSIONS\nDoses 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., 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., 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., 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 Pazopanib, drug_effect with Pazopanib, drug_effect with Pazopanib, drug_effect with Pazopanib, drug_effect with Sitaxentan, drug_effect with Sitaxentan.", "label": "no"}
{"id": "converted_2931", "sentence1": "Are Mesenchymal stem cells (MSC) multipotent cells?", "sentence2": "multipotent mesenchymal bone marrow-derived stem cells, multipotent hESC-derived mesenchymal cells (MCs)[SEP]Relations: intellectual developmental disorder has relations: disease_phenotype_positive with Macrocephaly, disease_phenotype_positive with Macrocephaly, disease_phenotype_positive with Generalized myoclonic-atonic seizure, disease_phenotype_positive with Generalized myoclonic-atonic seizure, disease_phenotype_positive with Smooth philtrum, disease_phenotype_positive with Smooth philtrum, disease_phenotype_positive with Long palpebral fissure, disease_phenotype_positive with Long palpebral fissure, disease_phenotype_positive with Striae distensae, disease_phenotype_positive with Striae distensae.", "label": "yes"}
{"id": "converted_827", "sentence1": "Are histone deacetylase (HDAC) inhibitors good candidates to control metastasis of solid tumors?", "sentence2": "JNJ-26481585 also fully inhibited the growth of C170HM2 colorectal liver metastases, whereas again 5-fluorouracil/Leucovorin showed modest activity., Although not meeting the RECIST response criteria for adequate single-agent activity, the observed tolerable toxicities and the potential for clinical benefit in terms of stable disease suggest that further assessment of vorinostat as a part of combination therapy with either chemotherapeutic or targeted agents in metastatic breast might be undertaken., Treatments of different structural classes of HDACi simultaneously induced cell death and promoted cell migration and metastasis in multiple cancer cell types. Suppression of HDACi-induced PKCs leads to development of low toxic and long-term therapeutic strategies to potentially treat cancer as a chronic disease., mRNA expression analysis of lung tumor bearing mice suggested that the enhanced chemopreventive activity of the combination is related to atorvastatin modulation of DNA repair, SAHA modulation of angiogenesis, and both drugs modulating invasion and metastasis pathways., Histone deacetylase (HDAC) inhibitors induced morphologic differentiation, cell-cycle exit, and a shift to a differentiated, melanocytic gene expression profile in cultured UM cells. VPA inhibited the growth of UM tumors in vivo., When both drugs were used in concert additive effects were observed on the migratory and invasive behavior but not on tumor-endothelium and tumor-matrix interaction. Separate mTOR or HDAC inhibition slows processes related to tumor metastasis. The RAD001-VPA combination showed advantage over VPA monotreatment with particular respect to migration and invasion., In conclusion, sequential treatments of mice with MS-275 followed by TRAIL may target multiple pathways to reverse EMT and inhibit tumor progression, angiogenesis, and metastasis and represent a novel therapeutic approach to treat cancer., In vivo, AA98 synergized with vorinostat to inhibit tumor growth and metastasis., We report the first preclinical data for the prevention of brain metastasis of triple-negative breast cancer. Vorinostat is brain permeable and can prevent the formation of brain metastases by 62%. Its mechanism of action involves the induction of DNA double-strand breaks, suggesting rational combinations with DNA active drugs or radiation., Combining vorinostat with radiation may be a potential treatment option for patients with breast cancer who develop brain metastases., Although single-agent PCI-24781 had modest effects on STS growth and metastasis, marked inhibition was observed when combined with chemotherapy., In a 4T1 metastatic breast carcinoma model, AN-7 inhibited the formation of lung lesions by 76% and AN-9 by 47%, further demonstrating the greater efficacy of AN-7 compared to AN-9 (P<0.02). Both AN-7 and AN-9 exhibited antimetastatic and antiangiogenic activities by reducing vascularization, bFGF expression and HIF-1alpha., Since prolonged oral administration with 50 mg/kg or a single oral dose of 1.2 g/kg AN-7 did not cause adverse effects and the former exhibited significant anticancer activity, AN-7 is likely to display a high therapeutic index and may be beneficial for prostate cancer patients., We show that apicidin significantly inhibits H-ras-induced invasive phenotype of MCF10A human breast epithelial cells in parallel with a specific downregulation of matrix metalloproteinase (MMP)-2, but not MMP-9. We also show that apicidin induces a morphological reversal and growth inhibition of H-ras MCF10A cells similar to that induced by other HDAC inhibitors., We also found that NaB induced three genes, which are known metastatic suppressors, and downregulated 11 genes, which have been shown to promote metastasis.[SEP]Relations: Valproic acid has relations: drug_protein with HDAC9, drug_protein with HDAC9, drug_protein with HDAC2, drug_protein with HDAC2. Vorinostat has relations: drug_protein with HDAC3, drug_protein with HDAC3, drug_protein with HDAC1, drug_protein with HDAC1, drug_protein with HDAC6, drug_protein with HDAC6.", "label": "yes"}
{"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_4481", "sentence1": "Can Isradipine slow progression of Early Parkinson Disease?", "sentence2": "Adjusted least-squares mean changes in total UPDRS score in the antiparkinson medication ON state over 36 months for isradipine and placebo recipients were 2.99 (95% CI, 0.95 to 5.03) points versus 3.26 (CI, 1.25 to 5.26) points, respectively, with a treatment effect of -0.27 (CI, -3.02 to 2.48) point (P = 0.85)., Conclusion: Long-term treatment with immediate-release isradipine did not slow the clinical progression of early-stage PD., ONS: These results are consistent with the recent secondary analysis of the STEADY-PD III clinical trial-suggesting that clinically attainable brain exposure to isradipine may slow early-stage PD progression. © 2021 , These findings suggest that greater exposure to isradipine might slow disease progression., erm treatment with immediate-release isradipine did not slow the clinical progression of early-stage PD.Primary Funding So, BACKGROUND: Recent examination of the STEADY-PD III isradipine clinical trial data concluded that early-stage Parkinson's disease (PD) participants who had longer exposure to isradipine had a significant delay in their need for symptomatic medication, as well as a lower medication burden at the end of t, RESULTS: Isradipine exposures did not correlate with the primary clinical outcome, changes in the antiparkinson therapy-adjusted Unified Parkinson's Disease Rating Scale parts I-III score over 36 months (Spearman rank correlation coefficient, rs : ,  These findings suggest that greater exposure to isradipine might slow disease progressio, Conclusion: Long-term treatment with immediate-release isradipine did not slow the clinical progression of early-stage P, However, in a recently completed phase 3 clinical trial, the dihydropyridine (DHP) LTCC inhibitor isradipine failed to slow disease progression in early PD patients, questioning the feasibility of DHPs for PD therapy., BACKGROUND: Recent examination of the STEADY-PD III isradipine clinical trial data concluded that early-stage Parkinson's disease (PD) participants who had longer exposure to isradipine had a significant delay in their need for symptomatic medication, as well as a lower medication burden at the end o[SEP]Relations: Isradipine has relations: drug_effect with Hyperkinetic movements, drug_effect with Hyperkinetic movements, drug_drug with Prenalterol, drug_drug with Prenalterol. Parkinson disease has relations: contraindication with Etidocaine, contraindication with Etidocaine, contraindication with Articaine, contraindication with Articaine, contraindication with Epinephrine, contraindication with Epinephrine.", "label": "no"}
{"id": "converted_4428", "sentence1": "Is there a dependence between chromatin organization and dorsoventral gene expression in Drosophila?", "sentence2": "Independence of chromatin conformation and gene regulation during Drosophila dorsoventral patterning., Here, using the dorsoventral patterning of the Drosophila melanogaster embryo as a model system, we provide evidence for the independence of chromatin organization and dorsoventral gene expression. We define tissue-specific enhancers and link them to expression patterns using single-cell RNA-seq. Surprisingly, despite tissue-specific chromatin states and gene expression, chromatin organization is largely maintained across tissues. Our results indicate that tissue-specific chromatin conformation is not necessary for tissue-specific gene expression but rather acts as a scaffold facilitating gene expression when enhancers become active.[SEP]Relations: bone tissue has relations: anatomy_anatomy with endochondral bone tissue, anatomy_anatomy with endochondral bone tissue, anatomy_anatomy with trabecular bone tissue, anatomy_anatomy with trabecular bone tissue, anatomy_anatomy with intramembranous bone tissue, anatomy_anatomy with intramembranous bone tissue, anatomy_anatomy with lamellar bone, anatomy_anatomy with lamellar bone, anatomy_anatomy with osteoid, anatomy_anatomy with osteoid.", "label": "no"}
{"id": "converted_2476", "sentence1": "Can canagliflozin cause euglycemic diabetic ketoacidosis?", "sentence2": "CASE REPORT: We present a case of a 57-year-old woman with type 2 diabetes mellitus taking a combination of canagliflozin and metformin who presented with progressive altered mental status over the previous 2 days. Her work-up demonstrated a metabolic acidosis with an anion gap of 38 and a venous serum pH of 7.08. The serum glucose was 168 mg/dL. The urinalysis showed glucose>500 mg/dL and ketones of 80 mg/dL. Further evaluation demonstrated an elevated serum osmolality of 319 mOsm/kg and an acetone concentration of 93 mg/dL. She was treated with intravenous insulin and fluids, and the metabolic abnormalities and her altered mental status resolved within 36 h. This was the first episode of diabetic ketoacidosis (DKA) for this patient. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Diabetic patients on SGLT2 inhibitor medications are at risk for ketoacidosis. Due to the renal glucose-wasting properties of these drugs, they may present with ketoacidosis with only mild elevations in serum glucose, potentially complicating the diagnosis. , Euglycemic Diabetic Ketoacidosis with Persistent Diuresis Treated with Canagliflozin., We herein report the case of a 27-year-old Asian woman with type 2 diabetes who was treated with a sodium-glucose cotransporter 2 (SGLT2) inhibitor (canagliflozin) who developed euglycemic diabetic ketoacidosis and persistent diuresis in the absence of hyperglycemia., Canagliflozin raised the risk of amputations and the rate of fractures in the CANVAS trial, although more data are necessary before drawing definite conclusions. The risk of euglycemic diabetic ketoacidosis seems to be minimal when the drugs are prescribed properly., Severe Ketoacidosis Associated with Canagliflozin (Invokana): A Safety Concern.,  However, some serious side effects, including severe anion gap metabolic acidosis and euglycemic diabetic ketoacidosis (DKA), have been reported. , At present, the Food and Drug Administration (FDA) has only approved three medications (canagliflozin, dapagliflozin and empagliflozin) in this drug class for the management of Type 2 diabetes. In May 2015, the FDA issued a warning of ketoacidosis with use of this drug class., We present a case of euglycemic diabetic ketoacidosis secondary to canagliflozin in a type 2 diabetic patient., Nonconvulsive Status Epilepticus in Elderly Patients Receiving SSRIs; Euglycemic Diabetic Ketoacidosis Associated with Canagliflozin Use in a Type 1 Diabetic Patient; Duloxetine-Induced Galactorrhea; Canagliflozin-Associated Severe Hypercalcemia and Hypernatremia; Vemurafenib-Induced Fanconi Syndrome., Euglycemic Diabetic Ketoacidosis in a 27 year-old female patient with type-1-Diabetes treated with sodium-glucose cotransporter-2 (SGLT2) inhibitor Canagliflozin., We are reporting a timely case of atypical euglycemic diabetic ketoacidosis in a type 1 diabetic patient treated with sodium-glucose cotransporter-2 (SGLT-2) inhibitor canagliflozin., Euglycemic ketoacidosis did not recur in our patient after discontinuing canagliflozin. , Euglycemic Diabetic Ketoacidosis With Prolonged Glucosuria Associated With the Sodium-Glucose Cotransporter-2 Canagliflozin., In this article, we present a case of a 50-year-old woman with type 2 diabetes who developed euglycemic DKA after initiating therapy with canagliflozin. , SGLT2 inhibitors such as canagliflozin may predispose patients not only to diabetic ketoacidosis but also to prolonged glucosuria., We present a case of euglycemic diabetic ketoacidosis secondary to canagliflozin in a type 2 diabetic patient.<br>, We present a case of euglycemic diabetic ketoacidosis secondary to canagliflozin in a type 2 diabetic patient., CONCLUSION Treatment with canagliflozin was associated with development of euglycemic ketoacidosis., Euglycemic Diabetic Ketoacidosis with Persistent Diuresis Treated with Canagliflozin., We present a case of euglycemic diabetic ketoacidosis secondary to canagliflozin in a type 2 diabetic patient.., Euglycemic Diabetic Ketoacidosis With Prolonged Glucosuria Associated With the Sodium-Glucose Cotransporter-2 Canagliflozin., Euglycemic Diabetic Ketoacidosis in a 27 year-old female patient with type-1-Diabetes treated with sodium-glucose cotransporter-2 (SGLT2) inhibitor Canagliflozin.[SEP]Relations: Canagliflozin has relations: drug_drug with Carbetocin, drug_drug with Carbetocin, drug_drug with Ketobemidone, drug_drug with Ketobemidone. diabetic ketoacidosis has relations: contraindication with Norfloxacin, contraindication with Norfloxacin, contraindication with Inositol, contraindication with Inositol, contraindication with Inositol nicotinate, contraindication with Inositol nicotinate.", "label": "yes"}
{"id": "converted_3348", "sentence1": "Is Figitumumab effective for non-small cell lung cancer?", "sentence2": "A phase III study failed for carboplatin, paclitaxel, with or without figitumumab in first-line treating metastatic non-small cell lung cancer (NSCLC)., CONCLUSION: Adding figitumumab to standard chemotherapy failed to increase OS in patients with advanced nonadenocarcinoma NSCLC., Median OS was 8.6 months for figitumumab plus chemotherapy and 9.8 months for chemotherapy alone (hazard ratio [HR], 1.18; 95% CI, 0.99 to 1.40; P = .06); median progression-free survival was 4.7 months (95% CI, 4.2 to 5.4) and 4.6 months (95% CI, 4.2 to 5.4), respectively (HR, 1.10; P = .27); the objective response rates were 33% and 35%, respectively. , Phase III trials of the anti-insulin-like growth factor-1 receptor (IGF1R) antibody figitumumab in non-small cell lung cancer (NSCLC) patients have been discontinued owing to lack of survival benefit., Two phase III trials of the anti-IGF-1R monoclonal antibody, figitumumab (CP-751,871), were discontinued in 2010 as it was considered unlikely either trial would meet their primary endpoints. In light of disappointing clinical data with figitumumab and other targeted agents, it is likely that the use of molecular markers will become important in predicting response to treatment. , Phase III trials of the anti-insulin-like growth factor-1 receptor ( IGF1R ) antibody figitumumab in non-small cell lung cancer ( NSCLC ) patients have been discontinued owing to lack of survival benefit . , Phase III trials of the anti-insulin-like growth factor type 1 receptor ( IGF-IR ) antibody figitumumab ( F ) in unselected non-small-cell lung cancer ( NSCLC ) patients were recently discontinued owing to futility . , One recent phase III trial of the IGF-1R inhibitor figitumumab in patients with non-small-cell lung cancer was discontinued after an interim analysis showed no survival improvement . , The insulin-like growth factor receptor ( IGF-1R ) monoclonal antibody figitumumab , while initially promising , appears to increase toxicity and death in combination with chemotherapy in the treatment of patients with NSCLC of squamous histology; therefore , clinical development of this class of agents will need to proceed with caution . , Two phase III trials of the anti-IGF-1R monoclonal antibody , figitumumab ( CP-751,871) , were discontinued in 2010 as it was considered unlikely either trial would meet their primary endpoints . , A phase III study failed for carboplatin , paclitaxel , with or without figitumumab in first-line treating metastatic non-small cell lung cancer ( NSCLC) . , Median OS was 8.6 months for figitumumab plus chemotherapy and 9.8 months for chemotherapy alone (hazard ratio [HR], 1.18; 95% CI, 0.99 to 1.40; P = .06); median progression-free survival was 4.7 months (95% CI, 4.2 to 5.4) and 4.6 months (95% CI, 4.2 to 5.4), respectively (HR, 1.10; P = .27); the objective response rates were 33% and 35%, respectively.[SEP]Relations: Figitumumab has relations: drug_drug with Necitumumab, drug_drug with Necitumumab, drug_drug with Inebilizumab, drug_drug with Inebilizumab, drug_drug with Concizumab, drug_drug with Concizumab, drug_drug with Catumaxomab, drug_drug with Catumaxomab, drug_drug with Tositumomab, drug_drug with Tositumomab.", "label": "no"}
{"id": "converted_607", "sentence1": "Is microRNA(miRNA) 30 involved in post-ischemic cardiac remodeling?", "sentence2": "The myocardium of the failing heart undergoes a number of structural alterations, most notably hypertrophy of cardiac myocytes and an increase in extracellular matrix proteins, often seen as primary fibrosi, Connective tissue growth factor (CTGF) is a key molecule in the process of fibrosis and therefore seems an attractive therapeutic target, CTGF is importantly regulated by 2 major cardiac microRNAs (miRNAs), miR-133 and miR-30., the expression of both miRNAs was inversely related to the amount of CTGF in 2 rodent models of heart disease and in human pathological left ventricular hypertrophy. Second, in cultured cardiomyocytes and fibroblasts, knockdown of these miRNAs increased CTGF levels. Third, overexpression of miR-133 or miR-30c decreased CTGF levels, which was accompanied by decreased production of collagens., miR-30 importantly limit the production of CTGF, miR-30 directly downregulate CTGF, a key profibrotic protein, and thereby establish an important role for these miRNAs in the control of structural changes in the extracellular matrix of the myocardium.[SEP]Relations: myocardium has relations: anatomy_protein_present with MIR1245A, anatomy_protein_present with MIR1245A, anatomy_protein_present with MIRLET7D, anatomy_protein_present with MIRLET7D, anatomy_protein_present with MIR22HG, anatomy_protein_present with MIR22HG, anatomy_protein_present with MIR99AHG, anatomy_protein_present with MIR99AHG, anatomy_protein_present with SNRNP25, anatomy_protein_present with SNRNP25.", "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]Relations: GLI proteins bind promoters of Hh responsive genes to promote transcription has relations: pathway_protein with GLI2, pathway_protein with GLI2, pathway_protein with GLI1, pathway_protein with GLI1, pathway_protein with GLI3, pathway_protein with GLI3.", "label": "no"}
{"id": "converted_3384", "sentence1": "Does the chromatin remodeling complex, RSC target H2A.Z nucleosomes?", "sentence2": "In contrast, the upstream nucleosome which covers the TATA box under repressed conditions is shifted approximately 50 bp further upstream by the ATP-dependent chromatin remodeler RSC upon activation. It is marked with the histone variant H2A.Z and H4K16 acetylation in active state, In RSC-depleted cells, NFRs shrink such that the average positions of flanking nucleosomes move toward predicted sites., In contrast, H2A.Z deposition is dispensable for nucleosome positioning. , Emerging lines of evidence indicate that histone variants (H2AX and H2A.Z), histone post-translational modifications (acetylation, phosphorylation, methylation and ubiquitination) and chromatin-remodeling complexes (INO80, SWR1, SWI/SNF, RSC and NuRD) are important and direct players in the DNA double-strand break (DSB) response as well., H2A.Z probably helps RSC in keeping the gene nucleosome-fre, Accordingly, the absence of SWR-C or histone H2A.Z results in compromised chromatin remodeling and impaired gene expression in the absence of RSC and H3K4 methylation.[SEP]Relations: nucleosome mobilization has relations: bioprocess_bioprocess with chromatin remodeling, bioprocess_bioprocess with chromatin remodeling. nucleosome has relations: cellcomp_protein with H3C6, cellcomp_protein with H3C6, cellcomp_protein with H2AC4, cellcomp_protein with H2AC4, cellcomp_protein with H4C6, cellcomp_protein with H4C6, cellcomp_protein with H3C4, cellcomp_protein with H3C4.", "label": "yes"}
{"id": "converted_820", "sentence1": "Is Lysine-specific demethylase 1 (LSD1) a critical regulator of hematopoiesis?", "sentence2": "Histone lysine-specific demethylase 1 (LSD1) protein is involved in Sal-like protein 4 (SALL4)-mediated transcriptional repression in hematopoietic stem cells, shRNA-mediated knockdown of LSD1 in hematopoietic precursor cells resulted in altered SALL4 downstream gene expression and increased cellular activity, our data revealed that histone demethylase LSD1 may negatively regulate SALL4-mediated transcription, and the dynamic regulation of SALL4-associated epigenetic factors cooperatively modulates early hematopoietic precursor proliferation, Lysine-specific demethylase 1 restricts hematopoietic progenitor proliferation and is essential for terminal differentiation,  LSD1 represents a central regulator of hematopoietic stem and progenitor cells,  LSD1-kd led to an extensive expansion of granulomonocytic, erythroid and megakaryocytic progenitors, LSD1-kd was associated with the upregulation of key hematopoietic genes, our findings distinguish LSD1 as a critical regulator of hematopoiesis, A short Gfi-1B isoform controls erythroid differentiation by recruiting the LSD1-CoREST complex through the dimethylation of its SNAG domain, Dynamic interaction between TAL1 oncoprotein and LSD1 regulates TAL1 function in hematopoiesis and leukemogenesis, Here, we reported that protein kinase A (PKA)-mediated phosphorylation regulates TAL1 interaction with the lysine-specific demethylase (LSD1) that removes methyl group from methylated Lys 4 on histone H3 tails. Phosphorylation of serine 172 in TAL1 specifically destabilizes the TAL1-LSD1 interaction leading to promoter H3K4 hypermethylation and activation of target genes that have been suppressed in normal and malignant hematopoiesis, LSD1-mediated epigenetic modification is required for TAL1 function and hematopoiesis, we show that TAL1 is associated with histone demethylase complexes containing lysine-specific demethylase 1 (LSD1), RE1 silencing transcription factor corepressor (CoREST), histone deacetylase 1 (HDAC1), and histone deacetylase 2 in erythroleukemia and T cell leukemia cells, we demonstrate that the TAL1-associated LSD1, HDAC1, and their enzymatic activities are coordinately down-regulated during the early phases of erythroid differentiation, TAL1 recruits LSD1 to the silenced p4.2 promoter in undifferentiated, but not in differentiated, murine erythroleukemia (MEL) cells, the dynamic regulation of TAL1-associated LSD1/HDAC1 complex may determine the onset of erythroid differentiation programs, Epigenetic regulation of hematopoietic differentiation by Gfi-1 and Gfi-1b is mediated by the cofactors CoREST and LSD1, Inhibition of CoREST and LSD1 perturbs differentiation of erythroid, megakaryocytic, and granulocytic cells as well as primary erythroid progenitors, we show that chromatin regulatory proteins CoREST and LSD1 mediate transcriptional repression by Gfi proteins. Lineage-restricted deployment of these cofactors through interaction with Gfi proteins controls hematopoietic differentiation, Taken together, our findings distinguish LSD1 as a critical regulator of hematopoiesis and point to severe, but reversible, side effects of a LSD1-targeted therapy., LSD1-mediated epigenetic modification is required for TAL1 function and hematopoiesis., Dynamic interaction between TAL1 oncoprotein and LSD1 regulates TAL1 function in hematopoiesis and leukemogenesis., Phosphorylation of serine 172 in TAL1 specifically destabilizes the TAL1-LSD1 interaction leading to promoter H3K4 hypermethylation and activation of target genes that have been suppressed in normal and malignant hematopoiesis., Histone lysine-specific demethylase 1 (LSD1) protein is involved in Sal-like protein 4 (SALL4)-mediated transcriptional repression in hematopoietic stem cells., Taken together, our findings distinguish LSD1 as a critical regulator of hematopoiesis and point to severe, but reversible, side effects of a LSD1-targeted therapy.[SEP]Relations: melorheostosis has relations: disease_phenotype_positive with Skeletal dysplasia, disease_phenotype_positive with Skeletal dysplasia, disease_phenotype_positive with Lymphedema, disease_phenotype_positive with Lymphedema, disease_protein with LEMD3, disease_protein with LEMD3. HDMs demethylate histones has relations: pathway_protein with KDM1A, pathway_protein with KDM1A. site-specific DNA-methyltransferase (adenine-specific) activity has relations: molfunc_protein with N6AMT1, molfunc_protein with N6AMT1.", "label": "yes"}
{"id": "converted_2227", "sentence1": "Is Downs syndrome associated with decreased risk of leukemia?", "sentence2": "The association of Down's syndrome and leukemia has been documented for over 50 years. Multiple studies have established the incidence of leukemia in Down's syndrome patients to be 10- to 20-fold higher than that in the general population., We present a case of congenital acute myeloid leukemia manifesting from the very first day of birth. Diagnosis of acute myeloid leukemia was suspected by the presence of blasts in the peripheral blood smear and was confirmed on bone marrow by flowcytometry. Karyotyping revealed Trisomy 21., Juvenile myelomonocytic leukemia (JMML) and a solitary cases of acute myeloid leukemia (AML) in Downs syndrome. , This was thus confirmed to be a case with transient leukemia with Downs syndrome.[SEP]Relations: Down syndrome has relations: disease_phenotype_positive with Decreased fertility, disease_phenotype_positive with Decreased fertility, disease_phenotype_positive with Acute megakaryocytic leukemia, disease_phenotype_positive with Acute megakaryocytic leukemia, disease_phenotype_positive with Sporadic, disease_phenotype_positive with Sporadic, disease_phenotype_positive with Short palm, disease_phenotype_positive with Short palm, disease_phenotype_positive with Short neck, disease_phenotype_positive with Short neck.", "label": "no"}
{"id": "converted_3176", "sentence1": "Can mitochondria pass through membrane nanotubes?", "sentence2": "Membrane nanotubes (MNTs) act as \"highways\" between cells to facilitate the transfer of multiple signals and play an important role in many diseases. Our previous work reported on the transfer of mitochondria via MNTs between cardiomyocytes (CMs) and cardiac myofibroblasts (MFs), Membrane nanotubes play important functional roles in numerous cell activities such as cellular transport and communication.[SEP]Relations: mitochondrion has relations: cellcomp_protein with POR, cellcomp_protein with POR, cellcomp_protein with SLIT3, cellcomp_protein with SLIT3, cellcomp_protein with BID, cellcomp_protein with BID, cellcomp_protein with TRAP1, cellcomp_protein with TRAP1, cellcomp_protein with PSMB4, cellcomp_protein with PSMB4.", "label": "yes"}
{"id": "converted_2088", "sentence1": "Are cutaneous porphyrias inherited with a recessive pattern?", "sentence2": "Five of the porphyrias are low-penetrance autosomal dominant conditions in which clinical expression results from additional factors that act by increasing demand for haem or by causing an additional decrease in enzyme activity or by a combination of these effects, Molecular mechanisms of dominant expression in porphyria., Variegate porphyria (VP) is an autosomal-dominant disorder that is caused by inheritance of a partial deficiency of the enzyme protoporphyrinogen oxidase (EC 1.3.3.4). It is characterized by cutaneous photosensitivity and/or various neurological manifestations. , The acute porphyrias constitute a group of metabolic disorders engaging enzymes in the haem synthetic chain and generally following dominant inheritance patterns.[SEP]Relations: variegate porphyria has relations: disease_disease with inherited porphyria, disease_disease with inherited porphyria, disease_phenotype_positive with Autosomal dominant inheritance, disease_phenotype_positive with Autosomal dominant inheritance, disease_phenotype_positive with Behavioral abnormality, disease_phenotype_positive with Behavioral abnormality, disease_phenotype_positive with Cutaneous photosensitivity, disease_phenotype_positive with Cutaneous photosensitivity. inborn disorder of porphyrin metabolism has relations: disease_disease with inherited porphyria, disease_disease with inherited porphyria.", "label": "no"}
{"id": "converted_3373", "sentence1": "Is the drug Exubera currently (March 2020) available?", "sentence2": "Despite discontinuation of the first inhalable insulin, Exubera®, due to suboptimal market acceptance, development of orally inhaled insulin delivery systems has been galvanized by the recent approval of Afrezza® and several others awaiting approval.[SEP]", "label": "no"}
{"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]Relations: nuclear speck has relations: cellcomp_protein with SPOP, cellcomp_protein with SPOP, cellcomp_protein with SPRTN, cellcomp_protein with SPRTN, cellcomp_protein with MBD4, cellcomp_protein with MBD4, cellcomp_protein with ERBIN, cellcomp_protein with ERBIN, cellcomp_protein with ILRUN, cellcomp_protein with ILRUN.", "label": "no"}
{"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_162", "sentence1": "Is there an increased risk for cancer in Dyskeratosis Congenita?", "sentence2": "People with DC are at increased risk for progressive bone marrow failure (BMF), myelodysplastic syndrome (MDS) or acute myelogenous leukemia (AML), solid tumors (usually squamous cell carcinoma of the head/neck or anogenital cancer), and pulmonary fibrosis, Clinical progression of the disease can lead to aplastic anemia (86% of all patients) and to pulmonary or hepatic complications. These patients also have an increased risk of cancer., Fanconi anaemia (FA), dyskeratosis congenita (DC), Diamond-Blackfan anaemia (DBA), and Shwachman-Diamond syndrome (SDS) comprise major inherited bone marrow failure syndromes (IBMFS). Adverse events include severe bone marrow failure (BMF), myelodysplastic syndrome (MDS), acute myeloid leukaemia (AML), and solid tumours (ST), Patients with FA had earlier onset of cancers, need for stem cell transplant, and death; followed by DC; DBA and SDS were mildest. While FA and DC patients had markedly increased risks of cancer, AML and MDS, there were no cases of leukaemia in DBA or SDS patients, The findings demonstrate that both FA and DC are major cancer susceptibility syndromes, People with DC are at increased risk for progressive bone marrow failure (BMF), myelodysplastic syndrome (MDS) or acute myelogenous leukemia (AML), solid tumors (usually squamous cell carcinoma of the head/neck or anogenital cancer), and pulmonary fibrosis, Patients with dyskeratosis congenita (DC) have an increased risk of cancer, but also exhibit heightened radiation sensitivity., Dyskeratosis congenita (DC) is characterized by the clinical triad of reticular skin pigmentation, oral leukoplakia, and nail dystrophy associated with bone marrow failure (BMF) and an high risk to develop cancer and pulmonary complications., CONCLUSION: Dyskeratosis congenita is a rare condition; however, it is vital to recognise the increased risk of upper aerodigestive tract cancers in these patients., Point mutations in the DKC1 gene that encodes dyskerin cause the rare inherited syndrome called X-linked dyskeratosis congenita, characterized by a failure of proliferating tissues and increased susceptibility to cancer., Dyskeratosis Congenita (DC) also known as Zinsser-Engman-Cole syndrome is a rare multi-system bone marrow failure syndrome characterised by mucocutaneous abnormalities and an increased predisposition to cancer\"., Dyskeratosis congenita is an inherited syndrome characterised by mucocutaneous features, bone marrow failure, an increased risk of malignancy and other somatic abnormalities., Dyskeratosis congenita is a rare condition; however, it is vital to recognise the increased risk of upper aerodigestive tract cancers in these patients., Epidermal atrophy, hair growth defects, bone marrow failure and increased risk of cancer are also common in DC patients., Telomere dysfunction and tumor suppression responses in dyskeratosis congenita: balancing cancer and tissue renewal impairment., Patients with dyskeratosis congenita (DC) have an increased risk of cancer, but also exhibit heightened radiation sensitivity, Dyskeratosis congenita is a rare condition; however, it is vital to recognise the increased risk of upper aerodigestive tract cancers in these patients, Dyskeratosis congenita is an inherited syndrome characterised by mucocutaneous features, bone marrow failure, an increased risk of malignancy and other somatic abnormalities, While FA and DC patients had markedly increased risks of cancer, AML and MDS, there were no cases of leukaemia in DBA or SDS patients, As in Fanconi anemia and dyskeratosis congenita, DBA is both an inherited bone marrow failure syndrome and a cancer predisposition syndrome; cancer risks appear lower in DBA than in Fanconi anemia or dyskeratosis congenita, Severe pancytopenia frequently causes early mortality of DC patients, who have an increased risk of developing oropharyngeal squamous cell carcinoma, Here different aspects of telomere biology, concerning adult stem cells senescence, tumor suppression and cancer are considered in the context of DC, resulting in two translational models: late onset of DC symptoms in telomere-related mutations carriers is a potential indicator of increased cancer risk and differences in tumor suppression capacities among the genetic subgroups are (at least partial) causes of different clinical manifestations of the disease, Point mutations in the DKC1 gene that encodes dyskerin cause the rare inherited syndrome called X-linked dyskeratosis congenita, characterized by a failure of proliferating tissues and increased susceptibility to cancer, Dyskeratosis congenita is a cancer-prone bone marrow failure syndrome caused by aberrations in telomere biology.[SEP]Relations: dyskeratosis congenita has relations: disease_protein with TERC, disease_protein with TERC, disease_protein with TERT, disease_protein with TERT. dyskeratosis congenita, X-linked has relations: disease_phenotype_positive with Carcinoma, disease_phenotype_positive with Carcinoma, disease_protein with TERT, disease_protein with TERT, disease_disease with X-linked disease, disease_disease with X-linked disease.", "label": "yes"}
{"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_3510", "sentence1": "Are there interactions between short and long noncoding RNAs?", "sentence2": "It is now evident that noncoding RNAs play key roles in regulatory networks determining cell fate and behavior, in a myriad of different conditions, and across all species. Among these noncoding RNAs are short RNAs, such as MicroRNAs, snoRNAs, and Piwi-interacting RNAs, and the functions of those are relatively well understood. Other noncoding RNAs are longer, and their modes of action and functions are also increasingly explored and deciphered. Short RNAs and long noncoding RNAs (lncRNAs) interact with each other with reciprocal consequences for their fates and functions. LncRNAs serve as precursors for many types of small RNAs and, therefore, the pathways for small RNA biogenesis can impinge upon the fate of lncRNAs. In addition, lncRNA expression can be repressed by small RNAs, and lncRNAs can affect small RNA activity and abundance through competition for binding or by triggering small RNA degradation. Here, I review the known types of interactions between small and long RNAs, discuss their outcomes, and bring representative examples from studies in mammals., Short RNAs and long noncoding RNAs (lncRNAs) interact with each other with reciprocal consequences for their fates and functions., Short RNAs and long noncoding RNAs (lncRNAs) interact with each other with reciprocal consequences for their fates and functions.[SEP]Relations: long noncoding RNA binding has relations: molfunc_protein with MIR384, molfunc_protein with MIR384. PIWI-interacting RNA (piRNA) biogenesis has relations: pathway_protein with HSP90AA1, pathway_protein with HSP90AA1, pathway_protein with TDRD9, pathway_protein with TDRD9, pathway_protein with TDRD6, pathway_protein with TDRD6, pathway_protein with MAEL, pathway_protein with MAEL.", "label": "yes"}
{"id": "converted_3832", "sentence1": "Is the Paramyxovirus geneome segmented, negative-sense RNA?", "sentence2": "The paramyxovirus family has a genome consisting of a single strand of negative sense RNA, The avian paramyxovirus type 1 (APMV-1), or Newcastle disease virus (NDV), comprise a diverse group of viruses with a single-stranded, negative-sense RNA genome., Members of the Paramyxoviridae such as measles, mumps, and parainfluenza viruses have pleomorphic, enveloped virions that contain negative-sense unsegmented RNA genomes., UNLABELLED: Mumps virus (MuV), a paramyxovirus containing a negative-sense nonsegmented RNA genome, is a human pathogen that causes an acute infection with symptoms ranging from parotitis to mild meningitis and severe encephalitis., UNLABELLED: Mumps virus (MuV) is a paramyxovirus with a negative-sense nonsegmented RNA genome., Paramyxoviridae, a large family of enveloped viruses harboring a nonsegmented negative-sense RNA genome, include important human pathogens as measles, mumps, respiratory syncytial virus (RSV), parainfluenza viruses, and henipaviruses, which cause some of the deadliest emerging zoonoses. There , Parainfluenza virus 5 (PIV5) is a member of the Paramyxoviridae family of membrane-enveloped viruses with a negative-sense RNA genome that is packaged and protected by long filamentous nucleocapsid-helix structures (RNPs). , The paramyxovirus genome, a nonsegmented, negative-polarity, single-stranded RNA of approximately 15 kb, contains six transcription units flanked at the 3' and 5' ends by a short (approximately 50- to 60-nucleotide) extracistronic sequence, dubbed the positive and negative leader regions. These, The replication of nonsegmented minus-strand RNA genomes, like that of Sendai paramyxovirus (SeV), are controlled by the short leader regions present at each end of the linear genomes and antigenomes; the left and right promoters (PL and PR), respectively. Wil, UNLABELLED: Mumps virus (MuV), a paramyxovirus containing a negative-sense nonsegmented RNA genome, is a human pathogen that causes an acute infection with symptoms ranging from parotitis to mild meningitis and severe enc, s viral glycoprotein cytoplasmic domains may play a role in this coordination, we have investigated the importance of the hemagglutinin-neuraminidase (HN) protein cytoplasmic domain in the assembly of the nonsegmented negative-strand RNA paramyxovirus simian virus 5 (SV5). By, Beilong virus, a novel paramyxovirus with the largest genome of non-segmented negative-stranded RNA viruses., The paramyxovirus genome, a nonsegmented, negative-polarity, single-stranded RNA of approximately 15 kb, contains six transcription units flanked at the 3' and 5' ends by a short (approximately 50- to 60-nucleotide) extracistronic sequence, dubbed the positive and negative leader regions., Paramyxovirus particles are pleomorphic, with a lipid envelope, nonsegmented RNA genomes of negative polarity, and densely packed glycoproteins on the virion surface., An alternative method to determine the 5' extremities of non-segmented, negative sense RNA viral genomes using positive replication intermediate 3' tailing: application to two members of the Paramyxoviridae family., Simian parainfluenza virus 5 (SV5) is a prototype of the Paramyxoviridae family of nonsegmented negative-sense RNA viruses., Human metapneumovirus (HMPV), a single-stranded negative-sense RNA virus belonging to the family Paramyxoviridae, is associated with respiratory tract illness, primarily in young children and persons with underlying disease.[SEP]Relations: Parotitis has relations: disease_phenotype_positive with sarcoidosis, disease_phenotype_positive with sarcoidosis. Protein S human has relations: drug_drug with Deferasirox, drug_drug with Deferasirox, drug_drug with Dactinomycin, drug_drug with Dactinomycin, drug_drug with Interferon beta-1b, drug_drug with Interferon beta-1b, drug_drug with Ximelagatran, drug_drug with Ximelagatran.", "label": "no"}
{"id": "converted_2585", "sentence1": "Can CD55 deficiency cause thrombosis?", "sentence2": " The loss of CD55 and CD59 renders PNH erythrocytes susceptible to intravascular haemolysis, which can lead to thrombosis and to much of the morbidity and mortality of PNH. , CD55 Deficiency, Early-Onset Protein-Losing Enteropathy, and Thrombosis., CONCLUSIONS: CD55 deficiency with hyperactivation of complement, angiopathic thrombosis, and protein-losing enteropathy (the CHAPLE syndrome) is caused by abnormal complement activation due to biallelic loss-of-function mutations in CD55. , It is caused by the expansion of a hematopoietic progenitor cell that has acquired a mutation in the X-linked phosphatidylinositol glycan class A (PIGA) gene that results in deficiency of the glycosylphosphatidylinositol anchor structure responsible for fixing a wide spectrum of proteins particularly CD55 and CD59. The clinical features of this disease arise as a result of complement-mediated hemolysis in unprotected red cells, leukocytes, and platelets as well as the release of free hemoglobin. Patients may present with a variety of clinical manifestations, such as anemia, thrombosis, kidney disease, smooth muscle dystonias, abdominal pain, dyspnea, and extreme fatigue., The lack of one of the GPI-AP complement regulatory proteins (CD55, CD59) leads to hemolysis. The disease is diagnosed with hemolytic anemia, marrow failure and thrombosis., Paroxysmal nocturnal hemoglobinuria (PNH) is a rare bone marrow failure disorder that manifests with hemolytic anemia, thrombosis, and peripheral blood cytopenias. The absence of two glycosylphosphatidylinositol (GPI)-anchored proteins, CD55 and CD59, leads to uncontrolled complement activation that accounts for hemolysis and other PNH manifestations., RESULTS: CD55 and/or CD59 deficiencies were found in 1.6% (2/127) of patients with primary BCS, 1.0% (1/100) of non-malignant and non-cirrhotic patients with PVT, and 4.7% (4/85) of cirrhotic patients with PVT., Data of this study indicate that the PNH defect as detected with CD55, CD59, and CD16 is not an important cause of intra-abdominal thrombosis in northwestern India., PNH testing of red blood cells revealed a CD55 and CD59 deficiency consistent with PNH in both cases. The systemic complications typically associated with thrombosis were not observed for the following several months with early conservative treatments including eculizumab., Deficiency of the GPI-anchored complement inhibitors CD55 and CD59 on erythrocytes leads to intravascular hemolysis upon complement activation. Apart from hemolysis, another prominent feature is a highly increased risk of thrombosis., Genetic reconstitution of CD55 or treatment with a complement-inhibitory therapeutic antibody reversed abnormal complement activation.<br><b>CONCLUSIONS</b>: CD55 deficiency with hyperactivation of complement, angiopathic thrombosis, and protein-losing enteropathy (the CHAPLE syndrome) is caused by abnormal complement activation due to biallelic loss-of-function mutations in CD55., Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal disorder characterized by a decrease or absence of glycosylphosphatidylinositol (GPI)-anchored molecules such as CD55 and CD59 from the surface of affected cells, resulting in intravascular hemolysis, cytopenia, and venous thrombosis., CONCLUSIONS CD55 deficiency with hyperactivation of complement, angiopathic thrombosis, and protein-losing enteropathy (the CHAPLE syndrome) is caused by abnormal complement activation due to biallelic loss-of-function mutations in CD55., CD55 deficiency with hyperactivation of complement, angiopathic thrombosis, and protein-losing enteropathy (the CHAPLE syndrome) is caused by abnormal complement activation due to biallelic loss-of-function mutations in CD55., CD55 Deficiency, Early-Onset Protein-Losing Enteropathy, and Thrombosis.[SEP]Relations: Venous thrombosis has relations: disease_phenotype_positive with hereditary thrombophilia due to congenital protein C deficiency, disease_phenotype_positive with hereditary thrombophilia due to congenital protein C deficiency, drug_effect with Metolazone, drug_effect with Metolazone. Thrombocytosis has relations: disease_phenotype_positive with vasculitis due to ADA2 deficiency, disease_phenotype_positive with vasculitis due to ADA2 deficiency, disease_phenotype_positive with leukocyte adhesion deficiency, disease_phenotype_positive with leukocyte adhesion deficiency. Hemolytic anemia has relations: disease_phenotype_positive with primary CD59 deficiency, disease_phenotype_positive with primary CD59 deficiency.", "label": "yes"}
{"id": "converted_1775", "sentence1": "Is exon skipping correlated with exon circularization?", "sentence2": "Exon Skipping Is Correlated with Exon Circularization, We find that circularization of exons is widespread and correlates with exon skipping, a feature that adds considerably to the regulatory complexity of the human transcriptome, Exon Skipping Is Correlated with Exon Circularization., We find that circularization of exons is widespread and correlates with exon skipping, a feature that adds considerably to the regulatory complexity of the human transcriptome. <CopyrightInformation>Copyright © 2015 Elsevier Ltd. All rights reserved.</, We find that circularization of exons is widespread and correlates with exon skipping, a feature that adds considerably to the regulatory complexity of the human transcriptome. <CopyrightInformation>Copyright © 2015 Elsevier Ltd. All rights reserved.</C, Exon Skipping Is Correlated with Exon Circularization.[SEP]", "label": "yes"}
{"id": "converted_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_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]Relations: interleukin-1 binding has relations: molfunc_protein with NLRP7, molfunc_protein with NLRP7, molfunc_protein with TRIM16, molfunc_protein with TRIM16, molfunc_protein with HAX1, molfunc_protein with HAX1, molfunc_protein with A2M, molfunc_protein with A2M, molfunc_protein with IL1R1, molfunc_protein with IL1R1.", "label": "yes"}
{"id": "converted_3117", "sentence1": "Are there tools for visualizing and processing long-read sequencing data?", "sentence2": "NanoPack: visualizing and processing long-read sequencing data., Here we describe NanoPack, a set of tools developed for visualization and processing of long-read sequencing data from Oxford Nanopore Technologies and Pacific Biosciences.Availability and implementation: The NanoPack tools are written in Python3 and released under the GNU GPL3.0 License. The source code can be found at https://github.com/wdecoster/nanopack, together with links to separate scripts and their documentation. The scripts are compatible with Linux, Mac OS and the MS Windows 10 subsystem for Linux and are available as a graphical user interface, a web service at http://nanoplot.bioinf.be and command line tools., Summary\nHere we describe NanoPack, a set of tools developed for visualization and processing of long-read sequencing data from Oxford Nanopore Technologies and Pacific Biosciences., NanoPack: visualizing and processing long-read sequencing data.Supplementary data are available at Bioinformatics online., <b>Summary</b>: Here we describe NanoPack, a set of tools developed for visualization and processing of long-read sequencing data from Oxford Nanopore Technologies and Pacific Biosciences.<br><b>Availability and implementation</b>: The NanoPack tools are written in Python3 and released under the GNU GPL3.0 License., Here we describe NanoPack, a set of tools developed for visualization and processing of long-read sequencing data from Oxford Nanopore Technologies and Pacific Biosciences.[SEP]", "label": "yes"}
{"id": "converted_3874", "sentence1": "Is isradipine effective for Parkinson's disease?", "sentence2": "Adjusted least-squares mean changes in total UPDRS score in the antiparkinson medication ON state over 36 months for isradipine and placebo recipients were 2.99 (95% CI, 0.95 to 5.03) points versus 3.26 (CI, 1.25 to 5.26) points, respectively, with a treatment effect of -0.27 (CI, -3.02 to 2.48) point (P = 0.85)., Conclusion: Long-term treatment with immediate-release isradipine did not slow the clinical progression of early-stage PD.[SEP]Relations: Isradipine has relations: contraindication with liver disease, contraindication with liver disease, drug_effect with Vertigo, drug_effect with Vertigo, drug_effect with Hepatitis, drug_effect with Hepatitis, drug_effect with Hyperhidrosis, drug_effect with Hyperhidrosis, contraindication with hypotensive disorder, contraindication with hypotensive disorder.", "label": "no"}
{"id": "converted_4367", "sentence1": "Can bergapten cross the blood-brain barrier?", "sentence2": "Moreover, pharmacokinetic studies showed that bergapten has higher absolute bioavailability and can cross the blood-brain barrier and has a great potential for treating brain disease, but the mechanism needs further clarification to make greater use of its ability to treat brain diseases. [SEP]Relations: blood brain barrier has relations: anatomy_anatomy with glial blood brain barrier, anatomy_anatomy with glial blood brain barrier, anatomy_anatomy with cell layer, anatomy_anatomy with cell layer. brain disease has relations: contraindication with Cefepime, contraindication with Cefepime, contraindication with Cyclopentolate, contraindication with Cyclopentolate, contraindication with Edrophonium, contraindication with Edrophonium.", "label": "yes"}
{"id": "converted_2491", "sentence1": "Has ATF4 transcription factor been linked to cancer and neoplastic transformation?", "sentence2": "aken together, we discovered a novel axis of BCL10-regulated OSCC progression via STAT1/ATF4/S100P/P65 signaling, which could predict the prognosis of OSCC and will be beneficial for developing therapeutic strategy against advanced OSCC, s a result, the level of phosphorylated Eukaryotic Initiation Factor 2 alpha (eIF2α) is markedly elevated, resulting in the promotion of a pro-adaptive signaling pathway by the inhibition of global protein synthesis and selective translation of Activating Transcription Factor 4 (ATF4). , Many cancers overexpress ATF4, a stress-induced transcription factor that promotes cell survival under hypoxic conditions and other stresses of the tumor microenvironment, but the potential contributions of ATF4 to oncogenesis itself have been little explored. Here, we report that ATF4 promotes oncogene-induced neoplastic transformation by suppressing the expression of cellular senescence-associated genes. , Here, we report that ATF4 promotes oncogene-induced neoplastic transformation by suppressing the expression of cellular senescence-associated genes., Elevated levels of ATF4 were sufficient to suppress expression of these proteins and drive oncogenic transformation., Our findings define a central function for ATF4 in promoting oncogenic transformation by suppressing a central pathway of cellular senescence.<br>, ATF4 expression is upregulated in cancer., Activating transcription factor 4 (ATF4), an endoplasmic reticulum stress-inducible transcription factor, plays important roles in cancer progression and resistance to therapy., Activating transcription factor 4 (ATF4) is a stress-induced transcription factor that is frequently upregulated in cancer cells., Our findings define a central function for ATF4 in promoting oncogenic transformation by suppressing a central pathway of cellular senescence., Stress-regulated transcription factor ATF4 promotes neoplastic transformation by suppressing expression of the INK4a/ARF cell senescence factors., Activating transcription factor 4 (ATF4), a member of the ATF/CREB family, has been reported to be related to tumor angiogenesis[SEP]Relations: transcription coactivator activity has relations: molfunc_protein with IRF4, molfunc_protein with IRF4, molfunc_protein with TAF6, molfunc_protein with TAF6, molfunc_protein with YAF2, molfunc_protein with YAF2, molfunc_protein with UTF1, molfunc_protein with UTF1, molfunc_protein with PHF2, molfunc_protein with PHF2.", "label": "yes"}
{"id": "converted_1861", "sentence1": "Is treatment resistant depression related to vitamin B9?", "sentence2": "Suboptimal serum and red blood cell folate levels have been associated with a poorer response to antidepressant therapy, a greater severity of symptoms, later onset of clinical improvement, and overall treatment resistance. This article reviews the evidence for L-methylfolate and folic acid as antidepressive agents in depression and discusses their clinical use, Although further randomized controlled trials in this area appear warranted, SAMe and L-methylfolate may represent a useful addition to the AD armamentarium., Patients with depression have consistently been found to have lower levels of serum and red blood cell folate than normal or nondepressed psychiatric patients. Decreased folate levels have been associated with lowered response rates to standard antidepressant pharmacotherapy. Recent studies have shown that augmentation with a folate supplement increases medication response in both treatment-naïve and treatment-resistant depressed patients irrespective of whether there is folate deficiency., Depressed patients with both low and normal folate levels may benefit from augmenting a primary antidepressant medication either initially, at the onset of treatment, or later after some degree of treatment resistance has been recognized., The results of this study suggest that intake of vitamin B9 may modulate the total score of Center for Epidemiological Studies Depression Scale (CES-D) and two subscales of the CES-D including depressive affect and interpersonal difficulties., The results of this study suggest that intake of vitamin B9 may modulate the total score of Center for Epidemiological Studies Depression Scale (CES-D) and two subscales of the CES-D including depressive affect and interpersonal difficulties. , This article reviews the metabolic and clinical importance of folate, vitamin B12, and SAMe, as well as clinical trials in relation to depression and dementia, In particular, vitamins B1, B3, B6, B9 and B12 are essential for neuronal function and deficiencies have been linked to depression.[SEP]Relations: Folic acid has relations: drug_drug with Amphotericin B, drug_drug with Amphotericin B, contraindication with diabetes mellitus (disease), contraindication with diabetes mellitus (disease), drug_drug with Blonanserin, drug_drug with Blonanserin, drug_drug with Brincidofovir, drug_drug with Brincidofovir. Thiamine has relations: drug_protein with SLC19A2, drug_protein with SLC19A2.", "label": "yes"}
{"id": "converted_231", "sentence1": "Do orphan and gene related CpG islands follow power-law-like distributions?", "sentence2": "Orphan and gene related CpG Islands follow power-law-like distributions in several genomes: evidence of function-related and taxonomy-related modes of distribution., Here, an investigation of their distributional characteristics in a variety of genomes is undertaken for both whole CGI populations as well as for CGI subsets that lie away from known genes (gene-unrelated or \"orphan\" CGIs). In both cases power-law-like linearity in double logarithmic scale is found.,  Our results on power-law-like linearity found in orphan CGI populations suggest that the observed distributional pattern is independent of the analogous pattern that protein coding segments were reported to follow. The power-law-like patterns in the genomic distributions of CGIs described herein are found to be compatible with several other features of the composition, abundance or functional role of CGIs reported in the current literature across several genomes, on the basis of the proposed evolutionary model., Our results on power-law-like linearity found in orphan CGI populations suggest that the observed distributional pattern is independent of the analogous pattern that protein coding segments were reported to follow., The power-law-like patterns in the genomic distributions of CGIs described herein are found to be compatible with several other features of the composition, abundance or functional role of CGIs reported in the current literature across several genomes, on the basis of the proposed evolutionary model., Our results on power-law-like linearity found in orphan CGI populations suggest that the observed distributional pattern is independent of the analogous pattern that protein coding segments were reported to follow. , Our results on power-law-like linearity found in orphan CGI populations suggest that the observed distributional pattern is independent of the analogous pattern that protein coding segments were reported to follow. The power-law-like patterns in the genomic distributions of CGIs described herein are found to be compatible with several other features of the composition, abundance or functional role of CGIs reported in the current literature across several genomes, on the basis of the proposed evolutionary model., Initially, they were assigned the role of transcriptional regulation of protein-coding genes, especially the house-keeping ones, while more recently there is found evidence that they are involved in several other functions as well, which might include regulation of the expression of RNA genes, DNA replication etc. Here, an investigation of their distributional characteristics in a variety of genomes is undertaken for both whole CGI populations as well as for CGI subsets that lie away from known genes (gene-unrelated or \"orphan\" CGIs). In both cases power-law-like linearity in double logarithmic scale is found. , Our results on power-law-like linearity found in orphan CGI populations suggest that the observed distributional pattern is independent of the analogous pattern that protein coding segments were reported to follow., The power-law-like patterns in the genomic distributions of CGIs described herein are found to be compatible with several other features of the composition, abundance or functional role of CGIs reported in the current literature across several genomes, on the basis of the proposed evolutionary model., Our results on power-law-like linearity found in orphan CGI populations suggest that the observed distributional pattern is independent of the analogous pattern that protein coding segments were reported to follow.[SEP]", "label": "yes"}
{"id": "converted_1563", "sentence1": "Are cyclophilins ubiquitously expressed?", "sentence2": "Cyclophilin from Leishmania donovani (LdCyp) is a ubiquitous peptidyl-prolyl cis-trans isomerase, Cyclophilins (CYPs) and FK506-binding proteins (FKBPs) are ubiquitous proteins belonging to the peptidyl-prolyl cis/trans isomerase (PPIase) family.,  However, their wide distribution and ubiquitous nature signifies their fundamental importance in plant survival., Cyclophilins (Cyps) are ubiquitous proteins that effect the cis-trans isomerization of Pro amide bonds, and are thus crucial to protein folding., FK506 binding proteins (FKBPs) and cyclophilins (CYPs) are abundant and ubiquitous proteins belonging to the peptidyl-prolyl cis/trans isomerase (PPIase) superfamily, which regulate much of metabolism through a chaperone or an isomerization of proline residues during protein folding., Cyclophilin is a ubiquitous peptidyl prolyl cis/trans isomerase that plays critical roles in many biological processes., The receptor for cyclosporin is the protein cyclophilin, which is a ubiquitous peptidylprolyl isomerase. , Cyps (cyclophilins) are ubiquitous proteins of the immunophilin superfamily with proposed functions in protein folding, protein degradation, stress response and signal transduction. , Cyclophilins are folding helper enzymes belonging to the class of peptidyl-prolyl cis-trans isomerases (PPIases; EC 5.2.1.8) that catalyze the cis-trans isomerization of peptidyl-prolyl bonds in proteins. They are ubiquitous proteins present in almost all living organisms analyzed to date, with extremely rare exceptions., Immunophilins are ubiquitous enzymes responsible for proline isomerisation during protein synthesis and for the chaperoning of several membrane proteins., Cyclophilins (CyPs) are a large class of highly conserved ubiquitous peptidyl-prolyl cis-trans isomerases., Cyclophilins belong to the family of peptidyl-prolyl cis/trans isomerases (PPIases), which are ubiquitous and highly conserved enzymes capable of cis/trans isomerizing Xaa-Pro peptide bonds. , Originally identified as the cellular targets of immunosuppressant drugs, the immunophilins encompass two ubiquitous protein families: the FK-506 binding proteins or FKBPs, and the cyclosporin-binding proteins or cyclophilins.[SEP]Relations: Cyclosporine has relations: drug_drug with Gatifloxacin, drug_drug with Gatifloxacin, drug_drug with Etoposide, drug_drug with Etoposide, drug_drug with Genistein, drug_drug with Genistein, drug_drug with Hypericin, drug_drug with Hypericin, drug_drug with Alogliptin, drug_drug with Alogliptin.", "label": "yes"}
{"id": "converted_1950", "sentence1": "Do T-Cells regulate neuropathic pain?", "sentence2": "here is evidence for a considerable impact of the immune system also in neuropathic pain. However, the role of the adaptive immune system is still unclear.,  Our investigation revealed a clear shift of T-cell subsets towards anti-inflammation in patients with neuropathic pain. ,  GITRL expressed on macrophages drives cytokine release and T cell activation, resulting in neuropathic pain via GITR-dependent actions. , Thus, this T-cell subset may be specifically targeted to alleviate chronic neuropathic pain.<CopyrightInformation>Copyright © 2012 International Association for the Study of Pain, Recent studies show that T cells play an important role in neuropathic pain following nerve injury in rats, These results show a peripheral pivotal role of CatS in the development of neuropathic pain through the antigen-specific activation of CD4(+) T-cells, Chemokine (C-C motif) ligand 1 (CCL-1), a well-characterized chemokine secreted by activated T cells, has been shown to play an important role in neuropathic pain induced by nerve injury and is also produced in various cell types in the CNS, especially in dorsal root ganglia (DRG), In the present study, we investigated systemic T-cell subset responses and T-cell related cytokine profiles in patients with chronic neuropathic pain., Anti-inflammatory T-cell shift in neuropathic pain., Thus, this T-cell subset may be specifically targeted to alleviate chronic neuropathic pain.., Regulatory T cells attenuate neuropathic pain following peripheral nerve injury and experimental autoimmune neuritis., Macrophage-T cell interactions mediate neuropathic pain through the glucocorticoid-induced tumor necrosis factor ligand system.[SEP]Relations: neuropathy, painful has relations: disease_phenotype_positive with Peripheral neuropathy, disease_phenotype_positive with Peripheral neuropathy, disease_protein with THBD, disease_protein with THBD, disease_phenotype_positive with Fever, disease_phenotype_positive with Fever, disease_phenotype_positive with Skeletal muscle atrophy, disease_phenotype_positive with Skeletal muscle atrophy. Chronic pain has relations: phenotype_phenotype with Pain, phenotype_phenotype with Pain.", "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]Relations: positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator has relations: bioprocess_bioprocess with positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage, bioprocess_bioprocess with positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage, bioprocess_bioprocess with regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator, bioprocess_bioprocess with regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator, bioprocess_protein with RPL26, bioprocess_protein with RPL26, bioprocess_bioprocess with positive regulation of intrinsic apoptotic signaling pathway by p53 class mediator, bioprocess_bioprocess with positive regulation of intrinsic apoptotic signaling pathway by p53 class mediator. mitochondrial matrix has relations: cellcomp_protein with AASS, cellcomp_protein with AASS.", "label": "yes"}
{"id": "converted_2040", "sentence1": "Does Yersinia pestis causes a respiratory infection?", "sentence2": "Inhalation of Yersinia pestis results in primary pneumonic plague, a highly lethal and rapidly progressing necrotizing pneumonia, Yersinia pestis causes the fatal respiratory disease pneumonic plague., Pulmonary infection by Yersinia pestis causes pneumonic plague, a rapidly progressing and often fatal disease., Pulmonary infection with the bacterium Yersinia pestis causes pneumonic plague, an often-fatal disease for which no vaccine is presently available., Yersinia pestis causes the fatal respiratory disease pneumonic plague, Pneumonic plague is a deadly respiratory disease caused by Yersinia pestis, On July 8, 2014, the Colorado Department of Public Health and Environment (CDPHE) laboratory identified Yersinia pestis, the bacterium that causes plague, in a blood specimen collected from a man (patient A) hospitalized with pneumonia., Early emergence of Yersinia pestis as a severe respiratory pathogen., The aerosol form of the bacterium Yersinia pestis causes the pneumonic plague, a rapidly fatal disease,  plague bacterium, Yersinia pestis, has historically been regarded as one of the deadliest pathogens known to mankind, having caused three major pandemics. After being transmitted by the bite of an infected flea arthropod vector, Y. pestis can cause three forms of human plague: bubonic, septicemic, and pneumonic,, Plague is an infectious disease caused by the Yersinia pestis microorganism, which is transmitted to the human host from a natural reservoir (different rodent species) by a flea bite. Plague is still encountered in humans in the areas of its enzootic prevalence in local rodent populations. Infection by flea bite results in a bubonic or septicemic plague, possibly complicated by secondary pneumonia. The person with pneumonic symptoms may be a source of a droplet-borne inhalatory infection for other people who consequently develop primary pneumonic plague. , uring pneumonic plague, the bacterium Yersinia pestis elicits the development of inflammatory lung lesions that continue to expand throughout infection. , In November 2006, the Uganda Ministry of Health received reports of an increase in bubonic plague cases and a possible outbreak of pneumonic plague among residents in the Arua and Nebbi districts. , Pneumonic plague is a fatal disease caused by Yersinia pestis that is associated with a delayed immune response in the lungs[SEP]Relations: lower respiratory tract disease has relations: contraindication with Fluticasone furoate, contraindication with Fluticasone furoate, disease_disease with lung disease, disease_disease with lung disease, contraindication with Fluticasone propionate, contraindication with Fluticasone propionate, disease_disease with respiratory system disease, disease_disease with respiratory system disease, contraindication with Flunisolide, contraindication with Flunisolide.", "label": "yes"}
{"id": "converted_856", "sentence1": "Is Dicer part of the RISC loading complex?", "sentence2": "Dicer is a component of the protein machinery (the RNA Induced Silencing Complex [RISC]) which is involved in catalyzing the formation of mature microRNAs from their precursors in the process of microRNA biogenesis., RNA-induced silencing complex (RISC) Proteins PACT, TRBP, and Dicer are SRA binding nuclear receptor coregulators., The cytoplasmic RNA-induced silencing complex (RISC) contains dsRNA binding proteins, including protein kinase RNA activator (PACT), transactivation response RNA binding protein (TRBP), and Dicer, that process pre-microRNAs into mature microRNAs (miRNAs) that target specific mRNA species for regulation. ,  Although the major RNAi pathway proteins are found in most subcellular compartments, the miRNA- and siRNA-loaded Ago2 populations co-sediment almost exclusively with the rER membranes, together with the RISC loading complex (RLC) factors Dicer, TAR RNA binding protein (TRBP) and protein activator of the interferon-induced protein kinase (PACT)., RNA interference (RNAi) is mediated by small interfering RNAs (siRNAs), which are liberated from double-stranded (ds)RNA precursors by Dicer and guide the RNA-induced silencing complex (RISC) to targets., . Dicer, an RNase III enzyme, plays a central role in the RNAi pathway by cleaving precursors of both of these classes of RNAs to form mature siRNAs and miRNAs, which are then loaded into the RNA-induced silencing complex (RISC). , Canonical siRNAs are 21 nucleotides (nt) in length and are loaded to the RNA Induced Silencing Complex when introduced into the cells, while longer siRNA molecules are first processed by endogenous Dicer and thus termed Dicer-substrate siRNA (DsiRNA). [SEP]Relations: protein binding has relations: molfunc_protein with DICER1, molfunc_protein with DICER1, molfunc_protein with ECSCR, molfunc_protein with ECSCR, molfunc_protein with RILP, molfunc_protein with RILP, molfunc_protein with TRIR, molfunc_protein with TRIR. chromatin silencing complex has relations: cellcomp_protein with RRP8, cellcomp_protein with RRP8.", "label": "yes"}
{"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]Relations: Elevated hemoglobin A1c has relations: disease_phenotype_positive with neonatal diabetes mellitus, disease_phenotype_positive with neonatal diabetes mellitus, disease_phenotype_positive with maturity-onset diabetes of the young, disease_phenotype_positive with maturity-onset diabetes of the young, phenotype_phenotype with Abnormal hemoglobin, phenotype_phenotype with Abnormal hemoglobin. hemoglobinopathy has relations: disease_protein with HBA1, disease_protein with HBA1, disease_protein with HBA2, disease_protein with HBA2.", "label": "no"}
{"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_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_904", "sentence1": "Are there any desmins present in plants?", "sentence2": "Inherited mutations in the gene coding for the intermediate filament protein desmin have been demonstrated to cause severe skeletal and cardiac myopathies., Mutations in the intermediate filament (IF) protein desmin cause severe forms of myofibrillar myopathy characterized by partial aggregation of the extrasarcomeric desmin cytoskeleton and structural disorganization of myofibrils., The family of 70 intermediate filament genes (including those encoding keratins, desmins, and lamins) is now known to be associated with a wide range of diverse diseases, at least 72 distinct human pathologies, including skin blistering, muscular dystrophy, cardiomyopathy, premature aging syndromes, neurodegenerative disorders, and cataract. , Mutations in desmin have been associated with a subset of human myopathies., Characterization of a zebrafish (Danio rerio) desmin cDNA: an early molecular marker of myogenesis., Acute effects of desmin mutations on cytoskeletal and cellular integrity in cardiac myocytes., Desmin is a muscle-specific protein and a constitutive subunit of the intermediate filaments (IF) in skeletal, cardiac and smooth muscles. It is an early marker of skeletal muscle myogenesis. We have characterized a clone of desmin cDNA from an embryonic zebrafish (Danio rerio) cDNA library. , Immunohistochemical investigation showed a positive reaction for smooth muscle actin and desmins in the spindle cells proliferated in the lymph nodes; no cytokeratin positivity was detected. , We have raised monoclonal antibodies (Mab) to the Mr 55,000 desmin polypeptide, electrophoretically purified from cytoskeletal preparations of isolated bovine heart Purkinje fibers. , Mesothelial and ovarian carcinoma cells could not be distinguished by (intermediate) filament typing, using monoclonal antibodies (MAbs) to keratins, vimentins and desmins., A fast and convenient procedure for the purification of polymerization-competent smooth-muscle desmin is described. Desmin from chicken gizzard and hog stomach were compared by fingerprint techniques. [SEP]Relations: Protein S human has relations: drug_drug with Desmoteplase, drug_drug with Desmoteplase, drug_drug with Desirudin, drug_drug with Desirudin, drug_drug with Desogestrel, drug_drug with Desogestrel, drug_drug with Desvenlafaxine, drug_drug with Desvenlafaxine. smooth muscle tissue has relations: anatomy_protein_present with DESI2, anatomy_protein_present with DESI2.", "label": "no"}
{"id": "converted_878", "sentence1": "Is dichlorphenamide effective for periodic paralysis?", "sentence2": "BACKGROUND AND PURPOSE: Acetazolamide and dichlorphenamide are carbonic anhydrase (CA) inhibitors effective in the clinical condition of hypokalemic periodic paralysis (hypoPP)., In one study dichlorphenamide (DCP) vs placebo was tested in two groups of participants: 42 with hypokalemic periodic paralysis (HypoPP) and 31 with hyperkalemic periodic paralysis (HyperPP), based on clinical criteria. Thirty-four of 42 participants with hypokalemic periodic paralysis completed both treatment phases. For the 34 participants having attack rate data for both treatment phases, the mean improvement in attack rate (P = 0.02) and severity-weighted attack rate (P = 0.01) on DCP relative to placebo were statistically significant. , AUTHORS' CONCLUSIONS: The largest included study that met our inclusion criteria suggested that DCP was effective in the prevention of episodic weakness in both hypokalemic and hyperkalemic periodic paralyses., For periodic paralysis, dichlorphenamide--a carbonic anhydrase inhibitor--has been shown in a controlled trial to prevent attacks for many patients with both hypokalemic and hypokalemic periodic paralysis. , Chronically, acetazolamide, dichlorphenamide, or potassium-sparing diuretics decrease attack frequency and severity but are of little value acutely. ,  In the HypoPP trial, there were 13 subjects who exhibited a preference (in terms of the end point) for either DCP or placebo, and 11 of these preferred DCP. In the PSPP trial, DCP significantly reduced attack rates relative to placebo. DCP also significantly reduced attack rates relative to placebo in the HypoPP subjects. We conclude that DCP is effective in the prevention of episodic weakness in both HypoPP and PSPP., Diclofenamid has now already been administered for 2 years. It is well tolerated and has suppressed further attacks., Three patients with Hypokalemic Periodic Paralysis (HOPP)-associated progressive interattack muscle weakness, who became unresponsive or worsened by acetazolamide, responded favorably to dichlorophenamide, a more potent carbonic anhydrase inhibitor. Dichlorophenamide in single-blind placebo-controlled trials, considerably improved functional strength in two of the patients and had a moderate but definite effect in the third., Dichlorophenamide should be considered as an alternate to acetazolamide in the treatment of patients with HOPP-associated interattack muscle weakness who have become unresponsive or worsened by acetazolamide., Acetazolamide and dichlorphenamide are carbonic anhydrase (CA) inhibitors effective in the clinical condition of hypokalemic periodic paralysis (hypoPP)., For periodic paralysis, dichlorphenamide--a carbonic anhydrase inhibitor--has been shown in a controlled trial to prevent attacks for many patients with both hypokalemic and hypokalemic periodic paralysis., BACKGROUND AND PURPOSE: Acetazolamide and dichlorphenamide are carbonic anhydrase (CA) inhibitors effective in the clinical condition of hypokalemic periodic paralysis (hypoPP). Whether these drugs prevent vacuolar myopathy, which is a pathogenic factor in hypoPP, is unknown. , Acetazolamide and dichlorphenamide are carbonic anhydrase (CA) inhibitors effective in the clinical condition of hypokalemic periodic paralysis (hypoPP)., For periodic paralysis, dichlorphenamide--a carbonic anhydrase inhibitor--has been shown in a controlled trial to prevent attacks for many patients with both hypokalemic and hypokalemic periodic paralysis. A second trial, comparing dichlorphenamide with acetazolamide versus placebo, is currently in progress., Despite our better understanding of the pathogenesis of these disorders, current treatments are largely empirical and the evidence in favor of specific therapy largely anecdotal. For periodic paralysis, dichlorphenamide--a carbonic anhydrase inhibitor--has been shown in a controlled trial to prevent attacks for many patients with both hypokalemic and hypokalemic periodic paralysis.[SEP]Relations: hypokalemic periodic paralysis has relations: contraindication with Desflurane, contraindication with Desflurane. hyperkalemic periodic paralysis has relations: contraindication with Phenylephrine, contraindication with Phenylephrine, contraindication with Ammonium chloride, contraindication with Ammonium chloride, contraindication with Sodium citrate, contraindication with Sodium citrate, contraindication with Calcium chloride, contraindication with Calcium chloride.", "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]Relations: progressive supranuclear palsy has relations: disease_phenotype_positive with Parkinsonism with favorable response to dopaminergic medication, disease_phenotype_positive with Parkinsonism with favorable response to dopaminergic medication, disease_disease with supranuclear oculomotor palsy, disease_disease with supranuclear oculomotor palsy, disease_disease with syndromic disease, disease_disease with syndromic disease, disease_phenotype_positive with Neuromuscular dysphagia, disease_phenotype_positive with Neuromuscular dysphagia, disease_phenotype_positive with Retrocollis, disease_phenotype_positive with Retrocollis.", "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]Relations: alpha-amylase activity has relations: molfunc_protein with AMY1A, molfunc_protein with AMY1A, molfunc_protein with AMY2A, molfunc_protein with AMY2A, molfunc_protein with AMY1C, molfunc_protein with AMY1C, molfunc_protein with AMY2B, molfunc_protein with AMY2B, molfunc_protein with AMY1B, molfunc_protein with AMY1B.", "label": "yes"}
{"id": "converted_3561", "sentence1": "Is Niraparib effective for ovarian cancer?", "sentence2": "Niraparib and olaparib have been approved by the US FDA for maintenance therapy after partial or complete remission in recurrent ovarian cancer., PURPOSE OF REVIEW: The recent United States Food and Drug Administration approvals of niraparib and olaparib as maintenance monotherapy for platinum-sensitive, high-grade ovarian cancers independent of BRCA status reflect a willingness to seek indications for poly-ADP-ribose polymerase (PARP) inhibitors beyond cancers with deleterious breast cancer 1 and breast cancer 2 mutations., PURPOSE: Niraparib is a highly selective inhibitor of PARP-1 and PARP-2 approved in the United States for maintenance treatment of adult patients with recurrent ovarian cancer in complete or partial response to platinum-based chemotherapy., Indeed, three PARP1 inhibitors (Olaparib, Rucaparib, and Niraparib) have recently been approved by the Food and Drug Administration for the treatment of ovarian cancer., Niraparib is an oral poly(ADP ribose) polymerase (PARP) inhibitor that is currently approved by the United States Food and Drug Administration (US FDA) as well as recently approved by the European Medicines Agency (EMA) for the maintenance treatment of women with recurrent ovarian cancer who are in complete or partial response to platinum-based chemotherapy. , Niraparib is a poly adenosine diphosphate ribose polymerase inhibitor that has shown to be clinically effective as maintenance therapy in patients with platinum sensitive, recurrent ovarian cancer., Niraparib Maintenance Therapy in Platinum-Sensitive, Recurrent Ovarian Cancer., Niraparib for the treatment of ovarian cancer., BACKGROUND\n\nNiraparib is an oral poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) 1/2 inhibitor that has shown clinical activity in patients with ovarian cancer., Niraparib Slows Ovarian Cancer Progression., Niraparib for the treatment of ovarian cancer., INTRODUCTION\n\nNiraparib, an orally available selective inhibitor of poly(adenosine diphosphate-ribose) polymerase (PARP), is the first PARP inhibitor approved for use in patients with ovarian cancer who do not harbor a germ-line or somatic mutation in the breast cancer gene (BRCA)., The role of niraparib as maintenance following frontline platinum-based chemotherapy as well as in the treatment of recurrent high-grade serous ovarian cancer is an active area of investigation., Niraparib in ovarian cancer: results to date and clinical potential., Niraparib , an orally available selective inhibitor of poly(adenosine diphosphate-ribose ) polymerase ( PARP) , is the first PARP inhibitor approved for use in patients with ovarian cancer who do not harbor a germ-line or somatic mutation in the breast cancer gene ( BRCA) . , Results from a phase III trial indicate that maintenance therapy with the PARP inhibitor niraparib is more effective than placebo in slowing the progression of recurrent platinum-sensitive ovarian cancer . , Niraparib (Zejula®), a poly (ADP-ribose) polymerase (PARP) inhibitor, is approved for the maintenance treatment of recurrent, epithelial ovarian, fallopian tube, or primary peritoneal cancer in patients who are in complete or partial response to platinum-based chemotherapy., Niraparib, an orally available selective inhibitor of poly(adenosine diphosphate-ribose) polymerase (PARP), is the first PARP inhibitor approved for use in patients with ovarian cancer who do not harbor a germ-line or somatic mutation in the breast cancer gene (BRCA)., Current evidence suggests that niraparib is an effective new option with a manageable tolerability profile for the maintenance treatment of recurrent, platinum-sensitive epithelial ovarian, fallopian tube, or primary peritoneal cancer in adults, with or without BRCA1/2 mutation or HRD., Oral niraparib, a highly-selective, potent poly(ADP-ribose) polymerase (PARP)-1 and PARP-2 inhibitor, is approved in the USA for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy., This article summarizes the milestones in the development of niraparib leading to its first global approval for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube or primary peritoneal cancer., Niraparib (Zejula ), a poly (ADP-ribose) polymerase (PARP) inhibitor, is approved for the maintenance treatment of recurrent, epithelial ovarian, fallopian tube, or primary peritoneal cancer in patients who are in complete or partial response to platinum-based chemotherapy., INTRODUCTION: Niraparib, an orally available selective inhibitor of poly(adenosine diphosphate-ribose) polymerase (PARP), is the first PARP inhibitor approved for use in patients with ovarian cancer who do not harbor a germ-line or somatic mutation in the breast cancer gene (BRCA).[SEP]Relations: Niraparib has relations: drug_protein with PARP1, drug_protein with PARP1, drug_drug with Erythropoietin, drug_drug with Erythropoietin, drug_protein with GUSB, drug_protein with GUSB, drug_protein with PARP2, drug_protein with PARP2, drug_drug with Peginesatide, drug_drug with Peginesatide.", "label": "yes"}
{"id": "converted_3677", "sentence1": "Has the Spanich flu virus been reconstructed?", "sentence2": "Reconstruction of the 1918 influenza virus has facilitated considerable advancements in our understanding of this extraordinary pandemic virus., These viral RNA sequences eventually permitted reconstruction of the complete 1918 virus, which has yielded, almost a century after the deaths of its victims, novel insights into influenza virus biology and pathogenesis and has provided important information about how to prevent and control future pandemics., Reconstruction of the 1918 virus and studies elucidating the exceptional virulence and transmissibility of the virus are providing exciting new insights into this devastating pandemic strain. [SEP]Relations: Cessation of head growth has relations: disease_phenotype_positive with leukoencephalopathy with vanishing white matter, disease_phenotype_positive with leukoencephalopathy with vanishing white matter, disease_phenotype_positive with Angelman syndrome due to a point mutation, disease_phenotype_positive with Angelman syndrome due to a point mutation, disease_phenotype_positive with Angelman syndrome due to paternal uniparental disomy of chromosome 15, disease_phenotype_positive with Angelman syndrome due to paternal uniparental disomy of chromosome 15, disease_phenotype_positive with Angelman syndrome due to maternal 15q11q13 deletion, disease_phenotype_positive with Angelman syndrome due to maternal 15q11q13 deletion, disease_phenotype_positive with neurodevelopmental disorder with progressive microcephaly, spasticity, and brain anomalies, disease_phenotype_positive with neurodevelopmental disorder with progressive microcephaly, spasticity, and brain anomalies.", "label": "yes"}
{"id": "converted_3006", "sentence1": "Is galcanezumab effective for treatment of migraine?", "sentence2": "Importance: Galcanezumab (LY2951742), a monoclonal antibody against calcitonin gene-related peptide (CGRP), is one of a novel class of new medicines for migraine prevention., Conclusions and Relevance: Monthly subcutaneous injections of galcanezumab, both 120 mg and 300 mg, demonstrated efficacy (repeated-measures analysis) for the preventive treatment of migraine and support further development in larger phase 3 studies. , PURPOSE OF REVIEW: Monoclonal antibodies (mAbs) targeting the calcitonin-gene-related peptide (CGRP) pathway have been developed for episodic and chronic migraine prevention, either through binding the CGRP ligand (eptinezumab, fremanezumab, galcanezumab) or the CGRP receptor (erenumab)., Background Safety findings from a Phase 2b study of galcanezumab, a humanized monoclonal antibody against calcitonin gene-related peptide, for prevention of migraine (NCT02163993) are reported here., Safety of galcanezumab in patients with episodic migraine: A randomized placebo-controlled dose-ranging Phase 2b study., Currently, there is considerable excitement regarding monoclonal antibodies against calcitonin gene-related peptide (eptinezumab, galcanezumab, fremanezumab) and the calcitonin gene-related peptide receptor (erenumab). To date, these monoclonal antibodies have shown promising efficacy in clinical trials, with no major safety concerns. If ongoing long-term studies show that their efficacy can be maintained, this may herald a new era for effective antimigraine therapies., CGRP receptor antagonists such as ubrogepant are effective for acute relief of migraine headache, whereas monoclonal antibodies against CGRP (eptinezumab, fremanezumab and galcanezumab) or the CGRP receptor (erenumab) effectively prevent migraine attacks. , Four monoclonal antibodies (mAbs) targeting the CGRP pathway are currently under evaluation for the prevention of episodic and chronic migraine: eptinezumab (ALD403), fremanezumab (TEV-48125), galcanezumab (LY2951742), and erenumab (AMG334). , Introduction Galcanezumab is a humanized monoclonal antibody binding calcitonin gene-related peptide, used for migraine prevention., Efficacy and safety of galcanezumab for the prevention of episodic migraine: Results of the EVOLVE-2 Phase 3 randomized controlled clinical trial., Galcanezumab induced a robust, dose-dependent, and durable inhibition of capsaicin-induced increase in DBF, supporting the continued clinical development of galcanezumab for prophylaxis in migraine patients., The efficacy and safety of calcitonin gene-related peptide monoclonal antibody for episodic migraine: a meta-analysis.Based on the results of this meta-analysis, CGRP monoclonal antibodies significantly reduced the monthly migraine days and acute migraine-specific medication. , Importance\nGalcanezumab (LY2951742), a monoclonal antibody against calcitonin gene-related peptide (CGRP), is one of a novel class of new medicines for migraine prevention., Galcanezumab appears efficacious, safe, and well tolerated for the preventive treatment of chronic migraine., BACKGROUND\nGalcanezumab is a humanized monoclonal antibody that selectively binds to the calcitonin gene-related peptide (CGRP) and has demonstrated efficacy in reducing migraine headache days (MHD) in patients with episodic and chronic migraine., BACKGROUND\nGalcanezumab, a humanized monoclonal antibody that selectively binds to the calcitonin gene-related peptide, has demonstrated in previous Phase 2 and Phase 3 clinical studies (≤6-month of treatment) a reduction in the number of migraine headache days and improved patients' functioning., CONCLUSION\nTwelve months of treatment with self-administered injections of galcanezumab was safe and associated with a reduction in the number of monthly migraine headache days., CGRP receptor antagonists such as ubrogepant are effective for acute relief of migraine headache, whereas monoclonal antibodies against CGRP (eptinezumab, fremanezumab and galcanezumab) or the CGRP receptor (erenumab) effectively prevent migraine attacks., Conclusions and Relevance\nMonthly subcutaneous injections of galcanezumab, both 120 mg and 300 mg, demonstrated efficacy (repeated-measures analysis) for the preventive treatment of migraine and support further development in larger phase 3 studies., Importance Galcanezumab (LY2951742), a monoclonal antibody against calcitonin gene-related peptide (CGRP), is one of a novel class of new medicines for migraine prevention., BACKGROUND Galcanezumab, a humanized monoclonal antibody that selectively binds to the calcitonin gene-related peptide, has demonstrated in previous Phase 2 and Phase 3 clinical studies (≤6-month of treatment) a reduction in the number of migraine headache days and improved patients' functioning., BACKGROUND Galcanezumab is a humanized monoclonal antibody that selectively binds to the calcitonin gene-related peptide (CGRP) and has demonstrated efficacy in reducing migraine headache days (MHD) in patients with episodic and chronic migraine., Both galcanezumab dose groups demonstrated greater overall mean reduction in the number of monthly MHDs compared to placebo (placebo -2.7, galcanezumab 120 mg -4.8, galcanezumab 240 mg -4.6) (<br><b>CONCLUSIONS</b>: Both doses of galcanezumab were superior to placebo in reducing the number of monthly MHDs., Galcanezumab appears efficacious, safe, and well tolerated for the preventive treatment of chronic migraine.<br><b>CLINICALTRIALSGOV IDENTIFIER</b>: NCT02614261.<br><b>CLASSIFICATION OF EVIDENCE</b>: This interventional study provides Class I evidence that galcanezumab is superior to placebo in the reduction of the number of monthly MHDs.<br>, In September 2018, the US FDA approved galcanezumab as a once-monthly subcutaneous injection for the preventive treatment of migraine in adults., This article summarizes the milestones in the development of galcanezumab leading to its first approval for the preventive treatment of migraine in adults.<br>, Galcanezumab appears efficacious, safe, and well tolerated for the preventive treatment of chronic migraine., This article summarizes the milestones in the development of galcanezumab leading to its first approval for the preventive treatment of migraine in adults., Twelve months of treatment with self-administered injections of galcanezumab was safe and associated with a reduction in the number of monthly migraine headache days.[SEP]Relations: Galcanezumab has relations: drug_drug with Galiximab, drug_drug with Galiximab, drug_drug with Abrilumab, drug_drug with Abrilumab, drug_drug with Matuzumab, drug_drug with Matuzumab, drug_drug with Fremanezumab, drug_drug with Fremanezumab, drug_drug with Erenumab, drug_drug with Erenumab.", "label": "yes"}
{"id": "converted_900", "sentence1": "Are there plasma membrane receptors for thyroid hormones?", "sentence2": "ntegrins are heterodimeric structural components of the plasma membrane whose ligands include a large number of extracellular matrix (ECM) proteins. , Recently, integrin αvβ3 has been shown to have a panel of previously unappreciated small molecule receptor sites for thyroid hormone and hormone analogues, for dihydrotestosterone, and for resveratrol, a polyphenol that has certain estrogen-like features., The integrin receptor activation by T4 may take a role in plasma membrane processes involved in the male reproductive system., Rapid signaling via this plasma membrane binding site appears to be responsible for many nongenomic effects of thyroid hormones, independent of the classic nuclear receptors.[SEP]Relations: plasma membrane has relations: cellcomp_protein with DTNA, cellcomp_protein with DTNA, cellcomp_protein with TSHR, cellcomp_protein with TSHR, cellcomp_protein with DTNB, cellcomp_protein with DTNB, cellcomp_protein with WAS, cellcomp_protein with WAS, cellcomp_protein with TDG, cellcomp_protein with TDG.", "label": "yes"}
{"id": "converted_1477", "sentence1": "Does HuR protein regulate the splicing process?", "sentence2": "HuR and TIA1/TIAL1 are involved in regulation of alternative splicing of SIRT1 pre-mRNA, Here we describe experiments showing that HuR and TIA1/TIAL1, two kinds of RNA-binding proteins, were involved in the regulation of alternative splicing of SIRT1 pre-mRNA under normal and stress circumstances, HuR increased SIRT1-∆Exon8 by promoting SIRT1 exon 8 exclusion, whereas TIA1/TIAL1 inhibition of the exon 8 exclusion led to a decrease in SIRT1-∆Exon8 mRNA levels. , HuR regulates alternative splicing of the TRA2β gene in human colon cancer cells under oxidative stress, Hu antigen R (HuR) regulates stress responses through stabilizing and/or facilitating the translation of target mRNAs, We show here that the RBP embryonic lethal abnormal vision like 1 (ELAVL1, also know as HuR) regulates the alternative splicing of eukaryotic translation initiation factor 4E nuclear import factor 1 (Eif4enif1), which encodes an eukaryotic translation initiation factor 4E transporter (4E-T) protein and suppresses the expression of capped mRNAs, Further, endothelial-specific Elavl1 knockout mice exhibited reduced revascularization after hind limb ischemia and tumor angiogenesis in oncogene-induced mammary cancer, resulting in attenuated blood flow and tumor growth, respectively. , Changes in cellular mRNA stability, splicing, and polyadenylation through HuR protein sequestration by a cytoplasmic RNA virus, Furthermore, significant changes can be observed in nuclear alternative polyadenylation and splicing events on cellular pre-mRNAs as a result of sequestration of HuR protein by the 3' UTR of transcripts of this cytoplasmic RNA virus., Here we demonstrate that expression of 2A(pro) induces a selective nucleo-cytoplasm translocation of several important RNA binding proteins and splicing factors. Subcellular fractionation studies, together with immunofluorescence microscopy revealed an asymmetric distribution of HuR and TIA1/TIAR in 2A(pro) expressing cells, which modulates splicing of the human Fas exon 6, knockdown of HuR or overexpression of TIA1/TIAR, leads to Fas exon 6 inclusion in 2A(pro)-expressing cells, The differential expression levels of T-cell intracellular antigens (TIA) and Hu antigen R (HuR) are concomitant with a splicing switch in apoptosis receptor Fas in HCT-116 cells, overexpression and knockdown of HuR led to Fas exon 6 skipping and inclusion, respectively. These results suggest that the TIA and HuR cellular ratio influences cell-type specific Fas exon 6 splicing pattern., Hu antigen R (HuR) functions as an alternative pre-mRNA splicing regulator of Fas apoptosis-promoting receptor on exon definition, antiapoptotic regulator Hu antigen R (HuR, ELAVL1), a member of the embryonic lethal, abnormal vision, Drosophila-like (ELAVL) family, promotes Fas exon 6 skipping by binding to an exonic splicing silencer, ELAV/Hu proteins bind to AU-rich elements (ARE) in mRNAs and regulate their stability from splicing to translation, and the ubiquitous HuR protein has been implicated in cancerous cell growth., The HuR protein regulates the expression of thousands of cellular transcripts by modulating mRNA splicing, trafficking, translation, and stability., Hu antigen R (HuR) functions as an alternative pre-mRNA splicing regulator of Fas apoptosis-promoting receptor on exon definition., I report that antiapoptotic regulator Hu antigen R (HuR, ELAVL1), a member of the embryonic lethal, abnormal vision, Drosophila-like (ELAVL) family, promotes Fas exon 6 skipping by binding to an exonic splicing silencer. , Changes in cellular mRNA stability, splicing, and polyadenylation through HuR protein sequestration by a cytoplasmic RNA virus., Further, the silencing capacity of HuR as splicing regulator resides in the RRM1 and hinge-RRM3 domains. , HuR and TIA1/TIAL1 are involved in regulation of alternative splicing of SIRT1 pre-mRNA., HuR regulates alternative splicing of the TRA2β gene in human colon cancer cells under oxidative stress., The HuR protein regulates the expression of thousands of cellular transcripts by modulating mRNA splicing, trafficking, translation, and stability. , Further, the silencing capacity of HuR as splicing regulator resides in the RRM1 and hinge-RRM3 domains. Taken together, these results support a functional link between HuR as repressor of alternative Fas splicing and the molecular mechanisms modulating programmed cell death., We are interested in interactions involving hnRNP proteins participating in several steps of mRNA processing (mainly pre-mRNA splicing) and HuR with an established role in stability/translation of associated mRNAs. hnRNP and HuR proteins have a major nucleoplasmic localization and ability to shuttle between nucleus and cytoplasm. We report here on interactions between hnRNP and HuR proteins that were identified in the context of isolated hnRNP and mRNP complexes. , Despite the fact that HuR sites are observed in intronic regions, our data do not support a role for HuR in regulating splicing.[SEP]Relations: RNA splicing has relations: bioprocess_protein with ZRSR2, bioprocess_protein with ZRSR2, bioprocess_protein with KHSRP, bioprocess_protein with KHSRP, bioprocess_protein with CIR1, bioprocess_protein with CIR1, bioprocess_protein with LARP7, bioprocess_protein with LARP7. protein binding has relations: molfunc_protein with HUS1, molfunc_protein with HUS1.", "label": "yes"}
{"id": "converted_3470", "sentence1": "Is overexpression of LY6K associated with better prognosis for non-small cell lung cancer patients?", "sentence2": "Gene expression profile analyses of non-small cell lung carcinomas (NSCLC) and esophageal squamous cell carcinomas (ESCC) revealed that lymphocyte antigen 6 complex locus K (LY6K) was specifically expressed in testis and transactivated in a majority of NSCLCs and ESCCs. Immunohistochemical staining using 406 NSCLC and 265 ESCC specimens confirmed that LY6K overexpression was associated with poor prognosis for patients with NSCLC (P = 0.0003), as well as ESCC (P = 0.0278), and multivariate analysis confirmed its independent prognostic value for NSCLC (P = 0.0035). , Immunohistochemical staining using 406 NSCLC and 265 ESCC specimens confirmed that LY6K overexpression was associated with poor prognosis for patients with NSCLC (P = 0.0003), as well as ESCC (P = 0.0278), and multivariate analysis confirmed its independent prognostic value for NSCLC (P = 0.0035)., Immunohistochemical staining using 406 NSCLC and 265 ESCC specimens confirmed that LY6K overexpression was associated with poor prognosis for patients with NSCLC (P = 0.0003), as well as ESCC (P = 0.0278), and multivariate analysis confirmed its independent prognostic value for NSCLC (P = 0.0035).[SEP]Relations: small cell lung carcinoma has relations: disease_protein with LYRM9, disease_protein with LYRM9, disease_protein with STK31, disease_protein with STK31, disease_protein with CYP2A6, disease_protein with CYP2A6, disease_protein with DMPK, disease_protein with DMPK, disease_protein with PYCARD, disease_protein with PYCARD.", "label": "no"}
{"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_2871", "sentence1": "Are de novo mutations in regulatory elements responsible for neurodevelopmental disorders?", "sentence2": "The role of de novo mutations in regulatory elements affecting genes associated with developmental disorders, or other genes, has been essentially unexplored. We identified de novo mutations in three classes of putative regulatory elements in almost 8,000 patients with developmental disorders. Here we show that de novo mutations in highly evolutionarily conserved fetal brain-active elements are significantly and specifically enriched in neurodevelopmental disorders. We identified a significant twofold enrichment of recurrently mutated elements. We estimate that, genome-wide, 1-3% of patients without a diagnostic coding variant carry pathogenic de novo mutations in fetal brain-active regulatory elements and that only 0.15% of all possible mutations within highly conserved fetal brain-active elements cause neurodevelopmental disorders with a dominant mechanism., We estimate that, genome-wide, 1-3% of patients without a diagnostic coding variant carry pathogenic de novo mutations in fetal brain-active regulatory elements and that only 0.15% of all possible mutations within highly conserved fetal brain-active elements cause neurodevelopmental disorders with a dominant mechanism., Here we show that de novo mutations in highly evolutionarily conserved fetal brain-active elements are significantly and specifically enriched in neurodevelopmental disorders., We estimate that, genome-wide, 1-3% of patients without a diagnostic coding variant carry pathogenic de novo mutations in fetal brain-active regulatory elements and that only 0.15% of all possible mutations within highly conserved fetal brain-active elements cause neurodevelopmental disorders with a dominant mechanism. , Here we show that de novo mutations in highly evolutionarily conserved fetal brain-active elements are significantly and specifically enriched in neurodevelopmental disorders. , De novo mutations in regulatory elements in neurodevelopmental disorders.We previously estimated that 42% of patients with severe developmental disorders carry pathogenic de novo mutations in coding sequences. [SEP]Relations: complex neurodevelopmental disorder has relations: disease_disease with developmental and epileptic encephalopathy, disease_disease with developmental and epileptic encephalopathy, disease_disease with nervous system disorder, disease_disease with nervous system disorder, disease_disease with pervasive developmental disorder, disease_disease with pervasive developmental disorder, disease_disease with Prader-Willi syndrome, disease_disease with Prader-Willi syndrome. developmental disability has relations: disease_protein with NTRK2, disease_protein with NTRK2.", "label": "yes"}