{"id": "converted_572", "sentence1": "Is phospholamban phosphorylated by Protein kinase A?", "sentence2": "cAMP-dependent protein kinase (PKA) phosphorylation of PLB, phosphorylation of PLN, at either Ser(16) by PKA , Activation of cardiac muscle sarcoplasmic reticulum Ca2+-ATPase (SERCA2a) by beta1-agonists involves cAMP- and PKA-dependent phosphorylation of phospholamban (PLB), which relieves the inhibitory effects of PLB on SERCA2a. , Phospholamban (PLB) is a sarcoplasmic reticulum (SR) protein that when phosphorylated at Ser16 by PKA, phosphorylation of PLB by the Ca2+-calmodulin-dependent protein kinase (CaMK) and cAMP-dependent protein kinase (PKA). , cAMP-dependent protein kinase (PKA)-mediated phospholamban (PLB) phosphorylation at serine-16, Phospholamban (PLB) is a major target of the beta-adrenergic cascade in the heart, functioning to modulate contractile force by altering the rate of calcium re-sequestration by the Ca-ATPase. Functionally, inhibition by PLB binding is manifested by shifts in the calcium dependence of Ca-ATPase activation toward higher calcium levels; phosphorylation of PLB by PKA reverses the inhibitory action of PLB., phosphorylation of both PLB residues (Ser16, PKA site, and Thr17, CaMKII site) , Phosphorylation of Ser(16) by PKA, stabilization of the structure of PLB following phosphorylation of Ser(16), Phospholamban (PLB) inhibits the sarcoplasmic reticulum (SR) Ca(2+)-ATPase, and this inhibition is relieved by cAMP-dependent protein kinase (PKA)-mediated phosphorylation. , Two-dimensional tryptic peptide maps of phosphorylated phospholamban indicated that cAMP-dependent protein kinase phosphorylates at a single site, A, and Ca2+-calmodulin-dependent protein kinase phosphorylates at sites C1 and C2 in the low molecular weight form, where A is different from C1 but may be the same as C2., Because SR function is regulated by phosphorylation of phospholamban (PLB), a SR protein phosphorylated by cAMP-dependent protein kinase (PKA) at Ser(16)and Ca(2+)-calmodulin-dependent protein kinase (CaMKII) at Thr(17), the phosphorylation of these residues during ischemia and reperfusion was examined in Langendorff-perfused rat hearts, These changes were associated with reduced protein expression of sarcoplasmic reticulum Ca(2+)-ATPase (SERCA2a) and protein kinase A phosphorylated phospholamban (PLB), which was reduced in HF, but essentially abolished in VD-HF, The data indicate that 1) phosphorylation of phospholamban at Ser16 by cAMP-dependent protein kinase is the main regulator of beta-adrenergic-induced cardiac relaxation definitely preceding Thr17 phosphorylation and 2) the beta-adrenergic-mediated phosphorylation of Thr17 by Ca2+-calmodulin-dependent protein kinase required influx of Ca2+ through the L-type Ca2+ channel, Here we extend this model to explain the reversal of SERCA2a inhibition that occurs after phosphorylation of PLB at Ser(16) by protein kinase A (PKA) and after binding of the anti-PLB monoclonal antibody 2D12, which recognizes residues 7-13 of PLB, Phospholamban is phosphorylated in heart by cAMP-dependent protein kinase, cGMP-dependent protein kinase and calcium/calmodulin-dependent protein kinase II (CM-kinase-II) and in smooth muscle cells by cGMP-dependent protein kinase, Phospholamban, the cardiac sarcoplasmic reticulum proteolipid, is phosphorylated by cAMP-dependent protein kinase, by Ca2+/phospholipid-dependent protein kinase, and by an endogenous Ca2+/calmodulin-dependent protein kinase, the identity of which remains to be defined[SEP]", "label": "yes"}
{"id": "converted_3884", "sentence1": "Is there high nucleotide diversity in the Drosophila suzukii species?", "sentence2": "Native to Asia, the soft-skinned fruit pest Drosophila suzukii has recently invaded the United States and Europe. The eastern United States represents the most recent expansion of their range, and presents an opportunity to test alternative models of colonization history. Here, we investigate the genetic population structure of this invasive fruit fly, with a focus on the eastern United States. We sequenced six X-linked gene fragments from 246 individuals collected from a total of 12 populations. We examine patterns of genetic diversity within and between populations and explore alternative colonization scenarios using approximate Bayesian computation. Our results indicate high levels of nucleotide diversity in this species and suggest that the recent invasions of Europe and the continental United States are independent demographic events. [SEP]", "label": "yes"}
{"id": "converted_3114", "sentence1": "Is there any association between suicide and autism in adolescents, yes or no?", "sentence2": ": In all subjects from our research on PubMed, 21.3% of subjects with autism spectrum disorder reported suicidal ideation, have attempted suicide or died by suicide (115 out of 539 subjects) and 7.7% of subjects supported for suicidal thoughts or attempted suicide exhibited an autism spectrum disorder (62 out of 806 subjects), all ages combined. , Suicide attempts are accompanied by a willingness for death and can lead to suicide. They are more common in high-functioning autism and Asperger subjects.,  A total sample of 10 adolescents and young adults diagnosed with AS was obtained. The high proportion of respondents with scores above the cutoff point on the overt victimization and relational victimization scales suggests that these adolescents and young adults experienced high levels of victimization. Of the sample, 20 percent met criteria for a diagnosis of Major Depressive Disorder, 30 percent met criteria for Generalized Anxiety Disorder and 50 percent had clinically significant level of suicidal ideation., Previous studies reported a high prevalence of depression among patients with autism spectrum disorder (ASD) and suggested a relationship between ASD and suicidality, Patients with ASD had an increased risk of suicide attempts compared with those without ASD., The suicidal behaviors are frequently observed in the adolescents and adults with an ASD without intellectual deficience. , Suicide is a major problem in Western society. However we have very little understanding of suicidal behaviour among individuals with autism spectrum disorders. , The available research provides little empirical evidence for the processes underlying suicidal behaviour in adolescents and young adults with autism,  The present study aims to assess the rate of suicidality (suicidal ideation, behaviors and attempts) and associated risk factors for suicidality in high functioning ASD, here is a lack of clinical awareness on suicidal behaviors of children and adolescents with autism spectrum disorder (ASD), suicidality in children and adolescents with diagnosis of high functioning autism spectrum disorder , Consistent with the previous findings, rate of suicidality is higher in individuals with ASD, Detection of Suicidality in Adolescents with Autism Spectrum Disorders, Over 15% of young people with autism spectrum disorders (ASD) will contemplate or attempt suicide during adolescence. Yet,, Until recently, suicidality in autism spectrum disorder (ASD) was rarely discussed. , Suicidality in Autism Spectrum Disorder., highlighted not only that suicidal thoughts and suicide attempts can occur in adolescents and young adults with ASD, but also that suicidality is likely more common in ASD than in the general population. , The emerging studies indicate that the increased risk of self-injurious behavior in younger and less cognitively able children with ASD3,4 is matched by an increased risk of suicidality in those at a more advanced developmental level., RESULTS\nIn all subjects from our research on PubMed, 21.3% of subjects with autism spectrum disorder reported suicidal ideation, have attempted suicide or died by suicide (115 out of 539 subjects) and 7.7% of subjects supported for suicidal thoughts or attempted suicide exhibited an autism spectrum disorder (62 out of 806 subjects), all ages combined., Risk of Suicide Attempts Among Adolescents and Young Adults With Autism Spectrum Disorder: A Nationwide Longitudinal Follow-Up Study., Although the suicide risk of autism spectrum disorder (ASD) has been suggested to be higher than previously recognized, there are few case reports focusing on the process for preventing suicide reattempts.[SEP]", "label": "yes"}
{"id": "converted_4399", "sentence1": "Is gabapentin effective for chronic pelvic pain?", "sentence2": "There were no significant between-group differences in both worst and average numerical rating scale (NRS) pain scores at 13-16 weeks after randomisation. The mean worst NRS pain score was 7·1 (standard deviation [SD] 2·6) in the gabapentin group and 7·4 (SD 2·2) in the placebo group. Mean change from baseline was -1·4 (SD 2·3) in the gabapentin group and -1·2 (SD 2·1) in the placebo group (adjusted mean difference -0·20 [97·5% CI -0·81 to 0·42]; p=0·47). The mean average NRS pain score was 4·3 (SD 2·3) in the gabapentin group and 4·5 (SD 2·2) in the placebo group. Mean change from baseline was -1·1 (SD 2·0) in the gabapentin group and -0·9 (SD 1·8) in the placebo group (adjusted mean difference -0·18 [97·5% CI -0·71 to 0·35]; p=0·45)., INTERPRETATION: This study was adequately powered, but treatment with gabapentin did not result in significantly lower pain scores in women with chronic pelvic pain, and was associated with higher rates of side-effects than placebo. Given the increasing reports of abuse and evidence of potential harms associated with gabapentin use, it is important that clinicians consider alternative treatment options to off-label gabapentin for the management of chronic pelvic pain and no obvious pelvic pathology., Gabapentin not effective for chronic pelvic pain in women., Gabapentin not effective for chronic pelvic pain in women[SEP]", "label": "no"}
{"id": "converted_1365", "sentence1": "Is Mammaprint approved by the United States Food and Drug Administration?", "sentence2": "an FDA-cleared 70-gene signature of MammaPrint panel , on MammaPrint, the first and only assay for breast cancer management that has been cleared by the FDA., The MammaPrint assay has the advantages of a 510(k) clearance by the US Food and Drug Administration, a larger gene number which may enhance further utility, and the potentially wider patient eligibility including lymph node-positive, ER-negative, , The MammaPrint assay has the advantages of a 510(k) clearance by the U.S. Food and Drug Administration, a larger gene number, which may enhance further utility, and a potentially wider patient eligibility, including lymph node-positive, estrogen receptor (ER)-negative, and younger patients being accrued into the prospective trial (Microarray in Node-Negative Disease May Avoid Chemotherapy). [SEP]", "label": "yes"}
{"id": "converted_2267", "sentence1": "Is there any role of 5hmC in T-cell development and differentiation?", "sentence2": "We have mapped 5-hydroxymethylcytosine (5hmC) at different stages of T-cell development in the thymus and T-cell differentiation in the periphery. We show that 5hmC is enriched in the gene body of highly expressed genes at all developmental stages and that its presence correlates positively with gene expression. Further emphasizing the connection with gene expression, we find that 5hmC is enriched in active thymus-specific enhancers and that genes encoding key transcriptional regulators display high intragenic 5hmC levels in precursor cells at those developmental stages where they exert a positive effect. Our data constitute a valuable resource that will facilitate detailed analysis of the role of 5hmC in T-cell development and differentiation., We show that 5hmC is enriched in the gene body of highly expressed genes at all developmental stages and that its presence correlates positively with gene expression., Further emphasizing the connection with gene expression, we find that 5hmC is enriched in active thymus-specific enhancers and that genes encoding key transcriptional regulators display high intragenic 5hmC levels in precursor cells at those developmental stages where they exert a positive effect., We show that 5hmC is enriched in the gene body of highly expressed genes at all developmental stages and that its presence correlates positively with gene expression., Here, we report early and widespread 5mC/5hmC remodeling during human CD4(+) T cell differentiation ex vivo at genes and cell-specific enhancers with known T cell function., Our results support 5hmC-mediated DNA de-methylation as a key component of CD4(+) T cell biology in humans, with important implications for gene regulation and lineage commitment., 5hmC plays important roles in regulation of gene expression and differentiation and has been implicated in T cell malignancies and autoimmunity.[SEP]", "label": "yes"}
{"id": "converted_2190", "sentence1": "Is there an association between Histone H3.3 mutations and glioma?", "sentence2": "PURPOSE: Histone H3.3 (H3F3A) mutation in the codon for lysine 27 (K27M) has been found as driver mutations in pediatric glioblastoma and has been suggested to play critical roles in the pathogenesis of thalamic gliomas and diffuse intrinsic pontine gliomas. We report a case of thalamic glioma with H3F3A K27M mutation, which was detected in both the primary tumor diagnosed as diffuse astrocytoma obtained during the first surgery and also in the tumor diagnosed as anaplastic astrocytoma obtained at the second surgery., CONCLUSION: This report demonstrates minute neuroradiological and pathological features of malignant transformation from thalamic low grade glioma with H3F3A K27M mutation., Recently, sequencing of tumor cells revealed that histone H3 is frequently mutated in pediatric HGG, with up to 78 % of diffuse intrinsic pontine gliomas (DIPGs) carrying K27M and 36 % of non-brainstem gliomas carrying either K27M or G34R/V mutations., The pathological diagnosis was anaplastic oligodendroglioma, and we identified a mutation in histone H3.3 in the tumor specimen., CONCLUSIONS: Pediatric brainstem oligodendroglial tumors can include histone H3.3-mutated tumors and have a tendency to disseminate throughout the neuroaxis at the time of relapse., We highlight the genetic aberrations recently discovered in isocitrate dehydrogenase, alpha thalassemia/mental retardation syndrome X-linked, death-domain-associated protein, histone H3.3, and telomerase reverse transcriptase and discuss how these mutations lead to unexpected changes in the epigenetic landscape in gliomas., Particularly striking is the discovery of frequent histone H3.3 mutations in pediatric glioma, a particularly aggressive neoplasm that has long remained poorly understood, Exon sequencing has identified a mutation in K27M of the histone H3.3 gene (H3F3A K27M and G34R/V) in about 20% of pediatric glioblastomas, but it remains to be seen whether these mutations can be considered specific for pediatric diffuse high-grade astrocytomas or also occur in other pediatric brain tumors, The histone H3.3K27M mutation in pediatric glioma reprograms H3K27 methylation and gene expression, A lesson learned from the H3.3K27M mutation found in pediatric glioma: a new approach to the study of the function of histone modifications in vivo, Pediatric glioblastoma multiforme (GBM) is rare, and there is a single study, a seminal discovery showing association of histone H3.3 and isocitrate dehydrogenase (IDH)1 mutation with a DNA methylation signature., Over 70% of diffuse intrinsic pediatric gliomas, an aggressive brainstem tumor, harbor heterozygous mutations that create a K27M amino acid substitution (methionine replaces lysine 27) in the tail of histone H3.3., Mutations in H3F3A, which encodes histone H3.3, commonly occur in pediatric glioblastoma., Somatic mutations of the H3F3A and HIST1H3B genes encoding the histone H3 variants, H3.3 and H3.1, were recently identified in high-grade gliomas arising in the thalamus, pons and spinal cord of children and young adults., K27M mutation in histone H3.3 defines clinically and biologically distinct subgroups of pediatric diffuse intrinsic pontine gliomas., Recurrent mutations affecting the histone H3.3 residues Lys27 or indirectly Lys36 are frequent drivers of pediatric high-grade gliomas (over 30% of HGGs)., Use of human embryonic stem cells to model pediatric gliomas with H3.3K27M histone mutation., Recent studies on high-grade pediatric GBM have identified two recurrent mutations (K27M and G34R/V) in genes encoding histone H3 (H3F3A for H3.3 and HIST1H3B for H3.1)., Driver mutations in histone H3.3 and chromatin remodelling genes in paediatric glioblastoma.[SEP]Relations: TERT has relations: disease_protein with glioma, disease_protein with glioma.", "label": "yes"}
{"id": "converted_3557", "sentence1": "Are astronauts in higher risk for developing cancer?", "sentence2": "Understanding space radiation health effects is critical due to potential increased morbidity and mortality following spaceflight. ,  No significant associations between space radiation dose and mortality were found using logistic regression with an internal reference group, adjusting for medical radiation., Despite years of research, understanding of the space radiation environment and the risk it poses to long-duration astronauts remains limited. There is a disparity between research results and observed empirical effects seen in human astronaut crews[SEP]", "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]", "label": "yes"}
{"id": "converted_3027", "sentence1": "Can mogamulizumab be used for the treatment of cutaneous T-cell lymphoma?", "sentence2": "In the large international phase III MAVORIC trial, patients with previously treated cutaneous T-cell lymphoma who received the anti-CCR4 monoclonal antibody mogamulizumab experienced significantly longer progression-free survival and higher response rates, as well as better quality of life, than those who received vorinostat, a standard therapy.[SEP]", "label": "yes"}
{"id": "converted_3855", "sentence1": "Does IL18 signaling have a role in thymus?", "sentence2": "IL18 signaling promotes homing of mature Tregs into the thymus., Collectively, this study provides a detailed characterization of the mature Treg subsets in the mouse thymus and identifies a key role of IL18 signaling in controlling the CCR6-CCL20-dependent migration of Tregs into the thymus., er, we show that IL18R+ Tregs are endowed with higher capacity to populate the thymus than their IL18R- or IL18R-/- counterparts, highlighting the key role of IL18R in this process, IL18 signaling promotes homing of mature Tregs into the thymus, inally, we demonstrate that IL18 signaling is critical for the induction of the key thymus-homing chemokine receptor - CCR6 on Tregs. , Moreover, we show that IL18R+ Tregs are endowed with higher capacity to populate the thymus than their IL18R- or IL18R-/- counterparts, highlighting the key role of IL18R in this process.[SEP]", "label": "yes"}
{"id": "converted_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: cryoglobulinemia has relations: disease_disease with cryofibrinogenemia, disease_disease with cryofibrinogenemia. cryofibrinogenemia has relations: disease_disease with cryoglobulinemia, disease_disease with cryoglobulinemia.", "label": "yes"}
{"id": "converted_3556", "sentence1": "Is GRG5 involved only in late embryonic mouse development?", "sentence2": "Groucho related gene 5 (GRG5) is a multifunctional protein that has been implicated in late embryonic and postnatal mouse development. Here, we describe a previously unknown role of GRG5 in early developmental stages by analyzing its function in stem cell fate decisions. By both loss and gain of function approaches we demonstrate that ablation of GRG5 deregulates the Embryonic Stem Cell (ESC) pluripotent state whereas its overexpression leads to enhanced self-renewal and acquisition of cancer cell-like properties. The malignant characteristics of teratomas generated by ESCs that overexpress GRG5 reveal its pro-oncogenic potential. [SEP]", "label": "no"}
{"id": "converted_3210", "sentence1": "Are cardenolides inhibitors of Na+/K+ ATPase?", "sentence2": ". Previously, we reported that a variety of cardenolides impart anti-transmissible gastroenteritis coronavirus (TGEV) activity in swine testicular (ST) cells, through targeting of the cell membrane sodium/potassium pump, Na+/K+-ATPase. , : We found evidence for low cardenolides by HPLC, but substantial toxicity when extracts were assayed on Na+ /K+ -ATPases., Cardenolides have shown significant antitumor activity due to their ability to inhibit the Na+K+ATPase enzyme, and the expression of this enzyme is increased in tumor cells. [SEP]", "label": "yes"}
{"id": "converted_3371", "sentence1": "Does clinical trial data support the use of minocycline for amyotrophic lateral sclerosis?", "sentence2": "Two double-blind, randomized, placebo-controlled feasibility trials of minocycline in ALS were conducted. , This pilot study shows that minocycline and riluzole can be taken safely together. Further trials are needed to assess efficacy of such treatment., It reduces apoptosis in mouse models of Huntington's disease and familial amyotrophic lateral sclerosis (ALS) and is in clinical trial for sporadic ALS., Efficacy of minocycline in patients with amyotrophic lateral sclerosis: a phase III randomised trial., FINDINGS: ALSFRS-R score deterioration was faster in the minocycline group than in the placebo group (-1.30 vs -1.04 units/month, 95% CI for difference -0.44 to -0.08; p=0.005). Patients on minocycline also had non-significant tendencies towards faster decline in FVC (-3.48 vs -3.01, -1.03 to 0.11; p=0.11) and MMT score (-0.30 vs -0.26, -0.08 to 0.01; p=0.11), and greater mortality during the 9-month treatment phase (hazard ratio=1.32, 95% CI 0.83 to 2.10; p=0.23) than did patients on placebo. Quality-of-life scores did not differ between the treatment groups. , INTERPRETATION: Our finding that minocycline has a harmful effect on patients with ALS has implications for trials of minocycline in patients with other neurological disorders, and for how potential neuroprotective agents are screened for use in patients with ALS., A recent publication of the results of a clinical trial of minocycline in 412 ALS patient has aroused considerable controversy in the ALS scientific community. As on previous occasions, the results obtained in the laboratory are not reproduced in clinical practice., A recent publication of the results of a clinical trial of minocycline in 412 ALS patient has aroused considerable controversy in the ALS scientific community., INTERPRETATION\n\nOur finding that minocycline has a harmful effect on patients with ALS has implications for trials of minocycline in patients with other neurological disorders, and for how potential neuroprotective agents are screened for use in patients with ALS., A recent publication of the results of a clinical trial of minocycline in 412 ALS patient has aroused considerable controversy in the ALS scientific community, A recent publication of the results of a clinical trial of minocycline in 412 ALS patient has aroused considerable controversy in the ALS scientific community., Our finding that minocycline has a harmful effect on patients with ALS has implications for trials of minocycline in patients with other neurological disorders, and for how potential neuroprotective agents are screened for use in patients with ALS., Patients on minocycline also had non-significant tendencies towards faster decline in FVC (-3.48 vs -3.01, -1.03 to 0.11; p=0.11) and MMT score (-0.30 vs -0.26, -0.08 to 0.01; p=0.11), and greater mortality during the 9-month treatment phase (hazard ratio=1.32, 95% CI 0.83 to 2.10; p=0.23) than did patients on placebo.[SEP]", "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: glycerol kinase activity has relations: molfunc_protein with GK, molfunc_protein with GK.", "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: peptidyl-dipeptidase activity has relations: molfunc_protein with ACE2, molfunc_protein with ACE2.", "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: malignant giant cell tumor has relations: disease_disease with cancer, disease_disease with cancer.", "label": "yes"}
{"id": "converted_2783", "sentence1": "Can pets affect infant microbiomed?", "sentence2": "Since there is some evidence that pets also alter the gut microbial composition of infants, changes to the gut microbiome are putative pathways by which pet exposure can reduce these risks to health., The impact of pet ownership varies under different birth scenarios; however, in common, exposure to pets increased the abundance of two bacteria, Ruminococcus and Oscillospira, which have been negatively associated with childhood atopy and obesity., As a common effect in all birth scenarios, pre- and postnatal pet exposure enriched the abundance of Oscillospira and/or Ruminococcus (P < 0.05) with more than a twofold greater likelihood of high abundance. Among vaginally born infants with maternal intrapartum antibiotic prophylaxis exposure, Streptococcaceae were substantially and significantly reduced by pet exposure (P < 0.001, FDRp = 0.03), reflecting an 80% decreased likelihood of high abundance (OR 0.20, 95%CI, 0.06-0.70) for pet exposure during pregnancy alone and a 69% reduced likelihood (OR 0.31, 95%CI, 0.16-0.58) for exposure in the pre- and postnatal time periods., Exposure to household furry pets influences the gut microbiota of infant at 3-4 months following various birth scenarios.[SEP]", "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]", "label": "yes"}
{"id": "converted_1535", "sentence1": "Are immune cells affected in Amyotrophic Lateral Sclerosis?", "sentence2": "Therapeutic immunization of mSOD1 mice with a myelin-derived peptide led to CP activation, and was followed by the accumulation of immunoregulatory cells, including IL-10-producing monocyte-derived macrophages and Foxp3(+) regulatory T cells, and elevation of the neurotrophic factors IGF-1 and GDNF in the diseased spinal cord parenchyma, Immunization with a Myelin-Derived Antigen Activates the Brain's Choroid Plexus for Recruitment of Immunoregulatory Cells to the CNS and Attenuates Disease Progression in a Mouse Model of ALS., Amyotrophic lateral sclerosis (ALS) is a rapidly progressing fatal neurodegenerative disorder characterized by the selective death of motor neurons (MN) in the spinal cord, and is associated with local neuroinflammation., T-cell deficiency increases neuronal loss, while boosting T cell levels reduces it., As disease accelerates, a shift occurs from beneficial immune responses (involving M2 microglia and regulatory T-cells) to deleterious immune responses (involving M1 microglia and Th1 cells). In this review, we underscore the importance of immune-mediated mechanisms in the pathogenesis of ALS and discuss the alterations and distinct phenotypes of immune cells at the different stages of disease.,  Immunological disturbances have been implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS). Chemokines are involved in the recruitment of immune cells., The immune system has been found to be involved with positive and negative effects in the nervous system of amyotrophic lateral sclerosis (ALS) patients. In general, T cells, B cells, NK cells, mast cells, macrophages, dendritic cells, microglia, antibodies, complement and cytokines participate in limiting damage., Immunological disturbances have been implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS). Chemokines are involved in the recruitment of immune cells., We propose the following mechanism for the effect of mesenchymal stem cells (MSCs) administered intrathecally in amyotrophic lateral sclerosis (ALS): MSCs increase infiltration of peripheral immune cells into CNS and skew the infiltrated immune cells toward regulatory T lymphocytes (Treg ) and Th2 lymphocytes., Immune cell infiltration to the brain&apos;s territory was considered for decades to reflect a pathological process in which immune cells attack the central nervous system (CNS); such a process is observed in the inflammatory autoimmune disease, multiple sclerosis (MS).[SEP]Relations: spinal cord has relations: anatomy_protein_present with CP, anatomy_protein_present with CP. glial cell-derived neurotrophic factor receptor binding has relations: molfunc_protein with GDNF, molfunc_protein with GDNF. Neuronal loss in central nervous system has relations: disease_phenotype_positive with amyotrophic lateral sclerosis, disease_phenotype_positive with amyotrophic lateral sclerosis. central nervous system has relations: anatomy_protein_present with CP, anatomy_protein_present with CP.", "label": "yes"}
{"id": "converted_2787", "sentence1": "Is cohesin linked to myeloid differentiation?", "sentence2": "Consistent with a role for inflammatory signals in promoting myeloid differentiation of hematopoietic stem and progenitor cells (HPSCs), cohesin mutations in HSPCs led to reduced inflammatory gene expression and increased resistance to differentiation-inducing inflammatory stimuli. These findings uncover an unexpected dependence of inducible gene expression on cohesin, link cohesin with myeloid differentiation, and may help explain the prevalence of cohesin mutations in human acute myeloid leukemia., Consistent with a role for inflammatory signals in promoting myeloid differentiation of hematopoietic stem and progenitor cells (HPSCs), cohesin mutations in HSPCs led to reduced inflammatory gene expression and increased resistance to differentiation-inducing inflammatory stimuli., These findings uncover an unexpected dependence of inducible gene expression on cohesin, link cohesin with myeloid differentiation, and may help explain the prevalence of cohesin mutations in human acute myeloid leukemia.<br>[SEP]", "label": "yes"}
{"id": "converted_1444", "sentence1": "Is arimoclomol a co-inducer of the heat shock response?", "sentence2": "Arimoclomol is a hydroxylamine derivative, a group of compounds which have unique properties as co-inducers of heat shock protein expression, but only under conditions of cellular stress. , In this review we summarize the evidence for the neuroprotective effects of enhanced heat shock protein expression by Arimoclomol and other inducers of the Heat Shock Response. , arimoclomol, a co-inducer of the heat shock stress response,, The heat-shock response (HSR) was activated in P23H retinae, and this was enhanced with arimoclomol treatment. ,  We also assessed these functions in mice treated with a known heat shock protein inducer, arimoclomol.,  Under conditions of excessive stress, arimoclomol induces amplification of the cytoprotective heat shock response in order to protect motor neurons from death. , Although both arimoclomol and celastrol induced the expression of Hsp70, Arimoclomol, an amplifier of heat shock protein expression involved in cellular stress response, has emerged as a potential therapeutic candidate in amyotrophic lateral sclerosis (ALS) in recent years., The mechanism of action of arimoclomol involves potentiation of the heat shock response, and treatment with arimoclomol increased Hsp70 expression. , Arimoclomol is an investigational drug for amyotrophic lateral sclerosis (ALS) that amplifies heat shock protein gene expression during cell stress., Arimoclomol, a coinducer of heat shock proteins, delayed progression of amyotrophic lateral sclerosis (ALS) in a mouse model in which motor neurons in the spinal cord and motor cortex degenerate.[SEP]", "label": "yes"}
{"id": "converted_169", "sentence1": "Are there any specific antidotes for rivaroxaban?", "sentence2": "Novel oral anticoagulants (NOACs)--apixaban, dabigatran, and rivaroxaban--have a significantly smaller risk of intracerebral hemorrhage (ICH). However, two facts make this situation complicated: First, the risk of hematoma expansion is unknown for NOACs. Second, there is no specific antidote for neither of the NOACs., he new oral anticoagulants dabigatran etexilate (Pradaxa), rivaroxaban (Xarelto), and apixaban (Eliquis) have predictable pharmacokinetic and pharmacodynamic profiles and are alternatives to warfarin. However, many physicians are wary of these drugs, since there is limited evidence on how to manage bleeding in patients taking them, and since no specific antidote is known to reverse their anticoagulant effect. , Given the absence of a specific antidote, the action to be taken in these situations must be defined. , The fact that there is no specific antidote to reverse the anticoagulant action of the new anticoagulants can impair management of hemorrhagic complications; , Like any new therapy, the potential benefits must be weighed against the potential challenges and one of the most concerning aspects of the new target-specific oral anticoagulants is the lack of a proven method to reverse their effect. Unlike the vitamin K antagonist, i.e. warfarin, there is no specific antidote for these medications. , Two major drawbacks are on the one hand the risk of drug accumulation in kidney and/or liver disease and, on the other hand, the lack of specific antidotes., NOA also have other unresolved problems: drug interactions are still possible, specific coagulation test to assess them must be developed, and no specific antidote is currently available in case of hemorrhagic complication., But they have disadvantages also, they depend on renal clearance, they can interact with other medicaments and they lack a specific antidote. , While these trial data are extremely encouraging, several practical issues (e.g., lack of specific antidote, safety of long-term treatment or cost-effectiveness in \"real-life\" clinical practice) still need to be elucidated., In case of massive bleeding, management is unclear and none of these newer agents has a specific antidote that completely reverses its anticoagulant effect., The short half-life of these new agents compensates for the lack of any specific antidote in many instances. , Currently, none of these new agents has a specific antidote, and little advise can be given on how to manage a major bleeding event., Rivaroxaban, which inhibits activated factor X (Xa), is currently in clinical trials and is the most advanced factor Xa inhibitor. The drug offers once-daily oral dosing, with no need for injections, dose titration, or frequent blood tests to monitor the international normalised ratio. It has a rapid onset of action and, although there is no specific antidote, it has a short plasma elimination half-life (about 5-9 hours). , Increased use of dabigatran, rivaroxaban, and apixaban as oral anticoagulants for the treatment of atrial fibrillation and acute deep venous thrombosis has increased despite the lack of known antidotes to these medications., There is no antidote for reversal and no reliable laboratory monitoring of the anticoagulant effect for emergency situations. , Further concerns about the use of NOAC in the elderly are the high prevalence of renal insufficiency in AF patients >75 years of age, the largely unknown risk of drug-drug and drug-food interactions, the lack of easily available laboratory monitoring tests of anticoagulant activity and the lack of an antidote., Specific antidotes for the reversal of the anticoagulant effect of these drugs, such as monoclonal antibodies against the direct thrombin inhibitor dabigatran or recombinant Xa-analog in the case of factor Xa inhibitors, are still being investigated in early clinical trials., In early 2013 there is no antidote for dabigatran, rivaroxaban or apixaban, nor any specific treatment with proven efficacy for severe bleeding linked to these drugs. [SEP]Relations: Rivaroxaban has relations: contraindication with liver disease, contraindication with liver disease. Warfarin has relations: contraindication with intracerebral hemorrhage, contraindication with liver disease, contraindication with intracerebral hemorrhage, contraindication with liver disease. hepatobiliary disease has relations: disease_disease with liver disease, disease_disease with liver disease. Dabigatran etexilate has relations: contraindication with intracerebral hemorrhage, contraindication with intracerebral hemorrhage.", "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]", "label": "yes"}
{"id": "converted_2004", "sentence1": "Are there methods for generating highly multiplexed ChIP-seq libraries?", "sentence2": "A method for generating highly multiplexed ChIP-seq libraries., The barcoding of next generation sequencing libraries has become an essential part of the experimental design. Barcoding not only allows the sequencing of more than one sample per lane, but also reduces technical bias. However, current barcoding strategies impose significant limitations and/or technical barriers in their implementation for ChIP-sequencing.FINDINGS: Converting Y-shaped sequencing adapters to double stranded DNA prior to agarose gel size selection reduces adapter dimer contamination and quantitating the number of cycles required for amplification of the library with qPCR prior to library amplification eliminates library over-amplification.CONCLUSIONS: We describe an efficient and cost effective method for making barcoded ChIP-seq libraries for sequencing on the Illumina platform., A method for generating highly multiplexed ChIP-seq libraries, A method for generating highly multiplexed ChIP-seq libraries., We describe an efficient and cost effective method for making barcoded ChIP-seq libraries for sequencing on the Illumina platform..[SEP]", "label": "yes"}
{"id": "converted_1283", "sentence1": "Is factor XI deficient in Hemophilia C?", "sentence2": "Factor XI deficiency is a rare hematologic disorder. Hemophilia C (factor XI deficiency) affects both genders and it is usually asymptomatic,, Congenital factor XI deficiency (also known as the Rosenthal syndrome or hemophilia C), rare case of an acute cerebral aneurysm rupture in a patient with a known factor XI deficiency. Aneurysmal subarachnoid hemorrhage (SAH) accounts for a high mortality and morbidity rate. When SAH is associated with an inherited coagulation disorder such as hemophilia C, Factor XI deficiency (Hemophilia C), Factor XI deficiency, also called hemophilia C,[SEP]", "label": "yes"}
{"id": "converted_2379", "sentence1": "Are loop domains preserved upon cohesin loss?", "sentence2": "Cohesin Loss Eliminates All Loop Domains., The human genome folds to create thousands of intervals, called \"contact domains,\" that exhibit enhanced contact frequency within themselves. \"Loop domains\" form because of tethering between two loci-almost always bound by CTCF and cohesin-lying on the same chromosome. \"Compartment domains\" form when genomic intervals with similar histone marks co-segregate. Here, we explore the effects of degrading cohesin. All loop domains are eliminated, but neither compartment domains nor histone marks are affected. Loss of loop domains does not lead to widespread ectopic gene activation but does affect a significant minority of active genes., cohesin loss eliminates all loop domains[SEP]", "label": "no"}
{"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]", "label": "no"}
{"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: peptidyl-dipeptidase activity has relations: molfunc_protein with ACE2, molfunc_protein with ACE2.", "label": "no"}
{"id": "converted_1723", "sentence1": "Does fibronectin constitute a serum biomarker for Duchenne muscular dystrophy?", "sentence2": "Fibronectin is a serum biomarker for Duchenne muscular dystrophy, There was a significant increase in fibronectin levels in DMD patients compared to age-matched controls. Fibronectin levels in patients with Becker muscular dystrophy, Bethlem myopathy, or myasthenia gravis were comparable to control levels. Progressive elevation in fibronectin levels was observed in longitudinal samples from 22 DMD patients followed up for a period of 6 months up to 4 years, This study suggests that serum fibronectin levels may constitute a promising biomarker to monitor disease progression in DMD patients, Fibronectin is a serum biomarker for Duchenne muscular dystrophy., Progressive elevation in fibronectin levels was observed in longitudinal samples from 22 DMD patients followed up for a period of 6 months up to 4 years.CONCLUSION AND CLINICAL RELEVANCE: This study suggests that serum fibronectin levels may constitute a promising biomarker to monitor disease progression in DMD patients., There was a significant increase in fibronectin levels in DMD patients compared to age-matched controls., Progressive elevation in fibronectin levels was observed in longitudinal samples from 22 DMD patients followed up for a period of 6 months up to 4 years., This study suggests that serum fibronectin levels may constitute a promising biomarker to monitor disease progression in DMD patients., Progressive elevation in fibronectin levels was observed in longitudinal samples from 22 DMD patients followed up for a period of 6 months up to 4 years. This study suggests that serum fibronectin levels may constitute a promising biomarker to monitor disease progression in DMD patients., This study suggests that serum fibronectin levels may constitute a promising biomarker to monitor disease progression in DMD patients. © 2014 The Authors PROTEOMICS - Clinical Applications Published by Wiley-VCH Verlag GmbH & Co., There was a significant increase in fibronectin levels in DMD patients compared to age-matched controls. Fibronectin levels in patients with Becker muscular dystrophy, Bethlem myopathy, or myasthenia gravis were comparable to control levels., Fibronectin levels in patients with Becker muscular dystrophy, Bethlem myopathy, or myasthenia gravis were comparable to control levels. Progressive elevation in fibronectin levels was observed in longitudinal samples from 22 DMD patients followed up for a period of 6 months up to 4 years., Fibronectin is a serum biomarker for Duchenne muscular dystrophy., This study suggests that serum fibronectin levels may constitute a promising biomarker to monitor disease progression in DMD patients.[SEP]Relations: Bethlem myopathy has relations: disease_protein with DMD, disease_protein with DMD. Duchenne muscular dystrophy has relations: disease_protein with DMD, disease_protein with DMD.", "label": "yes"}
{"id": "converted_1045", "sentence1": "Is clathrin involved in E-cadherin endocytosis?", "sentence2": "We demonstrated that GnT-III induced a stabilizing effect on E-cadherin at the cell membrane by inducing a delay in the turnover rate of the protein, contributing for the formation of stable and functional adherens-junctions, and further preventing clathrin-dependent E-cadherin endocytosis., Conversely, GnT-V promotes the destabilization of E-cadherin, leading to its mislocalization and unstable adherens-junctions with impairment of cell-cell adhesion., Here we show that E-cadherin polarity is controlled by the polarized regulation of clathrin- and dynamin-mediated endocytosis., We delineate a pathway that controls the initiation of E-cadherin endocytosis through the regulation of AP2 and clathrin coat recruitment by E-cadherin., Clathrin dependent endocytosis of E-cadherin is regulated by the Arf6GAP isoform SMAP1, E-cadherin is a central component of the adherens junction in epithelial cells and continuously undergoes endocytosis via clathrin-coated vesicles and/or caveolae depending on the cell type., Collectively, SMAP1 likely represents a key Arf6GAP in clathrin dependent endocytosis of E-cadherin in MDCK cells., Consistent with these observations, we found that selective uncoupling of p120 from E-cadherin by introduction of amino acid substitutions in the p120-binding site increased the level of E-cadherin endocytosis. The increased endocytosis was clathrin-dependent, because it was blocked by expression of a dominant-negative form of dynamin or by hypertonic shock., We found that in this experimental system E-cadherin entered a transferrin-negative compartment before transport to the early endosomal compartment, where it merged with classical clathrin-mediated uptake pathways.[SEP]", "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_2834", "sentence1": "Is obesity related to cognitive decline?", "sentence2": "The initial results suggests that obese children have higher cognitive scores and that this result is driven by those who are female, non-indigenous and live in an urban region., On the other end of the weight distribution, indigenous children who are severely thin or thin have significantly lower cognitive scores, a relationship that holds after correcting for possible bias and appears to strengthen between ages of five and eight., Obesity is associated with decreased cognitive function, reduced gray matter volume, and impaired white matter integrity in cognition-related brain areas in patients with MDD., The data suggest that being overweight or obese in midlife may be more detrimental to subsequent age-related cognitive decline than being overweight or obese at later stages of the life span, Poor cognitive performance was present in 37% of the sample. General obesity (BMI>or = 25) and poor cognition were strongly associated in the presence of abdominal obesity. Poor cognition was negatively associated with overweight (BMI 23-25) with normal waist circumference., BMI could be used as a candidate risk marker to identify people at higher risk of cognitive deficits, and as an intervention target for modifications of cognitive outcomes., Obesity is a common medical illness that is increasingly recognised as conferring risk of decline in cognitive performance, independent of other comorbid medical conditions., Overweight and obesity are associated with an increased risk of subnormal intellectual performance in young adult males. Subjects with low birth weight and adolescent overweight/obesity are at particular risk of subnormal performance., Impairments in cognitive function have been associated with obesity in both people and rodents., Obesity in the pre-school years was associated with poorer outcomes for some cognitive measures in this study. Stronger relationships between obesity and cognition or educational attainment may emerge later in childhood., There is parallel evidence that people who are overweight or obese tend to perform worse on a variety of cognitive tasks, While research in this area is growing, our knowledge of obesity-related cognitive dysfunction and brain alterations has not yet been synthesized., The present review integrates the recent literature regarding patterns of obesity-related cognitive dysfunction and brain alterations and also indicates potential mechanisms for these neuropathological changes., The review culminates in a preliminary model of obesity-related cognitive dysfunction and suggestions for future research, including the potential reversibility of these changes with weight-loss.<br>, Evidence for the increased prevalence of diabetes and obesity is reviewed as it relates to cognitive decline., These articles indicate that the age of onset of Type 1 diabetes may be relevant to future cognitive function and that disease duration of Type 2 diabetes and sociocultural factors are related to cognitive decline during the aging process., This special issue concludes with a conceptual framework for linking obesity and diabetes with accelerated cognitive decline as related to the aging process., The adverse effects of diabetes and obesity on cognitive functioning are increasingly well recognized., Moreover, these studies show that distressing environmental circumstances can adversely influence neurocognitive dysfunction associated with obesity and diabetes.[SEP]", "label": "yes"}
{"id": "converted_3174", "sentence1": "Was stelara developed by Amgen?", "sentence2": "NICE does not specifically recommend switching from one biologic to another, and only ustekinumab (UST; STELARA®, Janssen Pharmaceuticals, Inc., Horsham, PA, USA) is recommended after anti-tumour necrosis factor failure.[SEP]", "label": "no"}
{"id": "converted_2423", "sentence1": "Is Solanezumab effective for Alzheimer's Disease?", "sentence2": "An analysis of publicly available data from the Phase II studies for bapineuzumab and solanezumab indicates that neither compound produced compelling evidence of drug-like behavior that would justify their progression into pivotal trials. , Notably, a recent study of solanezumab, an amyloid β monoclonal antibody, raises hope for the further therapeutic potential of immunotherapy, not only in Alzheimer's disease, but also for other neurodegenerative disorders, including Parkinson's disease. , For example, Eli Lilly announced a major change to its closely watched clinical trial for the Alzheimer's drug solanezumab which failed to reach statistical significance. , Areas covered: This contradiction prompted us to review all study phases of Intravenous Immunoglobulin (IVIG), Bapineuzumab, Solanezumab, Avagacestat and Dimebolin to shed more light on these recent failures. ,  Results from phase III clinical trials in mild-to-moderate Alzheimer's disease (AD) patients with two monoclonal antibodies bapineuzumab and solanezumab and intravenous immunoglobulin have been disappointing. Subsequent analysis of pooled data from both phase III trials with solanezumab showed a reduction in cognitive decline in patients with mild AD., Secondary analyses of EXPEDITION studies suggested a smaller functional effect of solanezumab relative to cognition. An increasing effect of solanezumab over 18 months was shown for cognition and function., RESULTS: In the mild AD population, less cognitive and functional decline was observed with solanezumab (n = 659) versus placebo (n = 663), measured by Alzheimer's Disease Assessment Scale Cognitive subscale, Mini-Mental State Examination, and Alzheimer's Disease Cooperative Study-Activities of Daily Living functional scale Instrumental ADLs. , The promising results obtained with aducanumab and solanezumab against Alzheimer's disease (AD) strengthen the vaccine approach to prevent AD, despite of the many clinical setbacks. , CONCLUSIONS: Solanezumab, a humanized monoclonal antibody that binds amyloid, failed to improve cognition or functional ability. , Results from phase III clinical trials in mild-to-moderate Alzheimer's disease (AD) patients with two monoclonal antibodies bapineuzumab and solanezumab and intravenous immunoglobulin have been disappointing.[SEP]Relations: Bapineuzumab has relations: drug_drug with Solanezumab, drug_drug with Solanezumab. Solanezumab has relations: drug_drug with Bapineuzumab, drug_drug with Bapineuzumab.", "label": "no"}
{"id": "converted_3674", "sentence1": "Thymoquinone is ineffective against radiation induced enteritis, yes or no?", "sentence2": "n this study, we found that thymoquinone (TQ) could mitigate intestinal damages induced by irradiation. , In this study, we found that thymoquinone (TQ) could mitigate intestinal damages induced by irradiation., In this study, we found that thymoquinone (TQ) could mitigate intestinal damages induced by irradiation., TQ might be used for radiation enteritis treatment.[SEP]", "label": "no"}
{"id": "converted_3683", "sentence1": "Is there an increased risk for meningiomas in childhood leukemia survivors?", "sentence2": "Cranial radiotherapy improves survival of the most common childhood cancers, including brain tumors and leukemia. Unfortunately, long-term survivors are faced with consequences of secondary neoplasia, including radiation-induced meningiomas (RIMs). , Combined chemotherapy and prophylactic cranial irradiation has improved the prognosis of children with acute leukemia. However cranial irradiation carries a latent risk of the induction of secondary intracranial tumors. We encountered a patient who developed multiple intracranial radiation-induced meningiomas (RIMs) 25 years after prophylactic cranial irradiation for the treatment of acute leukemia in childhood. , Focal cranial hyperostosis from meningioma: a complication from previous radiation treatment for childhood T-cell acute lymphoblastic leukemia., Presented is a case of a 20 year man with a history of T-cell lymphoblastic leukemia diagnosed at age 22 months, treated with chemotherapy and cranial irradiation. He had developed increasing prominence of the top of his head over several months. Plain radiograph showed frontal calvarium thickening with focal \"hair-on-end\" periosteal reaction. Magnetic resonance imaging revealed an enhancing dural-based mass with transcalvarial extension, confirmed after resection to be meningioma (World Health Organization Grade I). , RESULTS: Acute myeloid leukemia (AML; n = 186), myelodysplastic syndrome (MDS; n = 69), and nonmeningioma brain tumor (n = 116) were the most common types of SMNs and had the poorest outcome (5-year survival rate, 18.1% ± 2.9%, 31.1% ± 6.2%, and 18.3% ± 3.8%, respectively). , Radiation-induced World Health Organization grade II meningiomas in young patients following prophylactic cranial irradiation for acute lymphoblastic leukemia in childhood. Three case reports., Current chemotherapeutic regimens have been used to successfully treat many children with acute lymphoblastic leukemia (ALL), but have resulted in an increased risk of late central nervous system tumors, most commonly meningioma, particularly in patients who have received cranial irradiation. , RESULTS: Fifty-nine MRI abnormalities (32 cavernomas, nine focal areas of gliosis, seven dystrophic mineralizations, five cerebral atrophies, four pituitary atrophies, one diffuse radiation leukoencephalopathy, and one meningioma) were found in 43 patients. , Intraventricular meningioma after cranial irradiation for childhood leukemia., Radiation-induced meningiomas may also have predilection to recur. The authors describe a case of an intraventricular meningioma occurring 23 years after cranial irradiation for childhood acute lymphoblastic leukemia., Cumulative incidence at 30 years after the childhood cancer diagnosis was 20.5% (95% confidence interval [CI] = 19.1% to 21.8%) for all subsequent neoplasms, 7.9% (95% CI = 7.2% to 8.5%) for second malignant neoplasms (excluding nonmelanoma skin cancer), 9.1% (95% CI = 8.1% to 10.1%) for nonmelanoma skin cancer, and 3.1% (95% CI = 2.5% to 3.8%) for meningioma. , Radiation-induced meningiomas: a shadow in the success story of childhood leukemia., Although the cohort is small, it seems probable that the increasing incidence of meningioma will shadow the future of cranially irradiated leukemia survivors., Age at the time of irradiation, gender, or cumulative doses of chemotherapeutic agents showed no significant association with the development of meningiomas., Meningioma Screening With MRI in Childhood Leukemia Survivors Treated With Cranial Radiation., High incidence of meningioma in cranial irradiated survivors of childhood acute lymphoblastic leukemia., Radiation-induced World Health Organization grade II meningiomas in young patients following prophylactic cranial irradiation for acute lymphoblastic leukemia in childhood., Radiation-induced meningioma following prophylactic radiotherapy for acute lymphoblastic leukemia in childhood., Current chemotherapeutic regimens have been used to successfully treat many children with acute lymphoblastic leukemia ( ALL) , but have resulted in an increased risk of late central nervous system tumors , most commonly meningioma , particularly in patients who have received cranial irradiation, Survivors of childhood ALL treated with high-dose cranial irradiation are at risk both for early radiation injury in radiosensitive organs , such as the lens and pituitary gland , and for the later development of a radiation-induced meningioma, Radiation-induced meningiomas: a shadow in the success story of childhood leukemia, We treated 3 young patients with World Health Organization grade II meningiomas who had previously received cranial irradiation for the treatment of childhood ALL: a cerebellopontine angle tumor in a 19-year-old woman , a petroclival tumor in a 28-year-old man , and a frontal parasagittal tumor in a 19-year-old woman, We treated 3 young patients with World Health Organization grade II meningiomas who had previously received cranial irradiation for the treatment of childhood ALL: a cerebellopontine angle tumor in a 19-year-old woman, a petroclival tumor in a 28-year-old man, and a frontal parasagittal tumor in a 19-year-old woman., Current chemotherapeutic regimens have been used to successfully treat many children with acute lymphoblastic leukemia (ALL), but have resulted in an increased risk of late central nervous system tumors, most commonly meningioma, particularly in patients who have received cranial irradiation., Current chemotherapeutic regimens have been used to successfully treat many children with acute lymphoblastic leukemia (ALL), but have resulted in an increased risk of late central nervous system tumors, most commonly meningioma, particularly in patients who have received cranial irradiation., Long-term survivors who received radiotherapy for ALL in childhood are at risk for late complications, including radiation-induced meningioma.[SEP]Relations: childhood leukemia has relations: disease_disease with acute lymphoblastic leukemia, disease_disease with acute lymphoblastic leukemia. acute lymphoblastic/lymphocytic leukemia has relations: disease_disease with acute lymphoblastic leukemia, disease_disease with acute lymphoblastic leukemia.", "label": "yes"}
{"id": "converted_2159", "sentence1": "Is autophagy the process where bacteria ingest viral particles?", "sentence2": "Autophagy, a cellular degradation process, Autophagy, a form of lysosomal degradation capable of eliminating dysfunctional proteins and organelles, is a cellular process associated with homeostasis., Autophagy, a programmed process in which cell contents are delivered to lysosomes for degradation, appears to have both tumor-suppressive and tumor-promoting functions; both stimulation and inhibition of autophagy have been reported to induce cancer cell death, and particular genes and proteins have been associated both positively and negatively with autophagy, Autophagy is a lysosome-mediated catabolic process involving the degradation of intracellular contents (e.g., proteins and organelles) as well as invading microbes (e.g., parasites, bacteria and viruses)., Autophagy is a cellular process that targets proteins, lipids and organelles to lysosomes for degradation, but it has also been shown to combat infection with various pathogenic bacteria., Autophagy, an intracellular degradation process highly conserved from yeast to humans, is viewed as an important defence mechanism to clear intracellular bacteria., Autophagy has intracellular anti-viral and anti-bacterial functions, and plays a role in the initiation of innate and adaptive immune system responses to viral and bacterial infections., documented abundant autophagy within VZV-infected cells throughout the infectious cycle but also demonstrated that VZV-induced autophagy facilitated VZV glycoprotein biosynthesis and processing., Autophagy is a highly conserved process by which cells can recycle organelles and proteins by degrading them in the lysosomes.[SEP]", "label": "yes"}
{"id": "converted_4679", "sentence1": "Is there any role of the 'Greek islands' in olfactory receptor choice?", "sentence2": "Chromatin conformation capture using in situ Hi-C on fluorescence-activated cell-sorted olfactory sensory neurons and their progenitors shows that olfactory receptor gene clusters from 18 chromosomes make specific and robust interchromosomal contacts that increase with differentiation of the cells. These contacts are orchestrated by intergenic olfactory receptor enhancers, the 'Greek islands', which first contribute to the formation of olfactory receptor compartments and then form a multi-chromosomal super-enhancer that associates with the single active olfactory receptor gene. The Greek-island-bound transcription factor LHX2 and adaptor protein LDB1 regulate the assembly and maintenance of olfactory receptor compartments, Greek island hubs and olfactory receptor transcription, providing mechanistic insights into and functional support for the role of trans interactions in gene expression.[SEP]", "label": "yes"}
{"id": "converted_1898", "sentence1": "Is Stat4 a transcription factor?", "sentence2": "transcription factors T-bet and STAT4, STAT4 is a member of the signal transducer and activator of transcription (STAT) family of molecules that localizes to the cytoplasm. STAT4 regulates various genes expression as a transcription factor after it is phosphorylated, dimerizes and translocates to the nucleus. , STAT4 is a latent cytosolic factor that encodes a transcription factor transmitting signals stimulated by cytokines. ,  To investigate the role of signal transduction and activation of transcription 4 (STAT4) in the development and progression of human hepatocellular carcinoma (HCC)[SEP]", "label": "yes"}
{"id": "converted_2832", "sentence1": "Is durvalumab used for lung cancer treatment?", "sentence2": " In the phase III PACIFIC trial consolidation with durvalumab, an anti-PDL-1 antibody, was associated with survival benefit in patients diagnosed with LA-NSCLC who responded to concurrent chemoradiotherapy., METHODS: An electronic literature search was performed of public databases (MEDLINE, Excerpta Medica dataBASE [EMBASE], and Cochrane) and conference proceedings for trials using PD-1 inhibitors (nivolumab and pembrolizumab) and PD-L1 inhibitors (atezolizumab, durvalumab, and avelumab) in patients with NSCLC., Durvalumab in non-small-cell lung cancer patients: current developments., Single-agent durvalumab showed clinical efficacy and a manageable safety profile in advanced non-small-cell lung cancer, particularly the ≥25% PD-L1+ population., Six drugs including one CTLA-4 blocker (ipilimumab), two PD-1 blockers (nivolumab and pembrolizumab) and three PD-L1 blockers (atezolizumab, avelumab and durvalumab) are approved for the treatment of different types of cancers including both solid tumors such as melanoma, lung cancer, head and neck cancer, bladder cancer and Merkel cell cancer as well as hematological tumors such as classic Hodgkin's lymphoma. , PURPOSE OF REVIEW: The therapeutic armamentarium for advanced non-small-cell lung cancer has evolved considerably over the past years. Immune checkpoint inhibitors targeting programmed cell death-1 such as pembrolizumab and nivolumab or programmed cell death ligand 1 such as atezolizumab, durvalumab and avelumab have shown favorable efficacy results in this patient population in the first-line and second-line setting., In addition, preclinical and early clinical evidence suggests that chemotherapy and radiation may work synergistically with anti-PD-1/PD-L1 therapy to promote antitumor immunity, which has led to the initiation of clinical trials testing these drugs in patients with stage III NSCLC. A preliminary report of a randomized phase III trial, the PACIFIC trial, demonstrated an impressive increase in median progression-free survival with consolidative durvalumab, a PD-L1 inhibitor, compared with observation after cCRT. , ICI, such as the PD-1 inhibitors nivolumab and pembrolizumab and the PD-L1 inhibitor atezolizumab, have already been marketed for the treatment of pretreated patients with advanced NSCLC., The PACIFIC trial assessing durvalumab after standard chemoradiotherapy for locally advanced NSCLC has already met its primary endpoint and the potential of durvalumab will be reinforced if phase III randomized studies of first-line (MYSTIC trial) and second or subsequent (ARCTIC trial) lines of therapy demonstrate superiority over the current standard of care.<br>[SEP]Relations: melanocytic neoplasm has relations: disease_disease with melanoma, disease_disease with melanoma. head and neck neoplasm has relations: disease_disease with head and neck cancer, disease_disease with head and neck cancer. malignant ear neoplasm has relations: disease_disease with head and neck cancer, disease_disease with head and neck cancer, disease_disease with head and neck cancer, disease_disease with head and neck cancer.", "label": "yes"}
{"id": "converted_4634", "sentence1": "Is HDAC1 required for GATA-1 transcriptional activity?", "sentence2": "HDAC1 is required for GATA-1 transcription activity, global chromatin occupancy and hematopoiesis., GATA-12RA knock-in (KI) mice suffer mild anemia and thrombocytopenia with accumulation of immature erythrocytes and megakaryocytes in bone marrow and spleen. Single cell RNA-seq analysis of Lin- cKit+ (LK) cells further reveal a profound change in cell subpopulations and signature gene expression patterns in HSC, myeloid progenitors, and erythroid/megakaryocyte clusters in KI mice. Thus, GATA-1 deacetylation and its interaction with HDAC1 modulates GATA-1 chromatin binding and transcriptional activity that control erythroid/megakaryocyte commitment and differentiation.[SEP]", "label": "yes"}
{"id": "converted_1383", "sentence1": "Is there an association between c-reactive protein concentrations and outcomes of subarachnoid hemorrhage patients? ", "sentence2": "Besides the baseline characteristics, daily interleukin-6 (IL-6), procalcitonin, C-reactive protein levels, and leukocyte counts were prospectively measured until day 14 after subarachnoid hemorrhage. Occurrence of infectious complications and application of therapeutic hypothermia were assessed as confounding factors. The primary end point was outcome after 3 months, assessed by Glasgow Outcome Scale; the secondary end point was the occurrence of DINDs. RESULTS: : During a 3-year period, a total of 138 patients were included. All inflammatory parameters measured were higher in patients with unfavorable outcome (Glasgow Outcome Scale score, 1-3)., Twenty-three and 28 patients showed poor outcome and symptomatic vasospasm after SAH, respectively. Both preoperative and postoperative CRP levels were significantly higher in patients with a poor outcome compared with patients with a good outcome (P<0.05)., e area under the receiver operating characteristic curve of CRP measured on postoperative day 1 or 2 (CRP POD1-2) for predicting a poor clinical outcome was 0.870, and its cutoff point of 4 mg/dL had a sensitivity of 0.826 and a specificity of 0.843., A high CRP level after aneurysm treatment was associated with severe neurological deterioration on admission, cerebral infarction, intracerebral hemorrhage, and surgical decompression (P<0.05)., CRP POD1-2, and not the preoperative CRP, was an independent factor in predicting symptomatic vasospasm (P<0.05). In patients with symptomatic vasospasm, an increase in the postoperative CRP was associated with the time profile of developing symptomatic vasospasm., Postoperative CRP, especially CRP POD1-2, can be a useful prognostic factor for both poor outcome and symptomatic vasospasm in patients with aneurysmal SAH., Serum CRP levels were related to severity of aSAH. Patients with lower GCS scores and higher Hunt and Hess and Fisher grades presented statistically significant higher serum CRP levels. Patients with higher serum CRP levels had a less favorable prognosis., Increased serum CRP levels were strongly associated with worse clinical prognosis in this study., After SAH, the value of C-reactive protein (CRP)--an acute phase sensitive inflammatory marker--as a prognostic factor has been poorly studied, with conflicting results., Admission (18.0 ± 35.7 vs 8.5 ± 8.4 mg/l) and postoperative (41.0 ± 40.2 vs 21.1 ± 24.1 mg/l) CRP levels were higher (p < 0.001) in those with a poor outcome than in those with a favourable outcome, but CRP values did not predict delayed cerebral ischaemia or cerebral infarction., Higher increase in CRP level between admission and postoperative morning, however, independently predicted poor outcome (p = 0.004)., CRP levels correlate with outcome but do not seem to predict delayed cerebral ischaemia or infarction after SAH., Systemic oxygen consumption is associated with hsCRP levels in the first 14 days after SAH and is an independent predictor of DCI., Intracranial hypertension was associated with an inflammatory response, indicating activation of the inflammatory cascade in the brain (ECF) and systemic circulation with high IL-6 and C-reactive protein (CRP) plasma levels after SAH, the latter associated with unfavourable outcome., Patients with angiographic vasospasm had higher CRP measurements in serum and CSF, in a statistically significant fashion (p < 0.0001). Additionally, patients with higher CRP levels in serum and CSF had less favorable outcome in this cohort., Furthermore, patients developing angiographically proven vasospasm demonstrated significantly elevated CRP levels in serum and CSF, and increased CRP measurements were strongly associated with poor clinical outcome in this cohort., Finally, serum concentrations of ICAM-1, VCAM-1, and hsCRP during the early (P = .0055, P = .0266, and P = .0266) and late (P = .0423, P = .0041, and P = .0004) period were significantly higher in patients with DIND than in patients without DIND. CONCLUSIONS: Serum levels of ICAM-1, VCAM-1 and hsCRP during the early and late period following SAH correlate with DIND, CRP levels on days 5, 6, 7, and 8 were statistically significantly higher in the group of patients developing a DIND (P < 0.025, P < 0.016, P < 0.011, P < 0.0002)., Overall CRP values were higher with increasing severity of the initial ictus according to the Hunt and Hess Scale and to the outcome according to the Glasgow Outcome Scale from day 3 on., The presented data do not prove that WBCs and CRP values have a direct contribution to the pathogenesis of ischemic complications following SAH, but it supports the assertion that inflammation may present a common pathogenic pathway in the development of such complications., The CRP and TGF-beta1 levels in CSF are strongly concerned with communicating hydrocephalus after SAH.[SEP]Relations: brain infarction has relations: disease_disease with cerebral infarction, disease_disease with cerebral infarction.", "label": "yes"}
{"id": "converted_3994", "sentence1": "Is there an association of alterations in ADCY7 and ulcerative colitis?", "sentence2": "To further resolve the genetic architecture of the inflammatory bowel diseases ulcerative colitis and Crohn's disease, we sequenced the whole genomes of 4,280 patients at low coverage and compared them to 3,652 previously sequenced population controls across 73.5 million variants. We then imputed from these sequences into new and existing genome-wide association study cohorts and tested for association at ∼12 million variants in a total of 16,432 cases and 18,843 controls. We discovered a 0.6% frequency missense variant in ADCY7 that doubles the risk of ulcerative colitis. Despite good statistical power, we did not identify any other new low-frequency risk variants and found that such variants explained little heritability. [SEP]Relations: inflammatory bowel disease has relations: disease_phenotype_positive with Crohn's disease, disease_phenotype_positive with Crohn's disease.", "label": "yes"}
{"id": "converted_839", "sentence1": "Are seizures among the neurological symptoms of incontinentia pigmenti?", "sentence2": "High-dose glucocorticoid therapy in the management of seizures in neonatal incontinentia pigmenti, Incontinentia pigmenti is an X-linked dominant disorder resulting from a mutation of IKBKG. This disorder has a classic dermatologic presentation, but neurologic involvement, with seizures and cortical infarction, can arise shortly after birth, Some children with incontinentia pigmenti exhibit encephalopathic features with severe seizures and disturbed consciousness, from the neonatal through the early infantile period, Incontinentia pigmenti (IP) is a rare X-linked dominant neurocutaneous disorder affecting ectodermal tissue: skin, eyes, central nervous system, hair, nails, and teeth. It is usually lethal for males in utero. The involved gene is NEMO, an essential component of the nuclear factor-kappa B (NF-κB) signaling pathway. Skin lesions are highly diagnostic, occurring in neonates, with a particular distribution on Blaschko lines. The severity of the disease is related to ocular and neurological impairment. The hallmark of ocular IP is retinal vasculopathy including peripheral retinal vascular nonperfusion, macular infarction and neovascularization, and preretinal neovascularization. CNS involvement consists of seizures, mental retardation, hemiparesis, spasticity, microcephaly, cerebellar ataxia, and coma, Incontinentia Pigmenti is a rare X-linked multisystem disorder with well described and pathognomonic skin manifestations. Neurological manifestations are found in 30% of IP patients, forming one of the major causes of morbidity and mortality of the condition. In this review, clinical and brain imaging data of 45 IP patients with a neurological phenotype are reviewed. Several clinical presentations could be identified, comprising seizures, infantile encephalopathy, acute disseminated encephalomyelitis and ischemic stroke, Incontinentia pigmenti presenting as seizures., Neonatal seizures in two sisters with incontinentia pigmenti., High-dose glucocorticoid therapy in the management of seizures in neonatal incontinentia pigmenti: a case report., Incontinentia Pigmenti is an X-linked dominant neurocutaneous disorder with central nervous system manifestations in 30% of cases, including seizures and mental retardation., Neonatal seizures in two sisters with incontinentia pigmenti, A rare cause of neonatal seizure: incontinentia pigmenti., Here, we describe the clinical, electrographic, and neuroradiologic effect of systemic glucocorticoid therapy in a neonate with incontinentia pigmenti manifesting an epileptic encephalopathy., Incontinentia pigmenti presenting as seizures., Neonatal seizures in two sisters with incontinentia pigmenti.[SEP]", "label": "yes"}
{"id": "converted_404", "sentence1": "Is endostatin a proangiogenic factor?", "sentence2": "endostatin (antiangiogenic factor, antiangiogenic factors include thrombospondin-1, angiostatin, and endostatin,  human endostatin (rh-endostatin), a potential antiangiogenic agent, , antiangiogenic PF4 and endostatin, Angiostatin and endostatin are endogenous inhibitors of angiogenesis with anticancer effects, the antiangiogenic factors, cystatin C and endostatin, were measured, accumulation of endostatin and Abeta peptides which have been shown to be antiangiogenic, antioangiogenic factors such as pigment epithelial derived factor (PEDF), angiostatin, endostatin, Endostatin is an antiangiogenic growth factor., angiogenesis inhibitor endostatin, Circulating and cellular proangiogenic and antiangiogenic proteins such as vascular endothelial growth factor (VEGF) and endostatin contribute to the local angiogenic balance, Thrombospondin-1 (Tsp1), endostatin, and tumstatin are extracellular matrix-associated proteins that inhibit angiogenesis, specific inhibitors of angiogenesis such as platelet factor, angiostatin, endostatin, endostatin, an endogenous inhibitor of angiogenesis., antiangiogenic factors (pigment epithelium-derived factor [PEDF]; angiostatin; restin; and endostatin, endostatin peptide, a potent inhibitor of angiogenesis derived from type XVIII collagen,, endogenous angiogenesis inhibitors endostatin , ndostatin is a potent inhibitor of angiogenesis and tumor growth., endogenous angiogenesis inhibitor - endostatin , Endostatin (ES), a fragment of collagen XVIII, is an endogenous inhibitor of angiogenesis, antiangiogenic protein endostatin, A number of endogenous inhibitors of angiogenesis are found in the body. Some of these are synthesized by specific cells in different organs, and others are created by extracellular proteolytic cleavage of plasma-derived or extracellular matrix-localized proteins. In this review, we focus on angiostatin, endostatin,, endostatin (a direct inhibitor of angiogenesis) , endogenous angiogenesis inhibitor endostatin, Endostatin, a peptide derived from proteolysis of collagen XVIII, is an endogenous inhibitor of angiogenesis and tumor growth. , anti-angiogenic factor endostatin, Endostatin is the first endogenous angiogenesis inhibitor to enter clinical trials, angiogenic inhibitors such as endostatin, endostatin inhibits the angiogenic switch, antiangiogenic endostatin , direct acting antiangiogenic agents (e.g., endostatin) , Endostatin is an antiangiogenic fragment of the basement membrane protein, collagen XVIII., specific inhibitors of angiogenesis such as platelet factor-4, angiostatin, endostatin, Endostatin, which is a natural inhibitor of angiogenesis, Angiostatin and endostatin are two powerful inhibitors of angiogenesis in experimental models[SEP]", "label": "no"}
{"id": "converted_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 pulmonary tuberculosis, disease_disease with pulmonary tuberculosis.", "label": "yes"}
{"id": "converted_3707", "sentence1": "Has MLE4901 been tested in phase III clinical trials?", "sentence2": "METHODS\n\nThis phase 2, randomised, double-blind, placebo-controlled, single-centre, crossover trial assessed the effectiveness of an oral neurokinin 3 receptor antagonist (MLE4901) on menopausal hot flushes., Neurokinin 3 receptor antagonism as a novel treatment for menopausal hot flushes: a phase 2, randomised, double-blind, placebo-controlled trial.[SEP]", "label": "no"}
{"id": "converted_1716", "sentence1": "Is the PTPN22 gene a biomarker for Rheumatoid Arthritis?", "sentence2": "Combined longitudinal analysis of the 2 cohorts suggests further association of several loci with Larsen score (KIF5A, PTPN22, AFF3, TAGAP) and therefore a significant accumulation of RA severity markers among RA susceptibility markers (p = 0.016), A non-intronic marker at TNFAIP3, GIN1/C5orf30, STAT4, ANKRD55/IL6ST, BLK and PTPN22 showed association with RA susceptibility, irrespective of the serological status, the latter three markers remaining significantly associated with anti-CCP negative RA, after correction for multiple testing, A C-to-T single nucleotide polymorphism (SNP) located at position 1858 of human PTPN22 cDNA and converting an arginine (R620) to tryptophan (W620) confers the highest risk of rheumatoid arthritis among non-HLA genetic variations that are known to be associated with this disease, TPN22 is a tyrosine phosphatase and functions as a damper of TCR signals. A C-to-T single nucleotide polymorphism (SNP) located at position 1858 of human PTPN22 cDNA and converting an arginine (R620) to tryptophan (W620) confers the highest risk of rheumatoid arthritis among non-HLA genetic variations that are known to be associated with this disease, In addition, how the overall activity of PTPN22 is regulated and how the R-to-W conversion contributes to rheumatoid arthritis is still poorly understood, Our data depict a model that can reconcile the conflicting observations on the functional impact of the C1858T SNP and also suggest that PTPN22.6 is a novel biomarker of rheumatoid arthritis., the level of PTPN22.6 in peripheral blood correlates with disease activity of rheumatoid arthritis, Lack of association of common variants in PTPN22 with RA in Han Chinese was confirmed, This study identifies MMEL1 and CTLA4 as RA susceptibility genes, provides suggestive evidence of association for a further six loci in the Han Chinese population and confirms lack of PTPN22 association in Asian populations, PTPN22 R620W genotype-phenotype correlation analysis and gene-environment interaction study in early rheumatoid arthritis: results from the ESPOIR cohort,  PTPN22 620W risk allele was associated with ACPA production [odds ratio (OR) = 2.21, 95% CI 1.4, 3.4, P < 0.0001], Hormonal treatment exposition and smoking were found to act with a protective effect against ACPA production (OR = 0.44, 95% CI 0.3, 0.7, P = 0.001) and early bone erosion (OR = 0.56, 95% CI 0.4-0.8, P = 0.003), respectively, and independently of HLADR and PTPN22 status,  RA patients (n=333) and controls (n=490) from the Cree/Ojibway NAN population in Central Canada were HLA-DRB1 typed and tested for 21 single-nucleotide polymorphisms (SNPs) that have previously been associated with RA, including PTPN22, TRAF1-C5, CTLA4, PADI4, STAT4, FCRL3, CCL21, MMEL1-TNFRSF14, CDK6, PRKCQ, KIF5A-PIP4K2C, IL2RB, TNFAIP3, IL10-1082G/A and REL, 21 single-nucleotide polymorphisms (SNPs) that have previously been associated with RA, including PTPN22, TRAF1-C5, CTLA4, PADI4, STAT4, FCRL3, CCL21, MMEL1-TNFRSF14, CDK6, PRKCQ, KIF5A-PIP4K2C, IL2RB, TNFAIP3, IL10-1082G/A and REL, Several other genes, including PTPN22 and PADI4, show modest association with RA, he HLA locus, particularly HLA-DRB1, is its strongest genetic risk determinant across ethnicities. Several other genes, including PTPN22 and PADI4, show modest association with RA. , Other variants in potentially pathogenic genes located in non-MHC regions have been implicated by recently performed genome wide analysis studies. These genes include PTPN22, TRAF1-C5, PADI4, STAT4, Several alleles in the epitope-recognition part of the HLA molecule that show the highest association with RA susceptibility, also share a common string of amminoacid residues (the so-called shared-epitope hypothesis). Other variants in potentially pathogenic genes located in non-MHC regions have been implicated by recently performed genome wide analysis studies. These genes include PTPN22, TRAF1-C5, PADI4, STAT4. , Among these genes, PTPN22 plays an outstanding role. CD40, STAT4, PRM1, and TNFAIP3 also seem to be of relevance., n particular, genome-wide association studies (GWAS) have provided supportive evidence that RA is a disease with a strong genetic background. Interestingly, a series of candidate genes have been identified outside of the classical major histocompatibility (MHC) locus, which had long been regarded as the major contributor to the pathogenesis of this disease. Among these genes, PTPN22 plays an outstanding role., HLA-DRB1 and the R620W single-nucleotide polymorphism of PTPN22 were genotyped, In addition, evidence of a significant interaction between the shared epitope and the risk allele of PTPN22 was observed only in these patients, Although SNPs in PADI4 had similar allele frequency among three groups [maximal difference 11%; (P >0.05)], the other three loci revealed statistically significant allele frequency differences (maximal difference 39% (P <0.00001), 13% (P <0.00001), and 8% (P <0.00001) in SLC22A4, PDCD1, and PTPN22, respectively), Several multiple, large-scale, genetic studies on autoimmune-disease-associated SNPs have been reported recently: peptidylarginine deiminase type 4 (PADI4) in rheumatoid arthritis (RA); solute carrier family 22 members 4 and 5 (SLC22A4 and 5) in RA and Crohn's disease (CD); programmed cell death 1 (PDCD1) in systemic lupus erythematosus (SLE), type 1 diabetes mellitus (T1D), and RA; and protein tyrosine phosphatase nonreceptor type 22 (PTPN22) in T1D, RA, and SLE,  Recently a number of convincing candidate genes have begun to emerge and an update has been provided for three of these: PTPN22, CTLA-4 and MIF., Recently a number of convincing candidate genes have begun to emerge and an update has been provided for three of these: PTPN22, challenges in identifying genetic polymorphisms that influence the susceptibility to rheumatoid arthritis are the same as those faced in most complex diseases, Association studies support a role for several genes, including TNFR2, PADI4, SLC22A4, RUNX1, and PTPN22, Although HLA-DRB1 is the main RA gene, it accounts for only part of the familial risk for RA. HLA-DRB1 alleles are neither necessary nor sufficient to cause the development of RA in a given individual. Several genome scans conducted in populations from France, Japan, North America and UK have confirmed the role of the HLA region and suggested several other susceptibility loci. Association studies support a role for several genes, including TNFR2, PADI4, SLC22A4, RUNX1, and PTPN22., Analyses of families with multiple autoimmune disorders have revealed a functional polymorphism, 620W, in the intracellular tyrosine phosphatase gene PTPN22 as a predisposing factor for type 1 diabetes, seropositive rheumatoid arthritis, systemic lupus erythematosus, and Hashimoto thyroiditis, and the presence of the PTPN22 protein appears to herald the development of autoantibodies in these disorders, Replication of putative candidate-gene associations with rheumatoid arthritis in >4,000 samples from North America and Sweden: association of susceptibility with PTPN22, CTLA4, and PADI4., We found strong evidence of an association of PTPN22 with the development of anti-citrulline antibody-positive RA (odds ratio [OR] 1.49; P=.00002), using previously untested EIRA samples.,  Exploration of our data set with clinically relevant subsets of RA reveals that PTPN22 is associated with an earlier age at disease onset (P=.004) and that PTPN22 has a stronger effect in males than in females (P=.03),  Given the strong statistical power to replicate a true-positive association in this study, our results provide support for PTPN22, CTLA4, and PADI4 as RA susceptibility genes and demonstrate novel associations with clinically relevant subsets of RA, In logistic regression analysis, ACPA predicted RA-development independent of PTPN22, while the PTPN22 polymorphism had no independent effect., In this Dutch cohort of UA-patients, the PTPN22 1858T allele does not markedly improve individual decision-making to predict RA-development, Risk of progression from undifferentiated arthritis to rheumatoid arthritis: the effect of the PTPN22 1858T-allele in anti-citrullinated peptide antibody positive patients, progression from undifferentiated arthritis to rheumatoid arthritis: the effect of the PTPN22 1858T-allele, Anti-citrullinated peptide antibodies (ACPA) and the C1858T missense single-nucleotide polymorphism (SNP) in the PTPN22 gene are both associated with the development of rheumatoid arthritis (RA), Associations between human leukocyte antigen, PTPN22, CTLA4 genotypes and rheumatoid arthritis phenotypes of autoantibody status, age at diagnosis and erosions in a large cohort study, HLA-DRB1 shared epitope (HLA-SE), PTPN22 and CTLA4 alleles are associated with cyclic citrullinated peptide (CCP) and rheumatoid arthritis (RA), Auto-antibodies, HLA and PTPN22: susceptibility markers for rheumatoid arthritis, The combination of the PTPN22 1858T variant and anti-CCP antibodies gave a high specificity for the disease, and was significantly associated with RA (P = 8.86 x 10(-5), OR 10.05, 95% CI 1.88-53.73), The combination of the T variant of the 1858 polymorphism of the PTPN22 gene in combination with the presence of anti-CCP antibodies, preferentially in a SE-positive individual, is associated with the development of RA, No association of the PTPN22 gene with mortality was detected, Cox proportional hazards regression models were used to assess the association of the HLA-DRB1 (including the shared epitope [SE]) and PTPN22 genes with the risk of death from all causes and from cardiovascular disease (CVD) and to assess the interactions between SE, smoking, and anti-cyclic citrullinated peptide (anti-CCP) status, adjusted by age at symptom onset and sex, The disease association of the common 1858C>T Arg620Trp (rs2476601) nonsynonymous single nucleotide polymorphism (SNP) of protein tyrosine phosphatase; nonreceptor type 22 (PTPN22) on chromosome 1p13 has been confirmed in type 1 diabetes and also in other autoimmune diseases, including rheumatoid arthritis and Graves' disease, To evaluate the predictive values for disease progression of various antibodies against citrullinated peptide proteins (ACPA) and their relation to PTPN22 1858C/T polymorphism and HLA-DRB1 alleles in early rheumatoid arthritis (RA), PTPN22, PADI-4, and CTLA-4 have been associated with risk for rheumatoid arthritis (RA), A significant multiplicative interaction between PTPN22 and smoking for more than 10 pack-years was observed (P = 0.04), No gene-gene interaction was observed between PTPN22 and HLA-SE, After adjusting for smoking and reproductive factors, PTPN22 was associated with RA risk among Caucasian women in these cohorts. We found both additive and multiplicative interactions between PTPN22 and heavy cigarette smoking., After adjusting for smoking and reproductive factors, PTPN22 was associated with RA risk among Caucasian women in these cohorts, Weak evidence for an effect at the PTPN22 locus was also observed, Association of the PTPN22 gene (-1123G > C) polymorphism with rheumatoid arthritis in Chinese patients, These data suggest, the CC genotype and C allele of the -1123G > C in the PTPN22 gene are associated with an increased risk for RA in Chinese population, Therefore, the CC genotype and C allele of the -1123G > C in the PTPN22 gene may be used as a genetic marker for the predisposition of RA in Chines, A longer duration of breastfeeding increased the risk of developing RA, especially among individuals seropositive for ACPA or IgM-RF or carrying the PTPN22 1858T variant, In a multiple logistic regression analysis, increasing time of breastfeeding (OR 9.5, 95% CI 2.14-42.43 for ≥ 17 months), seropositivity for ACPAs (OR 19.5, 95% CI 4.47-84.81), and carriage of the PTPN22 1858T variant (OR 3.2, 95% CI 1.36-7.54) remained significant predictors of RA, After quality control, 3209 patients and 3692 controls were included in the study. Eight markers (ie, rs1160542 (AFF3), rs1678542 (KIF5A), rs2476601 (PTPN22), rs3087243 (CTLA4), rs4810485 (CD40), rs5029937 (6q23), rs10760130 (TRAF1/C5) and rs7574865 (STAT4)) were significantly associated with RA by meta-analysis, Recent genome-wide association studies (GWAS) on RA identified known and novel susceptibility genes like HLA-DRB1, PTPN22, STAT4, TRAF1/C5, OLIG3/TNFAIP3, CD40, CCL21, MMEL1-TNFRSF14, CDK6, PRKCQ, IL2RB, and KIF5A-PIP4K2C, In the total RA inception cohort, the HLA-DRB1 shared epitope (per-allele odds ratio (OR) = 2.1, trend P < 0.0001), PTPN22 (per-allele OR = 1.5, trend P < 0.0001), OLIG3/TNFAIP3 locus (per-allele OR = 1.2, trend P = 0.009) and TRAF1/C5 locus (per-allele OR = 1.1, trend P = 0.04) were associated with RA, This study investigated five confirmed rheumatoid arthritis (RA) susceptibility genes/loci (HLA-DRB1, PTPN22, STAT4, OLIG3/TNFAIP3 and TRAF1/C5) for association with susceptibility and severity in an inception cohort, Progress has been made in determining the relative contributions and the interaction of the shared epitope, PTPN22 and smoking in conferring the risk of anticitrullinated protein antibodies-positive and negative RA, Homozygous and heterozygous carriers of the PTPN22 1858T allele had a decreased probability of remission, Our analyses have confirmed previous findings for genes PTPN22 and C5, Fifty-five percent of the FDRs had > or =1 copy of the shared epitope, 20% had > or =1 copy of the PTPN22 polymorphism, and approximately 16% were positive for rheumatoid factor (RF; including isotypes) and/or anti-cyclic citrullinated peptide antibody, As an effect several new genes have been recognized as an HLA-independent genetic risk factors of RA. PTPN22 gene polymorphism, C5/TRAF1 genes region polymorphism and TNFAIP3-OLIG3 genes region polymorphism(s) are among newly identified and already confirmed genetic risk factors, whereas STAT 4, CTLA4, PADI4 and IRF5 genes polymorphisms are listed among probable RA development genetic risk factors, After initial completion of the Human Genome Project on the 16th February 2001, significant progress has been made in identifying other than HLA genome regions linked to the increased RA susceptibility. As an effect several new genes have been recognized as an HLA-independent genetic risk factors of RA. PTPN22 gene polymorphism, C5/TRAF1 genes region polymorphism and TNFAIP3-OLIG3 genes region polymorphism(s) are among newly identified and already confirmed genetic risk factors, Patients were analysed for anti-MCV and anti-cyclic citrullinated peptide (CCP), and were genotyped for human leukocyte antigen (HLA)-DRB1 \"shared epitope\" (SE) and protein tyrosine phosphatase, non-receptor type 22 (PTPN22) 1858T, As well as the major susceptibility gene HLA-DRB1, recent genome-wide and candidate-gene studies reported additional evidence for association of single nucleotide polymorphism (SNP) markers in the PTPN22, STAT4, OLIG3/TNFAIP3 and TRAF1/C5 loci with RA., However, we were able to replicate the association signals between RA and HLA-DRB1 alleles, STAT4 (rs7574865), PTPN22 (rs2476601) and OLIG3/TNFAIP3 (rs10499194 and rs6920220), Additionally, SNPs rs7574865STAT4 (P = 9.2*10-6; OR = 1.71, 95% CI = 1.35 - 2.18) and rs2476601PTPN22 (P = 9.5*10-4; OR = 1.67, 95% CI = 1.23 - 2.26) were associated with susceptibility to RA, whereas after permutation testing OLIG3/TNFAIP3 SNPs rs10499194 and rs6920220 missed our criteria for significance (Pcorr = 0.114 and Pcorr = 0.180, respectively, In our Slovak population, HLA-DRB1 alleles as well as SNPs in STAT4 and PTPN22 genes showed a strong association with RA, Recent advances have led to novel identification of genetic polymorphisms that are associated with susceptibility to rheumatoid arthritis (RA). Currently, 5 loci (HLA, PTPN22, TRAF1/C5, TNFAIP3, and STAT4) have been consistently reported, whereas others have been observed less systematically, Genetic markers such as shared epitope alleles and PTPN22 1858T variant increase the relative risk for disease development, Particularly, ACPAs in combination with human leukocyte antigen-shared epitope alleles and PTPN22 1858T carriage increased the relative risks of developing RA compared with not having these factors, However, inconsistent results of the contributions of non-HLA susceptibility genes have been described, with the exception of a few genes repeatedly associated with RA-susceptibility, such as PTPN22 gene in populations of European ancestry and PADI4 gene in populations of Asian ancestry, revealing the presence of genetic heterogeneity in RA., Functional polymorphisms of PTPN22 and FcgR genes in Tunisian patients with rheumatoid arthritis, We found strong evidence of an association of PTPN22 620W allele and RA, In conclusion, we have confirmed that PTPN22 620W allele is associated with Tunisian RA but does not constitute a factor influencing clinical manifestations., The C1858T allele of the PTPN22 gene has been reported to confer risk for RA, Similarly, the presence or absence of the HLA-DRB1 shared epitope or the RA-associated PTPN22 allele had no influence on this association, Although some genetic risk factors for RA are well-established, most notably HLA-DRB1 and PTPN22, these markers do not fully account for the observed heritability, Lastly, in combination with the other two known genetic risk factors, HLA-DRB1 and PTPN22, the variants reported here generate more than a 45-fold RA-risk differential, Contribution of PTPN22 1858T, TNFRII 196R and HLA-shared epitope alleles with rheumatoid factor and anti-citrullinated protein antibodies to very early rheumatoid arthritis diagnosis, PTPN22 1858T, TNFRII 196R and HLA-SE alleles do not improve the predictive value of RF and ACPA for RA diagnosis in our cohort, and do not contribute to an earlier diagnosis in undifferentiated patients initially negative for RF and ACPA[SEP]Relations: protein kinase C activity has relations: molfunc_protein with PRKCQ, molfunc_protein with PRKCQ. protein-arginine deiminase activity has relations: molfunc_protein with PADI4, molfunc_protein with PADI4. Arginine has relations: drug_protein with SLC22A4, contraindication with cardiovascular disease, drug_protein with SLC22A4, contraindication with cardiovascular disease. Graves disease has relations: disease_protein with PTPN22, disease_protein with PTPN22.", "label": "yes"}
{"id": "converted_1037", "sentence1": "Is Vitamin D deficiency in pregnant women associated with gestational diabetes?", "sentence2": "Insufficient serum levels of 25-OHD were associated with gestational diabetes (pooled odds ratio 1.49, 95% confidence interval 1.18 to 1.89, Vitamin D insufficiency is associated with an increased risk of gestational diabetes, p, Therefore, it is important to identify potentially modifiable risk factors for GDM. Accumulating evidence links vitamin D deficiency with abnormal glucose metabolism, and epidemiological studies have shown that women who develop GDM are more likely to be vitamin D deficient, This review discusses the prevalence, risk factors, and outcomes of GDM and vitamin D deficiency in pregnant women, outlines the possible mechanism of action of vitamin D in glucose homeostasis, and summarizes emerging evidence that associates vitamin D deficiency with the risk of developing GDM, Women with circulating 25-hydroxyvitamin D [25(OH)D] level less than 50 nmol/l in pregnancy experienced an increased risk of preeclampsia [OR 2.09 (95%CI 1.50 -2.90)], gestational diabetes mellitus [OR1.38 (1.12-1.70)], Low maternal vitamin D levels in pregnancy may be associated with an increased risk of preeclampsia, gestational diabetes mellitus,, Association between vitamin D insufficiency and the risk for gestational diabetes mellitus in pregnant Chinese women, 25OHD insufficiency is very common in Chinese women. Low 25OHD status may be associated with insulin resistance and act as a risk factor for GDM., Second-trimester 25(OH)D levels were associated inversely with glucose levels after 1-hour 50-g glucose challenge test; low 25(OH)D levels may be associated with increased risk of GDM., Two hundred sixty-six women were screened. Vitamin D deficiency (25[OH]D <20 ng/mL) was observed in 157 women (59%). We observed an inverse correlation between 25(OH)D levels and hemoglobin A1c, homeostasis model assessment of insulin resistance, serum insulin, and fasting and 1-hour oral glucose tolerance test glucose levels, Lower 25(OH)D levels are associated with disorders of glucose homeostasis and adverse obstetric and newborn outcomes., An association between mid-gestational 25-hydroxy vitamin D and fasting glucose was confirmed in a largely normoglycaemic and vitamin D-replete pregnant population. The correlation between 25-hydroxy vitamin D and β-cell function suggests that vitamin D may influence glucose metabolism through this mechanism., Women with gestational diabetes had significantly lower serum 25-hydroxyvitamin D compared with control subjects (56.3 vs. 62.0 nmol/l, P = 0.018). After adjusting for gestational age and maternal weight, serum 25-hydroxyvitamin D below the top quartile (< 73.5 nmol/l) was associated with a twofold greater likelihood of gestational diabetes (adjusted odds ratio 2.21, 95% confidence interval 1.19-4.13). CONCLUSIONS: Lower vitamin D status in early pregnancy was associated with a significantly increased risk of subsequent gestational diabetes that was independent of race, age, season and maternal weight. This study suggests that vitamin D may influence glucose tolerance during pregnancy, Vitamin D deficiency among pregnant women is frequent in many populations over the world. It is associated with an increased risk of preeclampsia, gestational diabetes mellitus, and caesarean section, Consequences in newborns are low birth weight, neonatal rickets, a risk of neonatal hypocalcemia, asthma and/or type 1 diabetes., A single injection of 300,000 IU of vitamin D3 achieves a 3-month serum 25-hydroxyvitamin D range of 50-80 nmol/l and is an efficient, effective and safe procedure for improving the vitamin status and indices of insulin resistance in mothers with gestational diabetes after delivery., In a cohort of pregnant women with mostly sufficient levels of serum 25(OH)D, vitamin D deficiency was not associated with GDM., The aim of the study is evaluating the associations of FokI vitamin D receptor (VDR) gene polymorphisms with gestational diabetes mellitus (GDM), and its relations with postpartum metabolic syndrome., Our results indicate a meaningful association between FokI VDR genotypes and an increase risk of GDM in Iranian population as well as its effects on postpartum metabolic syndrome., The first-trimester maternal serum level of 25(OH)D is not altered in women with type 2 diabetes, those who develop GDM or those who deliver LGA neonates., Lower 25(OH)D levels are independently associated with poorer glycaemic control. Future randomised trials are needed to determine whether vitamin D plays a role in glycaemic control in GDM., These results suggested that rates of vitamin D deficiency are higher among women with IGT/GDM, and the relationship between vitamin D status and glucose tolerance in pregnancy needs further study., It appears that vitamin D insufficiency during pregnancy is potentially associated with increased risk of preeclampsia, insulin resistance and gestational diabetes mellitus, Mean serum 25OHD concentration was 53.8 +/- 23.9 nmol/l (sd). Ln-25OHD was negatively correlated with serum parathyroid hormone as expected (r -0.24, confidence intervals -0.35 to -0.12). Ln-25OHD was also negatively correlated with fasting plasma glucose (r-0.20, -0.31 to -0.08), fasting insulin (r -0.20, -0.31 to -0.08) and insulin resistance as calculated by homeostasis model assessment (r -0.21, -0.32 to -0.09). The association between fasting glucose and log-transformed 25OHD concentration was of borderline significance after accounting for ethnicity, age and body mass index in multivariate analyses (-0.13, -0.26 to 0.01). The odds ratio of gestational diabetes in women with 25OHD < 50 nmol/l did not reach statistical significance (1.92, 95% confidence interval 0.89-4.17). CONCLUSIONS: Maternal 25OHD concentrations are inversely related to fasting glucose, although further studies are required to establish whether this is independent of the effects of ethnic background., Vitamin D insufficiency is common in Indian mothers but is not associated with gestational diabetes or variation in newborn size., There was no association between maternal 25(OH)D and gestational diabetes (incidence 7% in women with and without hypovitaminosis D), In mothers with hypovitaminosis D, higher 25(OH)D concentrations were associated with lower 30-min glucose concentrations (P=0.03) and higher fasting proinsulin concentrations (P=0.04), Hypovitaminosis D at 30 weeks gestation is common in Mysore mothers. It is not associated with an increased risk of gestational diabetes,, Total prevalence of vitamin D deficiency (<25 nmol/L) was found in 70.6% of pregnant women. Prevalence of severe vitamin D deficiency (<12.5) in GDM patients was higher than in normoglycaemic pregnancies., These results show that a positive correlation of 25(OH) vitamin D concentrations with insulin sensitivity and vitamin D deficiency could be a confirmative sign of insulin resistance., was to examine whether maternal dietary intake of vitamin D, omega-3 fatty acids, and omega-6 fatty acids during pregnancy is associated with the appearance of islet autoimmunity (IA) in offspring, Maternal intake of vitamin D via food was significantly associated with a decreased risk of IA appearance in offspring, independent of HLA genotype, family history of type 1 diabetes, presence of gestational diabetes mellitus, and ethnicity (adjusted HR = 0.37; 95% CI 0.17-0.78). Vitamin D intake via supplements, omega-3 fatty acids, and omega-6 fatty acids intake during pregnancy were not associated with appearance of IA in offspring. CONCLUSIONS: Our findings suggest that maternal intake of vitamin D through food during pregnancy may have a protective effect on the appearance of IA in offspring.[SEP]Relations: Ergocalciferol has relations: drug_drug with Vitamin D, drug_drug with Vitamin D. Cholecalciferol has relations: drug_drug with Vitamin D, drug_drug with Vitamin D.", "label": "yes"}
{"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]", "label": "yes"}
{"id": "converted_995", "sentence1": "Is Growth factor independence 1b (GFI1B) important for hematopoiesis?", "sentence2": "Growth Factor Independence (Gfi) transcription factors play essential roles in hematopoiesis, differentially activating and repressing transcriptional programs required for hematopoietic stem/progenitor cell (HSPC) development and lineage specification, gfi1aa and gfi1b have distinct roles in regulating primitive and definitive hematopoietic progenitors,, gfi1b is required for definitive hematopoiesis, LSD1-kd was associated with the upregulation of key hematopoietic genes, including Gfi1b, GFI1 and GFI1B control the loss of endothelial identity of hemogenic endothelium during hematopoietic commitment,  Taken together, our findings demonstrate a critical and specific role of the GFI1 transcription factors in the first steps of the process leading to the generation of hematopoietic progenitors from hemogenic endothelium, A short Gfi-1B isoform controls erythroid differentiation, Gfi-1B is a transcriptional repressor essential for the regulation of erythropoiesis and megakaryopoiesis, Among the few down-regulated genes was Gfi1b, a known repressor of erythroid differentiation, This reversible modulation of endothelial-haematopoietic state is accomplished by targeting key haematopoietic transcription factors for downregulation, including Runx1, Gata1, Gfi1B, Ikaros, and PU.1, Gfi1 and Gfi1b: key regulators of hematopoiesis, we review how Gfi1 and its paralogue Gfi1b control the development of blood cells, discuss how changes in Gfi1 and Gfi1b function contribute to hematological disease and report on the molecular function of these proteins., Gfi-1B controls human erythroid and megakaryocytic differentiation by regulating TGF-beta signaling at the bipotent erythro-megakaryocytic progenitor stage, Growth factor independence-1B (Gfi-1B) is a transcriptional repressor essential for erythropoiesis and megakaryopoiesis, Targeted gene disruption of GFI1B in mice leads to embryonic lethality resulting from failure to produce definitive erythrocytes, hindering the study of Gfi-1B function in adult hematopoiesis, We here show that, in humans, Gfi-1B controls the development of erythrocytes and megakaryocytes by regulating the proliferation and differentiation of bipotent erythro-megakaryocytic progenitors, To date, we have identified two common integration sites involving genes encoding transcription factors that play a critical role in hematopoiesis (Evi1 and Gfi1b loci), Transcription factors play essential roles in both normal and malignant hematopoiesis. This is the case for the growth factor independent 1b (GFI1B) transcription factor, which is required for erythroid and megakaryocytic differentiation and over-expressed in leukemic patients and cell lines, We localized several conserved non-coding elements containing multiple erythroid specific transcription factor binding sites at the GFI1B locus. In GFI1B-expressing cells a subset of these conserved non-coding elements and the promoter adopt a close spatial conformation, localize with open chromatin sites, harbor chromatin modifications associated with gene activation and bind multiple transcription factors and co-repressors, Our findings indicate that GFI1B regulatory elements behave as activators and repressors, To investigate the molecular effects of growth factor independence 1B (Gfi-1B), a transcription factor essential for the development of hematopoietic cells and differentiation of erythroid and megakaryocytic lineages, Our data indicate that Gfi-1B signalling is important for commitment and maturation of hematopoietic cell populations, Gfi-1 and Gfi-1b are homologous transcriptional repressors involved in diverse developmental contexts, including hematopoiesis and oncogenesis, Gfi1b:green fluorescent protein knock-in mice reveal a dynamic expression pattern of Gfi1b during hematopoiesis that is largely complementary to Gfi1, We found highly dynamic expression patterns of Gfi1b in erythroid cells, megakaryocytes, and their progenitor cells (MEPS) where Gfi1 is not detected. Vice versa, Gfi1b could not be found in granulocytes, activated macrophages, or their granulomonocytic precursors (GMPs) or in mature naive or activated lymphocytes where Gfi1 is expressed, suggesting a complementary regulation of both loci during hematopoiesis, Gfi1 and Gfi1b act equivalently in haematopoiesis, our findings show that an intact SNAG domain is essential for all functions of Gfi1 and that Gfi1b can replace Gfi1 functionally in haematopoiesis, Gfi-1 oncoproteins in hematopoiesis, Recent gene targeting experiments and mutational screening in humans have revealed an essential role for Gfi-1 and Gfi-1B in hematopoiesis, Gfi-1B disruption is embryonic lethal due to a block of erythropoiesis. Gfi-1B is required for both erythroid and megakaryocyte development, Erythroid expansion mediated by the Gfi-1B zinc finger protein: role in normal hematopoiesis,  we identified that the expression of Gfi-1B (growth factor independence-1B) is highly restricted to hematopoietic stem cells, erythroblasts, and megakaryocytes, These findings establish Gfi-1B as a novel erythroid regulator and reveal its specific involvement in the regulation of erythroid cell growth through modulating erythroid-specific gene expression, The zinc-finger proto-oncogene Gfi-1b is essential for development of the erythroid and megakaryocytic lineages, we establish that Gfi-1b is required for the development of two related blood lineages, erythroid and megakaryocytic, in mice, Gfi-1b(-/-) embryonic stem cells fail to contribute to red cells of adult chimeras. Gfi-1b(-/-) embryos exhibit delayed maturation of primitive erythrocytes and subsequently die with failure to produce definitive enucleated erythrocytes, Gfi-1b is an essential transcriptional regulator of erythroid and megakaryocyte development, Growth factor independence 1b (GFI1B) is a DNA binding repressor of transcription with vital functions in hematopoiesis., Conversely, loss of gfi1b silences runx-1, c-myb, ikaros and cd41, indicating that gfi1b is required for definitive hematopoiesis., Gfi1b:green fluorescent protein knock-in mice reveal a dynamic expression pattern of Gfi1b during hematopoiesis that is largely complementary to Gfi1., Gfi1 and Gfi1b: key regulators of hematopoiesis., We show that gfi1aa and gfi1b are expressed in the primitive and definitive sites of hematopoiesis in zebrafish., Targeted gene disruption of GFI1B in mice leads to embryonic lethality resulting from failure to produce definitive erythrocytes, hindering the study of Gfi-1B function in adult hematopoiesis., Growth factor independence 1b (gfi1b) is important for the maturation of erythroid cells and the regulation of embryonic globin expression., Growth factor-independence 1b (Gfi1b) is a zinc finger transcription factor essential for erythroid and megakaryocytic development., Gfi1b (growth factor independence 1b) is a zinc finger transcription factor essential for development of the erythroid and megakaryocytic lineages., In fact, we demonstrate that VPA treatment is able to induce the expression of growth factor-independent protein 1B (GFI1B) and of mixed-lineage leukemia translocated to chromosome 3 protein (MLLT3), which are crucial regulators of erythrocyte and megakaryocyte differentiation, and that the up-regulation of these genes is mediated by the histone hyperacetylation at their promoter sites., Growth factor independence-1B (Gfi-1B) is a transcriptional repressor essential for erythropoiesis and megakaryopoiesis., Gfi-1B (growth factor independence-1B) gene is an erythroid-specific transcription factor, whose expression plays an essential role in erythropoiesis., Evidence that growth factor independence 1b regulates dormancy and peripheral blood mobilization of hematopoietic stem cells., We report here that adult mice conditionally deficient for the transcription Growth factor independence 1b (Gfi1b) show a significant expansion of functional HSCs in the bone marrow and blood., Growth factor-independence 1b (Gfi1b) is a zinc finger transcription factor essential for erythroid and megakaryocytic development, Teleost growth factor independence (gfi) genes differentially regulate successive waves of hematopoiesis., Gfi-1B (growth factor independence-1B) gene is an erythroid-specific transcription factor, whose expression plays an essential role in erythropoiesis, Our data indicate that Gfi-1B signalling is important for commitment and maturation of hematopoietic cell populations., We report here that adult mice conditionally deficient for the transcription Growth factor independence 1b (Gfi1b) show a significant expansion of functional HSCs in the bone marrow and blood[SEP]Relations: transcription repressor complex has relations: cellcomp_protein with GFI1, cellcomp_protein with GFI1. hemopoiesis has relations: bioprocess_protein with GFI1, bioprocess_protein with GFI1.", "label": "yes"}
{"id": "converted_84", "sentence1": "Is valproic acid effective for glioblastoma treatment?", "sentence2": "A Phase 2 Study of Concurrent Radiation Therapy, Temozolomide, and the Histone Deacetylase Inhibitor Valproic Acid for Patients With Glioblastoma., PURPOSE: Valproic acid (VPA) is an antiepileptic agent with histone deacetylase inhibitor (HDACi) activity shown to sensitize glioblastoma (GBM) cells to radiation in preclinical models.,  Median overall survival (OS) was 29.6 months (range: 21-63.8 months), and median progression-free survival (PFS) was 10.5 months (range: 6.8-51.2 months). OS at 6, 12, and 24 months was 97%, 86%, and 56%, respectively. PFS at 6, 12, and 24 months was 70%, 43%, and 38% respectively. , CONCLUSIONS: Addition of VPA to concurrent RT/TMZ in patients with newly diagnosed GBM was well tolerated. Additionally, VPA may result in improved outcomes compared to historical data and merits further study., Treatment of GDSCs with histone deacetylase inhibitors, TSA and VPA, significantly reduced proliferation rates of the cells and expression of the stem cell markers, indicating differentiation of the cells. Since differentiation into GBM makes them susceptible to the conventional cancer treatments, we posit that use of histone deacetylase inhibitors may increase efficacy of the conventional cancer treatments for eliminating GDSCs., Several clinical studies have reported that valproic acid could prolong survival of GBM patients. , Our meta-analysis confirmed the benefit of using VPA (HR, 0.56; 95% CI, 0.44-0.71). Sub-group analysis shows that patients treated with VPA had a hazard ratio of 0.74 with a 95% confidence interval of 0.59-0.94 vs. patients treated by other-AEDs and a hazard ratio of 0.66 with a 95% confidence interval of 0.52-0.84 vs. patients treated by administration of non-AEDs. , .CONCLUSION: The results of our study suggest that glioblastoma patients may experience prolonged survival due to VPA administration. , A new and exciting insight is the potential contribution of VPA to prolonged survival, particularly in glioblastomas. , Valproic acid (VPA) is an antiepileptic agent with histone deacetylase inhibitor (HDACi) activity shown to sensitize glioblastoma (GBM) cells to radiation in preclinical models, Valproic acid use during radiation therapy for glioblastoma associated with improved survival, Valproic acid (VA) is an antiepileptic drug (AED) and histone deacetylase (HDAC) inhibitor taken by patients with glioblastoma (GB) to manage seizures, and it can modulate the biologic effects of radiation therapy (RT), Valproic acid use during radiation therapy for glioblastoma associated with improved survival., Prolonged survival with valproic acid use in the EORTC/NCIC temozolomide trial for glioblastoma., PURPOSE: Valproic acid (VA) is an antiepileptic drug (AED) and histone deacetylase (HDAC) inhibitor taken by patients with glioblastoma (GB) to manage seizures, and it can modulate the biologic effects of radiation therapy (RT). We investigated whether VA use during RT for GB was associated with overall survival (OS).METHODS AND MATERIALS: Medical records of 544 adults with GB were retrospectively reviewed. Analyses were performed to determine the association of Radiation Therapy Oncology Group recursive partitioning analysis (RTOG RPA) class, seizure history, and concurrent temozolomide (TMZ) and AED use during RT with OS.RESULTS: Seizures before the end of RT were noted in 217 (40%) patients, and 403 (74%) were taking an AED during RT; 29 (7%) were taking VA. , When the analysis was restricted to patients who received concurrent TMZ, VA use was marginally associated with OS (P=.057; HR, 0.54; 95% CI, -0.09 to 1.17), independently of RTOG RPA class and seizure history., Patients using VPA in combination with temozolomide showed a longer median survival of 69 weeks (95% confidence interval [CI]: 61.7-67.3) compared with 61 weeks (95% CI: 52.5-69.5) in the group without VPA (hazard ratio, 0.63; 95% CI: 0.43-0.92; P = .016), adjusting for age, extent of resection, and O(6)-DNA methylguanine-methyltransferase promoter methylation status., Use of VPA together with chemoradiation with temozolomide results in a 2-months' longer survival of patients with GBM.[SEP]", "label": "yes"}
{"id": "converted_370", "sentence1": "Is intense physical activity associated with longevity?", "sentence2": "Our major finding is that repeated very intense exercise prolongs life span in well trained practitioners., Death rates declined with increased levels of total activity (estimated in kilocalories), and declined also with increased intensity of effort measured as from none, to light, to moderately vigorous or vigorous sports play. Death rates at any given quantity of physical exercise were lower for men playing moderately intense sports than for less vigorous men., he purpose of this study was to investigate if jogging, which can be very vigorous, is associated with increased all-cause mortality in men and women., This long-term study of joggers showed that jogging was associated with significantly lower all-cause mortality and a substantial increase in survival for both men and women., Light activities (<4 multiples of resting metabolic rate (METs)) were not associated with reduced mortality rates, moderate activities (4-<6 METs) appeared somewhat beneficial, and vigorous activities (> or =6 METs) clearly predicted lower mortality rates (p, trend = 0.72, 0.07, and <0.001, respectively)., These data demonstrate a graded inverse relationship between total physical activity and mortality. Furthermore, vigorous activities but not nonvigorous activities were associated with longevity., The capacity for prolonged and vigorous physical exercise, particularly if the exercise is recreational, is a strong indicator of longevity.[SEP]", "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: Norepinephrine has relations: drug_drug with Vortioxetine, drug_drug with Duloxetine, drug_drug with Vortioxetine, drug_drug with Duloxetine. anxiety disorder has relations: disease_disease with anxiety, disease_disease with anxiety, disease_disease with anxiety, disease_disease with anxiety. Vortioxetine has relations: drug_drug with Duloxetine, drug_drug with Duloxetine. Duloxetine has relations: drug_drug with Vortioxetine, drug_drug with Vortioxetine. neurotransmitter uptake has relations: bioprocess_bioprocess with neurotransmitter reuptake, bioprocess_bioprocess with neurotransmitter reuptake. Agomelatine has relations: drug_drug with Duloxetine, drug_drug with Vortioxetine, drug_drug with Duloxetine, drug_drug with Vortioxetine. Dopamine has relations: drug_drug with Duloxetine, drug_drug with Vortioxetine, drug_drug with Duloxetine, drug_drug with Vortioxetine. Venlafaxine has relations: drug_drug with Vortioxetine, drug_drug with Duloxetine, drug_drug with Vortioxetine, drug_drug with Duloxetine. Vilazodone has relations: drug_drug with Duloxetine, drug_drug with Vortioxetine, drug_drug with Duloxetine, drug_drug with Vortioxetine. Protein S human has relations: drug_drug with Duloxetine, drug_drug with Duloxetine.", "label": "yes"}
{"id": "converted_2782", "sentence1": "Can breastfeeding confer protection from type I diabetes?", "sentence2": "In the neonate and infant, among other benefits, lactation confers protection from future both type 1 and type 2 diabetes.[SEP]", "label": "yes"}
{"id": "converted_1432", "sentence1": "Do U6-associated proteins Lsm4 and Lsm6 interact with SMN?", "sentence2": "SMN also interacts with at least two of the U6-associated Sm-like (Lsm) proteins, Lsm4 and Lsm6. , Interestingly, SMN also interacts with at least two of the U6-associated Sm-like (Lsm) proteins, Lsm4 and Lsm6, Furthermore, we present evidence for two separate binding sites in SMN for Sm/Lsm proteins., Interestingly, SMN also interacts with at least two of the U6-associated Sm-like (Lsm) proteins, Lsm4 and Lsm6. , Symmetrical dimethylation of arginine residues in spliceosomal Sm protein B/B' and the Sm-like protein LSm4, and their interaction with the SMN protein., Interestingly, SMN also interacts with at least two of the U6-associated Sm-like (Lsm) proteins, Lsm4 and Lsm6. Furthermore, the carboxyl-terminal arginine- and glycine-rich domain of Lsm4 directly interacts with SMN., This entity promotes the binding of a set of factors, termed LSm/Sm proteins, onto snRNA to form the core structure of these particles. , Toward an assembly line for U7 snRNPs: interactions of U7-specific Lsm proteins with PRMT5 and SMN complexes., In this report, we demonstrate that the coilin C-terminal domain binds directly to various Sm and Lsm proteins via their Sm motifs. We show that the region of coilin responsible for this binding activity is separable from that which binds to SMN., Thus, the ability to interact with free Sm (and Lsm) proteins as well as with intact snRNPs, indicates that coilin and CBs may facilitate the modification of newly formed snRNPs, the regeneration of 'mature' snRNPs, or the reclamation of unassembled snRNP components., Moreover this structure has important consequences for snRNP assembly that is mediated by two complexes containing the PRMT5 methyltransferase and the SMN (survival of motor neurons) protein, respectively., Arginine/glycine (RG)-rich domains in components of the SMN complex interact with Sm, like-Sm (LSm), fibrillarin, RNA helicase A (Gu), and coilin proteins, all of which are antigen targets in a variety of diseases. [SEP]", "label": "yes"}
{"id": "converted_530", "sentence1": "Is there an association between bruxism and reflux", "sentence2": "Rhythmic masticatory muscle activity, including sleep bruxism (SB), can be induced in healthy individuals by experimental esophageal acidification, which plays an important role in the pathogenesis of gastroesophageal reflux disease (GERD). However, no robust evidence supports the association between SB and GERD., Sleep bruxism is prevalent in GERD patients, and GERD is highly associated with SB., Our large-scale cross-sectional study found that problem behaviors in adolescents were associated with sleep problems, including sleep bruxism, as well as lifestyle and food habits and GERD symptoms., The frequencies of EMG bursts, rhythmic masticatory muscle activity (RMMA) episodes, grinding noise, and the RMMA/microarousal ratio were significantly higher in the 20-minute period after acidic infusion than after saline infusion. RMMA episodes including SB were induced by esophageal acidification. , Direct restorative treatment of dental erosion caused by gastroesophageal reflux disease associated with bruxism:, This article presents a case report of a 27-year-old male smoker with tooth wear and dentin sensitivity caused by GERD associated with bruxism, Dental wear caused by association between bruxism and gastroesophageal reflux disease:, This paper presents a case report in which bruxism associated with acid feeding, smoking habit and episodes of gastric reflow caused severe tooth wear and great muscular discomfort with daily headache episodes., most jaw muscle activities, ie, RMMA, single short-burst, and clenching episodes, occur in relation to gastroesophageal reflux mainly in the supine position., Association between nocturnal bruxism and gastroesophageal reflux., Nocturnal bruxism may be secondary to nocturnal gastroesophageal reflux, occurring via sleep arousal and often together with swallowing.[SEP]Relations: Gastroesophageal reflux has relations: disease_phenotype_positive with gastroesophageal reflux disease, disease_phenotype_positive with gastroesophageal reflux disease.", "label": "yes"}
{"id": "converted_1274", "sentence1": "Is Fanconi anemia presented as a genetically and clinically heterogeneous disease entity?", "sentence2": "Fanconi anaemia (FA) is a rare, autosomal recessive, genetically complex, DNA repair deficiency syndrome in man. Patients with FA exhibit a heterogeneous spectrum of clinical features. The most significant and consistent phenotypic characteristics are stem cell loss, causing progressive bone marrow failure and sterility, diverse developmental abnormalities and a profound predisposition to neoplasia. To date, 15 genes have been identified, biallelic disruption of any one of which results in this clinically defined syndrome, Fanconi anemia (FA) is a clinically and genetically heterogeneous disorder, Significant phenotypic differences were found. FA-G patients had more severe cytopenia and a higher incidence of leukemia. Somatic abnormalities were less prevalent in FA-C, but more common in the rare groups FA-D, FA-E, and FA-F. In FA-A, patients homozygous for null mutations had an earlier onset of anemia and a higher incidence of leukemia than those with mutations producing an altered protein, Fanconi anemia (FA), an autosomal recessive disorder characterized by a progressive pancytopenia associated with congenital anomalies and high predisposition to malignancies, is a genetically and clinically heterogeneous disease. At least eight complementation groups (FA-A to FA-H) have been identified, Fanconi anemia (FA), an autosomal recessive disorder characterized by a progressive pancytopenia associated with congenital anomalies and high predisposition to malignancies, is a genetically and clinically heterogeneous disease. At least eight complementation groups (FA-A to FA-H) have been identified with their relative prevalence varying among the ethnical backgrounds, Fanconi anemia is a rare autosomal recessive disorder characterized clinically by congenital abnormalities, progressive bone marrow failure, and a predisposition to malignancy. FA cells are sensitive to DNA cross-linking agents. Complementation analysis of FA cells using somatic cell fusion has facilitated the identification of eight complementation groups, suggesting that FA is a genetically heterogeneous disorder. Six genes (FANCA, FANCC, FANCD2, FANCE, FANGF, FANCG) have been cloned so far, Fanconi anemia (FA), an autosomal recessive disorder characterized by a progressive pancytopenia associated with congenital anomalies and high predisposition to malignancies, is a genetically and clinically heterogeneous disease., Fanconi anemia (FA), an autosomal recessive disorder characterized by a progressive pancytopenia associated with congenital anomalies and high predisposition to malignancies, is a genetically and clinically heterogeneous disease., Among patients with bone marrow failure (BMF) syndrome, some are happened to have underlying Fanconi anemia (FA), a genetically heterogeneous disease, which is characterized by progressive pancytopenia and cancer susceptibility., Fanconi anemia (FA) is a genetically and phenotypically heterogeneous inherited disease., Fanconi anemia is a genetically heterogeneous recessive disease characterized mainly by bone marrow failure and cancer predisposition., INTRODUCTION: Fanconi anemia (FA) is a genetically and phenotypically heterogeneous inherited disease., Fanconi anemia (FA) is a genetically heterogeneous, autosomal recessive disorder characterized by pediatric bone marrow failure and congenital anomalies., Fanconi anemia (FA) is a heterogeneous disease associated with a bone marrow failure, cancer predisposition and hypersensitivity to DNA crosslinking agents., Fanconi anemia is a genetically heterogeneous chromosomal instability syndrome, characterized by multiple congenital anomalies, progressive bone marrow failure, and a predisposition to malignancy., Fanconi anemia (FA) is a heterogeneous disease characterized by spontaneous chromosomal breaks and abnormal DNA repair., Fanconi anemia (FA) is a genetically heterogeneous disease with at least eight genes on the basis of complementation groups (FAA to FAH)., Fanconi anemia (FA) is a clinically and genetically heterogeneous disorder., Fanconi anaemia (FA) is a genetically heterogeneous disease with at least eight complementation groups (A-H)., FA is a genetically heterogeneous disease with at least seven genes so far identified., Fanconi anemia (FA) is an autosomal recessive rare disease characterized by progressive pancytopenia, congenital malformations and predisposition to acute myeloid leukemia., Fanconi anemia is genetically heterogeneous, with at least eight complementation groups of FA (FAA to FAD2)., Fanconi anemia (FA), an autosomal recessive disorder characterized by a progressive pancytopenia associated with congenital anomalies and high predisposition to malignancies, is a genetically and clinically heterogeneous disease, Fanconi anemia (FA), an autosomal recessive disorder characterized by a progressive pancytopenia associated with congenital anomalies and high predisposition to malignancies, is a genetically and clinically heterogeneous disease, The disease is clinically heterogeneous; eight different complementation groups (FA A-H) and, thus, genetic loci have been discovered, The hereditary genetic disorder Fanconi anemia (FA) belongs to the heterogeneous group of diseases associated with defective DNA damage repair, The clinical manifestations of FA are heterogeneous, but one common outcome in the majority of patients is the development of life-threatening hematologic disease, Fanconi anemia is a genetically heterogeneous chromosomal breakage disorder exhibiting a high degree of clinical variability, Fanconi anemia (FA) is a genetically heterogeneous chromosomal instability syndrome associated with multiple congenital abnormalities, aplastic anemia, and cancer, Fanconi anemia (FA) is a genetically heterogeneous autosomal recessive syndrome associated with chromosomal instability, hypersensitivity to DNA cross-linking agents, and predisposition to malignancy, Fanconi anemia (FA) is a rare autosomal recessive disease characterized by progressive pancytopenia, congenital malformations, and predisposition to acute myeloid leukemia, Fanconi anemia (FA) is a heterogeneous disease characterized by spontaneous chromosomal breaks and abnormal DNA repair, Fanconi anemia (FA) is a genetically and phenotypically heterogeneous recessive disorder characterized by diverse congenital malformations, progressive pancytopenia and predisposition to both hematologic malignancies and solid tumors, Fanconi anemia is a genetically heterogeneous chromosomal instability syndrome, characterized by multiple congenital anomalies, progressive bone marrow failure, and a predisposition to malignancy[SEP]Relations: Fanconi anemia complementation group has relations: disease_protein with FANCG, disease_protein with FANCC, disease_protein with FANCD2, disease_protein with FANCE, disease_protein with FANCA, disease_protein with FANCG, disease_protein with FANCC, disease_protein with FANCD2, disease_protein with FANCE, disease_protein with FANCA, disease_protein with FANCG, disease_protein with FANCC, disease_protein with FANCD2, disease_protein with FANCE, disease_protein with FANCA, disease_protein with FANCG, disease_protein with FANCC, disease_protein with FANCD2, disease_protein with FANCE, disease_protein with FANCA, disease_protein with FANCG, disease_protein with FANCC, disease_protein with FANCD2, disease_protein with FANCE, disease_protein with FANCA, disease_protein with FANCG, disease_protein with FANCC, disease_protein with FANCD2, disease_protein with FANCE, disease_protein with FANCA, disease_protein with FANCG, disease_protein with FANCC, disease_protein with FANCD2, disease_protein with FANCE, disease_protein with FANCA, disease_protein with FANCG, disease_protein with FANCC, disease_protein with FANCD2, disease_protein with FANCE, disease_protein with FANCA, disease_protein with FANCG, disease_protein with FANCC, disease_protein with FANCD2, disease_protein with FANCE, disease_protein with FANCA, disease_protein with FANCG, disease_protein with FANCC, disease_protein with FANCD2, disease_protein with FANCE, disease_protein with FANCA. Fanconi anemia has relations: disease_protein with FANCG, disease_protein with FANCC, disease_protein with FANCE, disease_protein with FANCD2, disease_protein with FANCA, disease_protein with FANCG, disease_protein with FANCC, disease_protein with FANCE, disease_protein with FANCD2, disease_protein with FANCA.", "label": "yes"}
{"id": "converted_2315", "sentence1": "Is propranolol used for treatment of infantile hemangioma?", "sentence2": "Low-dose propranolol for infantile hemangioma of the head and neck: Analysis of 23 consecutive patients., BACKGROUND: More and more infantile hemangiomas (IH) are being treated with propranolol, but the effectiveness, dosage, and treatment course are still in dispute., CONCLUSIONS: Low-dose propranolol appears to be effective and safe for IH, especially for those patients previously treated with corticosteroid and who had no response or severe side-effects., Cardiovascular Profile of Propranolol after Multiple Dosing in Infantile Hemangioma., Propranolol is becoming the treatment of choice for complicated infantile hemangioma., In conclusion, propranolol 2 mg/kg of body weight daily causes a statistically though not clinically relevant decrease in blood pressure and heart rate in cardially healthy infants affected by infantile hemangioma. , Importance: Propranolol hydrochloride has become the primary medical treatment for problematic infantile hemangioma; however, the expression of propranolol's target receptors during growth, involution, and treatment of hemangioma remains unclear., BACKGROUND: Infantile hemangiomas (IHs) are the most common benign vascular tumors of childhood. Propranolol is an effective drug in treating IH. , Ultrasonography as an objective tool for assessment of infantile hemangioma treatment with propranolol., CONCLUSION: Ultrasonographic measurements contribute to demonstrate tumor regression and IH response to propranolol., Propranolol treatment was recently reported to be successful for the management of severe infantile hemangioma., We conclude that the initial use of propranolol as the sole treatment for infantile airway hemangioma is promising., Propranolol has been proposed for the treatment of infantile hemangiomas., Propranolol therapy is changing the treatment paradigm for infantile hemangioma., Propranolol has been successfully used recently in a limited number of children with Infantile hemangioma., Propranolol has been proposed for the treatment of infantile hemangiomas., CONCLUSIONS This is the first report of successful therapy of an intracranial infantile hemangioma with propranolol., PURPOSE The successful use of nadolol as an alternative to propranolol therapy in three cases of infantile hemangioma is reported., Propranolol has been used successfully in a limited number of children with infantile hemangiomas., CONCLUSIONS High-dose Propranolol is very effective in the treatment of infantile hemangioma with minor side effects and short disease period., Propranolol is novel and safe medication for treatment of infantile hemangioma., Propranolol is the only Food and Drug Administration approved therapy for treatment of patients with this vascular anomaly and should be considered first-line therapy for genital infantile hemangiomas., CONCLUSION Propranolol may be a promising therapeutic modality for infantile hemangioma., Propranolol, which is often used to treat cutaneous infantile hemangiomas, is not currently standard treatment for intracranial infantile hemangiomas., Preliminary results of propranolol treatment for patients with infantile hemangioma., Propranolol therapy is changing the treatment paradigm for infantile hemangioma., Propranolol should be considered as a first-line treatment of infantile hemangiomas.., Propranolol, a non-selective beta-blocker, has recently been introduced as a treatment for infantile hemangiomas.[SEP]Relations: capillary infantile hemangioma has relations: disease_disease with hemangioma, disease_disease with hemangioma.", "label": "yes"}
{"id": "converted_2843", "sentence1": "Is ADP-ribosylation a PTM?", "sentence2": "ADP-ribosylation is a PTM, in which ADP-ribosyltransferases use nicotinamide adenine dinucleotide (NAD+) to modify target proteins with ADP-ribose, Poly-ADP-ribosylation (PARylation) is a protein posttranslational modification (PTM) that is critically involved in many biological processes that are linked to cell stress responses., ADP-ribosylation is a post-translational modification (PTM) implicated in several crucial cellular processes, ranging from regulation of DNA repair and chromatin structure to cell metabolism and stress responses.[SEP]", "label": "yes"}
{"id": "converted_1671", "sentence1": "Is LPS a microbial product?", "sentence2": "and microbial translocation [lipopolysaccaride (LPS), microbial 16S rDNA and sCD14] , Lipopolysaccharide sensing an important factor in the innate immune response to Gram-negative bacterial infections, bacterial lipopolysaccharide (LPS), sterile bacterial wall lipopolysaccharide (LPS) to investigate the changes in innate lung microbiota[SEP]", "label": "yes"}
{"id": "converted_539", "sentence1": "Are integrins part of the extracellular matrix?", "sentence2": "Several constituents of the ECM provide adhesive cues, which serve as binding sites for cell trans-membrane receptors, such as integrins., We also determined that blocking β1integrins, the major class of receptors for all ECM proteins tested,, Here, we elucidate a cross-scale mechanism for tissue assembly and ECM remodeling involving Cadherin 2, the ECM protein Fibronectin, and its receptor Integrin α5. , due to the diverse functions and variable expression of proteoglycans, matrix proteins, and integrins, it is rather difficult to identify a comprehensive therapeutic target among ECM components., Integrin-dependent cell-extracellular matrix (ECM) adhesion is a determinant of spindle orientation., The extracellular matrix component periostin is a secreted protein that functions as both a cell attachment protein and an autocrine or paracrine factor that signals through the cell adhesion molecule integrins αvβ3 and αvβ5. , Integrin receptors connect the extracellular matrix to the cell cytoskeleton to provide essential forces and signals. ,  the integrin, talin, and actin filament form a linear complex of which both ends are typically anchored to the extracellular matrices via integrins., Integrins, a central family of cellular ECM receptors, have been implicated in these processes but their specific role in ES cell self-renewal remains unclear., Attachment to the extracellular matrix is mediated by a complex of adhesion proteins, including integrins, signaling molecules, actin and actin-binding proteins, and scaffolding proteins., Beta 1 integrin binding plays a role in the constant traction force generation in response to varying stiffness for cells grown on mature cardiac extracellular matrix.[SEP]", "label": "yes"}
{"id": "converted_3863", "sentence1": "Is liraglutide effective for weight reduction?", "sentence2": "Liraglutide has been approved at higher dose for obesity. , This meta-analysis finds a significant reduction in body weight with orlistat (N = 10,435; ∆ -3.07 Kg, 95% CI, -3.76 to -2.37), phentermine plus topiramate (N = 2985; ∆ -9.77 Kg; 95% CI, -11.73 to -7.81), lorcaserin (N = 16,856; ∆ -3.08 Kg; 95% CI, -3.49 to -2.66), naltrexone plus bupropion (N = 3239; ∆ -4.39 Kg; 95% CI, -5.05 to -3.72) and liraglutide (N = 4978; ∆ -5.25 Kg; 95% CI, -6.17 to -4.32), compared to placebo (all p < 0.00001)., CONCLUSION: In patients with T1D, liraglutide might prove be an adjunct to insulin, improving glycemic control, inducing body weight loss and decreasing exogenous insulin requirements and severe hypoglycemia., Data from most recent meta-analyses showed that the overall placebo-subtracted weight reduction (%) with the use of anti-obesity drugs for at least 12 months ranges from 2.9% to 6.8%; phentermine/topiramate (-6.8%) liraglutide (-5.4%), naltrexone/bupropion (-4.0%), lorcaserin (-3.1%), and orlistat (-2.9%). , RESULTS: Currently, the FDA has approved several molecules for the treatment of obesity, both in monotherapy and in combination. Pharmacological monotherapies focus mainly on a single protein target and include orlistat, lorcaserin and liraglutide while the combination molecules propose a multitarget approach and include phentermine/topiramate and naltrexone/bupropion. , Phentermine-topiramate and liraglutide have been associated with the highest probability of at least 5% weight loss. , Currently, high-dose liraglutide has been used for weight control in non-diabetic patients. , CONCLUSIONS: Low-dose liraglutide still has high efficacy in weight reduction in Taiwanese people, especially for those of younger age., BACKGROUND: Liraglutide, a glucagon-like peptide-1 (GLP-1) analogue, has been shown to possess pleiotropic effects including body weight reduction., INTRODUCTION: For people with type 2 diabetes (T2DM) inadequately controlled with oral antidiabetic drugs (OADs), evidence from both randomized controlled trials (RCTs) and real-world studies has demonstrated that treatment intensification with liraglutide offers effective glycemic control, weight reduction, and a lower risk of hypoglycemia compared to treatment intensification with insulin or additional OADs., wise regression analysis demonstrated that baseline BMI and previous insulin dose were positively associated with body weight reduction and baseline HbA1c was positively associated with reduction of HbA1c at 2 years after liraglutide introduction.CONC,  control (placebo, sitagliptin, glimepiride, dulaglutide, insulin glargine, and NPH), liraglutide in combination with metformin resulted in significant reductions in HbA1c, bodyweight, FPG, and PPG, and similar reductions in SBP, and DBP. Moreover, liraglutide comb, Liraglutide (LIRA) treatment is associated with the dose-dependent reduction of weight. Hig, Liraglutide, a glucagon-like peptide (GLP-1) receptor agonist, has showed favorable effects in the glycaemic control and weight reduction in patients with type 2 diabetes mellitus (T2DM). The me, Here, we determined that liraglutide does not activate GLP-1-producing neurons in the hindbrain, and liraglutide-dependent body weight reduction in rats was independent of GLP-1 receptors (GLP-1Rs) in the vagus nerve, area postrema, and paraventricular nucleus., Liraglutide is associated with body weight loss, and reductions in systolic blood pressure have been observed throughout the clinical trials., CONCLUSIONS AND RELEVANCE: Among overweight and obese participants with type 2 diabetes, use of subcutaneous liraglutide (3.0 mg) daily, compared with placebo, resulted in weight loss over 56 weeks., CONCLUSION: Liraglutide (monotherapy or added to metformin) significantly reduced fat mass and fat percentage vs. glimepiride in patients with T2D., CONCLUSIONS: In adolescents with obesity, the use of liraglutide (3.0 mg) plus lifestyle therapy led to a significantly greater reduction in the BMI standard-deviation score than placebo plus lifestyle therapy., Five weeks of treatment with the GLP-1 analogue liraglutide improves glycaemic control and lowers body weight in subjects with type 2 diabetes., In the latter case, body weight was reduced in comparison to metformin plus glimepiride.[SEP]Relations: diabetes mellitus, noninsulin-dependent has relations: disease_disease with type 2 diabetes mellitus, disease_disease with type 2 diabetes mellitus, disease_disease with type 2 diabetes mellitus, disease_disease with type 2 diabetes mellitus, disease_disease with type 2 diabetes mellitus, disease_disease with type 2 diabetes mellitus. Metformin has relations: drug_drug with Liraglutide, contraindication with hypoglycemia, drug_drug with Liraglutide, contraindication with hypoglycemia. Glimepiride has relations: drug_drug with Liraglutide, contraindication with hypoglycemia, drug_drug with Liraglutide, contraindication with hypoglycemia. Dulaglutide has relations: drug_drug with Liraglutide, drug_drug with Liraglutide. Phentermine has relations: drug_drug with Liraglutide, drug_drug with Liraglutide, drug_drug with Liraglutide, drug_drug with Liraglutide. Sitagliptin has relations: contraindication with hypoglycemia, drug_drug with Liraglutide, contraindication with hypoglycemia, drug_drug with Liraglutide. Liraglutide has relations: contraindication with hypoglycemia, contraindication with hypoglycemia. Insulin glargine has relations: drug_drug with Liraglutide, drug_drug with Liraglutide.", "label": "yes"}
{"id": "converted_3012", "sentence1": "Is pimavanserin effective for Parkinson's disease psychosis?", "sentence2": "Two cases of Parkinson's disease with an unusual delusional misidentification, intermetamorphosis, are presented, along with their improvement with pimavanserin, a novel atypical antipsychotic medication., RATIONALE: Pimavanserin, a selective serotonin 2A receptor inverse agonist, is a promising candidate for treating Parkinson's disease psychosis., OBJECTIVE: Our aim was to describe the efficacy and tolerability of pimavanserin, a highly selective serotonin 5-HT2A receptor inverse agonist/antagonist indicated for the treatment of hallucinations and delusions associated with Parkinson's disease psychosis (PDP), using the metrics of number needed to treat (NNT) and number needed to harm (NNH)., Pimavanserin: novel pharmacotherapy for Parkinson's disease psychosis., INTRODUCTION: Pimavanserin is the first FDA-approved atypical antipsychotic drug indicated for the treatment of hallucinations and delusions associated with Parkinson's disease psychosis (PDP), A pivotal phase III clinical trial demonstrated significant improvement in PDP symptoms in patients receiving pimavanserin compared to placebo-treated patients. , Pimavanserin's mechanism of action might contribute to its unique psychopharmacological properties in the improved treatment of PDP, and perhaps psychosis in other diseases including schizophrenia and dementia-related psychosis., Pimavanserin (Nuplazid™) for the treatment of Parkinson disease psychosis: A review of the literature.Options for the treatment of Parkinson disease psychosis are limited. , Pimavanserin for the treatment of Parkinson's disease psychosis.Pimavanserin is an antipsychotic with a unique mechanism of action (5-HT2A receptor inverse agonist) and no measurable dopaminergic activity; it has been demonstrated to be efficacious, well tolerated and safe for the treatment of PDP. , A Retrospective Study of Pimavanserin Use in a Movement Disorders Clinic.Pimavanserin, a 5-HT2A inverse agonist, was commercially released in the United States in April 2016 for the treatment of Parkinson disease psychosis. , receptor inverse agonist pimavanserin was recently approved by the US FDA for the treatment of PDP and may prove to be a more targeted therapy without the downsides of atypical antipsychotics., Evidence-Based Review of Pharmacotherapy Used for Parkinson's Disease Psychosis.Despite lack of rigor in study designs, published data to date suggest that clozapine and pimavanserin should be considered drugs of choice to treat PD psychosis., Pimavanserin: A novel therapeutic option for Parkinson disease psychosis.While pimavanserin appears to be a safe, effective, and well-tolerated therapeutic option for PDP, additional clinical trials and open-label extension studies are needed to determine the long-term safety and efficacy of this promising therapy. , Objective: Pimavanserin is the first United States Food and Drug Administration (FDA)-approved treatment for Parkinson's disease psychosis (PDP)., Pimavanserin: A Novel Drug Approved to Treat Parkinson's Disease Psychosis., CONCLUSIONS\nPimavanserin is the only FDA-approved treatment for the hallucinations and delusions seen in patients with psychosis of Parkinson's disease., OBJECTIVE\nTo summarize the US Food and Drug Administration's (FDA's) review of the safety and effectiveness for pimavanserin, an atypical antipsychotic, for the treatment of hallucinations and delusions associated with Parkinson's disease psychosis., RESULTS\nPimavanserin 34 mg/d was effective in treating hallucinations and delusions associated with Parkinson's disease., BACKGROUND\nPimavanserin is a selective 5-HT2A receptor inverse agonist and antagonist approved in the USA for the treatment of hallucinations and delusions associated with Parkinson's disease psychosis., Pimavanserin is the first FDA-approved atypical antipsychotic drug indicated for the treatment of hallucinations and delusions associated with Parkinson's disease psychosis (PDP)., INTERPRETATION\nPimavanserin may benefit patients with Parkinson's disease psychosis for whom few other treatment options exist., Pimavanserin (ACP-103) is a selective inverse agonist of the 5-hydroxytryptamine 2A (5-HT2A) receptor intended to treat patients with Parkinson's disease psychosis (PDP)., INTERPRETATION\nPimavanserin showed efficacy in patients with Alzheimer's disease psychosis at the primary endpoint (week 6) with an acceptable tolerability profile and without negative effect on cognition., [Pimavanserin: a new treatment for the Parkinson's disease psychosis]., Pimavanserin, a serotonin(2A) receptor inverse agonist, for the treatment of parkinson's disease psychosis., Pimavanserin, a selective 5-HT2A inverse agonist/antagonist, was approved in the U.S. for treating hallucinations and delusions associated with Parkinson's disease psychosis (PDP)., Pimavanserin: A Novel Antipsychotic for Parkinson's Disease Psychosis., CONCLUSIONS Pimavanserin is the only FDA-approved treatment for the hallucinations and delusions seen in patients with psychosis of Parkinson's disease., OBJECTIVE To summarize the US Food and Drug Administration's (FDA's) review of the safety and effectiveness for pimavanserin, an atypical antipsychotic, for the treatment of hallucinations and delusions associated with Parkinson's disease psychosis., RESULTS Pimavanserin 34 mg/d was effective in treating hallucinations and delusions associated with Parkinson's disease., If this is granted, we believe the evidence of Pimavanserin efficacy, safety and tolerability will position this medication as the first choice for treatment of Parkinson's disease psychosis., The development of pimavanserin as an antipsychotic opened a new therapeutic avenue in the treatment of PDP as well as targeting psychosis in other disorders such as Alzheimer's disease., OBJECTIVE To review the pharmacology, pharmacokinetics, efficacy, safety, and place in therapy of pimavanserin for the treatment of hallucinations and delusions of Parkinson's disease psychosis (PDP)., INTERPRETATION Pimavanserin may benefit patients with Parkinson's disease psychosis for whom few other treatment options exist., <b>OBJECTIVE</b>: To summarize the US Food and Drug Administration's (FDA's) review of the safety and effectiveness for pimavanserin, an atypical antipsychotic, for the treatment of hallucinations and delusions associated with Parkinson's disease psychosis., Data were available from 616 patients with Parkinson's disease with hallucinations and delusions who received at least 1 dose of pimavanserin, with a total exposure of 825 patient-years in the Parkinson's disease psychosis population.<br><b>RESULTS</b>: Pimavanserin 34 mg/d was effective in treating hallucinations and delusions associated with Parkinson's disease., Pimavanserin did not worsen motor function, an adverse effect commonly observed with other antipsychotics, probably because of a lack of consequential dopamine binding.<br><b>CONCLUSIONS</b>: Pimavanserin is the only FDA-approved treatment for the hallucinations and delusions seen in patients with psychosis of Parkinson's disease., Pimavanserin (Nuplazid™) is a selective and potent serotonin 2A (5-HT2A) receptor inverse agonist and antagonist developed by ACADIA Pharmaceuticals that has been approved in the US as a treatment for patients with hallucinations and delusions associated with Parkinson's disease psychosis., This article summarizes the milestones in the development of pimavanserin leading to this first approval for the treatment of hallucinations and delusions in patients with Parkinson's disease psychosis., In a Phase 2 study with pimavanserin in Alzheimer's disease psychosis, pimavanserin significantly (p=0.045) improved psychosis at Week 6 vs. placebo on the NPI-NH Psychosis Score (PS)., To summarize the US Food and Drug Administration's (FDA's) review of the safety and effectiveness for pimavanserin, an atypical antipsychotic, for the treatment of hallucinations and delusions associated with Parkinson's disease psychosis., Pimavanserin is the only FDA-approved treatment for the hallucinations and delusions seen in patients with psychosis of Parkinson's disease., Pimavanserin 34 mg/d was effective in treating hallucinations and delusions associated with Parkinson's disease.[SEP]Relations: autosomal recessive Parkinson disease has relations: disease_disease with Parkinson disease, disease_disease with Parkinson disease. Delusions has relations: disease_phenotype_positive with schizophrenia, disease_phenotype_positive with schizophrenia. Hallucinations has relations: disease_phenotype_positive with schizophrenia, disease_phenotype_positive with Parkinson disease, disease_phenotype_positive with schizophrenia, disease_phenotype_positive with Parkinson disease. psychotic disorder has relations: disease_disease with schizophrenia, disease_disease with schizophrenia.", "label": "yes"}
{"id": "converted_1493", "sentence1": "Was modafinil tested for schizophrenia treatment?", "sentence2": "Modafinil improves antipsychotic-induced parkinsonism but not excessive daytime sleepiness, psychiatric symptoms or cognition in schizophrenia and schizoaffective disorder: a randomized, double-blind, placebo-controlled study., CONCLUSION: The data suggest that modafinil was a safe adjunctive treatment which improved parkinsonian symptoms and signs in patients with schizophrenia or schizoaffective disorder. , A review of its effects in schizophrenia suggests that modafinil facilitates cognitive functions, with pro-mnemonic effects and problem solving improvements. Emotional processing also appears to be enhanced by the drug, although to date there are only a limited number of studies., BACKGROUND: Modafinil, a putative cognitive enhancing drug, has previously been shown to improve performance of healthy volunteers as well as patients with attention deficit disorder and schizophrenia, mainly in tests of executive functions. , A review of modafinil and armodafinil as add-on therapy in antipsychotic-treated patients with schizophrenia., It has been suggested that modafinil and its isomer armodafinil as an add-on strategy to antipsychotic treatment in patients with schizophrenia may improve cognitive functioning, attenuate fatigue, inactiveness and other negative functions as well as weight gain., Evidence for the use of modafinil or armodafinil as add-on therapy to antipsychotic drugs to alleviate fatigue, sleepiness and inactivity is inconclusive. One cohort study and one out of two single-dose crossover RCTs in which modafinil addition was studied could demonstrate a positive effect. All five RCTs of modafinil (three RCTs) and armodafinil (two RCTs) addition with a longer study duration could not demonstrate a positive effect. , In RCTs with a treatment duration of 4 weeks or more, however, no positive effect could be demonstrated on cognitive functioning with modafinil and armodafinil addition. Yet, four single-dose crossover RCTs of modafinil addition show significant positive effects on executive functioning, verbal memory span, visual memory, working memory, spatial planning, slowing in latency, impulse control and recognition of faces expressing sadness and sadness misattribution in the context of disgust recognition. The addition of modafinil or armodafinil to an antipsychotic regime, despite theoretical and preclinical considerations, has not been proved to enhance cognitive function, attenuate fatigue, enhance activity, improve negative symptoms and reduce weight in patients with schizophrenia., RATIONAL: In recent years, evidence suggests that modafinil may be useful for certain symptom domains of schizophrenia, especially for the negative and cognitive symptoms. , CONCLUSION: The present study indicates modafinil as a potential adjunctive treatment strategy for treatment of schizophrenia particularly the negative symptoms. , Modafinil is a wake-promoting drug that has been shown to improve attention, memory and executive function in the healthy population and in patients with schizophrenia., CONCLUSIONS: Results of this pilot trial do not support routine use of modafinil to counteract increased weight and metabolic diseases in patients taking clozapine., Modafinil (2-((diphenylmethyl)sulfinyl)acetamide) is described as an atypical stimulant and is a putative cognition enhancer for schizophrenia, but the precise mechanisms of action remain unclear., Modafinil is a wake-promoting drug that has been shown to improve emotion discrimination in healthy individuals and attention and executive function in schizophrenia. , CONCLUSIONS: These data support clinical evidence that modafinil may alleviate cognitive deficits in schizophrenia and also demonstrate the benefit of applying PLSR modeling to characterize functional brain networks in translational models relevant to central nervous system dysfunction., Modafinil improves working memory in healthy subjects and individuals diagnosed with schizophrenia and Attention Deficit/Hyperactivity Disorder, though the effects of modafinil have not been evaluated on working memory in methamphetamine-dependent subjects., Modafinil is a psychostimulant approved for treating excessive sleepiness in adults; off-label uses (e.g., treatment of cognitive impairment in schizophrenia, ADHD and age-related dementias) are currently being explored. , CONCLUSIONS: Results of this pilot trial do not support routine use of modafinil to treat negative symptoms, cognitive deficits, or wakefulness/fatigue in patients on clozapine., We have previously shown that the amount of movement exhibited by patients with schizophrenia is positively correlated with the volume of left anterior cingulate cortex and that this quantity of movement can be increased by modafinil. , OBJECTIVE: Given recent reports about the off-label use of modafinil as an adjuvant for the treatment of antipsychotic-associated sedation in schizophrenia patients and the recent interest in its putative cognitive-enhancing effects in this population, we present a systematic review of available data on trials of modafinil as an adjuvant in the treatment of cognitive deficits, negative symptoms, and antipsychotic-induced fatigue, and its tolerability. , RESULTS: One of 4 reviewed studies found a significant effect of modafinil as an alerting agent for antipsychotic-induced fatigue and sedation. Neither of 2 reviewed studies found modafinil to improve negative symptoms of schizophrenia. Three of 6 reviewed studies showed that modafinil may improve short-term memory, attention, and the ability to shift mental sets. , CONCLUSIONS: While the available data suggest that modafinil is generally well tolerated and may have some efficacy in the treatment of antipsychotic-induced sedation and cognitive domains, the small sample sizes, contradictory results, and methodological differences between trials, especially with respect to cognitive testing, make it difficult to draw firm conclusions about the overall effectiveness of modafinil as an adjunct in the treatment of schizophrenia. , Hence, before prescribing modafinil to a schizophrenia patient, the possible risks and benefits of each particular case should be evaluated., Modafinil had a substantial placebo effect on outcomes such as fatigue, excessive sleepiness and depression in patients with traumatic brain injury, major depressive disorder, schizophrenia, post-polio fatigue and multiple sclerosis; however, it did not provide any benefit greater than placebo., RATIONALE: The wake-promoting agent modafinil selectively improves neuropsychological task performance in healthy volunteers, in adults with attention deficit hyperactivity disorder (ADHD) and in schizophrenia. , Recently, however, modafinil has been shown to improve attentional set-shifting performance in patients with schizophrenia., In addition, modafinil shows initial promise for a variety of off-label indications in psychiatry, including treatment-resistant depression, attention-deficit/hyperactivity disorder, and schizophrenia., There is increasing interest in the use of modafinil to improve cognition in schizophrenia as well as in other disorders such as attention-deficit/hyperactivity disorder., Initial findings indicate that modafinil may lead to better executive functioning and attentional performance in patients with schizophrenia. , CONCLUSIONS: Although no effect on negative symptoms was found, adjunctive therapy with modafinil may result in global improvements in patients with schizophrenia who have prominent negative symptoms., CONCLUSIONS: Modafinil did not improve cognitive control in all schizophrenia patients., . These data suggest that modafinil increases quantifiable motor behaviour in schizophrenia and may have an impact on avolition., One patient was on treatment with both modafinil and trazodone and reported no change after tapering each in separate discontinuation trials, while another 3 patients were taking sleeping medications and also noted no change after discontinuation.,  Neuroprotective agents as add-on therapies (e.g., modafinil, erythropoietin, glycine, D-serine, memantine and celecoxib) are currently being evaluated in schizophrenia and related disorders. , In the modafinil (N = 10) and placebo (N = 10) groups, fatigue improved significantly over time (p < .01), but there were no differences between groups on changes in fatigue, positive and negative symptoms, or cognition. , CONCLUSIONS: Modafinil modulates anterior cingulate cortex function in chronic schizophrenia but its beneficial cognitive effects may be restricted to a subset of patients requiring further characterisation., Modafinil significantly improved overall clinical condition, with 64% and 82% of patients rated as clinically improved at week 4 by a blinded clinician and the investigator respectively., Modafinil significantly improved fatigue (P = 0.025, week 3) and tended to improve cognitive functioning scores. , Although preliminary, these results suggest modafinil may be an effective and well-tolerated adjunct treatment that improves global functioning and clinical condition, and reduces fatigue in patients with schizophrenia or schizoaffective disorder. , Modafinil had some cognitive enhancing properties in schizophrenia similar to those observed in healthy adults and adult patients with ADHD. , Modafinil may have potential as an important therapy for cognitive impairment in patients with schizophrenia, particularly because of its beneficial effects on attentional set shifting., While the available data suggest that modafinil is generally well tolerated and may have some efficacy in the treatment of antipsychotic-induced sedation and cognitive domains, the small sample sizes, contradictory results, and methodological differences between trials, especially with respect to cognitive testing, make it difficult to draw firm conclusions about the overall effectiveness of modafinil as an adjunct in the treatment of schizophrenia., Given recent reports about the off-label use of modafinil as an adjuvant for the treatment of antipsychotic-associated sedation in schizophrenia patients and the recent interest in its putative cognitive-enhancing effects in this population, we present a systematic review of available data on trials of modafinil as an adjuvant in the treatment of cognitive deficits, negative symptoms, and antipsychotic-induced fatigue, and its tolerability., The present study indicates modafinil as a potential adjunctive treatment strategy for treatment of schizophrenia particularly the negative symptoms.,  It has been suggested that modafinil and its isomer armodafinil as an add-on strategy to antipsychotic treatment in patients with schizophrenia may improve cognitive functioning, attenuate fatigue, inactiveness and other negative functions as well as weight gain., CONCLUSION: The present study indicates modafinil as a potential adjunctive treatment strategy for treatment of schizophrenia particularly the negative symptoms., OBJECTIVE: Given recent reports about the off-label use of modafinil as an adjuvant for the treatment of antipsychotic-associated sedation in schizophrenia patients and the recent interest in its putative cognitive-enhancing effects in this population, we present a systematic review of available data on trials of modafinil as an adjuvant in the treatment of cognitive deficits, negative symptoms, and antipsychotic-induced fatigue, and its tolerability., CONCLUSIONS: While the available data suggest that modafinil is generally well tolerated and may have some efficacy in the treatment of antipsychotic-induced sedation and cognitive domains, the small sample sizes, contradictory results, and methodological differences between trials, especially with respect to cognitive testing, make it difficult to draw firm conclusions about the overall effectiveness of modafinil as an adjunct in the treatment of schizophrenia., The present study indicates modafinil as a potential adjunctive treatment strategy for treatment of schizophrenia particularly the negative symptoms., Although preliminary, these results suggest modafinil may be an effective and well-tolerated adjunct treatment that improves global functioning and clinical condition, and reduces fatigue in patients with schizophrenia or schizoaffective disorder., While the available data suggest that modafinil is generally well tolerated and may have some efficacy in the treatment of antipsychotic-induced sedation and cognitive domains, the small sample sizes, contradictory results, and methodological differences between trials, especially with respect to cognitive testing, make it difficult to draw firm conclusions about the overall effectiveness of modafinil as an adjunct in the treatment of schizophrenia, The present study indicates modafinil as a potential adjunctive treatment strategy for treatment of schizophrenia particularly the negative symptoms, Modafinil, a putative cognitive enhancing drug, has previously been shown to improve performance of healthy volunteers as well as patients with attention deficit disorder and schizophrenia, mainly in tests of executive functions[SEP]Relations: Modafinil has relations: contraindication with schizoaffective disorder, contraindication with schizoaffective disorder. Armodafinil has relations: contraindication with schizoaffective disorder, contraindication with schizoaffective disorder. Cognitive impairment has relations: disease_phenotype_positive with schizophrenia, disease_phenotype_positive with schizophrenia.", "label": "yes"}
{"id": "converted_2492", "sentence1": "Are patients with Sjogren syndrome at increased risk for lymphoma?", "sentence2": "The heightened risk of non-Hodgkin lymphoma (NHL) development in primary Sjogren syndrome (SS) is well established., Primary Diffuse Large B-Cell Lymphoma of the Liver in a Patient with Sjogren Syndrome., Immunohistochemical and molecular features of the tumors allowed diagnosis of diffuse large B-cell lymphoma (DLBCL). , To our knowledge, the patient described here represents the first reported case of DLBCL with primary liver involvement in SS., Rituximab is also effective in the treatment of SS-associated (extrasalivary) lymphomas, although the therapeutic response in salivary lymphoma is poorer., Rituximab treatment for Sjogren syndrome-associated non-Hodgkin's lymphoma: case series., Five per cent of patients with primary Sjogren's syndrome (pSS) develop malignant non-Hodgkin's lymphoma (NHL), usually of the mucosa-associated lymphoid tissue (MALT) and most frequently located in the major salivary glands. , [A case of Sjogren syndrome coexistent with MALT lymphoma occurring along the parotid gland and trachea]., Both histological examinations revealed MALT-type marginal zone B-cell lymphoma. , In the majority of patients, it is a late event and frequently associated with systemic disease or risk factors for lymphoma development., The incidence of lymphoma is higher in patients with Sjögren's syndrome than in the general population., Among the clinical and serological parameters that have been associated with lymphoma development in SS patients, the presence of palpable purpura, low C4, and mixed monoclonal cryoglobulinemia constitute the main predictive markers, and patients displaying these risk factors should be monitored closely., A case of pulmonary pseudolymphoma and Sjogren syndrome is presented., Furthermore, RA, Sjögren's syndrome, systemic lupus erythematosus, and possibly celiac disease may share an association with risk of diffuse large B-cell lymphoma, in addition to well-established links of Sjögren's syndrome with risk of mucosa-associated lymphoid tissue lymphoma and of celiac disease with risk of small intestinal lymphoma., Predicting the risk for lymphoma development in Sjogren syndrome: An easy tool for clinical use., Lymphoma is a very severe complication of primary Sjögren's syndrome: 5 to 10% of patients followed for more than 10 years will develop a lymphoma., Hematologic manifestations and predictors of lymphoma development in primary Sjögren syndrome: clinical and pathophysiologic aspects., Recent results clearly indicate an association between severity of chronic inflammation and lymphoma risk in RA and Sjögren's syndrome., Several autoimmune diseases, including primary Sjögren's syndrome (pSS), are associated with an increased risk for lymphoma., Primary Sjogren's syndrome (pSS) confers increased risk for non-Hodgkin lymphoma (NHL) development., Furthermore, we review the emerging role of ELS and lymphoid chemokines in driving extranodal B cell lymphomagenesis in SS and we focus on recent evidence suggesting that ELS identify subsets of SS patients at increased risk of developing systemic manifestations and lymphoma., Sjogren's syndrome (SS) is a chronic autoimmune disorder with the highest risk for lymphoma development among all autoimmune diseases., In contrast to secondary SS, the risk for developing non-Hodgkin's lymphoma is highly increased in patients with primary SS., Predicting the risk for lymphoma development in Sjogren syndrome: An easy tool for clinical use., Primary Sjogren's syndrome (pSS) is complicated by B-cell lymphoma in 5-10% of patients., Patients with Sjögren syndrome are at increased risk of lymphoma development., Sjogren's syndrome is an autoimmune disease with a known predisposition for lymphoma development., Certain autoimmune and chronic inflammatory conditions, such as Sjögren's syndrome and rheumatoid arthritis (RA), have consistently been associated with an increased risk of malignant lymphomas, but it is unclear whether elevated lymphoma risk is a phenomenon that accompanies inflammatory conditions in general.[SEP]Relations: Rheumatoid arthritis has relations: disease_phenotype_positive with Sjogren syndrome, disease_phenotype_positive with Sjogren syndrome. B-cell lymphoma has relations: disease_phenotype_positive with MALT lymphoma, disease_phenotype_positive with MALT lymphoma. Lymphoma has relations: disease_phenotype_positive with Sjogren syndrome, disease_phenotype_positive with Sjogren syndrome. Non-Hodgkin lymphoma has relations: phenotype_phenotype with B-cell lymphoma, phenotype_phenotype with B-cell lymphoma, phenotype_phenotype with B-cell lymphoma, phenotype_phenotype with B-cell lymphoma. lymphoma, non-Hodgkin, familial has relations: disease_disease with non-Hodgkin lymphoma, disease_disease with non-Hodgkin lymphoma.", "label": "yes"}
{"id": "converted_1182", "sentence1": "Is macroautophagy a selective degradation process?", "sentence2": "Selective autophagy, Macroautophagy (autophagy) is a bulk degradation system for cytoplasmic components and is ubiquitously found in eukaryotic cells, Here we show that selective autophagy downregulates Ty1 transposition, We propose that selective autophagy safeguards genome integrity against excessive insertional mutagenesis caused during nutrient starvation by transposable elements in eukaryotic cells., Moreover, it is becoming apparent that proteins, organelles, and pathogens can be targeted for autophagic clearance by selective mechanisms, Cell spreading required ref(2)P, the Drosophila p62 multiadaptor, implicating selective autophagy as a novel mechanism for modulating cortical dynamics, The selective macroautophagic degradation, There is growing evidence that macroautophagic cargo is not limited to bulk cytosol in response to starvation and can occur selectively for substrates, including aggregated proteins., It remains unclear, however, whether starvation-induced and selective macroautophagy share identical adaptor molecules to capture their cargo. Here, we report that Alfy, a phosphatidylinositol 3-phosphate-binding protein, is central to the selective elimination of aggregated proteins., We propose that Alfy plays a key role in selective macroautophagy by bridging cargo to the molecular machinery that builds autophagosomes., Thus, cytoplasmic NBR1 might be important to maintain basal levels of selective macroautophagy in these neurons., we could show that Smatg8 and Smatg4 are not only required for nonselective macroautophagy, but for selective macropexophagy as well., The latter is performed by proteasome-mediated degradation, chaperone-mediated autophagy (CMA), and selective macroautophagy,, Here we demonstrate a role for PtdIns 4-kinases and PtdIns4P 5-kinases in selective and nonselective types of autophagy in yeast., Macroautophagy (hereafter autophagy) is a degradative cellular pathway that protects eukaryotic cells from stress, starvation, and microbial infection., Previously, we showed that macroautophagy is necessary for conidiation in the rice-blast fungus Magnaporthe oryzae. Here, we analyzed the physiological function(s) of selective autophagy in Magnaporthe, Serine 403 phosphorylation of p62/SQSTM1 regulates selective autophagic clearance of ubiquitinated proteins., Selective macroautophagy (autophagy) of ubiquitinated protein is implicated as a compensatory mechanism of the ubiquitin-proteasome system. p62/SQSTM1 is a key molecule managing autophagic clearance of polyubiquitinated proteins., Whole organelle turnover is mediated through macroautophagy, a process by which autophagosomes deliver mitochondria to the lysosome for hydrolytic degradation. While mitochondrial autophagy can occur as part of a nonselective upregulation of autophagy, selective degradation of damaged or unneeded mitochondria (mitophagy) is a rapidly growing area in development, cancer, and neurodegeneration, particularly with regard to Parkinson's disease, BAG3 was recently described as a mediator of a novel macroautophagy pathway that uses the specificity of heat shock protein 70 (HSP70) to misfolded proteins and also involves other protein partners, such as HSPB8., two Parkinson disease (PD) associated genes, PINK1 and Parkin, were shown to mediate the degradation of damaged mitochondria via selective autophagy (mitophagy), Here we show that whole mitochondria are turned over via macroautophagy., Does Huntingtin play a role in selective macroautophagy?, In the discussion here I suggest that Htt may have a normal function in the lysosomal mechanism of selective macroautophagy involved in its own degradation, Macroautophagy induced by ethanol seemed to be selective for damaged mitochondria and accumulated lipid droplets, but not long-lived proteins, which could account for its protective effects, Although macroautophagy can be nonspecific, there are many examples of selective sequestration including pexophagy, mitophagy and the cytoplasm to vacuole targeting (Cvt) pathway., Mitochondria autophagy (mitophagy) is the process of selective degradation of mitochondria that has an important role in mitochondrial quality control., One of the genes identified, YLR356W, is required for mitophagy, but not for macroautophagy or other types of selective autophagy., A genomic screen for yeast mutants defective in selective mitochondria autophagy., Mitophagy is the process of selective mitochondrial degradation via autophagy, which has an important role in mitochondrial quality control., Analysis of this set of targeted deletion mutants demonstrated that loss of any of the 16 genes necessary for nonselective macroautophagy renders the fungus unable to cause rice blast disease, due to impairment of both conidial programmed cell death and appressorium maturation. In contrast, genes necessary only for selective forms of autophagy, such as pexophagy and mitophagy, are dispensable for appressorium-mediated plant infection., This gene is not required for other types of selective autophagy or for nonspecific macroautophagy., However, in contrast to the core autophagy genes such as atg5 and atg7, expression of ulk1 is not essential for induction of macroautophagy in response to nutrient deprivation or for survival of newborn mice. Together, these data suggest that the ATG1 homologue, Ulk1, is a component of the selective autophagy machinery that leads to the elimination of organelles in erythroid cells rather that an essential mechanistic component of autophagy., Growing evidence supports an active role for dysregulated macroautophagy (autophagic stress) in neuronal cell death and neurodegeneration. Alterations in mitochondrial function and dynamics are also strongly implicated in neurodegenerative diseases. Interestingly, whereas the core autophagy machinery is evolutionarily conserved and shared among constitutive and induced or selective autophagy, recent studies implicate distinct mechanisms regulating mitochondrial autophagy (mitophagy) in response to general autophagic stimuli., We discovered that activation of the UPR in yeast also induces a new branch of macroautophagy that selectively targets the ER. We term this process \"ER-phagy\", in analogy to pexophagy and mitophagy, the two other known forms of organelle-specific marcoautophagy. ER-phagy involves the generation of autophagosomes that selectively include ER membranes and whose delimiting double membranes also derive, at least in part, from the ER., This suggests that in fungi an organism-specific form of selective autophagy may occur, for which specialized Atg proteins have evolved., ransfer of Y. lipolytica cells from oleate/ethylamine to glucose/ammonium chloride medium leads to selective macroautophagy of peroxisomes., Insulin-dependent signaling regulates azurophil granule-selective macroautophagy in human myeloblastic cells., We show that insulin-dependent signals regulate azurophil granule-selective macroautophagy in human myeloid cells., By contrast, other organelles, including the mitochondria, endoplasmic reticulum, and Golgi apparatus remained intact, indicating that the macroautophagy selectively targeted azurophil granules., Thus, insulin-dependent signals are responsible for the control of azurophil granule-selective macroautophagy via Akt-dependent pathways, Eukaryotic cells have the ability to degrade proteins and organelles by selective and nonselective modes of micro- and macroautophagy., For example, pexophagy is a selective process for the regulated degradation of peroxisomes by autophagy., We have characterized biochemically, morphologically, and genetically two distinct pathways for the selective degradation of peroxisomes in Pichia pastoris. These pathways are independently regulated and analogous to microautophagy and macroautophagy that have been defined in mammalian cells., If we are willing to slightly modify our definition of autophagy, with a focus on \"degradation of a cell's own components through the lysosomal/vacuolar machinery,\" we can include a newly documented process, programmed nuclear destruction (PND)., Autophagy is a lysosomal degradation pathway that can sequester cytosolic material, including organelles, nonspecifically in a process called nonselective macroautophagy, or target specific protein aggregates designated for destruction in a process called selective autophagy., Selective macroautophagy uses double-membrane vesicles, termed autophagosomes, to transport cytoplasmic pathogens, organelles and protein complexes to the vacuole for degradation., Autophagy (macroautophagy), a highly conserved eukaryotic mechanism, is a non-selective degradation process, helping to maintain a balance between the synthesis, degradation and subsequent recycling of macromolecules to overcome various stress conditions., Whole organelle turnover is mediated through macroautophagy, a process by which autophagosomes deliver mitochondria to the lysosome for hydrolytic degradation., Macroautophagy is a catabolic process by which the cell degrades cytoplasmic components through the lysosomal machinery., Macroautophagy maintains cellular homeostasis through targeting cytoplasmic contents and organelles into autophagosomes for degradation., Macroautophagy is a catabolic process by which cytosolic components are sequestered by double membrane vesicles called autophagosomes and sorted to the lysosomes/vacuoles to be degraded., Macroautophagy (hereafter autophagy) is a cellular degradation process, which in yeast is induced in response to nutrient deprivation., Macroautophagy was thought to be an unspecific bulk degradation process., Autophagy is a highly regulated intracellular degradation process by which cells remove cytosolic long-lived proteins and damaged organelles, and can be monitored by imaging the incorporation of microtubule-associated light chain 3 (LC3) fused to a fluorescent protein (GFP or mCherry) into nascent autophagosomes., Beside macroautophagy, there are several forms of selective autophagy, including chaperone-mediated autophagy (CMA), cytoplasm to vacuole targeting (Cvt), pexophagy and mitophagy., Macroautophagy (commonly referred to as autophagy) is the process by which intact organelles and/or large portions of the cytoplasm are engulfed within double-membraned autophagic vacuoles for degradation., This analysis demonstrated that Atg proteins required for non-selective macroautophagy are conserved from yeast to man, stressing the importance of this process in cell survival and viability., Part of the degradation of intracellular proteins occurs in the lysosomes and is mediated by macroautophagy.[SEP]Relations: chaperone-mediated autophagy has relations: bioprocess_protein with BAG3, bioprocess_protein with BAG3. heat shock protein binding has relations: molfunc_protein with BAG3, molfunc_protein with BAG3, molfunc_protein with BAG3, molfunc_protein with BAG3, molfunc_protein with BAG3, molfunc_protein with BAG3. cytoplasm has relations: cellcomp_protein with HSPB8, cellcomp_protein with BAG3, cellcomp_protein with HSPB8, cellcomp_protein with BAG3, cellcomp_protein with HSPB8, cellcomp_protein with BAG3, cellcomp_protein with HSPB8, cellcomp_protein with BAG3. autosomal recessive Parkinson disease has relations: disease_disease with Parkinson disease, disease_disease with Parkinson disease.", "label": "yes"}
{"id": "converted_784", "sentence1": "Can NXY-059 be used for treatment of acute ischemic stroke patients?", "sentence2": "Even when the international recommendations for preclinical stroke research, the Stroke Academic Industry Roundtable (STAIR) criteria, were followed, we have still seen limited success in the clinic, examples being NXY-059 and haematopoietic growth factors which fulfilled nearly all the STAIR criteria, This occurred during 1993-2006, when the 2,4-disulfonylphenyl PBN derivative, called NXY-059 in the stroke studies, was shown to be safe in humans and was taken all the way through clinical phase 3 trials and then was deemed to be ineffective. , The nitrone-based compound NXY-059, which is the first drug to reach clinical trials for the treatment of acute ischemic stroke, has provided promise for the development of more robust pharmacological agents. , OKN-007 is a proprietary compound that has had extensive commercial development (designated as NXY-059) for another indication, acute ischemic stroke, and after extensive clinical studies was shown to lack efficacy for this indication but was shown to be very safe for human use. , NXY-059, a polar compound with limited transport across the blood-brain barrier, has demonstrated neuroprotection in several animal models of acute ischemic stroke but failed to confirm clinical benefit in the second phase III trial (SAINT-II)., NXY-059 is no longer in development following a lack of efficacy found in a Phase III trial in patients with acute ischemic stroke. , We analyzed the quality and adequacy of animal studies supporting the efficacy of NXY-059 and other neuroprotective agents that are currently being investigated in phase II/III trials,  In the aftermath of the failed stroke clinical trials with the nitrone spin trap/radical scavenger, NXY-059, a number of articles raised the question: are we doing the right thing? ,  In 2006, the first positive trial of neuroprotection was published: the SAINT I (Stroke-Acute Ischemic NXY Treatment) study. In February 2008, the SAINT II study was published, indicating that NXY-059 was not effective for AIS treatment., CONCLUSIONS: NXY-059 is ineffective for treatment of AIS within 6 hours of symptom onset. , BACKGROUND AND PURPOSE: The SAINT I trial that showed a significant benefit of the neuroprotectant NXY-059 used a novel outcome for acute ischemic stroke trials: a shift toward good functional outcome on the 7-category modified Rankin scale (mRS)., BACKGROUND: The free-radical-trapping agent NXY-059 showed promise as a neuroprotectant in the Stroke-Acute Ischemic NXY Treatment I (SAINT I) trial, reducing disability when given to patients who had acute ischemic stroke. , CONCLUSIONS: NXY-059 is ineffective for the treatment of acute ischemic stroke within 6 hours after the onset of symptoms., The continued failure in approving new drugs for treatment of acute stroke has been recently set back by the failure of the NXY-059 (Stroke-Acute Ischemic NXY Treatment (SAINT) II) trial., The SAINT II Trial, a large randomized multicenter clinical trial of the putative neuroprotectant, NXY-059, failed to demonstrate a treatment benefit in acute ischemic stroke. , The positive results from the first Stroke-Acute-Ischaemic-NXY-Treatment (SAINT-I) trial of the free-radical spin-trap drug, NXY-059, which followed many of the STAIR guidelines, reinvigorated enthusiasm in neuroprotection, but the SAINT-II trial did not replicate the positive effect on the same primary prespecified outcome measure. , NXY-059, a free radical spin trap agent, was felt by many to have followed these criteria and it was recently shown to improve outcome in AIS patients in the SAINT I trial. However, the repeat, SAINT II trial was a neutral study, the results of which cast doubt on neuroprotection as a viable strategy for AIS. , NXY-059 is a novel free radical-trapping neuroprotectant that reduces infarct size and preserves brain function in animal models of acute ischemic stroke. It is the first neuroprotectant to demonstrate a reduction in global disability in a phase III clinical trial, as measured by the modified Rankin Scale., BACKGROUND AND PURPOSE: NXY-059 is a free radical-trapping neuroprotectant demonstrated to reduce disability from ischemic stroke., CONCLUSIONS: NXY-059 within 6 hours of acute ischemic stroke significantly reduced disability. , CONCLUSIONS: The administration of NXY-059 within six hours after the onset of acute ischemic stroke significantly improved the primary outcome (reduced disability at 90 days), but it did not significantly improve other outcome measures, including neurologic functioning as measured by the NIHSS score. Additional research is needed to confirm whether NXY-059 is beneficial in ischemic stroke. , BACKGROUND: The free-radical-trapping agent NXY-059 showed promise as a neuroprotectant in the Stroke-Acute Ischemic NXY Treatment I (SAINT I) trial, reducing disability when given to patients who had acute ischemic stroke., NXY-059 is no longer in development following a lack of efficacy found in a Phase III trial in patients with acute ischemic stroke., The free-radical-trapping agent NXY-059 showed promise as a neuroprotectant in the Stroke-Acute Ischemic NXY Treatment I (SAINT I) trial, reducing disability when given to patients who had acute ischemic stroke, The continued failure in approving new drugs for treatment of acute stroke has been recently set back by the failure of the NXY-059 (Stroke-Acute Ischemic NXY Treatment (SAINT) II) trial[SEP]", "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.", "label": "no"}
{"id": "converted_3965", "sentence1": "Is co-loss of BRCA2-RB1 associated with better prognosis for prostate cancer patients?", "sentence2": "In human prostate cancer cell lines (LNCaP and LAPC4), loss of BRCA2 leads to the castration-resistant phenotype. Co-loss of BRCA2-RB1 in human prostate cancer cells induces an epithelial-to-mesenchymal transition, which is associated with invasiveness and a more aggressive disease phenotype. Importantly, PARP inhibitors attenuate cell growth in human mCRPC-derived organoids and human CRPC cells harboring single-copy loss of both genes.CONCLUSIONS: Our findings suggest that early identification of this aggressive form of prostate cancer offers potential for improved outcomes with early introduction of PARP inhibitor-based therapy.[SEP]", "label": "no"}
{"id": "converted_362", "sentence1": "Is there a package in R/bioconductor for classification of alternative splicing?", "sentence2": "spliceR: an R package for classification of alternative splicing and prediction of coding potential from RNA-seq data., Recent software improvements in full-length transcript deconvolution prompted us to develop spliceR, an R package for classification of alternative splicing and prediction of coding potential., spliceR uses the full-length transcript output from RNA-seq assemblers to detect single or multiple exon skipping, alternative donor and acceptor sites, intron retention, alternative first or last exon usage, and mutually exclusive exon events. For each of these events spliceR also annotates the genomic coordinates of the differentially spliced elements, facilitating downstream sequence analysis. For each transcript isoform fraction values are calculated to identify transcript switching between conditions. Lastly, spliceR predicts the coding potential, as well as the potential nonsense mediated decay (NMD) sensitivity of each transcript., Recent software improvements in full-length transcript deconvolution prompted us to develop spliceR, an R package for classification of alternative splicing and prediction of coding potential., Recent software improvements in full-length transcript deconvolution prompted us to develop spliceR, an R package for classification of alternative splicing and prediction of coding potential. , Recent software improvements in full-length transcript deconvolution prompted us to develop spliceR, an R package for classification of alternative splicing and prediction of coding potential.[SEP]", "label": "yes"}
{"id": "converted_4631", "sentence1": "Is taxilin a cancer marker?", "sentence2": "Αlpha-Taxilin (α-Taxilin) has been found as one of the novel, significantly up regulated protein in RA, Expression of α-taxilin has been implicated in the development of human glioblastoma, hepatocellular carcinoma and renal cell carcinoma. , α-Taxilin, a binding partner of the syntaxin family, is a candidate tumor marker. , Expression of α-taxilin in hepatocellular carcinoma correlates with growth activity and malignant potential of the tumor.[SEP]", "label": "yes"}
{"id": "converted_1589", "sentence1": "Has proteomics been used in the study of the dry eye syndrome?", "sentence2": "Tear proteomic analysis of patients with type 2 diabetes and dry eye syndrome by two-dimensional nano-liquid chromatography coupled with tandem mass spectrometry., Dry eye syndrome in diabetic patients is associated with aberrant expression of tear proteins, and the findings could lead to identification of novel pathways for therapeutic targeting and new diagnostic markers.,  2D electrophoresis (2DE) and Differential gel electrophoresis (DIGE) was done to identify differentially expressed proteins. , Two dimensional electrophoretic analysis of human tears: collection method in dry eye syndrome., Identification of tear fluid biomarkers in dry eye syndrome using iTRAQ quantitative proteomics., This study demonstrated that iTRAQ technology combined with 2D-nanoLC-nanoESI-MS/MS quantitative proteomics is a powerful tool for biomarker discovery.[SEP]", "label": "yes"}
{"id": "converted_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.", "label": "no"}
{"id": "converted_908", "sentence1": "Is miR-126 involved in heart failure?", "sentence2": "he miRNAs miR-126 and miR-508-5p are associated with the outcome of ICM and NICM patients with CHF. These two miRNAs could be useful in the diagnosis of CHF patients, and might provide novel targets for prevention and treatment of CHF., The plasma concentration of miR-126 was negatively correlated with age and NYHA class, and could be a useful biomarker for heart failure., In 10 patients with heart failure, plasma concentrations of miR-126 were up-regulated with improvement of the NYHA class from IV to III.[SEP]", "label": "yes"}
{"id": "converted_1360", "sentence1": "Is triadin involved in cardiac function?", "sentence2": "Junctin (JCN), a 26-kd sarcoplasmic reticulum (SR) transmembrane protein, forms a quaternary protein complex with the ryanodine receptor, calsequestrin, and triadin in the SR lumen of cardiac muscle. Within this complex, calsequestrin, triadin, and JCN appear to be critical for normal regulation of ryanodine receptor-mediated calcium (Ca) release., Recent studies have uncovered functional roles of both JCN and triadin in the mouse heart, using transgenic overexpression strategies, which exhibit varying phenotypes including mild SR structural alterations, prolongation of Ca transient decay, impaired relaxation, and cardiac hypertrophy and/or heart failure., Triadin is involved in the regulation of cardiac excitation-contraction coupling. , Thus the maintenance of triadin expression is essential for normal SR Ca cycling and contractile function., Ca2+ release from the cardiac junctional sarcoplasmic reticulum (SR) is regulated by a complex of proteins, including the ryanodine receptor (RyR), calsequestrin (CSQ), junctin (JCN), and triadin 1 (TRD)., Impaired sarcoplasmic reticulum (SR) Ca release has been suggested to contribute to the depressed cardiac function in heart failure. The release of Ca from the SR may be regulated by the ryanodine receptor, triadin, junctin, calsequestrin, and a histidine-rich, Ca-binding protein (HRC).[SEP]", "label": "yes"}
{"id": "converted_3335", "sentence1": "Does BNN27 promote memory loss?", "sentence2": "The novel dehydroepiandrosterone (DHEA) derivative BNN27 counteracts delay-dependent and scopolamine-induced recognition memory deficits in rats., BNN27 is a novel 17C spiroepoxy-DHEA derivative, which devoid of steroidogenic activity. The neuroprotective effects of BNN27 have been recently reported. The present study was designed to investigate the effects of BNN27 on recognition memory in rats. For this purpose, the novel object task (NOT), a procedure assessing non-spatial recognition memory and the novel location task (NLT), a procedure evaluating spatial recognition memory were used. Intraperitoneal (i.p.) administration of BNN27 (3 and 10mg/kg) antagonized delay-dependent deficits in the NOT in the normal rat, suggesting that this DHEA derivative affected acquisition, storage and retrieval of information. In addition, BNN27 (3 and 10mg/kg, i.p.) counteracted the scopolamine [0.2mg/kg, subcutaneously (s.c.)]-induced non-spatial and spatial recognition memory deficits. These findings suggest that BNN27 may modulate different aspects of recognition memory, potentially interacting with the cholinergic system, relevant to cognition.[SEP]", "label": "no"}
{"id": "converted_367", "sentence1": "Is bapineuzumab effective for treatment of patients with Alzheimer's disease?", "sentence2": " Thus far, results from two large phase 3 trial programs with bapineuzumab and solaneuzumab, respectively, have brought rather disappointing results., More recently, in phase III studies, bapineuzumab has been discontinued because it did not prove clinically effective (despite its significant effect on biomarkers), while solaneuzumab has been found effective in slowing AD progression. , Passive immunotherapy with monoclonal antibodies (mAbs) against Aβ is in late clinical development but recently the two most advanced mAbs, Bapineuzumab and Solanezumab, targeting an N-terminal or central epitope, respectively, failed to meet their target of improving or stabilizing cognition and function., The marginal effects observed in recent clinical studies of solanezumab, targeting monomeric Aβ, and bapineuzumab, targeting amyloid plaques, prompted expert comments that drug discovery efforts in Alzheimer's disease should focus on soluble forms of Aβ rather than fibrillar Aβ deposits found in amyloid plaques., Phase III trials showed that bapineuzumab failed to improve cognitive and functional performances in AD patients, and was associated with a high incidence of amyloid-related imaging abnormalities (ARIA)., Clinical trials on various drugs, including AN1792, bapineuzumab, and solanezumab, have been carried out; however, all trials have failed to demonstrate apparent clinical benefits. , Despite the alteration in biochemical composition, all 3 immunized subjects exhibited continued cognitive decline., Despite negative topline phase 3 clinical trial results for bapineuzumab and solanezumab in mild to moderate AD, findings from these trials and recent advances suggest renewed optimism for anti-amyloid therapies. , The lack of progress in the development of disease-modifying therapy in Alzheimer's disease (AD) was highlighted recently by the cessation of a phase 3 clinical trial studying the effects of bapineuzumab on mild to moderate disease. No treatment benefit was apparent, whereas several serious side effects occurred more commonly in the treatment group compared to placebo. , Clinical studies using the N-terminal-directed anti-Aβ antibody bapineuzumab have demonstrated reduced brain PET-Pittsburg-B signals, suggesting the reduction of Aβ plaques, and reduced levels of total and phosphorylated tau protein in the CSF of treated AD patients. Preclinical studies using 3D6 (the murine form of bapineuzumab) have demonstrated resolution of Aβ plaque and vascular burdens, neuritic dystrophy, and preservation of synaptic density in the transgenic APP mouse models., The clinical results of the initial studies with bapineuzumab were equivocal in terms of cognitive benefit. The occurrence of vasogenic edema after bapineuzumab, and more rarely brain microhemorrhages (especially in Apo E ε4 carriers), has raised concerns on the safety of these antibodies directed against the N-terminus of the Aβ peptide. ,  The most advanced of these immunological approaches is bapineuzumab, composed of humanized anti-Aβ monoclonal antibodies, that has been tested in two Phase II trials, demonstrating to reduce Aβ burden in the brain of AD patients. However, the preliminary cognitive efficacy of bapineuzumab appears uncertain. The occurrence of vasogenic edema, especially in apolipoprotein E 4 carriers, may limit its clinical use and have led to abandon the highest dose of the drug (2 mg/kg)., However, the preliminary cognitive efficacy of bapineuzumab, a humanized anti-Aβ monoclonal antibody, appears uncertain. Moreover, the occurrence of vasogenic edema and, more rarely, brain microhemorrhages, especially in apolipoprotein E ϵ4 carriers, have led to abandoning of the highest dose of the drug. , However, the preliminary equivocal cognitive results obtained with bapineuzumab as well as the detrimental cognitive effects observed with semagacestat, a potent γ-secretase inhibitor, raise the possibility that targeting Aβ may not be clinically efficacious in AD. , The patient received four bapineuzumab infusions over a 39 week period. During the course of this treatment, there was no remarkable change in cognitive impairment as determined by MMSE scores. Forty-eight days after the fourth bapineuzumab infusion was given, MRI revealed that the patient had developed lacunar infarcts and possible vasogenic edema, probably related to immunotherapy, but a subsequent MRI scan 38 days later demonstrated resolution of vasogenic edema. The patient expired due to acute congestive heart failure complicated by progressive AD and cerebrovascular accident 378 days after the first bapineuzumab infusion and 107 days after the end of therapy. Neuropathological and biochemical analysis did not produce evidence of lasting plaque regression or clearance of Aβ due to immunotherapy., These results suggest that, in this particular case, bapineuzumab immunotherapy neither resulted in detectable clearance of amyloid plaques nor prevented further cognitive impairment., Bapineuzumab has been shown to reduce Aβ burden in the brain of AD patients. However, its preliminary cognitive efficacy appears uncertain, particularly in ApoE ε4 carriers, and vasogenic edema may limit its clinical use. , Bapineuzumab appears capable of reducing the cerebral beta-amyloid peptide burden in patients with Alzheimer's disease. However, particularly in APOE 4 carriers, its ability to slow disease progression remains uncertain, and vasogenic edema - a dose-limiting and potentially severe adverse reaction - may limit its clinical applicability., The first is a phase 2 study of passive immunotherapy with bapineuzumab, a humanized anti-Abeta monoclonal antibody directed against the N-terminus of Abeta. This trial showed no differences within dose cohorts on the primary efficacy analysis. Exploratory analyses showed potential treatment differences on cognitive and functional endpoints in study completers and apolipoprotein E epsilon4 noncarriers. A safety concern was the occurrence of reversible vasogenic edema. , The first passive immunotherapy trial with bapineuzumab, a humanized monoclonal antibody against the end terminus of Abeta, also encountered some dose dependent adverse events during the Phase II portion of the study, vasogenic edema in 12 cases, which were significantly over represented in ApoE4 carriers.[SEP]Relations: Solanezumab has relations: drug_drug with Bapineuzumab, drug_drug with Bapineuzumab. Bapineuzumab has relations: drug_drug with Solanezumab, drug_drug with Solanezumab.", "label": "no"}
{"id": "converted_2307", "sentence1": "Do cephalopods use RNA editing less frequently than other species?", "sentence2": "Extensive messenger RNA editing generates transcript and protein diversity in genes involved in neural excitability, as previously described, as well as in genes participating in a broad range of other cellular functions, By adopting a method originally designed to detect linkage disequilibrium of DNA mutations, we examined the editomes of ten metazoan species and detected extensive linkage of editing in Drosophila and cephalopods., We here show that RNA editing is particularly common in behaviorally sophisticated coleoid cephalopods, with tens of thousands of evolutionarily conserved sites., Even for the subset of RNA editing sites shared by deeply divergent cephalopod lineages, the primary effect of nuclear editing is an increase-not a decrease-in protein divergence., Coleoid cephalopods (octopus, squid and cuttlefish) are active, resourceful predators with a rich behavioural repertoire., We identified hundreds of cephalopod-specific genes, many of which showed elevated expression levels in such specialized structures as the skin, the suckers and the nervous system., Our analysis suggests that substantial expansion of a handful of gene families, along with extensive remodelling of genome linkage and repetitive content, played a critical role in the evolution of cephalopod morphological innovations, including their large and complex nervous systems.[SEP]", "label": "no"}
{"id": "converted_222", "sentence1": "Is there any association between Jarid2 and miR-155 in Th17 cells?", "sentence2": "Jarid2 links MicroRNA and chromatin in Th17 cells., In this issue of Immunity, Escobar et al. (2014) bring microRNAs and chromatin together by showing how activation-induced miR-155 targets the chromatin protein Jarid2 to regulate proinflammatory cytokine production in T helper 17 cells., miR-155 activates cytokine gene expression in Th17 cells by regulating the DNA-binding protein Jarid2 to relieve polycomb-mediated repression., Mir155 was bound by Th17 cell transcription factors and was highly expressed during Th17 cell differentiation. miR-155-deficient Th17 and T regulatory (Treg) cells expressed increased amounts of Jarid2, a DNA-binding protein that recruits the Polycomb Repressive Complex 2 (PRC2) to chromatin. PRC2 binding to chromatin and H3K27 histone methylation was increased in miR-155-deficient cells, coinciding with failure to express Il22, Il10, Il9, and Atf3. Defects in Th17 cell cytokine expression and Treg cell homeostasis in the absence of Mir155 could be partially suppressed by Jarid2 deletion. Thus, miR-155 contributes to Th17 cell function by suppressing the inhibitory effects of Jarid2., Thus, miR-155 contributes to Th17 cell function by suppressing the inhibitory effects of Jarid2., Thus, miR-155 contributes to Th17 cell function by suppressing the inhibitory effects of Jarid2., Defects in Th17 cell cytokine expression and Treg cell homeostasis in the absence of Mir155 could be partially suppressed by Jarid2 deletion. Thus, miR-155 contributes to Th17 cell function by suppressing the inhibitory effects of Jarid2., Thus, miR-155 contributes to Th17 cell function by suppressing the inhibitory effects of Jarid2.[SEP]", "label": "yes"}
{"id": "converted_809", "sentence1": "Are conserved noncoding elements associated with developmental genes?", "sentence2": "Some characteristics of CNEs include their high frequency in mammalian genomes, their potential regulatory role in gene expression, and their enrichment in gene deserts nearby master developmental genes, we review recent findings that disruptions of CNEs, within or at long distance from the coding sequences of key genes involved in NCC development, result in neurocristopathies via the alteration of tissue- or stage-specific long-distance regulation of gene expression, Genomic regulatory blocks are chromosomal regions spanned by long clusters of highly conserved noncoding elements devoted to long-range regulation of developmental genes, Analysis of CNEs, at least some of which are candidate regulatory elements, suggests that ancestral CNEs partitioned between gene duplicates. These results help explain the evolutionary pathways by which the developmentally important family of FgfD molecules arose and the deduced principles that guided FgfD evolution are likely applicable to the evolution of developmental regulation in many vertebrate multigene families, Pan-vertebrate developmental cis-regulatory elements are discernible as highly conserved noncoding elements (HCNEs) and are often dispersed over large areas around the pleiotropic genes whose expression they control. On the loci of two developmental transcription factor genes, SOX3 and PAX6, we demonstrate that HCNEs conserved between human and zebrafish can be systematically and reliably tested for their regulatory function in multiple stable transgenes in zebrafish, and their genomic reach estimated with confidence using synteny conservation and HCNE density along these loci. HCNEs of both human and zebrafish function as specific developmental enhancers in zebrafish, We show that human HCNEs result in expression patterns in zebrafish equivalent to those in mouse, establishing zebrafish as a suitable model for large-scale testing of human developmental enhancers, HCNEs from the same area often drive overlapping patterns, suggesting that multiple regulatory inputs are required to achieve robust and precise complex expression patterns exhibited by developmental genes, Organization of conserved elements near key developmental regulators in vertebrate genomes, Further positional analysis of these conserved noncoding elements (CNEs) in the genome demonstrates that they cluster around genes involved in developmental regulation, Ancora: a web resource for exploring highly conserved noncoding elements and their association with developmental regulatory genes, Metazoan genomes contain arrays of highly conserved noncoding elements (HCNEs) that span developmental regulatory genes and define regulatory domains, The most highly conserved noncoding elements (HCNEs) in mammalian genomes cluster within regions enriched for genes encoding developmentally important transcription factors (TFs). This suggests that HCNE-rich regions may contain key regulatory controls involved in development, We found the largest mammal-teleost conserved chromosomal segments to be spanned by highly conserved noncoding elements (HCNEs), their developmental regulatory target genes, and phylogenetically and functionally unrelated \"bystander\" genes., Ancora: a web resource for exploring highly conserved noncoding elements and their association with developmental regulatory genes., Pan-vertebrate developmental cis-regulatory elements are discernible as highly conserved noncoding elements (HCNEs) and are often dispersed over large areas around the pleiotropic genes whose expression they control., Metazoan genomes contain arrays of highly conserved noncoding elements (HCNEs) that span developmental regulatory genes and define regulatory domains., Further positional analysis of these conserved noncoding elements (CNEs) in the genome demonstrates that they cluster around genes involved in developmental regulation., The most highly conserved noncoding elements (HCNEs) in mammalian genomes cluster within regions enriched for genes encoding developmentally important transcription factors (TFs)., Disruption of long-distance highly conserved noncoding elements in neurocristopathies., Fish-mammal genomic comparisons have proved powerful in identifying conserved noncoding elements likely to be cis-regulatory in nature, and the majority of those tested in vivo have been shown to act as tissue-specific enhancers associated with genes involved in transcriptional regulation of development., Despite this, attempts at unearthing genome-wide regulatory elements conserved throughout the vertebrate lineage using BLAST-like approaches have thus far detected noncoding conservation in only a few hundred genes, mostly associated with regulation of transcription and development., Further positional analysis of these conserved noncoding elements (CNEs) in the genome demonstrates that they cluster around genes involved in developmental regulation., We found the largest mammal-teleost conserved chromosomal segments to be spanned by highly conserved noncoding elements (HCNEs), their developmental regulatory target genes, and phylogenetically and functionally unrelated \"bystander\" genes., Organization of conserved elements near key developmental regulators in vertebrate genomes., Pan-vertebrate developmental cis-regulatory elements are discernible as highly conserved noncoding elements (HCNEs) and are often dispersed over large areas around the pleiotropic genes whose expression they control[SEP]", "label": "yes"}
{"id": "converted_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_protein with TSC1, disease_protein with TSC2, disease_protein with TSC1, disease_protein with TSC2, disease_protein with TSC1, disease_protein with TSC2, disease_protein with TSC1, disease_protein with TSC2, disease_protein with TSC1, disease_protein with TSC2, disease_protein with TSC1, disease_protein with TSC2, disease_protein with TSC1, disease_protein with TSC2, disease_protein with TSC1, disease_protein with TSC2. epilepsy has relations: disease_protein with TSC1, disease_protein with TSC2, disease_protein with TSC1, disease_protein with TSC2. TSC1-TSC2 complex has relations: cellcomp_protein with TSC1, cellcomp_protein with TSC2, cellcomp_protein with TSC1, cellcomp_protein with TSC2.", "label": "yes"}
{"id": "converted_3445", "sentence1": "Does radiation for tinea capitis increases brain tumor risk?", "sentence2": "Emphasis is placed on meningiomas resulting from childhood treatment for primary brain tumor or tinea capitis, exposure to dental x-rays, and exposure to atomic explosions in Hiroshima and Nagasaki. , It is well known that radiation can induce meningiomas. These tumors usually arise in patients with a history of low-dose radiation to the scalp for treatment of tinea capitis or high-dose radiation for a previous brain tumor. , This paper describes six cases of radiation-associated intracranial meningiomas in patients previously treated with low-dose radiation to the scalp for tinea capitis., After a median follow-up of 40 years, an ERR/Gy of 4.63 and 1.98 (95% CI = 2.43-9.12 and 0.73-4.69) and an EAR/Gy per 10(4) PY of 0.48 and 0.31 (95% CI = 0.28-0.73 and 0.12-0.53) were observed for benign meningiomas and malignant brain tumors, respectively. , The estimated ERR/Gy for malignant brain tumors decreased with increasing age at irradiation from 3.56 to 0.47 (P = 0.037), while no trend with age was seen for benign meningiomas. The ERR for both types of tumor remains elevated at 30-plus years after exposure., Although meningiomas are known to be induced by low doses of cranial irradiation, such as those given to treat tinea capitis, little experience has been reported on the induction of meningiomas by high-dose cranial irradiation. , The exposed rats had a greater incidence of pituitary chromophobe adenomas, epithelial and mesothelial cell tumors than the unexposed controls but the excessive occurrence of malignant gliomas that was observed in the monkeys was absent in the rats.  , We have analyzed 60 cases of intra-axial brain tumors associated with antecedent radiation therapy. These include four new cases. The patients had originally received radiation therapy for three reasons: (a) cranial irradiation for acute lymphoblastic leukemia (ALL), (b) definitive treatment of CNS neoplasia, and (c) treatment of benign disease (mostly cutaneous infections). , Long-term follow-up for brain tumor development after childhood exposure to ionizing radiation for tinea capitis., Benign and malignant thyroid neoplasms after childhood irradiation for tinea capitis., There is evidence to show that moderate doses of ionising radiations given in childhood for tinea capitis are associated with a late risk of developing a meningioma, This paper describes six cases of radiation-associated intracranial meningiomas in patients previously treated with low-dose radiation to the scalp for tinea capitis., These tumors usually arise in patients with a history of low-dose radiation to the scalp for treatment of tinea capitis or high-dose radiation for a previous brain tumor., There is evidence to show that moderate doses of ionising radiations given in childhood for tinea capitis are associated with a late risk of developing a meningioma., In addition to high dose radiation-induced meningiomas, intracranial meningiomas were observed in patients who underwent low-dose radiation for tinea capitis in childhood, applied en mass to immigrants coming to Israel from the North Africa and the Middle East during the 1950., A 39-year-old male developed primary brain lymphoma 33 years after receiving scalp irradiation for tinea capitis., Secondary glioblastoma multiforme (sGBM) can occur after a long latency period following radiation treatment of various diseases including brain tumors, leukemia, and more benign disorders like tinea capitis., The main data come from series of patients who underwent radiotherapy during childhood: a high incidence of tumors of the nervous system is found after irradiation of one to a few grays as treatment of a benign disease (especially tinea capitis), as well as after irradiation at higher doses of a few tens of grays for the treatment of cancer (in particular cerebral irradiation in acute lymphoblastic leukaemia).[SEP]Relations: acute lymphoblastic/lymphocytic leukemia has relations: disease_disease with acute lymphoblastic leukemia, disease_disease with acute lymphoblastic leukemia.", "label": "yes"}
{"id": "converted_4162", "sentence1": "Are somatic mutations positioned towards the nuclear periphery?", "sentence2": "lamina-associated regions, which are typically localized at the nuclear periphery, displayed higher somatic mutation frequencies than did the interlamina regions at the nuclear core., Furthermore, mutational signatures differed between the nuclear core and periphery, thus indicating differences in the patterns of DNA-damage or DNA-repair processes. For instance, smoking and UV-related signatures, as well as substitutions at certain motifs, were more enriched in the nuclear periphery. , We found that lamina-associated regions, which are typically localized at the nuclear periphery, displayed higher somatic mutation frequencies than did the interlamina regions at the nuclear core., found that lamina-associated regions, which are typically localized at the nuclear periphery, displayed higher somatic mutation frequencies than did the interlamina regions at the nuclear core. Thi[SEP]", "label": "yes"}
{"id": "converted_3094", "sentence1": "Can cardiospheres be produced from skin fibroblasts?", "sentence2": "Therefore, there is an emerging interest in generating cardiosphere-like stem cells from somatic cells via somatic reprogramming. , Here we provide the detailed protocol for generating induced cardiospheres (iCS) for cardiac regeneration by somatic reprogramming of mouse fibroblasts using a panel of pluripotent transcription factors and cardiotrophic growth factors.[SEP]", "label": "yes"}
{"id": "converted_1974", "sentence1": "Does mTOR regulate the translation of MAPKAPK2?", "sentence2": "mTOR regulates MAPKAPK2 translation to control the senescence-associated secretory phenotype., Senescent cells secrete a combination of factors collectively known as the senescence-associated secretory phenotype (SASP). The SASP reinforces senescence and activates an immune surveillance response, but it can also show pro-tumorigenic properties and contribute to age-related pathologies. In a drug screen to find new SASP regulators, we uncovered the mTOR inhibitor rapamycin as a potent SASP suppressor. Here we report a mechanism by which mTOR controls the SASP by differentially regulating the translation of the MK2 (also known as MAPKAPK2) kinase through 4EBP1. In turn, MAPKAPK2 phosphorylates the RNA-binding protein ZFP36L1 during senescence, inhibiting its ability to degrade the transcripts of numerous SASP components. Consequently, mTOR inhibition or constitutive activation of ZFP36L1 impairs the non-cell-autonomous effects of senescent cells in both tumour-suppressive and tumour-promoting contexts. Altogether, our results place regulation of the SASP as a key mechanism by which mTOR could influence cancer, age-related diseases and immune responses., Here we report a mechanism by which mTOR controls the SASP by differentially regulating the translation of the MK2 (also known as MAPKAPK2) kinase through 4EBP1., mTOR regulates MAPKAPK2 translation to control the senescence-associated secretory phenotype, Here we report a mechanism by which mTOR controls the SASP by differentially regulating the translation of the MK2 (also known as MAPKAPK2) kinase through 4EBP1, Here we report a mechanism by which mTOR controls the SASP by differentially regulating the translation of the MK2 (also known as MAPKAPK2) kinase through 4EBP1., Both Beclin1-PI3KIII and Beclin1-MAPKAPK2 interactions as were remarkably affected by silencing either ATM or MAPK14.ATM promoted IR-induced autophagy via the MAPK14 pathway, mTOR pathway and Beclin1/PI3KIII complexes., mTOR regulates MAPKAPK2 translation to control the senescence-associated secretory phenotype.[SEP]Relations: ZFP36L1 has relations: protein_protein with MAPKAPK2, protein_protein with MAPKAPK2. protein binding has relations: molfunc_protein with ZFP36L1, molfunc_protein with MAPKAPK2, molfunc_protein with ATM, molfunc_protein with ZFP36L1, molfunc_protein with MAPKAPK2, molfunc_protein with ATM. Sirolimus has relations: contraindication with cancer, contraindication with cancer.", "label": "yes"}
{"id": "converted_3773", "sentence1": "Do circular exons increase gene expression?", "sentence2": "Each of these species was present at very low copy numbers in primary and cultured cells; however, only the expression of ANRIL isoforms containing exons proximal to the INK4/ARF locus correlated with the ASVD risk alleles., These results identify novel circular RNA products emanating from the ANRIL locus and suggest causal variants at 9p21.3 regulate INK4/ARF expression and ASVD risk by modulating ANRIL expression and/or structure., To explore the potential for using this methodology to express circular RNA in vivo, circular forms of the HDV ribozyme and RNaseP RNA were produced in E. coli. , The activity of in vivo expressed circular ribozymes could be demonstrated indicating that they fold into active conformation, We found that: i) the circRNA expression profile revealed 1,285 significant differences in circRNA expression, with circRNA expression downregulated in 594 samples and upregulated in 691 samples via interactions with miRNAs., These circRNAs regulated the expression of target genes through interactions with miRNAs and might become new molecular biomarkers for GC in the future, 69 differentially expressed circRNAs were found that might adsorb specific miRNAs to regulate the expression of their target gene mRNAs., Novel coding, translation, and gene expression of a replicating covalently closed circular RNA of 220 nt., The highly structured (64% GC) covalently closed circular (CCC) RNA (220 nt) of the virusoid associated with rice yellow mottle virus codes for a 16-kDa highly basic protein using novel modalities for coding, translation, and gene expression, Recent evidence has demonstrated that circular RNAs (circRNAs) played crucial roles in fine-tuning the levels of gene expression by sequestering the corresponding microRNA (miRNAs). , It has been proposed that circRNA regulate gene expression at the transcriptional or post-transcriptional level by interacting with miRNAs and that circRNAs may have a role in regulating miRNA function in cancer initiation and progression.[SEP]", "label": "no"}
{"id": "converted_1564", "sentence1": "Are adenylyl cyclases always transmembrane proteins?", "sentence2": "ransmembrane adenylyl cyclase,  Transmembrane adenylyl cyclase (tmAC) and soluble AC (sAC) , Soluble adenylyl cyclase (sAC) is a recently recognized source of the signaling molecule cyclic AMP (cAMP) that is genetically and biochemically distinct from the classic G-protein-regulated transmembrane adenylyl cyclases (tmACs)., Soluble adenylyl cyclase , transmembrane adenylyl cyclases (tmACs), and soluble adenylyl cyclase (sAC). ,  Here, we showed that both transmembrane AC (tmAC) and soluble AC (sAC) are distinctly involved in the regulation of sperm motility in the ascidian Ciona intestinalis. , cAMP production in beta cells is mediated not simply by transmembrane adenylyl cyclases (TMACs), but also by sAC., In contrast to tmAC, sAC produces cAMP in various intracellular microdomains close to specific cAMP targets, e.g., in nucleus and mitochondria, soluble adenylyl cyclase (sAC, ADCY10), the ubiquitous, non-transmembrane adenylyl cyclase, was found to play a key role in neuronal survival and axon growth., Central role of soluble adenylyl cyclase[SEP]", "label": "no"}
{"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]", "label": "no"}
{"id": "converted_3608", "sentence1": "Is amantadine ER the first approved treatment for akinesia?", "sentence2": "Extended-release amantadine (amantadine ER) is the first approved medication for the treatment of dyskinesia.[SEP]", "label": "no"}
{"id": "converted_3432", "sentence1": "Is Dexmecamylamine effective for depression?", "sentence2": "At treatment end, no significant differences were seen for change in MADRS total score with TC-5214 versus placebo. Furthermore, there were no significant differences in any of the secondary endpoints. , TC-5214 (dexmecamylamine) is a nicotinic channel modulator that has previously been evaluated for treatment of major depression disorder (MDD) and is currently being evaluated by Targacept as a treatment for overactive bladder. , In these 2 flexibly-dosed studies, no specific therapeutic effects were observed for TC-5214 (1-4 mg BID) adjunct to antidepressant in the primary endpoint or any secondary endpoint; however, TC-5214 was generally well tolerated. In conclusion, no antidepressant effect of TC-5214 was observed in these studies., TC-5214 (dexmecamylamine) is a nicotinic channel modulator that has previously been evaluated for treatment of major depression disorder (MDD) and is currently being evaluated by Targacept as a treatment for overactive bladder., No notable differences were observed between dexmecamylamine and placebo for any secondary end point., TC-5214 ( dexmecamylamine ) is a nicotinic channel modulator that has previously been evaluated for treatment of major depression disorder ( MDD ) and is currently being evaluated by Targacept as a treatment for overactive bladder . , TC-5214 (dexmecamylamine) is a nicotinic channel modulator that has previously been evaluated for treatment of major depression disorder (MDD) and is currently being evaluated by Targacept as a treatment for overactive bladder., At treatment end, no significant differences were seen for change in MADRS total score with TC-5214 versus placebo., In these 2 flexibly-dosed studies, no specific therapeutic effects were observed for TC-5214 (1-4 mg BID) adjunct to antidepressant in the primary endpoint or any secondary endpoint; however, TC-5214 was generally well tolerated.[SEP]", "label": "no"}
{"id": "converted_4238", "sentence1": "Does daily atemoya juice intake change the pharmacokinetics of CYP1A2 substrates?", "sentence2": "Atemoya juice significantly inhibited CYP1A2 activity in human liver microsomes, but not the activities of CYP2C9 and CYP3A. In spite of this inhibition, preadministration of atemoya had no effect on the pharmacokinetics of phenacetin, a CYP1A2 substrate, in rats. , The results indicate that a daily intake of atemoya would not change the pharmacokinetics of CYP1A2 substrates such as phenacetin as well as CYP2C9- and CYP3A-substrate drugs.[SEP]Relations: Phenacetin has relations: drug_protein with CYP2C9, drug_protein with CYP2C9.", "label": "no"}
{"id": "converted_2072", "sentence1": "Is vemurafenib used for thyroid cancer?", "sentence2": "Vemurafenib in patients with BRAF(V600E)-positive metastatic or unresectable papillary thyroid cancer refractory to radioactive iodine: a non-randomised, multicentre, open-label, phase 2 trial., Vemurafenib, an oncogenic BRAF kinase inhibitor approved for BRAF-positive melanoma, showed clinical benefit in three patients with BRAF(V600E)-positive papillary thyroid cancer in a phase 1 trial., INTERPRETATION: Vemurafenib showed antitumour activity in patients with progressive, BRAF(V600E)-positive papillary thyroid cancer refractory to radioactive iodine who had never been treated with a multikinase inhibitor. , CONTEXT: Vemurafenib, a selective BRAF inhibitor, appears to have promising clinical activity in patients with papillary thyroid cancer (PTC) harboring the BRAF(V600E) mutation., Efficacy and tolerability of vemurafenib in patients with BRAF(V600E) -positive papillary thyroid cancer: M.D. Anderson Cancer Center off label experience., CONCLUSIONS: Vemurafenib is a potentially effective and well-tolerated treatment strategy in patients with advanced PTC harboring the BRAF(V600E) mutation., The US Food and Drug Administration-approved BRAF inhibitors, vemurafenib and dabrafenib, have demonstrated superior efficacy in patients with BRAF-mutant melanomas but have limited efficacy in BRAF-mutant colorectal cancer. Little is known at this time regarding BRAF inhibitors in thyroid cancer. Initial reports in patients with progressive, radioactive iodine-refractory BRAF-mutant papillary thyroid cancer suggest response rates of approximately 30-40%., Use of vemurafenib in anaplastic thyroid carcinoma: a case report., Finally, we found that propranolol can amplify the cytotoxicity of vemurafenib and sensitize thyroid cancer cells to cytotoxic effect of vemurafenib., CONTEXT: Vemurafenib, a selective BRAF inhibitor, appears to have promising clinical activity in patients with papillary thyroid cancer (PTC) harboring the BRAF(V600E) mutation.OBJECTIVE: To determine the efficacy and safety of vemurafenib when used outside of a clinical trial.DESIGN: A retrospective review at MD Anderson Cancer Center.METHODS: The best responses were evaluated using RECIST v1.1., Vemurafenib, a selective BRAF inhibitor, appears to have promising clinical activity in patients with papillary thyroid cancer (PTC) harboring the BRAF(V600E) mutation.To determine the efficacy and safety of vemurafenib when used outside of a clinical trial.A retrospective review at MD Anderson Cancer Center.The best responses were evaluated using RECIST v1.1, CONTEXT: Vemurafenib, a selective BRAF inhibitor, appears to have promising clinical activity in patients with papillary thyroid cancer (PTC) harboring the BRAF(V600E) mutation.OBJECTIVE: To determine the efficacy and safety of vemurafenib when used outside of a clinical trial.DESIGN: A retrospective review at MD Anderson Cancer Center.METHODS: The best responses were evaluated using RECIST v1.1. , Finally, we found that propranolol can amplify the cytotoxicity of vemurafenib and sensitize thyroid cancer cells to cytotoxic effect of vemurafenib., Metformin or rapamycin adjuvant treatment may provide clinical benefits with minimal side effects to BRAFV600E-positive advanced thyroid cancer patients treated with vemurafenib., Vemurafenib, a selective BRAF inhibitor, appears to have promising clinical activity in patients with papillary thyroid cancer (PTC) harboring the BRAF(V600E) mutation.To determine the efficacy and safety of vemurafenib when used outside of a clinical trial.A retrospective review at MD Anderson Cancer Center.The best responses were evaluated using RECIST v1.1., Our data demonstrate that vemurafenib induces ER stress response-mediated autophagy in thyroid cancer and autophagy inhibition may be a beneficial strategy to sensitize BRAF-mutant thyroid cancer to vemurafenib.., Combination of vemurafenib and metformin decreased cell viability and increased apoptosis in both BCPAP papillary thyroid cancer cells and 8505c anaplastic thyroid cancer cells., Targeting autophagy sensitizes BRAF-mutant thyroid cancer to vemurafenib., Propranolol sensitizes thyroid cancer cells to cytotoxic effect of vemurafenib., mTOR inhibitors sensitize thyroid cancer cells to cytotoxic effect of vemurafenib., Vemurafenib induced a high level of autophagy in BRAF-mutant thyroid cancer cells.[SEP]Relations: Metformin has relations: drug_drug with Propranolol, drug_drug with Vemurafenib, drug_drug with Propranolol, drug_drug with Vemurafenib. Vemurafenib has relations: drug_drug with Propranolol, drug_protein with BRAF, drug_drug with Propranolol, drug_protein with BRAF. Propranolol has relations: drug_drug with Vemurafenib, drug_drug with Vemurafenib. thyroid gland carcinoma has relations: disease_disease with thyroid cancer, disease_protein with BRAF, disease_disease with thyroid cancer, disease_protein with BRAF. malignant colon neoplasm has relations: disease_disease with colorectal cancer, disease_protein with BRAF, disease_disease with colorectal cancer, disease_protein with BRAF. Dabrafenib has relations: drug_drug with Propranolol, drug_drug with Vemurafenib, drug_protein with BRAF, drug_drug with Propranolol, drug_drug with Vemurafenib, drug_protein with BRAF. Sirolimus has relations: drug_drug with Vemurafenib, drug_drug with Propranolol, drug_drug with Vemurafenib, drug_drug with Propranolol.", "label": "yes"}
{"id": "converted_2049", "sentence1": "Are the genes for marneral biosynthesis scattered in the genome of A. thaliana?", "sentence2": "Here we characterize a second operon-like triterpene cluster (the marneral cluster) from A. thaliana, compare the features of these two clusters, and investigate the evolutionary events that have led to cluster formation, Here we characterize a second operon-like triterpene cluster (the marneral cluster) from A. thaliana, compare the features of these two clusters, and investigate the evolutionary events that have led to cluster formation., Previously in thale cress (Arabidopsis thaliana) we identified an operon-like gene cluster that is required for the synthesis and modification of the triterpene thalianol., Prediction of operon-like gene clusters in the Arabidopsis thaliana genome based on co-expression analysis of neighboring genes, Here we characterize a second operon-like triterpene cluster (the marneral cluster) from A. thaliana, compare the features of these two clusters, and investigate the evolutionary events that have led to cluster formation. , Here we characterize a second operon-like triterpene cluster (the marneral cluster) from A., the cyclic hydroxamic acid pathways in maize, the avenacin biosynthesis gene clusters in oat, the thalianol pathway in Arabidopsis thaliana, and the diterpenoid momilactone cluster in rice., Prediction of operon-like gene clusters in the Arabidopsis thaliana genome based on co-expression analysis of neighboring genes.[SEP]", "label": "no"}
{"id": "converted_3406", "sentence1": "Does xaliproden improve prognosis of amyotrophic lateral sclerosis?", "sentence2": "Treatment for crampsThere is evidence (13 RCTs, N = 4012) that for the treatment of cramps in MND, compared to placebo:- memantine and tetrahydrocannabinol (THC) are probably ineffective (moderate-quality evidence);- vitamin E may have little or no effect (low-quality evidence); and- the effects of L-threonine, gabapentin, xaliproden, riluzole, and baclofen are uncertain as the evidence is either very low quality or the trial specified the outcome but did not report numerical data., The medications comprised vitamin E, baclofen, riluzole, L-threonine, xaliproden, indinavir, and memantine. Six studies assessed cramps as an adverse event. The medications comprised creatine, gabapentin, dextromethorphan, quinidine, and lithium. In all 20 studies no favourable effect for the treatment of cramps in ALS/MND could be demonstrated, but many studies were underpowered to draw a definite conclusion., . The six months intent-to-treat analysis showed no statistically significant effect but a trend in favour of 2 mg xaliproden compared to placebo for reduction in the rate of deterioration of FVC, limbs functional score, and manual muscle testing score (MMT)., These results support the use of a staging process to select suitable patients for phase II studies, and suggest that xaliproden may have potential effects in ALS and deserve further study., An effect of xaliproden on functional parameters, especially VC, was noted. Although this effect did not reach statistical significance, xaliproden had a small effect on clinically noteworthy aspects of disease progression in ALS., The six months intent-to-treat analysis showed no statistically significant effect but a trend in favour of 2 mg xaliproden compared to placebo for reduction in the rate of deterioration of FVC, limbs functional score, and manual muscle testing score (MMT)., An effect of xaliproden on functional parameters, especially VC, was noted., These results support the use of a staging process to select suitable patients for phase II studies, and suggest that xaliproden may have potential effects in ALS and deserve further study., The six months intent-to-treat analysis showed no statistically significant effect but a trend in favour of 2 mg xaliproden compared to placebo for reduction in the rate of deterioration of FVC, limbs functional score, and manual muscle testing score (MMT)., Although this effect did not reach statistical significance, xaliproden had a small effect on clinically noteworthy aspects of disease progression in ALS.[SEP]", "label": "no"}
{"id": "converted_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]", "label": "no"}
{"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]", "label": "yes"}
{"id": "converted_855", "sentence1": "Do carmustine wafers improve survival of glioblastoma patients?", "sentence2": "At recurrence, treatment options include repeat surgery (with or without Gliadel wafer placement), reirradiation or systemic therapy. , DISCUSSION: Carmustine wafers for primary HGG surgery in accordance with the NICE TA121 were associated with a median survival of 15.3 months; this is improved compared with previously reported randomised trials. Multimodal treatment with carmustine wafers, radical radiotherapy and concomitant temozolomide was associated with improved survival., Gliadel wafer is a new approach to the treatment of glioblastoma, which involves controlled release delivery of carmustine from biodegradable polymer wafers. It has shown promising results and provides a silver lining for glioblastoma patients., For patient with and without Gliadel, median and 1-year RFS were 12.9 months and 52% vs. 14 months and 42%, respectively (p = 0.89)., According to pathology, Gliadel did not influence OS of patients with Grade III or glioblastoma, CONCLUSION: In patients with high-grade gliomas, adding Gliadel before performing a Stupp protocol did not improve survival., Randomized phase III trials have shown significant improvement of survival 1, 2, and 3 years after implantation of 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU) wafers for patients with newly diagnosed malignant glioma. , CONCLUSIONS: The combination of aggressive resection, Gliadel wafer implantation, and GKS in addition to standard fractionated RT in selected patients resulted in increased local control and increased survival compared with a historical control group treated with surgery and involved-field RT alone., OBJECT: Gliadel (BCNU) wafer and concomitant temozolomide (TMZ) therapy, when used individually as adjuvant therapies, extend survival from that achieved by resection and radiation therapy (XRT) for glioblastoma multiforme (GBM). , BACKGROUND: Gliadel (polifeprosan 20 with carmustine [BCNU] implant) is commonly used for local delivery of BCNU to high-grade gliomas after resection and is associated with increased survival., Temozolomide administered according to this protocol produced a median survival benefit of 2 months in glioblastomas, and carmustine a similar benefit in high-grade gliomas., Analysis of a large trial by Westphal and colleagues (n = 240) showed a 29% risk reduction (P = 0.03) in the BCNU wafer-treated group over the course of the 30-month trial., Median survival of patients treated with BCNU wafers was 13.8 months vs 11.6 months in placebo-treated patients (P = 0.017) with a hazard ratio of 0.73 (P = 0.018), representing a 27% significant risk reduction. This survival advantage was maintained at 1, 2, and 3 years and was statistically significant (P = 0.01) at 3 years., CONCLUSION: Malignant glioma patients treated with BCNU wafers at the time of initial surgery in combination with radiation therapy demonstrated a survival advantage at 2 and 3 years follow-up compared with placebo., OBJECTIVE: Recently a randomized placebo-controlled phase III trial of biodegradable polymers containing carmustine has demonstrated a significant survival benefit for patients treated with local chemotherapy. , CONCLUSION: In this subgroup analysis of a phase III trial population both the clinical progression and radiological progression were significantly delayed in patients treated with local chemotherapy, resulting in an increased survival time., A previous placebo-controlled trial has shown that biodegradable 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU) wafers (Gliadel wafers) prolong survival in patients with recurrent glioblastoma multiforme. A previously completed phase 3 trial, also placebo controlled, in 32 patients with newly diagnosed malignant glioma also demonstrated a survival benefit in those patients treated with BCNU wafers., Median survival in the intent-to-treat group was 13.9 months for the BCNU wafer-treated group and 11.6 months for the placebo-treated group (log-rank P -value stratified by country = 0.03), with a 29% reduction in the risk of death in the treatment group. When adjusted for factors affecting survival, the treatment effect remained positive with a risk reduction of 28% ( P = 0.03). , Controlled release delivery of carmustine from biodegradable polymer wafers was approved as an adjunct to surgical resection in the treatment of recurrent glioblastoma multiforme after it was shown in clinical trials to be well tolerated and effective. , Clinical trials have demonstrated significant improvements in survival and quality of life for patients after complete tumour resection and BCNU wafer implantation., BCNU wafers are an effective means of increasing survival and quality of life in patients diagnosed with malignant glioma, and are a valuable addition to the overall multimodal treatment strategy for these tumours., CONCLUSIONS: Carmustine wafer with concurrent TMZ and radiation followed by rotational chemotherapy is a well tolerated, effective therapy, and has a survival benefit compared with radiation alone., Median overall survival in 14 studies of newly-diagnosed patients suggested a modest improvement versus resection followed by Stupp protocol or resection with BCNU wafers, with an acceptable and manageable safety profile., The efficacy of carmustine wafers for older patients with glioblastoma multiforme: prolonging survival., DISCUSSION: Older patients with GBM may benefit from carmustine wafers. The survival for older patients who received carmustine wafers is significantly longer than matched patients who did not receive carmustine wafers., For glioblastoma patients who received ≥90% resection in the BCNU wafer study, median survival increased for BCNU wafer versus placebo (14.5 versus 12.4 months, respectively; P = 0.02), but no survival increase was found for <90% resection (11.7 versus 10.6 months, respectively; P = 0.98)., A wafer impregnated with carmustine, for use as an implant after surgical removal of recurrent GBM showed a prolongation in the median survival time of only 2 mo, from 20 to 28 wk in a study with a total of 222 patients. , No clear survival benefit associated with wafer implantation was identified., In three of the trials, patients with GBM who received carmustine wafers had significantly longer median survival than patients who did not receive wafers. , TMZ and carmustine (BCNU) biodegradable wafer (Gliadel) are the only adjuvant chemotherapies that have improved survival in randomised GB clinical trials . , The carmustine implant wafer was demonstrated to improve survival in blinded placebo-controlled trials in selected patients with newly diagnosed or recurrent malignant glioma, with little increased risk of adverse events. , For patients undergoing repeat resection for malignant glioma, a randomized, blinded, placebo-controlled trial demonstrated a median survival for 110 patients who received carmustine polymers of 31 weeks compared with 23 weeks for 122 patients who only received placebo polymers., Median survival was improved from 11.6 to 13.9 months (P = 0.03), with a 29% reduction in the risk of death. When patients with glioblastoma multiforme alone were analyzed, the median survival improved from 11.4 to 13.5 months, but this improvement was not statistically significant. , OBJECT: Locoregional chemotherapy with carmustine wafers, positioned at surgery and followed by radiation therapy, has been shown to prolong survival in patients with newly diagnosed glioblastoma, as has concomitant radiochemotherapy with temozolomide., Following the resection of newly diagnosed or recurrent glioblastomas, local implantation of carmustine-impregnated biodegradable wafers (Gliadel) in the resection cavity constitutes an adjuvant therapy that can improve the possibilities of survival., The carmustine implant wafer was demonstrated to improve survival in blinded placebo-controlled trials in selected patients with newly diagnosed or recurrent malignant glioma, with little increased risk of adverse events., However, patients with carmustine wafers demonstrated prolonged survival as compared to patients without wafers., The median survival for patients with carmustine wafers was 8.7 months, while median survival for patients without wafers was 5.5 months (P=0.007)., Likewise, in subgroup analysis, patients older than 70 years (P=0.0003) and 75 years (P=0.04) who had carmustine wafers had significantly longer survival than matched patients without wafers., Implantation of carmustine wafers did not significantly improve progression-free survival, In three of the trials, patients with GBM who received carmustine wafers had significantly longer median survival than patients who did not receive wafers, A previous placebo-controlled trial has shown that biodegradable 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU) wafers (Gliadel wafers) prolong survival in patients with recurrent glioblastoma multiforme, A previously completed phase 3 trial, also placebo controlled, in 32 patients with newly diagnosed malignant glioma also demonstrated a survival benefit in those patients treated with BCNU wafers, Following the resection of newly diagnosed or recurrent glioblastomas, local implantation of carmustine-impregnated biodegradable wafers (Gliadel) in the resection cavity constitutes an adjuvant therapy that can improve the possibilities of survival, Multimodal treatment with carmustine wafers, radical radiotherapy and concomitant temozolomide was associated with improved survival, The carmustine implant wafer was demonstrated to improve survival in blinded placebo-controlled trials in selected patients with newly diagnosed or recurrent malignant glioma, with little increased risk of adverse events, TMZ and carmustine (BCNU) biodegradable wafer (Gliadel) are the only adjuvant chemotherapies that have improved survival in randomised GB clinical trials [SEP]Relations: Temozolomide has relations: drug_drug with Carmustine, drug_drug with Carmustine.", "label": "yes"}
{"id": "converted_2780", "sentence1": "Is cariprazine effective for treatment of bipolar disorder?", "sentence2": "BACKGROUND: We evaluated the safety/tolerability of longer-term open-label treatment with cariprazine in patients who had responded to cariprazine for acute bipolar mania., Clinically relevant response and remission outcomes in cariprazine-treated patients with bipolar I disorder., Cariprazine is FDA approved for the acute treatment of schizophrenia and manic or mixed episodes associated with bipolar I disorder in adults., DISCUSSION: Cariprazine-treated patients with bipolar I disorder attained clinically significant improvement in manic symptoms as shown by significantly greater rates of response and remission versus placebo; improvement in manic symptoms did not induce depressive symptoms., OBJECTIVE: Cariprazine, a dopamine D3/D2 partial agonist atypical antipsychotic with preferential binding to D3 receptors, is approved for the treatment of schizophrenia and manic or mixed episodes associated with bipolar I disorder., <b>BACKGROUND</b>: Cariprazine was approved for treating schizophrenia and bipolar disorder, and currently is being evaluated for treating depression in clinical trials in the United States.[SEP]Relations: Dopamine has relations: drug_drug with Cariprazine, drug_drug with Cariprazine.", "label": "yes"}
{"id": "converted_4418", "sentence1": "Do SETD1A mutations predispose to schizophrenia?", "sentence2": "Recapitulation and Reversal of Schizophrenia-Related Phenotypes in Setd1a-Deficient Mice., SETD1A, a lysine-methyltransferase, is a key schizophrenia susceptibility gene. Mice carrying a heterozygous loss-of-function mutation of the orthologous gene exhibit alterations in axonal branching and cortical synaptic dynamics accompanied by working memory deficits. We show that Setd1a binds both promoters and enhancers with a striking overlap between Setd1a and Mef2 on enhancers. Setd1a targets are highly expressed in pyramidal neurons and display a complex pattern of transcriptional up- and downregulations shaped by presumed opposing functions of Setd1a on promoters and Mef2-bound enhancers. Notably, evolutionarily conserved Setd1a targets are associated with neuropsychiatric genetic risk burden. Reinstating Setd1a expression in adulthood rescues cognitive deficits. Finally, we identify LSD1 as a major counteracting demethylase for Setd1a and show that its pharmacological antagonism results in a full rescue of the behavioral and morphological deficits in Setd1a-deficient mice. Our findings advance understanding of how SETD1A mutations predispose to schizophrenia (SCZ) and point to novel therapeutic interventions.[SEP]Relations: SETD1A has relations: disease_protein with schizophrenia, disease_protein with schizophrenia.", "label": "yes"}
{"id": "converted_524", "sentence1": "Is the protein β1-integrin recycled?", "sentence2": "Pathways selectively regulating β1-integrin recycling are implicated in cancer invasion and metastasis,, integrin-positive early and recycling endosomes , LPA-induced recycling of β1 integrin,, RCP-mediated recycling of α5β1 integrin , CycD1 overexpression increased β1 integrin recycling , inhibition of autophagy slowed down the lysosomal degradation of internalized β1 integrins and promoted its membrane recycling, recycling pathway for β1-integrin,  β1 integrin recycling,  β1 integrin recycling,  controlling β1 integrin recycling to the plasma membrane , integrin recycling pathway, Distinct recycling of active and inactive β1 integrins., Integrin functions are controlled by regulating their affinity for ligand, and by the efficient recycling of intact integrins through endosomes.,  β1 integrins, resulting in their recycling to the cell surface where they can be reused.[SEP]", "label": "yes"}
{"id": "converted_3704", "sentence1": "Does radiotherapy for prostate cancer increase bladder cancer risk?", "sentence2": "External Beam Radiotherapy Increases the Risk of Bladder Cancer When Compared with Radical Prostatectomy in Patients Affected by Prostate Cancer: A Population-based Analysis., On multivariable competing risk regression analyses, treatment with EBRT was independently associated with the risk of developing a second primary BCa (hazard ratio: 1.35, CI: 1.18-1.55; p<0.001), but not RCa (p=0.4). , CONCLUSIONS: Patients treated with EBRT are at increased risk of developing a second primary BCa compared with those treated with RP. However, no differences were found considering RCa incidence in patients treated with RP or EBRT within the first 5 yr after primary therapy. , We found that those treated with external beam radiotherapy are at an increased risk of developing a second primary bladder cancer tumor., All radiation modalities were found to have an increased RR of developing BlCa after 10 years, with brachytherapy having a significantly higher RR than external beam radiation (EBRT) or combined EBRT and brachytherapy in Caucasian men and a significantly higher RR than EBRT in men of other/unknown ethnicity. , CONCLUSIONS: The increased risk of BlCa after prostate radiation occurs predominantly after 10 years, regardless of ethnicity. The RR of developing BlCa after 10 years is significantly higher following brachytherapy than after EBRT or EBRT and brachytherapy. , Based on the data in the literature, there is a consistently increased risk of bladder cancer (HR: 1.67, 95% CI 1.55-1.80), rectal cancer (HR: 1.79, 95% CI 1.34-2.38), and colorectal cancer (HR: 1.79, 95% CI 1.34-23.8) following percutaneous radiation therapy. Following brachytherapy only an increased for the development of bladder cancer (HR: 2.14, 95% CI 1.03-3.94) has been observed., When comparing with a matched general French population, the standard incidence ratio (SIR) for bladder cancer was 1.02 (95% CI: 0.46-1.93)., LDR resulted in lower bladder cancer risks than HDR, and lower or similar risks of rectal cancer., Compared to external beam techniques, second rectal and bladder cancer risks were lowest for brachytherapy., OBJECTIVE: Although it is well known that radiotherapy for prostate cancer increases comorbid rate of secondary bladder cancer, the effect of aging and smoking with radiotherapy on incidence rate of secondary bladder cancer remains unknown. , RESULTS: During the median follow-up period of 4.3 and 3.1 years, secondary bladder cancer occurred in 11 (3.4%) and 5 (1.1%) of patients with prostate cancer treated with external beam radiotherapy and radical prostatectomy, respectively. , CONCLUSIONS\n\nMen who receive radiotherapy for localized prostate cancer have an increased risk of bladder cancer compared to patients undergoing radical prostatectomy and compared to the general population., Radiation therapy for prostate cancer increases subsequent risk of bladder and rectal cancer: a population based cohort study., RESULTS\n\nThe relative risk of bladder cancer developing after external beam radiotherapy, brachytherapy and external beam radiotherapy-brachytherapy compared to radical prostatectomy was 1.88, 1.52 and 1.85, respectively., Compared to the general United States population the standardized incidence ratio for bladder cancer developing after radical prostatectomy, external beam radiotherapy, brachytherapy and external beam radiotherapy-brachytherapy was 0.99, 1.42, 1.10 and 1.39, respectively., OBJECTIVE\n\nAlthough it is well known that radiotherapy for prostate cancer increases comorbid rate of secondary bladder cancer, the effect of aging and smoking with radiotherapy on incidence rate of secondary bladder cancer remains unknown., OBJECTIVE\nAlthough it is well known that radiotherapy for prostate cancer increases comorbid rate of secondary bladder cancer, the effect of aging and smoking with radiotherapy on incidence rate of secondary bladder cancer remains unknown., CONCLUSIONS\nMen who receive radiotherapy for localized prostate cancer have an increased risk of bladder cancer compared to patients undergoing radical prostatectomy and compared to the general population., PURPOSE\nPre-prostate specific antigen era series demonstrated an increased risk of bladder cancer and rectal cancer in men who received radiotherapy for prostate cancer., RESULTS\nThe relative risk of bladder cancer developing after external beam radiotherapy, brachytherapy and external beam radiotherapy-brachytherapy compared to radical prostatectomy was 1.88, 1.52 and 1.85, respectively., CONCLUSIONS: Taken together, these findings suggest that smoking history might be one of criteria to choose radical prostatectomy than external beam radiotherapy for prostate cancer, and that age would not be a criterion for therapeutic selection in terms of secondary bladder cancer., PURPOSE: Pre-prostate specific antigen era series demonstrated an increased risk of bladder cancer and rectal cancer in men who received radiotherapy for prostate cancer., RESULTS: The relative risk of bladder cancer developing after external beam radiotherapy, brachytherapy and external beam radiotherapy-brachytherapy compared to radical prostatectomy was 1.88, 1.52 and 1.85, respectively., Compared to the general United States population the standardized incidence ratio for bladder cancer developing after radical prostatectomy, external beam radiotherapy, brachytherapy and external beam radiotherapy-brachytherapy was 0.99, 1.42, 1.10 and 1.39, respectively., Pre-prostate specific antigen era series demonstrated an increased risk of bladder cancer and rectal cancer in men who received radiotherapy for prostate cancer., Men who receive radiotherapy for localized prostate cancer have an increased risk of bladder cancer compared to patients undergoing radical prostatectomy and compared to the general population., The relative risk of bladder cancer developing after external beam radiotherapy, brachytherapy and external beam radiotherapy-brachytherapy compared to radical prostatectomy was 1.88, 1.52 and 1.85, respectively., Radiotherapy for prostate cancer is associated with an increased incidence of secondary bladder cancer (BC)., Radiation therapy for prostate cancer is associated with an increased risk of bladder cancer., Radiotherapy for prostate cancer was associated with higher risks of developing second malignancies of the bladder, colon, and rectum compared with patients unexposed to radiotherapy, but the reported absolute rates were low.[SEP]Relations: rectal carcinoma has relations: disease_disease with rectal cancer, disease_disease with rectal cancer. malignant colon neoplasm has relations: disease_disease with colorectal cancer, disease_disease with colorectal cancer.", "label": "yes"}
{"id": "converted_4489", "sentence1": "Is Mical an oxidoreductase?", "sentence2": "the MICALs, which are flavoprotein monooxygenase/hydroxylase enzymes that associate with flavin adenine dinucleotide (FAD) and use the co-enzyme nicotinamide adenine dinucleotide phosphate (NADPH) in Redox reactions, MICAL is an oxidoreductase, We have recently identified a new family of multidomain oxidoreductase (redox) enzymes, the MICALs,, the oxidoreductase MICAL[SEP]", "label": "yes"}
{"id": "converted_4409", "sentence1": "Does addition of valproic acid improve survival of patients with diffuse intrinsic pontine glioma?", "sentence2": "Median event-free survival (EFS) and overall survival (OS) for DIPG were 7.8 (95% CI 5.6-8.2) and 10.3 (7.4-13.4) months, and estimated one-year EFS was 12% (2%-31%). Median EFS and OS for HGG were 9.1 (6.4-11) and 12.1 (10-22.1) months, and estimated one-year EFS was 24% (7%-45%). , CONCLUSION: Addition of VPA and bevacizumab to radiation was well tolerated but did not appear to improve EFS or OS in children with DIPG or HGG., Event-free survival and overall survival of patients not treated with valproic acid were 6.5 and 7.8 months. Accelerated failure time model (a parametric multivariate regression test for time-to-failure data) showed a statistically significant superiority of the median event-free survival of treated patients (6.5 vs. 9.5 months in treated patients; HR 0.54-95 % CI 0.33-0.87; p < 0.05) and also of overall survival (7.8 vs. 13.4 months in treated patients; HR 0.60-95 % CI 0.37-0.98; p = 0.05).[SEP]", "label": "no"}
{"id": "converted_38", "sentence1": "Does physical activity influence gut hormones?", "sentence2": "Increases in blood PYY(3-36) levels were dependent on the exercise intensity (effect of session: P<0.001 by two-way ANOVA), whereas those in GLP-1 levels were similar between two different exercise sessions., A decrease in serum leptin levels (-48.4%, p < 0.001) was observed after intervention without changes in total peptide YY and insulin levels., ur data suggest that the control of spontaneous physical activity by gut hormones or their neuropeptide targets may represent an important mechanistic component of energy balance regulation, Hunger and gut hormones remained unchanged during the bed rest., weight-bearing exercise has a greater exercise-induced appetite suppressive effect compared with non-weight-bearing exercise, and both forms of exercise lowered acylated ghrelin and increased total PYY, but the changes did not differ significantly between exercise modes., Appetite (P < 0.0005) and acylated ghrelin (P < 0.002) were suppressed during exercise but more so during SIE. Peptide YY increased during exercise but most consistently during END (P < 0.05). Acylated ghrelin was lowest in the afternoon of SIE (P = 0.018) despite elevated appetite, Following the pre-exercise meal, ghrelin was suppressed ~17% and insulin and PYY were elevated ~157 and ~40%, respectively, relative to fasting (day 7). Following exercise, PYY, ghrelin, and GH were significantly (p < 0.0001) increased by ~11, ~16 and ~813%, respectively. The noted disruption in the typical inverse relationship between ghrelin and PYY following exercise suggests that interaction of these peptides may be at least partially responsible for post-exercise appetite suppression, Plasma levels of PYY and GLP-1 were increased by exercise, whereas plasma ghrelin levels were unaffected by exercise, These findings suggest ghrelin and PYY may regulate appetite during and after exercise,, significant (P < 0.05) interaction effects for hunger, acylated ghrelin, and PYY, indicating suppressed hunger and acylated ghrelin during aerobic and resistance exercise and increased PYY during aerobic exercise, 'exercise-induced anorexia' may potentially be linked to increased PYY, GLP-1 and PP levels., Hunger scores and PYY, GLP-1 and PP levels showed an inverse temporal pattern during the 1-h exercise/control intervention, Exercise significantly increased mean PYY, GLP-1 and PP levels, and this effect was maintained during the post-exercise period for GLP-1 and PP. No significant effect of exercise was observed on postprandial levels of ghrelin, following blood donation the strenuous exercise resulted in a marked reduction in the plasma leptin, We conclude that strenuous physical exercise; 1) fails to affect plasma leptin level but when performed after meal but not after blood withdrawal it results in an increase and fall in plasma leptin, and 2) the release of gut hormones (gastrin, CCK and PP) and stress hormones (norepinephrine, cortisol, GH) increase immediately after exercise independently of feeding or blood donation, the unrestricted exercise group has a significantly elevated SRIF-LI concentration, Exercise has recently been reported to influence ghrelin and PYY concentrations.[SEP]", "label": "yes"}
{"id": "converted_1835", "sentence1": "Do statins cause diabetes?", "sentence2": "Statin use has been associated with increased risk of developing type 2 diabetes (T2DM), and with impaired glycemic control in T2DM patients, The relationship between T2DM and statins is further complicated since these drugs can cause new onset diabetes (NOD) although there is an overall benefit in terms of preventing vascular events , It has been repeatedly reported that statins may cause new-onset diabetes mellitus (DM)., However, a small, but significant risk of new-onset diabetes has been reported in patients treated with statins., The National Lipid Association (NLA) Statin Diabetes Safety Task Force concluded that the cardiovascular benefit of statin therapy outweighs the risk for developing diabetes, It has been repeatedly reported that statins may cause new-onset diabetes mellitus (DM), It has been repeatedly reported that statins may cause new-onset diabetes mellitus (DM). However, limited evidence exists from direct head to head comparisons of statins on whether the risk of DM differs among statins., Short-term statin exposure is associated with reduced all-cause mortality in persons with diabetes., Despite the fact that higher statin doses are more likely to lead to new-onset diabetes, for every case of diabetes caused, there are approximately three cardiovascular events reduced with high dose versus moderate dose statin therapy., It has been repeatedly reported that statins may cause new-onset diabetes mellitus (DM).,  Statins are evidence-based drugs to prevent cardiovascular (CV) disease. However, their benefits have been disputed by a statin-related increased risk of new onset diabetes,  Compared with pravastatin, treatment with higher potency statins, especially atorvastatin and simvastatin, might be associated with an increased risk of new onset diabetes,  statins are associated with a small increase in incidence of diabetes in patients predisposed to glycemic alteration,  Higher potency statin use is associated with a moderate increase in the risk of new onset diabetes compared with lower potency statins in patients treated for secondary prevention of cardiovascular disease, An increased risk of new onset treated diabetes was found in those treated with statins showing significant duration and dose effect, Although most of the clinical studies suggest a worsening of insulin resistance and secretion, the cardiovascular benefits of statin therapy outweigh the risk of developing insulin resistance, thus the data suggest the need to treat dyslipidemia and to make patients aware of the possible risk of developing type 2 diabetes or, if they already are diabetic, of worsening their metabolic control, Statin therapy can slightly increase risk of incident diabetes in subjects with hypercholesterolemia.[SEP]", "label": "yes"}
{"id": "converted_227", "sentence1": "Can DNA intercalators function as topoisomerase inhibitors?", "sentence2": "The aporphine alkaloids (+)-dicentrine and (+)-bulbocapnine are non-planar molecules lacking features normally associated with DNA binding by intercalation or minor groove binding. Surprisingly, dicentrine showed significant activity as a topoisomerase II (EC 5.99.1.3) inhibitor and also was active in a DNA unwinding assay., The DNA unwinding suggests DNA intercalation, which could explain the inhibition of topoisomerase II., We found that several agents, including adriamycin (a DNA intercalator and inhibitor of topoisomerase II), Amsacrine, a DNA intercalator and topoisomerase II inhibitor, is efficacious as an antileukemogenic agent., Quinacrine was less effective. (ii) Inhibitors intercalating and binding to the 'cleavable' DNA-topoisomerase complex (m-AMSA, mitoxantrone, doxorubicin and daunorubicin) strongly suppressed reparative DNA incision. , DNA intercalation and inhibition of topoisomerase II., Among its many properties, amiloride is a DNA intercalator and topoisomerase II inhibitor., To determine whether the ability of amiloride to intercalate into DNA and to inhibit DNA topoisomerase II was dependent on the ability to assume a cyclized conformation, we studied the structure-activity relationship for 12 amiloride analogs, Empirical assays consisting of biophysical, biochemical, and cell biological approaches, as well as computational molecular modeling approaches, were used to determine conformational properties for these molecules, and to determine whether they intercalated into DNA and inhibited topoisomerase II. , Results indicated that only those analogs capable of cyclization could intercalate into DNA and inhibit topoisomerase II. Thus, the ability of amiloride and the 12 analogs studied to intercalate into DNA and to inhibit topoisomerase II appears dependent on the ability to exist in a planar, hydrogen-bonded, tricyclic conformation., Abnormal expression of the nuclear-associated enzyme DNA topoisomerase II (topoisomerase II) has been implicated in the in vitro phenotype of radiation hypersensitive ataxia-telangiectasia (A-T) cells and in modifying sensitivity of eukaryotic cells to topoisomerase II-inhibitor drugs [e.g., the DNA intercalator amsacrine (mAMSA)]. , All three tested anthraquinones, emodin, aloe-emodin, and danthron, showed capabilities to inhibit the non-covalent binding of bisbenzimide Hoechst 33342 to isolated DNA and in mouse lymphoma L5178Y cells comparable to the topoisomerase II inhibitor and intercalator m-amsacrine., These studies suggest that AD 288 inhibits topoisomerase II activity by preventing the initial non-covalent binding of topoisomerase II to DNA. Since AD 288 is a potent DNA intercalator, catalytic inhibition is achieved by prohibiting access of the enzyme to DNA binding sites. , AQ4N (1,4-bis[[2-(dimethylamino)ethyl] amino]-5,8-dihydroxyanthracene-9, 10-dione bis-N-oxide dihydrochloride) is a prodrug which is selectively activated within hypoxic tissues to AQ4, a topoisomerase II inhibitor and DNA intercalator., Amonafide is a DNA intercalator and topoisomerase II inhibitor in clinical development for the treatment of neoplastic diseases.,  We found that three compounds had similar cancer cell-selective growth inhibition to amonafide, while retaining similar subcellular localization, DNA intercalation and topoisomerase II inhibition activities., Amonafide is a novel topoisomerase II (Topo II) inhibitor and DNA intercalator that induces apoptotic signaling by blocking the binding of Topo II to DNA., At higher concentrations, inhibition of Top1 catalytic activity and DNA intercalation is observed., Design, synthesis and biological evaluation of new oligopyrrole carboxamides linked with tricyclic DNA-intercalators as potential DNA ligands or topoisomerase inhibitors., It was found that 1) morpholinyldoxorubicin, cyanomorpholinyldoxorubicin, and Actinomycin D (but not doxorubicin) stimulated DNA topoisomerase I-induced cleavage at specific DNA sites; 2) only doxorubicin and Actinomycin D stimulated DNA cleavage by DNA topoisomerase II; 3) at higher drug concentrations, DNA intercalators suppressed enzyme-mediated DNA cleavage induced by DNA topoisomerase I, as well as topoisomerase II; 4) only cyanomorpholinyldoxorubicin produced DNA-DNA cross-links; no DNA unwinding could be observed; and 5) DNA intercalation (unwinding) potency of morpholinyldoxorubicin was about 2-fold less than that of doxorubicin., The data indicate that some DNA intercalators are not only inhibitors of DNA topoisomerase II but act also on DNA topoisomerase I., The screen of cMAP for uncharacterized drugs indicated the signature of Epoxy anthraquinone derivative (EAD) matched the profiles of multiple known DNA targeted agents (topoisomerase I/II inhibitors, DNA intercalators, and DNA alkylation agents) as predicted by its structure., Cytotoxicity of several classes of antitumor DNA intercalators is thought to result from disturbance of DNA metabolism following trapping of the nuclear enzyme DNA topoisomerase II as a covalent complex on DNA., Most DNA intercalators and epipodophyllotoxins inhibit mammalian topoisomerase II by trapping the enzyme within DNA cleavage complexes that can be detected in cells as protein-associated DNA strand breaks., Many compounds capable of inhibiting DNA topoisomerase II are DNA intercalators., Numerous topoisomerase I poisons including DNA minor groove binders such as Hoechst 33258 and DNA intercalators such as benzophenanthridine alkaloids and indolocarbazole derivatives have been discovered and developed., The stabilization of cleavage intermediates by intercalators may have a common mechanism for DNA topoisomerase I and DNA topoisomerase II., Because structurally related antitumor alkaloids such as camptothecin and fagaronine are known to function as intercalative topoisomerase poisons, it is hypothesized that cytotoxic Stauranthus alkaloids may also serve as intercalative topoisomerase inhibitors., Taken together, our results suggest that much of the activity and specificity of m-AMSA as a topoisomerase II poison is embodied in the headgroup, while DNA intercalation is used primarily to increase the affinity of m-AMSA for the topoisomerase II-DNA cleavage complex., The cross-sensitivity patterns of the mutant were examined for covalently (anthramycin) and non-covalently (distamycin A) binding minor groove ligands, and DNA intercalating [adriamycin, mitoxantrone and 4'-(9-acridinylamino)methanesulphon-m-anisidide (mAMSA)] and non-intercalating (VP16-213) topoisomerase II poisons., Quinoline alkaloids as intercalative topoisomerase inhibitors., DNA intercalation and inhibition of topoisomerase II. Structure-activity relationships for a series of amiloride analogs., These include: (i) the production of improved topoisomerase inhibitors (by consideration of drug/protein as well as drug/DNA interactions); (ii) the development of reductively-activated chromophores as hypoxia-selective agents; and (iii) the use of DNA-intercalators of known DNA binding orientation as 'carriers' for the delivery of other reactive functionality specifically (sequence-, regio- and site-specifically) to DNA., Indolo[2,3-b]quinolines are a family of DNA intercalators and inhibitors of topoisomerase II, synthetic analogs of neocryptolepine, an alkaloid traditionally used in African folk medicine., Their ability to function as bis-intercalators was assessed by a novel and convenient topoisomerase fluorescent assay., Structure-activity relationship of polypyridyl ruthenium(II) complexes as DNA intercalators, DNA photocleavage reagents, and DNA topoisomerase and RNA polymerase inhibitors., In addition, fragments of about 900 kbp were detected in the cells treated with a topoisomerase inhibitor, 4'-(9-acridinylamino)methane-sulfon-m-anisidine, and fragments in the broad size range between 700 and 245 kbp in the cells treated with radical producers, bleomycin and neocarzinostatin. , The data indicate that some DNA intercalators are not only inhibitors of DNA topoisomerase II but act also on DNA topoisomerase I. , Long-term inhibition of DNA synthesis and the persistence of trapped topoisomerase II complexes in determining the toxicity of the antitumor DNA intercalators mAMSA and mitoxantrone., Effects of the DNA intercalators 4'-(9-acridinylamino)methanesulfon-m-anisidide and 2-methyl-9-hydroxyellipticinium on topoisomerase II mediated DNA strand cleavage and strand passage., Most DNA intercalators and epipodophyllotoxins inhibit mammalian topoisomerase II by trapping the enzyme within DNA cleavage complexes that can be detected in cells as protein-associated DNA strand breaks. , Here, molecular interactions of the potent antitumor drug amsacrine (m-AMSA), an inhibitor of topoisomerase II, within living K562 cancer cells have been studied using surface-enhanced Raman (SER) spectroscopy. , It has been shown previously that DNA intercalators can inhibit the action of amsacrine and several other topoisomerase II poisons, presumably as a result of interference with the DNA binding sites for the enzyme. , The gadd153 promoter was strongly activated by a broad spectrum of genotoxic agents including UV-mimetic agents, DNA-cross-linking and alkylating agents, DNA intercalators, and topoisomerase inhibitors. , Our study indicates that Epoxy anthraquinone derivative may be a novel DNA topoisomerase inhibitor that can be potentially used for treatment of neuroblastoma or other cancer patients., Organic intercalators can inhibit nucleic acid synthesis in vivo, and they are now common anticancer drugs in clinical therapy. , Because structurally related antitumor alkaloids such as camptothecin and fagaronine are known to function as intercalative topoisomerase poisons, it is hypothesized that cytotoxic Stauranthus alkaloids may also serve as intercalative topoisomerase inhibitors., Specifically, we measured the ability of these compounds to 1) alter the thermal denaturation profile of DNA, 2) modify the hydrodynamic behavior of DNA, 3) inhibit the catalytic activity of purified DNA topoisomerase II in vitro, 4) promote the topoisomerase II-dependent cleavage of DNA, and 5) inhibit functions associated with DNA topoisomerase II in intact cells. Results indicated that only those analogs capable of cyclization could intercalate into DNA and inhibit topoisomerase II., A function for topoisomerases I and II in DNA excision repair can be postulated from the organization of the mammalian chromosome, involving nucleosomal structures and matrix-attached DNA loops. To analyse this function we determined UV-induced DNA incision in confluent human fibroblasts in the presence of 16 inhibitors of topoisomerases I and II which belonged to at least five different drug categories, based on their mechanism of action., In experiments to determine the mechanism of inhibition of DNA synthesis by amiloride, we observed that amiloride inhibited both the catalytic activity of purified DNA topoisomerase II in vitro and DNA topoisomerase II-dependent cell functions in vivo. Many compounds capable of inhibiting DNA topoisomerase II are DNA intercalators., The pyridoacridines&apos; ability to inhibit TOPO II-mediated decatenation of kDNA correlated with their cytotoxic potencies and their ability to intercalate into calf thymus DNA. These results suggest that disruption of the function of TOPO II, subsequent to intercalation, is a probable mechanism by which pyridoacridines inhibit the proliferation of HCT cells., Evidence for DNA intercalation by AD41 is provided by the observation that the drug introduces positive supercoils into covalently closed plasmid DNA. Based on these data, a hypothesis is proposed that would provide a general mechanism whereby intercalating agents and epipodophyllotoxins alter topoisomerase function and presumably exert their antitumor effects., Therefore, to more fully analyze structure-function relationships and the role of DNA binding in the action of m-AMSA, we analyzed a series of derivatives for the ability to enhance DNA cleavage mediated by human topoisomerase IIα and topoisomerase IIβ and to intercalate DNA. Results indicate that the 3&apos;-methoxy (m-AMSA) positively affects drug function, potentially by restricting the rotation of the headgroup in a favorable orientation.[SEP]Relations: Daunorubicin has relations: drug_drug with Quinacrine, drug_drug with Quinacrine.", "label": "yes"}
{"id": "converted_1055", "sentence1": "Does splicing occur co-transcriptionally?", "sentence2": "Researchers working in multiple model organisms - notably yeast, insects and mammalian cells - have shown that pre-mRNA can be spliced during the process of transcription (i.e. co-transcriptionally), as well as after transcription termination (i.e. post-transcriptionally), The consensus view, based on four organisms, is that the majority of splicing events take place co-transcriptionally in most cells and tissues., Deep sequencing of subcellular RNA fractions shows splicing to be predominantly co-transcriptional, We show that in the human genome, splicing occurs predominantly during transcription., Consistent with co-transcriptional spliceosome assembly and splicing, we have found significant enrichment of spliceosomal snRNAs in chromatin-associated RNA compared with other cellular RNA fractions and other nonspliceosomal snRNAs. , The majority of introns in higher eukaryotes are excised prior to transcript release in a manner that is dependent on transcription through pol II, s a result of co-transcriptional splicing, variations in pol II elongation influence alternative splicing patterns, wherein a slower elongation rate is associated with increased inclusion of alternative exons within mature mRNA. , We show that the pattern of intronic sequence read coverage is explained by nascent transcription in combination with co-transcriptional splicing, Modelling reveals co-transcriptional splicing to be the most probable and most efficient splicing pathway for the reporter transcripts, due in part to a positive feedback mechanism for co-transcriptional second step splicing, RNA processing events that take place on the transcribed pre-mRNA include capping, splicing, editing, 3' processing, and polyadenylation. Most of these processes occur co-transcriptionally while the RNA polymerase II (Pol II) enzyme is engaged in transcriptional elongation, Abundant evidence indicates that splicing to excise introns occurs co-transcriptionally, prior to release of the nascent transcript from RNAP II, Together, our work establishes a system for co-transcriptional splicing in vitro, in which the spliceosome containing the 5' and 3' exons are tethered to RNAP II for splicing., Co-transcriptional splicing of constitutive and alternative exons, Current evidence supports co-transcriptional spliceosomal assembly, but there is little quantitative information on how much splicing is completed during RNA synthesis, Thus, we demonstrate that the decision to include or skip an alternative exon is made during transcription and not post-transcriptionally, Here, we demonstrated that the co-transcriptional splicing of the intron in vitro was blocked by antisense oligonucleotides (AONs) targeting the P3-P7 core of the intron, RNA editing and alternative splicing: the importance of co-transcriptional coordination, Co-transcriptional splicing of pre-messenger RNAs: considerations for the mechanism of alternative splicing, The realization that splicing occurs co-transcriptionally requires two important considerations[SEP]", "label": "yes"}
{"id": "converted_2207", "sentence1": "Is Prochlorococcus the most abundant photosynthetic organism?", "sentence2": "The marine cyanobacterium Prochlorococcus is the smallest and most abundant photosynthetic organism on Earth., The marine cyanobacterium Prochlorococcus is the numerically dominant photosynthetic organism in the oligotrophic oceans, and a model system in marine microbial ecology., The marine cyanobacterium Prochlorococcus is the most abundant photosynthetic organism in oligotrophic regions of the oceans., The oceanic picoplankton Prochlorococcus - probably the most abundant photosynthetic organism on our planet - can grow at great depths where light intensity is very low.[SEP]", "label": "yes"}
{"id": "converted_1392", "sentence1": "Do RNA:DNA hybrids preferentially form in high or low GC regions?", "sentence2": "Intrinsic termination signals for multisubunit bacterial RNA polymerases (RNAPs) encode a GC-rich stem-loop structure followed by a polyuridine [poly(U)] tract, and it has been proposed that steric clash of the stem-loop with the exit pore of the RNAP imposes a shearing force on the RNA in the downstream RNA:DNA hybrid, resulting in misalignment of the active site, We have observed that transcription through the GC-rich FMR1 5'UTR region favors R-loop formation, with the nascent (G-rich) RNA forming a stable RNA:DNA hybrid with the template DNA strand, thereby displacing the non-template DNA strand., Transcription termination by bacterial RNA polymerase (RNAP) occurs at sequences coding for a GC-rich RNA hairpin followed by a U-rich tract. We used single-molecule techniques to investigate the mechanism by which three representative terminators (his, t500, and tR2) destabilize the elongation complex (EC)., In the 5' flanking region, nucleotides -234 to -213 encompass a GC-rich region which exhibits high homology (greater than 70%) to the 5' flanking regions of the genes of all the apolipoproteins published to date, namely, apo-A-II (-497 to -471), apo-A-I (approximately -196 to -179), apo-E (-409 to -391), and apo-C-III (approximately -116 to -103)., Recently, we demonstrated that cotranscriptional RNA•DNA hybrids are preferentially formed at GC-rich trinucleotide and tetranucleotide repeat sequences in vitro as well as in human genomic DNA., Considering the extent of transcription through the human genome as well as the abundance of GC-rich and/or non-canonical DNA structure forming tandem repeats, RNA•DNA hybrids may represent a common mutagenic conformation., Recently, we demonstrated that cotranscriptional RNA•DNA hybrids are preferentially formed at GC-rich trinucleotide and tetranucleotide repeat sequences in vitro as well as in human genomic DNA. [SEP]", "label": "yes"}
{"id": "converted_1394", "sentence1": "Are shadow enhancers associated with development?", "sentence2": "Critical developmental control genes sometimes contain \"shadow\" enhancers that can be located in remote positions, including the introns of neighboring genes, These results suggest that shadow enhancers represent a novel mechanism of canalization whereby complex developmental processes \"bring about one definite end-result regardless of minor variations in conditions\", Shadow enhancers flanking the HoxB cluster direct dynamic Hox expression in early heart and endoderm development.,  This suggests that they function as shadow enhancers to modulate the expression of genes from the HoxB complex during cardiac development. Regulatory analysis of the HoxA complex reveals that it also has enhancers in the 3' flanking region which contain RAREs and have the potential to modulate expression in endoderm and heart tissues, This suggests that they function as shadow enhancers to modulate the expression of genes from the HoxB complex during cardiac development., Recent reports have shown that developmental genes often possess multiple discrete enhancer modules that drive transcription in similar spatio-temporal patterns: primary enhancers located near the basal promoter and secondary, or 'shadow', enhancers located at more remote positions., Together, the similarities in their location, enhancer output, and dependence on retinoid signaling suggest that a conserved cis-regulatory cassette located in the 3' proximal regions adjacent to the HoxA and HoxB complexes evolved to modulate Hox gene expression during mammalian cardiac and endoderm development. , This suggests that they function as shadow enhancers to modulate the expression of genes from the HoxB complex during cardiac development.[SEP]", "label": "yes"}
{"id": "converted_2216", "sentence1": "Is Hepatic mesenchymal hamartoma usually a malignant tumor?", "sentence2": "Mesenchymal hamartoma of the liver (MHL) is a benign and rare hepatic lesion, , Mesenchymal hamartoma of the liver (MHL) is an uncommon benign hepatic tumor typically affecting children under 2 years of age, This review on the pathology of hepatic tumors in childhood, from a personal series of 245 tumors, focuses on incidence, management, description of frequent tumors such as hepatoblastoma, fibrolamellar carcinoma, and undifferentiated sarcoma for malignant tumors, focal nodular hyperplasia, hepatocellular adenoma, and mesenchymal hamartoma for benign tumors., Mesenchymal hamartoma of the liver is a rare benign liver tumor in children, usually arising from the right liver lobe and represents about 5 to 6% of all primary hepatic tumors, Hepatic mesenchymal hamartoma (HMH) is the second most common benign hepatic tumor in children, Hepatic mesenchymal hamartoma is a rare benign tumor in children, and infantile hepatic hemangioendothelioma is also a rare liver neoplasm, This review on the pathology of hepatic tumors in childhood, from a personal series of 245 tumors, focuses on incidence, management, description of frequent tumors such as hepatoblastoma, fibrolamellar carcinoma, and undifferentiated sarcoma for malignant tumors, focal nodular hyperplasia, hepatocellular adenoma, and mesenchymal hamartoma for benign tumors, Mesenchymal hamartoma is a rare and benign tumor.. Representing 5 to 8 % of childrens hepatic tumors, it is rarely described in adults, We report a case of hepatic mesenchymal hamartoma, a rare benign tumour, in a 10-month-old infant., Hepatic mesenchymal hamartoma is a rare benign tumour in children., Mesenchymal hamartoma is a benign lesion best treated by surgical resection, which usually results in cure., Hepatic mesenchymal hamartoma are rare benign tumors., Hepatic mesenchymal hamartoma is a rare benign tumor in children, and infantile hepatic hemangioendothelioma is also a rare liver neoplasm., Mesenchymal hamartoma is an uncommon benign hepatic tumor arising from the mesenchyme of the portal triad., esenchymal hamartoma of the liver (MHL) is an uncommon benign tumor found primarily in children younger than 2 years of age,  case of a prenatally recognized hepatic mesenchymal hamartoma is presented and the literature reviewed. These tumors are benign and usually present in early infancy with symptoms that are related to the mass effect on adjacent organ[SEP]", "label": "no"}
{"id": "converted_694", "sentence1": "Is there a phylogenetic analysis for HIV?", "sentence2": "The results of Burst and phylogenetic analysis suggested that the C. neoformans var. grubii strains could be separated into three nonredundant evolutionary groups (Burst group 1 to group 3). , Phylogenetic trees were constructed to evaluate the relationships between the variants, We analyzed pol (protease/reverse transcriptase) sequences from 135 newly diagnosed HIV-1-infected patients during the years 2009-2011. For phylogenetic relationships, sequences were aligned to the most recent reference data set from the Los Alamos database using BioEdit (version 7.1.3). The resulting alignment was analyzed with the Phylip package (version 3.67) building a neighbor-joining tree based on the Kimura two-parameter substitution model, . Phylogenetic analysis of gag gene were then performed using the MEGA 3.1 software, the gene distances were calculated by Distance program. There were three different HIV-1 subtypes including B, CRF01-AE and CRF07-BC present among twenty four MSMs in Zhengzhou, Phylogenetic analysis showed interpatient and intrapatient clustering of LTR nucleotide sequences.,  We evaluated the risk factors for intrafamilial transmission of HIV-1 infection through qualitative epidemiology following pol and env gene sequencing and phylogenetic analysis, Phylogenetic analysis has shown that the Siberian 10.RU.6637 isolate displays the highest sequence identity to the HIV-1 subtype AG forms circulating in Uzbekistan, Phylogenetic analysis showed that the evolutionary relationship of Env between HIV and SIV was the closest and they appeared to descend from a common ancestor, and the relationship of HIV and EIAV was the furthest, DI was confirmed when maximum sequence divergence was excessive and supported by phylogenetic analysis,  (HIV-1) dual infection (DI) has been associated with decreased CD4 T-cell counts and increased viral loads; however, the frequency of intrasubtype DI is poorly understood., The aim of this study was to investigate the phylogenetic relationships of HIV-1 subtype C strains from Bangladesh and related strains from other countries, and thereby clarify when and from where subtype C was introduced in the country and how it subsequently spread within Bangladesh,  This study characterized HCV genotype 5 sequences from South Africa, including six near full-length genomes, as well as the E1 region from an additional 12 genotype 5 samples. Phylogenetic analysis of these near full-length genome sequences revealed that all genotype 5 sequences formed a close cluster with high bootstrap support,  The evolutionary history of the B subregion was not as clear as the C subregion, as the short length of this region yielded poor phylogenetic results,  Finally, a phylogenetic tree was constructed to elucidate the observed pattern of HIV TDR[SEP]", "label": "yes"}
{"id": "converted_1823", "sentence1": "Is Annexin V an apoptotic marker?", "sentence2": "The apoptosis of the MSCs was induced by subjecting the cells to OGD conditions for 4 h and was detected by Annexin V/PI and Hoechst 33258 staining. , In addition to the antimicrobial activity, we found that treatment of the cancer cell lines, Jurkat T-cells, Granta cells, and melanoma cells, with the Pseudomonas sp. In5 crude extract increased staining with the apoptotic marker Annexin V while no staining of healthy normal cells, i.e., naïve or activated CD4 T-cells, was observed., At the same time, the expressions of CD105, CD31, and the apoptotic marker of Annexin V were detected through flow cytometry for analyzing the relationship between the expression of cell surface markers and biological behavior., However, we found decreased sperm concentration, increase of morphologically abnormal spermatozoa and increased binding of apoptotic marker annexin V. , hCG enhanced viability of granulosa-lutein cells through antiapoptosis but not proliferation, because the apoptotic marker of annexin V was decreased, but the proliferative markers of Ki67 and proliferating cell nuclear antigen were not increased., However, as the DOTAP concentration increased from 50 to 800 microM, the apoptotic marker Annexin V and ROS double positive cells increased, suggesting that high dose of DOTAP-generated ROS causes cell apoptosis. , Expression of the apoptotic marker annexin V was unaffected by antibiotic exposure, whereas the uptake of the necrotic marker PI was increased by ofloxacin (5 mg/mL) but not by netilmicin (ofloxacin versus netilmicin, ANOVA, P<0.05)., he apoptotic marker of annexin V was decreased, the apoptotic marker Annexin V, Annexin V labels apoptotic neurons following hypoxia-ischemia., In the present study, the apoptotic cell population was identified immunocytochemically using Annexin V, a marker of cells in an early stage of apoptosis., Use of annexin V antibody to identify apoptotic cells during pregnancy., Only few SF Treg cells were apoptotic, as indicated by limited annexin V staining of these cells., Eosinophils 'aged' in vitro for 48 h exhibited endonuclease DNA degradation, apoptotic morphology, increased red autofluorescence and externalisation of phosphatidylserine (PS) as assessed by binding of FITC-labelled annexin V., In vivo detection of apoptotic cells with fluorescently labeled annexin V is an emerging technique that we evaluated for detecting apoptotic germ cells in a mouse model of testicular torsion.Annexin V labeled with an indocyanine fluorophore (bisfunctional succinimidyl ester of cyanine 5.5) (Amersham, Little Chalfont, United Kingdom) was injected intravenously in mice 18 hours after the repair of unilateral 720-degree testicular torsion for 2 hours, Here, we tested the hypothesis that enhanced endothelial apoptotic microparticles and decreased endothelial progenitor cell (EPC) levels might contribute to the pathophysiology of microalbuminuria or macroalbuminuria in cardiovascular disease.Flow cytometry was used to assess endothelial cell apoptosis and circulating EPC levels by quantification of circulating CD31/annexin V apoptotic microparticles and EPC markers (defined as KDRCD133, CD34CD133, CD34KDR) in peripheral blood.In total, 125 patients with hypertension were enrolled in the study, of whom 80 patients (64%) were with normoalbuminuria (albumin excretion rate of &lt;20 microg/min, overnight urine samples), 35 patients (28%) with microalbuminuria (an albumin excretion rate of 20-200 microg/min), and 10 patients (8%) with macroalbuminuria (an albumin excretion rate >200 microg/min)., Surfactant protein A (SP-A) binds to phosphatidylserine and competes with annexin V binding on late apoptotic cells, Targeting of apoptotic macrophages and experimental atheroma with radiolabeled annexin V: a technique with potential for noninvasive imaging of vulnerable plaque, Because annexin V has a high affinity for exposed phosphatidylserine on apoptotic cells, radiolabeled annexin V may be used for noninvasive detection of apoptosis in atherosclerotic lesions.Atherosclerotic plaques were produced in 5 rabbits by deendothelialization of the infradiaphragmatic aorta followed by 12 weeks of cholesterol diet; 5 controls were studied without manipulation, Apoptotic abscess imaging with 99mTc-HYNIC-rh-Annexin-V., Synthesis and evaluation of a 18F-labelled recombinant annexin-V derivative, for identification and quantification of apoptotic cells with PET., Sensitive and visible detection of apoptotic cells on Annexin-V modified substrate using aminophenylboronic acid modified gold nanoparticles (APBA-GNPs) labeling., Fluorescence-activated cell sorting (FACS) for expression of the early apoptosis marker Annexin V and for nuclear staining by 7-aminoactinomycin (7-AAD) revealed different extents of apoptosis versus non-apoptotic cell death for the three agents., At immunofluorescence these cells contained lipid vesicles positive for the apoptotic cell marker Annexin V suggesting the phagocytosis of apoptotic bodies derived from dead fat-laden hepatocytes., In this respect, we identified binding of Annexin V as an convenient marker for apoptotic cells., DR5 expression was elevated and associated with the apoptotic marker annexin V. Apoptosis was reduced in CD4(+) T cells when cultured with anti-DR5 antibody., Flow cytometric analysis using the apoptotic marker, Annexin V, shows that this endogenous re-expression is sufficient to drive the SCLC cells to apoptosis., Apoptotic cell death was evaluated by staining nuclei with propidium iodide and phosphatidylserine (a marker of early apoptotic events) with Annexin V as well as by DNA fragmentation assay., Decreased cell growth was not caused by cell death as BEL exposure did not alter nuclear morphology or increase annexin V (apoptotic cell marker) or propidium iodide (necrotic cell marker) staining after 48 h., Four populations of cells can be identified: region R1: vital cells (annexin V negative/PI negative), region R2: apoptotic cells (annexin V positive/PI negative), region R3: dead cells (annexin V positive/ PI positive); and region R4: damaged cells (annexin V negative/PI positive)., Furthermore, uptake of (111)In-DTPA-PEG-annexin V by tumors correlated with apoptotic index (r = 0.87, P = 0.02)., Annexin V(+)/PI(-) cells were characterized as early apoptotic, Annexin V(+)/PI(+) as late apoptotic and Annexin V(-)/PI(+) as dead., Targeting ability of Annexin V for apoptotic macrophages was kept and enhanced., [18F]annexin V accumulated in the infarct area of the left ventricle, where apoptotic cells were observed., The viability of SiHa cells was evaluated using the MTT assay, apoptosis by acridine orange/ethidium bromide, propidium iodide, TUNEL assay, and Annexin V-Cy3, cell cycle distribution and mitochondrial transmembrane potential using flow cytometry, and apoptotic marker genes using quantitative real-time PCR. , Furthermore, hesperetin-induced apoptosis was confirmed by TUNEL and Annexin V-Cy3., The procedure delivers two sperm fractions: annexin V-negative (nonapoptotic) and annexin V-positive (apoptotic)., The percentage of cells stained with annexin V, an early apoptotic marker, increased dramatically after cytoskeletal disruption with cytochalasin D compared with non-cytochalasin-D-treated controls (P<0.05). , Apoptotic marker Annexin V analysis showed that the apoptotic rate of NB4 cells was increased after treatment with quercetin., The cytomorphology of NB4 cells was assessed by Wright-stain, apoptosis rate by apoptotic marker Annexin V, and VEGF secretion level by ELISA.,  We have coupled annexin V with the bifunctional hydrazinonicotinamide reagent (HYNIC) to prepare technetium-99m HYNIC-annexin V and demonstrated localization of radioactivity in tissues undergoing apoptosis in vivo., In conlusion, these studies confirm the value of (99m)Tc-HYNIC-annexin V uptake as a marker for the detection and quantification of apoptotic cells in vivo., The application of Annexin V labeling at electron microscopy will allow a more refined description of the morphological events occurring during apoptosis., Apoptotic cells were identified by Annexin V-FITC/PI staining. [SEP]", "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: substantia nigra has relations: anatomy_protein_present with BDNF, anatomy_protein_present with BDNF. Parkinson disease has relations: disease_protein with BDNF, disease_protein with BDNF.", "label": "yes"}
{"id": "converted_4686", "sentence1": "Is retinol binding protein 4 an adipokine?", "sentence2": "Systematic Quantification of Neurotrophic Adipokines RBP4, PEDF, and Clusterin in Human Cerebrospinal Fluid and Serum., Retinol-binding protein 4 (RBP4) is a prominent adipokine i, Fetuin-A and retinol-binding protein 4 (RBP4) are secreted as both hepatokine and adipokine. [SEP]Relations: retinol binding has relations: molfunc_protein with RBP4, molfunc_protein with RBP4.", "label": "yes"}
{"id": "converted_4450", "sentence1": "Is SOX10 expressed in melanoma cells?", "sentence2": "Our study confirmed that SOX10 is an oncogene and activate Notch signaling pathway, which suggests the potential treatment for melanoma patients by target SOX10/Notch axis., The most commonly used melanocytic markers include S100, Melan-A, HMB45 and SOX10, melanocytic markers melan-A and SOX10 [SEP]Relations: melanocytic neoplasm has relations: disease_disease with melanoma, disease_disease with melanoma.", "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]", "label": "no"}
{"id": "converted_3226", "sentence1": "Is myc a tumour suppressor gene?", "sentence2": "oncogenic Myc, a master transcription factor that turns on anabolic metabolism to promote cell growth in many cancers. , he MYC oncogene,  the proto-oncogene protein c-MYC, however, other genes such as the proto-oncogene c-Myc are promising targets for anticancer therapy[SEP]", "label": "no"}
{"id": "converted_3168", "sentence1": "Tocilizumab is an anti-TNF antibody, yes or no?", "sentence2": "was treated with tocilizumab, an anti-interleukin-6 receptor monoclonal antibody , Tocilizumab (TCZ) is a humanized monoclonal antibody against IL-6 receptor licensed in 2009 that has demonstrated clinical efficacy in various adult RA populations. RA management guidelines and recommendations consider TCZ as one of the bDMARDS indicated after methotrexate or other conventional synthetic DMARDs and/or TNF inhibitors failure in adult RA, Tocilizumab (RoActemra or Actemra) is a recombinant humanized monoclonal antibody that acts as an interleukin (IL)-6 receptor antagonist., METHODS\nPatients (n = 93) were treated with an anti-IL-6 receptor antibody (tocilizumab) or TNF-α inhibitors for 16 weeks., The recent development of biological agents, namely, anti-tumour necrosis factor alpha (TNF-α) agents (infliximab, adalimumab and etanercept), anti- CD20 monoclonal antibody (rituximab) and anti-interleukin 6 receptor (IL-6R) monoclonal antibody (tocilizumab), represents a major breakthrough for the treatment of immune-mediated disorders., Recently, an anti-IL-6 receptor monoclonal antibody, tocilizumab, has been licensed for the treatment as monotherapy or in combination with methotrexate of moderate to severe RA, when disease modifying anti-rheumatic drugs or anti-tumour necrosis factors (TNF) have failed., Tocilizumab is a monoclonal humanized anti-IL-6-receptor antibody used for the treatment of rheumatoid arthritis., Indeed, worldwide clinical trials of TNF inhibiting biologic disease modifying antirheumatic drugs (bDMARDs) including infliximab, adalimumab, golimumab, certolizumab pegol, and etanercept as well as the humanized anti-human IL-6 receptor antibody, tocilizumab, have demonstrated outstanding clinical efficacy and tolerable safety profiles, resulting in worldwide approval for using these bDMARDs to treat moderate to severe active RA in patients with an inadequate response to synthetic disease modifying antirheumatic drugs (sDMARDs)., Tocilizumab is a humanized anti-IL-6 receptor monoclonal antibody, which binds to circulating soluble IL-6 receptor and membrane-expressed IL-6 receptor, inhibiting IL-6 binding to both forms of IL-6 receptor., Subsequent options include a TNF-alpha antagonist, followed by rituximab or possibly abatacept; (2) Tocilizumab, a monoclonal antibody, inhibits interleukin-6 receptors., Tocilizumab (TCZ) is a monoclonal antibody which inhibits the interleukin-6 receptor.[SEP]Relations: Abatacept has relations: drug_drug with Tocilizumab, drug_drug with Tocilizumab. Etanercept has relations: drug_drug with Tocilizumab, drug_protein with TNF, drug_drug with Tocilizumab, drug_protein with TNF. Golimumab has relations: drug_protein with TNF, drug_drug with Tocilizumab, drug_protein with TNF, drug_drug with Tocilizumab. Methotrexate has relations: drug_drug with Tocilizumab, drug_drug with Tocilizumab. Rituximab has relations: drug_drug with Tocilizumab, drug_drug with Tocilizumab. Adalimumab has relations: drug_protein with TNF, drug_drug with Tocilizumab, drug_protein with TNF, drug_drug with Tocilizumab. Infliximab has relations: drug_protein with TNF, drug_drug with Tocilizumab, drug_protein with TNF, drug_drug with Tocilizumab.", "label": "no"}
{"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]", "label": "yes"}
{"id": "converted_249", "sentence1": "Does burning mouth syndrome preferentially affect post-mepopausal women?", "sentence2": "It is observed principally in middle-aged patients and postmenopausal women and may be accompanied by xerostomia and altered taste., It occurs more commonly in middle-aged and elderly women and often affects the tongue tip and lateral borders, lips, and hard and soft palate. , BMS is a chronic disorder that frequently affects women and is characterised by burning symptoms of the oral mucosa without clinical signs., It mostly affects elderly citizens, especially postmenopausal women with prevalence up to 12-18%. [SEP]", "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]", "label": "no"}
{"id": "converted_2135", "sentence1": "Are hepadnaviral minichromosomes free of nucleosomes?", "sentence2": "Several nucleosome-protected sites in a region of the DHBV genome [nucleotides (nt) 2000 to 2700], known to harbor various cis transcription regulatory elements, were consistently identified in all DHBV-positive liver samples., In addition, we observed other nucleosome protection sites in DHBV minichromosomes that may vary among individual ducks, but the pattern of MNase mapping in those regions is transmittable from the adult ducks to the newly infected ducklings., nucleosomes along viral cccDNA in the minichromosomes are not random but sequence-specifically positioned., Investigators studying the structure and function of hepadnaviral CCC DNA (3) have provided evidence that suggests that this structure exists in the nucleus of infected hepatocytes as a heterogeneous population of viral minichromosomes, which range from half to fully chromatinized, thought to be owing to their association with variable numbers of nucleosomes., Characterization of nucleosome positioning in hepadnaviral covalently closed circular DNA minichromosomes., To obtain insight on the structure of hepadnaviral cccDNA minichromosomes, we utilized ducks infected with the duck hepatitis B virus (DHBV) as a model and determined the in vivo nucleosome distribution pattern on viral cccDNA by the micrococcal nuclease (MNase) mapping and genome-wide PCR amplification of isolated mononucleosomal DHBV DNA., Mature SV40 minichromosomes are estimated to contain about 27 nucleosomes (error +/- 2), except for those molecules with a nucleosome-free gap, which are interpreted to contain 25 nucleosomes (error +/- 2)., In vitro replication in the presence of protein-free competitor DNA shows that replicating trypsinized minichromosomes do not lose nucleosomes and replicating competitor DNA does not gain nucleosomes., In vitro replication in the presence of protein-free competitor DNA shows that replicating trypsinized minichromosomes do not lose nucleosomes and replicating competitor DNA does not gain nucleosomes., We conclude that in both cases parental nucleosomes are transferred to progeny DNA, and, in addition, that an assembly of new nucleosomes occurs during the replication of native minichromosomes., In contrast, the replicated untreated minichromosomes were found to be densely packed with nucleosomes, indicating that an assembly of new nucleosomes occurred during in vitro replication., Investigators studying the structure and function of hepadnaviral CCC DNA (3) have provided evidence that suggests that this structure exists in the nucleus of infected hepatocytes as a heterogeneous population of viral minichromosomes, which range from half to fully chromatinized, thought to be owing to their association with variable numbers of nucleosomes, To obtain insight on the structure of hepadnaviral cccDNA minichromosomes, we utilized ducks infected with the duck hepatitis B virus (DHBV) as a model and determined the in vivo nucleosome distribution pattern on viral cccDNA by the micrococcal nuclease (MNase) mapping and genome-wide PCR amplification of isolated mononucleosomal DHBV DNA, Characterization of nucleosome positioning in hepadnaviral covalently closed circular DNA minichromosomes., To obtain insight on the structure of hepadnaviral cccDNA minichromosomes, we utilized ducks infected with the duck hepatitis B virus (DHBV) as a model and determined the in vivo nucleosome distribution pattern on viral cccDNA by the micrococcal nuclease (MNase) mapping and genome-wide PCR amplification of isolated mononucleosomal DHBV DNA., Investigators studying the structure and function of hepadnaviral CCC DNA (3) have provided evidence that suggests that this structure exists in the nucleus of infected hepatocytes as a heterogeneous population of viral minichromosomes, which range from half to fully chromatinized, thought to be owing to their association with variable numbers of nucleosomes..[SEP]", "label": "no"}
{"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]", "label": "yes"}
{"id": "converted_393", "sentence1": "Is there an association between bruxism and reflux?", "sentence2": "Sleep bruxism is prevalent in GERD patients, and GERD is highly associated with SB., There was a statistical trend towards tooth wear progression being associated with gastric risk factors (p < 0.05). , This article presents a case report of a 27-year-old male smoker with tooth wear and dentin sensitivity caused by GERD associated with bruxism. , The aim of this cross-over, randomized, single-blinded trial was to examine whether intra-esophageal acidification induces sleep bruxism (SB). , RMMA episodes including SB were induced by esophageal acidification. , Chronic regurgitation of gastric acids in patients with gastroesophageal reflux disease may cause dental erosion, which can lead in combination with attrition or bruxism to extensive loss of coronal tooth tissue., This clinical report describes treatment of severe tooth wear of a gastroesophageal reflux disease patient who is 54-year-old Turkish male patient. After his medical treatment, severe tooth wear, bruxism and decreased vertical dimensions were determined. , Gastroesophageal reflux disease by itself or in combination with attrition, abrasion or bruxism may be responsible for the loss., The association between bruxism, feeding and smoking habits and digestive disorders may lead to serious consequences to dental and related structures, involving dental alterations (wear, fractures and cracks), periodontal signs (gingival recession and tooth mobility) and muscle-joint sensitivity, demanding a multidisciplinary treatment plan. This paper presents a case report in which bruxism associated with acid feeding, smoking habit and episodes of gastric reflow caused severe tooth wear and great muscular discomfort with daily headache episodes. , The frequencies of RMMA, single short-burst, and clenching episodes were significantly higher during decreased esophageal pH episodes than those during other times. , These results suggest that most jaw muscle activities, ie, RMMA, single short-burst, and clenching episodes, occur in relation to gastroesophageal reflux mainly in the supine position., Nocturnal bruxism may be secondary to nocturnal gastroesophageal reflux, occurring via sleep arousal and often together with swallowing.[SEP]Relations: Gastroesophageal reflux has relations: disease_phenotype_positive with gastroesophageal reflux disease, disease_phenotype_positive with gastroesophageal reflux disease.", "label": "yes"}
{"id": "converted_4699", "sentence1": "Are there roles for cohesin mutations in AML?", "sentence2": "Several landmark studies have shown that cohesin mutations perturb the balance between self-renewal and differentiation of hematopoietic stem and progenitor cells (HSPC). Emerging data now begin to uncover the molecular mechanisms that underpin this phenotype. Among these mechanisms is a role for cohesin in the control of inflammatory responses in HSPCs and myeloid cells. Inflammatory signals limit HSPC self-renewal and drive HSPC differentiation. Consistent with this, cohesin mutations promote resistance to inflammatory signals, and may provide a selective advantage for AML progression. [SEP]", "label": "yes"}
{"id": "converted_4469", "sentence1": "Is sacituzumab govitecan effective for breast cancer?", "sentence2": "Sacituzumab Govitecan (also known by the brand name TRODELVY®) is a new and available treatment for metastatic triple-negative breast cancer, or mTNBC for short. , Sacituzumab govitecan (sacituzumab govitecan-hziy; Trodelvy™) is a Trop-2-directed antibody conjugated to a topoisomerase I inhibitor (SN-38) that is being developed by Immunomedics for the treatment of solid tumours, including breast cancer., Results from a phase I/II trial suggest that an antibody-drug conjugate, sacituzumab govitecan, is active against refractory, metastatic triple-negative breast cancer. A, INTRODUCTION: Sacituzumab govitecan-hziy, approved in 2020 for treatment of metastatic triple-negative breast cancer, provides a new option for a population with a historically poor prognosis with standard , Sacituzumab govitecan (SG), the first antibody-drug conjugate (ADC) approved for triple-negative breast cancer, incorporates the anti-TROP2 antibody hRS7 conjugated to a topoisomerase-1 (TOP1) inhibitor payload. We so, Sacituzumab govitecan was initially approved in April 2020 under accelerated approval for the treatment of patients with metastatic triple-negative breast cancer who received at least two prior therapies for metastatic disease, The ASCENT trial reports impressive results with a median overall survival (OS) increased from 6.7 months to 12.1 months with sacituzumab govitecan over single-agent chemotherapy, in metastatic triple negative breast cancer (TNBC) patients in second and subsequent line of therapy. We , A phase II study indicates that sacituzumab govitecan (IMMU-132), a Trop-2-specific antibody linked to the irinotecan metabolite SN-38, prolongs the progression-free survival of patients with advanced triple-negative breast cancer. I, agents, sacituzumab govitecan, has been recently granted an accelerated approval for therapy of metastatic triple-negative breast cancer. In this artic, l 2020, sacituzumab govitecan received accelerated approval in the USA for the treatment of adult patients with metastatic triple-negative breast cancer (mTNBC) who have received at least two prior therapies for metastatic disease. Sacituzu, Sacituzumab Govitecan for Metastatic Triple-Negative Breast Cancer: Clinical Overview and Management of Potential Toxicities., ood and Drug Administration) recently approved the use of a Trop2-targeting ADC (antibody-drug conjugate), Sacituzumab Govitecan (IMMU-132), for metastatic, triple-negative breast cancer with at least two prior therapies. Here, we review, sive disease. Sacituzumab govitecan represents an important advance in the treatment of mTNBC because of its efficacy an, Sacituzumab govitecan (SG) is a novel antibody-drug conjugate (ADC) that has shown promising efficacy in mTNBC, The activity of sacituzumab govitecan likely extends beyond TNBC with promising early efficacy data in many other epithelial cancers, including hormone receptor-positive breast cancer., In a basket design phase I/II study, sacituzumab govitecan demonstrated promising single-agent therapeutic activity in multiple cancer cohorts, leading to accelerated approval by the U.S. Food and Drug Administration of sacituzumab govitecan-hziy (TRODELVY) for the treatment of patients with metastatic triple-negative breast cancer who had received at least two prior therapies in the metastatic setting., Efficacy and Safety of Anti-Trop-2 Antibody Drug Conjugate Sacituzumab Govitecan (IMMU-132) in Heavily Pretreated Patients With Metastatic Triple-Negative Breast Cancer., Expert opinion: Sacituzumab govitecan has promising anti-cancer activity in patients with metastatic TNBC previously treated with at least two prior lines of systemic therapy based on a single arm Phase I/II clinical trial., Sacituzumab govitecan has shown promise in cancers outside of TNBC, such as urothelial and lung and is being evaluated in HR-positive breast cancers.,  prognosis. Sacituzumab govitecan is an antibody-drug conjugate composed of an antibody targeting the human trophoblast cell-surface antigen 2 (Trop-2), which is expressed in the majority of breast cancers, coupled to SN-38 (topoisomerase I inhibitor) through a proprietary hydrolyzable linker.METHODS: In this randomized, phase 3 trial, we evaluated sacituzumab govitecan as compared with single-agent chemotherapy of the physician's choice (eribulin, vinorelbine, capecitabine, or gemcitabine) in patients with relapsed or refractory metastatic triple-ne, Expert opinion Sacituzumab govitecan has promising survival benefits in patients with previously treated mTNBC based on data from the ASCENT trial., Conclusion Sacituzumab govitecan was well tolerated and induced early and durable responses in heavily pretreated patients with metastatic TNBC., Sacituzumab Govitecan in Metastatic Triple-Negative Breast Cancer., Sacituzumab Govitecan (also known by the brand name TRODELVY®) is a new and available treatment for metastatic triple-negative breast cancer, or mTNBC for short.[SEP]Relations: Irinotecan has relations: drug_protein with TOP1, drug_protein with TOP1. Sacituzumab govitecan has relations: drug_protein with TOP1, drug_protein with TOP1.", "label": "yes"}
{"id": "converted_187", "sentence1": "Are proteasome inhibitors good candidates for treatment of leukemia and solid tumors?", "sentence2": "We show that treatment with b-AP15 inhibited tumor progression in four different in vivo solid tumor models and inhibited organ infiltration in an acute myeloid leukemia model. Our results show that the deubiquitinating activity of the 19S regulatory particle is a new anticancer drug target, We further found that ATO targets AME via both myelodysplastic syndrome 1 (MDS1) and EVI1 moieties and degrades EVI1 via the ubiquitin-proteasome pathway and MDS1 in a proteasome-independent manner. Our results suggest that ATO could be used as a part of targeted therapy for AME-, AML1/MDS1-, MDS1/EVI1-, and EVI1-positive human cancers., Previously we had shown the synergic effect of bortezomib and thiostrepton in breast cancer cells in vitro, where sub-apoptotic concentrations of both proteasome inhibitors resulted in synergic increase in cell death when combined as a treatment. Here, we administered such a combination to MDA-MB-231 xenograft tumors in vivo, and found that the effect of complementary proteasome inhibitors reduced tumor growth rates more efficiently than compared with when administered alone., Addition of a proteasome inhibitor to anti-hormonal therapy resulted in a clinical benefit rate of 22% in a limited number of patients with endocrine resistant and progressive metastatic breast cancer., Taken together, these data support the clinical development of MLN9708 for both hematologic and solid tumor indications., Bortezomib has minimal activity as a single-agent in the treatment of recurrent platinum-sensitive EOC/PPC, Our study indicates a molecular mechanism by which the sensitivity of thyroid cancer cells is regulated by the level of GRP78 as well as preferential induction of GRP78 or CHOP upon treatment with proteasome inhibitors. Our experiments therefore suggest a novel approach toward sensitization of thyroid cancer cells to proteasome inhibitors., Bortezomib (PS-341) is a novel antineoplastic agent that is well tolerated at doses not exceeding 3.0 mg (equivalent to 1.75 mg/m2), repeated on D1 and D4 every other week. This dose correlates with 70% inhibition of 20S proteasome activity., The maximum-tolerated dose and recommended phase II dose of bortezomib in this schedule is 1.6 mg/m(2). Biologic activity (inhibition of nuclear factor-kappa B-related markers) and antitumor activity is seen in AIPCa at tolerated doses of bortezomib., Given the results of this trial, it is safe and reasonable to recommend treatment with PS341 on the schedule used in this trial at 1.56 mg/m2/dose in Phase II trials. Particular care should be taken with patients with preexisting neuropathy, The successes of proteasome inhibitors in MM are now being translated to other hematologic malignancies, including acute leukemia, Such efforts have led to bortezomib, the first FDA approved proteasome inhibitor now used as a frontline treatment for newly diagnosed multiple myeloma (MM), relapsed/refractory MM and mantle cell lymphoma, We recently reported the impact and mechanisms of carfilzomib and oprozomib, second-in-class proteasome inhibitors with higher specificities and reduced toxicities, against head and neck squamous cell carcinoma (HNSCC). Carfilzomib and oprozomib potently inhibit HNSCC cell survival and the growth of HNSCC tumors[SEP]Relations: Bortezomib has relations: drug_drug with Carfilzomib, drug_drug with Carfilzomib.", "label": "yes"}
{"id": "converted_4112", "sentence1": "Is there a role for TFII-I in megakaryopoiesis?", "sentence2": "TFII-I/Gtf2i and Erythro-Megakaryopoiesis., TFII-I is a ubiquitously expressed transcription factor that positively or negatively regulates gene expression. TFII-I has been implicated in neuronal and immunologic diseases as well as in thymic epithelial cancer. Williams-Beuren Syndrome (WBS) is caused by a large hemizygous deletion on chromosome 7q11.23 which encompasses 26-28 genes, including GTF2I, the human gene encoding TFII-I. A subset of WBS patients has recently been shown to present with macrocytosis, a mild anemia characterized by enlarged erythrocytes. We conditionally deleted the TFII-I/Gtf2i gene in adult mice by tamoxifen induced Cre-recombination. Bone marrow cells revealed defects in erythro-megakaryopoiesis and an increase in expression of the adult β-globin gene. The data show that TFII-I acts as a repressor of β-globin gene transcription and that it is implicated in the differentiation of erythro-megakaryocytic cells.[SEP]Relations: Williams syndrome has relations: disease_protein with GTF2I, disease_protein with GTF2I.", "label": "yes"}
{"id": "converted_2391", "sentence1": "Does the association of PARP1 and CTCF follow a circadian rhythm?", "sentence2": "here we uncovered an inter-chromosomal network connecting active loci enriched in circadian genes to repressed lamina-associated domains (LADs)., Synchronization of the circadian rhythm by serum shock induces oscillations in PARP1-CTCF interactions, which is accompanied by oscillating recruitment of circadian loci to the lamina, followed by the acquisition of repressive H3K9me2 marks and transcriptional attenuation, PARP1- and CTCF-regulated contacts between circadian loci and the repressive chromatin environment at the lamina therefore mediate circadian transcriptional plasticity., Synchronization of the circadian rhythm by serum shock induces oscillations in PARP1-CTCF interactions, which is accompanied by oscillating recruitment of circadian loci to the lamina, followed by the acquisition of repressive H3K9me2 marks and transcriptional attenuation. Furthermore, depletion of H3K9me2/3, inhibition of PARP activity by olaparib, or downregulation of PARP1 or CTCF expression counteracts both recruitment to the envelope and circadian transcription. PARP1- and CTCF-regulated contacts between circadian loci and the repressive chromatin environment at the lamina therefore mediate circadian transcriptional plasticity., transcriptionally active and inactive chromatin domains tend to segregate into separate sub nuclear compartments to maintain stable expression patterns however here we uncovered an inter chromosomal network connecting active loci enriched in circadian genes to repressed lamina associated domains lads the interactome is regulated by parp1 and its co factor ctcf they not only mediate chromatin fiber interactions but also promote the recruitment of circadian genes to the lamina synchronization of the circadian rhythm by serum shock induces oscillations in parp1 ctcf interactions which is accompanied by oscillating recruitment of circadian loci to the lamina followed by the acquisition of repressive h3k9me2 marks and transcriptional attenuation furthermore depletion of h3k9me2 3 inhibition of parp activity by olaparib or downregulation of parp1 or ctcf expression counteracts both recruitment to the envelope and circadian transcription parp1 and ctcf regulated contacts between circadian loci and the repressive chromatin environment at the lamina therefore mediate circadian transcriptional plasticity., Synchronization of the circadian rhythm by serum shock induces oscillations in PARP1-CTCF interactions, which is accompanied by oscillating recruitment of circadian loci to the lamina, followed by the acquisition of repressive H3K9me2 marks and transcriptional attenuation.[SEP]Relations: Olaparib has relations: drug_protein with PARP1, drug_protein with PARP1.", "label": "yes"}
{"id": "converted_4223", "sentence1": "Has the companion diagnostic HercepTest received FDA approval?", "sentence2": "The FDA-Approved Breast Cancer HER2 Evaluation Kit (HercepTest; Dako) May Miss Some HER2-Positive Breast Cancers., HER2 fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) tests were performed on 52 cases using a US Food and Drug Administration (FDA)-approved kit (HercepTest, FDA kit) and a laboratory-developed test (LDT) with the HercepTest antibody and a Leica Bond automated stainer.[SEP]", "label": "yes"}
{"id": "converted_2877", "sentence1": "Can enasidenib be used for the treatment of acute myeloid leukemia?", "sentence2": "In August 2017, the United States Federal Drug Administration (FDA) approved enasidenib (Idhifa, Celgene/Agios) for adults with relapsed and refractory acute myelogenous leukemia (AML) with an IDH2 mutation. [SEP]", "label": "yes"}
{"id": "converted_3234", "sentence1": "Anaplasma phagocytophilum is an obligate gram-negative, intracellular bacterium, yes  or no", "sentence2": "The genus Anaplasma belonging to the Anaplasmataceae family (order Rickettsiales) comprises obligate intracellular Gram-negative bacteria of veterinary and public health importance. Six species and five types of strains genetically related are currently assigned to the genus Anaplasma including Anaplasma marginale, A. centrale, A. bovis, A. phagocytophilum, A. ovis and A. platys as classified species, and \"A. capra\", A. odocolei sp. nov., Human granulocytic anaplasmosis (HGA), an increasingly recognized febrile tick-borne illness, is caused by a gram-negative obligate intracellular bacterium Anaplasma phagocytophilum[SEP]", "label": "yes"}
{"id": "converted_2434", "sentence1": "Is Tofacitinib effective for Ulcerative Colitis?", "sentence2": "Tofacitinib, inhibiting signalling via all Janus kinase family members, was effective in phase 2 and 3 trials in moderate-severe ulcerative colitis., Among them, Janus kinase (JAK) inhibitors seem to have the lead, since tofacitinib has received regulatory approval in 2012 for the treatment of rheumatoid arthritis, and also it has shown a favorable risk-benefit ratio in phase 3 studies for ulcerative colitis, both in anti-TNF naïve and anti-TNF experienced patients. , Near future conventional drug options include oral agents such as tofacitinib and mongersen. , Tofacitinib showed dose related efficacy for induction therapy. , Tofacitinib as Induction and Maintenance Therapy for Ulcerative Colitis., BACKGROUND: Tofacitinib, an oral, small-molecule Janus kinase inhibitor, was shown to have potential efficacy as induction therapy for ulcerative colitis in a phase 2 trial. , CONCLUSIONS: In patients with moderately to severely active ulcerative colitis, tofacitinib was more effective as induction and maintenance therapy than placebo., Tofacitinib (CP-690,550), an oral small-molecule Janus kinase inhibitor, has been shown to be effective in the treatment of rheumatoid arthritis, autoimmune encephalomyelitis and ulcerative colitis. , Tofacitinib, an oral, small-molecule Janus kinase inhibitor, was shown to have potential efficacy as induction therapy for ulcerative colitis in a phase 2 trial., <b>BACKGROUND</b>: Tofacitinib, an oral, small-molecule Janus kinase inhibitor, was shown to have potential efficacy as induction therapy for ulcerative colitis in a phase 2 trial., Across all three trials, adjudicated nonmelanoma skin cancer occurred in five patients who received tofacitinib and in one who received placebo, and adjudicated cardiovascular events occurred in five who received tofacitinib and in none who received placebo; as compared with placebo, tofacitinib was associated with increased lipid levels.<br><b>CONCLUSIONS</b>: In patients with moderately to severely active ulcerative colitis, tofacitinib was more effective as induction and maintenance therapy than placebo., Tofacitinib (CP-690,550), an oral small-molecule Janus kinase inhibitor, has been shown to be effective in the treatment of rheumatoid arthritis, autoimmune encephalomyelitis and ulcerative colitis., Tofacitinib, an oral Janus kinase inhibitor, in active ulcerative colitis., Tofacitinib, a non-selective Janus kinase (JAK) inhibitor, is effective in inducing clinical and endoscopic remission in patients with active ulcerative colitis (UC)., BACKGROUND Tofacitinib, an oral, small-molecule Janus kinase inhibitor, was shown to have potential efficacy as induction therapy for ulcerative colitis in a phase 2 trial., BACKGROUND Tofacitinib, a novel, oral Janus kinase inhibitor, demonstrated a dose-dependent efficacy for induction of clinical response and remission in patients with active ulcerative colitis (UC)., CONCLUSIONS In patients with moderately to severely active ulcerative colitis, tofacitinib was more effective as induction and maintenance therapy than placebo., Tofacitinib, an oral janus kinase inhibitor, is a new biologic that has shown promise in the treatment of ulcerative colitis and may be effective in the treatment of Crohn's disease according to phase 2 trials., CONCLUSIONS Patients with moderately to severely active ulcerative colitis treated with tofacitinib were more likely to have clinical response and remission than those receiving placebo., Three patients treated with tofacitinib had an absolute neutrophil count of less than 1500.<br><b>CONCLUSIONS</b>: Patients with moderately to severely active ulcerative colitis treated with tofacitinib were more likely to have clinical response and remission than those receiving placebo., tofacitinib an oral small molecule janus kinase inhibitor was shown to have potential efficacy as induction therapy for ulcerative colitis in a phase 2 trial we further evaluated the efficacy of tofacitinib as induction and maintenance therapy we conducted three phase 3 randomized double blind placebo controlled trials of tofacitinib therapy in adults with ulcerative colitis in the octave induction 1 and 2 trials 598 and 541 patients respectively who had moderately to severely active ulcerative colitis despite previous conventional therapy or therapy with a tumor necrosis factor antagonist were randomly assigned to receive induction therapy with tofacitinib 10 mg twice daily or placebo for 8 weeks the primary end point was remission at 8 weeks in the octave sustain trial 593 patients who had a clinical response to induction therapy were randomly assigned to receive maintenance therapy with tofacitinib either 5 mg or 10 mg twice daily or placebo for 52 weeks the primary end point was remission at 52 weeks in the octave induction 1 trial remission at 8 weeks occurred in 18 5 of the patients in the tofacitinib group versus 8 2 in the placebo group p 0 007 in the octave induction 2 trial remission occurred in 16 6 versus 3 6 p 0 001 in the octave sustain trial remission at 52 weeks occurred in 34 3 of the patients in the 5 mg tofacitinib group and 40 6 in the 10 mg tofacitinib group versus 11 1 in the placebo group p 0 001 for both comparisons with placebo in the octave induction 1 and 2 trials the rates of overall infection and serious infection were higher with tofacitinib than with placebo in the octave sustain trial the rate of serious infection was similar across the three treatment groups and the rates of overall infection and herpes zoster infection were higher with tofacitinib than with placebo across all three trials adjudicated nonmelanoma skin cancer occurred in five patients who received tofacitinib and in one who received placebo and adjudicated cardiovascular events occurred in five who received tofacitinib and in none who received placebo as compared with placebo tofacitinib was associated with increased lipid levels in patients with moderately to severely active ulcerative colitis tofacitinib was more effective as induction and maintenance therapy than placebo funded by pfizer octave induction 1 octave induction 2 and octave sustain clinicaltrials gov numbers nct01465763 nct01458951 and nct01458574 respectively., ulcerative colitis is a chronic inflammatory disease of the colon for which current treatments are not universally effective one additional treatment may be tofacitinib cp 690 550 an oral inhibitor of janus kinases 1 2 and 3 with in vitro functional specificity for kinases 1 and 3 over kinase 2 which is expected to block signaling involving gamma chain containing cytokines including interleukins 2 4 7 9 15 and 21 these cytokines are integral to lymphocyte activation function and proliferation in a double blind placebo controlled phase 2 trial we evaluated the efficacy of tofacitinib in 194 adults with moderately to severely active ulcerative colitis patients were randomly assigned to receive tofacitinib at a dose of 0 5 mg 3 mg 10 mg or 15 mg or placebo twice daily for 8 weeks the primary outcome was a clinical response at 8 weeks defined as an absolute decrease from baseline in the score on the mayo scoring system for assessment of ulcerative colitis activity possible score 0 to 12 with higher scores indicating more severe disease of 3 or more and a relative decrease from baseline of 30 or more with an accompanying decrease in the rectal bleeding subscore of 1 point or more or an absolute rectal bleeding subscore of 0 or 1 the primary outcome clinical response at 8 weeks occurred in 32 48 61 and 78 of patients receiving tofacitinib at a dose of 0 5 mg p 0 39 3 mg p 0 55 10 mg p 0 10 and 15 mg p 0 001 respectively as compared with 42 of patients receiving placebo clinical remission defined as a mayo score 2 with no subscore 1 at 8 weeks occurred in 13 33 48 and 41 of patients receiving tofacitinib at a dose of 0 5 mg p 0 76 3 mg p 0 01 10 mg p 0 001 and 15 mg p 0 001 respectively as compared with 10 of patients receiving placebo there was a dose dependent increase in both low density and high density lipoprotein cholesterol three patients treated with tofacitinib had an absolute neutrophil count of less than 1500 patients with moderately to severely active ulcerative colitis treated with tofacitinib were more likely to have clinical response and remission than those receiving placebo funded by pfizer clinicaltrials gov number nct00787202., recently several medical treatments for ulcerative colitis uc have been developed including 5 aminosalicylic acids 5 asas corticosteroids thiopurine calcineurin inhibitors and anti tumor necrosis factor tnf α treatments treatment options including calcineurin inhibitors and anti tnf treatment for refractory uc are discussed in this article furthermore upcoming treatments are introduced such as golimumab vedolizumab ajm300 tofacitinib budesonide foamwill be used as one treatment option in patients with distal colitis herbal medicine such as qing dai is also effective for active uc and may be useful for patients who are refractory to anti tnfα treatments in the near future physicians will able to use many different treatments for uc patients however we should not forget 5 asa and corticosteroids as the fundamental treatments for uc patients., the inflammatory diseases ulcerative colitis and crohn s disease constitute the two main forms of inflammatory bowel disease ibd they are characterized by chronic relapsing inflammation of the gastrointestinal tract significantly impacting on patient quality of life and often requiring prolonged treatment existing therapies for ibd are not effective for all patients and an unmet need exists for additional therapies to induce and maintain remission here we describe the mechanism of action of the janus kinase jak inhibitor tofacitinib for the treatment of ibd and the effect of jak inhibition on the chronic cycle of inflammation that is characteristic of the disease the pathogenesis of ibd involves a dysfunctional response from the innate and adaptive immune system resulting in overexpression of multiple inflammatory cytokines many of which signal through jaks thus jak inhibition allows multiple cytokine signaling pathways to be targeted and is expected to modulate the innate and adaptive immune response in ibd thereby interrupting the cycle of inflammation tofacitinib is an oral small molecule jak inhibitor that is being investigated as a targeted immunomodulator for ibd clinical development of tofacitinib and other jak inhibitors is ongoing with the aspiration of providing new treatment options for ibd that have the potential to deliver prolonged efficacy and clinically meaningful patient benefits.[SEP]Relations: ulcerative colitis (disease) has relations: disease_disease with distal colitis, disease_disease with distal colitis. inflammatory bowel disease has relations: disease_phenotype_positive with Crohn's disease, disease_phenotype_positive with Crohn's disease. Protein S human has relations: drug_drug with Tofacitinib, drug_drug with Tofacitinib. Golimumab has relations: drug_drug with Tofacitinib, drug_drug with Tofacitinib. Rheumatoid arthritis has relations: disease_phenotype_positive with rheumatoid arthritis, disease_phenotype_positive with rheumatoid arthritis.", "label": "yes"}
{"id": "converted_2009", "sentence1": "Can Pentraxin 3 predict outcomes of sepsis?", "sentence2": "As compared with low serum PTX3and sTWEAK cases, cirrhotic patients with high serum PTX3/sTWEAK levels a have higher probability of new severe infections, severe sepsis, septic shock, type 1 hepatorenal syndrome, in-hospital, and 3-month follow-up mortalities. , Neonates with high nPTX3 concentrations also have lowered APGAR scores, increased rate of respiratory distress syndrome, clinical sepsis, IVH, necrotizing enterocolitis and prolonged NICU stay., In terms of predicting the prognosis of sepsis with heart failure complications, the PTX3 value's area under ROC curve was larger than that of BNP (respectively 0. 844, 0. 472).CONCLUSION: The PTX3 is an objective biochemical marker in diagnosis of sepsis; it is helpful in assessment of severity and prognosis of sepsis; it also has a certain clinical value in the assessment of sepsis cardiovascular function damage., Severe Acinetobacter baumannii sepsis is associated with elevation of pentraxin 3., Together, these results suggest that elevation of PTX3 is associated with fulminant disease during A. baumannii sepsis., Persisting high levels of plasma pentraxin 3 over the first days after severe sepsis and septic shock onset are associated with mortality., PTX3, as a mediator of inflammation, may represent an early marker of severity and outcome in sepsis., CONCLUSIONS: Persisting high levels of circulating PTX3 over the first days from sepsis onset may be associated with mortality. PTX3 correlates with severity of sepsis and with sepsis-associated coagulation/fibrinolysis dysfunction., Pentraxin 3 in patients with severe sepsis or shock: the ALBIOS trial., Pentraxin 3: an immune modulator of infection and useful marker for disease severity assessment in sepsis., Redox state of pentraxin 3 as a novel biomarker for resolution of inflammation and survival in sepsis., The prototypic long pentraxin, pentraxin 3, is an acute phase protein that is structurally related but distinct from C-reactive protein which has proven to correlate with the severity of bacterial infection in critically ill patients., Circulating levels of the long pentraxin PTX3 correlate with severity of infection in critically ill patients., Pentraxin 3 (PTX3) is associated with severe sepsis and fatal disease in emergency room patients with suspected infection: a prospective cohort study., In addition, high levels of PTX3 were associated with unfavorable outcome.CONCLUSIONS: The long pentraxin PTX3 is elevated in critically ill patients and correlates with severity of disease and infection., PTX3, as a mediator of inflammation, may represent an early marker of severity and outcome in sepsis., Redox state of pentraxin 3 as a novel biomarker for resolution of inflammation and survival in sepsis., Persisting high levels of plasma pentraxin 3 over the first days after severe sepsis and septic shock onset are associated with mortality., Pentraxin 3 (PTX3) is associated with severe sepsis and fatal disease in emergency room patients with suspected infection: a prospective cohort study., The proteomic profile of circulating pentraxin 3 (PTX3) complex in sepsis demonstrates the interaction with azurocidin 1 and other components of neutrophil extracellular traps.[SEP]", "label": "yes"}
{"id": "converted_3655", "sentence1": "Does gavestinel improve outcomes of stroke patients?", "sentence2": "CONCLUSION: Consistent with the clinical outcomes in the GAIN trials, no effects of gavestinel on ischemic infarction was observed., No effects of gavestinel on infarct volume were observed in the primary or other analyses. , Gavestinel does not improve outcome after acute intracerebral hemorrhage: an analysis from the GAIN International and GAIN Americas studies., Both trials reported that gavestinel was ineffective in ischemic stroke. , CONCLUSIONS: These observations from the combined GAIN International and GAIN Americas trials suggest that gavestinel is not of substantial benefit or harm to patients with primary intracerebral hemorrhage. , Glutamate N-methyl-D-aspartate (NMDA) receptor antagonists such as Selfotel, Aptiganel, Gavestinel and others failed to show neuroprotective efficacy in human clinical trials or produced intolerable central nervous system adverse effects., METHODS: We studied all patients of the Glycine Antagonist (gavestinel) In Neuroprotection (GAIN) International Trial with ischemic stroke alive at day 7, excluding patients with hemorrhagic events and deaths from nonstroke-related causes. The GAIN International Trial was a randomized, double-blind, placebo-controlled, and parallel-group trial; because the study drug had no effect on stroke outcome, treatment groups were combined for this analysis. , Gavestinel produces no benefit for stroke patients, study finds., The wonder drug, gavestinel, failed to produce any significant treatment benefits for patients treated within six hours after experiencing an acute ischemic stroke, according to the recent results of a major clinical trial of the neuroprotectant. , INTERPRETATION: Treatment with gavestinel within 6 h of acute ischaemic stroke did not improve outcome., INTERPRETATION\n\nTreatment with gavestinel within 6 h of acute ischaemic stroke did not improve outcome., CONCLUSION\n\nIn this study, gavestinel administered up to 6 hours after an acute ischemic stroke did not improve functional outcome at 3 months., Both trials reported that gavestinel was ineffective in ischemic stroke., INTERPRETATION Treatment with gavestinel within 6 h of acute ischaemic stroke did not improve outcome., Both trials reported that gavestinel was ineffective in ischemic stroke., Gavestinel produces no benefit for stroke patients , study finds ., The wonder drug, gavestinel, failed to produce any significant treatment benefits for patients treated within six hours after experiencing an acute ischemic stroke, according to the recent results of a major clinical trial of the neuroprotectant., The wonder drug, gavestinel, failed to produce any significant treatment benefits for patients treated within six hours after experiencing an acute ischemic stroke, according to the recent results of a major clinical trial of the neuroprotectant., Treatment with gavestinel within 6 h of acute ischaemic stroke did not improve outcome., In this study, gavestinel administered up to 6 hours after an acute ischemic stroke did not improve functional outcome at 3 months.[SEP]", "label": "no"}
{"id": "converted_4497", "sentence1": "Should istiratumab be used for Pancreatic Cancer?", "sentence2": "CONCLUSIONS: Istiratumab failed to improve the efficacy of SOC chemotherapy in this patient setting. , In the high IGF-1 cohort, median PFS was 3.6 and 7.3 months in the experimental versus control arms, respectively [hazard ratio (HR) = 1.88, P = 0.027]. In the high IGF-1/HRG+ subgroup (n = 44), median PFS was 4.1 and 7.3 months, respectively (HR = 1.39, P = 0.42).[SEP]", "label": "no"}
{"id": "converted_3205", "sentence1": "Does RUNX2 inhibit astrocyte differentiation?", "sentence2": "The method was able to recapitulate experimentally validated cell-fate determinants, and validation of two predicted cell-fate determinants confirmed that overexpression of ESR1 and RUNX2 in mouse neural stem cells induces neuronal and astrocyte differentiation, respectively.[SEP]Relations: regulation of intracellular estrogen receptor signaling pathway has relations: bioprocess_protein with ESR1, bioprocess_protein with ESR1.", "label": "no"}
{"id": "converted_2779", "sentence1": "Are there microbes in human breast milk?", "sentence2": "Contrary to long-held dogma, human milk is not sterile. Instead, it provides infants a rich source of diverse bacteria, particularly microbes belonging to the Staphylococcus, Streptococcus, and Pseudomonas genera., The origins of the bacteria in milk are thought to include the maternal gastrointestinal tract (via an entero-mammary pathway) and through bacterial exposure of the breast during nursing.[SEP]", "label": "yes"}
{"id": "converted_1166", "sentence1": "Are CpG islands located close to housekeeping genes?", "sentence2": "our analysis indicates that the association of CGIs with housekeeping genes is not as strong as previously estimated, CpG islands are preferentially located at the start of transcription of housekeeping genes and are associated with tissue-specific genes, It has been envisaged that CpG islands are often observed near the transcriptional start sites (TSS) of housekeeping genes., These regions represent about 1% of genomic DNA and are generally found in the promoter region of housekeeping genes., CpG islands are stretches of DNA sequence that are enriched in the (CpG)n repeat and are present in close association with all housekeeping genes as well as some tissue-specific genes in the mammalian genome., CpG islands, which are found almost exclusively at the 5'-end of housekeeping genes, In housekeeping and many tissue-specific genes, the promoter is embedded in a so-called CpG island., All housekeeping and widely expressed genes have a CpG island covering the transcription start, whereas 40% of the genes with a tissue-specific or limited expression are associated with islands, Methylation-free CpG clusters, so-called HTF islands, are most often associated with the promoter regions of housekeeping genes, whereas genes expressed in a single-cell type are usually deficient in these sequences., Unmethylated CpG rich islands are a feature of vertebrate DNA: they are associated with housekeeping and many tissue specific genes., CpG islands were associated with the 5' ends of all housekeeping genes and many tissue-specific genes, and with the 3' ends of some tissue-specific genes.[SEP]", "label": "yes"}
{"id": "converted_419", "sentence1": "Are there transposon-free regions in mammalian genomes?", "sentence2": "Transposon-free regions in mammalian genomes., Despite the presence of over 3 million transposons separated on average by approximately 500 bp, the human and mouse genomes each contain almost 1000 transposon-free regions (TFRs) over 10 kb in length. The majority of human TFRs correlate with orthologous TFRs in the mouse, despite the fact that most transposons are lineage specific. Many human TFRs also overlap with orthologous TFRs in the marsupial opossum, indicating that these regions have remained refractory to transposon insertion for long evolutionary periods. Over 90% of the bases covered by TFRs are noncoding, much of which is not highly conserved. Most TFRs are not associated with unusual nucleotide composition, but are significantly associated with genes encoding developmental regulators, suggesting that they represent extended regions of regulatory information that are largely unable to tolerate insertions, a conclusion difficult to reconcile with current conceptions of gene regulation., All three elements insert only rarely within many Polycomb-regulated regions, a property that may contribute to the origin of \"transposon-free regions\" (TFRs) in metazoan genomes., Despite the presence of over 3 million transposons separated on average by approximately 500 bp, the human and mouse genomes each contain almost 1000 transposon-free regions (TFRs) over 10 kb in length., RESULTS: Here we report that transposon-free regions (TFRs) are prominent genomic features of amphibian and fish lineages, and that many have been maintained throughout vertebrate evolution, although most transposon-derived sequences have entered these lineages after their divergence. , Despite the presence of over 3 million transposons separated on average by approximately 500 bp, the human and mouse genomes each contain almost 1000 transposon-free regions (TFRs) over 10 kb in length. , All three elements insert only rarely within many Polycomb-regulated regions, a property that may contribute to the origin of \"transposon-free regions\" (TFRs) in metazoan genomes. , Despite the presence of over 3 million transposons separated on average by approximately 500 bp, the human and mouse genomes each contain almost 1000 transposon-free regions (TFRs) over 10 kb in length., Here we report that transposon-free regions (TFRs) are prominent genomic features of amphibian and fish lineages, and that many have been maintained throughout vertebrate evolution, although most transposon-derived sequences have entered these lineages after their divergence.[SEP]", "label": "yes"}
{"id": "converted_3584", "sentence1": "Can PRL3-zumab inhibit PRL3+ cancer cells in vitro and in vivo?", "sentence2": "Here we show that PRL3-zumab specifically inhibits PRL3+ cancer cells in vivo, but not in vitro.[SEP]", "label": "no"}
{"id": "converted_1329", "sentence1": "Is p100 the precursor protein molecule of the NF-kappaB transcription factor subunit p50?", "sentence2": "We previously reported that alymphoplasia (aly/aly) mice, which have a natural loss-of-function mutation in the Nik gene, which encodes a kinase essential for the processing of p100 to p52 in the alternative nuclear factor-κB (NF-κB) pathway, show mild osteopetrosis with an increase in several parameters of bone formation: , Proteolytic processing of the nuclear factor (NF)-kappaB2 precursor protein p100 generates the active NF-kappaB2 subunit p52, which in turn transcriptionally up-regulates p100 expression. , The mammalian Rel/NF-kappaB family of transcription factors, including RelA, c-Rel, RelB, NF-kappaB1 (p50 and its precursor p105), and NF-kappaB2 (p52 and its precursor p100), plays a central role in the immune system by regulating several processes ranging from the development and survival of lymphocytes and lymphoid organs to the control of immune responses and malignant transformation., NF-kappaB functions as a hetero- or homo-dimer which can be formed from five NF-kappaB subunits, NF-kappaB1 (p50 and its precursor p105), NF-kappaB2 (p52 and its precursor p100), RelA (p65), RelB and c-Rel., The non-canonical pathway based on processing of NF-kappaB2 precursor protein p100 to generate p52 plays a critical role in controlling B cell function and lymphoid organogenesis., Processing of NF-kappaB2 precursor protein p100 to generate p52 is tightly controlled, which is important for proper function of NF-kappaB., Processing of NF-kappa B2 precursor protein p100 to generate p52 is tightly regulated. , Processing of the NF-kappaB2 precursor protein p100 to generate p52 is an important step of NF-kappaB regulation., Targeted disruption of the Rel/NF-kappaB family members NF-kappaB2, encoding p100/p52, and RelB in mice results in anatomical defects of secondary lymphoid tissues., Here, we show that in T cells infected with the human T-cell leukemia virus (HTLV), IKKalpha is targeted to a novel signaling pathway that mediates processing of the nfkappab2 precursor protein p100, resulting in active production of the NF-kappaB subunit, p52., nfkb2 encodes two members of the NF-kappa B/Rel family of proteins: p52 and p100. The p100 polypeptide has been proposed to serve as a precursor of p52, which corresponds to the N-terminal half of p100., In most cells, small amounts of p52 are produced relative to the levels of p100, unlike the usually balanced production of nfkb1-derived p50 and p105. , The alternative or second pathway proceeded via NF-kappaB-inducing kinase (NIK)-, IKKalpha-, and protein synthesis-dependent processing of the inhibitory NF-kappaB2 p100 precursor protein to the p52 form and resulted in a delayed but sustained activation of primarily RelB-containing NF-kappaB dimers., In one exceptional case, generation of the p50 subunit of the transcriptional regulator NF-kappaB, the precursor protein p105 is processed in a limited manner: the N-terminal domain yields the p50 subunit, whereas the C-terminal domain is degraded, Proteolytic processing of the p105 precursor (NF-kappa B1) generates the p50 subunit of NF-kappa B, p105 (NFKB1) acts in a dual way as a cytoplasmic IkappaB molecule and as the source of the NF-kappaB p50 subunit upon processing, The p50 subunit of NF-kappa B is derived from the amino terminus of a 105 kilodalton precursor, Regulation of the transcription factor NF-kappaB involves proteasome-mediated processing of the NF-kappaB1 p105 precursor protein, which generates the p50 subunit of NF-kappaB, This effort identified NF-kappaB1 (p105), an atypical IkappaB molecule and the precursor of NF-kappaB subunit p50, NF-kappaB functions as a hetero- or homo-dimer which can be formed from five NF-kappaB subunits, NF-kappaB1 (p50 and its precursor p105), NF-kappaB2 (p52 and its precursor p100), RelA (p65), RelB and c-Rel, The mammalian Rel/NF-kappaB family of transcription factors, including RelA, c-Rel, RelB, NF-kappaB1 (p50 and its precursor p105), and NF-kappaB2 (p52 and its precursor p100), plays a central role in the immune system by regulating several processes ranging from the development and survival of lymphocytes and lymphoid organs to the control of immune responses and malignant transformation[SEP]", "label": "no"}
{"id": "converted_3111", "sentence1": "Does Axitinib prolong survival of Pancreatic Cancer patients?", "sentence2": "CONCLUSIONS: Axitinib/gemcitabine, while tolerated, did not provide survival benefit over gemcitabine alone in patients with advanced pancreatic cancer from Japan or other regions., RESULTS: Among Japanese patients, median overall survival was not estimable (95% confidence interval, 7.4 months-not estimable) with axitinib/gemcitabine (n = 58) and 9.9 months (95% confidence interval, 7.4-10.5) with placebo/gemcitabine (n = 56) (hazard ratio 1.093 [95% confidence interval, 0.525-2.274]). Median survival follow-up (range) was 5.1 months (0.02-12.3) with axitinib/gemcitabine vs. 5.4 months (1.8-10.5) with placebo/gemcitabine. Similarly, no difference was detected in overall survival between axitinib/gemcitabine and placebo/gemcitabine in patients from North America or the European Union. , At an interim analysis in January, 2009, the independent data monitoring committee concluded that the futility boundary had been crossed. Median overall survival was 8·5 months (95% CI 6·9-9·5) for gemcitabine plus axitinib (n=314, data missing for two patients) and 8·3 months (6·9-10·3) for gemcitabine plus placebo (n=316; hazard ratio 1·014, 95% CI 0·786-1·309; one-sided p=0·5436). , INTERPRETATION: The addition of axitinib to gemcitabine does not improve overall survival in advanced pancreatic cancer. , INTERPRETATION\nThe addition of axitinib to gemcitabine does not improve overall survival in advanced pancreatic cancer., However, as with other tyrosine kinase inhibitors of the same class, axitinib does not prolong overall survival; therefore, selection of second-line tyrosine kinase inhibitor therapy, including axitinib, must be carefully considered to maximize outcomes for each patient., CONCLUSIONS\nAxitinib/gemcitabine, while tolerated, did not provide survival benefit over gemcitabine alone in patients with advanced pancreatic cancer from Japan or other regions., Similarly, no difference was detected in overall survival between axitinib/gemcitabine and placebo/gemcitabine in patients from North America or the European Union., Axitinib/gemcitabine, while tolerated, did not provide survival benefit over gemcitabine alone in patients with advanced pancreatic cancer from Japan or other regions., The addition of axitinib to gemcitabine does not improve overall survival in advanced pancreatic cancer.[SEP]Relations: Gemcitabine has relations: drug_drug with Axitinib, drug_drug with Axitinib.", "label": "no"}
{"id": "converted_4647", "sentence1": "Is telomestatin, a novel statin drug used to treat high cholesterol?", "sentence2": "Telomestatin is a natural product isolated from Streptomyces anulatus 3533-SV4 and has been shown to be a very potent telomerase inhibitor., Telomestatin, a potent telomerase inhibitor that interacts quite specifically with the human telomeric intramolecular g-quadruplex., Activity of a novel G-quadruplex-interactive telomerase inhibitor, telomestatin (SOT-095), ,  G-quadruplex-interactive telomerase inhibitor, telomestatin (SOT-095),,  We found that treatment with telomestatin reproducibly inhibited telomerase activity in the BCR-ABL-positive leukemic cell lines, A novel telomerase inhibitor, telomestatin, isolated from Streptomyces anulatus is the most potent telomerase inhibitor so far., Telomerase inhibitor, telomestatin, a specific mechanism to interact with telomere structure, Telomestatin specifically inhibited telomerase without affecting reverse transcriptases and polymerases., In addition, telomestatin induced telomere shortening, but its ratio was extremely faster than that observed in physiological telomere shortening., A novel telomerase inhibitor, telomestatin, isolated from Streptomyces anulatus is the most potent telomerase inhibitor so far. , ructure has been yet resolved for the complex with telomestatin, one of the most promising G-quadruplex-targeting anticancer drug candidates. Here, Telomestatin, a strong telomerase inhibitor with G-quadruplex stabilizing activity, is a potential therapeutic agent for treating cancers., Thus, telomestatin provide the novel therapeutic molecular target for cancer chemotherapy., Telomerase inhibition with a novel G-quadruplex-interactive agent, telomestatin: in vitro and in vivo studies in acute leukemia., Activity of a novel G-quadruplex-interactive telomerase inhibitor, telomestatin (SOT-095), against human leukemia cells: involvement of ATM-dependent DNA damage response pathways.[SEP]", "label": "no"}
{"id": "converted_4061", "sentence1": "Is acupotomy used to treat muscle stiffness?", "sentence2": "All the included studies reviewed musculoskeletal disorders and reported a significantly higher total effective and cure rates in the acupotomy group for frozen shoulder, cervical spondylosis, third lumbar vertebrae transverse process syndrome, trigger finger, knee osteoarthritis, and lumbar spinal stenosis, compared to the other active control groups, Acupotomy showed promising results for some musculoskeletal disorders; however, additional high-quality evidence is required to make clinical recommendations regarding this procedure., Acupotomy has been widely used to treat nerve entrapment syndrome, To evaluate the clinical efficacy and safety of acupotomy in treatment of knee osteoarthritis , Effect and safety of acupotomy in treatment of knee osteoarthritis, Acupotomy Therapy for Knee Osteoarthritis Pain: Systematic Review and Meta-Analysis., We included only randomized controlled trials (RCTs) that used acupotomy therapy as the major intervention in adults with knee OA,, Acupotomy, which involves the addition of a scalpel function to the conventional acupuncture treatment, has recently been applied as a conservative treatment method for lumbar disc herniation (LDH), LTS: The systematic review will provide high-quality evidence to assess the efficacy and safety of acupotomy for KOA by pain, stiffness, and dysfunction of knee joint, and quality of life, as well as adverse events.CONC, Acupotomy has been widely used to treat KOA., Acupotomy, a biomechanical therapy guided by traditional Chinese medicine theory, alleviates cartilage degradation and is widely used in the clinic to treat KOA by correcting abnormal mechanics., BACKGROUND: Acupotomy has been widely used to treat nerve entrapment syndrome., Acupotomy has been widely used to treat calcaneodynia., The aim of this study is to evaluate the efficacy and safety of the acupotomy treatment in patients with calcaneodynia., otomy combined with rehabilitation was associated with significantly higher TER (RR 1.24, 95% CI 1.01-1.52, I = 77%) and gross motor function measure score (MD 12.62, 95% CI 11.75-13.49, I = 54%), and significantly lower muscle tone of gastrocnemius measured by the Ashworth scale or the modified Ashworth scale (MD -0.97, 95% CI -1.07 to -0.88, I = 0%) compared with rehabilitation alone. No , Both acupotomy and acupuncture have been widely used clinically to treat CSR in China with satisfied efficacy., GN AND METHODS: Total 75 patients were participated in acupotomy therapy and ultrasonic drug penetration to treat joint osteoarthritis. The, Acupotomy Alleviates Energy Crisis at Rat Myofascial Trigger Points, its in the acupotomy and EA groups underwent bilateral acupotomylysis intervention; those in the acupotomy-EA group underwent acupotomylysis and EA interventions. On the, LTS: The systematic review will provide high-quality evidence to assess the efficacy and safety of acupotomy for KOA by pain, stiffness, and dysfunction of knee joint, and quality of life, as well as adverse events.CON, Acupotomy for knee osteoarthritis: A systematic review protocol.,  The aim of this study is to evaluate the efficacy and safety of acupotomy for the treatment of patients with KOA, SION: The systematic review will provide evidence to assess the effectiveness and safety of acupotomy therapy for KOA patients.PROSP, e systematic review will provide high-quality evidence to assess the efficacy and safety of acupotomy for KOA by pain, stiffness, and dysfunction of knee joint, and quality of life, as well as adverse events.CON, The aim of this study is to evaluate the efficacy and safety of acupotomy for the treatment of patients with KOA.M,  systematic review will provide evidence to assess the effectiveness and safety of acupotomy therapy for KOA patients.PROS, To observe the clinical efficacy of minimally invasive acupotomy-injection technique with targeted three-point in the treatment of frozen shoulder.M, [Percutaneous dynamic release in stress position by acupotomy in treating severe scapulohumeral periarthritis]., To investigate the clinical efficacy of acupotomy stress position percutaneous dynamic release for severe shoulder periarthritis.M, l sequelae. Acupotomy, a modernized acupuncture form combining the effects of microsurgery and conventional acupuncture, may show specific benefits in the treatment of CP, especially with respect to, Background: Acupotomy, which involves the addition of a scalpel function to the conventional acupuncture treatment, has recently been applied as a conservative treatment method for lumbar disc herni, he methodological quality was medium-to-high in AMSTAR. All the included studies reviewed musculoskeletal disorders and reported a significantly higher total effective and cure rates in the acupotomy group for frozen shoulder, cervical spondylosis, third lumbar vertebrae transverse process syndrome, trigger finger, knee osteoarthritis, and lumbar spinal stenosis, compared to the other active control groups.CONCLUSION: Acupotomy showed promising results for some musculoskeletal disorders; however, additional high-quality evidence is[SEP]", "label": "no"}
{"id": "converted_3040", "sentence1": "Is baricitinib effective for rheumatoid arthritis?", "sentence2": "CONCLUSION: Baricitinib 2 mg and 4 mg administered once daily, in combination with DMARD, were efficacious interventions for active RA that had no significant risk of TEAE development., CONCLUSIONS: The efficacy and safety profile of baricitinib was maintained during long-term treatment of Japanese patients with RA and background methotrexate therapy., CONCLUSION: In a phase IIb study in RA, the safety and tolerability profile of baricitinib, up to 128 weeks, remained consistent with earlier observations, without unexpected late signals. Clinical improvements seen in the 24-week blinded period were maintained during the OLE., CONCLUSION: Data for baricitinib, with/without methotrexate, in Japanese subpopulations across all stages of the RA treatment continuum accord with the efficacy/safety profile in overall study populations., Conclusion: Baricitinib demonstrated a consistent, beneficial treatment effect in bDMARD-refractory patients across subgroups based on baseline characteristics and prior bDMARD use., Baricitinib is effective in treatment of RA, and did not appear to have significant safety concerns during the first 6 months of treatment., OBJECTIVE\nBaricitinib is an orally administered inhibitor of JAK1 and JAK2 that has been shown to be effective in treating rheumatoid arthritis (RA)., EXPERT OPINION\nJAK inhibitors are effective in the treatment of rheumatoid arthritis as evidenced by several inhibitors enabling the majority of treated patients to achieve ACR20 responses, with baricitinib and INCB-039110 both effective when administered once daily., OBJECTIVE\nBaricitinib is an oral, once-daily selective Janus kinase (JAK1/JAK2) inhibitor for adults with moderately to severely active rheumatoid arthritis (RA)., Two different Janus kinase (JAK) inhibitors-baricitinib and tofacitinib-are effective and licensed in active rheumatoid arthritis (RA)., Baricitinib for the treatment of rheumatoid arthritis., OBJECTIVES\nOral targeted synthetic disease-modifying anti-rheumatic drugs (DMARDs), including the Janus kinase inhibitors tofacitinib and baricitinib, are the latest addition to the therapeutic options for rheumatoid arthritis (RA)., Baricitinib (Olumiant™) is an orally-administered, small-molecule, janus-associated kinase (JAK) inhibitor developed by Eli Lilly and Incyte Corporation for the treatment of rheumatoid arthritis (RA), atopic dermatitis and systemic lupus erythematosus., EXPERT OPINION JAK inhibitors are effective in the treatment of rheumatoid arthritis as evidenced by several inhibitors enabling the majority of treated patients to achieve ACR20 responses, with baricitinib and INCB-039110 both effective when administered once daily., Tofacitinib 10 mg + methotrexate (MTX) and baricitinib 4 mg + MTX were among the most effective treatments for active RA with an inadequate DMARD or biologic response, followed by baricitinib 2 mg + MTX, tofacitinib 5 mg + MTX, and adalimumab + MTX., OBJECTIVE Baricitinib is an orally administered inhibitor of JAK1 and JAK2 that has been shown to be effective in treating rheumatoid arthritis (RA)., CONCLUSIONS In patients with rheumatoid arthritis who had had an inadequate response to methotrexate, baricitinib was associated with significant clinical improvements as compared with placebo and adalimumab., Thus, once-daily baricitinib, as monotherapy or in combination with methotrexate, is an effective and generally well tolerated emerging treatment for patients with moderate to severe active RA who have responded inadequately to or are intolerant of ≥ 1 DMARD, and extends the options available for this population., OBJECTIVES Oral targeted synthetic disease-modifying anti-rheumatic drugs (DMARDs), including the Janus kinase inhibitors tofacitinib and baricitinib, are the latest addition to the therapeutic options for rheumatoid arthritis (RA)., Five phase 3 trials of Baricitinib, a JAK1 and JAK2 inhibitor, have been performed and showed high clinical efficacy in patients with active RA and naïve to sDMARDs or an inadequate response to sDMARDs, MTX or bDMARDs., It is also reported that safety was tolerable within the limited study period.<br><b>AREAS COVERED</b>: We here review the recent progress in the development of baricitinib and its potential for the treatment of RA., <b>OBJECTIVE</b>: Baricitinib is an orally administered inhibitor of JAK1 and JAK2 that has been shown to be effective in treating rheumatoid arthritis (RA)., In February 2017, baricitinib was approved in the EU, as monotherapy or in combination with methotrexate, for the treatment of moderate to severe active rheumatoid arthritis in adult patients who have responded inadequately to, or who are intolerant to one or more disease-modifying anti-rheumatic drugs (DMARDs)., In patients with rheumatoid arthritis who had had an inadequate response to methotrexate, baricitinib was associated with significant clinical improvements as compared with placebo and adalimumab., In pivotal multinational trials, once-daily baricitinib 4 mg, with/without methotrexate (± another csDMARD), improved the signs and symptoms of RA, disease activity and physical function in DMARD-naive patients and in patients with an inadequate response to methotrexate, csDMARDs or TNF inhibitors; baricitinib treatment also slowed structural joint damage in DMARD-naive patients and in those with an inadequate response to methotrexate and csDMARDs., Five phase 3 trials of Baricitinib, a JAK1 and JAK2 inhibitor, have been performed and showed high clinical efficacy in patients with active RA and naïve to sDMARDs or an inadequate response to sDMARDs, MTX or bDMARDs.[SEP]Relations: Baricitinib has relations: drug_protein with JAK2, drug_protein with JAK1, drug_protein with JAK2, drug_protein with JAK1. Rheumatoid arthritis has relations: disease_phenotype_positive with rheumatoid arthritis, disease_phenotype_positive with rheumatoid arthritis. Adalimumab has relations: drug_protein with TNF, drug_protein with TNF. Tofacitinib has relations: drug_protein with JAK2, drug_protein with JAK1, drug_protein with JAK2, drug_protein with JAK1.", "label": "yes"}
{"id": "converted_2101", "sentence1": "Is Obeticholic Acid used for treatment of Primary Biliary Cholangitis?", "sentence2": "Obeticholic acid in primary biliary cholangitis., In a double-blind, randomized, placebo-controlled study including 217 patients with primary biliary cholangitis, the authors show that obeticholic acid (a potent farnesoid X agonist) administered with ursodeoxycholic acid or as monotherapy significantly decreases serum alkaline phosphatase and bilirubin when compared to placebo., Obeticholic acid (Ocaliva(TM)) is a farnesoid-X receptor (FXR) agonist that is being developed by Intercept Pharmaceuticals for the treatment of various liver diseases, and has recently been granted accelerated approval in the USA for the treatment of primary biliary cholangitis in combination with ursodeoxycholic acid in adults with an inadequate response to ursodeoxycholic acid, or as monotherapy in adults unable to tolerate ursodeoxycholic acid. , Obeticholic Acid (OCA) is a farnesoid X receptor (FXR) agonist which has been evaluated as a second line therapy in PBC and has recently been licenced by the FDA., OCA will be the first stratified therapy introduced in PBC, however confirmatory trial and real life data are needed to confirm that suggestive biochemical improvements are matched by improvement in key clinical outcomes., Obeticholic acid for the treatment of primary biliary cholangitis in adult patients: clinical utility and patient selection., A series of clinical trials of OCA in PBC, primarily in combination with UDCA, have established that OCA leads to significant reductions in serum alkaline phosphatase that are predicted to lead to improved clinical outcomes, while dose-dependent pruritus has been the most common adverse effect. On the basis of these studies, OCA was given conditional approval by the US Food and Drug Administration with plans to establish the long-term clinical efficacy of OCA in patients with advanced PBC., Although obeticholic acid was approved by the FDA for the treatment of PBC in May 2016, this development occurred after the symposium presentation. , While several agents are being studied in combination with UDCA, monotherapy with the novel agent obeticholic acid, a farnesoid X receptor agonist, has also shown promising results., Obeticholic acid (Ocaliva(TM)) is a farnesoid-X receptor (FXR) agonist that is being developed by Intercept Pharmaceuticals for the treatment of various liver diseases, and has recently been granted accelerated approval in the USA for the treatment of primary biliary cholangitis in combination with ursodeoxycholic acid in adults with an inadequate response to ursodeoxycholic acid, or as monotherapy in adults unable to tolerate ursodeoxycholic acid., Obeticholic acid for the treatment of primary biliary cholangitis., Long-term clinical impact and cost-effectiveness of obeticholic acid for the treatment of primary biliary cholangitis., A Placebo-Controlled Trial of Obeticholic Acid in Primary Biliary Cholangitis., This article summarizes the milestones in the development of obeticholic acid leading to this first approval for primary biliary cholangitis., Obeticholic acid for the treatment of primary biliary cholangitis., Long-term Clinical Impact and Cost-Effectiveness of Obeticholic Acid for the Treatment of Primary Biliary Cholangitis., Obeticholic acid in primary biliary cholangitis., A Placebo-Controlled Trial of Obeticholic Acid in Primary Biliary Cholangitis., This article summarizes the milestones in the development of obeticholic acid leading to this first approval for primary biliary cholangitis.[SEP]", "label": "yes"}
{"id": "converted_1165", "sentence1": "Are there currently applications of deep learning in genomics?", "sentence2": "Deep learning of the tissue-regulated splicing code., Using a deep neural network, we developed a model inferred from mouse RNA-Seq data that can predict splicing patterns in individual tissues and differences in splicing patterns across tissues. Our architecture uses hidden variables that jointly represent features in genomic sequences and tissue types when making predictions. A graphics processing unit was used to greatly reduce the training time of our models with millions of parameters., We show that the deep architecture surpasses the performance of the previous Bayesian method for predicting AS patterns. With the proper optimization procedure and selection of hyperparameters, we demonstrate that deep architectures can be beneficial, even with a moderately sparse dataset. An analysis of what the model has learned in terms of the genomic features is presented., Machine learning applications in genetics and genomics[SEP]", "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]", "label": "yes"}
{"id": "converted_3364", "sentence1": "Is PRDM9 essential for meiosis?", "sentence2": "Our findings do not identify the nature of the underlying DNA sequences, but argue against the proposed role of Prdm9 as an essential transcription factor in mouse meiosis, PRDM9 gene polymorphism may not be associated with defective spermatogenesis in the Chinese Han population, PRDM9 is essential for the progression through early meiotic prophase, including double strand break repair, homologous chromosome pairing, and sex body formation during spermatogenesis. , PRDM9 (PR domain-containing protein 9) is a meiosis-specific protein that trimethylates H3K4 and controls the activation of recombination hot spots. It is an essential enzyme in the progression of early meiotic prophase., In many eukaryotes, sites of meiotic recombination, also called hotspots, are regions of accessible chromatin, but in many vertebrates, their location follows a distinct pattern and is specified by PR domain-containing protein 9 (PRDM9). ,  We found that although the post-SET zinc finger and the KRAB domains are not essential for the methyltransferase activity of PRDM9 in cell culture, the KRAB domain mutant mice show only residual PRDM9 methyltransferase activity and undergo meiotic arrest. In aggregate, our data indicate that domains typically involved in regulation of gene expression do not serve that role in PRDM9, but are likely involved in setting the proper chromatin environment for initiation and completion of homologous recombination., PRDM9 Methyltransferase Activity Is Essential for Meiotic DNA Double-Strand Break Formation at Its Binding Sites.[SEP]", "label": "yes"}
{"id": "converted_1519", "sentence1": "Does nifedipine inhibit L-type calcium channels?", "sentence2": "Nifedipine, an L-type calcium channel blocker, reduced the expression of synaptogamin and syntaxin and blocked the suppressive effect of vecuronium, suggesting that both agents inhibit presynaptic L-type calcium channels., Treatment with nifedipine to inhibit calcium influx via the L-type channel Cav1.2 (alpha(1C)) inhibited the TGFbeta stimulated increase in ANK expression at all phases of chondrogenesis., Finally, we found that PKCepsilon-induced stellation was significantly reduced by the specific L-type channel blocker nifedipine, indicating that calcium influx through VGCC mediates the change in astrocyte morphology induced by PKCepsilon., However, APV and nifedipine, an inhibitor of L-type calcium channels, failed to inhibit LTP when administered following the slow increase in ethanol., Both the metallic ions Cd2+ and Ni2+, known to inhibit voltage-gated calcium channels and T-type channels, respectively, and verapamil and nifedipine, typical blocker of L-type calcium channels completely prevented the hypoxic neuronal NO generation., Further, the L-type calcium channel blocker, nifedipine, was able to inhibit the initial increase in [Ca2+]i, suggesting that at least this phase of the TMT effect was mediated by calcium channels, although nifedipine had no significant effect on the time to reach the maximal [Ca2+]i level, Treatment with omega-conotoxin GVIA (3 microM) or nifedipine (10 microM) to inhibit Ca(2+) influx through N- or L-type voltage-dependent calcium channels (VDCCs), respectively, also decreased the rate of AP repolarization and increased AP duration, Concentrations of nifedipine (10 microM) and nimodipine (3 microM) that maximally inhibit L-type calcium channels reduced the sI(AHP) by 30 and 50%, respectively, Consequently, it was demonstrated in the present study that nimodipine and nitrendipine inhibit both L- and N-type calcium channels and thus seem to be unique among the dihydropyridines examined in their effects on calcium channels in dibutyryl cAMP-differentiated neuroblastoma x glioma hybrid NG 108-15 cells, whereas nifedipine and niguldipine appear to block mainly L-type calcium channels, However, APV and nifedipine, an inhibitor of L-type calcium channels, failed to inhibit LTP when administered following the slow increase in ethanol, Calcium-channel antagonists, omega-conotoxin GVIA (omega-CgTx GVIA; N-type), nifedipine (L-type), and omega-conotoxin MVIIC (omega-CmTx MVIIC; P/Q type), were used to characterize the voltage-operated Ca(2+) channels (VOCCs) involved in this release, The T- and L-type calcium channel blocker (CCB) mibefradil attenuates leg edema induced by the L-type CCB nifedipine in the spontaneously hypertensive rat: a novel differentiating assay., L-type calcium channel antagonist nifedipine reduces neurofilament restitution following traumatic optic nerve injury., Nifedipine, an L-type calcium channel blocker, restores the hypnotic response in rats made tolerant to the alpha-2 adrenergic agonist dexmedetomidine., Comparison of L-type calcium channel blockade by nifedipine and/or cadmium in guinea pig ventricular myocytes., Nifedipine inhibits picrotoxin-induced seizure activity: further evidence on the involvement of L-type calcium channel blockers in epilepsy.[SEP]", "label": "yes"}
{"id": "converted_277", "sentence1": "Is apixaban effective for treatment of acute venous thromboembolism?", "sentence2": "Apixaban is a direct inhibitor of factor Xa, and is a potential alternative for the treatment of acute venous thromboembolism. , These results suggest a lack of clear superiority of apixaban relative to enoxaparin. Apixaban is an oral alternative with similar efficacy and safety to existing anticoagulant therapies., A fixed-dose regimen of apixaban alone was noninferior to conventional therapy for the treatment of acute venous thromboembolism and was associated with significantly less bleeding, To critically review the effectiveness of the novel oral anticoagulants (rivaroxaban, dabigatran, ximelagatran, and apixaban) in the treatment of acute venous thromboembolism., ompared with vitamin K antagonists, the novel oral anticoagulants had a similar risk of recurrence of acute venous thromboembolism and all cause mortality, though rivaroxaban was associated with a reduced risk of bleeding, Nowadays, the new anticoagulants, such as dabigatran, rivaroxaban and apixaban, show potential advantages over classical treatments. These agents inhibit specific coagulation factors and are administered orally at fixed doses., In a recently completed phase III trial, apixaban also demonstrated promising efficacy and safety in that indication, the most advanced oral direct inhibitors to factor Xa (rivaroxaban and apixaban) and IIa (dabigatran)[SEP]Relations: Rivaroxaban has relations: drug_drug with Apixaban, drug_drug with Apixaban. Ximelagatran has relations: drug_drug with Apixaban, drug_drug with Apixaban. Dabigatran has relations: drug_drug with Apixaban, drug_drug with Apixaban. Enoxaparin has relations: drug_drug with Apixaban, drug_drug with Apixaban.", "label": "yes"}
{"id": "converted_1408", "sentence1": "Could Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT) cause sudden cardiac death?", "sentence2": "Here we refine our approach, and apply it to novel variants found in 2266 patients across two large cohorts with inherited sudden death syndromes, namely catecholaminergic polymorphic ventricular tachycardia (CPVT) or Brugada syndrome (BrS)., Calsequestrin-associated catecholaminergic polymorphic ventricular tachycardia (CPVT2) can cause sudden death in young individuals in response to stress. , Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmogenic cardiac disorder characterized by life-threatening arrhythmias induced by physical or emotional stress, in the absence structural heart abnormalities. The arrhythmias may cause syncope or degenerate into cardiac arrest and sudden death which usually occurs during childhood, In many cases the cause of death can be elucidated by medico-legal autopsy, however, a significant number of these cases remain unexplained despite a detailed postmortem investigation and are labeled as sudden unexplained death (SUD). Post-mortem genetic testing, so called molecular autopsy, revealed that primary arrhythmogenic disorders including long QT syndrome and catecholaminergic polymorphic ventricular tachycardia (CPVT) may account for a certain number of these cases., We report a family with repeat events of sudden cardiac death and recurrent ventricular fibrillation in a teenage girl, where autopsy data and clinical investigations were inconclusive. The diagnosis of catecholaminergic polymorphic ventricular tachycardia (CPVT) was established only following finding a gene mutation in the cardiac ryano, Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a devastating inherited disorder characterized by episodic syncope and/or sudden cardiac arrest during exercise or acute emotion in individuals without structural cardiac abnormalities. Although rare, CPVT is suspected to cause a substantial part of sudden cardiac deaths in young individuals. , In conclusion, patients with CASQ2-associated CPVT should be recommended to receive ICDs to prevent sudden death when medical therapy is not effective.,  Cardiac channelopathies associated with structurally normal hearts such as long QT syndrome (LQTS), catecholaminergic polymorphic ventricular tachycardia (CPVT), and Brugada syndrome (BrS) yield no evidence to be found at autopsy, leaving coroners, medical examiners, and forensic pathologists only to speculate that a lethal arrhythmia might lie at the heart of a sudden unexplained death (SUD)., Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a rare adrenergically mediated arrhythmogenic disorder classically induced by exercise or emotional stress and found in structurally normal hearts. It is an important cause of cardiac syncope and sudden death in childhood., We also compare CPVT to other notable cardiomyopathic and channelopathic causes of sudden death in youth including hypertrophic cardiomyopathy, arrhythmogenic right ventricular dysplasia, long QT syndrome, short QT syndrome, and Brugada syndrome., Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmogenic disease that can cause sudden cardiac death due to ventricular fibrillation (VF)., Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an arrhythmogenic disease that manifests as syncope or sudden death during high adrenergic tone in the absence of structural heart defects., Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a cardiac channelopathy characterized by altered intracellular calcium handling resulting in ventricular arrhythmias and high risk of cardiac sudden death in young cases with normal structural hearts, Early detection of CPVT is crucial because opportune medical intervention prevents sudden cardiac death. ,  If untreated, CPVT is highly lethal, as approximately 30% of affected individuals experience at least one cardiac arrest and up to 80% one or more syncopal spells. Sudden death may be the first manifestation of the disease. , Hereditary non-structural diseases such as catecholaminergic polymorphic ventricular tachycardia (CPVT), long QT, and the Brugada syndrome as well as structural disease such as hypertrophic cardiomyopathy (HCM) and arrhythmogenic right ventricular cardiomyopathy (ARVC) cause a significant percentage of sudden cardiac deaths in the young, Patients with CPVT present with exercise-induced syncope and sudden cardiac death but normal resting electrocardiograms., Although structural cardiovascular abnormalities explain most cases of sudden cardiac death in young people, the cause of death remains unexplained after autopsy in 10% to 30% of cases. Potentially lethal ion channel disorders (channelopathies) such as the long QT syndromes (LQTS), catecholaminergic polymorphic ventricular tachycardia (CPVT), and the Brugada syndrome (BrS) may account for at least one-third of these unexplained cases. , Based on these data, we propose that CPVT is a combined neurocardiac disorder in which leaky RyR2 channels in the brain cause epilepsy, and the same leaky channels in the heart cause exercise-induced sudden cardiac death., The inherited arrhythmogenic diseases associated with the transmembranous ionic channels, anchoring proteins or intracellular calcium regulating proteins are thought to be responsible for sudden cardiac death in infants, children, and young adults who have structurally normal hearts. Recent genetic analyses have identified congenital diseases such as the long-QT syndrome (LQTS), the Jervell and Lange-Nielsen syndrome (JLNS), the Brugada syndrome (BrS), the short-QT syndrome (SQTS), the arrhythmogenic right ventricular cardiomyopathy type 2 (ARVC2), and the catecholamine-induced polymorphic ventricular tachycardia (CPVT) /familial polymorphic ventricular tachycardia (FPVT). , At least some cases of sudden, unexplained death in young individuals may be ascribed to CPVT[SEP]Relations: Arrhythmia has relations: disease_phenotype_positive with hypertrophic cardiomyopathy, disease_phenotype_positive with sudden cardiac arrest, disease_phenotype_positive with hypertrophic cardiomyopathy, disease_phenotype_positive with sudden cardiac arrest. Ventricular arrhythmia has relations: disease_phenotype_positive with Brugada syndrome, disease_phenotype_positive with long QT syndrome, disease_phenotype_positive with Brugada syndrome, disease_phenotype_positive with long QT syndrome. Sudden death has relations: disease_phenotype_positive with long QT syndrome, disease_phenotype_positive with hypertrophic cardiomyopathy, disease_phenotype_positive with sudden cardiac arrest, disease_phenotype_positive with long QT syndrome, disease_phenotype_positive with hypertrophic cardiomyopathy, disease_phenotype_positive with sudden cardiac arrest. Hypertrophic cardiomyopathy has relations: disease_phenotype_positive with hypertrophic cardiomyopathy, disease_phenotype_positive with hypertrophic cardiomyopathy, disease_phenotype_positive with hypertrophic cardiomyopathy, disease_phenotype_positive with hypertrophic cardiomyopathy. Cardiac arrest has relations: disease_phenotype_positive with Brugada syndrome, disease_phenotype_positive with long QT syndrome, disease_phenotype_positive with hypertrophic cardiomyopathy, disease_phenotype_positive with Brugada syndrome, disease_phenotype_positive with long QT syndrome, disease_phenotype_positive with hypertrophic cardiomyopathy. Sudden cardiac death has relations: disease_phenotype_positive with Brugada syndrome, disease_phenotype_positive with hypertrophic cardiomyopathy, disease_phenotype_positive with long QT syndrome, disease_phenotype_positive with Brugada syndrome, disease_phenotype_positive with hypertrophic cardiomyopathy, disease_phenotype_positive with long QT syndrome. Ventricular tachycardia has relations: disease_phenotype_positive with Brugada syndrome, disease_phenotype_positive with hypertrophic cardiomyopathy, disease_phenotype_positive with Brugada syndrome, disease_phenotype_positive with hypertrophic cardiomyopathy. catecholaminergic polymorphic ventricular tachycardia has relations: disease_disease with long QT syndrome, disease_disease with long QT syndrome. Jervell-Lange Nielsen syndrome has relations: disease_disease with long QT syndrome, disease_disease with long QT syndrome.", "label": "yes"}
{"id": "converted_3854", "sentence1": "Are super enhancers structurally insulated in chromatin loops?", "sentence2": "Dissecting super-enhancer hierarchy based on chromatin interactions, Genetic ablation of hub enhancers results in profound defects in gene activation and local chromatin landscape., We also demonstrate that the Wap super-enhancer, which is built on STAT5 and other common transcription factors, retains its exquisite mammary specificity when placed into globally permissive chromatin, suggesting a limited role of chromatin in controlling cell specificity. , Although there is evidence that chromatin neighbourhoods, formed by the zinc-finger protein CTCF, can sequester enhancers and their target genes, there is limited in vivo evidence for CTCF demarcating super-enhancers and preventing cross talk between distinct regulatory elements., CTCF sites are porous borders, allowing a super-enhancer to activate a secondary target., Transcription factors and chromatin-remodeling complexes are key determinants of embryonic stem cell (ESC) identity. [SEP]Relations: mammary gland has relations: anatomy_protein_present with CTCF, anatomy_protein_present with CTCF.", "label": "no"}
{"id": "converted_2930", "sentence1": "Do raspberries improve postprandial glucose and acute and chronic inflammation in adults with type 2 Diabetes?", "sentence2": "The NLR family pyrin domain containing 3 (NLRP3) inflammasome plays a critical role in insulin resistance and the pathogenesis of type 2 diabetes. Red raspberry (RB) contains high amounts of dietary fibers and polyphenolic compounds, which are known for their anti-oxidative and anti-inflammatory effects. [SEP]", "label": "yes"}
{"id": "converted_1219", "sentence1": "Can ferric carboxymaltose be used to treat anemia in inflammatory bowel disease patients?", "sentence2": "Intravenous iron should be preferred where oral iron is poorly tolerated or where it has failed in moderate to severe anemia, and in combination with erythropoietin, Ferric carboxymaltose is much more convenient, and has been shown to be more effective than iron sucrose in a large randomized tria, nemia and iron deficiency anemia are very common in inflammatory bowel disease (IBD, Ferric carboxymaltose was associated with cost savings of 30-44 % per patient per treatment cycle compared to iron sucrose. , Iron deficiency is common in pregnancy, postpartum, inflammatory bowel disease, chronic kidney disease, chronic heart failure, heavy uterine bleeding, cancer and following surgery. We estimate the budget impact (BI) on the Swiss mandatory health insurance associated with substituting iron sucrose (standard) with ferric carboxymaltose (new treatment) using real-life data., reating iron deficiency involves substantial costs to the Swiss MHI which may be reduced by substituting iron sucrose with ferric carboxymaltose., e aim of this study was to observe, in a non-interventional way, how Swedish gastroenterologists adhere to guidelines in IBD outpatients treated with intravenous ferric carboxymaltose (FCM), and the result of treatment, FCM lowers platelet counts and platelet activation in patients with IBD-associated secondary thrombocytosis., We performed a randomized, single-blinded placebo-controlled trial testing the effect of ferric carboxymaltose (FCM) in patients with IBD with secondary thrombocytosis (platelets > 450 G/L), e performed a randomized, placebo-controlled trial to determine if administration of ferric carboxymaltose (FCM) prevents anemia in patients with IBD and low levels of serum ferritin, FCM prevents recurrence of anemia in patients with IBD, compared with placebo. ,  A subgroup was analyzed regarding efficacy and side effects of iron supplementation with ferric carboxymaltose., Iron deficiency and anemia are frequent in IBD patients. Treatment with ferric carboxymaltose is efficious, safe and well tolerated in iron-deficient IBD patients.,  Intravenous iron avoids these concerns, especially with the development of ferric carboxymaltose, which allow up to 1000mg to be given rapidly., What is the optimal treatment for anemia in inflammatory bowel disease?, We compared the efficacy and safety of a novel fixed-dose ferric carboxymaltose regimen (FCM) with individually calculated iron sucrose (IS) doses in patients with inflammatory bowel disease (IBD) and IDA, Study drugs were well tolerated and drug-related adverse events were in line with drug-specific clinical experience,  The simpler FCM-based dosing regimen showed better efficacy and compliance, as well as a good safety profile, compared with the Ganzoni-calculated IS dose regimen., Ferric carboxymaltose can be rapidly administered in doses of 15 mg/kg body weight, up to a ceiling dose of 1000 mg. A test dose is not required, and it can be used more widely across a spectrum of iron deficiency and iron deficiency anemia indication,  Intravenous iron offers a rapid means of iron repletion and is superior to oral iron in many circumstances, especially in the presence of anemia of chronic disease, where it appears to overcome the block to absorption of iron from the gastrointestinal tract and immobilization of stored iron. The clinical situations where high doses of iron are commonly required are reviewed. These include nondialysis-dependent chronic kidney disease, inflammatory bowel disease, obstetrics, menorrhagia, and anemia associated with cancer and its treatment. , Ferric carboxymaltose can be administered at 15 mg/kg body weight to a maximum dose of 1000 mg, whereas iron isomaltoside 1000 can be administered at 20 mg/kg body weight. The ability to give high doses of iron is important in the context of managing iron deficiency anemia in a number of clinical conditions where demands for iron are high (including chronic blood loss associated with inflammatory bowel disease, menorrhagia, and chronic kidney disease), erric carboxymaltose (FCM, Ferinject) was effective and well tolerated in the treatment of iron-deficiency anemia (IDA) in nine, Phase III, randomized, controlled, multicenter trials in a diverse range of indications, including patients with inflammatory bowel disease (IBD), post-partum anemia (PPA) or abnormal uterine bleeding (AUB), chronic heart failure (CHF), non-dialysis-dependent chronic kidney disease (CKD) and those undergoing hemodialysis (HD, In patients with IBD or PPA, improvements in Hb levels were more rapid with FCM than with FeSulf. , CM improved patient quality of life to an equivalent extent to oral FeSulf in patients with IBD or PPA, and to a greater extent than oral FeSulf in women with AUB, Four different products are principally used in clinical practice, which differ in their pharmacokinetic properties and safety profiles: iron gluconate and iron sucrose (lower single doses), and iron dextran and ferric carboxymaltose (higher single doses)., he prevalence of anemia across studies on patients with inflammatory bowel disease (IBD) is high (30%).,  novel intravenous iron formulation for treatment of anemia in inflammatory bowel disease: the ferric carboxymaltose (FERINJECT) randomized controlled trial., FeCarb is effective and safe in IBD-associated anemia. It is noninferior to FeSulf in terms of Hb change over 12 wk, and provides a fast Hb increase and a sufficient refill of iron stores., Treatment-related adverse events (AEs) occurred in 28.5% of the FeCarb and 22.2% of the FeSulf groups, with discontinuation of study medication due to AEs in 1.5% and 7.9%, respectively., The median Hb improved from 8.7 to 12.3 g/dL in the FeCarb group and from 9.1 to 12.1 g/dL in the FeSulf group, demonstrating noninferiority (P= 0.6967). , Ferric carboxymaltose prevents recurrence of anemia in patients with inflammatory bowel disease., Ferric carboxymaltose (FCM, Ferinject) was effective and well tolerated in the treatment of iron-deficiency anemia (IDA) in nine, Phase III, randomized, controlled, multicenter trials in a diverse range of indications, including patients with inflammatory bowel disease (IBD), post-partum anemia (PPA) or abnormal uterine bleeding (AUB), chronic heart failure (CHF), non-dialysis-dependent chronic kidney disease (CKD) and those undergoing hemodialysis (HD)., Ferric carboxymaltose (FCM, Ferinject) was effective and well tolerated in the treatment of iron-deficiency anemia (IDA) in nine, Phase III, randomized, controlled, multicenter trials in a diverse range of indications, including patients with inflammatory bowel disease (IBD), post-partum anemia (PPA) or abnormal uterine bleeding (AUB), chronic heart failure (CHF), non-dialysis-dependent chronic kidney disease (CKD) and those undergoing hemodialysis (HD)[SEP]Relations: Phenylpropanolamine has relations: contraindication with inflammatory bowel disease, contraindication with inflammatory bowel disease.", "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_protein with EGFR, drug_protein with EGFR. Erlotinib has relations: drug_protein with EGFR, drug_protein with EGFR. Cetuximab has relations: drug_protein with EGFR, drug_protein with EGFR. Gefitinib has relations: drug_protein with EGFR, drug_protein with EGFR.", "label": "yes"}
{"id": "converted_867", "sentence1": "Are psammoma bodies characteristic to meningiomas?", "sentence2": "Psammoma bodies (PBs) are concentric lamellated calcified structures, observed most commonly in papillary thyroid carcinoma (PTC), meningioma, and papillary serous cystadenocarcinoma of ovary but have rarely been reported in other neoplasms and nonneoplastic lesions., Studies on serous cystadenocarcinoma of ovary and meningioma, however, revealed that collagen production by neoplastic cells and subsequent calcification was responsible for the formation of PBs., The existence of some precursor forms of PBs was reported in meningiomas and more recently in PTC, which were mostly in the form of extracellular hyaline globules surrounded by well-preserved neoplastic cells or in a smaller number of cases intracytoplasmic bodies liberated from intact tumor cells., Light microscopy revealed abundant microcysts of varied size throughout the tumor tissue with the presence of whorl formation and psammoma body, but no malignancy was indicated. Electron microscopy further demonstrated interdigitation of the neighboring cell membranes, desmosomes, and intracytoplasmic filaments, which are pathognomonic findings of meningiomas., Unlike SFT, FMs were glycogen-containing and variously exhibited a storiform pattern (13 of 20), psammoma body formation (9 of 20), and calcification of collagen (4 of 20). Immunoreactivities included vimentin (100%), focal to patchy EMA (80%), S-100 protein (80%), collagen IV (25%), and patchy, mild-to-moderate CD34 staining (60%)., In contrast to the inner structure, three-dimensional structure of psammona bodies in meningiomas is not well defined., This study examined three cultured meningiomas, in which surface observation of psammoma bodies might be easier than in the tumor tissues since influence of interposing connective tissue is minimized in tissue culture., The results suggest that psammoma bodies in meningiomas arise in part from meningothelial whorls due to collagen production by tumor cells followed by obliteration and disappearance of tumor cell processes, although some of the alternative pathways for psammoma body formation proposed by other investigators cannot be ruled out by this study., To demonstrate that psammoma bodies in human meningiomas contain type VI collagen and laminin., This is the first report to describe the involvement of type VI collagen in psammoma bodies and whorl formations in meningiomas., Calcification such as psammoma body is sometimes found especially in spinal cord meningioma but ossification of the meningeal tumor was rarely observed., Histological diagnosis was transitional meningioma with psammoma body., In this study we analyzed the morphologic and ultrastructural characteristics of the psammoma bodies in ten meningiomas of different histologic subtypes, characterizing the components of the psammoma body and the elements of the tumor, such as the capillaries and degenerative cells that have been classically considered as initiators of the formation of these calcareous is structures., It is concluded that the mineralization of the psammoma bodies is induced principally by the collagen fibers synthesized by the meningocytes and that the form of mineralization is spherical and growth is radial, controlled by the tumoral cells., CSF cytology revealed benign fibroblastic or meningotheliomatous meningioma with whorl formation and psammoma body., Electron microscopic examination of the calculi showed membrane-bound vesicles and radially precipitated crystals that simulated hydroxyapatite of psammoma body in meningioma., Psammoma bodies in meningiomas resembled those in the choroid plexus stroma., The results of this study suggest that psammoma bodies in the choroid plexus, as in meningiomas, form by a process of dystrophic calcification associated with arachnoid cells and collagen fibres., An early stage of psammoma body formation was seen more frequently in these villous microcores than in the meningocytic whorls., Psammoma bodies in meningocytic whorls were investigated by electron microscopy., Psammoma body formation in the meningocytic whorls may represent degeneration in some whorls of the central cells which contain connective tissue fibers, producing cell debris such as membrane invested vesicles., Twenty human meningiomas were examined for IgG and IgM by the direct immunofluorescence of immunoperoxidase methods, or both. IgG was conspicuously found in and around the blood vessels, whorls, and psammoma bodies. It was also clearly present on the cytoplasmic membranes of the tumour cells., Significance of these findings is briefly discussed including possible humoral immune reactions in regard to whorl and psammoma body formation in meningioma., The fine structure of psammoma bodies was examined in four cases of fibroblastic meningioma., In general, large numbers of various-sized calcified bodies (psammoma bodies) were scattered among the interstitial fibers., These findings suggest that both matrix giant bodies and matrix vesicles may serve as initial nidus of calcification of psammoma bodies in fibroblastic meningioma., Psammoma body formation or dystrophic mineralization and gliosis of the intervening parenchyma was observed in all three cases.[SEP]Relations: papillary serous cystadenocarcinoma has relations: disease_disease with serous cystadenocarcinoma, disease_disease with serous cystadenocarcinoma. UBE2D1 has relations: anatomy_protein_present with connective tissue, anatomy_protein_present with connective tissue. serous cystadenocarcinoma has relations: disease_disease with papillary serous cystadenocarcinoma, disease_disease with papillary serous cystadenocarcinoma.", "label": "yes"}
{"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]", "label": "yes"}
{"id": "converted_3184", "sentence1": "Are Crocus sativus compounds being considered against Alzheimer's disease?", "sentence2": "Previous evidence suggested that Crocus sativus is linked to improving cognitive function in Alzheimer's disease (AD) patients. The aim of this study was to in vitro and in vivo investigate the mechanism(s) by which Crocus sativus exerts its positive effect against AD. , Collectively, findings from this study support the positive effect of Crocus sativus against AD by reducing Aβ pathological manifestations.[SEP]", "label": "yes"}
{"id": "converted_618", "sentence1": "Does molindone affect body weight?", "sentence2": "Mean weight increased by 0.54 kg, and mean body mass index by 0.24 kg/m(2). , A large-scale trial comparing a first-generation antipsychotic (molindone) with newer agents did not find significant differences in treatment response, although the newer antipsychotics were associated with more severe weight gain. , No agent demonstrated superior efficacy, and all were associated with side effects, including weight gain. , The three treatment arms did not significantly differ in symptom decrease or time to discontinuation. Akathisia was more common with molindone and elevated prolactin concentrations more common with risperidone. Although weight gain and metabolic adverse events had occurred more often with olanzapine and risperidone during the acute trial, no significant between-drug differences emerged in most of these parameters during maintenance treatment. , Olanzapine and risperidone were associated with significantly greater weight gain. Olanzapine showed the greatest risk of weight gain and significant increases in fasting cholesterol, low density lipoprotein, insulin, and liver transaminase levels. Molindone led to more self-reports of akathisia. , Molindone is no more or less likely than typical drugs to cause movement disorders, but it does cause significantly more weight loss (2RCTs n=60 RR 2.78, CI 1.10 to 6.99, NNH 5 CI 2 to 77). , Molindone may be an effective antipsychotic but its adverse effect profile does not differ significantly from that of typical antipsychotics (apart from the event of weight loss). , Convergent evidence suggests a hierarchy in the magnitude of BWG that may be induced by diverse agents, being very high for clozapine and olanzapine; high for quetiapine, zotepin, chlorpromazine, and thioridazine; moderate for risperidone and sertindole; and low for ziprazidone, amisulpiride, haloperidol, fluphenazine, pimozide, and molindone. , Loxapine and molindone induce weight decreases, and these exceptions are difficult to explain., It is no more or less likely than typical drugs to cause movement disorders, but causes significantly more weight loss (RR 2.78, CI 1.10 to 6.99)., Molindone may be an effective antipsychotic; however, its adverse effect profile does not differ significantly from that of typical antipsychotics, apart from the event of weight loss. , Among conventional agents, mean weight change ranged from a reduction of 0.39 kg with molindone to an increase of 3.19 kg with thioridazine., Weight gain has been reported with nearly every antipsychotic drug on the market (molindone is an exception). , Although almost all antipsychotics induce bodyweight gain, molindone and loxapine appear to induce bodyweight loss. , Clozapine and low-potency phenothiazines are associated with the largest gains and molindone with weight loss, but the mechanism is not known. , On average, molindone patients lost 5 pounds over the 6 weeks of treatment, whereas thioridazine patients gained 6 pounds. , Clinically, molindone has a tendency to cause weight loss and may have less effect on seizure threshold than conventional antipsychotic agents,  Monthly weights and neuroleptic dosages during the first three months of psychiatric hospitalization were compared between matched groups of patients receiving molindone, a combination of molindone and other neuroleptics, or other neuroleptic drugs. We found no significant differences in weight gain among the three groups. , The weight-reducing property of molindone, a recently introduced antipsychotic drug, was tested in 9 hospitalized chronic schizophrenic patients. There was an average weight loss of 7.6 kg after 3 months on molindone; most of the loss occurred during the first month.[SEP]Relations: Loxapine has relations: drug_drug with Olanzapine, drug_drug with Olanzapine. Thioridazine has relations: drug_drug with Olanzapine, drug_drug with Olanzapine. Risperidone has relations: drug_drug with Olanzapine, drug_drug with Olanzapine. Clozapine has relations: drug_drug with Olanzapine, drug_drug with Olanzapine. Molindone has relations: drug_drug with Olanzapine, drug_drug with Olanzapine. Chlorpromazine has relations: drug_drug with Olanzapine, drug_drug with Olanzapine. Fluphenazine has relations: drug_drug with Olanzapine, drug_drug with Olanzapine. Quetiapine has relations: drug_drug with Olanzapine, drug_drug with Olanzapine. Sertindole has relations: drug_drug with Olanzapine, drug_drug with Olanzapine. Ziprasidone has relations: drug_drug with Olanzapine, drug_drug with Olanzapine. Pimozide has relations: drug_drug with Olanzapine, drug_drug with Olanzapine. Seizure has relations: drug_effect with Olanzapine, drug_effect with Olanzapine.", "label": "yes"}
{"id": "converted_711", "sentence1": "Do proton pump inhibitors affect thyroxine absorption?", "sentence2": "Proton-pump inhibitors, antacids and a long list of drugs may decrease thyroxine absorption, Many commonly used drugs, such as bile acid sequestrants, ferrous sulphate, sucralfate, calcium carbonate, aluminium-containing antacids, phosphate binders, raloxifene and proton-pump inhibitors, have also been shown to interfere with the absorption of levothyroxine., Pantoprazole did not influence endocrine function in healthy male volunteers during short-term treatment., PPIs should be added to the list of medications affecting the level of thyroid hormone in patients with hypothyroidism treated with LT4 replacement. Patients with hypothyroidism and normal TSH values during LT4 replacement therapy may need additional thyroid function testing after treatment with PPIs and may need adjustment of their LT4 dose.[SEP]Relations: Levothyroxine has relations: drug_drug with Pantoprazole, drug_drug with Pantoprazole. Sucralfate has relations: drug_drug with Pantoprazole, drug_drug with Pantoprazole. Raloxifene has relations: drug_drug with Pantoprazole, drug_drug with Pantoprazole. Ferrous sulfate anhydrous has relations: drug_drug with Pantoprazole, drug_drug with Pantoprazole.", "label": "yes"}
{"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: hepatobiliary disease has relations: disease_disease with liver disease, disease_disease with liver disease.", "label": "no"}
{"id": "converted_712", "sentence1": "Is PER3 required for CHK2 activation in human cells?", "sentence2": "Per3, a circadian gene, is required for Chk2 activation in human cells., Depletion of Per3 by siRNA almost completely abolished activation of checkpoint kinase 2 (Chk2) after inducing DNA damage in human cells., Per3 overexpression induced Chk2 activation in the absence of exogenous DNA damage,, Per3 overexpression also led to the inhibition of cell proliferation and apoptotic cell death., These combined results suggest that Per3 is a checkpoint protein that plays important roles in checkpoint activation, cell proliferation and apoptosis., Depletion of Per3 by siRNA almost completely abolished activation of checkpoint kinase 2 (Chk2) after inducing DNA damage in human cells, Per3 overexpression induced Chk2 activation in the absence of exogenous DNA damage, and this activation depended on ATM, In addition, Per3 physically interacted with ATM and Chk2[SEP]Relations: PER3 has relations: protein_protein with ATM, protein_protein with ATM.", "label": "yes"}
{"id": "converted_384", "sentence1": "Is nintedanib effective for Idiopathic Pulmonary Fibrosis?", "sentence2": "In this review, we present the positive results of recently published clinical trials regarding therapy for IPF, with emphasis on pirfenidone and nintedanib., Nintedanib: evidence for its therapeutic potential in idiopathic pulmonary fibrosis,  In the Phase II TOMORROW trial, treatment with 150 mg of nintedanib twice daily showed a trend to slow the decline in lung function and significantly decrease acute exacerbations in patients with IPF, while showing an acceptable safety profile. The Phase III INPULSIS trials demonstrated a significant decrease in the annual rate of decline in forced vital capacity in IPF patients treated with 150 mg nintedanib twice daily. In the INPULSIS-2 trial, the time to the first acute exacerbation significantly increased in IPF patients who were treated with 150 mg of nintedanib twice daily.,  Effects on collagen secretion were compared with those of the drugs nintedanib and pirfenidone, recently approved for IPF., Nintedanib, an orally available, small-molecule tyrosine kinase inhibitor with selectivity for vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF) and fibroblast growth factor (FGF) receptors has recently been shown, in two pivotal phase III studies, to effectively slow IPF disease progression. Consequently, nintedanib was given accelerated approval by the FDA in October 2014 for the treatment of IPF. , Most recently, pirfenidone and nintedanib, two compounds with pleiotropic anti-fibrotic properties, have been proven effective in reducing functional decline and disease progression in IPF. , Meningococcal group B vaccine (Trumenba) to prevent more types of invasive meningococcal disease; antihemophilic factor (recombinant), porcine sequence (Obizur) to treat bleeding from acquired hemophilia A; and pirfenidone (Esbriet) and nintedanib (Ofev) for idiopathic pulmonary fibrosis.,  More importantly, the period ends with the publication of two groundbreaking studies that confirmed that two drugs, pirfenidone and nintedanib, slowed disease progression, leading to a historic approval by the FDA. , Nintedanib (Ofev(®)) is an orally available, small, multiple receptor tyrosine kinase inhibitor developed by Boehringer Ingelheim for the treatment of idiopathic pulmonary fibrosis (IPF) and cancer. Nintedanib received its first global approval in the US in October 2014 for the treatment of IPF. Nintedanib has received a positive opinion from the European Medicines Agency's Committee for Medicinal Products for Human Use for the treatment of IPF, and for the second-line treatment in combination with docetaxel of locally advanced, metastatic or locally recurrent non-small cell lung cancer of adenocarcinoma tumour histology. , This article summarizes the milestones in the development of nintedanib leading to this first approval for IPF., Efficacy and safety of nintedanib in idiopathic pulmonary fibrosis., Nintedanib: a novel therapeutic approach for idiopathic pulmonary fibrosis., Nintedanib is in clinical development as a treatment for idiopathic pulmonary fibrosis (IPF)., Reducing lung function decline in patients with idiopathic pulmonary fibrosis: potential of nintedanib., These results suggest that nintedanib may impact the progressive course of fibrotic lung diseases such as idiopathic pulmonary fibrosis., Findings from recently published placebo-controlled trials in idiopathic pulmonary fibrosis have established that pirfenidone and nintedanib prevent about 50% of the decline in forced vital capacity typically seen in this disease; future trials are therefore unlikely to use placebo as a control group for ethical reasons., The tyrosine kinase inhibitor nintedanib (BIBF 1120) is in clinical development for the treatment of idiopathic pulmonary fibrosis., A phase 2 trial suggested that treatment with 150 mg of nintedanib twice daily reduced lung-function decline and acute exacerbations in patients with idiopathic pulmonary fibrosis., A phase 2 trial suggested that treatment with 150 mg of nintedanib twice daily reduced lung-function decline and acute exacerbations in patients with idiopathic pulmonary fibrosis. , Data from the Phase II TOMORROW study suggested that nintedanib 150�mg twice daily had clinical benefits with an acceptable safety profile.METHODS: The INPULSIS� trials are replicate Phase III, randomized, double-blind, studies comparing the efficacy and safety of nintedanib 150�mg twice daily with placebo in patients with IPF. , Nintedanib received its first global approval in the US in October 2014 for the treatment of IPF. , The most frequent adverse event in the nintedanib groups was diarrhea, with rates of 61.5% and 18.6% in the nintedanib and placebo groups, respectively, in INPULSIS-1 and 63.2% and 18.3% in the two groups, respectively, in INPULSIS-2. CONCLUSIONS: In patients with idiopathic pulmonary fibrosis, nintedanib reduced the decline in FVC, which is consistent with a slowing of disease progression; nintedanib was frequently associated with diarrhea, which led to discontinuation of the study medication in less than 5% of patients. , A phase 2 trial suggested that treatment with 150 mg of nintedanib twice daily reduced lung-function decline and acute exacerbations in patients with idiopathic pulmonary fibrosis. METHODS: We conducted two replicate 52-week, randomized, double-blind, phase 3 trials (INPULSIS-1 and INPULSIS-2) to evaluate the efficacy and safety of 150 mg of nintedanib twice daily as compared with placebo in patients with idiopathic pulmonary fibrosis. , Nintedanib (Ofev(�)) is an orally available, small, multiple receptor tyrosine kinase inhibitor developed by Boehringer Ingelheim for the treatment of idiopathic pulmonary fibrosis (IPF) and cancer. Nintedanib received its first global approval in the US in October 2014 for the treatment of IPF. , Nintedanib: evidence for its therapeutic potential in idiopathic pulmonary fibrosis., A phase 2 trial suggested that treatment with 150 mg of nintedanib twice daily reduced lung-function decline and acute exacerbations in patients with idiopathic pulmonary fibrosis. We conducted two replicate 52-week, randomized, double-blind, phase 3 trials (INPULSIS-1 and INPULSIS-2) to evaluate the efficacy and safety of 150 mg of nintedanib twice daily as compared with placebo in patients with idiopathic pulmonary fibrosis.[SEP]", "label": "yes"}
{"id": "converted_2090", "sentence1": "Can methylenetetrahydrofolate reductase (MTHFR) gene mutations cause homocystinuria?", "sentence2": "Methylenetetrahydrofolate reductase (MTHFR) deficiency is a rare autosomal recessive disorder. , Several mutations seen in methylenetetrahydrofolate reductase (MTHFR) give rise to the formation of hyperhomocysteinemia and homocystinuria, a considerable risk factor for cardiovascular and cerebrovascular disorders, by leading to enzymatic inactivation., At admission, he had significantly elevated plasma and urine levels of total homocysteine, significantly decreased levels of folate in serum and cerebrospinal fluid, and a normal blood concentration of methionine., Response to treatment demonstrated B(6)-non-responsive homocystinuria. Molecular study showed compound heterozygous T353 N and D444 N mutations of the cystathionine beta-synthase (CBS) gene, and also a C667T homozygous mutation of the methylenetetrahydrofolate-reductase (MTHFR) gene. , Our case is atypical because of the absence of thromboembolism and the mild phenotype, in spite of being B(6)-non-responsive, and the association of a rare compound heterozygous mutation of the CBS gene and also an homozygous mutation of the MTHFR gene., Molecular characterization of five patients with homocystinuria due to severe methylenetetrahydrofolate reductase deficiency., Methylenetetrahydrofolate reductase (MTHFR) is a key regulatory enzyme in folate and homocysteine metabolism. Research performed during the past decade has clarified our understanding of MTHFR deficiencies that cause homocystinuria or mild hyperhomocysteinemia. Our cloning of the MTHFR coding sequence was initially followed by the identification of the first deleterious mutations in MTHFR, in patients with homocystinuria and marked hyperhomocysteinemia., Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in the regulation of plasma homocysteine levels. MTHFR deficiency, an autosomal recessive disorder, results in homocystinuria and hypomethioninaemia and presents with highly variable symptoms affecting many organs but predominantly the central nervous system. , Some methylenetetrahydrofolate reductase (MTHFR) gene mutations cause hyperhomocysteinemia and homocystinuria., Rare mutations in the MTHFR gene have been associated with autosomal recessive MTHFR deficiency leading to homocystinuria., Characterization of six novel mutations in the methylenetetrahydrofolate reductase (MTHFR) gene in patients with homocystinuria., Five patients suspected of having non-classical homocystinuria due to MTHFR deficiency were examined with respect to their symptoms, MTHFR enzyme activity and genotypes of the MTHFR gene., The results of our study render the full-length characterisation of affected alleles in severe homocystinuria and moderate hyperhomocysteinaemia due to MTHFR deficiency and provide a basis for investigating the regulation of the human MTHFR gene., Our cloning of the MTHFR coding sequence was initially followed by the identification of the first deleterious mutations in MTHFR, in patients with homocystinuria and marked hyperhomocysteinemia., Different MTHFR mutations lead either to severe homocystinuria as a multisystem disorder or to moderate hyperhomocysteinaemia, which is a common risk factor for disorders ranging from cardiovasculopathy to spina bifida., We studied 24 patients with homocystinuria caused by homozygous CBS deficiency from 18 unrelated kindreds for FVL and for the 677C-->T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene and investigated their possible interaction in the risk of venous thrombosis., On the contrary, thermolabile MTHFR caused by the 677C-->T mutation, was frequently observed among homocystinuria patients, especially among those with thromboembolic complications: three of six homocystinuria patients who had suffered from a thromboembolic event had thermolabile MTHFR., We studied 24 patients with homocystinuria caused by homozygous CBS deficiency from 18 unrelated kindreds for FVL and for the 677C-->T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene and investigated their possible interaction in the risk of venous thrombosis., Some methylenetetrahydrofolate reductase (MTHFR) gene mutations cause hyperhomocysteinemia and homocystinuria, We studied 24 patients with homocystinuria caused by homozygous CBS deficiency from 18 unrelated kindreds for FVL and for the 677C-->T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene and investigated their possible interaction in the risk of venous thrombosis, Characterization of six novel mutations in the methylenetetrahydrofolate reductase (MTHFR) gene in patients with homocystinuria, The most common genetic cause of hyperhomocysteinemia is the 677C-->T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene, The 677C-->T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene is an important cause of mild hyperhomocysteinemia, but this polymorphism does not seem to be a risk factor for venous thrombosis, Hyperhomocysteinemia and methylenetetrahydrofolate reductase (MTHFR) gene mutation have been postulated as a possible cause of recurrent miscarriage (RM), The 677C>T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene is an important cause of mild hyperhomocysteinaemia, We studied 24 patients with homocystinuria caused by homozygous CBS deficiency from 18 unrelated kindreds for FVL and for the 677C-->T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene and investigated their possible interaction in the risk of venous thrombosis. , AIM: Some methylenetetrahydrofolate reductase (MTHFR) gene mutations cause hyperhomocysteinemia and homocystinuria. , Betaine for treatment of homocystinuria caused by methylenetetrahydrofolate reductase deficiency., Severe deficiency of methylenetetrahydrofolate reductase (MTHFR) with homocystinuria can result in early demise or later-onset neurological impairment, including developmental delay, motor dysfunction, and seizures. , Deficiency of 5,10-methylenetetrahydrofolate reductase (MTHFR) leads to deficient remethylation of homocysteine and is one of the causes of homocystinuria. , Neurological disturbances have been described in homocystinuria caused by severe MTHFR deficiency. , The 677C-->T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene is an important cause of mild hyperhomocysteinemia, but this polymorphism does not seem to be a risk factor for venous thrombosis., Research performed during the past decade has clarified our understanding of MTHFR deficiencies that cause homocystinuria or mild hyperhomocysteinemia., The 677C>T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene is an important cause of mild hyperhomocysteinaemia., The most common genetic cause of hyperhomocysteinemia is the 677C-->T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene., Our cloning of the MTHFR coding sequence was initially followed by the identification of the first deleterious mutations in MTHFR, in patients with homocystinuria and marked hyperhomocysteinemia., Characterization of six novel mutations in the methylenetetrahydrofolate reductase (MTHFR) gene in patients with homocystinuria., Molecular characterization of five patients with homocystinuria due to severe methylenetetrahydrofolate reductase deficiency., On the contrary, thermolabile MTHFR caused by the 677C-->T mutation, was frequently observed among homocystinuria patients, especially among those with thromboembolic complications: three of six homocystinuria patients who had suffered from a thromboembolic event had thermolabile MTHFR.[SEP]Relations: methylenetetrahydrofolate reductase (NAD(P)H) activity has relations: molfunc_protein with MTHFR, molfunc_protein with MTHFR. spina bifida has relations: disease_protein with MTHFR, disease_protein with MTHFR. hyperhomocysteinemia has relations: disease_protein with MTHFR, disease_protein with MTHFR. homocystinuria due to methylene tetrahydrofolate reductase deficiency has relations: disease_protein with MTHFR, disease_protein with MTHFR. Methionine has relations: drug_protein with MTHFR, drug_protein with MTHFR.", "label": "yes"}
{"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: Ipilimumab has relations: drug_drug with Nivolumab, drug_drug with Nivolumab. Tremelimumab has relations: drug_drug with Nivolumab, drug_drug with Nivolumab. melanocytic neoplasm has relations: disease_disease with melanoma, disease_disease with melanoma. Pembrolizumab has relations: drug_drug with Nivolumab, drug_drug with Nivolumab.", "label": "yes"}
{"id": "converted_1372", "sentence1": "Does nimotuzumab improve survival of glioblastoma patients?", "sentence2": "The survival times were similar to those seen in historical data of standard therapy., The survival time of a matched population treated at the same hospital with irradiation alone was decreased (median 8.0 and 12.2 mo for GBM and AA patients, respectively) compared with that of the patients who received nimotuzumab and curative-intent radiotherapy., This study, in a poor prognosis population, validates the previous data of survival gain after combining nimotuzumab and radiotherapy, in newly diagnosed high-grade glioma patients., The mean and median survival time for subjects treated with nimotuzumab was 31.06 and 17.76 vs. 21.07 and 12.63 months for the control group. CONCLUSIONS: In this randomized trial, nimotuzumab showed an excellent safety profile and significant survival benefit in combination with irradiation., Nimotuzumab was well-tolerated and treatment with the antibody yielded a survival benefit: median survival time was 32.66 mo and the 2-y survival rate was 54.2%. This study demonstrated the feasibility of prolonged administration of nimotuzumab and showed preliminary evidence of clinical benefit in HGG patients with poor prognosis.,  Recent clinical studies show that patients with malignant gliomas could benefit from nimotuzumab treatment., CONCLUSIONS: Nimotuzumab in combination with chemotherapy has moderate activity in patients with malignant gliomas and the toxicities are well tolerable, therefore, worth further investigation., It has been evaluated in malignant brain tumors in adults and children, and shown to be therapeutically safe and effective in terms of increased survival and improved quality of life. , Conclusions As used in this study, nimotuzumab demonstrated a broad safety profile, making it acceptable for chronic use, and implied clinical benefits in terms of increased survival and improved functional status in these patients, compared to findings described in the literature. , Nimotuzumab prolongs survival in patients with malignant gliomas: A phase I/II clinical study of concomitant radiochemotherapy with or without nimotuzumab., Conclusions As used in this study, nimotuzumab demonstrated a broad safety profile, making it acceptable for chronic use, and implied clinical benefits in terms of increased survival and improved functional status in these patients, compared to findings described in the literature., This study, in a poor prognosis population, validates the previous data of survival gain after combining nimotuzumab and radiotherapy, in newly diagnosed high-grade glioma patients, Conclusions As used in this study, nimotuzumab demonstrated a broad safety profile, making it acceptable for chronic use, and implied clinical benefits in terms of increased survival and improved functional status in these patients, compared to findings described in the literature, A multicenter exploratory study combining nimotuzumab and radiotherapy showed disease control and an overall patient survival similar to previous experiences along with an improvement in the quality of patient survival and no severe side effects., Combining craniospinal irradiation (CSI) with concurrent temozolomide and nimotuzumab therapy may slightly improve tumor control and overall survival[SEP]", "label": "yes"}
{"id": "converted_4697", "sentence1": "Is disruption of immune regulation mechanisms associated with adverse pregnancy outcomes, including preeclampsia (PE)?", "sentence2": " Maternal systemic and placental inflammatory responses participate in the pathogenesis of hypertensive disorders of pregnancy including preeclampsia, a pregnancy-specific syndrome, although the role of inflammation remains unclear. , Our results indicate these proteins are new factors that play important roles in the immunological pathomechanism of preeclampsia., Inflammation and oxidative stress at the maternal-fetal interface characterize the placental dysfunction that underlies the pregnancy disorder preeclampsia., The abnormal expression of Tim-3 on MDSC might be involved in the pathogenesis of PE, and could be a marker to evaluate the immune function in PE., Maternal immune tolerance is important for maintaining pregnancy, and researchers have increasingly focused on the critical roles of cytokines in the pathogenesis of PE in recent years., Disruption of well-controlled immune functions leads to infertility, placental inflammation, and numerous pregnancy complications, including preeclampsia (PE)., Effect of Endogenic and Exogenic Oxidative Stress Triggers on Adverse Pregnancy Outcomes: Preeclampsia, Fetal Growth Restriction, Gestational Diabetes Mellitus and Preterm Birth., Disruption of complex immune regulation mechanisms is associated with adverse pregnancy outcomes, including preeclampsia (PE)., In addition, it has been demonstrated that immune disturbance may be responsible for some adverse pregnancy outcomes such as preeclampsia (PE), recurrent spontaneous abortion (RSA) and intrauterine growth restriction (IUGR)., esponse. In previous models of preeclampsia (PE), defective immune function caused by disruption of lymphangiogenesis was shown to be involved in the disease pathophy, OBJECTIVE: Increased oxidative stress and immune dysfunction are implicated in preeclampsia (PE) and may contribute to the two- to fourfold increase in PE prevalence among women with type 1 , r, in preeclampsia, the regulation of immune responses is disrupted as a result of aberrant activation of innate immune cells and imbalanced differentiation of T-helper cell subsets creating a cytotoxic environment in uter, Disruption in the Regulation of Immune Responses in the Placental Subtype of Preeclampsia, a disrupted immune system might be a predisposing factor or result of placental oxidative stress or excessive inflammation in preeclampsia. Preeclampsia c, clude insufficient control of inflammation, failure of tolerance toward paternal antigens at the fetal-maternal interface, and subsequent over- or insufficient activation of immune mediators. It is als, PROBLEM: The purpose of this study is to clarify whether the disruption of immune regulation occurs in early pregnancy before the clinical manifestations of pre, s review, we focus on the role of excessive systemic inflammation as the result of a dysregulated immune system in the development of preeclampsia. These, PROBLEM: The purpose of this study is to clarify whether the disruption of immune regulation occurs in early pregnancy before the clinical manifestations of pree, However, in preeclampsia, the regulation of immune responses is disrupted as a result of aberrant activation of innate immune cells and imbalanced differentiation of T-helper cell subsets creating a cytotoxic environment in utero., In conclusion, a disrupted immune system might be a predisposing factor or result of placental oxidative stress or excessive inflammation in preeclampsia., esponse. In previous models of preeclampsia (PE), defective immune function caused by disruption of lymphangiogenesis was shown to be involved in the disease pathoph, Disruption of this immune balance and/or inadequate placental perfusion is believed to be associated with a lot of pregnancy-related complications, such as recurrent spontaneous abortion, pre-eclampsia, and fetal intrauterine growth restriction., Therefore, a delicate immune balance is critical for the maintenance of a successful pregnancy, while disruption of this balance can induce complications such as implantation failure, miscarriage, preterm birth/labor, preeclampsia and fetal growth restriction., antigens during pregnancy. Disruption of complex immune regulation mechanisms is associated with adverse pregnancy outcomes, including preeclampsia (P, ccessful pregnancy. It has been demonstrated that innate immune disturbances may be responsible for some adverse pregnancy outcomes such as preeclamps, ever, in preeclampsia, the regulation of immune responses is disrupted as a result of aberrant activation of innate immune cells and imbalanced differ, PROBLEM: The purpose of this study is to clarify whether the disruption of immune regulation occurs in early pregnancy before the clinical manifestations of preeclampsia, However, immune maladaptation and hemostatic imbalance have been suggested to be responsible for adverse pregnant outcomes, such as preeclampsia (PE), miscarriage, recurrent spontaneous abortion (RSA) and intrauterine growth restriction (IUGR)., PROBLEM: The purpose of this study is to clarify whether the disruption of immune regulation occurs in early pregnancy before the clinical manifestations of preeclampsia.METHOD OF STUDY: The serum concentrations of interleukin-2 (IL-2) and tumor necrosis factor-alpha (TNF-alpha) were determined by using enzyme-linked immunoadsorbent assay (ELISA) in the first trimester of pregnancy in women who had preeclampsia develop after 28 weeks of pregnancy (preeclamptic group) and in women who completed pregnancy uneventfully (control group).RESULTS: Serum concentrations of both IL-2 and TNF-alpha in the first trimester of the preeclamptic group were significantly higher than those of the control group.CONCLUSIONS: That the perturbation of feto-maternal immune regulation may precede the clinical manifestations of preeclampsia, which may be of relevance i, Preeclampsia can thus be considered a hyperinflammatory state associated with defective regulation of the immune system proposed as a key element in the pathological events of the placental subtype of this disorder., Disruption in the Regulation of Immune Responses in the Placental Subtype of Preeclampsia., It has been demonstrated that innate immune disturbances may be responsible for some adverse pregnancy outcomes such as preeclampsia (PE); hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome; intrauterine growth restriction (IUGR); and recurrent spontaneous abortion (RSA).[SEP]", "label": "yes"}
{"id": "converted_1845", "sentence1": "Can the Micro-C XL method achieve mononucleosome resolution?", "sentence2": "We present Micro-C XL, an improved method for analysis of chromosome folding at mononucleosome resolution, We present Micro-C XL, an improved method for analysis of chromosome folding at mononucleosome resolution., Micro-C XL: assaying chromosome conformation from the nucleosome to the entire genome., Micro-C XL provides a single assay to interrogate chromosome folding at length scales from the nucleosome to the full genome.[SEP]", "label": "yes"}
{"id": "converted_3167", "sentence1": "Can miR-122 target RUNX2?", "sentence2": "MiR-122 functions as a tumor suppressor by inhibiting proliferation and inducing apoptosis, which is achieved by directly targeting RUNX2.[SEP]", "label": "yes"}
{"id": "converted_1477", "sentence1": "Does HuR protein regulate the splicing process?", "sentence2": "HuR and TIA1/TIAL1 are involved in regulation of alternative splicing of SIRT1 pre-mRNA, Here we describe experiments showing that HuR and TIA1/TIAL1, two kinds of RNA-binding proteins, were involved in the regulation of alternative splicing of SIRT1 pre-mRNA under normal and stress circumstances, HuR increased SIRT1-∆Exon8 by promoting SIRT1 exon 8 exclusion, whereas TIA1/TIAL1 inhibition of the exon 8 exclusion led to a decrease in SIRT1-∆Exon8 mRNA levels. , HuR regulates alternative splicing of the TRA2β gene in human colon cancer cells under oxidative stress, Hu antigen R (HuR) regulates stress responses through stabilizing and/or facilitating the translation of target mRNAs, We show here that the RBP embryonic lethal abnormal vision like 1 (ELAVL1, also know as HuR) regulates the alternative splicing of eukaryotic translation initiation factor 4E nuclear import factor 1 (Eif4enif1), which encodes an eukaryotic translation initiation factor 4E transporter (4E-T) protein and suppresses the expression of capped mRNAs, Further, endothelial-specific Elavl1 knockout mice exhibited reduced revascularization after hind limb ischemia and tumor angiogenesis in oncogene-induced mammary cancer, resulting in attenuated blood flow and tumor growth, respectively. , Changes in cellular mRNA stability, splicing, and polyadenylation through HuR protein sequestration by a cytoplasmic RNA virus, Furthermore, significant changes can be observed in nuclear alternative polyadenylation and splicing events on cellular pre-mRNAs as a result of sequestration of HuR protein by the 3' UTR of transcripts of this cytoplasmic RNA virus., Here we demonstrate that expression of 2A(pro) induces a selective nucleo-cytoplasm translocation of several important RNA binding proteins and splicing factors. Subcellular fractionation studies, together with immunofluorescence microscopy revealed an asymmetric distribution of HuR and TIA1/TIAR in 2A(pro) expressing cells, which modulates splicing of the human Fas exon 6, knockdown of HuR or overexpression of TIA1/TIAR, leads to Fas exon 6 inclusion in 2A(pro)-expressing cells, The differential expression levels of T-cell intracellular antigens (TIA) and Hu antigen R (HuR) are concomitant with a splicing switch in apoptosis receptor Fas in HCT-116 cells, overexpression and knockdown of HuR led to Fas exon 6 skipping and inclusion, respectively. These results suggest that the TIA and HuR cellular ratio influences cell-type specific Fas exon 6 splicing pattern., Hu antigen R (HuR) functions as an alternative pre-mRNA splicing regulator of Fas apoptosis-promoting receptor on exon definition, antiapoptotic regulator Hu antigen R (HuR, ELAVL1), a member of the embryonic lethal, abnormal vision, Drosophila-like (ELAVL) family, promotes Fas exon 6 skipping by binding to an exonic splicing silencer, ELAV/Hu proteins bind to AU-rich elements (ARE) in mRNAs and regulate their stability from splicing to translation, and the ubiquitous HuR protein has been implicated in cancerous cell growth., The HuR protein regulates the expression of thousands of cellular transcripts by modulating mRNA splicing, trafficking, translation, and stability., Hu antigen R (HuR) functions as an alternative pre-mRNA splicing regulator of Fas apoptosis-promoting receptor on exon definition., I report that antiapoptotic regulator Hu antigen R (HuR, ELAVL1), a member of the embryonic lethal, abnormal vision, Drosophila-like (ELAVL) family, promotes Fas exon 6 skipping by binding to an exonic splicing silencer. , Changes in cellular mRNA stability, splicing, and polyadenylation through HuR protein sequestration by a cytoplasmic RNA virus., Further, the silencing capacity of HuR as splicing regulator resides in the RRM1 and hinge-RRM3 domains. , HuR and TIA1/TIAL1 are involved in regulation of alternative splicing of SIRT1 pre-mRNA., HuR regulates alternative splicing of the TRA2β gene in human colon cancer cells under oxidative stress., The HuR protein regulates the expression of thousands of cellular transcripts by modulating mRNA splicing, trafficking, translation, and stability. , Further, the silencing capacity of HuR as splicing regulator resides in the RRM1 and hinge-RRM3 domains. Taken together, these results support a functional link between HuR as repressor of alternative Fas splicing and the molecular mechanisms modulating programmed cell death., We are interested in interactions involving hnRNP proteins participating in several steps of mRNA processing (mainly pre-mRNA splicing) and HuR with an established role in stability/translation of associated mRNAs. hnRNP and HuR proteins have a major nucleoplasmic localization and ability to shuttle between nucleus and cytoplasm. We report here on interactions between hnRNP and HuR proteins that were identified in the context of isolated hnRNP and mRNP complexes. , Despite the fact that HuR sites are observed in intronic regions, our data do not support a role for HuR in regulating splicing.[SEP]Relations: ELAVL1 has relations: cellcomp_protein with nucleus, cellcomp_protein with nucleus. protein binding has relations: molfunc_protein with RRM1, molfunc_protein with RRM1. EIF4ENIF1 has relations: cellcomp_protein with nucleus, cellcomp_protein with nucleus.", "label": "yes"}
{"id": "converted_3938", "sentence1": "Is carpal tunnel syndrome a type of nerve entrapment?", "sentence2": " Carpal tunnel syndrome (CTS) is a common entrapment neuropathy, often requiring carpal tunnel release (CTR) surgery., Carpal tunnel syndrome (CTS) is an entrapment neuropathy accounting for up to 90% of nerve compression syndromes,  Carpal tunnel syndrome (CTS) is the most frequent entrapment neuropathy in humans. , Carpal tunnel syndrome (CTS) is the most common focal entrapment mononeuropathy, comprising medium nerve chronic inflammation and fibrosis., Carpal tunnel syndrome (CTS) is the most common nerve entrapment neuropathy which is the result of the compression of the median nerve in the wrist. , Dear sir, one of the most common entrapment neuropathy syndromes in clinical practice is \"Entrapment of median nerve in carpal tunnel\" also called \"Carpal tunnel syndrome (CTS)\" (Aydin et al., 2007; Huisstede et al., 2010)., BACKGROUND: Carpal tunnel syndrome (CTS) is the most common type of peripheral nerve entrapment and is a significant cause of morbidity., BACKGROUND: Carpal tunnel syndrome and ulnar nerve entrapment at the elbow are the most common entrapment neuropathies seen in adults., Entrapment neuropathies are of various types, but the most common type is carpal tunnel syndrome., Carpal Tunnel Syndrome and Other Entrapment Neuropathies., Unlike Guyon's canal syndrome, carpal tunnel syndrome (CTS) is the most common nerve entrapment of the upper extremity.,  chronic renal failure tend to develop peripheral nerve entrapment and carpal tunnel syndrome is the best-known peripheral entrapment neuropathy among them. Contrary to ca, Carpal tunnel syndrome (CTS) is a common form of peripheral nerve entrapment, which is observed due to compression of the median nerve at the level of the carpal tunnel in the wrist. Bifi, INTRODUCTION: Carpal tunnel syndrome (CTS) is considered a simple entrapment of the median nerve at the carp, Compressive neuropathy of the median nerve at the level of the carpal tunnel, known as carpal tunnel syndrome, is the most common entrapment neuropathy, affecting about 0.1-1% of the general population. Magne, BACKGROUND: Carpal tunnel syndrome (CTS) is entrapment of median nerve in carpal tunnel of th, Dear sir, one of the most common entrapment neuropathy syndromes in clinical practice is \"Entrapment of median nerve in carpal tunnel\" also called \"Carpal tunnel syndrome (CTS)\" (Aydin et al., 2007; Huisstede et al., 2010). This syndr, OBJECTIVE: Carpal tunnel syndrome (CTS) is a common median nerve entrapment neuropathy characterized by pain, paresthesias, diminished peripheral nerve conduction velocity (NCV) and maladaptive functional brain neuroplastici, Carpal tunnel syndrome (CTS), caused by entrapment of the median nerve in the carpal tunnel, impairs hand function including dexterous manipulation. The , This review focuses on three of the most common entrapment neuropathies in the upper limbs: carpal tunnel syndrome (median nerve entrapment at the wrist), cubital tunnel syndrome (ulnar nerve entrapment at the elbow), and radial tunnel syndrome (posterior interosseous nerve entrapment)., Electrodiagnostic (EDX) testing is usually an essential part of the evaluation of entrapment neuropathies, and examinations for the most common entrapment neuropathies, carpal tunnel syndrome and ulnar neuropathy at the elbow, constitute a significant part of the daily work in EDX laboratories., This study reviews the existing, more or less, detailed EDX criteria or practice parameters that are suggested by consensus groups in peer-reviewed journals for the most common entrapment neuropathies: carpal tunnel syndrome, ulnar neuropathy at the elbow, common peroneal (fibular) neuropathy at the fibular head, and tibial neuropathy at the tarsal tunnel., This report demonstrates that the Semmes-Weinstein monofilament test and nerve conduction studies can identify entrapment of the palmar cutaneous branch of the median nerve concomitant with carpal tunnel syndrome., Entrapment neuropathy of the palmar cutaneous branch of the median nerve concomitant with carpal tunnel syndrome: a case report., A case of the entrapment neuropathy of the palmar cutaneous branch of the median nerve, concomitant with carpal tunnel syndrome is presented., The entrapment syndromes discussed are suprascapular nerve entrapment, carpal tunnel syndrome, cubital tunnel syndrome, meralgia paraesthetica, thoracic outlet syndrome and anterior interosseous nerve syndrome., Carpal tunnel syndrome is a neuropathy resulting from compression of the median nerve as it passes through a narrow tunnel in the wrist on its way to the hand., More typically, carpal tunnel syndrome is the most common peripheral entrapment neuropathy encountered in industry., Carpal tunnel syndrome is the most frequently encountered peripheral nerve entrapment., Carpal tunnel syndrome, an entrapment neuropathy of the median nerve, is rarely seen in childhood., Carpal tunnel syndrome (CTS) is the most common type of peripheral nerve entrapment and is a significant cause of morbidity., Carpal tunnel syndrome (CTS) is a nerve entrapment disorder, involving the median nerve when it passes the carpal tunnel at the wrist., The carpal tunnel syndrome is the most frequent entrapment syndrome of peripheral nerves., BACKGROUND: Compression of the median nerve at the wrist, or carpal tunnel syndrome, is the most commonly recognized nerve entrapme, Carpal tunnel syndrome is the most common of the median nerve entrapments., BACKGROUND: Carpal tunnel syndrome (CTS) is by far the most common entrapment neuropathy (, Introduction: Carpal tunnel syndrome, entrapment of median nerve at the wrist, is one of the most commonly encountered peripheral neuropathies in the up, Carpal tunnel syndrome, a median nerve entrapment neuropathy, is characterized by sensorimotor deficits., Carpal tunnel syndrome (CTS) is a common form of peripheral nerve entrapment, which is observed due to compression of the median nerve at the level of the carpal tunnel in the wrist., [Carpal tunnel syndrome and other nerve entrapment syndromes].[SEP]Relations: cubital tunnel syndrome has relations: disease_disease with ulnar neuropathy, disease_disease with ulnar neuropathy. tarsal tunnel syndrome has relations: disease_disease with tibial neuropathy, disease_disease with tibial neuropathy. ulnar neuropathy has relations: disease_disease with cubital tunnel syndrome, disease_disease with cubital tunnel syndrome. Paresthesia has relations: disease_phenotype_positive with thoracic outlet syndrome, disease_phenotype_positive with thoracic outlet syndrome.", "label": "yes"}
{"id": "converted_3471", "sentence1": "Are the members of the KRAB-ZNF  gene family promoting gene repression?", "sentence2": " The proteins encoded by these genes, whose expression is often tissue-specific, act as epigenetic suppressors contributing to the addition of repressive chromatin marks and DNA methylation., Here, using a reporter system, we show that TRIM28/KRAB-ZNFs alter DNA methylation patterns in addition to H3K9me3 to cause stable gene repression during reprogramming. Using several expression datasets, we identified KRAB-ZNFs (ZNF114, ZNF483, ZNF589) in the human genome that maintain pluripotency., Further analyses of our data sets link GABPa to cognitive disorders, diabetes, KRAB zinc finger (KRAB-ZNF), and human-specific genes., The stem cell zinc finger 1 (SZF1)/ZNF589 protein belongs to the large family of Krüppel-associated box domain-zinc finger (KRAB-ZNF) transcription factors, which are present only in higher vertebrates and epigenetically repress transcription by recruiting chromatin-modifying complexes to the promoter regions of their respective target genes, Because KAP1 is recruited to the DNA via interaction with KRAB-ZNF proteins, we suggest that expression of KRAB-ZNF genes may be controlled via an auto-regulatory mechanism involving KAP1., Interestingly, although most KAP1 binding sites were within core promoter regions, the binding sites near ZNF genes were greatly enriched within transcribed regions of the target gene[SEP]", "label": "yes"}
{"id": "converted_3375", "sentence1": "Are breaks in double stranded DNA associated with ionizing radiation?", "sentence2": "DNA double-strand breaks (DSBs) are major DNA lesions that are constantly formed during physiological processes such as DNA replication, transcription, and recombination, or as a result of exogenous agents such as ionizing radiation, radiomimetic drugs, and genome editing nucleases, Whereas most endogenous and exogenous DNA damaging agents typically generate lesions that are relatively isolated and can be repaired easily, ionizing radiation (IR) also induces clustered lesions causing DNA double strand breaks (DSBs), The induction of DNA interstrand cross-links by ionizing radiation has been largely ignored in favour of studies on double-strand break formation and repair., While much is known about radiation-induced DNA double-strand breaks (DSBs) and their repair, , Exposure of cells to ionizing radiation induces DNA double-strand breaks., DNA double-strand breaks are considered to be the most deleterious lesion induced by ionizing radiation., Influence of chromatin structure on the induction of DNA double strand breaks by ionizing radiation., Ionizing radiation and radiomimetic drugs such as bleomycin, calichieamycin, neocarzinostatin chromophore, and other synthetic agents can produce both single and double strand breaks in DNA., RESULTS BRCA2-defective cells were unable to repair the double-strand DNA breaks induced by ionizing radiation., BACKGROUND Induction of DNA double strand breaks and alterations in the repair of these breaks is implicated in breast carcinogenesis., Double-stranded breaks ( DSBs ) are the most injurious type of DNA damage , being induced by ionizing radiation ( IR ) and cytotoxic agents used in cancer treatment, Double-stranded breaks ( DSBs ) are cytotoxic DNA lesions caused by oxygen radicals , ionizing radiation , and radiomimetic chemicals, Gamma-ray irradiation introduces single and/or double strand breaks into the DNA molecule of the cells.[SEP]", "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]", "label": "yes"}
{"id": "converted_3812", "sentence1": "Can secondary glioblastoma be caused by brain irradiation?", "sentence2": "Prolonged survival in secondary glioblastoma following local injection of targeted alpha therapy with , [Radiation induced glioblastoma: a case report]., We report a surgical case of a 54-year-old woman with a radiation induced glioblastoma., Glioblastoma multiforme following cranial irradiation and chemotherapy for acute lymphocytic leukaemia., The occurrence of glioblastoma multiforme following radiation and chemotherapy in acute lymphocytic leukaemia (ALL) is rare., Glioblastoma multiforme following cranial irradiation and chemotherapy for acute lymphocytic leukaemia. R, exact cause for the development of glioblastoma multiforme following therapy for ALL is not clear. A gen, ndary malignant and benign brain tumors such as astrocytoma, meningioma and glioblastoma have been described in long-term survivors of conventional myeloablative alloBMT. Here w, The authors consider irradiation-induced glioblastomas secondary to primarily verified medulloblastomas in patients who had previously undergone craniospinal irradiation as a component of combined treatment after tumor resection., The authors analyzed patterns of occurrence of irradiation-induced glioblastomas depending on the molecular genetic group and clinical characteristics of patients after primary surgery., Secondary brain tumors rarely arise after cranial irradiation; among them, meningiomas and glioblastomas are the most common and secondary oligodendroglial tumors the most rare., Secondary glioblastoma multiforme (sGBM) can occur after a long latency period following radiation treatment of various diseases including brain tumors, leukemia, and more benign disorders like tinea capitis., Irradiation, however, acts as an oncogenic factor as a delayed effect and it is rare that glioblastoma multiforme develops during the remission period of ALL., A cerebellar glioblastoma was discovered in a 28 year old woman, 5 years after a focal 50 grays brain irradiation for meningioma of the clivus., Glioblastoma multiforme following cranial irradiation and chemotherapy for acute lymphocytic leukaemia. Report of 3 cases., Secondary tumors including glioblastomas are under special attention since their occurrence is associated with a fatal outcome., We describe a case of radiation-induced glioblastoma after radiotherapy for germinoma., [A Case of Radiation-induced Glioblastoma 29 Years after Treatments for Germinoma]., Paradoxically, radiation is also a risk factor for GBM development, raising the possibility that radiotherapy of brain tumors could promote tumor recurrence or trigger secondary gliomas., An SMN may have a benign course, as in meningioma, or be a dilemma for the patient, as in glioblastoma., During a median of 2 years of follow-up review after the diagnosis of a secondary tumour, 3 patients died related to the secondary tumours (2 sarcomas, 1 glioblastoma), one died of a recurrent primary glioma, while the remaining 7 have been alive for from 10 months to 12 years after being treated for the secondary tumours (median: 3 years). , In particular, children treated with X-irradiation for acute lymphoblastic leukemia show a significantly elevated risk of developing gliomas and primitive neuroectodermal tumor (PNET), often within 10 years after therapy. TP53 mutations are frequent in low-grade gliomas and secondary glioblastomas derived therefrom., Pathologic diagnoses were one glioblastoma, two cases of anaplastic astrocytoma, one medulloblastoma, one low-grade glioma, one high-grade glial tumor, and one atypical meningioma., A 22 year-old-man with acute lymphoblastic leukaemia had received prophylactic cranial irradiation and intrathecal chemotherapy. Eighteen years later a cerebellar glioblastoma multiforme was diagnosed. , She developed glioblastoma 5.7 years after the initial GK surgery.[SEP]Relations: acute lymphoblastic/lymphocytic leukemia has relations: disease_disease with acute lymphoblastic leukemia, disease_disease with acute lymphoblastic leukemia. Medulloblastoma has relations: disease_phenotype_positive with medulloblastoma, disease_phenotype_positive with medulloblastoma.", "label": "yes"}
{"id": "converted_2259", "sentence1": "Does TUC.338 inhibit colorectal cancer?", "sentence2": "TUC.338 promotes invasion and metastasis in colorectal cancer., Until now, the role of TUC.338 in colorectal cancers remains undefined. This study revealed that TUC.338 is significantly up-regulated in colorectal cancers (CRC) tissue and CRC cell lines, and the up-regulated TUC.338 is associated with lymph node metastasis.,  Thus, these findings suggested that TUC.338 acts as a novel oncogene by targeting the TIMP-1 gene thus promoting colorectal cancer cell migration and invasion., Thus, these findings suggested that TUC.338 acts as a novel oncogene by targeting the TIMP-1 gene thus promoting colorectal cancer cell migration and invasion., This study revealed that TUC.338 is significantly up-regulated in colorectal cancers (CRC) tissue and CRC cell lines, and the up-regulated TUC.338 is associated with lymph node metastasis., TUC.338 promotes invasion and metastasis in colorectal cancer.[SEP]Relations: malignant colon neoplasm has relations: disease_disease with colorectal cancer, disease_disease with colorectal cancer. colorectal carcinoma has relations: disease_disease with colorectal cancer, disease_disease with colorectal cancer.", "label": "no"}
{"id": "converted_1548", "sentence1": "Is the gene SLC6A2 associated with orthostatic intolerance?", "sentence2": "Orthostatic intolerance is a debilitating syndrome characterized by tachycardia on assumption of upright posture. The norepinephrine (NE) transporter (NET) has been implicated in a genetic form of the disorder. , Thus attenuated baroreflex function and reduced sympathetic outflow may contribute to the orthostatic intolerance of severe NET deficiency., A mutation in the human norepinephrine transporter gene (SLC6A2) associated with orthostatic intolerance disrupts surface expression of mutant and wild-type transporters.,  Recently, our laboratory reported a polymorphism in the human NET (hNET) gene A457P in an individual with the autonomic disorder orthostatic intolerance (OI). , Nonsynonymous single nucleotide polymorphisms (SNPs) in the human NET (hNET) gene that influence transporter function can contribute to disease, such as the nonfunctional transporter, A457P, identified in orthostatic intolerance. , Orthostatic intolerance is not necessarily related to a specific mutation (Ala457Pro) in the human norepinephrine transporter gene., We propose that chromatin-modifying events associated with SLC6A2 gene suppression may constitute a mechanism of POTS., The goal of the present study was to further characterize the role and regulation of the SLC6A2 gene in POTS., In the absence of altered SLC6A2 gene sequence or promoter methylation, this reduced expression was directly correlated with chromatin modifications.  We propose that chromatin-modifying events associated with SLC6A2 gene suppression may constitute a mechanism of POTS., A coding mutation in the norepinephrine transporter gene (SLC6A2) sequence has been reported in 1 family kindred only. The goal of the present study was to further characterize the role and regulation of the SLC6A2 gene in POTS.[SEP]Relations: Defective SLC6A2 causes orthostatic intolerance (OI) has relations: pathway_protein with SLC6A2, pathway_protein with SLC6A2.", "label": "yes"}
{"id": "converted_732", "sentence1": "Is autism one of the characteristics of Moebius syndrome?", "sentence2": "The diagnosis of Moebius syndrome, a rare congenital disorder, is primarily based on congenital facial and abducent nerve palsy. Involvement of other cranial nerves is also common. Occasionally the V, X, XI, and XII cranial nerves are involved, resulting in a difficulty to chew, swallow, and cough, which often leads to respiratory complications. Mental retardation and autism have been reported in some cases, Moebius sequence is a rare congenital disorder usually defined as a combination of facial weakness with impairment of ocular abduction. A strong association of Moebius sequence with autism spectrum disorders (ASDs) has been suggested in earlier studies with heterogenous age groups, Certain genetic syndromes are providing us with extremely valuable information about the role played by genetics in autism. This is the case of the following syndromes: Angelman syndrome, Prader-Willi syndrome, 15q11-q13 duplication, fragile X syndrome, fragile X premutation, deletion of chromosome 2q, XYY syndrome, Smith-Lemli-Opitz syndrome, Apert syndrome, mutations in the ARX gene, De Lange syndrome, Smith-Magenis syndrome, Williams syndrome, Rett syndrome, Noonan syndrome, Down syndrome, velo-cardio-facial syndrome, myotonic dystrophy, Steinert disease, tuberous sclerosis, Duchenne's disease, Timothy syndrome, 10p terminal deletion, Cowden syndrome, 45,X/46,XY mosaicism, Myhre syndrome, Sotos syndrome, Cohen syndrome, Goldenhar syndrome, Joubert syndrome, Lujan-Fryns syndrome, Moebius syndrome, hypomelanosis of Ito, neurofibromatosis type 1, CHARGE syndrome and HEADD syndrome., Seventeen children and young adults with Moebius syndrome were examined with a view to finding symptoms of autism. Some 40% of the group showed all or many of the symptoms typical of autistic disorder, Fifty-nine cases with infantile autism/autistic disorder were subclassified according to associated medical condition (fragile-X, tuberous sclerosis, neurofibromatosis, hypo-melanosis of Ito, Moebius syndrome, Rett syndrome, and a 'new' syndrome associated with a marker chromosome)., Autism spectrum disorders in children and adolescents with Moebius sequence., Moebius sequence and autism spectrum disorders--less frequently associated than formerly thought., A strong association of Moebius sequence with autism spectrum disorders (ASDs) has been suggested in earlier studies with heterogenous age groups., Autistic behaviour in Moebius syndrome., The high frequency of autistic symptoms in Moebius syndrome might be a marked overrepresentation and could be suggestive of a common underlying neurobiological deficit at the brainstem level., Autism spectrum disorders in children and adolescents with Moebius sequence., Moebius sequence and autism spectrum disorders--less frequently associated than formerly thought., Autistic behaviour in Moebius syndrome.[SEP]Relations: Intellectual disability has relations: disease_phenotype_positive with Sotos syndrome, disease_phenotype_positive with Smith-Magenis syndrome, disease_phenotype_positive with CHARGE syndrome, disease_phenotype_positive with tuberous sclerosis, disease_phenotype_positive with Williams syndrome, disease_phenotype_positive with Down syndrome, disease_phenotype_positive with Joubert syndrome, disease_phenotype_positive with Smith-Lemli-Opitz syndrome, disease_phenotype_positive with Noonan syndrome, disease_phenotype_positive with Sotos syndrome, disease_phenotype_positive with Smith-Magenis syndrome, disease_phenotype_positive with CHARGE syndrome, disease_phenotype_positive with tuberous sclerosis, disease_phenotype_positive with Williams syndrome, disease_phenotype_positive with Down syndrome, disease_phenotype_positive with Joubert syndrome, disease_phenotype_positive with Smith-Lemli-Opitz syndrome, disease_phenotype_positive with Noonan syndrome. Iris hypopigmentation has relations: disease_phenotype_positive with Prader-Willi syndrome, disease_phenotype_positive with Prader-Willi syndrome. congenital nervous system disorder has relations: disease_disease with Williams syndrome, disease_disease with Angelman syndrome, disease_disease with Smith-Lemli-Opitz syndrome, disease_disease with Smith-Magenis syndrome, disease_disease with fragile X syndrome, disease_disease with neurofibromatosis, disease_disease with Williams syndrome, disease_disease with Angelman syndrome, disease_disease with Smith-Lemli-Opitz syndrome, disease_disease with Smith-Magenis syndrome, disease_disease with fragile X syndrome, disease_disease with neurofibromatosis.", "label": "yes"}
{"id": "converted_944", "sentence1": "Has protein citrullination been implicated in rheumatoid arthritis?", "sentence2": ": Citrullination has become a hot topic within recent years due to its involvement in diseases such as rheumatoid arthritis (RA), multiple sclerosis and fibrosis. , Current literature suggests that increased levels of citrullinated proteins are found in several if not all inflammatory diseases. , Antibodies directed against citrullinated proteins and peptides (ACPAs) are the most specific serological markers available for diagnosing RA. , Citrullination of proteins is well described in rheumatoid arthritis (RA), and hypercitrullination of proteins may be related to inflammation in general. , Some ACPA are remarkably effective as diagnostics in autoimmune disorders, most notably rheumatoid arthritis (RA). Several ACPA can be observed before other clinical RA manifestations are apparent. , Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by the presence of rheumatoid factor (RF) and anti-citrullinated protein/peptide autoantibodies (ACPAs). , Anti-citrullinated peptides as autoantigens in rheumatoid arthritis-relevance to treatment., The implications of citrullination affecting integrin binding in disease open up a new area of study and might have implications for the pathogenesis of inflammatory diseases like rheumatoid arthritis and periodontitis., In this paper, we will review the three of the main classes of PTMs already associated with RA: citrullination, carbamylation, and oxidation., Citrullinated collagen II (CII) is a well-known autoantigen in rheumatoid arthritis (RA). , Among the RA-associated autoantibodies, especially anti-citrullinated protein antibodies (ACPAs) have been studied intensively in the last decade., Protein citrullination is a posttranslational modification that has attracted increased attention, especially for its involvement in rheumatoid arthritis (RA)., Identification of citrullinated cellular fibronectin in synovial fluid from patients with rheumatoid arthritis., Cellular fibronectin (cFn) has been implicated in the pathogenesis of rheumatoid arthritis (RA), and we previously demonstrated the presence of citrullinated cFn in rheumatoid synovial tissues. , . In rheumatoid arthritis, PAD4 and protein citrullination are increased in inflamed joints, and anti-citrullinated protein antibodies (ACPAs) form against citrullinated antigens are formed. [SEP]Relations: Rheumatoid arthritis has relations: disease_phenotype_positive with rheumatoid arthritis, disease_phenotype_positive with rheumatoid arthritis. Anti-citrullinated protein antibody positivity has relations: disease_phenotype_positive with rheumatoid arthritis, disease_phenotype_positive with rheumatoid arthritis. Rheumatoid factor positive has relations: disease_phenotype_positive with rheumatoid arthritis, disease_phenotype_positive with rheumatoid arthritis.", "label": "yes"}
{"id": "converted_983", "sentence1": "Have mutations in the ZEB2 gene been found in any human syndrome?", "sentence2": "Mowat-Wilson syndrome is a genetic disease caused by heterozygous mutations or deletions of the zinc finger E-box-binding homeobox 2 (ZEB2) gene, Mowat-Wilson syndrome (MWS; OMIM#235730) have characteristic facial features, a variety of congenital anomalies such as Hirschsprung disease, and intellectual disabilities caused by mutation or deletion of ZEB2 gene., owat-Wilson syndrome (MWS) is a genetic disease caused by heterozygous mutations or deletions of the ZEB2 gene, MWS is caused by de novo heterozygous mutations in the ZEB2 gene, The cause of MWS is a de novo mutation in the ZEB2 gene, owat-Wilson syndrome (MWS) is a genetic disease caused by heterozygous mutations or deletions of the ZEB2 gene, MWS have a heterozygous loss-of-function mutation in the zinc finger E-box protein 2 (ZEB2) gene, also called SIP1 (Smad-interacting protein 1) and ZFHX1B,,  human Mowat-Wilson syndrome, we suggest that deletion of ZEB2, is responsible for most of the effects of the mutation, Mutations at the hZeb2 locus cause Mowat-Wilson syndrome (MWS), Mowat-Wilson syndrome and a mutation in ZEB2, owat-Wilson syndrome (MWS) is caused by a heterozygous mutation or deletion of the ZEB2 gene, The syndrome is caused by mutations or deletions of the ZEB2 gene, owat-Wilson syndrome (MWS) is an autosomal dominant intellectual disability syndrome, single-copy ZEB2 gene deletion at 2q22.3 consistent with Mowat-Wilson syndrome, Mowat-Wilson syndrome, confirmed by molecular analysis as a heterozygous deletion of the ZEB2 gene., deletion encompassing ZEB2, the gene responsible for the Mowat-Wilson syndrome,  Six patients had deletions in the ZEB2 gene, ZEB2 gene analysis for Mowat-Wilson syndrome, Mowat-Wilson syndrome (MWS) like appearance was noted. The disease is caused by mutation or deletion of ZEB2 gene, owat-Wilson syndrome (MWS; OMIM #235730) is a genetic condition caused by heterozygous mutations or deletions of the ZEB2 gene, owat-Wilson syndrome (MWS) is an autosomal dominant developmental disorder with mental retardation and variable multiple congenital abnormalities due to mutations of the ZEB2 (ZFHX1B) , MWS is caused by heterozygous mutations or deletions in the Zinc finger E-box-binding homeobox 2 gene, ZEB2, previously called ZFHX1B (SIP1), owat-Wilson syndrome (MWS) is a multiple congenital anomaly-mental retardation complex caused by mutations in the Zinc Finger Homeobox 1 B gene (ZFHX1B), the ZFHX1B gene, which is known to be involved in the Mowat-Wilson syndrom, de novo heterozygous mutations or deletions of the ZFHX1B gene located at 2q22, owat-Wilson syndrome (MWS) is a recently delineated mental retardation (MR)-multiple congenital anomaly syndrome, FHX1B mutations in patients with Mowat-Wilson syndrome, Mutations leading to haploinsufficiency of the ZFHX1B gene, mutation in the ZFHX1B gene associated with an atypical Mowat-Wilson syndrome phenotype, ZFHX1B mutation associated with a mild Mowat-Wilson syndrome, Patients with zinc finger homeo box 1B (ZFHX1B) mutations or deletions develop multiple congenital anomalies including Hirschsprung disease, known as Mowat-Wilson syndrome (MWS), Heterozygous mutations or deletions involving the gene ZFHX1B (previously SIP1) [OMIM 605802] have recently been found to cause MWS,  ZFHX1B deletions, splice site or truncating mutations were detected in all 28 patients classified as typical MWS, Mowat-Wilson syndrome with deletion/mutation in the zinc finger homeo box 1B gene (ZFHX1B),  mutations in the zinc finger homeo box 1B gene, ZFHX1B (SIP1), ZFHX1B gene transcripts during mouse and human development supports the various clinical manifestations of the \"Mowat-Wilson\" syndrome,  ZFHX1B mutations cause a complex developmental phenotype characterized by severe mental retardation (MR) and multiple congenital defects, mutation of the zinc finger homeo box 1 B gene in syndromic corpus callosum agenesis (Mowat-Wilson syndrome, syndrome is the result of heterozygous deletions or truncating mutations of the ZFHX1B (SIP1) gene, humans with Zfhx1b mutations (Mowat-Wilson syndrome, syndrome occurs as a result of heterozygous mutations or deletions in the zinc finger E-box-binding homeobox 2 gene, ZEB2, previously called ZFHX1B (SIP1), owat-Wilson syndrome (MWS) is a recently delineated mental retardation;, Mowat-Wilson syndrome is a congenital syndrome caused by a defect of the transcriptional repressor ZFHX1B (SIP1), Mowat-Wilson syndrome patients, and all siblings had the same E87X nonsense mutation in ZFHX1B[SEP]Relations: hirschsprung disease, susceptibility to has relations: disease_disease with Hirschsprung disease, disease_disease with Hirschsprung disease. ZEB2 has relations: disease_protein with Hirschsprung disease, disease_protein with Hirschsprung disease. Mowat-Wilson syndrome has relations: disease_protein with ZEB2, disease_protein with ZEB2. Muckle-Wells syndrome has relations: disease_protein with ZEB2, disease_protein with ZEB2. Intellectual disability has relations: disease_phenotype_positive with Hirschsprung disease, disease_phenotype_positive with Hirschsprung disease.", "label": "yes"}
{"id": "converted_2186", "sentence1": "Can acupuncture cause spinal epidural hematoma?", "sentence2": "RESULTS: A 54-year-old woman, a 38-year-old woman, and a 60-year-old man with hemiplegia by cervical subdural or epidural hematoma after cervical posterior paraspinal muscle needling without direct invasion (intramuscular stimulation, acupuncture, or intramuscular lidocaine) were observed., Acute spinal subdural hematoma with hemiplegia after acupuncture: a case report and review of the literature., Although acupuncture has been a popular method for the management of pain control, we encountered the first case of SDH after acupuncture.PURPOSE: The purpose of this case report was to present the first case of subdural hematoma after acupuncture and the reasons for the risks of blind cervical acupuncture., SUMMARY OF BACKGROUND DATA: Epidural hematomas after dry needling are quite unusual and only a few cases of epidural hematoma after acupuncture have been reported in the literature., Spinal epidural hematoma is a rare complication associated with pain control procedures such as facet block, acupuncture, epidural injection, etc. , Unintentional acupuncture needling of the thoracic spinal canal produced a spinal epidural hematoma and subarachnoid hemorrhage., Spinal epidural hematoma is a rare complication associated with pain control procedures such as facet block, acupuncture, epidural injection, etc., Spinal epidural hematoma with subarachnoid hemorrhage caused by acupuncture., However, subarachnoid hemorrhage and spinal epidural hematoma have been reported to occur after acupuncture in the posterior neck., A retrospective case report.The objective of this article is to report an unusual complication of dry needling.Epidural hematomas after dry needling are quite unusual and only a few cases of epidural hematoma after acupuncture have been reported in the literature, Spinal epidural hematoma with subarachnoid hemorrhage caused by acupuncture, Spinal epidural hematoma is a rare complication associated with pain control procedures such as facet block, acupuncture, epidural injection, etc, Unintentional acupuncture needling of the thoracic spinal canal produced a spinal epidural hematoma and subarachnoid hemorrhage, Spinal epidural hematoma with subarachnoid hemorrhage caused by acupuncture.[SEP]", "label": "yes"}
{"id": "converted_4036", "sentence1": "Is colistin an antibiotic?", "sentence2": "all antibiotics tested, apart from colistin, , Among the selected antibiotics, there were 12 fluoroquinolone antibiotics (tosufloxacin, levofloxacin, sparfloxacin, clinafloxacin, pazufloxacin, gatifloxacin, enrofloxacin, lomefloxacin, norfloxacin, fleroxacin, flumequine, ciprofloxacin), 15 beta-lactam or cephalosporin antibiotics (cefmenoxime, cefotaxime, ceftizoxime, cefotiam, cefdinir, cefoperazone, cefpiramide, cefamandole, cefixime, ceftibuten, cefmetazole, cephalosporin C, aztreonam, piperacillintazobactam, mezlocillin), 3 tetracycline antibiotics (meclocycline, doxycycline, tetracycline), 2 membrane-acting agents (colistin and clofoctol),,  Mice received an antibiotic cocktail (kanamycin, gentamicin, colistin, metronidazole, and vancomycin) for 96 h.[SEP]", "label": "yes"}
{"id": "converted_3785", "sentence1": "Is yeast fbp1 affected by glucose starvation stress?", "sentence2": "Histone Chaperone Asf1 Is Required for the Establishment of Repressive Chromatin in Schizosaccharomyces pombe fbp1 Gene Repression, chromatin is reconstituted in the fission yeast Schizosaccharomyces pombefbp1 gene, which is robustly induced upon glucose starvation but tightly repressed under glucose-rich conditions., The Schizosaccharomyces pombe fbp1 gene, which encodes fructose-1,6-bis-phosphatase, is transcriptionally repressed by glucose through the activation of the cAMP-dependent protein kinase A (PKA) and transcriptionally activated by glucose starvation through the activation of a mitogen-activated protein kinase (MAPK). , Antisense transcripts from the fission yeast fbp1 locus (fbp1-as) are expressed in glucose-rich conditions and anticorrelated with transcription of metabolic stress-induced lncRNA (mlonRNA) and mRNA on the sense strand during glucose starvation., In fission yeast, glucose starvation triggers lncRNA transcription across promoter regions of stress-responsive genes including fbp1 (fructose-1,6-bisphosphatase1)., We herein show that the chromatin configuration is altered into an accessible state within 290 bp downstream from the initiation site of metabolic-stress-induced lncRNAs (mlonRNAs) in the promoter of the fission yeast fbp1 gene, whose transcription is massively induced upon glucose starvation., Cation stress and glucose starvation selectively caused chromatin structure alteration around CRE-like sequences in cta3(+) and fbp1(+) promoters, respectively, in correlation with transcriptional activation.,  herein show that the chromatin configuration is altered into an accessible state within 290 bp downstream from the initiation site of metabolic-stress-induced lncRNAs (mlonRNAs) in the promoter of the fission yeast fbp1 gene, whose transcription is massively induced upon glucose starvation. Chr, fission yeast, glucose starvation triggers lncRNA transcription across promoter regions of stress-responsive genes including fbp1 (fructose-1,6-bisphosphatase1). At, isense transcripts from the fission yeast fbp1 locus (fbp1-as) are expressed in glucose-rich conditions and anticorrelated with transcription of metabolic stress-induced lncRNA (mlonRNA) and mRNA on the sense strand during glucose starvation. Here,, locus (fbp1-as) are expressed in glucose-rich conditions and anticorrelated with transcription of metabolic stress-induced lncRNA (mlonRNA) and mRNA on the sense strand during glucose starvation., Furthermore, fbp1-as and antisense RNA at other stress-responsive loci are promptly degraded via the cotranslational nonsense-mediated decay (NMD) pathway., These results suggest NMD may potentiate the swift disappearance of antisense RNAs in response to cellular stress., Antisense RNA has emerged as a crucial regulator of opposite-strand protein-coding genes in the long noncoding RNA (lncRNA) category, but little is known about their dynamics and decay process in the context of a stress response., xic growth. The stress-activated protein kinase (SAPK) pathway and its effectors, Sty1 MAPK and transcription factor Atf1, play a critical role in the adaptation of fission yeast to grow on alternative non-fermentable carbon sources by inducing the expression of fbp1+ gene, coding for the gluconeogenic enzyme fructose-1,6-bis[SEP]", "label": "yes"}
{"id": "converted_3792", "sentence1": "Is tocilizumab a csDMARD?", "sentence2": "The task force agreed on 5 overarching principles and 12 recommendations concerning use of conventional synthetic (cs) DMARDs (methotrexate (MTX), leflunomide, sulfasalazine); glucocorticoids (GCs); biological (b) DMARDs (tumour necrosis factor inhibitors (adalimumab, certolizumab pegol, etanercept, golimumab, infliximab), abatacept, rituximab, tocilizumab, sarilumab and biosimilar (bs) DMARDs) and targeted synthetic (ts) DMARDs (the Janus kinase (JAK) inhibitors tofacitinib, baricitinib, filgotinib, upadacitinib). [SEP]", "label": "no"}
{"id": "converted_4377", "sentence1": "Can bergapten cause phototoxicity?", "sentence2": "Furthermore, the phototoxicity of bergapten combined with ultraviolet light has always been mentioned., The phototoxicity of bergapten as a side effect should be further avoided. [SEP]", "label": "yes"}
{"id": "converted_3169", "sentence1": "Is it possible to analyze exosomes with FACS?", "sentence2": "whose presence was validated by a bead-exosome FACS assay., We analyzed exosomes from mouse (C57Bl/6) and breast, lung, and ovarian cancer patient samples and cultured cancer cells with different approaches, including nanoparticle tracking analysis, biolayer interferometry, FACS, and electron microscopy., we applied a technique to generate native fluorescent exosomes characterized by vesicles integrity, size, density, markers expression, and quantifiable by direct FACS analysis, we used a novel strategy for generating metabolically-labeled fluorescent exosomes that can be counted by flow cytometry assay (FACS) and characterized.[SEP]", "label": "yes"}
{"id": "converted_1097", "sentence1": "Does thyroid hormone affect cardiac remodeling?", "sentence2": "The aim of this brief paper is to highlight new developments in understanding the cardioprotective role of thyroid hormone in reverting regulatory networks involved in adverse cardiac remodeling., Thyroid hormone receptor α1 (TRα1) is shown to be critical for the maturation of cardiomyocytes and for the cellular response to stress. TRα1 is altered during post ischemic cardiac remodeling but the physiological significance of this response is not fully understood. , AMI induces downregulation of thyroid hormone signaling and pharmacological inhibition of TRα1 further depresses post-ischemic cardiac function., These findings reveal crucial roles for Dio3 in heart function and remodeling, which may have pathophysiologic implications for human restrictive cardiomyopathy., TH administration after AMI prevented tissue hypothyroidism and resulted in decreased beta-MHC expression, increased wall thickening and normalized wallstress, while stretch-induced p38 MAPK activation was increased. We conclude that diabetes exacerbates post-ischemic cardiac remodeling and that tissue hypothyroidism may be involved in this response., Thyroid hormone can favorably remodel the diabetic myocardium after acute myocardial infarction., It has been previously shown that regulators of physiological growth such as thyroid hormone (TH) can favorably remodel the post ischaemic myocardium., Acute myocardial infarction in diabetic rats results in TH receptor down-regulation with important physiological consequences. TH treatment prevents this response and improves cardiac hemodynamics., TH affects cardiac remodeling by limiting reperfusion injury, and, at later states, by inducing distinct changes in cardiac chamber geometry in a time-dependent manner., Furthermore, administration of TH can convert pathologic to physiologic hypertrophy. These effects are the result of favorable cellular remodeling., Thyroid hormone (TH) is critical in cardiac cell differentiation (regulating contractile proteins and cell geometry) and this effect could be potentially exploited therapeutically in reversing the process of de-differentiation which underlies postischemic cardiac remodeling. , TH treatment partially reverses cardiac dysfunction in rats with old myocardial infarction by favorably changing cardiac chamber geometry and expression of myosin isoforms. Thyroid hormone, unlike current treatments, appears to be a paradigm of therapeutic intervention which aims at restoring cardiac geometry and may prove new effective treatment for heart failure., Changes in thyroid hormone (TH)-TH receptors (TRs) axis occur in the course of post-infarction cardiac remodeling and seem to contribute to cardiac fetal phenotype. TH can \"rebuild\" the post-infarcted heart by preventing the fetal-like pattern of contractile proteins expression, normalizing wall tension, and optimizing cardiac chamber geometry. , TH, apart from its \"classical\" actions on cardiac contractility and heart rhythm, appears to regulate various intracellular signaling pathways related to stress responses and cardiac remodelling., More importantly, experimental and clinical studies demonstrate that TH can limit ischaemic injury, attenuate cardiac remodeling and improve cardiac hemodynamics. , Thyroid hormone attenuates cardiac remodeling and improves hemodynamics early after acute myocardial infarction in rats., Thyroid hormone administration early after infarction attenuates cardiac remodeling and significantly improves myocardial performance., It has previously been shown that thyroid hormone can reverse cardiac remodeling in failing hearts by reducing myocardial wall stress due to the unique changes induced in cardiac myocyte shape. [SEP]Relations: tyrosine 3-monooxygenase activity has relations: molfunc_protein with TH, molfunc_protein with TH.", "label": "yes"}
{"id": "converted_2598", "sentence1": "Does MC1R palmitoylation reduce pigmentation?", "sentence2": "The melanocortin-1 receptor (MC1R), a G-protein-coupled receptor, has a crucial role in human and mouse pigmentation. Activation of MC1R in melanocytes by α-melanocyte-stimulating hormone (α-MSH) stimulates cAMP signalling and melanin production and enhances DNA repair after ultraviolet irradiation. , MC1R palmitoylation, primarily mediated by the protein-acyl transferase ZDHHC13, is essential for activating MC1R signalling, which triggers increased pigmentation, ultraviolet-B-induced G1-like cell cycle arrest and control of senescence and melanomagenesis in vitro and in vivo., The results highlight a central role for MC1R palmitoylation in pigmentation and protection against melanoma.[SEP]Relations: melanocytic neoplasm has relations: disease_disease with melanoma, disease_disease with melanoma. melanocyte-stimulating hormone receptor activity has relations: molfunc_protein with MC1R, molfunc_protein with MC1R.", "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]", "label": "no"}
{"id": "converted_471", "sentence1": "Is there a crystal structure of the full-length of the flaviviridae NS5(Methyltransferase - RNA depended RNA Polymerase) ?", "sentence2": " flavivirus NS5 harbors a methyltransferase (MTase) in its N-terminal ≈ 265 residues and an RNA-dependent RNA polymerase (RdRP) within the C-terminal part. One of the major interests and challenges in NS5 is to understand the interplay between RdRP and MTase as a unique natural fusion protein in viral genome replication and cap formation. Here, we report the first crystal structure of the full-length flavivirus NS5 from Japanese encephalitis virus. , (DENV) nonstructural protein 5 (NS5) is composed of two globular domains separated by a 10-residue linker. The N-terminal domain participates in the synthesis of a mRNA cap 1 structure ((7Me)GpppA(2'OMe)) at the 5' end of the viral genome and possesses guanylyltransferase, guanine-N7-methyltransferase, and nucleoside-2'O-methyltransferase activities. The C-terminal domain is an RNA-dependent RNA polymerase responsible for viral RNA synthesis. Although crystal structures of the two isolated domains have been obtained, there are no structural data for full-length NS5. It is also unclear whether the two NS5 domains interact with each other to form a stable structure in which the relative orientation of the two domains is fixed. To investigate the structure and dynamics of DENV type 3 NS5 in solution, we conducted small-angle X-ray scattering experiments with the full-length protein. NS5 was found to be monomeric and well-folded under the conditions tested., West Nile virus (WNV) NS5 protein contains a methyltransferase (MTase) domain involved in RNA capping and an RNA-dependent RNA polymerase (RdRp) domain essential for virus replication. Crystal structures of individual WNV MTase and RdRp domains have been solved; however, the structure of full-length NS5 has not been determined. To gain more insight into the structure of NS5 and interactions between the MTase and RdRp domains, we generated a panel of seven monoclonal antibodies (mAbs) to the NS5 protein of WNV (Kunjin strain) and mapped their binding sites using a series of truncated NS5 proteins and synthetic peptides. Binding sites of four mAbs (5D4, 4B6, 5C11 and 6A10) were mapped to residues 354-389 in the fingers subdomain of the RdRp. This is consistent with the ability of these mAbs to inhibit RdRp activity in vitro and suggests that this region represents a potential target for RdRp inhibitors. Using a series of synthetic peptides, we also identified a linear epitope (bound by mAb 5H1) that mapped to a 13 aa stretch surrounding residues 47 and 49 in the MTase domain, a region predicted to interact with the palm subdomain of the RdRp. The failure of one mAb (7G6) to bind both N- and C-terminally truncated NS5 recombinants indicates that the antibody recognizes a conformational epitope that requires the presence of residues in both the MTase and RdRp domains. [SEP]", "label": "yes"}
{"id": "converted_828", "sentence1": "Is muscle lim protein (MLP) involved in cardiomyopathies?", "sentence2": "Muscle LIM protein (MLP) has been proposed to be a central player in the pathogenesis of heart muscle disease. In line with this notion, the homozygous loss of MLP results in cardiac hypertrophy and dilated cardiomyopathy. Moreover, MLP is induced in several models of cardiac hypertrophy such as aortic banding and myocardial infarction. , Muscle LIM protein (MLP) null mice are often used as a model for human dilated cardiomyopathy., A lack of MLP leads to an age-dependent impairment of excitation-contraction coupling with resulting contractile dysfunction and secondary fibrosis., Loss of murine MLP results in dilated cardiomyopathy, and mutations in human MLP lead to cardiac hypertrophy, indicating a critical role for MLP in maintaining normal cardiac function., Our data indicate that MLP contributes to muscle stiffness and is necessary for maximum work and power generation., Interestingly, MLP was also found to be down-regulated in humans with heart failure (Zolk et al. Circulation 101:2674-2677, 2000) and MLP mutations are able to cause hypertrophic and dilated forms of cardiomyopathy in humans (Bos et al. Mol Genet Metab 88:78-85, 2006; Geier et al. Circulation 107:1390-1395, 2003; Hershberger et al. Clin Transl Sci 1:21-26, 2008; Knöll et al. Cell 111:943-955, 2002; Knöll et al. Circ Res 106:695-704, 2010; Mohapatra et al. Mol Genet Metab 80:207-215, 2003)., MLP soon became an important model for experimental cardiology when it was first demonstrated that MLP deficiency leads to myocardial hypertrophy followed by a dilated cardiomyopathy and heart failure phenotype (Arber et al. Cell 88:393-403, 1997). , Previous studies have shown an association between CSRP3 missense mutations and either dilated cardiomyopathy (DCM) or HCM, but all these studies were unable to provide comprehensive genetic evidence for a causative role of CSRP3 mutations. , We used a newly designed monoclonal antibody to show that muscle LIM protein (MLP), the protein encoded by CSRP3, is mainly a cytosolic component of cardiomyocytes and not tightly anchored to sarcomeric structures. Our functional data from both in vitro and in vivo analyses suggest that at least one of MLP's mutated forms seems to be destabilized in the heart of HCM patients harbouring a CSRP3 missense mutation., Muscle LIM protein (MLP) is a cytoskeletal protein located at the Z-disc of sarcomeres. Mutations in the human MLP gene are associated with hypertrophic and dilated cardiomyopathy., Our data demonstrate that Mlp84B is essential for normal cardiac function and establish the Drosophila model for the investigation of the mechanisms connecting defective cardiac Z-disc components to the development of cardiomyopathy., Muscle LIM protein (MLP) is a cytoskeletal LIM-only protein expressed in striated muscle. Mutations in human MLP are associated with cardiomyopathy;, TTN-encoded titin, CSRP3-encoded muscle LIM protein, and TCAP-encoded telethonin are Z-disc proteins essential for the structural organization of the cardiac sarcomere and the cardiomyocyte's stretch sensor. All three genes have been established as cardiomyopathy-associated genes for both dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM). , Approximately 4.1% of unrelated patients had HCM-associated MLP or TCAP mutations. MLP/TCAP-HCM phenotypically mirrors myofilament-HCM and is more severe than the subset of patients who still remain without a disease-causing mutation. The precise role of W4R-MLP in the pathogenesis of either DCM or HCM warrants further investigation., MLP (muscle-LIM-protein) deficient mice develop DCM and changes in the mechanical coupling of cardiomyocytes result in alterations at the intercalated disks and enhanced accumulation of adherens junction proteins., Targeted deletion of cytoskeletal muscle LIM protein (MLP) in mice consistently leads to dilated cardiomyopathy (DCM) after one or more months. , In summary, young MLPKO mice revealed substantial alterations in passive myocardial properties and relaxation time, but not in most systolic characteristics. These results indicate that the progression to heart failure in the MLPKO model may be driven by diastolic myocardial dysfunction and abnormal passive properties rather than systolic dysfunction., Mice lacking the muscle LIM protein (MLP) develop morphological and clinical signs resembling human dilated cardiomyopathy and heart failure., Our results show that the absence of MLP causes a local loss of mitochondria. We hypothesize that this is caused by a disturbed interaction between cytoskeleton and mitochondria, which interferes with energy sensing and energy transfer. Recovery of energy depletion by stimulating mitochondrial biogenesis might be a useful therapeutic strategy for improving the energy imbalance in heart failure., Previous work has shown that mutations in muscle LIM protein (MLP) can cause hypertrophic cardiomyopathy (HCM). In order to gain an insight into the molecular basis of the disease phenotype, we analysed the binding characteristics of wild-type MLP and of the (C58G) mutant MLP that causes hypertrophic cardiomyopathy., The molecular basis for HCM-causing mutations in the MLP gene might therefore be an alteration in the equilibrium of interactions of the ternary complex MLP-N-RAP-alpha-actinin., Muscle LIM protein (MLP) is a member of the cysteine-rich protein (CRP) family and has been implicated in both myogenesis and sarcomere assembly. In the latter role, it binds zyxin and alpha-actinin, both of which are involved in actin organization. An MLP-deficient mouse has been described; these mice develop dilated cardiomyopathy and heart failure., We identified a patient with DCM and EFE, having a mutation in MLP with the residue lysine 69 substituted by arginine (K69R). , MLP-knockout mice develop a marked cardiac hypertrophy reaction and dilated cardiomyopathy (DCM). MLP is therefore a candidate gene for heritable forms of hypertrophic cardiomyopathy (HCM) and DCM in humans., Family studies revealed cosegregation of clinically affected individuals with the respective mutations in MLP. CONCLUSION: Here, we present evidence that mutations in the CRP3/MLP gene can cause HCM., The skeletal muscle LIM protein 1 (SLIM1) is highly expressed in skeletal and cardiac muscle, and its expression is downregulated significantly in dilated human cardiomyopathy. , Targeted disruption of muscle LIM protein (MLP) has previously been shown to result in dilated cardiomyopathy with many of the clinical signs of heart failure, although the effects of MLP disruption on passive ventricular mechanics and myocyte architecture are not known., These results suggest that the disruption of the cytoskeletal protein MLP results in less compliant passive tissue and concomitant structural alterations in the three-dimensional myocyte architecture that may in part explain the ventricular dysfunction in the dilated heart.,  Mutations in cysteine and glycine-rich protein 3 (CSRP3), the gene encoding MLP, have been directly associated with human cardiomyopathies, whereas aberrant expression patterns are reported in human cardiac and skeletal muscle diseases., Muscle LIM protein (MLP) has been proposed to be a central player in the pathogenesis of heart muscle disease., Previous work has shown that mutations in muscle LIM protein (MLP) can cause hypertrophic cardiomyopathy (HCM)[SEP]Relations: Cardiomyopathy has relations: disease_phenotype_positive with hypertrophic cardiomyopathy, disease_phenotype_positive with dilated cardiomyopathy, disease_phenotype_positive with hypertrophic cardiomyopathy, disease_phenotype_positive with dilated cardiomyopathy. Congestive heart failure has relations: disease_phenotype_positive with hypertrophic cardiomyopathy, disease_phenotype_positive with dilated cardiomyopathy, disease_phenotype_positive with hypertrophic cardiomyopathy, disease_phenotype_positive with dilated cardiomyopathy. MARCKSL1 has relations: anatomy_protein_present with heart, cellcomp_protein with cytoskeleton, anatomy_protein_present with heart, cellcomp_protein with cytoskeleton. Hypertrophic cardiomyopathy has relations: disease_phenotype_positive with hypertrophic cardiomyopathy, disease_phenotype_positive with dilated cardiomyopathy, disease_phenotype_positive with hypertrophic cardiomyopathy, disease_phenotype_positive with dilated cardiomyopathy, disease_phenotype_positive with hypertrophic cardiomyopathy, disease_phenotype_positive with dilated cardiomyopathy, disease_phenotype_positive with hypertrophic cardiomyopathy, disease_phenotype_positive with dilated cardiomyopathy. dilated cardiomyopathy has relations: disease_disease with hypertrophic cardiomyopathy, disease_disease with hypertrophic cardiomyopathy. Cardiomyocyte hypertrophy has relations: disease_phenotype_positive with dilated cardiomyopathy, disease_phenotype_positive with dilated cardiomyopathy.", "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]", "label": "no"}
{"id": "converted_3776", "sentence1": "Is MAGE-A3 immunotherapeutic effective for non-small-cell lung cancer?", "sentence2": "INTERPRETATION: Adjuvant treatment with the MAGE-A3 immunotherapeutic did not increase disease-free survival compared with placebo in patients with MAGE-A3-positive surgically resected NSCLC. Based on our results, further development of the MAGE-A3 immunotherapeutic for use in NSCLC has been stopped., In the overall population, median disease-free survival was 60·5 months (95% CI 57·2-not reached) for the MAGE-A3 immunotherapeutic group and 57·9 months (55·7-not reached) for the placebo group (hazard ratio [HR] 1·02, 95% CI 0·89-1·18; p=0·74). Of the patients who did not receive chemotherapy, median disease-free survival was 58·0 months (95% CI 56·6-not reached) in those in the MAGE-A3 group and 56·9 months (44·4-not reached) in the placebo group (HR 0·97, 95% CI 0·80-1·18; p=0·76). Because of the absence of treatment effect, we could not identify a gene signature predictive of clinical benefit to MAGE-A3 immunotherapeutic. , uvant treatment with the MAGE-A3 immunotherapeutic did not increase disease-free survival compared with placebo in patients with MAGE-A3-positive surgically resected NSCLC. Ba[SEP]", "label": "no"}
{"id": "converted_1272", "sentence1": "Is curcumin a phytochemical?", "sentence2": "we analyzed turmeric from different agroclimatic regions for influence of various factors on its growth and yield of important phytochemicals, The phytochemical, curcumin, has been reported to play many beneficial roles., Curcumin (CUR), the major component in Curcuma longa, has been shown as a potent chemopreventive phytochemical that modulates various signaling pathways. , Curcumin (CUR) is a phytochemical that inhibits the xenobiotic ABC efflux transporters implicated in cancer multidrug resistance (MDR), such as P-glycoprotein (P-gp), breast cancer resistance protein (BCRP) and multidrug resistance-associated proteins 1 and 5 (MRP1 and MRP5). , In this study, we tested the efficacy of combining temozolomide with curcumin, a phytochemical known to inhibit glioblastoma growth, and investigated the mechanisms involved.,  In the present study, we investigate whether curcumin (cur), a phytochemical compound with potent anti-inflammatory effect, the Phytochemicals Curcumin , in combination with the phytochemicals curcumin and quercetin, Curcumin is a phytochemical derived from rhizome of turmeric Curcuma longa, present in the curry spice. , Curcumin, a naturally occurring polyphenolic phytochemical isolated from the medicinal plant Curcuma longa, has anti-inflammatory activities, In the present study curcumin (CUR), a known anticancer phytochemical, ,  Curcumin, a natural phytochemical, exhibits potent anticancer activities., hat curcumin, a phytochemical compound with potent anti-inflammatory properties , curcumin, a phytochemical[SEP]", "label": "yes"}
{"id": "converted_4538", "sentence1": "Is lumbar puncture the first test that should be performed on a patient with increased intracranial pressure?", "sentence2": "As an emergency diagnostic procedure, spinal puncture is indicated when CNS infection is suspected or to establish the diagnosis of subarachnoid hemorrhage when results of cranial computed tomography are normal. The major contraindication is elevated intracranial pressure with evidence of a mass lesion., Brain shift is a contraindication to LP, whether CSF pressure is raised or not, and whether papilloedema is present or not. Subsequently, recommendations are offered for indications to perform CT before LP, grouped according to the safety and clinical utility of LP., Death following lumbar puncture (LP) is feared by physicians. Many opinions are found in literature on the question whether computed cranial tomography (CT) should be performed before LP, to prevent herniation., Headache, caused by cerebrospinal fluid (CSF) hypotension, is a frequent complication of lumbar puncture; hematic patch is a therapeutic option for severe cases. The most serious complication is cerebral herniation and, for its prevention, computed tomography (CT) or cerebral magnetic resonance imaging (MRI) must always be performed before lumbar puncture: a lesion with evident mass effect is a contraindication., Lumbar puncture (LP) is usually contra-indicated in situations where the ICP is suspected to be high., Low-dose cranial computed tomography (LD-CCT) based on iterative reconstruction has been shown to have sufficient image quality to assess cerebrospinal fluid spaces (CSF) and midline structures but not to exclude subtle parenchymal pathologies. Patients without focal neurological deficits often undergo CCT before lumbar puncture (LP) to exclude contraindications to LP including brain herniation or increased CSF pressure., Lumbar puncture is performed routinely for diagnostic and therapeutic purposes in idiopathic intracranial hypertension, despite lumbar puncture being classically contraindicated in the setting of raised intracranial pressure., Although generally considered innocuous, there may be considerable danger when lumbar puncture is performed in the presence of increased intracranial pressure, especially when a mass lesion is present., Lumbar puncture should be avoided if focal neurologic findings suggest concomitant mass lesion, as in brain abscess, and lumbar puncture should be approached with great caution if meningitis is accompanied by evidence of significant intracranial hypertension., There are few abnormal CT scans presenting a contraindication for lumbar puncture and the majority of these patients usually have clinical signs to suggest raised intracranial pressure.[SEP]Relations: pseudotumor cerebri has relations: disease_phenotype_positive with Headache, disease_disease with intracranial hypertension, disease_phenotype_positive with Headache, disease_disease with intracranial hypertension.", "label": "no"}
{"id": "converted_2542", "sentence1": "Is polyadenylation a process that stabilizes a protein by adding a string of Adenosine residues to the end of the molecule?", "sentence2": "The addition of poly(A) tails to eukaryotic nuclear mRNAs promotes their stability, export to the cytoplasm and translation. , Most eukaryotic genes express mRNAs with alternative polyadenylation sites at their 3' ends, Polyadenylation is the non-template addition of adenosine nucleotides at the 3'-end of RNA, which occurs after transcription and generates a poly(A) tail up to 250-300 nucleotides long., Polyadenylation is a process of endonucleolytic cleavage of the mRNA, followed by addition of up to 250 adenosine residues to the 3' end of the mRNA., Plant mitochondrial polyadenylated mRNAs are degraded by a 3'- to 5'-exoribonuclease activity, which proceeds unimpeded by stable secondary structures., We show that a 3'- to 5'-exoribonuclease activity is responsible for the preferential degradation of polyadenylated mRNAs as compared with non-polyadenylated mRNAs, and that 20-30 adenosine residues constitute the optimal poly(A) tail size for inducing degradation of RNA substrates in vitro., The diversity of polyadenylation sites suggests that mRNA polyadenylation in prokaryotes is a relatively indiscriminate process that can occur at all mRNA's 3'-ends and does not require specific consensus sequences as in eukaryotes., Polyadenylation of premessenger RNAs occurs posttranscriptionally in the nucleus of eukaryotic cells by cleavage of the precursor and polymerization of adenosine residues., However, under certain conditions, poly(A) tracts may lead to mRNA stabilization., From these results, we propose that in plant mitochondria, poly(A) tails added at the 3' ends of mRNAs promote an efficient 3'- to 5'- degradation process.., Auxiliary downstream elements are required for efficient polyadenylation of mammalian pre-mRNAs., Transcription in these cells is polycistronic. Tens to hundreds of protein-coding genes of unrelated function are arrayed in long clusters on the same DNA strand. Polycistrons are cotranscriptionally processed by trans-splicing at the 5' end and polyadenylation at the 3' end, generating monocistronic units ready for degradation or translation, We have devised a simple chromatographic procedure which isolates five polyadenylation factors that are required for polyadenylation of eukaryotic mRNA. , During mammalian oocyte maturation, protein synthesis is mainly controlled through cytoplasmic polyadenylation of stored maternal mRNAs., Identification and characterization of a polyadenylated small RNA (s-poly A+ RNA) in dinoflagellates., Thus, polyadenylation seems to be a major component of the RNA editing machinery that affects overlapping genes in animal mitochondria., Pre-mRNA 3'-end processing, the process through which almost all eukaryotic mRNAs acquire a poly(A) tail is generally inhibited during the cellular DNA damage, Almost all eukaryotic mRNAs possess 3' ends with a polyadenylate (poly(A)) tail., We previously demonstrated, by limited mutagenesis, that conserved sequence elements within the 5' end of influenza virus virion RNA (vRNA) are required for the polyadenylation of mRNA in vitro., Polyadenylation of mRNA precursors by poly(A) polymerase depends on two specificity factors and their recognition sequences, The majority of eukaryotic pre-mRNAs are processed by 3'-end cleavage and polyadenylation, Formation of mRNA 3' termini involves cleavage of an mRNA precursor and polyadenylation of the newly formed end. , The polyadenylation of RNA is a near-universal feature of RNA metabolism in eukaryotes., The mechanism of RNA degradation in Escherichia coli involves endonucleolytic cleavage, polyadenylation of the cleavage product by poly(A) polymerase, and exonucleolytic degradation by the exoribonucleases, , The addition of poly(A)-tails to RNA is a process common to almost all organisms. , The addition of poly(A) tails to RNA is a phenomenon common to all organisms examined so far. , The addition of poly(A)-tails to RNA is a phenomenon common to almost all organisms. , Polyadenylation contributes to the destabilization of bacterial mRNA.[SEP]", "label": "no"}
{"id": "converted_1626", "sentence1": "Can adult humans be induced to produce fetal hemoglobin?", "sentence2": " At the time of birth, HbF accounts for approximately 70% of the total Hb. ,  whereas in the trace amounts of HbF that is found in the adult it reverses to 40:60 because of a gamma- to beta-globin gene switch, With the increased understanding and discovery of molecular regulators of haemoglobin switching, such as BCL11A, new avenues of research may lead ultimately to novel therapeutic, mechanism-based approaches to fetal haemoglobin reactivation in patients., The data suggest that TGF-beta reactivates gamma-globin expression, combined with a sequential stimulation and suppression of erythropoiesis. [SEP]", "label": "yes"}
{"id": "converted_1695", "sentence1": "Is calcium overload involved in the development of diabetic cardiomyopathy?", "sentence2": "High-glucose treatment resulted in increased intracellular calcium ([Ca2+]i) which was mobilized to the mitochondria. Concomitant intra-mitochondrial calcium ([Ca2+]m) increase resulted in enhanced reactive oxygen and nitrogen species generation. These events led to mitochondrial dysfunction and apoptosis., The novel findings of the study reveal that high glucose induces apoptosis by both mitochondria-dependent and independent pathways via concomitant rise in intracellular calcium., Diabetes-induced myocardial dysfunction has been attributed, in part, to calcium overload within individual myocytes., It seems that intracellular calcium overload is intimately involved in the development of diabetic cardiomyopathy;, BACKGROUND: It has been suggested that intracellular Ca2+ overload in cardiac myocytes leads to the development of diabetic cardiomyopathy., The results from the alloxan-rat model of diabetes support the view that membrane abnormalities with respect to Ca2+ handling may lead to the occurrence of intracellular Ca2+ overload and the development of diabetic cardiomyopathy., It seems that intracellular calcium overload is intimately involved in the development of diabetic cardiomyopathy; however, a concentrated research effort is required to understand the primary biochemical lesion in the pathogenesis of cardiac dysfunction in diabetes., It has been suggested that the occurrence of an intracellular Ca2+ overload may result in the development of diabetic cardiomyopathy, which is associated with depletion of high-energy phosphate stores and a derangement of ultrastructure and cardiac dysfunction.[SEP]", "label": "yes"}
{"id": "converted_374", "sentence1": "Is desmin an intermediate filament protein involved in Dilated Cardiomyopathy (DCM)?", "sentence2": "Desmin-related myofibrillar myopathy (DRM) is a cardiac and skeletal muscle disease caused by mutations in the desmin (DES) gene. Mutations in the central 2B domain of DES cause skeletal muscle disease that typically precedes cardiac involvement. However, the prevalence of DES mutations in dilated cardiomyopathy (DCM) without skeletal muscle disease is not known., The lack of severe disruption of cytoskeletal desmin network formation seen with mutations in the 1A and tail domains suggests that dysfunction of seemingly intact desmin networks is sufficient to cause DCM., According to the predominant view, desmin mutations cause dilated cardiomyopathy (DCM). We evaluated a family with restrictive cardiomyopathy (RCM) associated with a novel desmin mutation and reviewed recent reports regarding the frequency of RCM in patients with desmin myopathy., Dilated cardiomyopathy (DCM) is characterized by enlargement and dilation of all heart compartments associated with serious decrease of its contractile function. DCM hallmark is the combination of dystrophic and hypertrophic alterations of cardiomyocytes. Since the power output of cardiac cells is directly related to remodeling of their contractile machinery we investigated expression of selected contractile and cytoskeletal proteins in the left ventricle of DCM patients using immunoblotting. The content of the recognized protein markers of cardiomyocyte hypertrophy such as tubulin, desmin and slow skeletal myosin heavy chain isoform, MHCbeta, was significantly elevated in DCM compared to normal myocardium., In contrast, overexpression of desmin filaments by itself is not detrimental to the heart. Although loss-of-function studies have been more limited, ablation of the desmin gene causes mitochondrial dysfunction and apoptosis, resulting in cardiomyopathy in mice. From function studies, abnormal desmin aggregation and disruption of the desmin networks resulting from expression of either mutant desmin or mutant CryAB have been shown to remodel the heart and compromise cardiac function, suggesting their synergistic roles in disease pathogenesis., A missense mutation in the desmin gene (DES) causes DCM in a human family., Mice deficient in desmin, the muscle-specific member of the intermediate filament gene family, display defects in all muscle types and particularly in the myocardium. Desmin null hearts develop cardiomyocyte hypertrophy and dilated cardiomyopathy (DCM) characterized by extensive myocyte cell death, calcific fibrosis and multiple ultrastructural defects. Several lines of evidence suggest impaired vascular function in desmin null animals., Familial DCM is commonly inherited as autosomal dominant trait; less frequently it is autosomal recessive, X-linked or matrilinear. The disease is clinically and genetically heterogeneous. Genes causally linked to this phenotype include dystrophin, dystrophin-associated glycoproteins, actin, desmin, beta-miosin heavy chain, cardiac troponin T, and mitochondrial DNA genes, mostly transfer RNAs., Examination of families has identified so far eight disease genes, namely the dystrophin, tafazzin, cardiac actin, desmin, lamin A/C, delta- sarcoglycan, cardiac beta-myosin heavy chain, and cardiac troponin T gene., Mutations of the desmin,   delta-sarcoglycan, the cardiac actin and beta-myosin heavy chain as well as the troponin T gene are known to cause autosomal dominant-dilated cardiomyopathy without other abnormalities., Autosomal dominant DCM is the most frequent form (56% of our cases), and several candidate disease loci have been identified by linkage analysis. Three disease genes are presently known: the cardiac actin gene, the desmin gene, and the lamin A/C gene., Dilated cardiomyopathy (DCM) is a major cause of morbidity and mortality. Two genes have been identified for the X-linked forms (dystrophin and tafazzin), whereas three other genes (actin, lamin A/C, and desmin) cause autosomal dominant DCM;, Desmin defects were also recently identified in 1 familial dilated cardiomyopathy., By candidate gene screening, the molecular diagnosis can be provided for dystrophin, DAG, mitochondrial DNA, actin and desmin gene defects., Desmin (z-bands) are partly destroyed in DCM. Anti-desmin antibody titers as indicators of a possible secondary immune response are found high in patients with acute myocarditis declining during reconvalescence and are also elevated in DCM. , Desmin, the muscle-specific intermediate filament protein, is a major target in dilated cardiomyopathy and heart failure in humans and mice, Desmin, the muscle-specific intermediate filament, is involved in myofibrillar myopathies, dilated cardiomyopathy and muscle wasting[SEP]Relations: cytoskeletal protein binding has relations: molfunc_protein with DES, molfunc_protein with DES. Congestive heart failure has relations: disease_phenotype_positive with dilated cardiomyopathy, disease_phenotype_positive with dilated cardiomyopathy. Cardiomyopathy has relations: disease_phenotype_positive with dilated cardiomyopathy, disease_phenotype_positive with dilated cardiomyopathy. dilated cardiomyopathy has relations: disease_protein with DES, disease_protein with DES. myofibrillar myopathy has relations: disease_protein with DES, disease_protein with DES. X-linked inheritance has relations: disease_phenotype_positive with dilated cardiomyopathy, disease_phenotype_positive with dilated cardiomyopathy. muscle contraction has relations: bioprocess_protein with DES, bioprocess_protein with DES. myocardium has relations: anatomy_protein_present with DES, anatomy_protein_present with DES.", "label": "yes"}
{"id": "converted_1223", "sentence1": "Is there any association of the chromosomal region harboring the gene ITIH3 with schizophrenia?", "sentence2": "The most widely shared subset of genes-common to five of six disorders-included ANK3, AS3MT, CACNA1C, CACNB2, CNNM2, CSMD1, DPCR1, ITIH3, NT5C2, PPP1R11, SYNE1, TCF4, TENM4, TRIM26, and ZNRD1. , Genome-wide significant associations in schizophrenia to ITIH3/4, CACNA1C and SDCCAG8, and extensive replication of associations reported by the Schizophrenia PGC., After combining the new schizophrenia data with those of the PGC, variants at three loci (ITIH3/4, CACNA1C and SDCCAG8) that had not previously been GWS in schizophrenia attained that level of support., In a joint analysis with a bipolar disorder sample (16,374 affected individuals and 14,044 controls), three loci reached genome-wide significance: CACNA1C (rs4765905, P = 7.0 × 10(-9)), ANK3 (rs10994359, P = 2.5 × 10(-8)) and the ITIH3-ITIH4 region (rs2239547, P = 7.8 × 10(-9))., Finally, a combined GWAS analysis of schizophrenia and bipolar disorder yielded strong association evidence for SNPs in CACNA1C and in the region of NEK4-ITIH1-ITIH3-ITIH4. , A recent genome-wide analysis indicated that a polymorphism (rs2535629) of ITIH3 showed the strongest association signal with susceptibility to psychiatric disorders in Caucasian populations., We detected a novel association between suicide attempt and the ITIH3/4-region in a combined group of patients with BD, SCZ and related psychosis spectrum disorders. , These include variations in chromosomal structure at 16p11.2, rare de novo point mutations at the gene SCN2A, and common single nucleotide polymorphisms (SNPs) mapping near loci encoding the genes ITIH3, AS3MT, CACNA1C and CACNB2. These selected examples point to the challenges to current diagnostic approaches. , STAB1 is located in close proximity to PBMR1 and the NEK4-ITIH1-ITIH3-ITIH4 region, which are the top findings from GWAS meta-analyses of mood disorder, and a combined BD and schizophrenia data set., Our findings suggest that rs2535629 influences the susceptibility to psychiatric disorders by affecting the expression level of GLT8D1.[SEP]Relations: CNNM2 has relations: disease_protein with schizophrenia, disease_protein with schizophrenia. TENM4 has relations: disease_protein with bipolar disorder, disease_protein with schizophrenia, disease_protein with bipolar disorder, disease_protein with schizophrenia. GLT8D1 has relations: protein_protein with TCF4, protein_protein with TCF4. bipolar disorder has relations: disease_protein with SYNE1, disease_protein with CACNA1C, disease_protein with TCF4, disease_protein with CSMD1, disease_protein with TENM4, disease_protein with CACNB2, disease_protein with SYNE1, disease_protein with CACNA1C, disease_protein with TCF4, disease_protein with CSMD1, disease_protein with TENM4, disease_protein with CACNB2. CACNA1C has relations: disease_protein with bipolar disorder, disease_protein with schizophrenia, protein_protein with CACNB2, disease_protein with bipolar disorder, disease_protein with schizophrenia, protein_protein with CACNB2. CACNB2 has relations: disease_protein with bipolar disorder, protein_protein with CACNA1C, disease_protein with schizophrenia, disease_protein with bipolar disorder, protein_protein with CACNA1C, disease_protein with schizophrenia. SDCCAG8 has relations: disease_protein with schizophrenia, disease_protein with schizophrenia. SYNE1 has relations: disease_protein with bipolar disorder, disease_protein with bipolar disorder.", "label": "yes"}
{"id": "converted_108", "sentence1": "Are stress granules involved in the pathogenesis of Amyotrophic Lateral Sclerosis?", "sentence2": "SGs have been linked to several pathologies including inflammatory diseases, cancer, viral infection, and neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD)., Like several other ALS-associated proteins, CREST is recruited to induced stress granules., Our data indicate that CREST and certain other ALS-linked proteins share several features implicated in ALS pathogenesis, namely the ability to aggregate, be recruited to stress granules and alter paraspeckle integrity., A unifying feature of many proteins associated with ALS, including TDP-43 and ataxin-2, is that they localize to stress granules. , Two RNA-binding proteins, TDP-43 and FUS, aggregate in the degenerating motor neurons of ALS patients, and mutations in the genes encoding these proteins cause some forms of ALS., Recent work connecting TDP-43 and FUS to stress granules has suggested how this cellular pathway, which involves protein aggregation as part of its normal function, might be coopted during disease pathogenesis., Amyotrophic lateral sclerosis (ALS)-linked fused in sarcoma/translocated in liposarcoma (FUS/TLS or FUS) is concentrated within cytoplasmic stress granules under conditions of induced stress. Since only the mutants, but not the endogenous wild-type FUS, are associated with stress granules under most of the stress conditions reported to date, the relationship between FUS and stress granules represents a mutant-specific phenotype and thus may be of significance in mutant-induced pathogenesis., Fused in sarcoma (FUS) belongs to the group of RNA-binding proteins implicated as underlying factors in amyotrophic lateral sclerosis (ALS) and certain other neurodegenerative diseases. Multiple FUS gene mutations have been linked to hereditary forms, and aggregation of FUS protein is believed to play an important role in pathogenesis of these diseases. In cultured cells, FUS variants with disease-associated amino acid substitutions or short deletions affecting nuclear localization signal (NLS) and causing cytoplasmic mislocalization can be sequestered into stress granules (SGs)., Profilin 1 associates with stress granules and ALS-linked mutations alter stress granule dynamics, Here we report that profilin 1 and related protein profilin 2 are novel stress granule-associated proteins in mouse primary cortical neurons and in human cell lines and that ALS-linked mutations in profilin 1 alter stress granule dynamics, providing further evidence for the potential role of stress granules in ALS pathogenesis, Furthermore, in response to oxidative stress or heat shock conditions in cultures and in vivo, the ALS-linked FUS mutants, but not wild-type FUS, assembled into perinuclear stress granules in proportion to their cytoplasmic expression levels., Mutant FUS proteins that cause amyotrophic lateral sclerosis incorporate into stress granules., Our results suggest that the ALS mutations in FUS NLS can impair FUS nuclear localization, induce cytoplasmic inclusions and stress granules, and potentially perturb RNA metabolism., RNA-binding ability of FUS regulates neurodegeneration, cytoplasmic mislocalization and incorporation into stress granules associated with FUS carrying ALS-linked mutations., TDP-43 is an RNA-binding protein linked to amyotrophic lateral sclerosis (ALS) that is known to regulate the splicing, transport, and storage of specific mRNAs into stress granules, In amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration, TAR DNA binding protein 43 (TDP-43) accumulates in the cytoplasm of affected neurons and glia, where it associates with stress granules (SGs) and forms large inclusions, Amyotrophic lateral sclerosis (ALS)-linked fused in sarcoma/translocated in liposarcoma (FUS/TLS or FUS) is concentrated within cytoplasmic stress granules under conditions of induced stress, Mutant FUS proteins that cause amyotrophic lateral sclerosis incorporate into stress granules, Mutations in Fus cause amyotrophic lateral sclerosis (ALS) and the mutant protein forms inclusions that appear to correspond to stress granules, Recent work also suggests that TDP-43 associates with cytoplasmic stress granules, which are transient structures that form in response to stress. , We found that in response to oxidative stress and to environmental insults of different types TDP-43 is capable to assemble into stress granules (SGs), ribonucleoprotein complexes where protein synthesis is temporarily arrested. , Moreover, proteins known to be stress granule markers co-deposit with inclusions in fALS and FTLD-FUS patients, implicating stress granule formation in the pathogenesis of these diseases. We propose that two pathological hits, namely nuclear import defects and cellular stress, are involved in the pathogenesis of FUS-opathies., Amyotrophic lateral sclerosis (ALS)-linked fused in sarcoma/translocated in liposarcoma (FUS/TLS or FUS) is concentrated within cytoplasmic stress granules under conditions of induced stress., Amyotrophic lateral sclerosis-linked FUS/TLS alters stress granule assembly and dynamics., Moreover, proteins known to be stress granule markers co-deposit with inclusions in fALS and FTLD-FUS patients, implicating stress granule formation in the pathogenesis of these diseases. We propose that two pathological hits, namely nuclear import defects and cellular stress, are involved in the pathogenesis of FUS-opathies.  ., Autophagy regulates amyotrophic lateral sclerosis-linked fused in sarcoma-positive stress granules in neurons, However, the role of autophagy in regulation of FUS-positive stress granules (SGs) and aggregates remains unclear. , Although co-localized primarily in the nucleus in normal condition, FUS/TLS and PRMT1 were partially recruited to the cytoplasmic granules under oxidative stress, which were merged with stress granules (SGs) markers in SH-SY5Y cell., The effect of PRMT1-mediated arginine methylation on the subcellular localization, stress granules, and detergent-insoluble aggregates of FUS/TLS, Stress granules are cytoplasmic inclusions that repress translation of a subset of RNAs in times of cellular stress, and several proteins implicated in neurodegeneration (i.e. Ataxin-2 and SMN) interact with stress granules, These findings support a two-hit hypothesis, whereby cytoplasmic mislocalization of FUS protein, followed by cellular stress, contributes to the formation of cytoplasmic aggregates that may sequester FUS, disrupt RNA processing and initiate motor neuron degeneration., Here, we exploited a Drosophila model of ALS and neuronal cell lines to elucidate the role of the RNA-binding ability of FUS in regulating FUS-mediated toxicity, cytoplasmic mislocalization and incorporation into stress granules (SGs). , Stress granules as crucibles of ALS pathogenesis[SEP]Relations: amyotrophic lateral sclerosis has relations: disease_protein with FUS, disease_protein with FUS. Frontotemporal dementia has relations: disease_phenotype_positive with amyotrophic lateral sclerosis, disease_phenotype_positive with amyotrophic lateral sclerosis. protein-arginine N-methyltransferase activity has relations: molfunc_protein with PRMT1, molfunc_protein with PRMT1. cytoplasm has relations: cellcomp_protein with PRMT1, cellcomp_protein with PRMT1, cellcomp_protein with PRMT1, cellcomp_protein with PRMT1. protein binding has relations: molfunc_protein with FUS, molfunc_protein with PRMT1, molfunc_protein with FUS, molfunc_protein with PRMT1, molfunc_protein with FUS, molfunc_protein with PRMT1, molfunc_protein with FUS, molfunc_protein with PRMT1. Motor neuron atrophy has relations: disease_phenotype_positive with amyotrophic lateral sclerosis, disease_phenotype_positive with amyotrophic lateral sclerosis.", "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]", "label": "no"}
{"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_72", "sentence1": "Are transcribed ultraconserved regions involved in cancer?", "sentence2": "Although most cancer research has focused in mRNA, non-coding RNAs are also an essential player in tumorigenesis. In addition to the well-recognized microRNAs, recent studies have also shown that epigenetic silencing by CpG island hypermethylation of other classes of non-coding RNAs, such as transcribed ultraconserved regions (T-UCRs) or small nucleolar RNAs (snoRNAs), also occur in human neoplasia, Starting from a genome-wide expression profiling, we demonstrate for the first time a functional link between oxygen deprivation and the modulation of long noncoding transcripts from ultraconserved regions, termed transcribed-ultraconserved regions (T-UCRs). Interestingly, several hypoxia-upregulated T-UCRs, henceforth named 'hypoxia-induced noncoding ultraconserved transcripts' (HINCUTs), are also overexpressed in clinical samples from colon cancer patients, Consistent with the hypothesis that T-UCRs have important function in tumor formation, The importance of other classes of non-coding RNAs, such as long intergenic ncRNAs (lincRNAs) and transcribed ultraconserved regions (T-UCRs) as altered elements in neoplasia, is also gaining recognition, Expression levels of transcribed ultraconserved regions uc.73 and uc.388 are altered in colorectal cancer, Transcribed ultraconserved regions (T-UCRs) are a subset of 481 sequences longer than 200 bp, which are absolutely conserved between orthologous regions of human, rat and mouse genomes, and are actively transcribed. It has recently been proven in cancer systems that differentially expressed T-UCRs could alter the functional characteristics of malignant cells. Genome-wide profiling revealed that T-UCRs have distinct signatures in human leukemia and carcinoma,  Our preliminary results suggest that uc.73 and uc.388 could be potential diagnostic and prognostic biomarkers in CRC patients, The transcribed-ultraconserved regions: a novel class of long noncoding RNAs involved in cancer susceptibility, This review gives a picture of the state of the art of a novel class of long ncRNA known as transcribed-ultraconserved regions (T-UCRs). Most recent studies show that they are significantly altered in adult chronic lymphocytic leukemias, carcinomas, and pediatric neuroblastomas, leading to the hypothesis that UCRs may play a role in tumorigenesis and promising innovative future T-UCR-based therapeutic approaches, CpG island hypermethylation-associated silencing of non-coding RNAs transcribed from ultraconserved regions in human cancer, We focused on the transcribed-ultraconserved regions (T-UCRs), a subset of DNA sequences that are absolutely conserved between orthologous regions of the human, rat and mouse genomes and that are located in both intra- and intergenic regions. We used a pharmacological and genomic approach to reveal the possible existence of an aberrant epigenetic silencing pattern of T-UCRs by treating cancer cells with a DNA-demethylating agent followed by hybridization to an expression microarray containing these sequences. We observed that DNA hypomethylation induces release of T-UCR silencing in cancer cells. 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. The analysis of a large set of primary human tumors (n=283) demonstrated that hypermethylation of the described T-UCR CpG islands was a common event among the various tumor types. Our finding that, in addition to microRNAs, another class of ncRNAs (T-UCRs) undergoes DNA methylation-associated inactivation in transformed cells supports a model in which epigenetic and genetic alterations in coding and non-coding sequences cooperate in human tumorigenesis, An integrative genomics screen uncovers ncRNA T-UCR functions in neuroblastoma tumours, Different classes of non-coding RNAs, including microRNAs, have recently been implicated in the process of tumourigenesis. In this study, we examined the expression and putative functions of a novel class of non-coding RNAs known as transcribed ultraconserved regions (T-UCRs) in neuroblastoma, our results define a T-UCR expression landscape in neuroblastoma and suggest widespread T-UCR involvement in diverse cellular processes that are deregulated in the process of tumourigenesis, Moreover, the recent demonstration that other ncRNAs, the ultraconserved genes (UCGs) or transcribed ultraconserved regions (T-UCRs), are involved in human cancerogenesis, suggests that the wider family of ncRNAs (including both miRNAs and UCGs) could contribute to the development of the malignant phenotype. Here we review the main studies investigating the role of miRNAs and UCRs in both normal hemopoiesis and hematological malignancies, and identify the molecular, clinical and therapeutic implications of these recent findings, The transcribed-ultraconserved regions: a novel class of long noncoding RNAs involved in cancer susceptibility., Expression levels of transcribed ultraconserved regions uc.73 and uc.388 are altered in colorectal cancer., CpG island hypermethylation-associated silencing of non-coding RNAs transcribed from ultraconserved regions in human cancer., Starting from a genome-wide expression profiling, we demonstrate for the first time a functional link between oxygen deprivation and the modulation of long noncoding transcripts from ultraconserved regions, termed transcribed-ultraconserved regions (T-UCRs)., The importance of other classes of non-coding RNAs, such as long intergenic ncRNAs (lincRNAs) and transcribed ultraconserved regions (T-UCRs) as altered elements in neoplasia, is also gaining recognition., Moreover, the recent demonstration that other ncRNAs, the ultraconserved genes (UCGs) or transcribed ultraconserved regions (T-UCRs), are involved in human cancerogenesis, suggests that the wider family of ncRNAs (including both miRNAs and UCGs) could contribute to the development of the malignant phenotype., Moreover, the recent demonstration that other ncRNAs, the ultraconserved genes (UCGs) or transcribed ultraconserved regions (T-UCRs), are involved in human cancerogenesis, suggests that the wider family of ncRNAs (including both miRNAs and UCGs) could contribute to the development of the malignant phenotype, Starting from a genome-wide expression profiling, we demonstrate for the first time a functional link between oxygen deprivation and the modulation of long noncoding transcripts from ultraconserved regions, termed transcribed-ultraconserved regions (T-UCRs)[SEP]Relations: malignant giant cell tumor has relations: disease_disease with cancer, disease_disease with cancer. malignant colon neoplasm has relations: disease_disease with colorectal cancer, disease_disease with colorectal cancer. carcinoma has relations: disease_disease with cancer, disease_disease with cancer. Somatic mutation has relations: disease_phenotype_positive with colorectal cancer, disease_phenotype_positive with colorectal cancer.", "label": "yes"}
{"id": "converted_2788", "sentence1": "Is pembrolizumab effective against Ewing's sarcoma?", "sentence2": "None of the 13 patients with Ewing's sarcoma had an objective response. , Between March 13, 2015, and Feb 18, 2016, we enrolled 86 patients, 84 of whom received pembrolizumab (42 in each disease cohort) and 80 of whom were evaluable for response (40 in each disease cohort). [SEP]", "label": "no"}
{"id": "converted_552", "sentence1": "Is zyxin a focal adhesion protein?", "sentence2": " zyxin from FAs, zyxin relocation from focal adhesions , . Here we systematically examined the expression, localization, and function of zyxin, a focal adhesion protein, focal adhesion protein zyxin, Focal adhesions formed in the absence of α-actinins are delayed in their maturation, exhibit altered morphology, have decreased amounts of Zyxin and VASP, and reduced adhesiveness to extracellular matrix, one focal adhesion protein (zyxin), Zyxin is a focal adhesion protein that has been implicated in the modulation of cell adhesion and motility,  focal adhesion proteins (vinculin, talin, zyxin, FAK, and paxilin), Such paxillin-positive complexes mature into focal adhesions by tyrosine phosphorylation and recruitment of zyxin. , Zyxin concentrates at focal adhesions , zyxin, a focal adhesion protein,, Focal adhesion proteins Zyxin and Vinculin are co-distributed at tubulobulbar complexes.,  Here we explore the prediction that zyxin, a focal adhesion protein known to be present at podosomes, also is present at apical TBCs, the association of zyxin with focal adhesions is force-dependent, smaller zyxin-positive adhesion as well as its higher turnover rate suggests that the traction force in focal adhesion on 350 nm topography is decreased., . Zyxin is a focal adhesion protein that responds to external mechanical forces;, Vinculin and zyxin in focal adhesions but not integrins are seen to bridge ligand gaps. , The focal adhesion protein zyxin, . To explore how this response is regulated by focal adhesion-associated proteins the expression levels of paxillin, focal adhesion kinase (FAK), and zyxin were knocked down using gene silencing techniques,  Zyxin is an adaptor protein at focal adhesion plaque, ocked localization of zyxin at focal adhesion sites[SEP]Relations: focal adhesion has relations: cellcomp_protein with VASP, cellcomp_protein with VASP, cellcomp_protein with VASP, cellcomp_protein with VASP.", "label": "yes"}
{"id": "converted_1917", "sentence1": "Is there a role for gamma knife in treatment of Obsessive-Compulsive Disorder?", "sentence2": "OBJECTIVE Functional Gamma Knife radiosurgery (GKRS) procedures have been increasingly used for treating patients with tremor, trigeminal neuralgia (TN), and refractory obsessive-compulsive disorder., METHODS The authors constructed a linear-quadratic model of BED in functional GKRS with a dose-protraction factor to correct for intrafraction DNA-damage repair and used standard single-fraction doses for trigeminal nerve ablation for TN (85 Gy), thalamotomy for tremor (130 Gy), and capsulotomy for obsessive-compulsive disorder (180 Gy). , Gamma knife for obsessive compulsive disorder: can it be detrimental?, Gamma knife radiosurgery (GKRS) is also being practised to treat refractory obsessive- compulsive disorder (OCD)., Radio and neurosurgical procedures, including gamma knife radiation and deep brain stimulation, are reserved for severe, treatment-refractory disease that has not responded to multiple treatments, and some patients may benefit from transcranial magnetic stimulation.,  We close with a discussion of gamma knife capsulotomy, a modality with deep historical roots., Results following gamma knife radiosurgical anterior capsulotomies for obsessive compulsive disorder., Gamma knife radiosurgery (GKRS) is also being practised to treat refractory obsessive- compulsive disorder (OCD)., Lesion topography and outcome after thermocapsulotomy or gamma knife capsulotomy for obsessive-compulsive disorder: relevance of the right hemisphere., Neuropsychological outcome of ventral capsular/ventral striatal gamma capsulotomy for refractory obsessive-compulsive disorder: a pilot study, Gamma ventral capsulotomy for treatment of resistant obsessive-compulsive disorder: a structural MRI pilot prospective study, Results following gamma knife radiosurgical anterior capsulotomies for obsessive compulsive disorder, At 28 months, the third patient is living and working independently, and her YBOCS score is 18.CONCLUSION: Within a strict protocol, gamma knife radiosurgery provided improvement of OCD behavior with no adverse effects., Gamma knife for obsessive compulsive disorder: can it be detrimental?[SEP]", "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]", "label": "yes"}
{"id": "converted_1215", "sentence1": "Is zolpidem an antibiotic?", "sentence2": "Zolpidem is a short-acting imidazopyridine hypnotic drug that is metabolized mainly by CYP3A4., FGIN-1-27 and alpidem, like the neurosteroid 3 alpha,21-dehydroxy-5 alpha-pregnane-20-one (THDOC), clonazepam and zolpidem (the direct allosteric modulators of gamma-aminobutyric acidA receptors) delay the onset of isoniazid and metrazol-induced convulsions., olpidem is a new, short-acting hypnotic of imidazopyridine structure which binds selectively to a subpopulation of receptors involved in the action of benzodiazepines [omega 1 (BZ1) sites of the gamma-aminobutyric acidA receptors], lpidem is a new, short-acting hypnotic of imidazopyridine structure which binds selectively to a subpopulation of receptors involved in the action of benzodiazepines [omega 1 (BZ1) sites of the gamma-aminobutyric acidA receptors], In contrast, after repeated treatment with zolpidem, there was no change in its ability to produce sedative and anticonvulsant effects., Zolpidem, a novel nonbenzodiazepine hypnotic. I. Neuropharmacological and behavioral effects., Zolpidem [N,N,6-trimethyl-2-(4-methylphenyl)imidazo[1,2-a]pyridine-3-acetamide hemitartrate] is reported to be a rapid onset, short duration hypnotic that interacts at the benzodiazepine recognition site., The imidazopyridine zolpidem is a short-acting hypnotic chemically distinct from benzodiazepines (BZs)., According to its peculiar neuropharmacologic activity (selectivity for the omega 1-BZ receptors), zolpidem is expected to be a pure hypnotic, without the other effects of BZs.[SEP]Relations: Zolpidem has relations: drug_protein with CYP3A4, drug_protein with CYP3A4. Benzodiazepine has relations: drug_protein with CYP3A4, drug_protein with CYP3A4, drug_protein with CYP3A4, drug_protein with CYP3A4. Clonazepam has relations: drug_protein with CYP3A4, drug_protein with CYP3A4. Desoxycorticosterone acetate has relations: drug_protein with CYP3A4, drug_protein with CYP3A4. Isoniazid has relations: drug_protein with CYP3A4, drug_protein with CYP3A4.", "label": "no"}
{"id": "converted_4485", "sentence1": "Is nerinetide effective for ischaemic stroke?", "sentence2": "337 (61·4%) of 549 patients with nerinetide and 329 (59·2%) of 556 with placebo achieved an mRS score of 0-2 at 90 days (adjusted risk ratio 1·04, 95% CI 0·96-1·14; p=0·35). Secondary outcomes were similar between groups. , INTERPRETATION: Nerinetide did not improve the proportion of patients achieving good clinical outcomes after endovascular thrombectomy compared with patients receiving placebo.,  patients receiving alteplase. Serious adverse events occurred equally between groups.INTERPRETATION: Nerinetide did not improve the proportion of patients achieving good clinical outcomes after endovascular thrombectomy compared with patients receiving placebo.FUNDING: Canadian Inst[SEP]", "label": "no"}
{"id": "converted_1599", "sentence1": "Is there any protein that undergoes both mono-ubiquitination and poly-ubiquitination?", "sentence2": "The yeast G protein alpha subunit Gpa1 represents a rare example of a protein that undergoes both mono- and poly-ubiquitination. , Expression of p34 promotes PTEN poly-ubiquitination, leading to PTEN protein degradation, whereas p34 knockdown results in PTEN mono-ubiquitination., These fingers possess E3 activities of mono-ubiquitination and poly-ubiquitination, respectively, with ubiquitin-conjugating enzyme (E2)-binding capabilities. , Instead of promoting poly-ubiquitination and degradation, we show that Smurf2 actually induces multiple mono-ubiquitination of Smad3 in vivo., mono-ubiquitination of CIITA dramatically increases its transactivity whereas poly-ubiquitination leads to CIITA degradation., This leads to a model in which Lys134 of LDB1 can be either mono-ubiquitinated, leading to stabilization, or poly-ubiquitinated, leading to degradation by the proteasome pathway. ,  mono-ubiquitination of CIITA increases its transactivity, whereas poly-ubiquitination of CIITA leads to its degradation, PS1 ubiquitination after PI3K inhibition is represented by the multiple mono-ubiquitination, instead of poly-ubiquitination, Our observations support a novel functional relationship between parkin and Hsc/Hsp70 and support the notion that parkin is a multi-purpose E3 ubiquitin ligase capable of modifying proteins either via attachment of alternatively linked poly-ubiquitin chains or through multiple mono-ubiquitination to achieve alternate biological outcomes, our results indicate that Hsp70 facilitates CHIP-mediated poly-ubiquitination of Smad1 whereas it attenuates CHIP-meditated mono-ubiquitination of Smad1., Whereas poly-ubiquitination targets protein substrates for proteasomal degradation, mono-ubiquitination is known to regulate protein trafficking in the endosomal system and to target cargo proteins for lysosomal degradation., Our results suggest that oxidative stress induces not only poly-ubiquitination but also mono-ubiquitination of LDH-A, which may be involved in its lysosomal degradation during unloading., wild type Smad4 is a relatively stable protein that undergoes mono- or oligo-ubiquitination, a modification not linked to protein degradation, These data suggest that oligo-ubiquitination positively regulates Smad4 function, whereas poly-ubiquitination primarily occurs in unstable cancer mutants and leads to protein degradation., We found that Ro52 was strongly conjugated by a single molecule of ubiquitin in cells. Although the biological relevance of this mono-ubiquitination was not defined, the function of Ro52 might be modified by the mono-ubiquitination. We also found that Ro52 was conjugated with poly-ubiquitin chain in cells (poly-ubiquitination)[SEP]", "label": "yes"}
{"id": "converted_1395", "sentence1": "Does prudent diet reduce cardiovascular risk?", "sentence2": "Using this approach, large prospective studies have reported reductions in CVD risk ranging from 10 to 60% in groups whose diets can be variously classified as ‘Healthy’, ‘Prudent’, Mediterranean’ or ‘DASH compliant’., Our findings suggest that a heart healthy dietary pattern is associated with moderately reduced risk of MI, but not related to risk of VTE., The systematically reviewed studies reveal that a high adherence to a Mediterranean type of diet or \"prudent diet\" is associated with reduced risk of CVD and some types of cancer, even in the elderly., In a large healthy Italian population, non-predefined dietary patterns including foods considered to be rather unhealthy, were associated with higher levels of cardiovascular risk factors, CRP and individual global CVD risk, whereas a \"prudent-healthy\" pattern was associated with lower levels., We observed an inverse association between the prudent pattern and AMI, with higher levels being protective., After multivariable adjustment, the prudent diet was associated with a 28% lower risk of cardiovascular mortality (95% confidence interval [CI], 13 to 40) and a 17% lower risk of all-cause mortality (95% CI, 10 to 24) when the highest quintile was compared with the lowest quintile. , Greater adherence to the prudent pattern may reduce the risk of cardiovascular and total mortality, whereas greater adherence to the Western pattern may increase the risk among initially healthy women., Composite diets (such as DASH diets, Mediterranean diet, 'prudent' diet) have been demonstrated to reduce the risk of hypertension and CHD.[SEP]", "label": "yes"}
{"id": "converted_1331", "sentence1": "Is there a difference in the rate between gene fusion and gene fission?", "sentence2": "we illustrate arrangement diversity within closely related organisms, estimate arrangement turnover frequency and establish, for the first time, branch-specific rate estimates for fusion, fission, domain addition and terminal loss., Rate and polarity of gene fusion and fission in Oryza sativa and Arabidopsis thaliana, We have identified all differentially composite or split genes in 2 fully sequenced plant genomes, Oryza sativa and Arabidopsis thaliana, Polarizing these events by outgroup comparison revealed differences in the rate of gene fission but not of gene fusion in the rice and Arabidopsis lineages. Gene fission occurred at a higher rate than gene fusion in the O. sativa lineage and was furthermore more common in rice than in Arabidopsis., Gene fusion and fission are thus rare and slow processes in higher plant genomes; they should be of utility to address deeper evolutionary relationships among plants--and the relationship of plants to other eukaryotic lineages--where sequence-based phylogenies provide equivocal or conflicting results., Primary factors correlating with fusion rates are the presence of transmembrane helices in HKs and the presence of DNA-binding domains in RRs, features that require correct (and separate) spatial location. In the absence of such features, there is a relative abundance of fused genes., We show that indels are the most frequent elementary events and that they occur in most cases at either the N- or C-terminus of the proteins. As revealed by the genomic neighbourhood/context of the corresponding genes, we show that a substantial number of these terminal indels are the consequence of gene fusions/fissions. We provide evidence showing that the contribution of gene fusion/fission to the evolution of multi-domain bacterial proteins is lower-bounded by 27% and upper-bounded by 64%. We conclude that gene fusion/fission is a major contributor to the evolution of multi-domain bacterial proteins., We found that fusion events are approximately four times more common than fission events, and we established that, in most cases, any particular fusion or fission event only occurred once during the course of evolution., Analyzing the most parsimonious pathways, we find 87% of architectures to gain complexity over time through simple changes, among which fusion events account for 5.6 times as many architectures as fission., These trees defined timelines of architectural discovery and revealed remarkable evolutionary patterns, including the explosive appearance of domain combinations during the rise of organismal lineages, the dominance of domain fusion processes throughout evolution, and the late appearance of a new class of multifunctional modules in Eukarya by fission of domain combinations, We searched for examples which have arisen by one of the three postulated mechanisms: independent fusion/fission, \"duplication/deletion,\" and plasmid-mediated \"cut and paste.\" We conclude that all three mechanisms can be observed, with the independent fusion/fission being the most frequent.[SEP]", "label": "yes"}
{"id": "converted_3130", "sentence1": "Are apoE mimetics being considered as a treatment against Alzheimer's disease?", "sentence2": "The apolipoprotein-E-mimetic COG112 protects amyloid precursor protein intracellular domain-overexpressing animals from Alzheimer's disease-like pathological features., Studies show that administration of apolipoprotein E (apoE) and apoE-derived small peptide mimetics protect AD mouse models against these AD-like features.[SEP]", "label": "yes"}
{"id": "converted_2590", "sentence1": "Does temsirolimus improve survival of glioblastoma patients?", "sentence2": "RESULTS: fourteen randomized clinical trials were identified (7 with bevacizumab, 2 cilengitide, 1 enzastaurin, 1 dasatinib, 1 vandetanib, 1 temsirolimus, 1 cediranib) including 4330 patients. Antiangiogenic drugs showed no improvement in overall survival with a pooled HR of 1.00, a trend for an inferior outcome, in terms of overall survival, was observed in the group of patients receiving antiangiogenic drug alone compared to cytotoxic drug alone (HR=1.24, p=0.056)., CONCLUSIONS: Temsirolimus was not superior to temozolomide in patients with an unmethylated MGMT promoter., The actuarial 1-year survival was 72.2% [95% confidence interval (CI), 58.2-82.2] in the temozolomide arm and 69.6% (95% CI, 55.8-79.9) in the temsirolimus arm [hazard ratio (HR) 1.16; 95% CI, 0.77-1.76; P = 0.47]., CONCLUSION: The combination of bevacizumab with temsirolimus was well-tolerated and resulted in stable disease of at least four months/partial response in three out of six pediatric patients with chemorefractory CNS tumors., CONCLUSIONS: Temsirolimus administered weekly at the dose of 75 mg/m(2) did not meet the primary objective efficacy threshold in children with high-grade glioma, neuroblastoma or rhabdomyosarcoma; however, meaningful prolonged stable disease merits further evaluation in combination therapy., Novel targeted agents such as bevacizumab, imatinib, erlotinib, temsirolimus, immunotherapy, cilengitide, talampanel, etc. are helping classical chemotherapeutic agents, like temozolomide, to achieve an increase in overall survival., CONCLUSIONS: CCI-779 was well tolerated at this dose schedule; however, there was no evidence of efficacy in patients with recurrent GBM, The addition of temsirolimus to interferon did not improve survival., CONCLUSIONS Temsirolimus was not superior to temozolomide in patients with an unmethylated MGMT promoter., The addition of temsirolimus to interferon did not improve survival.[SEP]Relations: Vandetanib has relations: drug_drug with Temsirolimus, drug_drug with Temsirolimus. Erlotinib has relations: drug_drug with Temsirolimus, drug_drug with Temsirolimus. Bevacizumab has relations: drug_drug with Temsirolimus, drug_drug with Temsirolimus. Temozolomide has relations: drug_drug with Temsirolimus, drug_drug with Temsirolimus. Dasatinib has relations: drug_drug with Temsirolimus, drug_drug with Temsirolimus. Imatinib has relations: drug_drug with Temsirolimus, drug_drug with Temsirolimus.", "label": "no"}
{"id": "converted_1751", "sentence1": "Is Thalidomide currently a marketed drug?", "sentence2": "In this retrospective study, pharmacy claims were analyzed for those patients with a diagnosis of MM who received thalidomide,, The Japanese POEMS syndrome with Thalidomide (J-POST) Trial is a phase II/III multicentre, double-blinded, randomised, controlled trial that aims to evaluate the efficacy and safety of a 24-week treatment with thalidomide in POEMS syndrome,, Thalidomide could relieve clinical symptoms and intestinal mucosal lesions effectively in children with refractory inflammatory bowel disease (IBD) from the pre-clinical study., Thalidomide is now available as an investigational drug in the USA., The STEPStrade mark (System for Thalidomide Education and Prescribing Safety) Program has been developed by Celgene, the commercial manufacturer of thalidomide, to ensure compliance with prescription and usage protocols., New uses of thalidomide., Thalidomide is an anti-angiogenesis agent that currently is being evaluated in the treatment of various types of cancer., The comeback of thalidomide to the legitimate status of a marketed drug came in 1998 when it received FDA approval for the treatment of erythema nodosum leprosum (ENL), Thalidomide is considered the drug of choice for the treatment of ENL, but for other conditions, it is recommended only when resistance to the currently available form of therapy is encountered, Thalidomide is an anti-inflammatory and anti-angiogenic drug currently used for the treatment of several diseases, including erythema nodosum leprosum, which occurs in patients with lepromatous leprosy, Thalidomide, once banned, has returned to the center of controversy with the Food and Drug Administration's (FDA's) announcement that thalidomide will be placed on the market for the treatment of erythema nodosum leprosum, a severe dermatological complication of Hansen's disease. , In 1998, FDA approved the marketing of thalidomide (Thalomid, Celgene). , In 1998 the US Food and Drug Administration approved thalidomide exclusively for the treatment of ENL, and strict conditions were stipulated for its use in order to prevent teratogenic adverse effects., BACKGROUND: The use of thalidomide during the 1950s resulted in teratogenic effects in thousands of infants. Although thalidomide is currently approved for the treatment of a complication of leprosy, it is commercially available to treat other diseases through a controlled distribution system., The comeback of thalidomide to the legitimate status of a marketed drug came in 1998 when it received FDA approval for the treatment of erythema nodosum leprosum (ENL).[SEP]Relations: Erythema nodosum has relations: drug_effect with Thalidomide, drug_effect with Thalidomide.", "label": "yes"}
{"id": "converted_4499", "sentence1": "Does Amblyopia affect the eye?", "sentence2": "The main goal of our study is to assess the effect of transcranial magnetic stimulation, specifically theta burst stimulation (TBS), in a group of amblyopic volunteers measuring several visual parameters: visual acuity, suppressive imbalance, and stereoacuity, This study was undertaken to determine if optometrists in Ghana screen, diagnose and manage paediatric ocular conditions (for example, strabismus, amblyopia), and further assessed if optometrists in Ghana have the requisite paediatric instrumentation in their practices., Many bilateral amblyopia patients have asymmetric visual acuity (VA)., LTS: In patients with persistent amblyopia and in those with recovered amblyopia, the affected eyes were significantly more hyperopic than the fellow eyes. The, e RNFLT was compared between the affected and fellow eyes in patients with persistent amblyopia and in those with recovered amblyopia, and between the amblyopic eyes of patients with persistent amblyopia and the previously amblyopic eyes of patients with recovered amblyopia.RE, We compared the optic nerve head topography and retinal nerve fiber layer (RNFL) thickness of the strabismic and anisometropic amblyopic eyes with the normal fellow eyes and age-matched controls and concluded that, although amblyopia is a functional visual loss, RNFL thickness and optic nerve head topographic changes in strabismic and anisometropic amblyopic eyes may be affected by amblyopia., ODS: Four consecutive infants between 7 and 19 months of age with unilateral periocular vascular lesions that intermittently obstructed vision in the affected eye and no clinical evidence of amblyopia were evaluated. No , Histologic study of the LGNs from a patient with ophthalmologically confirmed anisometropic amblyopia shows a decrease of cell sizes in the parvocellular layers innervated by the amblyopic eye., S: Neutral density filters affect eyes with strabismic amblyopia differently than they do non-amblyopic eyes. A signifi, Together with recent advances in our theoretical understanding of amblyopia and technological advances in amblyopia treatment, we anticipate improved visual outcomes for children affected by this very common eye condition., OBJECTIVE: Amblyopia or lazy eye is a common visual problem affecting children that cannot correct with lenses., Experimental amblyopia in animal models causes a reduction of cell sizes in lateral geniculate nucleus (LGN) laminae connected with the amblyopic eye., Amblyopia cannot be cured by treating the cause alone; the weaker eye must be made stronger in order to see normally., To correct amblyopia, a child must be made to use the weak eye., Similarly, decreased activation of the LGN as well as the visual cortex by the affected eye was demonstrated in the patient with anisometropic amblyopia., Amblyopia is defined as a loss of letter recognition visual acuity in the affected eye; however, studies in both nonhuman primates and man have shown that other important aspects of vision, including color, motion, and contour perception, are also abnormal. The, Amblyopia is a developmental disorder that affects the spatial vision of one or both eyes in the absence of an obvious organic cause; it is associated with a history of abnormal visual experience during childhood, Amblyopia is defined as the reduction of best-corrected visual acuity of one or both eyes caused by conditions that affect normal visual development, Amblyopia is a reduced best-corrected visual acuity of one or both eyes that cannot be attributed to a structural abnormality; it is a functional reduction in the vision of an eye caused by disuse during a critical period of visual development, Amblyopia is defined as reduced and uncorrectable vision in a structurally normal eye, Amblyopia or \"lazy eye\" represents a disorder of the visual system characterized by poor vision in an eye that is otherwise physically normal. , Amblyopia is a common visual disorder that results in a spatial acuity deficit in the affected eye, Amblyopia is a common deficit in spatial vision that could be based on either unreliable local estimates of image structure, irregularities in global image integration or a combination of errors at both these stages., Amblyopia is a disorder of visual acuity in one eye, thought to arise from suppression by the other eye during development of the visual cortex., Amblyopia is characterised by decrease in vision in one or both eyes as a result of processing defect in the visual pathways of the brain, Amblyopia is defined as a loss of letter recognition visual acuity in the affected eye; however, studies in both nonhuman primates and man have shown that other important aspects of vision, including color, motion, and contour perception, are also abnormal, Amblyopia, commonly known as \"lazy eye,\" is a frequent but preventable cause of decreased vision, Here, we consider four explanations that may account for decreased fellow eye sensitivity: the fellow eye is adversely impacted by treatment for amblyopia; the maturation of the fellow eye is delayed by amblyopia; fellow eye sensitivity is impacted for visual functions that rely on binocular cortex; and fellow eye deficits reflect an adaptive mechanism that works to equalize the sensitivity of the two eyes, Therefore, the aim of this review paper is to provide a comprehensive review of current knowledge about the effects of amblyopia on eye movements, upper limb reaching and grasping movements, as well as balance and gait, Atropine occlusion in the treatment of strabismic amblyopia and its effect upon the non-amblyopic eye., Amblyopia is the most common cause of monocular visual impairment in children, with a prevalence of 2-3%, Amblyopia is a neurodevelopmental disorder of the visual system, as a result of discordant visual experience during infancy or early childhood, By its nature, however, amblyopia has an adverse effect on the development of a binocular visual system and the interactions between signals from two eyes., Unilateral Amblyopia Affects Two Eyes: Fellow Eye Deficits in Amblyopia., PURPOSE: Impairment of spatiotemporal visual processing is the hallmark of amblyopia, but its effects on eye movements during visuomotor tasks have rarely been, Amblyopia is defined as a loss of letter recognition visual acuity in the affected eye; however, studies in both nonhuman primates and man have shown that other important aspects of vision, including color, motion, and contour perception, are also abnormal., Further research targeted at exploring fellow eye deficits in amblyopia will provide us with a broader understanding of normal visual development and how amblyopia impacts the developing visual system., While these fellow eye deficits have been noted, no overarching theory has been proposed to describe why and under what conditions the fellow eye is impacted by amblyopia., Here, we consider four explanations that may account for decreased fellow eye sensitivity: the fellow eye is adversely impacted by treatment for amblyopia; the maturation of the fellow eye is delayed by amblyopia; fellow eye sensitivity is impacted for visual functions that rely on binocular cortex; and fellow eye deficits reflect an adaptive mechanism that works to equalize the sensitivity of the two eyes., In anisometropes, the amblyopic eye influenced a relatively small proportion of cortical neurons; in strabismics, the influence of the two eyes was more nearly equal., studied. Here the authors investigate how visual deficits in anisometropic amblyopia affect saccadic eye movements.METHODS: Thirteen patients with anisometropic amblyopia and 13 control subj, Unilateral amblyopia is a visual disorder that arises after selective disruption of visual input to one eye during critical periods of development., Amblyopia is a developmental disorder resulting in poor vision in one eye., In the clinic, amblyopia is understood as poor visual acuity in an eye that was deprived of pattern vision early in life., Ocular misalignment or unilateral blur often causes amblyopia, a disorder that has become a standard for understanding developmental plasticity., Amblyopia is a developmental disorder of pattern vision.,  amblyopia are associated with poor PS. PS of amblyopic and fellow eyes is differentially , The contrast sensitivity function of both eyes of subjects with functional amblyopia has been measured. A clinically significant difference was found between the amblyopic and the normal eye., t appears that the functionally amblyopic eye takes more information from the peripheral parts of the stimulus than does the normal eye, Previous studies focused on the differences between amblyopic patients and normal controls without evaluating amblyopic eyes after patching. To evaluate differences in the superficial vascular density of amblyopic eyes, normal eyes, and amblyopic eyes reaching normal BCVA after patch therapy,[SEP]Relations: VANGL2 has relations: anatomy_protein_present with eye, anatomy_protein_present with eye. Strabismus has relations: drug_effect with Atropine, drug_effect with Atropine.", "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]", "label": "no"}
{"id": "converted_2316", "sentence1": "Can the CEP290 gene mutations be targeted by AAV-mediated gene therapy?", "sentence2": "The large size of the CEP290 gene prevents its use in adeno-associated virus (AAV)-mediated gene augmentation therapy.[SEP]", "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]", "label": "yes"}
{"id": "converted_154", "sentence1": "Does strenuous physical activity affect thyroid hormone metabolism?", "sentence2": "The results of the present study in a unique experimental human model of maximal exposure to altitude and physical exercise demonstrate that extreme HA and strenuous physical exercise are coupled with specific endocrine adaptations. These include increased activity of the GH/IGF-I axis and a low T(3) syndrome, 3,5,3'-triiodothyronine (T3) and T4 levels increase during strenuous exercise, and, at the end of the exercise bout, a decrease of T3 and T4 levels, with an increase in TSH during the following 4-5 days, is seen., the obtained results indicate that in intense exercise, causing the rapid development of fatigue, rapid increases in serum levels of hormones of the pituitary-adrenocortical, pituitary-gonadal and pituitary-thyroid systems occur., Mean levels of fasting plasma estradiol, luteinizing hormone, follicle-stimulating hormone, free thyroxine and triiodothyronine were significantly lower in AR compared to ER and SE., Reductions in plasma T4, T3 and T3/T4 ratio are probably due to inhibition of T4 secretion and 5'-monodeiodination with possible conversion of T4 to reverse T3 (rT3). These processes may represent a mechanism for regulation of thyroid hormone metabolism during strenuous and extended flight., Strenuous endurance training seems to have minor changes on the function of the thyroid gland. Depressed T4 levels in runners may rather be due to lowered TBG levels than due to direct effect of training., brief strenuous swimming or moderate bicycle exercise had minor or no effect on thyroid hormone concentrations when consideration was given to the attendant hemoconcentration., thyroxine were determined in 26 men participating in a 90-km cross-country ski race, before, immediately after, and on the following days, Total thyroxine and free thyroxine in serum were significantly increased at the end of the race, but had returned to the pre-raced levels during the rest of the observation period., There are controversial results concerning thyroid hormone metabolism during strenuous exercise in adult athletes and only scant data concerning the impact of strenuous exercise on thyroid hormone metabolism in children and adolescents.[SEP]Relations: thyroid gland has relations: anatomy_protein_present with AR, anatomy_protein_present with AR.", "label": "yes"}
{"id": "converted_1544", "sentence1": "Could Hyperthermic intraperitoneal chemotherapy (HIPEC) be effective for the treatment of recurrent ovarian cancer?", "sentence2": "The use of HIPEC after aggressive cytoreductive surgery in patients with ovarian cancer with peritoneal dissemination can be performed with acceptable postoperative morbidity rates. Knowledge of the factors associated with the onset of these postoperative adverse events allows better management of the same and offers the patient a safe procedure, These results showed that the association of HIPEC with a complete cytoreduction for recurrent ovarian cancer presents acceptable morbidity and survival, There is level-one evidence suggesting the benefit of postoperative adjuvant intraperitoneal chemotherapy for patients with advanced ovarian cancer after cytoreductive surgery, albeit catheter-related complications resulted after treatment discontinuation. Studies report the use of HIPEC predominantly in the setting of recurrent disease and have demonstrated encouraging results, which merits further investigation in future clinical trials,  The combination of SCR and HIPEC seems to improve survival rate in patients suffering from platinum-sensitive EOC recurrence with respect to no-HIPEC treatments. This result further supports the need of a randomized trial,  Cautious extrapolation of data from standard normothermic, nonintraoperative, intraperitoneal chemotherapy and data from Phase II and nonrandomized comparative studies suggest that HIPEC delivered at the time of surgery for ovarian cancer has definite potential, The available evidence suggests that a potential survival benefit of adding HIPEC may be largest in the settings of secondary CRS for stage III ovarian cancer and salvage CRS for recurrent ovarian cancer, two time-points representing failure of initial standard therapy. There is much less evidence for a potential benefit of HIPEC for less advanced stages (I-II) and for earlier time-points in the treatment of ovarian cancer (upfront, interval and consolidation), Survival benefit of adding Hyperthermic IntraPEritoneal Chemotherapy (HIPEC) at the different time-points of treatment of ovarian cancer, Patients suffering from peritoneal recurrence of ovarian cancer should be considered for radical reoperation with HIPEC in a center with expertise in multimodal therapeutic options. Organ-preserving cytoreductive surgery allows complete cytoreduction with the goal of decreasing morbidity,  In recurrent platinum-sensitive ovarian cancer patients, the use of CRS plus HIPEC represents a safe treatment, able to significantly influence the survival rates compared to chemotherapy alone or surgery plus standard chemotherapy,  The results of our study indicate the feasibility and the potential benefit of a protocol including systemic chemotherapy, surgical cytoreduction and HIPEC in patients with peritoneal carcinomatosis from ovarian cancer. A phase III trial to compare this approach with conventional treatment is needed, In selected patients with heavily pretreated recurrent ovarian cancer, cytoreduction combined with HIPEC may provide a meaningful OS with acceptable morbidity. Optimal results are achieved in patients with a macroscopically complete resection and biologically favorable disease,  HIPEC is a complement to radical surgery/ peritonectomy, which has been shown to be a surgical procedure with high tolerability, low morbimortality, enhanced survival and prolonged disease-free interval in patients with peritoneal carcinomatosis for recurrent ovarian cancer,  Despite the heterogeneity of the studies reviewed, current evidence suggest that complete CRS and HIPEC may be a feasible option with potential benefits that are comparable with the current standard of care. A randomized trial is required to establish the role of HIPEC in ovarian cancer, in the majority of patients with primary and recurrent advanced ovarian cancer, cytoreductive surgery combined with HIPEC can lead to a substantial increase in subsequent rates of disease-free and overall survival,  Peritonectomy procedures combined with HIPEC offer promising long-term survival in patients with diffuse peritoneal ovarian carcinomatosis. They achieve high adequate primary and secondary surgical cytoreduction rates with acceptable morbidity and mortality, Cytoreduction surgery with hyperthermic intraperitoneal chemotherapy in recurrent ovarian cancer improves progression-free survival, especially in BRCA-positive patients- a case-control study., Survival benefit of adding Hyperthermic IntraPEritoneal Chemotherapy (HIPEC) at the different time-points of treatment of ovarian cancer: review of evidence., Some encouraging results have been reported by the treatment of peritoneal carcinomatosis (PC) from ovarian cancer by complete surgical cytoreduction, peritonectomy and hyperthermic intraperitoneal chemotherapy (HIPEC)., Although standard treatment for advanced epithelial ovarian cancer (EOC) consists of surgical debulking and intravenous platinum- and taxane-based chemotherapy, favorable oncological outcomes have been recently reported with the use of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC)., Trabectedin, Hyperthermic intraperitoneal chemotherapy (HIPEC) and chemo-immunotherapy may be become a promising therapy for the treatment of ovarian cancer., Hyperthermic intraperitoneal chemotherapy (HIPEC) represents a new treatment strategy aimed to improve outcome of patients with advanced ovarian cancer., Favorable oncological outcomes have been reported in several trials with the introduction of Cytoreductive Surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in the treatment of Advanced Epithelial Ovarian Cancer (EOC)., Based on theoretical and experimental basis, HIPEC should stand as an effective treatment for ovarian cancer., Some encouraging results have been reported by the treatment of peritoneal carcinomatosis (PC) from ovarian cancer by complete surgical cytoreduction, peritonectomy and hyperthermic intraperitoneal chemotherapy (HIPEC), Based on theoretical and experimental basis, HIPEC should stand as an effective treatment for ovarian cancer, Hyperthermic intraperitoneal chemotherapy (HIPEC) represents a new treatment strategy aimed to improve outcome of patients with advanced ovarian cancer, [Importance of hyperthermic intraperitoneal chemotherapy (HIPEC) in ovarian cancer].[SEP]", "label": "yes"}
{"id": "converted_2599", "sentence1": "A bite from the Lone Star Tick Amblyomma americanum, can cause the victim to become allergic to red meat, yes or no?", "sentence2": "A recent discovery of an IgE antibody specific to galactose-α-1,3-galactose, which is a carbohydrate abundantly expressed on cells and tissues of beef, pork, and lamb, adds one more tool to aid the clinician in making the appropriate diagnosis. A link has been discovered between the bite of the Lone Star Tick (Amblyomma americanum) and the development of sensitivity to galactose-α-1,3-galactose. , . Recently described conditions such as Southern tick-associated rash illness and anaphylaxis to red meat following tick bites have been attributed to the lone star tick., Recently described conditions such as Southern tick-associated rash illness and anaphylaxis to red meat following tick bites have been attributed to the lone star tick.[SEP]", "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]", "label": "yes"}
{"id": "converted_436", "sentence1": "Is progesterone effective for treatment of patients with traumatic brain injury based on clinical trial data?", "sentence2": "BACKGROUND: Progesterone has been associated with robust positive effects in animal models of traumatic brain injury (TBI) and with clinical benefits in two phase 2 randomized, controlled trials. , The proportion of patients with a favorable outcome on the Glasgow Outcome Scale (good recovery or moderate disability) was 50.4% with progesterone, as compared with 50.5% with placebo. Mortality was similar in the two groups. No relevant safety differences were noted between progesterone and placebo. CONCLUSIONS: Primary and secondary efficacy analyses showed no clinical benefit of progesterone in patients with severe TBI. These data stand in contrast to the robust preclinical data and results of early single-center trials that provided the impetus to initiate phase 3 trials., BACKGROUND: Traumatic brain injury (TBI) is a major cause of death and disability worldwide. Progesterone has been shown to improve neurologic outcome in multiple experimental models and two early-phase trials involving patients with TBI. , There was no significant difference between the progesterone group and the placebo group in the proportion of patients with a favorable outcome (relative benefit of progesterone, 0.95; 95% confidence interval [CI], 0.85 to 1.06; P=0.35). Phlebitis or thrombophlebitis was more frequent in the progesterone group than in the placebo group (relative risk, 3.03; CI, 1.96 to 4.66). , CONCLUSIONS: This clinical trial did not show a benefit of progesterone over placebo in the improvement of outcomes in patients with acute TBI. , Numerous studies, however, show that progesterone has substantial pleiotropic properties as a neuroprotective agent in both animal models and humans., RESULTS: There was a better recovery rate and GOS score for the patients who were given progesterone than for those in the control group in a 3-months follow-up period (50% vs. 21%); subgroup analysis showed a significant difference in the percentage of favorable outcome between the two groups with GCS of 5-8 (p=0.03). CONCLUSION: The use of progesterone may significantly improve neurologic outcome of patients suffering severe TBI up to 3 months after injury, especially those with 5≤GCS≤8, providing a potential benefit to the treatment of acute severe TBI patients. Considering this drug had no significant side effects, so progesterone could be used in patients with severe TBI as a neuro-protective drug., While progesterone and ciclosporin have shown promise in phase II studies, success in larger phase III, randomized, multicentre, clinical trials is pending.,  All three studies reported the effects of progesterone on mortality. The pooled risk ratio (RR) for mortality at end of follow-up was 0.61, 95% confidence interval (CI) 0.40 to 0.93. Three studies measured disability and found the RR of death or severe disability in patients treated with progesterone to be 0.77, 95% CI 0.62 to 0.96., AUTHORS' CONCLUSIONS: Current clinical evidence from three small RCTs indicates progesterone may improve the neurologic outcome of patients suffering TBI. This evidence is still insufficient and further multicentre randomised controlled trials are required., GOS was classified to 2 main categories of favorable and unfavorable recovery, of which, favorable recovery in placebo, progesterone, and progesterone-vitamin D was 25%, 45%, and 60%, respectively which showed a statistical significant difference among the groups (P-value = 0.03). CONCLUSION: The results showed that recovery rate in patients with severe brain trauma in the group receiving progesterone and vitamin D together was significantly higher than that of progesterone group, which was in turn higher than that of placebo group.,  The pooled relative risk (RR) for mortality at end of follow-up is 0.61, 95% confidence interval (CI) 0.40 to 0.93. Three studies measured disability and found the RR of death or severe disability in patients treated with progesterone was 0.77, 95% confidence interval (CI) 0.62 to 0.96., AUTHORS' CONCLUSIONS: Current clinical evidence from three small RCTs indicates progesterone may improve the neurologic outcome of patients suffering TBI. This evidence is still insufficient and further multicentre randomised controlled trials are required., Clinical trials have shown that short-and long-term progesterone treatment induces a significant improvement in the level of disability among patients with brain injury. , Improved outcomes from the administration of progesterone for patients with acute severe traumatic brain injury: a randomized controlled trial., CONCLUSION: Our data suggest that acute severe TBI patients with administration of progesterone hold improved neurologic outcomes for up to 6 months. These results provide information important for further large and multicenter clinical trials on progesterone as a promising neuroprotective drug. , The modified Functional Independence Measure scores in the progesterone group were higher than those in the placebo group at both 3-month and 6-month follow-up (P < 0.05 and P < 0.01). The mortality rate of the progesterone group was significantly lower than that of the placebo group at 6-month follow-up (P < 0.05). , CONCLUSION: Our data suggest that acute severe TBI patients with administration of progesterone hold improved neurologic outcomes for up to 6 months. These results provide information important for further large and multicenter clinical trials on progesterone as a promising neuroprotective drug. , These data, combined with the results of the previously published ProTECT trial, show progesterone to be safe and potentially efficacious in the treatment of TBI. Larger phase III trials will be necessary to verify results prior to clinical implementation., CONCLUSION: It indicated that successive early application of PG will benefit the patients with acute severe head injury by improving the recovery and reducing the disability, which may be related to its alleviating inflammatory and lipid peroxidation response., Adverse and serious adverse event rates were similar in both groups, except that patients randomized to progesterone had a lower 30-day mortality rate than controls (rate ratio 0.43; 95% confidence interval 0.18 to 0.99). , However, moderate traumatic brain injury survivors who received progesterone were more likely to have a moderate to good outcome than those randomized to placebo. CONCLUSION: In this small study, progesterone caused no discernible harm and showed possible signs of benefit., After more than 30 years of research and 30 failed clinical trials with as many different treatments, progesterone is the first agent to demonstrate robust clinical efficacy as a treatment for traumatic brain injuries., After more than 30 years of research and 30 failed clinical trials with as many different treatments, progesterone is the first agent to demonstrate robust clinical efficacy as a treatment for traumatic brain injuries, A US National Institutes of Health-sponsored, nationwide Phase III clinical trial is now evaluating progesterone for moderate-to-severe TBI in 1200 patients, An industry-sponsored Phase III international trial is also under way, and planning for a trial using progesterone to treat pediatric brain injury has begun, More than two decades of pre-clinical research and two recent clinical trials have shown that progesterone (PROG) and its metabolites exert beneficial effects after traumatic brain injury (TBI) through a number of metabolic and physiological pathways that can reduce damage in many different tissues and organ systems, After more than 30 years of research and 30 failed clinical trials with as many different treatments, progesterone is the first agent to demonstrate robust clinical efficacy as a treatment for traumatic brain injuries, RESULTS: Analysis of these reviews yielded meanfuling observations: (1) The effectiveness of most ordinary treatments in TBI is inconclusive except that corticosteroids are likely to be ineffective or harmful, and tranexamic acid, nimodipine and progesterone show a promising effect in bleeding trauma, traumatic subarachnoid hemorrhage, TBI or severe TBI., Laboratory data strongly show that progesterone treatment after TBI reduces edema, improves outcomes, and restores blood-brain barrier function. Clinical studies to date agree with these data, and there are ongoing human trials for progesterone treatment after TBI.[SEP]Relations: Progesterone has relations: contraindication with thrombophlebitis, contraindication with thrombophlebitis. Tranexamic acid has relations: contraindication with thrombophlebitis, drug_drug with Progesterone, contraindication with thrombophlebitis, drug_drug with Progesterone. Cyclosporine has relations: drug_drug with Progesterone, drug_drug with Progesterone. Thrombophlebitis has relations: drug_effect with Progesterone, drug_effect with Progesterone. phlebitis has relations: disease_disease with thrombophlebitis, disease_disease with thrombophlebitis.", "label": "no"}
{"id": "converted_1238", "sentence1": "Is the Snord116 cluster associated with the Prader-Willi syndrome?", "sentence2": "All three deletions included SNORD116, but only two encompassed parts of SNURF-SNRPN, implicating SNORD116 as the major contributor to the Prader-Willi phenotype. Our case adds further information about genotype-phenotype correlation and supports the hypothesis that SNORD116 plays a major role in the pathogenesis of Prader-Willi syndrome, These results demonstrate that the AS candidate drug topotecan acts predominantly through stabilizing R loops and chromatin decondensation at the paternally expressed PWS Snord116 locus. Our study holds promise for targeted therapies to the Snord116 locus for both AS and PWS., Prader-Willi syndrome (PWS) is caused by the loss of RNA expression from an imprinted region on chromosome 15 that includes SNRPN, SNORD115, and SNORD116. , Recently published data strongly suggest a role for the paternally expressed small nucleolar RNA (snoRNA) cluster, SNORD116, in PWS etiology., Whereas loss of function of the SNORD116 genes appears to be responsible for the major features of PWS, the role of the other genes is less clear. , Recent data suggest that snoRNA Snord116 is important for the pathogenesis of Prader-Willi syndrome (PWS) characterized by hyperphagia and obesity. The current study was conducted to assess a potential cellular link between Snord116 and phenotypes of PWS. , The imprinted Snurf-Snrpn chromosomal domain contains two large arrays of tandemly repeated, paternally expressed box C/D small-nucleolar RNA (snoRNA) genes: the SNORD115 (H/MBII-52) and SNORD116 (H/MBII-85) gene clusters believed to play key roles in the fine-tuning of serotonin receptor (5-HT2C) pre-mRNA processing and in the etiology of the Prader-Willi Syndrome (PWS), respectively, There are multiple imprinted genes in this region, the loss of which contribute to the complete phenotype of Prader-Willi syndrome. However, absence of a small nucleolar organizing RNA gene, SNORD116, seems to reproduce many of the clinical features., Both kits should be made available for accurate characterization of PWS/AS deletion subtypes as well as evaluating for IC and SNORD116 microdeletions., There are multiple imprinted genes in this region, the loss of which contribute to the complete phenotype of Prader-Willi syndrome. However, absence of a small nucleolar organizing RNA gene, SNORD116, seems to reproduce many of the clinical features. , Although the SNORD116 gene cluster has become a prime candidate for PWS, it cannot be excluded that other paternally expressed genes in the chromosomal region 15q11q13 contribute to the full phenotype., In addition, recently published data provide strong evidence in support of a role for the snoRNA SNORD116 cluster (HBII-85) in PWS etiology., Identification and characterization of this case provide unequivocal evidence for a critical role for the SNORD116 snoRNA molecules in PWS pathogenesis. [SEP]Relations: SNRPN has relations: disease_protein with Prader-Willi syndrome, disease_protein with Prader-Willi syndrome. small nuclear ribonucleoprotein complex has relations: cellcomp_protein with SNRPN, cellcomp_protein with SNRPN. Prader-Willi syndrome has relations: disease_protein with SNRPN, disease_protein with SNRPN.", "label": "yes"}
{"id": "converted_3583", "sentence1": "Has amantadine ER been approved by the FDA?", "sentence2": "ADS-5102 (amantadine) extended-release (ER) capsules (GOCOVRITM) is a recent US FDA-approved treatment for dyskinesia in PD patients. [SEP]", "label": "yes"}
{"id": "converted_3830", "sentence1": "Should tirilazad be used for treatment of ischemic stroke?", "sentence2": "CONCLUSION: Tirilazad had no effect on clinical outcome but did decrease symptomatic vasospasm in five trials of aneurysmal SAH. , Tirilazad did not significantly decrease unfavorable clinical outcome on the GOS (odds ratio [OR] 1.04, 95% confidence interval [CI] 0.89-1.20) or cerebral infarction (OR 1.04, 95% CI 0.89-1.22). , The authors investigated whether the lack of effect of tirilazad on clinical outcome in patients with acute ischemic stroke is explained by failure of tirilazad to reduce infarct volume. , Tirilazad did not alter early case fatality (odds ratio [OR] 1.11, 95% confidence interval [CI] 0.79 to 1.56) or end-of-trial case fatality (OR 1.12, 95% CI 0.88 to 1.44). A just-significant increase in death and disability, assessed as either the expanded Barthel Index (OR 1.23, 95% CI 1.01 to 1.51) or Glasgow Outcome Scale (OR 1. 23, 95% CI 1.01 to 1.50) was observed., CONCLUSIONS: Tirilazad mesylate increases death and disability by about one fifth when given to patients with acute ischemic stroke. Although further trials of tirilazad are now unwarranted, analysis of individual patient data from the trials may help elucidate why tirilazad appears to worsen outcome in acute ischemic stroke.[SEP]", "label": "no"}
{"id": "converted_1167", "sentence1": "Is COL5A2 gene associated to ischemic heart disease?", "sentence2": "Analysis of a gene co-expression network establishes robust association between Col5a2 and ischemic heart disease, Col5a2, a gene previously not specifically linked to MI response but responsible for the classic type of Ehlers-Danlos syndrome, was found to have many and strong co-expression associations within this community, Col5a2 shows predictive potential in MI, and in principle may represent a novel candidate marker for the identification and treatment of ischemic cardiovascular disease, Analysis of a gene co-expression network establishes robust association between Col5a2 and ischemic heart disease.[SEP]", "label": "yes"}
{"id": "converted_3284", "sentence1": "Do de novo truncating mutations in WASF1 cause cancer?", "sentence2": "De Novo Truncating Mutations in WASF1 Cause Intellectual Disability with Seizures., Here, using exome sequencing and whole-genome sequencing, we identified three de novo truncating mutations in WAS protein family member 1 (WASF1) in five unrelated individuals with moderate to profound intellectual disability with autistic features and seizures. WASF1, also known as WAVE1, is part of the WAVE complex and acts as a mediator between Rac-GTPase and actin to induce actin polymerization. The three mutations connected by Matchmaker Exchange were c.1516C>T (p.Arg506Ter), which occurs in three unrelated individuals, c.1558C>T (p.Gln520Ter), and c.1482delinsGCCAGG (p.Ile494MetfsTer23). All three variants are predicted to partially or fully disrupt the C-terminal actin-binding WCA domain. Functional studies using fibroblast cells from two affected individuals with the c.1516C>T mutation showed a truncated WASF1 and a defect in actin remodeling. This study provides evidence that de novo heterozygous mutations in WASF1 cause a rare form of intellectual disability.[SEP]", "label": "no"}
{"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]", "label": "yes"}
{"id": "converted_1447", "sentence1": "Has silicon been used in treatment of  incontinence ?", "sentence2": "an artificial anal sphincter. Worldwide, there are two established devices on the market: the artificial bowel sphincter® (ABS) from A. M. S. (Minnetonka, MN, USA) and the soft anal band® from A. M. I. (Feldkirch, Austria). How to implant the artificial anal sphincter? Both devices consist of a silicon cuff which can be filled with fluid., The InVance™ system uses a silicon-coated polyester sling positioned under the bulbar urethra via a perineal incision., Through a perineal incision three titanium screws with a polipropylene suture were inserted in each ischiopubic rami, and a silicon/polipropylene mesh (Invance) is affixed to them, compressing the bulbar urethra, surgical treatment of female stress urinary incontinence with a trans-obturator sub-urethral tape of Uratape (Porgés). METHODS: Treatment and follow up of their complication were performed at the CHRU of Lille. RESULTS: In both cases, this complication is related to prolonged vaginal exposition of the tape. Vaginal erosion always occurs next to the silicon coated section of the tape, A non-elastic, polypropylene tape (UraTape, Mentor-Porgès) with a silicon coated central part was placed under the mid-urethra.,  Stress incontinence is a rare complication in men, usually following prostatic surgery. It can be treated conservatively with pelvic floor training and alpha-adrenergic receptor agonists and if necessary surgically with submucosal collagen or silicon injections in the sphincter area or implantation of a sphincter prosthesis, The Femassist is a medical-grade silicon dome-shaped device, worn over the urethra and held securely via suction and a commercially available adhesive lotion., To examine the performance of a silicon urinary control device for nonsurgical management of women with genuine stress incontinence, The \"FemAssist\" is a dome-shaped medical grade silicon device intended to be worn over the external urethral meatus and held in place by suction and an adhesive gel. Thirty eight women with varying degrees of genuine stress urinary incontinence (GSUI) or mixed incontinence on multichannel urodynamic testing were fitted with one of two sizes of \"FemAssist[SEP]", "label": "yes"}
{"id": "converted_822", "sentence1": "Could transcription factors act as cell-cell signalling molecules?", "sentence2": "Pax6 is a transcription factor essential for the development of tissues including the eyes, central nervous system and endocrine glands of vertebrates and invertebrates. It regulates the expression of a broad range of molecules, including transcription factors, cell adhesion and short-range cell-cell signalling molecules, hormones and structural proteins, Recent data support the view that transcription factors - in particular, homeoproteins - can be transferred from cell to cell and have direct non-cell-autonomous (and therefore paracrine) activities[SEP]", "label": "yes"}
{"id": "converted_4604", "sentence1": "Is Daprodustat effective for anemia?", "sentence2": "CONCLUSIONS: Oral daprodustat was noninferior to CERA in achieving and maintaining target hemoglobin levels in Japanese ND patients. , BACKGROUND: The Anemia Studies in chronic kidney disease (CKD): Erythropoiesis via a Novel prolyl hydroxylase inhibitor (PHI) Daprodustat-Dialysis (ASCEND-D) trial will test the hypothesis that daprodustat is non-inferior to comparator epoetin alfa or darbepoetin alfa for two co-primary endpoints: haemoglobin efficacy and cardiovascular safety., Daprodustat is one of the orally administrated small-molecule HIF-PH inhibitors, leading to an increase in erythropoietin production, which is regulated by HIF. Also, daprodustat is expected to improve iron metabolism. Recently, several clinical trials showed its efficacy and safety in both hemodialysis- and non-hemodialysis- dependent CKD patients. , Once-daily oral daprodustat treatment was generally well tolerated and mean hemoglobin was achieved and maintained within the target range in Japanese peritoneal dialysis participants., Daprodustat is a hypoxia-inducible factor-prolyl hydroxylase inhibitor for the treatment of anemia of chronic kidney disease. , Daprodustat, an oral hypoxia-inducible factor prolyl hydroxylase inhibitor, is being investigated for treatment of anemia in chronic kidney disease., Daprodustat for the Treatment of Anemia in Patients Not Undergoing Dialysis., ONCLUSIONS: Among patients with CKD and anemia who were not undergoing dialysis, daprodustat was noninferior to darbepoetin alfa with respect to the change in the hemoglobin level from baseline and with respect to cardiovascular outcomes. , Daprodustat for the Treatment of Anemia in Patients Undergoing Dialysis., CONCLUSIONS: Among patients with CKD undergoing dialysis, daprodustat was noninferior to ESAs regarding the change in the hemoglobin level from baseline and cardiovascular outcomes., Daprodustat (GSK1278863) is a hypoxia-inducible factor (HIF)-prolyl hydroxylase (PHD) inhibitor in development for treatment of anemia of chronic kidney disease., BACKGROUND: Daprodustat (GSK1278863) is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor being developed for treatment of anemia associated with chronic kidney disease (CKD)., Daprodustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor developed for treating anemia of chronic kidney disease., Daprodustat is under development as an emerging new class of agents for the treatment of anemia associated with chronic kidney disease (CKD)., Conclusion: Daprodustat was efficacious and well tolerated for anemia in both NDD and DD patients in the short term based on current RCTs., And daprodustat may become an effective alternative for treatment of anemia with CKD.[SEP]", "label": "yes"}
{"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]", "label": "yes"}
{"id": "converted_3384", "sentence1": "Does the chromatin remodeling complex, RSC target H2A.Z nucleosomes?", "sentence2": "In contrast, the upstream nucleosome which covers the TATA box under repressed conditions is shifted approximately 50 bp further upstream by the ATP-dependent chromatin remodeler RSC upon activation. It is marked with the histone variant H2A.Z and H4K16 acetylation in active state, In RSC-depleted cells, NFRs shrink such that the average positions of flanking nucleosomes move toward predicted sites., In contrast, H2A.Z deposition is dispensable for nucleosome positioning. , Emerging lines of evidence indicate that histone variants (H2AX and H2A.Z), histone post-translational modifications (acetylation, phosphorylation, methylation and ubiquitination) and chromatin-remodeling complexes (INO80, SWR1, SWI/SNF, RSC and NuRD) are important and direct players in the DNA double-strand break (DSB) response as well., H2A.Z probably helps RSC in keeping the gene nucleosome-fre, Accordingly, the absence of SWR-C or histone H2A.Z results in compromised chromatin remodeling and impaired gene expression in the absence of RSC and H3K4 methylation.[SEP]Relations: nucleosome mobilization has relations: bioprocess_protein with INO80, bioprocess_protein with INO80. nucleosome has relations: cellcomp_protein with H2AX, cellcomp_protein with H2AX.", "label": "yes"}
{"id": "converted_2197", "sentence1": "Is Pfh1 a component of the replisome?", "sentence2": "Pfh1 Is an Accessory Replicative Helicase that Interacts with the Replisome to Facilitate Fork Progression and Preserve Genome Integrity, Although the Schizosaccharomyces pombe 5'-to-3' DNA helicase Pfh1 is known to promote fork progression, its genomic targets, dynamics, and mechanisms of action are largely unknown. Here we address these questions by integrating genome-wide identification of Pfh1 binding sites, comprehensive analysis of the effects of Pfh1 depletion on replication and DNA damage, and proteomic analysis of Pfh1 interaction partners by immunoaffinity purification mass spectrometry., DNA replication through hard-to-replicate sites, including both highly transcribed RNA Pol II and Pol III genes, requires the S. pombe Pfh1 helicase., Here, we show that Pfh1 is required for efficient fork movement in the ribosomal DNA, the mating type locus, tRNA, 5S ribosomal RNA genes, and genes that are highly transcribed by RNA polymerase II. ,  Thus, Pfh1 promotes DNA replication and separation of converged replication forks and suppresses DNA damage at hard-to-replicate sites., Cells depleted of Pfh1 were inviable if they also lacked the human TIMELESS homolog Swi1, a replisome component that stabilizes stalled forks., Pfh1 Is an Accessory Replicative Helicase that Interacts with the Replisome to Facilitate Fork Progression and Preserve Genome Integrity., Thus, we conclude that Pfh1 is an accessory DNA helicase that interacts with the replisome and promotes replication and suppresses DNA damage at hard-to-replicate sites., Consistent with this interpretation, Pfh1 co-purified with many key replisome components, including the hexameric MCM helicase, replicative DNA polymerases, RPA, and the processivity clamp PCNA in an S phase dependent manner., Although Pfh1 affected replication and suppressed DNA damage at discrete sites throughout the genome, Pfh1 and the replicative DNA polymerase bound to similar extents to both Pfh1-dependent and independent sites, suggesting that Pfh1 is proximal to the replication machinery during S phase., Cells depleted of Pfh1 were inviable if they also lacked the human TIMELESS homolog Swi1, a replisome component that stabilizes stalled forks, Here, we show that Pfh1 is required for efficient fork movement in the ribosomal DNA, the mating type locus, tRNA, 5S ribosomal RNA genes, and genes that are highly transcribed by RNA polymerase II, Thus, Pfh1 promotes DNA replication and separation of converged replication forks and suppresses DNA damage at hard-to-replicate sites, Cells depleted of Pfh1 were inviable if they also lacked the human TIMELESS homolog Swi1, a replisome component that stabilizes stalled forks., Thus, we conclude that Pfh1 is an accessory DNA helicase that interacts with the replisome and promotes replication and suppresses DNA damage at hard-to-replicate sites., Consistent with this interpretation, Pfh1 co-purified with many key replisome components, including the hexameric MCM helicase, replicative DNA polymerases, RPA, and the processivity clamp PCNA in an S phase dependent manner., Pfh1 Is an Accessory Replicative Helicase that Interacts with the Replisome to Facilitate Fork Progression and Preserve Genome Integrity.[SEP]Relations: replisome has relations: cellcomp_protein with PCNA, cellcomp_protein with PCNA.", "label": "no"}
{"id": "converted_1978", "sentence1": "Do histone variant mH2A (macro-H2A) levels decrease upon differentiation?", "sentence2": "Through manipulation of macroH2A isoforms, we further demonstrate that macroH2A2 is the predominant barrier to reprogramming., In particular, we find macroH2A isoforms to be highly enriched at target genes of the K27me3 demethylase, Utx, which are reactivated early in iPS reprogramming,  Therefore, we propose that macroH2A isoforms provide a redundant silencing layer or terminal differentiation 'lock' at critical pluripotency genes that presents as an epigenetic barrier when differentiated cells are challenged to reprogram., Histone variant macroH2A confers resistance to nuclear reprogramming, Resistance to reprogramming is associated with incorporation of the histone variant macroH2A, which is retained on the Xi of differentiated cells, but absent from the Xi of EpiSCs., We highlight the role of macroH2A in the establishment and maintenance of differentiated states and we discuss its still poorly recognized function in transcriptional activation., Histone variant macroH2A marks embryonic differentiation in vivo and acts as an epigenetic barrier to induced pluripotency., MacroH2A.1 was found to be present at low levels upon the establishment of pluripotency in the inner cell mass and epiblast, but it was highly enriched in the trophectoderm and differentiated somatic cells later in mouse development., Chromatin immunoprecipitation revealed that macroH2A.1 is incorporated in the chromatin of regulatory regions of pluripotency genes in somatic cells such as mouse embryonic fibroblasts and adult neural stem cells, but not in embryonic stem cells., In addition, overexpression of macroH2A isoforms prevented efficient reprogramming of epiblast stem cells to naïve pluripotency. , Macro histone variants are critical for the differentiation of human pluripotent cells, Here we show that the knockdown of macro histone variants impaired the in vitro and in vivo differentiation of human pluripotent cells, likely through defects in the silencing of pluripotency-related genes, Furthermore, male and female mH2A-deficient ESCs proliferate normally under pluripotency culture conditions, and respond to several standard differentiation procedures efficiently.[SEP]", "label": "no"}
{"id": "converted_697", "sentence1": "Are there randomised controlled trials on sevoflurane?", "sentence2": "After Ethics Review Board approval, 44 ASA I-III patients undergoing elective gynaecological surgery were randomised after surgery to either hypercapnic hyperpnoea or control groups., Hypercapnic hyperpnoea in spontaneously breathing patients halves the time of recovery from sevoflurane-induced anaesthesia in the operating room., A total of 200 women undergoing first trimester abortion (American Society of Anesthesiologists physical status I) participated in the study. Patients were randomly assigned to receive either sevoflurane or propofol for short-term sedation., The results showed the incidence of dreaming was significantly different between anaesthesia groups with 60% (60/100) of the sevoflurane group and 33% (33/100) of the propofol group (P=0.000), Anaesthesia administered had no effect on patient satisfaction. The results suggest that the incidence of dreaming was not affected by recovery time. Patient satisfaction was not influenced by choice of sedative and/or by the occurrence of dreaming during sevoflurane or propofol short-term sedation., Prior reports suggest that dreaming during anaesthesia is dependent on recovery time. Dreaming during sedation may impact patient satisfaction, Sevoflurane vs. propofol in patients with coronary disease undergoing mitral surgery: a randomised study., We therefore performed a randomised controlled trial (sevoflurane vs. propofol) to compare cardiac troponin release in patients with coronary disease undergoing mitral surgery., Myocardial injury in remifentanil-based anaesthesia for off-pump coronary artery bypass surgery: an equipotent dose of sevoflurane versus propofol, This randomised controlled trial compared the effect of equipotent anaesthetic doses of sevoflurane (S group) versus propofol (P group), during remifentanil-based anaesthesia for off-pump coronary artery bypass surgery, on myocardial injury. Either sevoflurane or propofol was titrated to maintain bispectral index values between 40 and 50., This randomised, multicentre, parallel-group trial included 98 adult patients. Patients received intravenous propofol for induction followed by sevoflurane maintenance anaesthesia., Patients were randomly allocated to receive sugammadex 2.0 mg kg(-1) or neostigmine 50 microg, We compared the haemodynamics, emergence and recovery characteristics of total intravenous anaesthesia using propofol/remifentanil with sevoflurane/remifentanil anaesthesia, under bispectral index guidance, in 103 patients undergoing surgical procedures lasting > 3.5 h, A randomised controlled trial of paediatric conscious sedation for dental treatment using intravenous midazolam combined with inhaled nitrous oxide or nitrous oxide/sevoflurane, Intravenous midazolam, especially in combination with inhaled nitrous oxide or sevoflurane and nitrous oxide, are effective techniques, with the combination of midazolam and sevoflurane the one most likely to result in successful treatment., We randomly assigned 1063 adult and 322 paediatric elective patients to one of four (adult) or two (paediatric) anaesthesia groups, In both studies, there was no difference in postdischarge outcomes at Day 7. Sevoflurane/sevoflurane was more costly with higher PONV rates in both studies. In adults, the cost per extra episode of PONV avoided was pound 296 (propofol/propofol vs. propofol/ sevoflurane) and pound 333 (propofol/sevoflurane vs. propofol/isoflurane)., Comparison of sevoflurane and nitrous oxide mixture with nitrous oxide alone for inhalation conscious sedation in children having dental treatment: a randomised controlled trial., We studied 411 children aged 3-10 years who were referred for dental treatment. They were randomly allocated to have inhalation conscious sedation with either sevoflurane/nitrous oxide mixture or nitrous oxide alone[SEP]", "label": "yes"}
{"id": "converted_3377", "sentence1": "Is KAT2A involved in Acute myeloid leukemia (AML)?", "sentence2": "Acute myeloid leukemia (AML) is an aggressive cancer with a poor prognosis, for which mainstream treatments have not changed for decades. To identify additional therapeutic targets in AML, we optimize a genome-wide clustered regularly interspaced short palindromic repeats (CRISPR) screening platform and use it to identify genetic vulnerabilities in AML cells. We identify 492 AML-specific cell-essential genes, including several established therapeutic targets such as DOT1L, BCL2, and MEN1, and many other genes including clinically actionable candidates. We validate selected genes using genetic and pharmacological inhibition, and chose KAT2A as a candidate for downstream study. KAT2A inhibition demonstrated anti-AML activity by inducing myeloid differentiation and apoptosis, and suppressed the growth of primary human AMLs of diverse genotypes while sparing normal hemopoietic stem-progenitor cells. Our results propose that KAT2A inhibition should be investigated as a therapeutic strategy in AML and provide a large number of genetic vulnerabilities of this leukemia that can be pursued in downstream studies., Our results propose that KAT2A inhibition should be investigated as a therapeutic strategy in AML and provide a large number of genetic vulnerabilities of this leukemia that can be pursued in downstream studies., KAT2A inhibition demonstrated anti-AML activity by inducing myeloid differentiation and apoptosis, and suppressed the growth of primary human AMLs of diverse genotypes while sparing normal hemopoietic stem-progenitor cells., Our results propose that KAT2A inhibition should be investigated as a therapeutic strategy in AML and provide a large number of genetic vulnerabilities of this leukemia that can be pursued in downstream studies., KAT2A inhibition demonstrated anti-AML activity by inducing myeloid differentiation and apoptosis, and suppressed the growth of primary human AMLs of diverse genotypes while sparing normal hemopoietic stem-progenitor cells.[SEP]Relations: histone-lysine N-methyltransferase activity has relations: molfunc_protein with MEN1, molfunc_protein with DOT1L, molfunc_protein with MEN1, molfunc_protein with DOT1L. multiple endocrine neoplasia has relations: disease_protein with MEN1, disease_protein with MEN1.", "label": "yes"}
{"id": "converted_4145", "sentence1": "Is atenolol metabolized by CYP2D6?", "sentence2": "The study analysed the prescribing and dispensing of CYP2D6 drugs (metoprolol, donepezil, galantamine, codeine, tamoxifen) together with CYP2D6-blocking SSRIs (paroxetine/fluoxetine) or SSRIs without significant CYP2D6 inhibition (citalopram/escitalopram/sertraline), and the related prescribing of CYP2D6-independent comparator drugs (atenolol, rivastigmine, propoxyphene, anastrozole).[SEP]", "label": "no"}
{"id": "converted_525", "sentence1": "Are BBS mutations involved in syndromic Hirschsprung disease?", "sentence2": "Epistasis between RET and BBS mutations modulates enteric innervation and causes syndromic Hirschsprung disease, Here, we report 3 families with BBS and HSCR with concomitant mutations in BBS genes and regulatory RET elements, whose functionality is tested in physiologically relevant assays. Our data suggest that BBS mutations can potentiate HSCR predisposing RET alleles, which by themselves are insufficient to cause disease, Epistasis between RET and BBS mutations modulates enteric innervation and causes syndromic Hirschsprung disease., Our data suggest that BBS mutations can potentiate HSCR predisposing RET alleles, which by themselves are insufficient to cause disease., Here, we report 3 families with BBS and HSCR with concomitant mutations in BBS genes and regulatory RET elements, whose functionality is tested in physiologically relevant assays, Our data suggest that BBS mutations can potentiate HSCR predisposing RET alleles, which by themselves are insufficient to cause disease, Here, we report 3 families with BBS and HSCR with concomitant mutations in BBS genes and regulatory RET elements, whose functionality is tested in physiologically relevant assays[SEP]Relations: hirschsprung disease, susceptibility to has relations: disease_protein with RET, disease_protein with RET.", "label": "yes"}
{"id": "converted_3035", "sentence1": "Is Lasmiditan effective for migraine?", "sentence2": "Amongst the ditans, lasmiditan: (i) fails to constrict human coronary arteries; and (ii) is effective for the acute treatment of migraine in preliminary Phase III clinical trials., Although ongoing phase III clinical trials are needed to confirm its efficacy and safety, lasmiditan might offer an alternative to treat acute migraine with no associated cardiovascular risk., Lasmiditan is considered to be the first member of a new drug category, the neurally acting anti-migraine agent (NAAMA), Lasmiditan for the treatment of acute migraine: a review and potential role in clinical practice., Lasmiditan, a highly selective 5-HT1F agonist, has completed two Phase III randomized, double blind, placebo-controlled clinical trials, with a third - a long-term, open-label safety study - still underway. Research to date suggests lasmiditan lacks vasoconstrictive properties and may be a safe and effective treatment option in patients refractory to current acute migraine medications or who have cardiovascular risk factors., Lasmiditan is an effective acute treatment for migraine: A phase 3 randomized study., Compared with placebo, more patients dosed with lasmiditan 200 mg were free of headache pain at 2 hours after dosing (32.2% vs 15.3%; odds ratio [OR] 2.6, 95% confidence interval [CI] 2.0-3.6, p< 0.001), similar to those dosed with lasmiditan 100 mg (28.2%; OR 2.2, 95% CI 1.6-3.0, p< 0.001). Furthermore, compared with those dosed with placebo, more patients dosed with lasmiditan 200 mg (40.7% vs 29.5%; OR 1.6, 95% CI 1.3-2.1, p< 0.001) and lasmiditan 100 mg (40.9%; OR 1.7, 95% CI, 1.3-2.2, p< 0.001) were free of their MBS at 2 hours after dosing., CONCLUSIONS: Lasmiditan dosed at 200 and 100 mg was efficacious and well tolerated in the treatment of acute migraine among patients with a high level of cardiovascular risk factors, CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that for adult patients with migraine, lasmiditan increases the proportion of subjects who are headache pain free at 2 hours after treating a migraine attack., For the understanding of migraine pathophysiology, it is very important to note that a selective 5-HT(1F) receptor agonist like lasmiditan is effective in the acute treatment of migraine. , While lasmiditan most likely is effective in the treatment of migraine attacks it had, unfortunately, a high incidence of CNS related AEs in the oral RCT. , Acute treatment of migraine with the selective 5-HT1F receptor agonist lasmiditan--a randomised proof-of-concept trial.At intravenous doses of 20 mg and higher, lasmiditan proved effective in the acute treatment of migraine. , Lasmiditan for the treatment of acute migraine: a review and potential role in clinical practice. , BACKGROUND\nLasmiditan (COL-144) is a novel, centrally acting, highly selective 5-HT(1F) receptor agonist without vasoconstrictor activity that seemed effective when given as an intravenous infusion in a proof-of-concept migraine study., INTERPRETATION\nOral lasmiditan seems to be safe and effective in the acute treatment of migraine., The 5-HT1F receptor agonist lasmiditan, a drug acting through non-vasoconstrictive mechanisms, represents a promising safe, effective and tolerated acute migraine therapy also for patients at cardiovascular risk., For the understanding of migraine pathophysiology, it is very important to note that a selective 5-HT(1F) receptor agonist like lasmiditan is effective in the acute treatment of migraine., The 5-HT1F receptor agonist lasmiditan as a potential treatment of migraine attacks: a review of two placebo-controlled phase II trials., Within the past few years, new and promising drugs such as more specific 5-HT 1F receptor agonists (that is, lasmiditan) and monoclonal calcitonin gene-related peptide (CGRP) receptor antibodies entered advanced development phases while non-invasive neuromodulatory approaches were suggested to be potentially effective as non-pharmaceutical interventions for migraine., CLASSIFICATION OF EVIDENCE\nThis study provides Class I evidence that for adult patients with migraine, lasmiditan increases the proportion of subjects who are headache pain free at 2 hours after treating a migraine attack., BACKGROUND Lasmiditan (COL-144) is a novel, centrally acting, highly selective 5-HT(1F) receptor agonist without vasoconstrictor activity that seemed effective when given as an intravenous infusion in a proof-of-concept migraine study., INTERPRETATION Oral lasmiditan seems to be safe and effective in the acute treatment of migraine., Research to date suggests lasmiditan lacks vasoconstrictive properties and may be a safe and effective treatment option in patients refractory to current acute migraine medications or who have cardiovascular risk factors., The non-vascular, neural mechanism of action of lasmiditan may offer an alternative means to treat migraine especially in patients who have contra-indications for agents with vasoconstrictor activity., Compared with placebo, more patients dosed with lasmiditan 200 mg were free of headache pain at 2 hours after dosing (32.2% vs 15.3%; odds ratio [OR] 2.6, 95% confidence interval [CI] 2.0-3.6, <br><b>CONCLUSIONS</b>: Lasmiditan dosed at 200 and 100 mg was efficacious and well tolerated in the treatment of acute migraine among patients with a high level of cardiovascular risk factors.<br><b>CLINICALTRIALSGOV IDENTIFIER</b>: NCT02439320.<br><b>CLASSIFICATION OF EVIDENCE</b>: This study provides Class I evidence that for adult patients with migraine, lasmiditan increases the proportion of subjects who are headache pain free at 2 hours after treating a migraine attack.<br>, The most common adverse events were CNS related and included dizziness, fatigue, vertigo, paraesthesia, and somnolence.<br><b>INTERPRETATION</b>: Oral lasmiditan seems to be safe and effective in the acute treatment of migraine., Dizziness, paresthesia and sensations of heaviness (usually limb) were more common on lasmiditan.<br><b>CONCLUSIONS</b>: At intravenous doses of 20 mg and higher, lasmiditan proved effective in the acute treatment of migraine., <b>BACKGROUND</b>: Lasmiditan (COL-144) is a novel, centrally acting, highly selective 5-HT(1F) receptor agonist without vasoconstrictor activity that seemed effective when given as an intravenous infusion in a proof-of-concept migraine study., For the understanding of migraine pathophysiology, it is very important to note that a selective 5-HT(1F) receptor agonist like lasmiditan is effective in the acute treatment of migraine., This study provides Class I evidence that for adult patients with migraine, lasmiditan increases the proportion of subjects who are headache pain free at 2 hours after treating a migraine attack., While lasmiditan most likely is effective in the treatment of migraine attacks it had, unfortunately, a high incidence of CNS related AEs in the oral RCT.[SEP]", "label": "yes"}
{"id": "converted_1130", "sentence1": "Do DNA double-strand breaks play a causal role in carcinogenesis?", "sentence2": "The DNA non-homologous end-joining repair gene XRCC6/Ku70 plays an important role in the repair of DNA double-strand breaks (DSBs) induced by both exogenous and endogenous DNA-damaging agents. Defects in overall DSB repair capacity can lead to genomic instability and carcinogenesis., The tumor suppressor breast cancer susceptibility protein 1 (BRCA1) protects our cells from genomic instability in part by facilitating the efficient repair of DNA double-strand breaks (DSBs). BRCA1 promotes the error-free repair of DSBs through homologous recombination and is also implicated in the regulation of nonhomologous end joining (NHEJ) repair fidelity., The increased frequency of DSB mutagenesis and MMEJ repair in the absence of BRCA1 suggests a potential mechanism for carcinogenesis., Comet assay under neutral conditions allows detection of DNA double-strand breaks (DSBs), which has consequence to genome instability and carcinogenesis., Loss of p15/Ink4b accompanies tumorigenesis triggered by complex DNA double-strand breaks., Although DSBs are potentially carcinogenic, it is not clear whether complex DSBs that are refractory to repair are more potently tumorigenic compared with simple breaks that can be rapidly repaired, correctly or incorrectly, by mammalian cells., Zinc chromate induces chromosome instability and DNA double strand breaks in human lung cells., Our study shows that zinc chromate induced concentration-dependent increases in cytotoxicity, chromosome damage and DNA double strand breaks in human lung cells., Foci formation of P53-binding protein 1 in thyroid tumors: activation of genomic instability during thyroid carcinogenesis., Nitric oxide and acid induce double-strand DNA breaks in Barrett's esophagus carcinogenesis via distinct mechanisms., DNA double-strand break repair capacity and risk of breast cancer., A tumorigenic role of the non-homologous end-joining (NHEJ) pathway for the repair of DNA double-strand breaks (DSBs) has been suggested by our finding of a significant association between increased breast cancer risk and a cooperative effect of single-nucleotide polymorphisms in NHEJ genes., Carcinogen-induced DNA double strand break repair in sporadic breast cancer., Induction of DNA double strand breaks and alterations in the repair of these breaks is implicated in breast carcinogenesis. Prior studies have demonstrated that peripheral blood mononuclear cells (PBMC) from breast cancer patients exhibit increased numbers of DNA strand breaks after exposure to ionizing radiation, but these studies did not specifically measure DNA double strand breaks and it is not known whether chemical carcinogens produce similar effects., Abnormal DNA end-joining activity in human head and neck cancer., In human cells, DNA double-strand breaks (DSBs) are repaired primarily by the DNA end-joining (EJ) process and thus, abnormal DNA EJ activities lead to an accumulation of mutations and/or aneuploidy, resulting in genetic instability of cells. Since genetic instability is the hallmark of cancer cells, we studied the DNA EJ activities of normal, non-malignant immortalized and malignant human epithelial cells to investigate the association between DNA EJ and carcinogenesis., Homologous recombination repair plays an important role in DSB repair and impairment of this repair mechanism may lead to loss of genomic integrity, which is one of the hallmarks of cancer. Recent research has shown that the tumor suppressor genes p53 and BRCA1 and -2 are involved in the proper control of homologous recombination, suggesting a role of this type of repair in human cancer., In order to study the role of DNA damage processing in the development of cutaneous squamous cell carcinoma (SCC), we assessed the ability of six keratinocyte cell lines from a multistage-tumor progression model to repair three types of DNA damage: pyrimidine dimers, oxidative DNA lesions and DNA double strand breaks (DSB)., However, an acquired deficiency in repairing DNA double strand breaks can be one mechanism promoting progression towards malignancy, possibly through impairing chromosomal stability., Recent findings demonstrate that accelerated carcinogenesis following liver regeneration is associated with chronic inflammation-induced double-strand DNA breaks in cells, which escaped apoptosis due to proliferative stress., Although DNA double-strand breaks and apoptosis may relate to arsenite-induced damage and carcinogenesis, the mechanism of action remains obscure.[SEP]", "label": "yes"}
{"id": "converted_2626", "sentence1": "Can nanoparticles be used for afterglow imaging?", "sentence2": "Ultralong Phosphorescence of Water-Soluble Organic Nanoparticles for In Vivo Afterglow Imaging, Afterglow or persistent luminescence eliminates the need for light excitation and thus circumvents the issue of autofluorescence, holding promise for molecular imaging. However, current persistent luminescence agents are rare and limited to inorganic nanoparticles. This study reports the design principle, synthesis, and proof-of-concept application of organic semiconducting nanoparticles (OSNs) with ultralong phosphorescence for in vivo afterglow imaging. , This study not only introduces the first category of water-soluble ultralong phosphorescence organic nanoparticles but also reveals a universal design principle to prolong the lifetime of phosphorescent molecules to the level that can be effective for molecular imaging.[SEP]", "label": "yes"}
{"id": "converted_3523", "sentence1": "Is SATB1 positioned close to AT-rich sequences?", "sentence2": " Tryptic cleavage and peptide sequence analysis demonstrated that the 98-kD protein is identical to a recently cloned protein, special A-T-rich binding protein 1 (SATB1), Special AT-rich sequence-binding protein 1 (SATB1), a DNA-binding protein expressed predominantly in thymocytes, recognizes an ATC sequence context that consists of a cluster of sequence stretches with well-mixed A's, T's, and C's without G's on one strand. ,  We have purified and identified one of the core factors as the matrix attachment region (MAR) binding protein, SATB1, which is known to bind to AT-rich sequences with a high propensity to unwind, SATB1 (special AT-rich sequence-binding protein-1) provides a key link between DNA loop organization, chromatin modification/remodeling, and association of transcription factors at matrix attachment regions (MARs)., Over-expression of the special AT rich sequence binding protein 1 (SATB1) promotes the progression of nasopharyngeal carcinoma: association with EBV LMP-1 expression., pecial AT rich sequence binding protein 1 (SATB1) plays a crucial role in the biology of various types of human cancer. , Loss of special AT-rich sequence-binding protein 1 (SATB1), Special AT-rich sequence-binding protein 1 (SATB1) is a cell type-specific matrix attachment region binding protein, functioning as a global genome organizer. , SATB1 (special AT-rich binding protein 1) is a global chromatin organizer regulating the expression of a large number of genes, Special AT-rich Sequence-binding Protein 1 (SATB1) Functions as an Accessory Factor in Base Excision Repair., Rearrangement of the Chromatin Organizer Special AT-rich Binding Protein 1 Gene, The Special AT-rich Sequence Binding Protein 1 (SATB1) exerts multiple functions, by influencing the structural organization of chromatin and interacting with several co-activators and co-repressors of transcription., The Special AT-rich Sequence Binding Protein 1 (SATB1) and its role in solid tumors.[SEP]Relations: protein binding has relations: molfunc_protein with SATB1, molfunc_protein with SATB1.", "label": "yes"}
{"id": "converted_220", "sentence1": "Has depression been shown to be a predictor of frailty?", "sentence2": "significant role of frailty as a predictor of depression in a relatively younger old Chinese population, significant relationships between frailty and depressive symptoms and mortality at 1 year, These findings suggest that malnutrition is a major predictor of frailty or the \"failure to thrive\" syndrome in older persons. Depression is a major cause of poor nutritional status in older persons., Depressed mood was associated with increased risk of steep strength decline, in particular in older men with low body weight. Low body weight in combination with depressed mood may be an indicator of frailty or severe disease status that leads to accelerated strength loss and disability., Longitudinally, depressed mood was the only independent predictor of decline in cognition, functional ability, physician-rated health, and mortality;[SEP]", "label": "yes"}
{"id": "converted_2862", "sentence1": "Does lucatumumab bind to CD140?", "sentence2": "Lucatumumab is a fully humanized anti-CD40 antibody that blocks interaction of CD40L with CD40 and also mediates antibody-dependent cell-mediated cytotoxicity (ADCC). , Phase I study of the anti-CD40 humanized monoclonal antibody lucatumumab (HCD122) in relapsed chronic lymphocytic leukemia., Saturation of CD40 receptor on CLL cells was uniform at all doses post-treatment but also persisted at trough time points in the 3.0 mg/kg or greater cohorts.[SEP]", "label": "no"}