{"id": "converted_2308", "sentence1": "Is there an RNAi drug being developed to treat amyloidosis?", "sentence2": "Patisiran is an investigational RNA interference (RNAi) therapeutic in development for the treatment of hereditary ATTR (hATTR) amyloidosis, a progressive disease associated with significant disability, morbidity, and mortality.[SEP]", "label": "yes"}
{"id": "converted_2670", "sentence1": "The TRPM2 gene is associated with development of spontaneous thromboembolism?", "sentence2": "TheTransientReceptorPotentialMelastatin 2 (TRPM2) is a member of G protein coupled receptor superfamily and a novel dual-function protein that possesses both ion channel andAdenosine 5'-DiphosPhataseRibose (ADPR) hydrolase function. TRPM2 is involved in Ca2+signaling in various cells as an endogenous redox sensor for oxidative stress and reactive oxygen species, and contributes to cytokine production, insulin release, motility, Ca2+entry and Ca2+-dependent cellular reactions such as endothelial hyper-permeability and apoptosis., We show here that the redox-sensitive transient receptor potential (TRP) cation channel TRPM2 is expressed in the phagosomal membrane and regulates macrophage bactericidal activity through the activation of phagosomal acidification, The transient receptor potential melastatin-2 (TRPM2) is an oxidative stress sensing channel that is expressed in a number of inflammatory cells and therefore it has been suggested that inhibition of TRPM2 could lead to a beneficial effect in COPD patients., TRPM2 is a recently identified TRPM family cation channel which is unique among known ion channels in that it contains a C-terminal domain which is homologous to the NUDT9 ADP-ribose hydrolase and possesses intrinsic ADP-ribose hydrolase activity, These results suggest that TRPM2 may participate in antigen-induced extracellular Ca(2+) influx and subsequent degranulation. In addition, TRPM2 inhibitors were shown to improve food allergic reactions in a mouse model. Together, these results suggest that TRPM2 inhibitors suppress MMC degranulation via regulation of the increase in [Ca(2+)]cyt. Thus, TRPM2 may play a key role in degranulation by modulating intracellular Ca(2+) in MMCs., he Na+ and Ca(2+)-permeable melastatin related transient receptor potential 2 (TRPM2) channels can be gated either by ADP-ribose (ADPR) in concert with Ca(2+) or by hydrogen peroxide (H(2)O(2)), an experimental model for oxidative stress, binding to the channel's enzymatic Nudix domain, hese alterations of the extracellular milieu change the activity of transient receptor potential melastatin subfamily member 2 (TRPM2), a nonselective cation channel expressed in the central nervous system and the immune system. , TRPM2 (Transient Receptor Potential Melastatin 2) is a Ca2+-permeable ion channel that is activated under conditions of oxidative stress. , Transient receptor potential melastatin 2 (TRPM2) is a thermosensitive, Ca2+-permeable cation channel. TRPM2 contributes to the pathogenesis of inflammatory bowel disease, and inflammatory and neuropathic pain. We hypothesized that TRPM2 is important for visceral nociception and the development of visceral hypersensitivity., Here, we describe the computational identification of a melanoma-enriched antisense transcript, TRPM2-AS, mapped within the locus of TRPM2, an ion channel capable of mediating susceptibility to cell death, The transient receptor potential melastatin 2 (TRPM2) channel, a Ca(2+)-permeable nonselective cation channel activated by oxidative stress, has been implicated in neurodegenerative diseases, and more recently in amyloid-induced toxicity, Transient receptor potential melastatin 2 (TRPM2) is a calcium-permeable cation channel activated by ADP-ribose or reactive oxygen species.,  Transient receptor potential melastatin type 2 (TRPM2) is a Ca2+ permeable non-selective cation channel expressed in several cell types including hippocampal pyramidal neurons. Moreover, activation of TRPM2 during oxidative stress has been linked to cell death. [SEP]", "label": "no"}
{"id": "converted_2067", "sentence1": "Can glyburide reduce cerebral edema?", "sentence2": "Preclinical studies have shown that a continuous infusion of glyburide blocks edema formation and improves outcome. We hypothesize that treatment with RP-1127 (Glyburide for Injection) reduces formation of brain edema in patients after large anterior circulation infarction., CONCLUSIONS: GAMES-RP was designed to provide critical information regarding glyburide for injection in patients with large hemispheric stroke and will inform the design of future studies., Glyburide is associated with attenuated vasogenic edema in stroke patients., Glyburide is reported to prevent brain swelling in preclinical rodent models of ischemic stroke through inhibition of a non-selective channel composed of sulfonylurea receptor 1 and transient receptor potential cation channel subfamily M member 4. , RESULTS: We report that IV glyburide was associated with T2 fluid-attenuated inversion recovery signal intensity ratio on brain MRI, diminished the lesional water diffusivity between days 1 and 2 (pseudo-normalization), and reduced blood MMP-9 level.CONCLUSIONS: Several surrogate markers of vasogenic edema appear to be reduced in the setting of IV glyburide treatment in human stroke. , Pilot study of intravenous glyburide in patients with a large ischemic stroke., BACKGROUND AND PURPOSE: Preclinical and retrospective clinical data indicate that glyburide, a selective inhibitor of sulfonylurea receptor 1-transient receptor potential melastatin 4, is effective in preventing edema and improving outcome after focal ischemia. , Preclinical data suggest that glyburide, an inhibitor of SUR1-TRPM4, is effective in preventing edema., Glyburide in Treating Malignant Cerebral Edema. , Glyburide in Treating Malignant Cerebral Edema. Blocking Sulfonyl Urea One (SUR1) Receptors., The sulfonylurea receptor 1-regulated NC(Ca-ATP) channel is upregulated in rodent models of stroke with block of the channel by the sulfonylurea, glibenclamide (glyburide), significantly reducing mortality, cerebral edema, and infarct volume., Glyburide is a safe, inexpensive, and efficacious alternative to dexamethasone for the treatment of cerebral metastasis-related vasogenic edema., In this focused review, we explore preclinical data linking Sur1 channel formation to development of edema and reference evidence suggesting that the antidiabetic sulfonylurea drug glyburide (a Sur1 inhibitor) is an inexpensive and well-tolerated agent that can be clinically tested to reduce or prevent malignancy and/or treatment-associated edema., Potential of glyburide to reduce intracerebral edema in brain metastases., Glyburide Advantage in Malignant Edema and Stroke (GAMES-RP) Trial: Rationale and Design., Preclinical data suggest that glyburide, an inhibitor of SUR1-TRPM4, is effective in preventing edema., Inhibition of sulfonylurea receptor 1 (SUR1) by glyburide has been shown to decrease edema after subarachnoid hemorrhage., Glyburide is a safe, inexpensive, and efficacious alternative to dexamethasone for the treatment of cerebral metastasis-related vasogenic edema, RESULTS: We report that IV glyburide was associated with T2 fluid-attenuated inversion recovery signal intensity ratio on brain MRI, diminished the lesional water diffusivity between days 1 and 2 (pseudo-normalization), and reduced blood MMP-9 level. , Preclinical data suggest that glyburide, an inhibitor of SUR1-TRPM4, is effective in preventing edema. , Exploratory analysis of glyburide as a novel therapy for preventing brain swelling., Inhibition of sulfonylurea receptor 1 (SUR1) by glyburide has been shown to decrease edema after subarachnoid hemorrhage. , In this focused review, we explore preclinical data linking Sur1 channel formation to development of edema and reference evidence suggesting that the antidiabetic sulfonylurea drug glyburide (a Sur1 inhibitor) is an inexpensive and well-tolerated agent that can be clinically tested to reduce or prevent malignancy and/or treatment-associated edema., Glyburide is a safe, inexpensive, and efficacious alternative to dexamethasone for the treatment of cerebral metastasis-related vasogenic edema., Glyburide is reported to prevent brain swelling in preclinical rodent models of ischemic stroke through inhibition of a non-selective channel composed of sulfonylurea receptor 1 and transient receptor potential cation channel subfamily M member 4., Several surrogate markers of vasogenic edema appear to be reduced in the setting of IV glyburide treatment in human stroke., We hypothesize that treatment with RP-1127 (Glyburide for Injection) reduces formation of brain edema in patients after large anterior circulation infarction., Glyburide is a safe, inexpensive, and efficacious alternative to dexamethasone for the treatment of cerebral metastasis-related vasogenic edema.., Glyburide is associated with attenuated vasogenic edema in stroke patients.[SEP]", "label": "yes"}
{"id": "converted_3309", "sentence1": "Is induction of interferon by TLR7 higher in males?", "sentence2": "ur results suggest that variations of TLR7 impair the immune response to HCV and imply a gender-specific effect of this X-chromosomal variation., The c.32A>T variation was over-represented in female patients with chronic HCV-infection compared to patients with other chronic liver diseases and to healthy controls (P < 0.05). In contrast, c.2403 G>A was less prevalent in male patients with chronic HCV-infection (P < 0.05). No association was observed for the third variant, c.1-120T>G. Haplotype analysis confirmed the differential distribution of TLR7 variants between the groups. Within the group of female patients with chronic HCV-infection, c.32T was predictive of an unfavourable outcome of interferon-alpha therapy (P < 0.05)[SEP]", "label": "yes"}
{"id": "converted_1129", "sentence1": "Is Wnt16b secreted in response to chemotherapy?", "sentence2": " In this study, we found WNT16B could be expressed and secreted into the microenvironment by human ovarian fibroblasts after DNA damage-associated treatment, including chemotherapy drugs and radiation., In a recent article in Nature Medicine, Sun et al. show that increased expression of Wnt family member wingless-type MMTV integration site family member 16B (WNT16B) by the tumor microenvironment in response to cytotoxic damage and signals through the canonical Wnt pathway to promote tumor growth and chemotherapy resistance. , Using a genome-wide analysis of transcriptional responses to genotoxic stress induced by cancer therapeutics, we identified a spectrum of secreted proteins derived from the tumor microenvironment that includes the Wnt family member wingless-type MMTV integration site family member 16B (WNT16B).[SEP]", "label": "yes"}
{"id": "converted_4283", "sentence1": "Is AZD9668 a VEGF mRNA drug?", "sentence2": "AZD9668, a neutrophil elastase inhibitor, plus ongoing budesonide/formoterol in patients with COPD., AZD9668 is a reversible and selective inhibitor of NE, well tolerated at doses of 60 mg bid during Phase I/IIa development.[SEP]", "label": "no"}
{"id": "converted_2347", "sentence1": "Do bacteria from the genus Morexella cause respiratory infections?", "sentence2": "gainst pathogens associated with respiratory tract ailments [Staphylococcus aureus (ATCC 25923), Klebsiella pneumoniae (ATCC 13883) and Morexella cattarhalis (ATCC 14468)] , The efficacy and safety of oral ofloxacin, 400 mg once daily, for the treatment of patients with lower respiratory tract infections were studied. The most common species recovered from the sputum specimens of these patients were Haemophilus influenzae, followed by Streptococcus pneumoniae (S. pneumoniae), Staphylococcus aureus (S. aureus), Gram positive cocci unidentified, Pseudomonas aeruginosa (P. aeruginosa), Morexella catarrhalis,, the efficacy and safety of oral ofloxacin 400 mg once daily for the treatment of patients with lower respiratory tract infections were studied the most common species recovered from the sputum specimens of these patients were haemophilus influenzae followed by streptococcus pneumoniae s pneumoniae staphylococcus aureus s aureus gram positive cocci unidentified pseudomonas aeruginosa p aeruginosa morexella catarrhalis streptococcus epidermidis and another haemophilus species in this order all these bacteria were susceptible to ofloxacin except for one strain of methicillin resistant s aureus a satisfactory clinical outcome was achieved in 34 of 40 patients 85 it is concluded that ofloxacin 400 mg once daily is useful for patients with respiratory tract infections.[SEP]", "label": "yes"}
{"id": "converted_3380", "sentence1": "Does natalizumab improve disease course of secondary progressive multiple sclerosis?", "sentence2": "INTERPRETATION: Natalizumab treatment for secondary progressive multiple sclerosis did not reduce progression on the primary multicomponent disability endpoint in part 1, but it did reduce progression on its upper-limb component., In this review, we summarize the pathophysiological mechanisms involved in the development of SPMS and the rationale and clinical potential for natalizumab, which is currently approved for the treatment of relapsing forms of MS, to exert beneficial effects in reducing disease progression unrelated to relapses in SPMS. , INTERPRETATION\n\nNatalizumab treatment for secondary progressive multiple sclerosis did not reduce progression on the primary multicomponent disability endpoint in part 1, but it did reduce progression on its upper-limb component., Natalizumab did not achieve a statistically significant primary composite disability outcome in a trial of 887 patients with secondary progressive MS , but it did demonstrate a benefit on a prespecified component of the 9-Hole Peg Test . , INTERPRETATION\nNatalizumab treatment for secondary progressive multiple sclerosis did not reduce progression on the primary multicomponent disability endpoint in part 1, but it did reduce progression on its upper-limb component., In this review, we summarize the pathophysiological mechanisms involved in the development of SPMS and the rationale and clinical potential for natalizumab, which is currently approved for the treatment of relapsing forms of MS, to exert beneficial effects in reducing disease progression unrelated to relapses in SPMS., Natalizumab treatment for secondary progressive multiple sclerosis did not reduce progression on the primary multicomponent disability endpoint in part 1, but it did reduce progression on its upper-limb component.[SEP]", "label": "no"}
{"id": "converted_3370", "sentence1": "Is Nivolumab (Opdivo) a PD-L1 inhibitor?", "sentence2": "Fatal Myocarditis Following Treatment with the PD-1 Inhibitor Nivolumab,  PD-1 inhibitor nivolumab (Opdivo), programmed cell death protein 1 (PD-1)-blocking antibodies nivolumab or pembrolizumab , An improvement in the understanding of the role of the immune system in tumor immunosurveillance has led to the development of the programmed death-1 ( PD-1 ) immune checkpoint inhibitor nivolumab ( Opdivo) . , Nivolumab (Opdivo(®); Nivolumab BMS™) was the first programmed death (PD)-1 immune checkpoint inhibitor to be approved for use in advanced, squamous non-small cell lung cancer (NSCLC) following prior chemotherapy.[SEP]", "label": "no"}
{"id": "converted_214", "sentence1": "Are there focused databases from which you can retrieve gene expression data on renal disease?", "sentence2": "Proteomics database in chronic kidney disease, Naturally occurring human urinary peptides for use in diagnosis of chronic kidney disease[SEP]", "label": "yes"}
{"id": "converted_216", "sentence1": "Are there any DNMT3 proteins present in plants?", "sentence2": "De novo DNA methylation in Arabidopsis thaliana is catalyzed by the methyltransferase DRM2, a homolog of the mammalian de novo methyltransferase DNMT3., Here we describe DNA methyltransferase genes from both Arabidopsis and maize that show a high level of sequence similarity to Dnmt3, suggesting that they encode plant de novo methyltransferases. Relative to all known eukaryotic methyltransferases, these plant proteins contain a novel arrangement of the motifs required for DNA methyltransferase catalytic activity. The N termini of these methyltransferases contain a series of ubiquitin-associated (UBA) domains. , BLASTX searches and phylogenetic analysis suggested that five cDNAs belonged to four classes (Dnmt1, Dnmt2, CMT and Dnmt3) of DNA methyltransferase genes.[SEP]", "label": "yes"}
{"id": "converted_3460", "sentence1": "Can radiotherapy cause radiation induced osteosarcoma?", "sentence2": "A case of radiation-induced osteosarcoma of the skull presenting as a cutaneous epidermotropic tumor with a short latent period., Radiation-induced sarcoma (RIS) is an unusual but well documented tumor. , We report a case of a 34-year-old female who developed an osteosarcoma of the scalp, over a previous craniotomy scar, 3 years after excision of a frontal anaplastic oligodendroglioma which had been followed by a course of 6 weeks radiotherapy (58 Gy) and 6 cycles of temozolomide. , Radiation-induced osteosarcoma after Gamma Knife surgery for vestibular schwannoma: a case report and literature review., We present a rare case of radiation-induced osteosarcoma following Gamma Knife® surgery (GKS) for a vestibular schwannoma (VS). , The osteosarcoma was considered to be a radiation-induced malignancy. , Radiation-induced osteosarcoma of the maxilla and mandible after radiotherapy for nasopharyngeal carcinoma., The purpose of this study was to analyze the association of clinicopathologic characteristics with treatment outcomes and prognostic factors of patients who developed RIOSM after undergoing radiotherapy for nasopharyngeal carcinoma (NPC)., Of these patients, 47 who developed RISOM and met inclusion criteria were included in this study. , CONCLUSIONS: RISOM after radiotherapy for NPC is aggressive and often eludes early detection and timely intervention., Radiation-induced osteosarcoma of the skull base after radiation therapy in a patient with nasopharyngeal carcinoma: a case report and review of the literature., BACKGROUND: Radiation-induced osteosarcomas are a recognized complication of radiation therapy. , CASE PRESENTATION: We describe a rare case of a patient with a skull base radiation-induced osteosarcoma treated 11 years before with ionizing radiation for an undifferentiated carcinoma of the nasopharynx. , CONCLUSIONS: Radiation-induced osteosarcoma of the skull base after treatment of nasopharyngeal carcinoma is a very rare but very aggressive complication with a poor prognosis., Radiation-Associated Low-Grade Extraskeletal Osteosarcoma of the Neck Following Treatment for Thyroid Cancer., Low-grade extraskeletal osteosarcoma is a rare tumor that may arise de novo or following radiation therapy., While there is a report of a low-grade extraskeletal osteosarcoma arising following radiotherapy for a benign condition, to the best of our knowledge this is the first reported case of a low-grade extraskeletal osteosarcoma occurring following radiotherapy for thyroid cancer, and the only case reported in the soft tissue of the head and neck region. , Here we a report a case of radiation induced osteosarcoma which developed 11 years after a single fraction of 700 cGy., Osteosarcoma following single fraction radiation prophylaxis for heterotopic ossification., The radiotherapy dose for this patient is lower than classically reported for radiation induced sarcomas., The latency period between radiotherapy and osteosarcoma onset was 1.3 years shorter inside than outside the radiation field., Osteosarcoma after radiotherapy for prostate cancer., Osteosarcoma after external beam radiation therapy for recurrent choroidal melanoma., Diagnostic criteria were fulfilled and the lesion was classified as a radiation induced osteosarcoma, Although a rare complication of ionizing radiation, radiation-induced osteosarcoma is now more frequently recognized as radiation therapy has become common and cancer survival has increased, Here we a report a case of radiation induced osteosarcoma which developed 11 years after a single fraction of 700 cGy, Radiation-induced osteosarcoma usually occurs after a long latency period of more than 10 years after the radiotherapy, Osteosarcoma following radiotherapy: a case report., Radiation-induced fibrosarcoma after radiotherapy for osteosarcoma in the mandibular condyle., Post-radiation osteosarcoma of the scapula., Radiation-induced osteosarcomas generally occur 3-30 years after exposure and are most common after radiotherapy for cervical or breast carcinoma, Radiation-induced osteosarcoma is one of the rare types of radiation-induced sarcomas , with the risk of radiation-induced osteosarcomas being only 0.01 % -0.03 % among all patients treated with radiotherapy, Radiation-induced osteosarcoma is a well-known but rare complication of radiotherapy for brain neoplasms with a poor prognosis, The prognosis of patients developing osteosarcoma after radiotherapy for prostate cancer is similar to other radiation-induced osteosarcomas occurring in the axial skeleton , with a 50 % overall mortality within the first year after diagnosis, Radiation-induced osteosarcoma usually occurs after a long latency period of more than 10 years after the radiotherapy, Twenty-seven years 11 months after orthovoltage radiotherapy of the right breast a 69-year-old woman developed a radiation-induced osteosarcoma of the right thoracic wall, We report a case of radiation-induced osteosarcoma developed from skull after 7 years of craniospinal radiotherapy for pineoblastoma, Although the concepts of direct and indirect effects of radiation are fully applicable to low-LET ( linear energy transfer ) radioresistant tumor cells/normal tissues such as osteosarcoma cells and chondrocytes , it is believed that radiation-associated damage to DNA does not play a major role in the mechanism of cell death in low-LET radiosensitive tumors/normal tissues such as malignant lymphoma cells and lymphocytes, From these clinicopathological findings, both cases were diagnosed as radiation-induced osteosarcoma., Here we report two cases of radiation-induced osteosarcoma in the paranasal sinus after treatment for frontal glioma., As the prognosis of radiation-induced osteosarcoma is poorer than that of primary osteo-sarcoma, careful attention is required for consideration of the long-term survival of patients with glioma., Radiation-induced osteosarcomas appeared 16 and 12 years after radiotherapy in cases 1 and 2, respectively., Most radiation-induced osteosarcomas of the skull are reported to arise in the facial bone or paranasal sinus after radiotherapy for retinoblastoma and/or pituitary adenoma., Radiation-induced osteosarcomas after treatment for frontal gliomas: a report of two cases., Radiation-induced osteosarcoma of the skull mimicking cutaneous tumor after treatment for frontal glioma., Radiation-induced osteosarcoma is one of the rare types of radiation-induced sarcomas, with the risk of radiation-induced osteosarcomas being only 0.01%-0.03% among all patients treated with radiotherapy., Radiation-induced sarcomas are recognized complications of radiation therapy and are associated with poor prognosis., There have been only four reported cases of radiation-induced osteosarcomas after radiotherapy for gliomas., Here, we report a unique case of radiation-induced osteosarcomas arising on the skull and extending to the skin, with a short latent period., BACKGROUND\nThe increasing incidence of radiation-induced osteosarcoma of the maxilla and mandible (RIOSM) has become a significant problem that can limit long-term survival., In this case, osteosarcoma was possibly a radiation-induced osteosarcoma with a short latency period of 3 years., Radiation-induced osteosarcoma usually occurs after a long latency period of more than 10 years after the radiotherapy., A case of osteosarcoma arising in the craniofacial bone with a short latency period of 3 years after radiotherapy for maxillary squamous cell carcinoma is described., Osteosarcoma is one of the neoplasms that may occur following exposure to radiation., As the prognosis of radiation-induced osteosarcoma is poorer than that of primary osteo-sarcoma, careful attention is required for consideration of the long-term survival of patients with glioma., This report describes the late recurrence of choroidal melanoma and subsequent radiation-induced osteosarcoma., Radiation-induced osteosarcoma is one of the rare types of radiation-induced sarcomas, with the risk of radiation-induced osteosarcomas being only 0.01%-0.03% among all patients treated with radiotherapy., There have been only four reported cases of radiation-induced osteosarcomas after radiotherapy for gliomas., Although radiation-induced osteosarcoma is an uncommon but dire complication of radiotherapy, its incidence will probably increase in the future as the frequency of radiation treatment and cancer survival increase., We report a case of radiation-induced osteosarcoma developed from skull after 7 years of craniospinal radiotherapy for pineoblastoma., The prognosis of patients developing osteosarcoma after radiotherapy for prostate cancer is similar to other radiation-induced osteosarcomas occurring in the axial skeleton, with a 50% overall mortality within the first year after diagnosis., To our knowledge the only other case report of post-radiation osteosarcoma with a short latency period was a case of osteosarcoma in the craniofacial bone 3 years after radiotherapy for maxillary squamous cell carcinoma., Here, we report a unique case of radiation-induced osteosarcomas arising on the skull and extending to the skin, with a short latent period., Case of postradiation osteosarcoma with a short latency period of 3 years.[SEP]Relations: bone osteosarcoma has relations: disease_disease with osteosarcoma, disease_disease with osteosarcoma. Pituitary adenoma has relations: disease_phenotype_positive with pituitary adenoma, disease_phenotype_positive with pituitary adenoma. Glioma has relations: disease_phenotype_positive with retinoblastoma, disease_phenotype_positive with retinoblastoma.", "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_2073", "sentence1": "Are mutations in the C9orf72  gene associated with macular degeneration?", "sentence2": "Over the years, however, growing evidence from clinical, pathological and genetic findings has suggested that ALS and FTD belong to the same clinic-pathological spectrum disorder. This concept has been further supported by the identification of the most common genetic cause for both diseases, an aberrantly expanded hexanucleotide repeat GGGGCC/ CCCCGG sequence located in a non-coding region of the gene C9orf72., Amyotrophic lateral sclerosis (ALS) is characterized by motor neurone loss resulting in muscle weakness, spasticity and ultimately death. 5-10% are caused by inherited mutations, most commonly C9ORF72, SOD1, TARDBP and FUS., In this article, we will review the brief characterizations of the C9ORF72 gene, the expansion mutations, the related disorders, and their features, followed by a discussion of the deficiency knowledge of C9ORF72 mutations., Mutations in the C9ORF72 gene may be a major cause not only of frontotemporal dementia with motor neuron disease but also of late onset psychosis., Frontotemporal lobar degeneration (FTLD) is a genetically heterogenous syndrome and has been associated most recently with a hexanucleotide repeat expansion within the C9ORF72 gene., An expanded GGGGCC hexanucleotide repeat in C9ORF72 is the most common genetic cause of amyotrophic lateral sclerosis and frontotemporal lobar degeneration associated with TDP-43 pathology (FTLD-TDP)., Novel TARDBP sequence variant and C9ORF72 repeat expansion in a family with frontotemporal dementia., There was, as expected, a significant association between C9ORF72 mutations and presence of motor neuron disease., Expansion of a hexanucleotide repeat in the C9ORF72 gene has been identified as the most common pathogenic mutation in families with autosomal dominant frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis., C9ORF72 hexanucleotide repeat number in frontotemporal lobar degeneration: a genotype-phenotype correlation study., Hexanucleotide repeat expansions in chromosome 9 open reading frame 72 (C9orf72) have recently been linked to frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis, and may be the most common genetic cause of both neurodegenerative diseases., studies recently identified a GGGGCC hexanucleotide repeat expansion in a non-coding region of the chromosome 9 open-reading frame 72 gene (C9ORF72) as the cause of chromosome 9p-linked amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD)., GGGGCC hexanucleotide repeat expansion in the C9ORF72 gene was recently identified as an important cause of familial amyotrophic lateral sclerosis (ALS) and frontotemporal dementia in Caucasian populations.[SEP]Relations: amyotrophic lateral sclerosis has relations: disease_protein with FUS, disease_disease with familial amyotrophic lateral sclerosis, disease_disease with motor neuron disease, disease_protein with SOD1, disease_protein with FUS, disease_disease with familial amyotrophic lateral sclerosis, disease_disease with motor neuron disease, disease_protein with SOD1, disease_protein with FUS, disease_disease with familial amyotrophic lateral sclerosis, disease_disease with motor neuron disease, disease_protein with SOD1, disease_protein with FUS, disease_disease with familial amyotrophic lateral sclerosis, disease_disease with motor neuron disease, disease_protein with SOD1. Frontotemporal dementia has relations: disease_phenotype_positive with amyotrophic lateral sclerosis, disease_phenotype_positive with amyotrophic lateral sclerosis. Spasticity of facial muscles has relations: disease_phenotype_positive with amyotrophic lateral sclerosis, disease_phenotype_positive with amyotrophic lateral sclerosis. motor neuron disease has relations: disease_disease with amyotrophic lateral sclerosis, disease_protein with SOD1, disease_disease with amyotrophic lateral sclerosis, disease_protein with SOD1. Muscle weakness has relations: disease_phenotype_positive with amyotrophic lateral sclerosis, disease_phenotype_positive with amyotrophic lateral sclerosis. C9orf72 has relations: disease_protein with amyotrophic lateral sclerosis, disease_protein with amyotrophic lateral sclerosis.", "label": "no"}
{"id": "converted_996", "sentence1": "Has Revlimid been approved by the US Food and Drug Administration?", "sentence2": "In the past decade, immunomodulatory drugs have been approved by the US Food and Drug Administration for the treatment of multiple myeloma (MM)-and a number of emerging agents that target the cellular pathways or proteins involved in the pathophysiology of MM are currently in development. Lenalidomide (Revlimid) and pomalidomide induce apoptosis and sensitize MM cells while demonstrating superior efficacy and better tolerability than thalidomide (Thalomid)., In the past decade we have seen four new agents approved by the US Food and Drug Administration for treatment of multiple myeloma: the proteasome inhibitor (PI) bortezomib (Velcade), the immunomodulatory agents lenalidomide (Revlimid) and thalidomide (Thalomid), and liposomal doxorubicin. , In the past decade we have seen four new agents approved by the US Food and Drug Administration for treatment of multiple myeloma: the proteasome inhibitor (PI) bortezomib (Velcade), the immunomodulatory agents lenalidomide (Revlimid) and thalidomide (Thalomid), and liposomal doxorubicin., Thalidomide, lenalidomide (Revlimid), and bortezomib (Velcade) are directed not only at MM cells but also at the BM milieu and have moved rapidly from the bench to the bedside and United States Food and Drug Administration approval to treat MM., Lenalidomide (CC-5013, Revlimid; Celgene Corporation, Summit, NJ), a thalidomide analogue, was granted approval by the U.S. Food and Drug Administration (FDA) on June 29, 2006, for use in combination with dexamethasone in patients with multiple myeloma (MM) who have received at least one prior therapy., Lenalidomide, an IMiD drug (a novel type of immunomodulating drug) was recently approved by the US Food and Drug Administration for the treatment of transfusion-dependent anemia in patients with myelodysplastic syndromes (MDS) and interstitial deletions of chromosome 5q [del(5q)], Lenalidomide, a second-generation immunomodulatory drug (IMiD), is approved by the US Food and Drug Administration for treatment of transfusion-dependent anemia in lower-risk MDS patients with deletion 5q chromosomal abnormality, In the past decade we have seen four new agents approved by the US Food and Drug Administration for treatment of multiple myeloma: the proteasome inhibitor (PI) bortezomib (Velcade), the immunomodulatory agents lenalidomide (Revlimid) and thalidomide (Thalomid), and liposomal doxorubicin., lenalidomide (CC5103 or revlimid) are recently approved for the treatment of multiple myeloma.,  In the past decade, immunomodulatory drugs have been approved by the US Food and Drug Administration for the treatment of multiple myeloma (MM)-and a number of emerging agents that target the cellular pathways or proteins involved in the pathophysiology of MM are currently in development. Lenalidomide (Revlimid) and pomalidomide induce apoptosis and sensitize MM cells while demonstrating superior efficacy and better tolerability than thalidomide (Thalomid).[SEP]", "label": "yes"}
{"id": "converted_4416", "sentence1": "Is periampullary carcinoma (PAC) a relatively rare genitourinary malignancy", "sentence2": "Pancreaticobiliary subtype of Periampullary carcinoma (PAC) has a poor prognosis in comparison to the intestinal subtype., MUC1, CK20, and CDX2 immunohistochemical markers can sub-classify periampullary carcinomas into pancreaticobiliary, intestinal, and mixed subtypes., Pancreaticoduodenectomy (PD) is a complex surgical procedure involving resection of the duodenum, the pancreatic head and uncinate process, and the distal common bile duct. It is most commonly performed for periampullary malignancy but may also be indicated in select cases of chronic pancreatitis or benign periampullary tumors., In patients suspected of pancreatic or periampullary cancer, abdominal contrast-enhanced computed tomography (CT) is the standard diagnostic modality., The pre-operative neutrophil-to-lymphocyte ratio (NLR), when ≥5 has been associated with reduced survival for patients with various gastrointestinal tract cancers, however, it's prognostic value in patients with periampullary tumour has not been reported to date., Comparison Of Biliary Stenting And Surgical Bypass In Palliative Management Of Irresectable Periampullary Carcinoma.,  Some 20-40% of the periampullary carcinoma is irresectable at the time of diagnosis. Biliary stenting and surgical bypass are commonly used palliative procedure., Whereas Periampulary AdenoCarcinoma (PAC) having four anatomic subtypes, pancreatic, Common Bile Duct (CBD), ampullary and duodenum shows relative better prognosis, DEFINITION: Periampullary carcinomas are rare and constitute a special entity, as diagnosed earlier and having a better prognosis than other duodenal tumors.METHODS: In the present study, we retrospectively reviewed the medical records of 16 patients with periampullary carcinomas over 10 years.RESULTS: 16 patients, 10 men and 6 women (median age 66.7 years, range 42-80) had a , Periampullary carcinomas: a special entity of duodenal tumors., Periampullary adenocarcinomas are rare neoplasm that originates from the pancreatic head, the ampulla of vater, the distal bile duct or the duodenum.[SEP]", "label": "no"}
{"id": "converted_3302", "sentence1": "Is the tyrosine kinase BTK implicated in autoimmunity?", "sentence2": "Autoimmunity, hypersensitivity to B cell receptor (BCR) cross-linking, and splenomegaly caused by myeloerythroid hyperplasia were alleviated by Btk deficiency in lyn-/- mice., Augmented TLR9-induced Btk activation in PIR-B-deficient B-1 cells provokes excessive autoantibody production and autoimmunity., Autoimmunity was fully dependent on Btk kinase activity, because Btk inhibitor treatment (PCI-32765) could normalize B-cell activation and differentiation, and because autoantibodies were absent in Btk transgenic mice overexpressing a kinase inactive Btk mutant., Bruton's tyrosine kinase (Btk) is a proximal transducer of the BCR signal that allows for B-cell activation and differentiation. Recently, selective inhibition of Btk by PCI-32765 has shown promise in limiting activity of multiple cells types in various models of cancer and autoimmunity., Inhibitors of BTK and ITK: state of the new drugs for cancer, autoimmunity and inflammatory diseases., Tight control of B cell differentiation into plasma cells (PCs) is critical for proper immune responses and the prevention of autoimmunity, BTK Signaling in B Cell Differentiation and Autoimmunity, BTK function in B cells in the context of host defense and autoimmunity., promising effects of BTK inhibition were also seen in experimental animal models for lupus and rheumatoid arthritis, BTK may be a good target for controlling autoreactive B cells in patients with systemic autoimmune disease., Given the phenotype of affected patients, namely lack of B-lymphocytes and plasma cells with the ensuing inability to mount humoral immune responses, BTK inhibitors were anticipated to have beneficial effects on antibody-mediated pathologies, such as autoimmunity[SEP]Relations: autoimmune disease has relations: disease_disease with systemic autoimmune disease, disease_phenotype_positive with Autoimmunity, disease_disease with systemic autoimmune disease, disease_phenotype_positive with Autoimmunity. Rheumatoid arthritis has relations: disease_phenotype_positive with rheumatoid arthritis, disease_phenotype_positive with rheumatoid arthritis.", "label": "yes"}
{"id": "converted_4530", "sentence1": "Are functional tests a good biomarker for Duchenne Muscular Dystrophy?", "sentence2": "North Star Ambulatory Assessment is practical and reliable., allow assessment of high-functioning boys with Duchenne muscular dystrophy., agnosis and tracking of symptom progression of DMD usually relies on creatine kinase tests, evaluation of patient performance in various ambulatory assessments, and detection of dystrophin from muscle biopsies, which are invasive and painful for the patient. While the, Aim: Using baseline data from a clinical trial of domagrozumab in Duchenne muscular dystrophy, we evaluated the correlation between functional measures and quantitative MRI assessments of thigh muscle. Patients & methods: Analysis included timed functional tests, knee extension/strength and North St, A New Functional Scale and Ambulatory Functional Classification of Duchenne Muscular Dystrophy: Scale Development and Preliminary Analyses of Reliability and Validity., his preliminary investigation describes the relationship between community ambulation measured by the StepWatch activity monitor and the current standard of functional assessment, the 6-minute walk test, in ambulatory boys with Duchenne muscular dystrophy (n = 16) and healthy controls (n = 13). All, ith strength assessments. MV index, fat fraction and T2-mapping measures had moderate correlations (r ∼ 0.5) to all functional tests, North Star Ambulatory Assessment and age. Conclusion: The moderate correlation between functional tests, age and baseline MRI measures supports MRI as a biomarker in Duchenn, on with clinically meaningful outcome measures such as North Star Ambulatory Assessment (NSAA) and 6 minute walk test (6MWT) is paramount for biomarker qualification. In this stu, Quantitative muscle strength assessment in duchenne muscular dystrophy: longitudinal study and correlation with functional measures., The 6-minute walk test, timed 10-meter walk/run test, and supine-up time are commonly used timed functional tests that also sufficiently monitor changes in muscle function; however, they strongly depend on patient collaboration, Conclusion: The moderate correlation between functional tests, age and baseline MRI measures supports MRI as a biomarker in Duchenne muscular dystrophy clinical trials., Currently, functional measures continue to serve as the primary outcome for the majority of DMD clinical trials., Patients & methods: Analysis included timed functional tests, knee extension/strength and North Star Ambulatory Assessment., The 6-minute walk test, timed 10-meter walk/run test, and supine-up time are commonly used timed functional tests that also sufficiently monitor changes in muscle function; however, they strongly depend on patient collaboration., We have developed a new scale and the associated classification system, to assess the functional ability of children diagnosed with DMD. Preliminary evaluation of the psychometric properties of the functional scale and classification systems indicate sufficient reliability and concurrent validity., Quantitative MRI is an objective and sensitive biomarker to detect subclinical changes, though the examination costs may be a reason for its limited use. In this study, a high correlation between all clinical assessments and quantitative MRI scans was found. The combinational use of these methods provides a better understanding about disease progression; however, longitudinal studies are needed to validate their reliability., The children's functional performance was assessed using 6-minute walk tests and timed performance tests. The correlations between the flexibilities of the lower limb muscles and the performance tests were examined., The flexibilities of the lower extremity muscles were found to be correlated to the 6-minute walk tests and the timed performance tests. The flexibility of the hamstrings (r = -.825), the gastrocnemius muscles (r = .545), the hip flexors (r = .481), and the tensor fascia latae (r = .445) were found to be correlated with functional performance as measured by the 6-minute walk tests (P < .05), Nine biomarkers have been identified that correlate with disease milestones, functional tests and respiratory capacity. Together these biomarkers recapitulate different stages of the disorder that, if validated can improve disease progression monitoring.,  In conclusion, the motor function measure and timed function tests measure disease severity in a highly comparable fashion and all tests correlated with quantitative muscle MRI values quantifying fatty muscle degeneration.,  This study is to date the most thorough long-term evaluation of QMT in a cohort of DMD patients correlated with other measures, such as the North Star Ambulatory Assessment (NSAA) or three 6-min walk test (6MWT)., The MFM scale was a useful instrument in the follow up of patients with DMD. Moreover, it is a more comprehensive scale to assess patients and very good for conducting trials to evaluate treatment., MD subjects were evaluated using the Vignos lower extremity functional rating, and tests including 6 min walk test (6MWT) and 10 m walk., TFTs appear to be slightly more responsive and predictive of disease progression than the 6MWT in 7-12.9 year olds., herefore, in our group of ambulant patients with DMD, timed functional testing was the most sensitive parameter to determine the extent of disease progression. Timed functional testing may therefore be considered as an additional outcome measure in drug trials to evaluate the effects of therapy in ambulant patients with DMD and possibly in other neuromuscular disorders., Time to rise is a useful and simple tool in the screening of neuromuscular disorders such as Duchenne muscular dystrophy,, he muscle strength of the wrist extensors and the radial deviation range of motion at the wrist were found to be strongly correlated with six of the seven tasks assessed. These two clinical assessments appear to be good indicators of overall wrist and hand function.[SEP]Relations: Duchenne muscular dystrophy has relations: disease_protein with DMD, disease_protein with DMD.", "label": "yes"}
{"id": "converted_2071", "sentence1": "Has the gorilla genome been determined?", "sentence2": "Starting with human, chimpanzee, gorilla, and orangutan genomes, our software generated an exhaustive data set of 292 ALs (∼1 kb each) in ∼3 h. , We generated a high-quality assembly of the gorilla genome using single-molecule, real-time sequence technology and a string graph de novo assembly algorithm, Here we present the assembly and analysis of a genome sequence for the western lowland gorilla, and compare the whole genomes of all extant great ape genera., DNA sequencing reveals that the genomes of the human, gorilla and chimpanzee share more than 98% homology.[SEP]", "label": "yes"}
{"id": "converted_3529", "sentence1": "Are CD8+ (cytotoxic) T cells and  CD4+ Helper T cells generated in the thyroid and express the T-cell receptor?", "sentence2": "A fundamental question in developmental immunology is how bipotential thymocyte precursors generate both CD4+ helper and CD8+ cytotoxic T cell lineages., CD4+CD8+ progenitor thymocytes undergo selection following interaction with MHC class I and class II molecules bearing peptide self-antigens, giving rise to CD8+ cytotoxic and CD4+ helper or regulatory T cell lineages, respectively., Through positive selection, double-positive cells in the thymus differentiate into CD4(+) or CD8(+) T single-positive cells that subsequently develop into different types of effective T cells, such as T-helper and cytotoxic T lymphocyte cells,, Development, differentiation, and function of thymocytes and CD4(+) and CD8(+) T cells are controlled by a multitude of secreted and intracellular factors, . The CD4(+) helper versus CD8(+) cytotoxic T-cell fate decision serves as an excellent model to study binary fate decision processes. These two cell types are derived from common precursors in the thymus., Signals elicited by binding of the T-cell antigen receptor and the CD4/CD8 co-receptor to major histocompatibility complex (MHC) molecules control the generation of CD4+ (helper) or CD8+ (cytotoxic) T cells from thymic precursors that initially express both co-receptor proteins., In the thymus, mature CD4+CD8- and CD4-CD8+ T cells expressing alpha beta T-cell antigen receptors (TCR) develop from immature thymocytes through CD4+CD8+ alpha beta TCR+ intermediates., In the thymus, immature CD8(-4)-TCR- cells differentiate, possibly via a short stage of CD8+4- thymocytes, into CD8+4+ TCR+ T cells and mature further into the main T cell populations, the CD8+4- TCR+ cytotoxic T lymphocytes and the CD4+8- TCR+ T helper cells., In the mammalian thymus, CD4 helper T cells and CD8 cytotoxic T cells arise from a common precursor that expresses both CD4 and CD8.[SEP]Relations: T cell receptor complex has relations: cellcomp_protein with CD4, cellcomp_protein with CD4.", "label": "no"}
{"id": "converted_1411", "sentence1": "Is the ACE inhibitor indicated for lung cancer treatment?", "sentence2": "The angiotensin converting enzyme (ACE) inhibitors are used widely as antihypertensive agents, and it has been suggested that they decrease the risk of some cancers, although available data are conflicting. , Using cell viability and fluorescent activated cell sorting analysis tests, we demonstrated that captopril inhibited the viability of LNM35 cells by inducing apoptosis, providing insight about the mechanisms underlying its antitumorigenic activities. In view of these experimental findings, we conclude that captopril could be a promising option for the treatment of lung cancer., In order to determine the mechanism by which captopril inhibited tumor growth, we investigated the impact of this drug on cell proliferation, apoptosis, and angiogenesis. Immunohistochemical analysis demonstrated that captopril treatment significantly reduced the number of proliferating cells (Ki-67) in the tumor samples but was not associated with inhibition of tumor angiogenesis (CD31)., Using this model, we demonstrated that daily IP administration of captopril (2.8 mg/mouse) for 3 weeks resulted in a remarkable reduction of tumor growth (58%, P < 0.01) and lymph node metastasis (50%, P= 0.088). , Angiotensin-converting enzyme (ACE) inhibitors have been shown to mitigate radiation-induced lung injury in preclinical models, ACE inhibitors may decrease the incidence of radiation pneumonitis in patients receiving thoracic radiation for lung cancer.[SEP]", "label": "no"}
{"id": "converted_3501", "sentence1": "Do MAIT cells have a role in multiple myeloma?", "sentence2": "hus, MAIT cells are reduced in MM patients, which may contribute to disease in these individuals, and moreover, MAIT cells may represent new immunotherapeutic targets for treatment of MM and other malignancies., Here we have analysed the frequency and function of MAIT cells in multiple myeloma (MM) patients. We show that MAIT cell frequency in blood is reduced compared to healthy adult donors, but comparable to elderly healthy control donors, Newly diagnosed MM patient MAIT cells had reduced IFNγ production and CD27 expression, suggesting an exhausted phenotype, although IFNγ-producing capacity is restored in relapsed/refractory patient samples. , We describe recent observations with regard to functional exhaustion of iNKT and MAIT cells in MM pathology and discuss the potential application of checkpoint inhibition as an attractive target for prolonged activation of these immunomodulatory T cells in the treatment of MM., Enumeration, functional responses and cytotoxic capacity of MAIT cells in newly diagnosed and relapsed multiple myeloma., Thus, MAIT cells are reduced in MM patients, which may contribute to disease in these individuals, and moreover, MAIT cells may represent new immunotherapeutic targets for treatment of MM and other malignancies.[SEP]", "label": "yes"}
{"id": "converted_2476", "sentence1": "Can canagliflozin cause euglycemic diabetic ketoacidosis?", "sentence2": "CASE REPORT: We present a case of a 57-year-old woman with type 2 diabetes mellitus taking a combination of canagliflozin and metformin who presented with progressive altered mental status over the previous 2 days. Her work-up demonstrated a metabolic acidosis with an anion gap of 38 and a venous serum pH of 7.08. The serum glucose was 168 mg/dL. The urinalysis showed glucose>500 mg/dL and ketones of 80 mg/dL. Further evaluation demonstrated an elevated serum osmolality of 319 mOsm/kg and an acetone concentration of 93 mg/dL. She was treated with intravenous insulin and fluids, and the metabolic abnormalities and her altered mental status resolved within 36 h. This was the first episode of diabetic ketoacidosis (DKA) for this patient. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Diabetic patients on SGLT2 inhibitor medications are at risk for ketoacidosis. Due to the renal glucose-wasting properties of these drugs, they may present with ketoacidosis with only mild elevations in serum glucose, potentially complicating the diagnosis. , Euglycemic Diabetic Ketoacidosis with Persistent Diuresis Treated with Canagliflozin., We herein report the case of a 27-year-old Asian woman with type 2 diabetes who was treated with a sodium-glucose cotransporter 2 (SGLT2) inhibitor (canagliflozin) who developed euglycemic diabetic ketoacidosis and persistent diuresis in the absence of hyperglycemia., Canagliflozin raised the risk of amputations and the rate of fractures in the CANVAS trial, although more data are necessary before drawing definite conclusions. The risk of euglycemic diabetic ketoacidosis seems to be minimal when the drugs are prescribed properly., Severe Ketoacidosis Associated with Canagliflozin (Invokana): A Safety Concern.,  However, some serious side effects, including severe anion gap metabolic acidosis and euglycemic diabetic ketoacidosis (DKA), have been reported. , At present, the Food and Drug Administration (FDA) has only approved three medications (canagliflozin, dapagliflozin and empagliflozin) in this drug class for the management of Type 2 diabetes. In May 2015, the FDA issued a warning of ketoacidosis with use of this drug class., We present a case of euglycemic diabetic ketoacidosis secondary to canagliflozin in a type 2 diabetic patient., Nonconvulsive Status Epilepticus in Elderly Patients Receiving SSRIs; Euglycemic Diabetic Ketoacidosis Associated with Canagliflozin Use in a Type 1 Diabetic Patient; Duloxetine-Induced Galactorrhea; Canagliflozin-Associated Severe Hypercalcemia and Hypernatremia; Vemurafenib-Induced Fanconi Syndrome., Euglycemic Diabetic Ketoacidosis in a 27 year-old female patient with type-1-Diabetes treated with sodium-glucose cotransporter-2 (SGLT2) inhibitor Canagliflozin., We are reporting a timely case of atypical euglycemic diabetic ketoacidosis in a type 1 diabetic patient treated with sodium-glucose cotransporter-2 (SGLT-2) inhibitor canagliflozin., Euglycemic ketoacidosis did not recur in our patient after discontinuing canagliflozin. , Euglycemic Diabetic Ketoacidosis With Prolonged Glucosuria Associated With the Sodium-Glucose Cotransporter-2 Canagliflozin., In this article, we present a case of a 50-year-old woman with type 2 diabetes who developed euglycemic DKA after initiating therapy with canagliflozin. , SGLT2 inhibitors such as canagliflozin may predispose patients not only to diabetic ketoacidosis but also to prolonged glucosuria., We present a case of euglycemic diabetic ketoacidosis secondary to canagliflozin in a type 2 diabetic patient.<br>, We present a case of euglycemic diabetic ketoacidosis secondary to canagliflozin in a type 2 diabetic patient., CONCLUSION Treatment with canagliflozin was associated with development of euglycemic ketoacidosis., Euglycemic Diabetic Ketoacidosis with Persistent Diuresis Treated with Canagliflozin., We present a case of euglycemic diabetic ketoacidosis secondary to canagliflozin in a type 2 diabetic patient.., Euglycemic Diabetic Ketoacidosis With Prolonged Glucosuria Associated With the Sodium-Glucose Cotransporter-2 Canagliflozin., Euglycemic Diabetic Ketoacidosis in a 27 year-old female patient with type-1-Diabetes treated with sodium-glucose cotransporter-2 (SGLT2) inhibitor Canagliflozin.[SEP]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. Metformin has relations: contraindication with metabolic acidosis, contraindication with metabolic acidosis. diabetic ketoacidosis has relations: disease_disease with type 2 diabetes mellitus, disease_disease with type 2 diabetes mellitus. Empagliflozin has relations: drug_drug with Canagliflozin, drug_drug with Canagliflozin. Dapagliflozin has relations: drug_drug with Canagliflozin, drug_drug with Canagliflozin.", "label": "yes"}
{"id": "converted_3188", "sentence1": "Are artificial blood cells available?", "sentence2": "The critical point for the break through for artificial blood products did not come yet but could be ahead-, We suggest a novel method that uses artificial blood cells (hemoglobin vesicles, Hb-Vs) as photosensitizers in dye laser treatment (at 595-nm wavelength) for port-wine stains (i.e., capillary malformations presenting as red birthmarks) based on the results of animal experiments. [SEP]", "label": "no"}
{"id": "converted_3865", "sentence1": "Is Eflornithine and Sulindac are effective for prevention of progression in Familial Adenomatous Polyposis?", "sentence2": "Eflornithine plus Sulindac for Prevention of Progression in Familial Adenomatous Polyposis, BACKGROUND: The efficacy and safety of combination therapy with eflornithine and sulindac, as compared with either drug alone, in delaying disease progression in patients with familial adenomatous polyposis are unknown., CONCLUSIONS: In this trial involving patients with familial adenomatous polyposis, the incidence of disease progression was not significantly lower with the combination of eflornithine and sulindac than with either drug alone. , Disease progression occurred in 18 of 56 patients (32%) in the eflornithine-sulindac group, 22 of 58 (38%) in the sulindac group, and 23 of 57 (40%) in the eflornithine group, with a hazard ratio of 0.71 (95% confidence interval [CI], 0.39 to 1.32) for eflornithine-sulindac as compared with sulindac (P = 0.29) and 0.66 (95% CI, 0.36 to 1.24) for eflornithine-sulindac as compared with eflornithine., SIONS: In this trial involving patients with familial adenomatous polyposis, the incidence of disease progression was not significantly lower with the combination of eflornithine and sulindac than with either drug alone. (Fund, BACKGROUND: The efficacy and safety of combination therapy with eflornithine and sulindac, as compared with either drug alone, in delaying disease progression in patients with familial adenomatous polyposis a, this trial involving patients with familial adenomatous polyposis, the incidence of disease progression was not significantly lower with the combination of eflornithine and sulindac than with either drug alone. (F[SEP]", "label": "no"}
{"id": "converted_3241", "sentence1": "Can Enlimomab improve stroke outcomes?", "sentence2": "Treatment with a murine anti-ICAM-1 antibody (enlimomab) has been investigated in patients with acute ischemic stroke in the Enlimomab Acute Stroke Trial (EAST). Unfortunately, the case fatality rate in this trial was significantly higher in the enlimomab patient group than in the placebo group., The two clinical trials of therapy aimed at limiting the inflammatory response in acute stroke that have been carried out to date, however, have not shown a benefit to such therapy. , en classes of neuroprotective agents have reached phase III efficacy trials but have shown mixed results. They included calcium channel antagonists, NMDA receptor antagonists, lubeluzole, CDP-choline, the free radical scavenger tirilazad and ebselen, enlimomab, GABA agonist clomethiazole, the sodium channel antagonist fosphenytoin, magnesium, glycine site antagonist GV150526 and piracetam. , BACKGROUND AND PURPOSE: Enlimomab, a murine monoclonal anti-human intercellular adhesion molecule (ICAM)-1 antibody, had a negative outcome in a multicenter acute-stroke trial. , Examination of several potential mechanisms for the negative outcome in a clinical stroke trial of enlimomab, a murine anti-human intercellular adhesion molecule-1 antibody: a bedside-to-bench study., ESULTS: At day 90, the Modified Rankin Scale score was worse in patients treated with enlimomab than with placebo (p = 0.004). Fewer patients had symptom-free recovery on enlimomab than placebo (p = 0.004), and more died (22.2 versus 16.2%). The negative effect of enlimomab was apparent on days 5, 30, and 90 of treatment (p = 0.005). There were significantly more adverse events with enlimomab treatment than placebo, primarily infections and fever., CONCLUSIONS: The authors conclude that anti-ICAM therapy with enlimomab is not an effective treatment for ischemic stroke in the model studied and, indeed, may significantly worsen stroke outcome., CONCLUSIONS\n\nThe authors conclude that anti-ICAM therapy with enlimomab is not an effective treatment for ischemic stroke in the model studied and, indeed, may significantly worsen stroke outcome., There were significantly more adverse events with enlimomab treatment than placebo, primarily infections and fever., RESULTS\n\nAt day 90, the Modified Rankin Scale score was worse in patients treated with enlimomab than with placebo (p = 0.004)., The negative effect of enlimomab was apparent on days 5, 30, and 90 of treatment (p = 0.005)., However, this treatment failed to show benefit in the Enlimomab Acute Stroke Trial., There were significantly more adverse events with enlimomab treatment than placebo, primarily infections and fever., These observations provide several possible mechanisms for central nervous system-related clinical deterioration that occurred when Enlimomab was given in acute ischemic stroke., RESULTS\nAt day 90, the Modified Rankin Scale score was worse in patients treated with enlimomab than with placebo (p = 0.004)., Unfortunately, the case fatality rate in this trial was significantly higher in the enlimomab patient group than in the placebo group., CONCLUSIONS\nDoses of enlimomab between 140 and 480 mg administered over 5 days did not increase the risk of adverse events in patients with ischaemic or haemorrhagic stroke during an observation period of 30 +/- 10 days., PURPOSE: Enlimomab, a murine monoclonal anti-human intercellular adhesion molecule (ICAM)-1 antibody, had a negative outcome in a multicenter acute-stroke trial., These observations provide several possible mechanisms for central nervous system-related clinical deterioration that occurred when Enlimomab was given in acute ischemic stroke., Enlimomab, a murine monoclonal anti-human intercellular adhesion molecule (ICAM)-1 antibody, had a negative outcome in a multicenter acute-stroke trial., These observations provide several possible mechanisms for central nervous system-related clinical deterioration that occurred when Enlimomab was given in acute ischemic stroke., The authors conclude that anti-ICAM therapy with enlimomab is not an effective treatment for ischemic stroke in the model studied and, indeed, may significantly worsen stroke outcome.[SEP]", "label": "no"}
{"id": "converted_653", "sentence1": "Is delayed enhancement documented in patients with non-ischemic dilated cardiomyopathy?", "sentence2": "Myocardial fibrosis was present in 30% of patients, the majority of which was mid-myocardial (63%). ,  DCM patients frequently have myocardial fibrosis detected on CE-CMR, the majority of which is mid-myocardial., Fifty (40%) patients showed myocardial DE, representing 12±7% of LV mass., one case was dilated cardiomyopathy, in which the delayed enhancement was diffuse small midwall spots , In the dilated cardiomyopathy group, only seven (29%) patients showed delayed enhancement and its pattern was characterized by mid-wall, patchy or diffuse location., Patterns of delayed enhancement are different in dilated cardiomyopathy and ischemic cardiomyopathy, reflecting the presence of scarring or various degrees of fibrosis in left ventricular myocardium. The presence of subendocardial or transmural delayed enhancement at contrast-enhanced cardiovascular magnetic resonance allowed distinction between dilated cardiomyopathy and ischemic cardiomyopathy with high sensitivity (88%) and specificity (100%).[SEP]Relations: idiopathic cardiomyopathy has relations: disease_disease with cardiomyopathy, disease_disease with cardiomyopathy. Cardiomyopathy has relations: disease_phenotype_positive with dilated cardiomyopathy, disease_phenotype_positive with dilated cardiomyopathy.", "label": "yes"}
{"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_2496", "sentence1": "Does prolactinoma increase osteoporosis risk?", "sentence2": "Prolactinoma: A Massive Effect on Bone Mineral Density in a Young Patient., Osteoporosis has been noted to be an issue in postmenopausal women with prolactinomas. This case shows a similar impact on bone health in a young male resulting in low bone mineral density for age based on Z-score. This case report highlights the possible mechanisms for the bone loss in the setting of prolactinoma and the need for assessing bone health in such patients.,  Hyperprolactinaemia related to prolactinoma significantly (more than functional hyperprolactiaemia) increases the risk of osteopenia, osteoporosis and bone fractures. , Prolactinomas are the most common type of functional pituitary tumor. Effective hyperprolactinemia treatment is of great importance, due to its potential deleterious effects including infertility, gonadal dysfunction and osteoporosis. , Prolactinomas cause hypogonadism, infertility, osteoporosis, and tumor mass effects, and are the most common type of neuroendocrine tumor., We present a 22-year-old man with multiple osteoporotic fractures associated with prolactinoma despite the use of teriparatide for 18 months. We emphasize and highlight the importance of hyperprolactinemia and fractures caused by high prolactin levels., OBJECTIVE: Patients with prolactinoma seem to be at high risk for osteopenia. , RESULTS: Compared to the matched controls, BMD of patients with prolactinoma or craniopharyngioma significantly decreased. , CONCLUSION: In the premenopausal women, patients with prolactinoma or craniopharyngioma are often accompanied with osteopenia or osteoporosis, and disease duration and hypogonadism are the risk factors of bone loss in prolactinoma., Data on osteoporotic fractures in hyperprolactinemia are limited. An increased prevalence of radiological vertebral fractures was recently observed in women with prolactin (PRL)-secreting adenoma, whereas it is unknown whether this observation may reflect a more general increased risk of fractures in this disease and whether the prevalence of fractures in males is affected by gonadal status., Prolactinoma presenting as chronic anaemia with osteoporosis: a case report., Six years later, he was evaluated and diagnosed with a prolactinoma and resultant osteoporosis. Prolactinoma in old people may present insidiously with chronic anaemia and osteoporosis with or without sexual dysfunction., The relative risk for developing osteoporosis in women with prolactinoma was found to be 4.5, indicating that hyperprolactinemia in women is a major risk factor for osteoporosis.<br>, <b>INTRODUCTION</b>: Osteopenia and osteoporosis because of hyperprolactinaemia caused by prolactinoma may be followed by an increased risk of fracture., Univariate and multivariate regression analysis indicated that the bone loss in prolactinomas was significantly correlated to disease duration and hypogonadism.<br><b>CONCLUSION</b>: In the premenopausal women, patients with prolactinoma or craniopharyngioma are often accompanied with osteopenia or osteoporosis, and disease duration and hypogonadism are the risk factors of bone loss in prolactinoma., High serum prolactin levels lead to increase of the risk of osteopenia or/and osteoporosis., Prolactinoma in old people may present insidiously with chronic anaemia and osteoporosis with or without sexual dysfunction.<br><b>CASE PRESENTATION</b>: We describe the case of a 70-year-old Caucasian man who presented with mild anaemia and tiredness., In the premenopausal women, patients with prolactinoma or craniopharyngioma are often accompanied with osteopenia or osteoporosis, and disease duration and hypogonadism are the risk factors of bone loss in prolactinoma., The relative risk for developing osteoporosis in women with prolactinoma was found to be 4.5, indicating that hyperprolactinemia in women is a major risk factor for osteoporosis., CONCLUSION In the premenopausal women, patients with prolactinoma or craniopharyngioma are often accompanied with osteopenia or osteoporosis, and disease duration and hypogonadism are the risk factors of bone loss in prolactinoma., Prolactinoma in old people may present insidiously with chronic anaemia and osteoporosis with or without sexual dysfunction., Hyperprolactinaemia related to prolactinoma significantly (more than functional hyperprolactiaemia) increases the risk of osteopenia, osteoporosis and bone fractures., INTRODUCTION Osteopenia and osteoporosis because of hyperprolactinaemia caused by prolactinoma may be followed by an increased risk of fracture., In conclusion, men with prolactinoma have high prevalence of osteopenia and osteoporosis., Humans with prolactinoma are at risk for osteoporosis., Osteopenia and osteoporosis because of hyperprolactinaemia caused by prolactinoma may be followed by an increased risk of fracture., The relative risk for developing osteoporosis in women with prolactinoma was found to be 4.5, indicating that hyperprolactinemia in women is a major risk factor for osteoporosis.., In the premenopausal women, patients with prolactinoma or craniopharyngioma are often accompanied with osteopenia or osteoporosis, and disease duration and hypogonadism are the risk factors of bone loss in prolactinoma.[SEP]Relations: Hypogonadism has relations: disease_phenotype_positive with craniopharyngioma, disease_phenotype_positive with craniopharyngioma.", "label": "yes"}
{"id": "converted_3782", "sentence1": "Does radiotherapy for cervical cancer increases risk of colon cancer?", "sentence2": "After 8 years, the hazard ratio for developing colon cancer was 2.00 (95% CI 1.43-2.80) for women with radiation versus those without radiation treatment., After 35 years of follow-up, the absolute risk of developing colon cancer was 6.5% for those who received radiation versus 2.5% for those without, and 3.7 versus 0.8% for rectum. The risk of colon and rectum cancer over 20 years of follow-up after radiation remained the same across three eras (1973-1980, 1981-1990, and 1991-2000). Radiation-induced second cancers of the colon and rectum may occur 8 years after radiation treatment for cervical cancer., The data suggested that high-dose pelvic irradiation was associated with increase in cancers of the bladder, kidneys, rectum, ovaries, corpus uteri, and non-Hodgkin's lymphoma but, apparently, not leukemia, Hodgkin's disease, breast cancer, or colon cancer., Radiation-induced second cancers of the colon and rectum may occur 8 years after radiation treatment for cervical cancer., Cervical cancer patients treated with radiotherapy, but not those who did not receive radiotherapy, were at increased risk for all second cancers and cancers at heavily irradiated sites (colon, rectum/anus, urinary bladder, ovary, and genital sites) beyond 40 years of follow-up compared with women in the general population. [SEP]Relations: malignant germ cell tumor of cervix uteri has relations: disease_disease with cervical cancer, disease_disease with cervical cancer.", "label": "yes"}
{"id": "converted_2424", "sentence1": "Are organisms in the genus Morexella associated with sepsis?", "sentence2": "Out of 130 culture proven cases of neonatal sepsis, gram negative bacteria were found in 71 (54.6%) cases and gram positive bacteria in 59 (45.4%) cases. Staphylococcus aureus was the most common bacteria found in 35 (26.9%) cases followed by Escherichia coli in 30 (23.1%) cases. Acinetobacter species, Staphylococcus epidermidis, Klebseila, Streptococci, Enterobacter cloacae and Morexella species were found in 17 (13.1%), 17 (13.1%), 13 (10%), 7 (5.4%), 6 (4.6%), and 5 (3.8%) cases respectively. [SEP]", "label": "yes"}
{"id": "converted_3145", "sentence1": "Can TAD disruption lead to disease?", "sentence2": "its perturbation will lead to human disease, highlighting the accumulating evidence that links the diverse 3D genome architecture components to a multitude of human diseases and the emerging mechanisms by which 3D genome derangement causes disease phenotypes., TAD boundaries are insulators of genomic neighborhoods. In this issue, Sun et al. show that disease-associated tandem repeats are located to TAD boundaries and affect their insulation. , Recent studies of TAD boundaries disrupted in engineered mouse models show that boundary mutations can recapitulate human developmental disorders as a result of aberrant promoter-enhancer interactions in the affected TADs, Similar boundary disruptions in certain cancers can result in oncogene overexpression, and CTCF binding sites at boundaries appear to be hyper-mutated across cancers., the disruption of these structures by genomic rearrangements can result in gene misexpression and disease., TAD disruption as oncogenic driver., Recent studies have shown that TAD disruption is often found in cancer cells and contributes to oncogenesis through two mechanisms., Disruption of TAD boundaries results in aberrant gene expression by exposing genes to inappropriate regulatory elements., However, it is not clear to which extent TAD regions are conserved in evolution and whether disruption of TADs by evolutionary rearrangements can alter gene expression., Disruption of this organization by structural variations can lead to ectopic interactions between enhancers and promoters, and to alteration of genes expression patterns., Disruption of TADs can result in altered gene expression and is associated to genetic diseases and cancers., Deletion in 2q35 excluding the IHH gene leads to fetal severe limb anomalies and suggests a disruption of chromatin architecture., We demonstrate that disruption of TADs can rewire long-range regulatory architecture and result in pathogenic phenotypes. , Disruption of TAD boundaries results in aberrant gene expression by exposing genes to inappropriate regulatory elements. , Disruption of TADs can result in altered gene expression and is associated to genetic diseases and cancers. , Disruption of a TAD boundary causes ectopic chromosomal contacts and long-range transcriptional misregulation. , Recent studies of TAD boundaries disrupted in engineered mouse models show that boundary mutations can recapitulate human developmental disorders as a result of aberrant promoter-enhancer interactions in the affected TADs. , Recent studies have shown that TAD disruption is often found in cancer cells and contributes to oncogenesis through two mechanisms. , Disruption of this organization by structural variations can lead to ectopic interactions between enhancers and promoters, and to alteration of genes expression patterns. , Similar boundary disruptions in certain cancers can result in oncogene overexpression, and CTCF binding sites at boundaries appear to be hyper-mutated across cancers. , However, it is not clear to which extent TAD regions are conserved in evolution and whether disruption of TADs by evolutionary rearrangements can alter gene expression. [SEP]", "label": "yes"}
{"id": "converted_511", "sentence1": "Is Alpers disease inherited in an autosomal recessive mode?", "sentence2": "Alpers-Huttenlocher syndrome (AHS) is a very rare autosomal recessive disorder, Alpers syndrome is an autosomal recessive mitochondrial DNA depletion disorder that affects children and young adults, Alpers' syndrome is a fatal neurogenetic disorder first described more than 70 years ago. It is an autosomal recessive, developmental mitochondrial DNA depletion disorder characterized by deficiency in mitochondrial DNA polymerase gamma (POLG) catalytic activity, refractory seizures, neurodegeneration, and liver disease, Histopathological findings in both patients ((a) chronic hepatitis with prominent bile duct proliferation, fatty change, and fibrosis; (b) in the brain a patchy destruction of the cerebral cortex, predominantly involving striate cortex) were characteristic of progressive neuronal degeneration of childhood with liver disease--Alpers-Huttenlocher syndrome--a rare autosomal recessive disorder usually seen in infants and young children, Histopathological findings in both patients ((a) chronic hepatitis with prominent bile duct proliferation, fatty change, and fibrosis; (b) in the brain a patchy destruction of the cerebral cortex, predominantly involving striate cortex) were characteristic of progressive neuronal degeneration of childhood with liver disease--Alpers-Huttenlocher syndrome--a rare autosomal recessive disorder usually seen in infants and young children., Alpers syndrome is a rare autosomal recessive hepatocerebral degenerative disorder., Alpers disease is a recessive mitochondrial disorder caused by mutations in POLG1 and characterized primarily by progressive neurological and hepatic degeneration., Alpers syndrome is an autosomal recessive mitochondrial DNA depletion disorder that affects children and young adults., We conclude that Alpers disease can be a cause of rapidly progressive liver failure in early childhood. Although the cause of this autosomal recessive disease is not known, it does not appear to be related to peroxisomal dysfunction.[SEP]Relations: hepatobiliary disease has relations: disease_disease with liver disease, disease_disease with liver disease. cerebral cortex has relations: anatomy_protein_present with POLG, anatomy_protein_present with POLG. liver failure has relations: disease_disease with liver disease, disease_disease with liver disease.", "label": "yes"}
{"id": "converted_512", "sentence1": "Is vemurafenib effective for hairy-cell leukemia?", "sentence2": "CONCLUSIONS: A short oral course of vemurafenib was highly effective in patients with relapsed or refractory hairy-cell leukemia., Our results strongly support and inform the clinical use of BRAF and MEK inhibitors in HCL., The therapeutic approach of vemurafenib in treatment-refractory hairy cell leukemia is promising and offers an additional treatment option. , Successful re-treatment of a relapsed V600E mutated HCL patient with low-dose vemurafenib., Recent identification of the recurrent V600E BRAF mutation in a majority of HCL patients has led some teams to evaluate the clinical potential of vemurafenib, a BRAF V600 specific inhibitor in a limited number of refractory HCL patients. Recently, we published the case of an HCL patient successfully treated with a low dose of vemurafenib., We present here the successful retreatment of this patient with a second line of vemurafenib. Our data suggest for the first time that vemurafenib at the dose of 240 mg once a day could be sufficient to maintain a complete hematological remission after an initial induction treatment with low-dose vemurafenib (2 × 240 mg) daily without inducing major toxicity., The discovery of the BRAF mutation has created a therapeutic target exploited by oral inhibitors like vemurafenib and dabrafenib., [Successful use of vemurafenib in a patient with resistant hairy cell leukemia]., The frequent persistence of phosphorylated ERK-positive leukemic cells in bone marrow at the end of treatment suggests bypass reactivation of MEK and ERK as a resistance mechanism.CONCLUSIONS: A short oral course of vemurafenib was highly effective in patients with relapsed or refractory hairy-cell leukemia. , A short oral course of vemurafenib was highly effective in patients with relapsed or refractory hairy-cell leukemia., A short oral course of vemurafenib was highly effective in patients with relapsed or refractory hairy-cell leukemia., The therapeutic approach of vemurafenib in treatment-refractory hairy cell leukemia is promising and offers an additional treatment option.[SEP]Relations: Vemurafenib has relations: drug_protein with BRAF, drug_protein with BRAF. hairy cell leukemia has relations: disease_protein with BRAF, disease_protein with BRAF. Dabrafenib has relations: drug_protein with BRAF, drug_protein with BRAF.", "label": "yes"}
{"id": "converted_856", "sentence1": "Is Dicer part of the RISC loading complex?", "sentence2": "Dicer is a component of the protein machinery (the RNA Induced Silencing Complex [RISC]) which is involved in catalyzing the formation of mature microRNAs from their precursors in the process of microRNA biogenesis., RNA-induced silencing complex (RISC) Proteins PACT, TRBP, and Dicer are SRA binding nuclear receptor coregulators., The cytoplasmic RNA-induced silencing complex (RISC) contains dsRNA binding proteins, including protein kinase RNA activator (PACT), transactivation response RNA binding protein (TRBP), and Dicer, that process pre-microRNAs into mature microRNAs (miRNAs) that target specific mRNA species for regulation. ,  Although the major RNAi pathway proteins are found in most subcellular compartments, the miRNA- and siRNA-loaded Ago2 populations co-sediment almost exclusively with the rER membranes, together with the RISC loading complex (RLC) factors Dicer, TAR RNA binding protein (TRBP) and protein activator of the interferon-induced protein kinase (PACT)., RNA interference (RNAi) is mediated by small interfering RNAs (siRNAs), which are liberated from double-stranded (ds)RNA precursors by Dicer and guide the RNA-induced silencing complex (RISC) to targets., . Dicer, an RNase III enzyme, plays a central role in the RNAi pathway by cleaving precursors of both of these classes of RNAs to form mature siRNAs and miRNAs, which are then loaded into the RNA-induced silencing complex (RISC). , Canonical siRNAs are 21 nucleotides (nt) in length and are loaded to the RNA Induced Silencing Complex when introduced into the cells, while longer siRNA molecules are first processed by endogenous Dicer and thus termed Dicer-substrate siRNA (DsiRNA). [SEP]", "label": "yes"}
{"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_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_1430", "sentence1": "Is the UGT1A1*28 polymorphism associated with irinotecan response in Caucasians?", "sentence2": "These variants are associated with greater risk of serious toxicity., Homozygous carriers of UGT1A1*28 as well as those with additional UGT1A variants can suffer from severe irinotecan toxicity[SEP]", "label": "yes"}
{"id": "converted_137", "sentence1": "Is GAGA associated with nucleosome-free regions (NFR)?", "sentence2": "One of the three nuclease hypersensitive sites in the Fab-7 boundary, HS1, contains multiple consensus-binding sequences for the GAGA factor, a protein known to be involved in the formation and/or maintenance of nucleosome-free regions of chromatin., The HS3 sequence contains consensus binding sites for the GAGA factor, a protein implicated in the formation of nucleosome-free regions of chromatin, and Pleiohomeotic (Pho), a Polycomb group protein that is related to the mammalian transcription factor YY1., The interactions of GAGA factor and heat shock factor with their binding sites in chromatin occurred in two modes. Their interaction with binding sites in the nucleosome-free regions did not require ATP. In the presence of ATP both factors interacted also with nucleosomal binding sites, causing nucleosome rearrangements and a refinement of nucleosome positions, While chromatin remodeling upon transcription factor interaction has previously been interpreted to involve nucleosome disruption, the data suggest energy-dependent nucleosome sliding as main principle of chromatin reorganization.,  These (CT)n repeats are associated with a nonhistone protein(s) in vivo and are bound by a purified Drosophila protein, the GAGA factor, in vitro., This (CT)n element appears to contribute to formation of the wild-type chromatin structure of hsp26, an organized nucleosome array that leaves the HSEs in nucleosome-free, DNase I-hypersensitive (DH) site, The HS3 sequence contains consensus binding sites for the GAGA factor, a protein implicated in the formation of nucleosome-free regions of chromatin, and Pleiohomeotic (Pho), a Polycomb group protein that is related to the mammalian transcription factor YY1., One of the three nuclease hypersensitive sites in the Fab-7 boundary, HS1, contains multiple consensus-binding sequences for the GAGA factor, a protein known to be involved in the formation and/or maintenance of nucleosome-free regions of chromatin., The iab-7 polycomb response element maps to a nucleosome-free region of chromatin and requires both GAGA and pleiohomeotic for silencing activity., The HS3 sequence contains consensus binding sites for the GAGA factor, a protein implicated in the formation of nucleosome-free regions of chromatin, and Pleiohomeotic (Pho), a Polycomb group protein that is related to the mammalian transcription factor YY1. [SEP]", "label": "yes"}
{"id": "converted_3916", "sentence1": "Is HbA1c an ideal biomarker of well-controlled diabetes?", "sentence2": "HbA1c is a biomarker with a central role in the diagnosis and follow-up of patients with diabetes, although not a perfect one. Common comorbidities encountered in patients with diabetes mellitus, such as renal insufficiency, high output states (iron deficiency anaemia, haemolytic anaemia, haemoglobinopathies and pregnancy) and intake of specific drugs could compromise the sensitivity and specificity of the biomarker. COVID-19 pandemic poses a pressing challenge for the diabetic population, since maintaining optimal blood glucose control is key to reduce morbidity and mortality rates.[SEP]", "label": "no"}
{"id": "converted_3240", "sentence1": "Can mitochondria transfer from cell to cell?", "sentence2": "Interest in the recently discovered phenomenon of mitochondrial transfer between mammalian cells has gained momentum since it was first described in cell culture systems more than a decade ago., We show evidence that mitochondria transfer from Jurkat cells to MSCs, which is mediated by cell adhesion, This process of mitochondria transfer is mediated by tunneling nanotubes, which are protrusions that extend from the cell membrane .[SEP]", "label": "yes"}
{"id": "converted_4429", "sentence1": "Is vocimagene amiretrorepvec effective for recurrent high-grade glioma?", "sentence2": "Relevance: Among patients who underwent tumor resection for first or second recurrence of glioblastoma or anaplastic astrocytoma, administration of Toca 511 and Toca FC, compared with SOC, did not improve overall survival or other efficacy end points., The median OS was 11.10 months for the Toca 511/FC group and 12.22 months for the control group (hazard ratio, 1.06; 95% CI 0.83, 1.35; P = .62). The secondary end points did not demonstrate statistically significant differences. , Expert opinion: These early studies provide very encouraging results for Toca 511 and Toca FC in rHGG. This therapy had a response rate of 11.3% and a mOS of 11.9 months in 56 patients, an improvement compared to historical controls. , Findings from a phase I study suggest that delivering high concentrations of the chemotherapy 5-FU directly to brain tumors via the retroviral vector vocimagene amiretrorepvec, or Toca 511, may benefit patients with recurrent high-grade glioma., Overall survival for recurrent high-grade glioma was 13.6 months (95% confidence interval, 10.8 to 20.0) and was statistically improved relative to an external control (hazard ratio, 0.45; P = 0.003).[SEP]", "label": "no"}
{"id": "converted_1826", "sentence1": "Is the protein lefty an inhibitor of nodal?", "sentence2": "The expression of lefty, an inhibitor of nodal is often reduced in tumor cells.,  Nodal, and an inhibitor, Lefty., as well as the expression of Lefty, an inhibitor of nodal signaling,, he Nodal inhibitor lefty, The morphogen Nodal was proposed to form a long-range signaling gradient via a reaction-diffusion system, on the basis of differential diffusion rates of Nodal and its antagonist Lefty.[SEP]", "label": "yes"}
{"id": "converted_1255", "sentence1": "Is lenvatinib effective for thyroid cancer?", "sentence2": "New insights in the treatment of radioiodine refractory differentiated thyroid carcinomas: to lenvatinib and beyond., However, even more impressive responses and progression-free survival benefits were seen in the phase III SELECT trial with lenvatinib, giving even higher hopes for the future management of what was considered just a decade ago an orphan disease. , Sorafenib and lenvatinib, small-molecule multikinase inhibitors, were approved for the treatment of progressive, symptomatic, radioactive iodine refractory, advanced differentiated thyroid cancer in 2013 and 2015, respectively., A phase 2 trial of lenvatinib (E7080) in advanced, progressive, radioiodine-refractory, differentiated thyroid cancer: A clinical outcomes and biomarker assessment., CONCLUSIONS: In patients with and without prior exposure to VEGF therapy, the encouraging response rates, median time to response, and PFS for lenvatinib have prompted further investigation in a phase 3 trial. , Since 2011, four multikinase inhibitors (MKIs) have been approved by the US Food and Drug Administration for thyroid cancer - cabozantinib and vandetanib for medullary thyroid cancer and sorafenib and lenvatinib for differentiated thyroid cancer. , Moreover, four of those investigational drugs, vandetanib, cabozantinib, sorafenib and lenvatinib, have reached a phase III clinical trial with favorable results in progression-free survival and overall survival in medullary thyroid carcinoma and differentiated thyroid carcinoma., Since 2011, four multikinase inhibitors (MKIs) have been approved by the US Food and Drug Administration for thyroid cancer - cabozantinib and vandetanib for medullary thyroid cancer and sorafenib and lenvatinib for differentiated thyroid cancer, BACKGROUND: Lenvatinib, an oral inhibitor of vascular endothelial growth factor receptors 1, 2, and 3, fibroblast growth factor receptors 1 through 4, platelet-derived growth factor receptor �, RET, and KIT, showed clinical activity in a phase 2 study involving patients with differentiated thyroid cancer that was refractory to radioiodine (iodine-131).METHODS: In our phase 3, randomized, double-blind, multicenter study involving patients with progressive thyroid cancer that was refractory to iodine-131, we randomly assigned 261 patients to receive lenvatinib (at a daily dose of 24 mg per day in 28-day cycles) and 131 patients to receive placebo. , Positive phase 1 results in solid tumors prompted a phase 2 trial in patients with advanced, radioiodine-refractory, differentiated thyroid cancer (RR-DTC).METHODS: Fifty-eight patients with RR-DTC who had disease progression during the previous 12 months received lenvatinib 24 mg once daily in 28-day cycles until disease progression, unmanageable toxicity, withdrawal, or death. [SEP]Relations: medullary thyroid gland carcinoma has relations: disease_protein with RET, disease_protein with RET. Vandetanib has relations: drug_protein with RET, drug_drug with Sorafenib, drug_drug with Lenvatinib, drug_protein with RET, drug_drug with Sorafenib, drug_drug with Lenvatinib. Sorafenib has relations: drug_protein with RET, drug_protein with KIT, drug_drug with Lenvatinib, drug_protein with RET, drug_protein with KIT, drug_drug with Lenvatinib. stem cell factor receptor activity has relations: molfunc_protein with KIT, molfunc_protein with KIT. thyroid gland carcinoma has relations: disease_protein with RET, disease_disease with thyroid cancer, disease_protein with RET, disease_disease with thyroid cancer. Lenvatinib has relations: drug_drug with Sorafenib, drug_protein with KIT, drug_protein with RET, drug_drug with Sorafenib, drug_protein with KIT, drug_protein with RET. Cabozantinib has relations: drug_drug with Lenvatinib, drug_protein with RET, drug_drug with Sorafenib, drug_drug with Lenvatinib, drug_protein with RET, drug_drug with Sorafenib.", "label": "yes"}
{"id": "converted_3572", "sentence1": "Does the Mcm2-Ctf4-Polα axis play a role in transfer of histones to leading strand DNA at the replication forks?", "sentence2": "The Mcm2-Ctf4-Polα Axis Facilitates Parental Histone H3-H4 Transfer to Lagging Strands., Although essential for epigenetic inheritance, the transfer of parental histone (H3-H4)2 tetramers that contain epigenetic modifications to replicating DNA strands is poorly understood. Here, we show that the Mcm2-Ctf4-Polα axis facilitates the transfer of parental (H3-H4)2 tetramers to lagging-strand DNA at replication forks. Mutating the conserved histone-binding domain of the Mcm2 subunit of the CMG (Cdc45-MCM-GINS) DNA helicase, which translocates along the leading-strand template, results in a marked enrichment of parental (H3-H4)2 on leading strand, due to the impairment of the transfer of parental (H3-H4)2 to lagging strands. Similar effects are observed in Ctf4 and Polα primase mutants that disrupt the connection of the CMG helicase to Polα that resides on lagging-strand template. Our results support a model whereby parental (H3-H4)2 complexes displaced from nucleosomes by DNA unwinding at replication forks are transferred by the CMG-Ctf4-Polα complex to lagging-strand DNA for nucleosome assembly at the original location.[SEP]", "label": "no"}
{"id": "converted_129", "sentence1": "Is amantadine effective for treatment of disorders conciousness?", "sentence2": "We here provide a systematic overview of the therapeutic effects of amantadine, apomorphine and zolpidem in patients recovering from coma. Evidence from clinical trials using these commonly prescribed pharmacological agents suggests positive changes in the neurological status in patients, leading sometimes to dramatic improvements., Pharmaceuticals that act in the oxygen based amino acid systems of the brain include the GABAergic medications zolpidem and baclofen, while those that act in the monoamine axes include the dopaminergic medications L Dopa, amantadine, bromocriptine, apomorphine and methylphenidate, and the noradrenergic and serotonergic medications desipramine, amitriptyline, protriptyline and fluoxetine. , Sporadic cases of recovery from a DOC have been reported after the administration of various pharmacological agents (baclofen, zolpidem, amantadine etc.)., Amantadine hydrochloride is one of the most commonly prescribed medications for patients with prolonged disorders of consciousness after traumatic brain injury. Preliminary studies have suggested that amantadine may promote functional recovery.,  During the 4-week treatment period, recovery was significantly faster in the amantadine group than in the placebo group, as measured by the DRS score (difference in slope, 0.24 points per week; P=0.007), indicating a benefit with respect to the primary outcome measure. , Amantadine accelerated the pace of functional recovery during active treatment in patients with post-traumatic disorders of consciousness., Sporadic cases of dramatic recovery from DOC after the administration of various pharmacological agents, such as baclofen, zolpidem and amantadine, have been recently supported by intriguing scientific observations. , According to the 16 eligible studies, medical management by dopaminergic agents (levodopa, amantadine), zolpidem and median nerve stimulation, or surgical management by deep brain stimulation, extradural cortical stimulation, spinal cord stimulation and intrathecal baclofen have shown to improve the level of consciousness in certain cases. , Higher exposure of amantadine (average concentration of amantadine during 6 mg/kg/day > 1.5 mg/L) may be associated with better recovery of consciousness. , Based on the preliminary data, higher dosing may be considered in the setting of brain injury., Patients treated with PK-Merz exhibited the more significant restoration of consciousness and better dynamics (regress) of neurological deficit with the most intensive restoration of neurological deficit in the first day that allows to recommend the use of amantadine sulfate in the first hours of ischemic stroke and for the prevention of reperfusion damage in recanalisation therapy of ischemic stroke., There was no significant difference in the slopes of recovery during either arm for the Coma/Near-Coma Scale (P = 0.24) or the Coma Recovery Scale-Revised (P = 0.28), although improvements in consciousness were noted by the physician during weeks when amantadine was given (P = 0.02). , This study suggests that amantadine facilitates recovery of consciousness in pediatric acquired brain injury and provides important information necessary to design future more definitive studies., The study has shown a positive effect of this drug at coma emergence, which manifested itself as clinical improvement and a better outcome of the disease., This article will review the evidence for the use of psychostimulants (methylphenidate), antidepressants (amitriptyline, selective serotonin reuptake inhibitors, and buproprion), Parkinson's medications (amantadine, bromocriptine, carbidopa/levodopa), anticonvulsants (valproic acid), modafinil (Provigil), lactate, hyperbaric oxygen chamber, electroconvulsive therapy, and transmagnetic stimulation, in patients following a head injury., Of the psychoactive medications, amantadine hydrochloride was associated with greater recovery and dantrolene sodium was associated with less recovery, in terms of the DRS score at 16 weeks but not the time until commands were followed.[SEP]Relations: Baclofen has relations: drug_drug with Amantadine, drug_drug with Amantadine. Protriptyline has relations: drug_drug with Amantadine, drug_drug with Amantadine. Carbidopa has relations: drug_drug with Amantadine, drug_drug with Amantadine. Levodopa has relations: drug_drug with Amantadine, drug_drug with Amantadine. Amitriptyline has relations: drug_drug with Amantadine, drug_drug with Amantadine. Apomorphine has relations: drug_drug with Amantadine, drug_drug with Amantadine. Fluoxetine has relations: drug_drug with Amantadine, drug_drug with Amantadine. Valproic acid has relations: drug_drug with Amantadine, drug_drug with Amantadine. Methylphenidate has relations: drug_drug with Amantadine, drug_drug with Amantadine.", "label": "yes"}
{"id": "converted_2991", "sentence1": "Does Eucommia ulmoides leaf extract ameliorates steatosis/fatty liver induced by high-fat diet?", "sentence2": "These results demonstrate that the Du-zhong leaf extract exhibits antihyperlipidemic properties by suppressing hepatic fatty acid and cholesterol biosynthesis with the simultaneous reduction of plasma and hepatic lipids in high fat-fed hamsters.,  Together, these results suggest that EUE and its active components enhance lysosomal activity, resulting in decreased ER stress and hepatic dyslipidemi, Du-zhong (Eucommia ulmoides Oliver) leaf extract mediates hypolipidemic action in hamsters fed a high-fat diet.This study examined the effect of a Du-zhong (Eucommia ulmoides Oliver) leaf extract (0.175 g/100 g diet) that was supplemented with a high-fat diet (10% coconut oil, 0.2% cholesterol, wt/wt) on hyperlipidemic hamsters. , Preventive effect of Eucommia leaf extract on aortic media hypertrophy in Wistar-Kyoto rats fed a high-fat diet.Eucommia ulmoides Oliver leaf extract (ELE) has been shown to have anti-hypertensive and anti-obesity effects in rats that are fed a high-fat diet (HFD). , Eucommia ulmoides Oliver leaf extract (ELE) has been shown to have anti-hypertensive and anti-obesity effects in rats that are fed a high-fat diet (HFD)., The hepatic fatty acid synthase and HMG-CoA reductase activities were significantly lowered by a Du-zhong leaf extract supplement in high fat-fed hamsters., These results demonstrate that the Du-zhong leaf extract exhibits antihyperlipidemic properties by suppressing hepatic fatty acid and cholesterol biosynthesis with the simultaneous reduction of plasma and hepatic lipids in high fat-fed hamsters.<br>, Both forms of Eucommia leaves minimised increases in body weight and visceral fat in a dose-dependent fashion., These results demonstrate that the Du-zhong leaf extract exhibits antihyperlipidemic properties by suppressing hepatic fatty acid and cholesterol biosynthesis with the simultaneous reduction of plasma and hepatic lipids in high fat-fed hamsters., The hepatic fatty acid synthase and HMG-CoA reductase activities were significantly lowered by a Du-zhong leaf extract supplement in high fat-fed hamsters.[SEP]", "label": "yes"}
{"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_1733", "sentence1": "Is mitofusin 2 a receptor for parkin?", "sentence2": "Recent work demonstrates that a phosphorylated form of the mitochondrial fusion protein Mitofusin 2 serves as a receptor for Parkin translocation to damaged mitochondria., We show that the mitochondrial outer membrane guanosine triphosphatase mitofusin (Mfn) 2 mediates Parkin recruitment to damaged mitochondria. , Mfn2 functions as a mitochondrial receptor for Parkin and is required for quality control of cardiac mitochondria., Mitofusin 1 and mitofusin 2 are ubiquitinated in a PINK1/parkin-dependent manner upon induction of mitophagy[SEP]", "label": "yes"}
{"id": "converted_1501", "sentence1": "Have germline variants been associated to colorectal cancer?", "sentence2": "Overall, we identified aberrant transcripts in 8% of the patients (familial cases 30%; early-onset manifestation 21%). In eight of them, two different out-of-frame pseudoexons were found consisting of a 167-bp insertion from intron 4 in five families with a shared founder haplotype and a 83-bp insertion from intron 10 in three patients. The pseudoexon formation was caused by three different heterozygous germline mutations, which are supposed to activate cryptic splice sites, We apply OS-Seq to resequence the exons of either 10 or 344 cancer genes from human DNA samples. In our assessment of capture performance, >87% of the captured sequence originated from the intended target region with sequencing coverage falling within a tenfold range for a majority of all targets. Single nucleotide variants (SNVs) called from OS-Seq data agreed with >95% of variants obtained from whole-genome sequencing of the same individual., The minor alleles of CD44 rs8193 C>T, ALCAM rs1157 G>A, and LGR5 rs17109924 T>C were significantly associated with increased TTR (9.4 vs. 5.4 years; HR, 0.51; 95% CI: 0.35-0.93; P = 0.022; 11.3 vs. 5.7 years; HR, 0.56; 95% CI: 0.33-0.94; P = 0.024, and 10.7 vs. 5.7 years; HR, 0.33; 95% CI: 0.12-0.90; P = 0.023, respectively) and remained significant in the multivariate analysis stratified by ethnicity. In recursive partitioning, a specific gene variant profile including LGR5 rs17109924, CD44 rs8193, and ALDH1A1 rs1342024 represented a high-risk subgroup with a median TTR of 1.7 years (HR, 6.71, 95% CI: 2.71-16.63, P < 0.001)., In this study, we identified common germline variants in VEGF-dependent and -independent angiogenesis genes predicting clinical outcome and tumor response in patients with mCRC receiving first-line bevacizumab and oxaliplatin-based chemotherapy., We identified 22 nonsynonymous somatic mutations of which the majority was of missense type. In germline, three novel nonsynonymous variants were identified in the following genes: CSMD3, EPHB6 and C10orf137, and none of the variants were present in 890 population-matched healthy controls. It is possible that the identified germline variants modulate predisposition to CRC., One patient proved to carry an APC whole-gene deletion; 4 of 25 (16%) patients showed biallelic and 3 of 25 (12%) monoallelic MUTYH mutations. In the three heterozygous subjects no pathogenetic variants were found in OGG1, MTH1, APE1, MSH2, and MSH6 genes. Frequency assessment of MUTYH mutations in healthy subjects showed that only Y165C and G382D reach a subpolymorphic frequency., Scrutinizing the molecular genetic results and family data of 242 index patients with pathogenic APC mutations led to the identification of 10 mosaic cases (4%). C>T transitions were observed in CGA sites in four of the 10 cases with somatic mosaicism, which is significantly more than 26 of the 232 non-mosaic cases (p = 0.02). Phenotypes of patients with somatic mosaicism ranged from an attenuated form of polyposis coli to florid polyposis with major extracolonic manifestations., Altogether 12 previously reported changes and four novel genetic alterations, mostly in intronic sequences, were identified. The results revealed the presence of biallelic germline MYH mutations in two patients. These patients were compound heterozygotes for two of the most common germline mutations c.494 A>G (p.Y165C); c.1,145 G>A (p.G382D). These variants are established to be associated with adenomatous polyposis and colorectal cancer.[SEP]Relations: EDRF1 has relations: disease_protein with colorectal cancer, disease_protein with colorectal cancer. APEX1 has relations: protein_protein with MUTYH, protein_protein with MUTYH. malignant colon neoplasm has relations: disease_protein with APC, disease_disease with colorectal cancer, disease_protein with MUTYH, disease_protein with LGR5, disease_protein with APC, disease_disease with colorectal cancer, disease_protein with MUTYH, disease_protein with LGR5. familial adenomatous polyposis has relations: disease_protein with APC, disease_protein with MUTYH, disease_protein with TTR, disease_protein with APC, disease_protein with MUTYH, disease_protein with TTR. Somatic mutation has relations: disease_phenotype_positive with colorectal cancer, disease_phenotype_positive with colorectal cancer.", "label": "yes"}
{"id": "converted_3708", "sentence1": "Does ESN364 activate the hypothalamic-pituitary-gonadal axis?", "sentence2": "Oral administration of the NK3R antagonist, ESN364, suppressed the hypothalamic-pituitary-gonadal axis in healthy volunteers by selective modulation of gonadotropin secretion, leading to a restrained decrease in ovarian hormone levels in women.[SEP]", "label": "no"}
{"id": "converted_1526", "sentence1": "Is there an association between presenteeism and depression?", "sentence2": "Presenteeism was positively associated with severity of depression (Health and Work Performance Questionnaire, P < 0.0001; WPAI, P < 0.0001)., Statistically significant correlations (0.32-0.53) were found between presenteeism and increasing disability, fatigue, depression, anxiety, and reduced quality of life. , Presenteeism was associated with increasing fatigue, depression, anxiety, and reduced quality of life., Factors with less contribution to presenteeism included physical limitations, depression or anxiety, inadequate job training, and problems with supervisors and coworkers. , BACKGROUND: Subthreshold depression is highly prevalent in the general population and causes great loss to society especially in the form of reduced productivity while at work (presenteeism)., Two major causes of worker presenteeism (reduced on-the-job productivity as a result of health problems) are musculoskeletal pain and mental health issues, particularly depression. ,  Pain and depression were significantly associated with presenteeism. Pr, Survey adjusted multivariable logistic regression assessed classification of 12-month, depression-related presenteeism on the basis of socio-demographic, financial, work and health factors. , RESULTS: The LPT from absenteeism and presenteeism (reduced performance while present at work) was significantly higher among the MDD group., BACKGROUND: Depression is reported to be a major cause of illness-related sub-optimal work performance (presenteeism). , BACKGROUND: It is amply documented that mood disorders adversely affect job satisfaction, workforce productivity, and absenteeism/presenteeism. , The difference in productivity loss due to impaired presenteeism was significantly different between the two groups, but the productivity loss due to absenteeism was not. , Disease activity (OR 3.24, 95% CI 1.11-9.48) and depression (OR 3.22, 95% CI 1.22-8.48) were associated with absenteeism, while depression (OR 5.69, 95% CI 1.77-18.27, disease activity (OR 3.97, 95% CI 1.76-8.98), anxiety (OR 3.90, 95% CI 1.83-8.31), self-efficacy (OR 0.71, 95% CI 0.58-0.86), and increasing age (OR 1.04 per year, 95% CI 1.00-1.08) were associated with presenteeism. , Depression, in particular, appears to be associated with employment, absenteeism, and presenteeism, and should therefore be prioritized in clinical practice., Depression frequently causes unemployment, absenteeism, and presenteeism, which results in significantly reduced productivity., Presenteeism and absenteeism were significantly worse for the depression group at each time point (p < or = .001). In cross-sectional models, presenteeism was associated with more severe depression symptoms, poorer general physical health, psychologically demanding work, the interaction ofpsychologically demanding work with depression, and less job control (r2 range = .33-.54)., Chronic conditions such as depression/anxiety, obesity, arthritis, and back/neck pain are especially important causes of productivity loss. Comorbidities have significant non-additive effects on both absenteeism and presenteeism., RESULTS: At baseline, all presenteeism measures were sensitive to differences between those with (N=69) and without (N=363) depression/anxiety., Depression and anxiety were more consistently associated with \"presenteeism\" (that is, lost productivity while at work) than with absenteeism, whether this was measured by cutback days or by direct questionnaires., RESULTS: Substantial research exists about anxiety and depression costs, such as performance and productivity, absenteeism, presenteeism, disability, physical disability exacerbation, mental health treatment, increased medical care costs, exacerbating of physical illness, and studies of mental health care limitations and cost-offset., The author discusses the etiology and potential solutions for managing this new component in the productivity equation and in addressing depression, the major contributor to presenteeism., For employees who are currently depressed, recent research evidence has demonstrated that pharmacotherapy can have a dramatic and positive effect on lost productivity, absenteeism, and presenteeism., Among participants who were still employed, those with depression had significantly more job turnover, presenteeism, and absenteeism. , Only depression affected both absenteeism-presenteeism and critical incidents. , CONCLUSIONS: Depressive disorders in the workplace persist over time and have a major effect on work performance, most notably on \"presenteeism,\" or reduced effectiveness in the workplace. , The negative effects of depression include those on patients' occupational functioning, including absenteeism, presenteeism, and reduced opportunities for educational and work success. , The remitted group demonstrated a significant improvement in productivity (particularly presenteeism) when compared with the new visit group (Z = -3.29, p = 0.001)., Depression in workers leads to significant absenteeism, \"presenteeism\" (diminished capacity due to illness while still present at work), and significantly increased medical expenses in addition to the costs of psychiatric care. , Significant predictors of presenteeism and activity impairment at follow-up (controlled for gender, age, spondyloarthritis subgroups and presenteeism at baseline) were presenteeism at baseline, poor quality of life, worse disease activity, decreased physical function, lower self-efficacy pain and symptom, higher scores of anxiety, depression, smoking and low education level, and for activity impairment also female sex. , \" Pain and depression were significantly associated with presenteeism., Only depression affected both absenteeism-presenteeism and critical incidents., Factors with less contribution to presenteeism included physical limitations, depression or anxiety, inadequate job training, and problems with supervisors and coworkers.[SEP]Relations: anxiety disorder has relations: disease_disease with anxiety, disease_disease with anxiety.", "label": "yes"}
{"id": "converted_3048", "sentence1": "Can pazopanib be used for treatment von Hippel-Lindau disease?", "sentence2": "Variable response of CNS hemangioblastomas to Pazopanib in a single patient with von Hippel-Lindau disease: Case report., Treatment of RCCs with tyrosine kinase inhibitors (TKIs) such as Pazopanib is now first line therapy, but their effect on VHL-associated CNS HBs remains unknown. We report the use of Pazopanib in a patient with VHL disease for treatment of RCC who also harbored multiple CNS HBs. , Pazopanib in patients with von Hippel-Lindau disease: a single-arm, single-centre, phase 2 trial., INTERPRETATION: Pazopanib was associated with encouraging preliminary activity in von Hippel-Lindau disease, with a side-effect profile consistent with that seen in previous trials. Pazopanib could be considered as a treatment choice for patients with von Hippel-Lindau disease and growing lesions, or to reduce the size of unresectable lesions in these patients. , Recurrent multiple CNS hemangioblastomas with VHL disease treated with pazopanib: a case report and literature review.,  Here, we report a 37-year-old woman's case with recurrent and rapidly progressive VHL-associated hemangioblastomas, causing severe disability. She was treated 24 months with pazopanib, a multityrosine kinase inhibitor (TKI) targeting VEGF and PDGF-β pathways. , Pazopanib therapy for cerebellar hemangioblastomas in von Hippel-Lindau disease: case report., Here we provide the first report demonstrating clinical and radiological anti-tumor response using pazopanib, a small molecule multi-receptor tyrosine kinase inhibitor, in a patient with treatment-refractory VHL-associated CNS hemangioblastoma. , Pazopanib could be considered as a treatment choice for patients with von Hippel-Lindau disease and growing lesions, or to reduce the size of unresectable lesions in these patients., METHODS\nIn this non-randomised, single-centre, open-label, phase 2 trial, adult patients with clinical manifestations of von Hippel-Lindau disease were recruited from the University of Texas MD Anderson Cancer Center (Houston, TX, USA) and were treated with pazopanib (800 mg orally daily) for 24 weeks, with an option to continue treatment if desired by the patient and treating physician., We aimed to assess the activity and safety of pazopanib in patients with von Hippel-Lindau disease., INTERPRETATION\nPazopanib was associated with encouraging preliminary activity in von Hippel-Lindau disease, with a side-effect profile consistent with that seen in previous trials., FINDINGS\nBetween Jan 18, 2012, and Aug 10, 2016, we screened 37 patients with genetically confirmed or clinical features consistent with von Hippel-Lindau disease, of whom 31 eligible patients were treated with pazopanib., Pazopanib therapy for cerebellar hemangioblastomas in von Hippel-Lindau disease: case report.von Hippel-Lindau (VHL) disease is a genetically acquired multisystem tumor syndrome of the viscera and central nervous system (CNS). , Recurrent multiple CNS hemangioblastomas with VHL disease treated with pazopanib: a case report and literature review.Hemangioblastoma is a rare benign neoplasm, accounting for less than 2% of all primitive brain tumors. , We aimed to assess the activity and safety of pazopanib in patients with von Hippel-Lindau disease.<br><b>METHODS</b>: In this non-randomised, single-centre, open-label, phase 2 trial, adult patients with clinical manifestations of von Hippel-Lindau disease were recruited from the University of Texas MD Anderson Cancer Center (Houston, TX, USA) and were treated with pazopanib (800 mg orally daily) for 24 weeks, with an option to continue treatment if desired by the patient and treating physician., This study is registered with ClinicalTrials.gov, number NCT01436227, and is closed to accrual.<br><b>FINDINGS</b>: Between Jan 18, 2012, and Aug 10, 2016, we screened 37 patients with genetically confirmed or clinical features consistent with von Hippel-Lindau disease, of whom 31 eligible patients were treated with pazopanib., Treatment-related serious adverse events included one case each of appendicitis and gastritis and one patient had a fatal CNS bleed.<br><b>INTERPRETATION</b>: Pazopanib was associated with encouraging preliminary activity in von Hippel-Lindau disease, with a side-effect profile consistent with that seen in previous trials., Pazopanib could be considered as a treatment choice for patients with von Hippel-Lindau disease and growing lesions, or to reduce the size of unresectable lesions in these patients., We aimed to assess the activity and safety of pazopanib in patients with von Hippel-Lindau disease., In this non-randomised, single-centre, open-label, phase 2 trial, adult patients with clinical manifestations of von Hippel-Lindau disease were recruited from the University of Texas MD Anderson Cancer Center (Houston, TX, USA) and were treated with pazopanib (800 mg orally daily) for 24 weeks, with an option to continue treatment if desired by the patient and treating physician., Pazopanib was associated with encouraging preliminary activity in von Hippel-Lindau disease, with a side-effect profile consistent with that seen in previous trials., Pazopanib could be considered as a treatment choice for patients with von Hippel-Lindau disease and growing lesions, or to reduce the size of unresectable lesions in these patients., Between Jan 18, 2012, and Aug 10, 2016, we screened 37 patients with genetically confirmed or clinical features consistent with von Hippel-Lindau disease, of whom 31 eligible patients were treated with pazopanib.[SEP]Relations: Cerebellar hemangioblastoma has relations: phenotype_phenotype with Hemangioblastoma, disease_phenotype_positive with von Hippel-Lindau disease, phenotype_phenotype with Hemangioblastoma, disease_phenotype_positive with von Hippel-Lindau disease.", "label": "yes"}
{"id": "converted_545", "sentence1": "Have hESC been tested for the treatment of age-related macular degeneration?", "sentence2": "Development of human embryonic stem cell therapies for age-related macular degeneration, In this review, we describe recent approaches to develop cell-based therapies for the treatment of AMD. Recent research has focused on replacing the retinal pigment epithelium (RPE), a monolayer of cells vital to photoreceptor cell health. We discuss the various methods used to differentiate and purify RPE from human embryonic stem cells (HESC), and describe the surgical approaches being used to transplant these cells in existing and forthcoming clinical trials., Age-related macular degeneration (AMD) is characterized by the loss or dysfunction of retinal pigment epithelium (RPE) and is the most common cause of vision loss among the elderly. Stem-cell-based strategies, using human embryonic stem cells (hESCs) or human-induced pluripotent stem cells (hiPSCs), may provide an abundant donor source for generating RPE cells in cell replacement therapies., This study contributes to our understanding of the utility of hESC/hiPSC-derived RPE in AMD therapy., Two important early potential hESC applications are the use of retinal pigment epithelium (RPE) for the treatment of age-related macular degeneration and Stargardt disease, an untreatable form of macular dystrophy that leads to early-onset blindness., Human embryonic stem cells (hESCs) are a promising source of retinal pigment epithelium (RPE) cells: cells that can be used for the treatment of common and incurable forms of blindness, such as age-related macular degeneration., A potential application of human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) is the generation of retinal pigmented epithelium (RPE) to treat age-related macular degeneration (AMD), a common but incurable retinal disease., Human embryonic stem cells (hESCs) are a promising source of retinal pigment epithelium (RPE) cells: cells that can be used for the treatment of common and incurable forms of blindness, such as age-related macular degeneration, A potential application of human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) is the generation of retinal pigmented epithelium (RPE) to treat age-related macular degeneration (AMD), a common but incurable retinal disease, Assessments of safety and efficacy are crucial before human ESC (hESC) therapies can move into the clinic. Two important early potential hESC applications are the use of retinal pigment epithelium (RPE) for the treatment of age-related macular degeneration and Stargardt disease, an untreatable form of macular dystrophy that leads to early-onset blindness., A potential application of human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) is the generation of retinal pigmented epithelium (RPE) to treat age-related macular degeneration (AMD), a common but incurable retinal disease. RPE cells derived from hESCs (hESC-RPEs) and iPSCs (iPSC-RPEs) express essential RPE markers and can rescue visual function in animal models., Two important early potential hESC applications are the use of retinal pigment epithelium (RPE) for the treatment of age-related macular degeneration and Stargardt disease, an untreatable form of macular dystrophy that leads to early-onset blindness. Here we show long-term functional rescue using hESC-derived RPE in both the RCS rat and Elov14 mouse, which are animal models of retinal degeneration and Stargardt, respectively.[SEP]Relations: Retinal degeneration has relations: disease_phenotype_positive with retinal degeneration, disease_phenotype_positive with retinal degeneration. retinal disease has relations: disease_disease with retinal degeneration, disease_disease with retinal degeneration.", "label": "yes"}
{"id": "converted_2755", "sentence1": "Is Baloxavir effective for influenza?", "sentence2": "Baloxavir marboxil (Xofluza™; baloxavir) is an oral cap-dependent endonuclease inhibitor that has been developed by Roche and Shionogi. The drug blocks influenza virus proliferation by inhibiting the initiation of mRNA synthesis. In February 2018, baloxavir received its first global approval in Japan for the treatment of influenza A or B virus infections. , This article summarized the milestones in the development of baloxavir leading to this first global approval for influenza A or B virus infections., Baloxavir acid (BXA), derived from the prodrug baloxavir marboxil (BXM), potently and selectively inhibits the cap-dependent endonuclease within the polymerase PA subunit of influenza A and B viruses., Characterization of influenza virus variants induced by treatment with the endonuclease inhibitor baloxavir marboxil., Baloxavir Marboxil for Uncomplicated Influenza in Adults and Adolescents., BACKGROUND: Baloxavir marboxil is a selective inhibitor of influenza cap-dependent endonuclease. It has shown therapeutic activity in preclinical models of influenza A and B virus infections, including strains resistant to current antiviral agents., CONCLUSIONS: Single-dose baloxavir was without evident safety concerns, was superior to placebo in alleviating influenza symptoms, and was superior to both oseltamivir and placebo in reducing the viral load 1 day after initiation of the trial regimen in patients with uncomplicated influenza., A single oral dose of baloxavir is usually well tolerated; it hastens alleviation of influenza symptoms and shortens the duration of viral shedding., Japan was the first country to approve baloxavir marboxil as a treatment for influenza., This article summarized the milestones in the development of baloxavir leading to this first global approval for influenza A or B virus infections.<br>, In February 2018, baloxavir received its first global approval in Japan for the treatment of influenza A or B virus infections.[SEP]", "label": "yes"}
{"id": "converted_2410", "sentence1": "Is overproduction of transthyretin is associated with amyloidosis associated neuropathy?", "sentence2": "Transthyretin-associated familial amyloid polyneuropathy (TTR-FAP) is a disease caused by the deposit of abnormal transthyretin on tissues, mainly nerves, transthyretin familial amyloid polyneuropathy, We report a new transthyretin (ATTR) gene c.272C>G mutation and variant protein, p.Leu32Val, in a kindred of Bolivian origin with a rapid progressive peripheral neuropathy and cardiomyopat, Hereditary transthyretin amyloidosis is an autosomal dominant inherited disorder, first described in families with sensorimotor and autonomic neuropathy., Abnormal deposition of aggregated wild-type (WT) human transthyretin (TTR) and its pathogenic variants is responsible for cardiomyopathy and neuropathy related to TTR amyloidosis. , Transthyretin (TTR), normally a plasma circulating protein, can become misfolded and aggregated, ultimately leading to extracellular deposition of amyloid fibrils usually targeted to heart or nerve tissues. Referred to as TTR-associated amyloidoses (ATTR), this group of diseases is frequently life threatening and fatal if untreated, Hereditary transthyretin amyloidosis is an autosomal dominant inherited disorder, first described in families with sensorimotor and autonomic neuropathy., Hereditary transthyretin amyloidosis (ATTR) is usually characterised by a progressive peripheral and autonomic neuropathy often with associated cardiac failure and is due to dominantly inherited transthyretin mutations causing accelerated amyloid deposition.[SEP]Relations: peripheral nervous system disease has relations: disease_disease with peripheral neuropathy, disease_disease with peripheral neuropathy. amyloid fibril formation has relations: bioprocess_protein with TTR, bioprocess_protein with TTR. extracellular space has relations: cellcomp_protein with TTR, cellcomp_protein with TTR. autonomic neuropathy has relations: disease_disease with peripheral neuropathy, disease_disease with peripheral neuropathy.", "label": "yes"}
{"id": "converted_4390", "sentence1": "Can IFNg induce the expression of IDO?", "sentence2": "IFNG inducible IDO/GTPCH inflammation cascade, IFNG-induced up-regulation of indoleamine 2,3-dioxygenase (IDO), IFN-γ-induced indoleamine-2,3-dioxgenase (IDO) , strong and positive correlation between IDO1 and IFNG mRNA expression levels ,  The tryptophan-degrading activity of IDO1 was not induced significantly by Chlamydia infection alone, but the addition of IFNG greatly increased its activity. [SEP]Relations: indoleamine 2,3-dioxygenase activity has relations: molfunc_protein with IDO1, molfunc_protein with IDO1, molfunc_protein with IDO1, molfunc_protein with IDO1.", "label": "yes"}
{"id": "converted_4586", "sentence1": "Is Mediator present at super enhancers?", "sentence2": "BRD4 and Mediator were found to co-occupy thousands of enhancers associated with active genes., Master transcription factors and mediator establish super-enhancers at key cell identity genes, Master transcription factors Oct4, Sox2, and Nanog bind enhancer elements and recruit Mediator to activate much of the gene expression program of pluripotent embryonic stem cells (ESCs)., These domains, which we call super-enhancers, consist of clusters of enhancers that are densely occupied by the master regulators and Mediator, BRD4 maintains transcription of core stem cell genes such as OCT4 and PRDM14 by occupying their super-enhancers (SEs), large clusters of regulatory elements, and recruiting to them Mediator and CDK9, the catalytic subunit of the positive transcription elongation factor b (P-TEFb), to allow Pol-II-dependent productive elongation., The term 'super-enhancer' has been used to describe groups of putative enhancers in close genomic proximity with unusually high levels of Mediator binding, as measured by chromatin immunoprecipitation and sequencing (ChIP-seq)., Mediator kinase inhibition further activates super-enhancer-associated genes in AML., Furthermore, the binding of SIM2 marks a particular sub-category of enhancers known as super-enhancers. These regions are characterized by typical DNA modifications and Mediator co-occupancy (MED1 and MED12). , Many genes determining cell identity are regulated by clusters of Mediator-bound enhancer elements collectively referred to as super-enhancers. , A number of studies have recently demonstrated that super-enhancers, which are large cluster of enhancers typically marked by a high level of acetylation of histone H3 lysine 27 and mediator bindings, are frequently associated with genes that control and define cell identity during normal development. , Super-enhancers are characterized by high levels of Mediator binding and are major contributors to the expression of their associated genes. [SEP]Relations: NANOG has relations: protein_protein with MED12, protein_protein with MED12.", "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_1270", "sentence1": "Can administration of the thyrotropin releasing hormone reduce fatigue in cancer patients?", "sentence2": "TRH administration was associated with significant improvement (p < 0.05) in fatigue levels as measured by the Visual Analog Scale-Energy (VAS-E), was associated with significant (p < 0.05) improvement in sleep disturbances and improved quality of life. , This decrease in CRP level with TRH administration was associated with improvement in energy levels as measured by the VAS-E. , In the present pilot, randomized, placebo-controlled, crossover study, we investigated the efficacy and safety of TRH as a treatment for CF., TRH administration was associated with significant improvement in fatigue level as measured by the VAS-E, the fatigue and vigor subscales of the POMS, and the fatigue subscale of FACIT-F (p < 0.05). , TRH administration was efficacious, safe, and tolerable in the treatment of CF with a positive impact on quality of life. These results provide a crucial impetus for pursuing TRH therapeutics to treat CF., Thyrotropin-releasing hormone can relieve cancer-related fatigue: hypothesis and preliminary observations., Global assessment using both subjective and objective parameters showed that TRH exerted clear anti-fatigue effects in four of the six TRH treatments. , These initial findings support the proposal that TRH can ameliorate cancer-related fatigue.[SEP]", "label": "yes"}
{"id": "converted_3761", "sentence1": "Do nematodes contain architectural proteins like CTCF?", "sentence2": "A mode of genetic regulation that involves insulators and insulator binding proteins to establish independent transcriptional units is currently not known in nematodes including Caenorhabditis elegans. , the insulator protein CTCF has been secondarily lost in derived nematodes like C. elegans., he most highly enriched motif (LM1) corresponds to the X-box motif known from yeast and nematode, uggest that the insulator protein CTCF has been secondarily lost in derived nematodes like C. elegans. We , of CTCF from several nematodes is paralleled by a loss of two of its interactors, the polycomb repressive complex subunit SuZ12 and the multifunctional transcription factor TYY1. In contrast to earlier st, SULTS: While orthologs for other insulator proteins were absent in all 35 analysed nematode species, we find orthologs of CTCF in a subset of nematodes. A, Loss of the insulator protein CTCF during nematode evolution, que secondary loss of CTCF from several nematodes is paralleled by a loss of two of its interactors, the polycomb repressive complex subunit SuZ12 and the multifunctional transcription factor TYY1. In con, level. A mode of genetic regulation that involves insulators and insulator binding proteins to establish independent transcriptional units is currently not known in nematodes including Caenorhabditis ,  suggest that the insulator protein CTCF has been secondarily lost in derived nematodes like C. elegans. W, Loss of the insulator protein CTCF during nematode evolution.[SEP]", "label": "no"}
{"id": "converted_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_1427", "sentence1": "Can cffDNA be used for non-invasive testing?", "sentence2": "Non-invasive prenatal testing using cell-free fetal DNA in maternal circulation, The identification of cell-free fetal DNA (cffDNA) in maternal circulation has made non-invasive prenatal testing (NIPT) possible., In recent years, technical advances in the molecular analysis of fetal DNA (e.g., digital PCR and massively parallel sequencing (MPS)) has enabled the successful implementation of noninvasive testing into clinical practice, such as fetal sex assessment, RhD genotyping, and fetal chromosomal aneuploidy detection.With the ability to decipher the entire fetal genome from maternal plasma DNA, we foresee that an increased number of non-invasive prenatal tests will be available for detecting many single-gene disorders in the near future. This review briefly summarizes the technical aspects of the NIPT and application of NIPT in clinical practice., First identified in 1997, cell-free fetal DNA (cffDNA) has just recently been used to detect fetal aneuploidy of chromosomes 13, 18, and 21, showing its potential to revolutionize prenatal genetic testing as a non-invasive screening tool, To determine how adults in the United States view non-invasive prenatal testing using cell-free fetal DNA (cffDNA testing) in order to help estimate uptake, Non-invasive prenatal testing of cell-free fetal DNA (cffDNA) in maternal plasma can predict the fetal RhD type in D negative pregnant women, The identification of cell-free fetal DNA (cffDNA) in maternal circulation has made non-invasive prenatal testing (NIPT) possible, The effectiveness and clinical utility of non-invasive prenatal diagnosis (NIPD) for fetal sex determination using cell-free fetal DNA (cffDNA) was assessed by undertaking a prospective national audit of UK testing, The recent release of new, non-invasive prenatal tests for fetal aneuploidy using cell-free fetal DNA (cffDNA) has been hailed as a revolution in prenatal testing and has triggered significant commercial interest in the field, Non-invasive prenatal aneuploidy testing that utilizes cell-free fetal DNA (cffDNA) circulating in maternal blood is one example of an innovative technology that promises significant benefits for its intended end users; however, it is currently uncertain whether it will achieve widespread clinical implementation, Analysis of cell free fetal (cff) DNA in maternal plasma is used routinely for non invasive prenatal diagnosis (NIPD) of fetal sex determination, fetal rhesus D status and some single gene disorders, Non-invasive prenatal diagnosis (NIPD) using cell-free fetal DNA (cffDNA) in maternal plasma is an alternative to invasive prenatal diagnosis (IPD), which carries a 1% risk of miscarriage. , The recent release of new, non-invasive prenatal tests for fetal aneuploidy using cell-free fetal DNA (cffDNA) has been hailed as a revolution in prenatal testing and has triggered significant commercial interest in the field. , The effectiveness and clinical utility of non-invasive prenatal diagnosis (NIPD) for fetal sex determination using cell-free fetal DNA (cffDNA) was assessed by undertaking a prospective national audit of UK testing. , NIFTY (Non-invasive Fetal Trisomy Test) is a non-invasive prenatal test which is used for diagnosing fetal trisomy. The test is based on the analysis of cell free fetal DNA (cffDNA) present in the plasma and serum of a pregnant woman., Using non-invasive method of cffDNAs in the shortest time possible, as well as avoiding invasive tests for early determination of fetal gender, provides the opportunity of deciding and employing early treatment for fetuses at risk of genetic diseases., The identification of cell-free fetal DNA (cffDNA) in maternal circulation has made non-invasive prenatal testing (NIPT) possible., To determine how adults in the United States view non-invasive prenatal testing using cell-free fetal DNA (cffDNA testing) in order to help estimate uptake., Nowadays, new advances in the use of cell free fetal DNA (cffDNA) in maternal plasma of pregnant women has provided the possibility of applying cffDNA in prenatal diagnosis as a non-invasive method., Non-invasive prenatal testing of cell-free fetal DNA (cffDNA) in maternal plasma can predict the fetal RhD type in D negative pregnant women., Prevention of contamination following our anti-contamination criteria is a good practice for certain non-invasive sex determination, using cffDNA.[SEP]", "label": "yes"}
{"id": "converted_540", "sentence1": "Is Calcium homeostasis important in cardiac physiology and pathophysiology?", "sentence2": "Maintenance of cellular calcium homeostasis is critical to regulating mitochondrial ATP production and cardiac contraction. , the Ca(2+) signal regulates the most important activities of the cell, from the expression of genes, to heart and muscle contraction and other motility processes, to diverse metabolic pathways involved in the generation of cell fuels, Pharmacologic modification of cellular calcium handling recently moved into focus as an alternative for prevention and treatment of ventricular tachyarrhythmias, diabetic rats displayed abnormal cardiac structure and systolic and diastolic dysfunction, and spermine (CaSR agonist) could prevent or slow its progression. These results indicate that the CaSR expression of myocardium is reduced in the progress of DCM, and its potential mechanism is related to the impaired intracellular calcium homeostasis., calcium-sensing receptor (CaSR), Na(+)/Ca(2+) exchanger (NCX) plays important roles in cardiac electrical activity and calcium homeostasis., NCX current (I(NCX)) shows transmural gradient across left ventricle in many species. Previous studies demonstrated that NCX expression was increased and transmural gradient of I(NCX) was disrupted in failing heart, calcium homeostasis, the key process underlying excitation-contraction coupling, The results indicate the calcium handling properties of hiPSC-derived cardiomyocytes are relatively immature to hESC counterparts, Our understanding of the molecular processes which regulate cardiac function has grown immeasurably in recent years. Even with the advent of β-blockers, angiotensin inhibitors and calcium modulating agents, heart failure (HF) still remains a seriously debilitating and life-threatening condition. Here, we review the molecular changes which occur in the heart in response to increased load and the pathways which control cardiac hypertrophy, calcium homeostasis, and immune activation during HF., Calcium-sensing receptors (CaSRs) are G-protein coupled receptors which maintain systemic calcium homeostasis and participate in hormone secretion, activation of ion channels, cell apoptosis, proliferation, and differentiation., CaSRs are associated with I/R injury and apoptosis in neonatal rat ventricular cardiomyocytes via suppressing Bcl-2 and promoting caspase-3 expression., Important insights into the molecular basis of hypertrophic cardiomyopathy and related diseases have been gained by studying families with inherited cardiac hypertrophy. Integrated clinical and genetic investigations have demonstrated that different genetic defects can give rise to the common phenotype of cardiac hypertrophy. Diverse pathways have been identified, implicating perturbations in force generation, force transmission, intracellular calcium homeostasis, myocardial energetics, and cardiac metabolism in causing disease, HAX-1 as a regulator of contractility and calcium cycling in the heart. HAX-1 overexpression reduced sarcoplasmic reticulum Ca-ATPase (SERCA2) pump activity in isolated cardiomyocytes and in vivo, leading to depressed myocyte calcium kinetics and mechanics., Thus, HAX-1 represents a regulatory mechanism in cardiac calcium cycling and its responses to sympathetic stimulation, implicating its importance in calcium homeostasis and cell survival., Calcium ions are the most ubiquitous and versatile signaling molecules in eukaryotic cells. Calcium homeostasis and signaling systems are crucial for both the normal growth of the budding yeast Saccharomyces cerevisiae and the intricate working of the mammalian heart., this knowledge can be used to help treat relevant human diseases such as pathological cardiac hypertrophy and heart failure, With aging, the heart develops myocyte hypertrophy associated with impaired relaxation indices. To define the cellular basis of this adaptation, we examined the physiological changes that arise in calcium handling in the aging heart and contrasted the adaptations that occur following the imposition of a stimulus that alters calcium homeostasis in a young and an old heart, alterations in the calcium-handling machinery of the cardiocyte differ in the context of age and as such may predispose the older heart to the development of a hypertrophic phenotype., The cardiac sodium-calcium exchanger (NCX1) is a key sarcolemmal protein for the maintenance of calcium homeostasis in the heart. , Thus exchanger overexpression in mice leads to abnormal calcium handling and a decompensatory transition to heart failure with stress, Central to controlling intracellular calcium concentration ([Ca(2+)](i)) are a number of Ca(2+) transporters and channels with the L-type Ca(2+) channel, Na(+)-Ca(2+) exchanger and sarcoplasmic reticulum Ca(2+)-ATPase (SERCA) being of particular note in the heart. This review concentrates on the regulation of [Ca(2+)](i) in cardiac muscle and the homeostatic mechanisms employed to ensure that the heart can operate under steady-state conditions on a beat by beat basis., the tight regulation of SR Ca(2+) content is also required to prevent the abnormal, spontaneous or diastolic release of Ca(2+) from the SR. Such diastolic events are a major factor contributing to the genesis of cardiac arrhythmias in disease situations and in recently identified familial mutations in the SR Ca(2+) release channel (ryanodine receptor, RyR)., Calcium channels have a unique functional role, because not only do they participate in this activity, they form the means by which electrical signals are converted to responses within the cell. Calcium channels play an integral role in excitation in the heart and shaping the cardiac action potential. In addition, calcium influx through calcium channels is responsible for initiating contraction. Abnormalities in calcium homeostasis underlie cardiac arrhythmia, contractile dysfunction and cardiac remodelling. , Cardiac calcium (Ca(2+)) handling subsumes the mechanisms maintaining the myocardial Ca(2+) homeostasis that contribute essentially to cardiac performance., Calcium is an important mediator in cardiac excitation and disorders in cardiac Ca(2+) homeostasis have great influence on the cardiac action potential., We review the physiology of the cardiac calcium homeostasis, including the cardiac excitation contraction coupling and myocyte calcium cycling., We review the physiology of the cardiac calcium homeostasis, including the cardiac excitation contraction coupling and myocyte calcium cycling, Calcium is an important mediator in cardiac excitation and disorders in cardiac Ca(2+) homeostasis have great influence on the cardiac action potential, The role of calcium in cardiac and vascular smooth muscle physiology was reviewed, highlighting the major mechanisms responsible for maintaining calcium homeostasis in these cells, Energy metabolism and Ca(2+) handling serve critical roles in cardiac physiology and pathophysiology[SEP]Relations: Congestive heart failure has relations: disease_phenotype_positive with hypertrophic cardiomyopathy, disease_phenotype_positive with hypertrophic cardiomyopathy. Arrhythmia has relations: disease_phenotype_positive with hypertrophic cardiomyopathy, disease_phenotype_positive with hypertrophic cardiomyopathy. Hypertrophic cardiomyopathy has relations: disease_phenotype_positive with hypertrophic cardiomyopathy, disease_phenotype_positive with hypertrophic cardiomyopathy.", "label": "yes"}
{"id": "converted_1596", "sentence1": "Have thyronamines effects on fat tissue?", "sentence2": "Intraperitoneal or central injection of 3-T(1)AM or T(0)AM into mice, rats, or Djungarian hamsters caused various prompt effects, such as metabolic depression, hypothermia, negative chronotropy, negative inotropy, hyperglycemia, reduction of the respiratory quotient, ketonuria, and reduction of fat mass. [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_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_1913", "sentence1": "Is avanafil indicated for treatment of erectile dysfunction?", "sentence2": "CONTEXT: Avanafil (AVA) is used in the treatment of erectile dysfunction, but is reported for its poor aqueous solubility. , BACKGROUND: Phosphodiesterase 5 inhibitors (PDE5-Is) sildenafil, vardenafil, tadalafil and the recently approved avanafil represent the first-line choice for both on-demand and chronic treatment of erectile dysfunction (ED). , A survey on the experience of 136 Italian urologists in the treatment of erectile dysfunction with PDE5 inhibitors and recommendations for the use of Avanafil in the clinical practice., Efficacy of Avanafil 15 Minutes after Dosing in Men with Erectile Dysfunction: A Randomized, Double-Blind, Placebo Controlled Study., PURPOSE: We examined the therapeutic effects of avanafil 15 minutes after dosing in men with mild to severe erectile dysfunction., Sildenafil, vardenafil, tadalafil and avanafil are FDA approved drugs in market as PDE5 inhibitors for treating erectile dysfunction., CONCLUSION: Avanafil along with the other PDE5Is has shown to be a safe and effective oral treatment for ED, with avanafil's possible place in therapy for patients who want an on-demand option or as an alternative in patients who experience visual disturbances with the other agents., Avanafil (STENDRA™, SPEDRA™, Zepeeed™) is an oral phosphodiesterase type 5 inhibitor indicated for the treatment of erectile dysfunction., In a 12-week, randomized, double-blind, placebo-controlled, multicentre trial in patients with erectile dysfunction, avanafil 50, 100 and 200 mg recipients had significantly greater improvements from baseline than placebo recipients in mean international index of erectile dysfunction-erectile function domain scores and in successful vaginal penetration and sexual intercourse attempts (coprimary endpoints)., Avanafil for the treatment of erectile dysfunction. An updated review., Selectivity of avanafil, a PDE5 inhibitor for the treatment of erectile dysfunction: implications for clinical safety and improved tolerability., A randomized, double-blind, placebo-controlled evaluation of the safety and efficacy of avanafil in subjects with erectile dysfunction., Avanafil, a potent and highly selective phosphodiesterase-5 inhibitor for erectile dysfunction., Avanafil, a highly selective phosphodiesterase type 5 inhibitor for erectile dysfunction, shows good safety profiles for retinal function and hemodynamics in anesthetized dogs., Cumulative data suggest that avanafil has a promising pharmacological profile for erectile dysfunction., These findings suggest that intracavernosal administration of avanafil might be beneficial for the treatment of erectile dysfunction in patients with T2DM., An open-label, long-term evaluation of the safety, efficacy and tolerability of avanafil in male patients with mild to severe erectile dysfunction., The effect of intracavernosal avanafil, a newer phosphodiesterase-5 inhibitor, on neonatal type 2 diabetic rats with erectile dysfunction., A phase 3, placebo controlled study of the safety and efficacy of avanafil for the treatment of erectile dysfunction after nerve sparing radical prostatectomy., Avanafil is a potent selective phosphodiesterase type 5 (PDE5) inhibitor newly developed for treating erectile dysfunction (ED)., Adverse events most commonly reported with avanafil treatment were headache, nasopharyngitis, flushing, and sinus congestion.Avanafil was safe and effective for treating erectile dysfunction in men with diabetes and was effective as early as 15 minutes and more than 6 hours after dosing, Avanafil (STENDRA™, SPEDRA™, Zepeeed™) is an oral phosphodiesterase type 5 inhibitor indicated for the treatment of erectile dysfunction, Avanafil is rapidly absorbed after oral administration, with a median time to maximum plasma concentration of 30 to 45 min. In a 12-week, randomized, double-blind, placebo-controlled, multicentre trial in patients with erectile dysfunction, avanafil 50, 100 and 200 mg recipients had significantly greater improvements from baseline than placebo recipients in mean international index of erectile dysfunction-erectile function domain scores and in successful vaginal penetration and sexual intercourse attempts (coprimary endpoints), A phase II, single-blind, randomized, crossover evaluation of the safety and efficacy of avanafil using visual sexual stimulation in patients with mild to moderate erectile dysfunction, To evaluate the safety, efficacy and time course of three doses of avanafil (50 mg, 100 mg and 200 mg) compared with sildenafil 50 mg or placebo, given in conjunction with visual sexual stimulation (VSS) videos in men with mild to moderate erectile dysfunction (ED).Male patients, 35-70 years of age, with mild to moderate ED of ≥6 months duration, were included in the study, Avanafil for erectile dysfunction, To review the pharmacology, pharmacokinetics, safety, and efficacy of avanafil and evaluate relevant clinical trial data.A MEDLINE, International Pharmaceutical Abstracts, ClinicalTrials.gov, and Google Scholar searches (1966 to July 2013) were conducted using the key words: avanafil, erectile dysfunction, and phosphodiesterase type 5 (PDE5) inhibitor.Articles evaluating avanafil for erectile dysfunction (ED) published in English and using human subjects were selected, In trials in patients with erectile dysfunction in association with diabetes mellitus, and after nerve-sparing radical prostatectomy, avanafil 100 or 200 mg was significantly more efficacious than placebo for primary and most secondary endpoints, However, the potentiating effect of avanafil at 1 mg/kg was significantly weaker than that of sildenafil (p &lt;0.05).Data suggest that avanafil has a favorable safety profile for erectile dysfunction, which is attributable to its high inhibitory selectivity for phosphodiesterase type 5 against type 6 (retina) and 1 (vessels, etc), respectively, and its short acting pharmacodynamic property.<CopyrightInformation>Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.</, Avanafil for the treatment of erectile dysfunction: a multicenter, randomized, double-blind study in men with diabetes mellitus., The discovery of avanafil for the treatment of erectile dysfunction: a novel pyrimidine-5-carboxamide derivative as a potent and highly selective phosphodiesterase 5 inhibitor., Efficacy and safety of avanafil for treating erectile dysfunction: results of a multicentre, randomized, double-blind, placebo-controlled trial., Phosphodiesterase 5 inhibitors (PDE5-Is) sildenafil, vardenafil, tadalafil and the recently approved avanafil represent the first-line choice for both on-demand and chronic treatment of erectile dysfunction (ED)., The phosphodiesterese-5 (PDE5) inhibitors, including sildenafil (Viagra™), vardenafil (Levitra™), tadalafil (Cialis™) and avanafil (Stendra™) have been developed for the treatment of erectile dysfunction., To compare the efficacy and safety between different dosages of avanafil for the treatment of erectile dysfunction (ED).PubMed, Cochrane Library, and Embase were searched to identify randomized controlled trials which compared avanafil with placebo, or compared different dosages of avanafil for ED., We evaluated the safety and efficacy of 100 and 200 mg avanafil for the treatment of adult males with erectile dysfunction after bilateral nerve sparing radical prostatectomy.This was a double-blind, placebo controlled, parallel group, phase 3 study in males age 18 to 70 years with a history of erectile dysfunction of 6 months or more after bilateral nerve sparing radical prostatectomy., To determine the effect of avanafil, a novel phosphodiesterase-5 inhibitor, on the treatment of erectile dysfunction associated with type 2 diabetes mellitus (T2DM).In 2-day-old rats, T2DM was induced by single intraperitoneal injection of 90 mg/kg of streptozotocin (STZ; i.p.)., These findings suggest that intracavernosal administration of avanafil might be beneficial for the treatment of erectile dysfunction in patients with T2DM.<CopyrightInformation>Copyright © 2014 Elsevier Inc. All rights reserved.</C, Avanafil, a potent new selective phosphodiesterase type 5 (PDE5) inhibitor, has been developed for the treatment of erectile dysfunction (ED)., Adverse events most commonly reported with avanafil treatment were headache, nasopharyngitis, flushing, and sinus congestion.Avanafil was safe and effective for treating erectile dysfunction in men with diabetes and was effective as early as 15 minutes and more than 6 hours after dosing., Coprimary end points assessed changes in the percentage of sexual attempts in which men were able to maintain an erection of sufficient duration to have successful intercourse (Sexual Encounter Profile [SEP] 3), percentage of sexual attempts in which men were able to insert the penis into the partner's vagina (SEP 2), and International Index of Erectile Function erectile function domain score.RESULTS: Compared with placebo, least-squares mean change from baseline to study end in SEP 3, SEP 2, and International Index of Erectile Function erectile function domain score were significantly improved with both avanafil, 100 mg (P?.002), and avanafil, 200 mg (P<.001)., Adverse events most commonly reported with avanafil treatment were headache, nasopharyngitis, flushing, and sinus congestion.CONCLUSION: Avanafil was safe and effective for treating erectile dysfunction in men with diabetes and was effective as early as 15 minutes and more than 6 hours after dosing., Avanafil for the treatment of erectile dysfunction. An updated review., Avanafil for erectile dysfunction., Avanafil for the treatment of erectile dysfunction: a multicenter, randomized, double-blind study in men with diabetes mellitus., To compare the efficacy and safety between different dosages of avanafil for the treatment of erectile dysfunction (ED)., Selectivity of avanafil, a PDE5 inhibitor for the treatment of erectile dysfunction: implications for clinical safety and improved tolerability., A phase 3, placebo controlled study of the safety and efficacy of avanafil for the treatment of erectile dysfunction after nerve sparing radical prostatectomy., We evaluated the safety and efficacy of 100 and 200 mg avanafil for the treatment of adult males with erectile dysfunction after bilateral nerve sparing radical prostatectomy.[SEP]Relations: diabetes mellitus, noninsulin-dependent has relations: disease_disease with type 2 diabetes mellitus, disease_disease with type 2 diabetes mellitus. Tadalafil has relations: drug_drug with Sildenafil, drug_drug with Sildenafil. Avanafil has relations: drug_drug with Sildenafil, drug_drug with Sildenafil. Headache has relations: drug_effect with Sildenafil, drug_effect with Sildenafil. Vardenafil has relations: drug_drug with Sildenafil, drug_drug with Sildenafil.", "label": "yes"}
{"id": "converted_402", "sentence1": "Is paroxetine effective for treatment of premenstrual dysphoric disorder?", "sentence2": "To evaluate the cost effectiveness of the four medications with a US FDA-approved indication for PMDD: fluoxetine, sertraline, paroxetine and drospirenone plus ethinyl estradiol (DRSP/EE)., All SSRIs (fluoxetine, paroxetine, sertraline, fluvoxamine, citalopram, and clomipramine) were effective in reducing premenstrual symptoms., Paroxetine has been approved for the treatment of major depressive disorder (MDD), obsessive-compulsive disorder, panic disorder (PD), generalised anxiety disorder, post traumatic stress disorder (PTSD), and social anxiety disorder (SAD) in adults, whereas paroxetine CR is approved for the treatment of MDD, SAD, PD and premenstrual dysphoric disorder in adults., Selective serotonin-reuptake inhibitors (SSRIs) have been proven safe and effective for the treatment of PMDD and are recommended as first-line agents when pharmacotherapy is warranted. Currently fluoxetine, controlled-release paroxetine, and sertraline are the only Food and Drug Administration-approved agents for this indication., When compared with placebo, patients treated with paroxetine 20 mg attained a significant reduction in irritability (difference in median percent change: -23.9, 95% CI = -51.3 to -6.2, p = .014; difference in mean absolute change: -18.6, 95% CI = -32.5 to -4.6, p = .007). A statistically significant difference was not observed when the patients treated with the lower dose of paroxetine (10 mg) were compared with placebo. Treatment was well tolerated with no unexpected side effects., Intermittent administration of paroxetine 20 mg significantly reduced irritability symptoms in patients with PMDD., All these women had significant improvements in the HAMA, HAMD, CGI, and PRISM calendar. The rate of response to paroxetine treatment lay between 50% and 78.6% in the continuous-treatment group, and 37.5-93.8% in the intermittent-treatment group, as determined at the study end-point., The present results indicate that paroxetine is effective in both continuous and intermittent treatment of oriental PMDD women, and that the effects of active treatment lasted for six consecutive treatment menstrual cycles., Paroxetine CR is approved for the treatment of major depression, social anxiety disorder, panic disorder and premenstrual dysphoric disorder in adults., Continuous treatment with paroxetine reduced premenstrual symptoms effectively with a response rate of 85%., Intermittent treatment was as effective as continuous treatment in reducing irritability, affect lability, and mood swings, but had a somewhat weaker effect on depressed mood and somatic symptoms., Daily Record of Severity of Problems scores were lower in the paroxetine group compared with the placebo group, although the differences were not statistically significant., However, the mean on-treatment Inventory of Depressive Symptomatology (clinician-rated) score for the paroxetine group was 17.9 +/- 8.3 compared with 31.5 +/- 11.2 in the placebo group (adjusted mean difference = 13.6, P = 0.009)., Response (Clinical Global Impressions Scale score of 1 or 2) occurred in 70% of subjects randomized to paroxetine CR and 10% of those assigned to placebo (chi2(1) = 7.5, P = 0.006)., The US Food and Drug Administration and Health Canada recently approved paroxetine for the treatment of premenstrual dysphoric disorder., Patients treated with either dose of paroxetine CR demonstrated significantly greater improvements on the primary efficacy measure (change from baseline in mean luteal phase VAS-Mood scores) and on the majority of secondary efficacy measures compared with patients randomly assigned to placebo., For the treatment of PMDD, luteal phase dosing with 12.5 mg and 25 mg of paroxetine CR is effective and generally well tolerated., A statistically significant difference was observed in favor of paroxetine CR 25 mg versus placebo on the VAS-Mood (adjusted mean difference = -12.58 mm, 95% CI = -18.40 to -6.76; p < .001) and for paroxetine CR 12.5 mg versus placebo (adjusted mean difference = -7.51 mm, 95% CI = -13.40 to -1.62; p = .013)., Paroxetine CR doses of 12.5 mg/day and 25 mg/day are effective in treating PMDD and are well tolerated., At end point, subjects treated with paroxetine CR (12.5 mg and 25 mg) demonstrated significant improvement in VAS-Mood scores compared with those who received placebo (paroxetine CR 12.5 mg mean treatment difference vs. placebo, -8.7 mm; 95% CI, -15.7, -1.7; p =.015; paroxetine CR 25 mg mean treatment difference vs. placebo, -12.1 mm; 95% CI, -18.9, -5.3; p <.001)., Both doses of paroxetine CR 12.5 mg and 25 mg daily are effective and well tolerated in patients who suffer from PMDD., Of these agents, sertraline, fluoxetine and paroxetine (as an extended-release formulation) are approved by the US FDA for luteal phase, as well as continuous, administration., In well designed placebo-controlled trials in patients with major depressive disorder (including a study in the elderly), social anxiety disorder or premenstrual dysphoric disorder (PMDD), paroxetine CR was consistently superior to placebo with regards to primary endpoints (i.e. mean Hamilton Rating Scale for Depression total score [major depressive disorder], Liebowitz social anxiety scale total score and Clinical Global Impressions-Global Improvement score [social anxiety disorder] and Visual Analogue Scale-Mood score [PMDD])., Paroxetine is a potent selective serotonin reuptake inhibitor (SSRI) with indications for the treatment of depression, obsessive- compulsive disorder, panic disorder and social phobia. It is also used in the treatment of generalized anxiety disorder, post-traumatic stress disorder, premenstrual dysphoric disorder and chronic headache., Studies having compared the efficiency of antidepressants according to their serotonin activity (paroxetine or sertraline versus maprotiline, that is a selective noradrenaline re-uptake inhibitor), showed that serotonin re-uptake inhibitors were significantly more efficient on all symptoms than maprotiline, that was not more efficient than placebo., Paroxetine is a potent and selective serotonin reuptake inhibitor (SSRI) with currently approved indications for the treatment of depression, obsessive-compulsive disorder, panic disorder and social phobia. It is also used in the treatment of generalized anxiety disorder, post traumatic stress disorder, premenstrual dysphoric disorder and chronic headache., Preliminary data suggest that paroxetine has potential in the treatment of social phobia, premenstrual dysphoric disorder and chronic headache., The effects of active treatment were marked by the first active cycle with luteal phase 17-item Hamilton Rating Scale for Depression scores decreasing from 14.9 (+/- 5.3) to 8.2 (+/- 4.9) in the first, 7.8 (+/- 5.1) in the second, and 7.8 (+/- 6.8) in the third active treatment cycles (F[1,13] = 17.6; p < 0.0001)., The most conservative measure, the Clinical Global Impression (CGI), revealed that 7 of 14 patients had a complete response (CGI = 1 or 2) whereas 4 patients had a partial response (CGI = 3)., These open trial findings are consistent with the notion that paroxetine is effective in the acute phase for the treatment of PDD., The rating of premenstrual irritability, depressed mood, increase in appetite, and anxiety/tension was markedly lower during treatment with paroxetine than before, and this reduction in symptomatology appeared unabated for the entire treatment period.[SEP]Relations: Maprotiline has relations: drug_drug with Paroxetine, drug_drug with Paroxetine. Drospirenone has relations: drug_drug with Paroxetine, drug_drug with Paroxetine. Fluvoxamine has relations: drug_drug with Paroxetine, drug_drug with Paroxetine. Ethinylestradiol has relations: drug_drug with Paroxetine, drug_drug with Paroxetine. Sertraline has relations: drug_drug with Paroxetine, drug_drug with Paroxetine. Serotonin has relations: drug_drug with Paroxetine, drug_drug with Paroxetine. Citalopram has relations: drug_drug with Paroxetine, drug_drug with Paroxetine. Norepinephrine has relations: drug_drug with Paroxetine, drug_drug with Paroxetine. Fluoxetine has relations: drug_drug with Paroxetine, drug_drug with Paroxetine. Clomipramine has relations: drug_drug with Paroxetine, drug_drug with Paroxetine. major affective disorder has relations: contraindication with Paroxetine, contraindication with Paroxetine.", "label": "yes"}
{"id": "converted_1848", "sentence1": "Is rucaparib used for ovarian cancer treatment?", "sentence2": "While olaparib is the first PARP inhibitor to receive approval for ovarian cancer treatment, others including rucaparib and niraparib are clearly effective in this disease and, within the next year or two, the results of ongoing randomised trials will clarify their respective roles. , Similar trials with other PARP inhibitors (rucaparib, niraparib and veliparib) are in progress and include non-BRCA-mutated ovarian cancer. , IMPLICATIONS FOR PRACTICE: The poly(ADP-ribose) polymerase (PARP) inhibitor olaparib has recently received approval from the Food and Drug Administration (FDA) and European Medicines Agency (EMA), with a second agent (rucaparib) likely to be approved in the near future., Ovarian Cancers Harbour Defects in Non-Homologous End Joining Resulting in Resistance to Rucaparib., There are a number of other PARP inhibitors in late phase clinical development in ovarian cancer including rucaparib, niraparib, veliparib, and talazoparib. , Rucaparib in relapsed, platinum-sensitive high-grade ovarian carcinoma (ARIEL2 Part 1): an international, multicentre, open-label, phase 2 trial., INTERPRETATION: In patients with BRCA mutant or BRCA wild-type and LOH high platinum-sensitive ovarian carcinomas treated with rucaparib, progression-free survival was longer than in patients with BRCA wild-type LOH low carcinomas. Our results suggest that assessment of tumour LOH can be used to identify patients with BRCA wild-type platinum-sensitive ovarian cancers who might benefit from rucaparib. , Genomic LOH May Predict Rucaparib Response in Ovarian Cancer., High LOH is associated with response to the PARP inhibitor rucaparib in BRCA wild-type ovarian cancer., Therapeutic potential of the poly(ADP-ribose) polymerase inhibitor rucaparib for the treatment of sporadic human ovarian cancer., While olaparib is the first PARP inhibitor to receive approval for ovarian cancer treatment, others including rucaparib and niraparib are clearly effective in this disease and, within the next year or two, the results of ongoing randomised trials will clarify their respective roles., These results support further clinical evaluation of rucaparib either as a single agent or as an adjunct to chemotherapy for the treatment of sporadic ovarian cancer., Here, we investigate the potential role of the PARP inhibitor rucaparib (CO-338, formerly known as AG014699 and PF-01367338) for the treatment of sporadic ovarian cancer., Rucaparib received US FDA Breakthrough Therapy designation for treatment of platinum-sensitive BRCA-mutated advanced ovarian cancer patients who received greater than two lines of platinum-based therapy., These results support further clinical evaluation of rucaparib either as a single agent or as an adjunct to chemotherapy for the treatment of sporadic ovarian cancer., Ongoing clinical trials are assessing the efficacy of rucaparib alone or in combination with other cytotoxic drugs, mainly in breast and ovarian cancer patients with mutations in the breast cancer associated (BRCA) genes.PURPOSE: We aimed to establish whether the multidrug efflux transporters ABCG2 (BCRP) and ABCB1 (P-gp, MDR1) affect the oral availability and brain penetration of rucaparib in mice.RESULTS: In vitro, rucaparib was efficiently transported by both human ABCB1 and ABCG2, and very efficiently by mouse Abcg2., Therapeutic potential of the poly(ADP-ribose) polymerase inhibitor rucaparib for the treatment of sporadic human ovarian cancer, Here, we investigate the potential role of the PARP inhibitor rucaparib (CO-338, formerly known as AG014699 and PF-01367338) for the treatment of sporadic ovarian cancer, These results support further clinical evaluation of rucaparib either as a single agent or as an adjunct to chemotherapy for the treatment of sporadic ovarian cancer.<CopyrightInformation>©2013 AACR</, Ongoing clinical trials are assessing the efficacy of rucaparib alone or in combination with other cytotoxic drugs, mainly in breast and ovarian cancer patients with mutations in the breast cancer associated (BRCA) genes.We aimed to establish whether the multidrug efflux transporters ABCG2 (BCRP) and ABCB1 (P-gp, MDR1) affect the oral availability and brain penetration of rucaparib in mice.In vitro, rucaparib was efficiently transported by both human ABCB1 and ABCG2, and very efficiently by mouse Abcg2, Here, we investigate the potential role of the PARP inhibitor rucaparib (CO-338, formerly known as AG014699 and PF-01367338) for the treatment of sporadic ovarian cancer. , While olaparib is the first PARP inhibitor to receive approval for ovarian cancer treatment, others including rucaparib and niraparib are clearly effective in this disease and, within the next year or two, the results of ongoing randomised trials will clarify their respective roles., We investigated the efficacy and safety of single-agent rucaparib in germline (g) BRCA mutation carriers with advanced breast and ovarian cancers.Phase II, open-label, multicentre trial of rucaparib in proven BRCA-1/2 mutation carriers with advanced breast and or ovarian cancer, WHO PS 0-1 and normal organ function., These results support further clinical evaluation of rucaparib either as a single agent or as an adjunct to chemotherapy for the treatment of sporadic ovarian cancer.<CopyrightInformation>©2013 AACR</C, Similar trials with other PARP inhibitors (rucaparib, niraparib and veliparib) are in progress and include non-BRCA-mutated ovarian cancer., Rucaparib received US FDA Breakthrough Therapy designation for treatment of platinum-sensitive BRCA-mutated advanced ovarian cancer patients who received greater than two lines of platinum-based therapy., Therapeutic potential of the poly(ADP-ribose) polymerase inhibitor rucaparib for the treatment of sporadic human ovarian cancer., These results support further clinical evaluation of rucaparib either as a single agent or as an adjunct to chemotherapy for the treatment of sporadic ovarian cancer..[SEP]Relations: Olaparib has relations: drug_drug with Rucaparib, drug_drug with Rucaparib.", "label": "yes"}
{"id": "converted_3733", "sentence1": "Has saracatinib been tested in clinical trials?", "sentence2": "Saracatinib as a metastasis inhibitor in metastatic castration-resistant prostate cancer: A University of Chicago Phase 2 Consortium and DOD/PCF Prostate Cancer Clinical Trials Consortium Study., A phase II study of saracatinib (AZD0530), a Src inhibitor, administered orally daily to patients with advanced thymic malignancies., Phase II study of saracatinib (AZD0530) in patients with previously treated metastatic colorectal cancer., Metastatic colorectal cancer patients who had received one prior treatment and had measurable disease were enrolled in this phase 2 study., A phase Ib multiple ascending dose study of the safety, tolerability, and central nervous system availability of AZD0530 (saracatinib) in Alzheimer's disease., Herein, we present a Phase Ib trial of the repurposed investigational drug AZD0530, a Src family kinase inhibitor specific for Fyn and Src kinase, for the treatment of patients with mild-to-moderate AD., The study was a 4-week Phase Ib multiple ascending dose, randomized, double-blind, placebo-controlled trial of AZD0530 in AD patients with Mini-Mental State Examination (MMSE) scores ranging from 16 to 26.[SEP]Relations: PPP1R1A has relations: anatomy_protein_present with central nervous system, anatomy_protein_present with central nervous system. malignant colon neoplasm has relations: disease_disease with colorectal cancer, disease_disease with colorectal cancer.", "label": "yes"}
{"id": "converted_431", "sentence1": "Is invasion and metastasis one of the hallmarks of cancer?", "sentence2": "The pathogenesis of MM involves the accumulation of extensive cytogenetic changes, as well as cancer-related phenotypic alterations that facilitate tumor cell survival, invasion and metastasis. This review presents current knowledge regarding the biological characteristics of this disease that are linked to the so-called hallmarks of cancer.[SEP]", "label": "yes"}
{"id": "converted_865", "sentence1": "Have C12orf65 mutations been associated with axonal neuropathy and optic atrophy?", "sentence2": "Novel C12orf65 mutations in patients with axonal neuropathy and optic atrophy, Charcot-Marie Tooth disease (CMT) forms a clinically and genetically heterogeneous group of disorders. Although a number of disease genes have been identified for CMT, the gene discovery for some complex form of CMT has lagged behind. The association of neuropathy and optic atrophy (also known as CMT type 6) has been described with autosomaldominant, recessive and X-linked modes of inheritance. Mutations in Mitofusin 2 have been found to cause dominant forms of CMT6. Phosphoribosylpyrophosphate synthetase-I mutations cause X-linked CMT6, but until now, mutations in the recessive forms of disease have never been identified.METHODS: We here describe a family with three affected individuals who inherited in an autosomal recessive fashion a childhood onset neuropathy and optic atrophy. Using homozygosity mapping in the family and exome sequencing in two affected individuals we identified a novel protein-truncating mutation in the C12orf65 gene, which encodes for a protein involved in mitochondrial translation, Novel C12orf65 mutations in patients with axonal neuropathy and optic atrophy., Our study broadens the phenotypic spectrum of C12orf65 defects and highlights the triad of optic atrophy, axonal neuropathy and spastic paraparesis as its key clinical features., C12orf65 participates in the process of mitochondrial translation and has been shown to be associated with a spectrum of phenotypes, including early onset optic atrophy, progressive encephalomyopathy, peripheral neuropathy, and spastic paraparesis.We used whole-genome homozygosity mapping as well as exome sequencing and targeted gene sequencing to identify novel C12orf65 disease-causing mutations in seven affected individuals originating from two consanguineous families., A homozygous mutation of C12orf65 causes spastic paraplegia with optic atrophy and neuropathy (SPG55)., Optic atrophy and a Leigh-like syndrome due to mutations in the c12orf65 gene: report of a novel mutation and review of the literature., Recently, we identified the causative gene, C12orf65, that was reported the gene for Leigh syndrome, for autosomal recessive spastic paraplegia with optic atrophy and neuropathy (SPG55)., We describe 2 siblings with compound heterozygous mutations in the recently identified C12orf65 gene who presented with optic atrophy and mild developmental delays and subsequently developed bilateral, symmetric lesions in the brainstem reminiscent of Leigh syndrome., C12orf65 participates in the process of mitochondrial translation and has been shown to be associated with a spectrum of phenotypes, including early onset optic atrophy, progressive encephalomyopathy, peripheral neuropathy, and spastic paraparesis.We used whole-genome homozygosity mapping as well as exome sequencing and targeted gene sequencing to identify novel C12orf65 disease-causing mutations in seven affected individuals originating from two consanguineous families, Our study broadens the phenotypic spectrum of C12orf65 defects and highlights the triad of optic atrophy, axonal neuropathy and spastic paraparesis as its key clinical features, CONCLUSIONS: This work describes a mutation in the C12orf65 gene that causes recessive form of CMT6 and confirms the role of mitochondrial dysfunction in this complex axonal neuropathy., C12orf65 participates in the process of mitochondrial translation and has been shown to be associated with a spectrum of phenotypes, including early onset optic atrophy, progressive encephalomyopathy, peripheral neuropathy, and spastic paraparesis.We used whole-genome homozygosity mapping as well as exome sequencing and targeted gene sequencing to identify novel C12orf65 disease-causing mutations in seven affected individuals originating from two consanguineous families. , Our study broadens the phenotypic spectrum of C12orf65 defects and highlights the triad of optic atrophy, axonal neuropathy and spastic paraparesis as its key clinical features. , We described a large consanguineous family with neuropathy and optic atrophy carrying a loss of function mutation in the C12orf65 gene., In these patients, we identified a homozygous splice mutation, g.21043 T>A (c.282+2 T>A) which leads to skipping of exon 2. Our study broadens the phenotypic spectrum of C12orf65 defects and highlights the triad of optic atrophy, axonal neuropathy and spastic paraparesis as its key clinical features., This work describes a mutation in the C12orf65 gene that causes recessive form of CMT6 and confirms the role of mitochondrial dysfunction in this complex axonal neuropathy., Our study broadens the phenotypic spectrum of C12orf65 defects and highlights the triad of optic atrophy, axonal neuropathy and spastic paraparesis as its key clinical features., Novel C12orf65 mutations in patients with axonal neuropathy and optic atrophy., This work describes a mutation in the C12orf65 gene that causes recessive form of CMT6 and confirms the role of mitochondrial dysfunction in this complex axonal neuropathy., A homozygous mutation of C12orf65 causes spastic paraplegia with optic atrophy and neuropathy (SPG55)., C12orf65 participates in the process of mitochondrial translation and has been shown to be associated with a spectrum of phenotypes, including early onset optic atrophy, progressive encephalomyopathy, peripheral neuropathy, and spastic paraparesis.We used whole-genome homozygosity mapping as well as exome sequencing and targeted gene sequencing to identify novel C12orf65 disease-causing mutations in seven affected individuals originating from two consanguineous families.[SEP]Relations: peripheral nervous system disease has relations: disease_disease with peripheral neuropathy, disease_disease with peripheral neuropathy. axonal neuropathy has relations: disease_disease with peripheral neuropathy, disease_disease with peripheral neuropathy. Optic atrophy has relations: disease_phenotype_positive with optic atrophy, disease_phenotype_positive with Leigh syndrome, disease_phenotype_positive with optic atrophy, disease_phenotype_positive with Leigh syndrome.", "label": "yes"}
{"id": "converted_1754", "sentence1": "Could BRCA gene test used for breast and ovarian cancer risk?", "sentence2": "Participation of Korean families at high risk for hereditary breast and ovarian cancer in BRCA1/2 genetic testing., The prevalence of BRCA1/2 mutations in Korean ovarian cancer patients irrespective of the family history was significantly higher than previously reported. Possible founder mutations in Korean ovarian cancer patients were identified., Germline Mutations of BRCA1 and BRCA2 in Korean Ovarian Cancer Patients: Finding Founder Mutations., The assessment of BRCA1 and BRCA2 coding sequences to identify pathogenic mutations associated with inherited breast/ovarian cancer syndrome has provided a method to identify high-risk individuals, allowing them to seek preventative treatments and strategies. , Maximising survival: the main concern of women with hereditary breast and ovarian cancer who undergo genetic testing for BRCA1/2.,  Little is known about how women with hereditary breast and/or ovarian cancer who test positive for a BRCA gene manage the impact of a positive test result on their everyday lives and in the longer term. This study defined the experience and needs of women with hereditary breast and ovarian cancer and a positive BRCA test over time., The strongest evidence was for rs1466785 in the NEIL2 (endonuclease VIII-like 2) gene (HR: 1.09, 95% CI (1.03-1.16), p = 2.7 × 10(-3)) for association with breast cancer risk in BRCA2 mutation carriers, and rs2304277 in the OGG1 (8-guanine DNA glycosylase) gene, with ovarian cancer risk in BRCA1 mutation carriers (HR: 1.12 95%CI: 1.03-1.21, p = 4.8 × 10(-3))., Female BRCA (breast cancer gene)-1 and BRCA-2 mutations are significantly associated with risk of developing breast and ovarian cancers, in turn, associated with female infertility. , Large BRCA1 and BRCA2 genomic rearrangements in Polish high-risk breast and ovarian cancer families., BRCA1 and BRCA2 are two major genes associated with familial breast and ovarian cancer susceptibility., Until 2006, she supervised a diagnostic unit for BRCA gene testing at the Interdisciplinary Center for Hereditary Breast Cancer (Max Delbrück Center, Berlin, Germany). , Inherited BRCA gene mutations convey a high risk for breast and ovarian cancer, but current guidelines limit BRCA mutation testing to women with early-onset cancer and relatives of mutation-positive cases. , Women who carry a BRCA1 or BRCA2 gene mutation face a risk of developing breast or ovarian cancer at an earlier age than women without such a mutation., In 2006, participants were recruited from Web sites for women with breast cancer or BRCA gene mutations. , About 20 % of hereditary breast cancers are caused by mutations in BRCA1 and BRCA2 genes. Since BRCA1 and BRCA2 mutations may be spread throughout the gene, genetic testing is usually performed by direct sequencing of entire coding regions., Suggestion of an association between BRCA2 c.7806-2A>G and risk of breast cancer in males has emerged. , The presence of deleterious mutations in breast cancer (BRCA)-1 or BRCA-2 gene has a decisive influence on the development of various types of neoplasms, such as breast, ovarian, tubal, and peritoneal cancers. , OBJECTIVE: Female BRCA (breast cancer gene)-1 and BRCA-2 mutations are significantly associated with risk of developing breast and ovarian cancers, in turn, associated with female infertility., BRCA1 and BRCA2 genes are responsible for 5-10% of breast and ovarian cancer cases., She was daughter of a woman, a carrier of BRCA 1 gene mutation, with early onset of breast cancer and positive family history.CONCLUSIONS: BRCA 1 and BRCA 2 gene mutations are of particular importance in the increasing risk of ovarian cancer and early onset of breast cancer as well as some other malignancies., BACKGROUND: Women who are diagnosed with a deleterious mutation in either breast cancer (BRCA) gene have a high risk of developing breast and ovarian cancers at young ages., We identified AJ individuals with breast and/or ovarian cancer undergoing hereditary breast/ovarian cancer risk assessment since 2006 without evidence of a deleterious mutation on BRCA gene sequencing who were screened for major gene rearrangements in BRCA1 and BRCA2., Germline BRCA gene mutations are reportedly associated with hereditary breast and ovarian cancers., [Detection and occurrence of BRCA 1 gene mutation in patients with carcinoma of the breast and ovary]., We investigated the relationship between BRCA mutations and the distribution of familial cancers other than breast or ovary in high-risk breast cancer patients.PATIENTS WITH BREAST CANCER WHO HAD AT LEAST ONE OF THE FOLLOWING RISK FACTORS WERE ENROLLED: reported family history of breast or ovarian cancer; 40 years of age or younger age at diagnosis; bilateral breast cancer; or male gender, Mutations in breast cancer susceptibility genes (BRCA1 and BRCA2) are associated with increased risks for breast, ovarian, and other types of cancer.To review new evidence on the benefits and harms of risk assessment, genetic counseling, and genetic testing for BRCA-related cancer in women.MEDLINE and PsycINFO between 2004 and 30 July 2013, the Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews from 2004 through the second quarter of 2013, Health Technology Assessment during the fourth quarter of 2012, Scopus, and reference lists.English-language studies about accuracy of risk assessment and benefits and harms of genetic counseling, genetic testing, and interventions to reduce cancer incidence and mortality., The objective of this study was to assess the incidence of primary breast cancer (PBC) and contralateral breast cancer (CBC) in patients who had BRCA1/BRCA2-associated epithelial ovarian cancer (OC).From the database of the Rotterdam Family Cancer Clinic, patients who had BRCA-associated OC without a history of unilateral breast cancer (BC) (at risk of PBC; n = 79) or with a history of unilateral BC (at risk of CBC; n = 37) were selected, Statistically significant earlier ages at diagnosis also were observed within subgroups of BRCA1 and BRCA2 mutations, maternal inheritance, paternal inheritance, breast cancer only, and breast cancer-identified and ovarian cancer-identified families.Breast and ovarian cancers in BRCA mutation carriers appeared to be diagnosed at an earlier age in later generations, The USPSTF also reviewed interventions aimed at reducing the risk for BRCA-related cancer in women with potentially harmful BRCA mutations, including intensive cancer screening, medications, and risk-reducing surgery.This recommendation applies to asymptomatic women who have not been diagnosed with BRCA-related cancer.The USPSTF recommends that primary care providers screen women who have family members with breast, ovarian, tubal, or peritoneal cancer with 1 of several screening tools designed to identify a family history that may be associated with an increased risk for potentially harmful mutations in breast cancer susceptibility genes (BRCA1 or BRCA2), If a woman bearing a mutation develops cancer in one breast, her risk of developing cancer in the other breast depends on the particular gene that is mutated and on her age at the onset of disease.About half of all monogenically determined carcinomas of the breast and ovary are due to a mutation in one or the other of the highly penetrant BRCA genes (BRCA1 and BRCA2), A value of RHR greater than 1 indicated elevated breast cancer risk; a value of RHR less than 1 indicated elevated ovarian cancer risk.Mutations of BRCA1 or BRCA2.Breast and ovarian cancer risks.Among BRCA1 mutation carriers, 9052 women (46%) were diagnosed with breast cancer, 2317 (12%) with ovarian cancer, 1041 (5%) with breast and ovarian cancer, and 7171 (37%) without cancer, This study defined the experience and needs of women with hereditary breast and ovarian cancer and a positive BRCA test over time.METHODS: A grounded theory approach was taken using qualitative interviews (n = 49) and reflective diaries. , Little is known about how women with hereditary breast and/or ovarian cancer who test positive for a BRCA gene manage the impact of a positive test result on their everyday lives and in the longer term., This study defined the experience and needs of women with hereditary breast and ovarian cancer and a positive BRCA test over time.A grounded theory approach was taken using qualitative interviews (n = 49) and reflective diaries., Women with a harmful mutation in the BReast CAncer (BRCA) gene are at significantly increased risk of developing hereditary breast and ovarian cancer (HBOC) during their lifetime, compared to those without., Genetic testing for BRCA genes, associated with hereditary breast-ovarian cancer risk, is an accepted cancer control strategy., Younger patients, those with a family history of breast or ovarian cancer, and those diagnosed more recently were more likely to be BRCA tested., Mutations in BRCA genes elevate risk for breast and ovarian cancer., Observational studies of prophylactic surgeries report reduced risks for breast and ovarian cancer in mutation carriers.No data describe the range of risk associated with BRCA mutations, genetic heterogeneity, and moderating factors; studies conducted in highly selected populations contain biases; and information on adverse effects is incomplete.A primary care approach to screening for inherited breast and ovarian cancer susceptibility has not been evaluated, and evidence is lacking to determine benefits and harms for the general population., We identified AJ individuals with breast and/or ovarian cancer undergoing hereditary breast/ovarian cancer risk assessment since 2006 without evidence of a deleterious mutation on BRCA gene sequencing who were screened for major gene rearrangements in BRCA1 and BRCA2. For each proband, the pre-test probability of identifying a deleterious BRCA mutation was estimated using the Myriad II model. We identified 108 affected individuals who underwent large rearrangement testing (80 breast cancer, 19 ovarian cancer, nine both breast and ovarian cancer)., Truncated proteins are easily discriminated from full size.RESULTS: Three BRCA 1 gene alterations were identified in the investigated group of women suffering from ovarian or breast cancer. One asymptomatic person--carrier of BRCA 1 gene mutation--was identified in this study. She was daughter of a woman, a carrier of BRCA 1 gene mutation, with early onset of breast cancer and positive family history.CONCLUSIONS: BRCA 1 and BRCA 2 gene mutations are of particular importance in the increasing risk of ovarian cancer and early onset of breast cancer as well as some other malignancies., Germline BRCA gene mutations are reportedly associated with hereditary breast and ovarian cancers. Identification of BRCA mutations greatly improves the preventive strategies and management of breast cancer., Statistically significant earlier ages at diagnosis also were observed within subgroups of BRCA1 and BRCA2 mutations, maternal inheritance, paternal inheritance, breast cancer only, and breast cancer-identified and ovarian cancer-identified families.CONCLUSIONS: Breast and ovarian cancers in BRCA mutation carriers appeared to be diagnosed at an earlier age in later generations., Truncated proteins are easily discriminated from full size.RESULTS: Three BRCA 1 gene alterations were identified in the investigated group of women suffering from ovarian or breast cancer., However, some single risk factors without family histories (early-onset breast cancer, male breast cancer, or multiple organ cancers) may limit the utility of BRCA gene testing in the Korean population., BRCA Mutations Increase Fertility in Families at Hereditary Breast/Ovarian Cancer Risk., Because infertility is associated with breast and ovarian cancer risks, we hypothesized that the mutations in the BRCA gene may be associated with low response to fertility treatments., Moreover, in families of breast cancer patients without BRCA mutations, breast cancer risk depends on the patient's age at diagnosis., Among the 554 women who underwent genetic testing for BRCA mutation, 78 were found to have a deleterious mutation in the BRCA1 gene, and 54 had a mutation in the BRCA 2 gene., Frequent recurrent mutations in the breast and ovarian cancer susceptibility (BRCA) genes BRCA1 and BRCA2 among Hispanics, including a large rearrangement Mexican founder mutation (BRCA1 exon 9-12 deletion [ex9-12del]), suggest that an ancestry-informed BRCA-testing strategy could reduce disparities and promote cancer prevention by enabling economic screening for hereditary breast and ovarian cancer in Mexico., Individuals who carry a BRCA gene mutation have increased lifetime risks of developing hereditary breast and ovarian cancer syndrome-related cancers., BRCA gene mutations have been well described to carry an increased risk of both breast and ovarian cancer., Ovarian cancer among 8,005 women from a breast cancer family history clinic: no increased risk of invasive ovarian cancer in families testing negative for BRCA1 and BRCA2., Women who were BRCA carriers, women who had a history of breast cancer, DCIS, or breast biopsy, or had a family history of ovarian cancer were more likely to have undergone surgery for cancer risk reduction., Genetic testing for breast cancer susceptibility became a reality after two cancer predisposition genes, BRCA1 and BRCA2, were identified., Germline mutations in BRCA genes are associated with breast and ovarian cancer susceptibility., We used person-years at risk to assess ovarian cancer rates in the study population, subdivided by genetic status (BRCA1, BRCA2, BRCA negative, BRCA untested) compared with the general population.[SEP]Relations: Breast carcinoma has relations: disease_phenotype_positive with ovarian cancer, disease_phenotype_positive with ovarian cancer. carcinoma has relations: disease_disease with cancer, disease_disease with cancer.", "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_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_3962", "sentence1": "Is MIS-C or Multisystem  Inflammatory syndrome in children a complication of Covid-19?", "sentence2": "Much remains unknown about the risk factors, pathogenesis, prognosis, and specific therapy for this emerging manifestation of COVID-19 known as Multisystem Inflammatory Syndrome in Children (MIS-C)., Multisystem Inflammatory Syndrome in Children During the Coronavirus 2019 Pandemic: A Case Series, COVID-19 and Multisystem Inflammatory Syndrome in Latin American Children,  This study aims to assess COVID-19 and Multisystem Inflammatory Syndrome (MIS-C) in Latin American children,, A complication is the rare multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19, presenting 4-6 weeks after infection as high fever, organ dysfunction, and strongly elevated markers of inflammation., We apply systems-level analyses of blood immune cells, cytokines, and autoantibodies in healthy children, children with Kawasaki disease enrolled prior to COVID-19, children infected with SARS-CoV-2, and children presenting with MIS-C. We find that the inflammatory response in MIS-C differs from the cytokine storm of severe acute COVID-19, shares several features with Kawasaki disease, but also differs from this condition with respect to T cell subsets, interleukin (IL)-17A, and biomarkers associated with arterial damage., OBJECTIVE: Multisystem inflammatory syndrome in children (MIS-C) associated with coronavirus disease (COVID-19) is a rare and challenging diagnosis requiring early treatment., This syndrome is now known as either \"Pediatric Inflammatory Multisystem Syndrome temporally related with COVID-19\" (PIMS-TS) (1), or Multisystem Inflammatory Syndrome in Children (MIS-C) (2) and is currently considered a rare post-COVID-19 complication which, in a minority of cases, can lead to death., Multisystem Inflammatory Syndrome in Children (MIS-C) associated with Coronavirus Disease 2019 (COVID-19) is a newly recognized condition in which children with recent SARS-CoV-2 infection present with a constellation of symptoms including hypotension, multiorgan involvement, and elevated inflammatory markers. Thes, Background: Kawasaki-like syndrome occurring in children during the COVID-19 pandemic has been labelled multisystem inflammatory syndrome in children (MIS-C) by the CDC and paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 infection (PIMS-TS) by , em inflammatory syndrome in children (MIS-C), a possible complication of COVID-19, has been described as a hyperinflammatory condition with multiorgan involvement similar to that in Kawasaki disease or toxic shock syndrome in children with evidence of SARS-CoV-2 infection. This revie, BACKGROUND: A small subset of pediatric patients develop a rare syndrome associated with Coronavirus Disease 2019 (COVID-19) infection called multisystem inflammatory syndrome in childr,  adults. However, the newly described multisystem inflammatory syndrome in children (MIS-C) associated with coronavirus disease 2019 (COVID-19) has been associated with cardiac complicat, BACKGROUND: Multisystem inflammatory syndrome temporally associated with COVID-19 (MIS-C) has been described as a novel and often severe presentation of SARS-CoV-2 infection i, OBJECTIVE: Multisystem inflammatory syndrome in children (MIS-C) associated with coronavirus disease (COVID-19) is a rare and challenging diagnosis requiring early tr, Background: Multisystem inflammatory syndrome in children (MIS-C), also known as pediatric inflammatory multisystem syndrome, is a new dangerous childhood disease that is temporally associated with coronavirus disease 2019 (, Recent COVID-19 publications describe a variety of clinical presentations including an asymptomatic state, pneumonia, a hemophagocytic lymphohistiocytosis like syndrome, Multisystem Inflammatory Syndrome in Children (MIS-C) but, also called Pediatric Inflammatory Multisystem Syndrome-Toxic Shock (PIMS-TS), Kawasaki Disease, and myocarditis., We analyzed peripheral blood immune responses in hospitalized SARS-CoV-2 infected pediatric patients (pediatric COVID-19) and patients with MIS-C. MIS-C patients had patterns of T cell-biased lymphopenia and T cell activation similar to severely ill adults, and all patients with MIS-C had SARS-CoV-2 spike-specific antibodies at admission., Multisystem inflammatory syndrome in children (MIS-C), a possible complication of COVID-19, has been described as a hyperinflammatory condition with multiorgan involvement similar to that in Kawasaki disease or toxic shock syndrome in children with evidence of SARS-CoV-2 infection., It includes a discussion of multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19, as well as other aspects of the COVID-19 pandemic that are affecting children and families, such as poisonings, childhood immunizations, mental health, nonaccidental trauma, and neglect., Importance: To date, no study has characterized the mucocutaneous features seen in hospitalized children with multisystem inflammatory syndrome in children (MIS-C) or the temporal association of these findings with the onset of systemic symptoms.Objective: To describe the mucocutaneous findings seen in children with MIS-C during the height of the coronavirus disease 2019 (COVID-19) pandemic in New York City in 2020.Design, Setting, and Participants: A retrospective case series was conducted of 35 children admitted to 2 hospitals in New York City between April 1 and July 14, 2020, who met Centers for Disease Control and Prevention and/or epidemiologic criteria for MIS-C.Main Outcomes and Measures: Laboratory and clinical characteristics, with emphasis on mucocutaneous findings, of children who met criteria for MIS-C., This condition, since defined as the multisystem inflammatory syndrome in children (MIS-C), is assumed to be a delayed immune response to coronavirus disease 2019 (COVID-19), and there are frequently cardiac manifestations of ventricular dysfunction and/or coronary artery dilation.Methods: We surveyed the inpatient MIS-C management approaches of the members of the International Kawasaki Disease Registry across 38 institutions and 11 countries.Results: Among the respondents, 56% reported using immunomodulatory treatment for all MIS-C patients, regardless of presentation., DESIGN: Children ages 0-22 years with suspected severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection presenting to urgent care clinics or being hospitalized for confirmed/suspected SARS-CoV-2 infection or multisystem inflammatory syndrome in children (MIS-C) at Massachusetts General Hospital were offered enrollment in the Massachusetts General Hospital Pediatric COVID-19 Biorepository., We recently discovered a superantigen-like motif, similar to Staphylococcal enterotoxin B (SEB), near the S1/S2 cleavage site of SARS-CoV-2 Spike protein, which might explain the multisystem-inflammatory syndrome (MIS-C) observed in children and cytokine storm in severe COVID-19 patients., METHODS: An extensive search strategy was conducted by combining the terms multisystem inflammatory syndrome in children and coronavirus infection or using the term multisystem inflammatory syndrome in children in bibliographic electronic databases (PubMed, EMBASE, and CINAHL) and in preprint servers (BioRxiv.org and MedRxiv.org) following the Preferred Reporting Items for Systematic Reviews and Metaanalyses guidelines to retrieve all articles published from January 1, 2020, to July 31, 2020., Here, we show that pediatric patients with multisystem inflammatory syndrome in children (MIS-C) possess higher SARS-CoV-2 spike IgG titers compared to those with severe coronavirus disease 2019 (COVID-19), likely reflecting a longer time since onset of infection in MIS-C patients., Here, we show that pediatric patients with multisystem inflammatory syndrome in children (MIS-C) possess higher SARS-CoV-2 spike IgG titers compared to those with severe coronavirus disease 2019 (COVID-19), likely reflecting a longer time since onset of infection in MIS-C patients., Multisystem inflammatory syndrome in children (MIS-C) is a life-threatening post-infectious complication occurring unpredictably weeks after mild or asymptomatic SARS-CoV2 infection in otherwise healthy children., Data on multisystem inflammatory syndrome in children (MIS-C) related to coronavirus disease-19 (COVID-19) is increasing in the current COVID-19 pandemic., Introduction Multisystem inflammatory syndrome in children (MIS-C) is a unique clinical complication of SARS-CoV-2 infection observed in pediatric patients., New onset diabetes with diabetic ketoacidosis in a child with multisystem inflammatory syndrome due to COVID-19., Case presentation An eight-year-old female presented with hyperglycemia, ketosis and metabolic acidosis consistent with diabetic ketoacidosis (DKA) in the setting of fever, rash, respiratory distress, hemodynamic instability, reduced systolic function with dilation of the left anterior descending artery, and positive SARS-CoV-2 antibodies suggestive of MIS-C., However, the newly described multisystem inflammatory syndrome in children (MIS-C) associated with coronavirus disease 2019 (COVID-19) has been associated with cardiac complications.M, Toxic shock-like syndrome and COVID-19: Multisystem inflammatory syndrome in children (MIS-C)., Many of these cases feature a toxic shock-like syndrome or Kawasaki-like syndrome in the setting of SARS-CoV-2 positive diagnostic testing and the CDC has termed this presentation Multisystem Inflammatory Syndrome (MIS-C)., We describe a case of MIS-C in a child who presented to our Emergency Department (ED) twice and on the second visit was found to have signs of distributive shock, multi-organ injury and systemic inflammation associated with COVID-19., PURPOSE OF REVIEW: Here we summarize current knowledge about multisystem inflammatory syndrome in children (MIS-C), a presumed postinfectious inflammatory condition that has emerged as an important COVID-19-associated complication, to help clinicians identify and manage cases.RECENT FINDINGS: Clinical presentation of MIS-C is do, MIS-C is a rare yet severe and highly critical complication of COVID-19 infection in pediatrics, leading to serious and life-threatening illnesses., BACKGROUND: A multisystem inflammatory syndrome in children associated with COVID-19 (MIS-C) has recently been described.OBJECTIVE: To evaluate imaging findings of MIS-C associated with COVID-19.SUBJECTS AND METHODS: Imaging studies and medical records of sixteen patients (0-20 years) admit, BACKGROUND: Recently, cases of multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19 have been reporte, Recent reports have described a secondary Multisystem Inflammatory Syndrome in Children (MIS-C) after a prior COVID-19 infection that often has features of Kawasaki disease (KD).,  discharged home (length of hospital stay 3-20 days). There were no mortalities.CONCLUSION: MIS-C associated with COVID-19 is characterized predominantly by cardiovascular abnormalities, though also solid visceral organ, gallbladder, and bowel abnormalities as well as ascites, reflecting a multisystemic inflammatory process.CLINICAL IMPACT: The constellation of imaging findings in the setting of COVID-19 may alert pediatr, Multisystem Inflammatory Syndrome in Children Temporally Related to COVID-19: A Case Report From Saudi Arabia., BACKGROUND: Multisystem inflammatory syndrome temporally associated with COVID-19 (MIS-C) has been described as a novel and often severe presentation of SARS-CoV-2 infection , ric patients. An association between COVID-19 and a Kawasaki-like inflammatory syndrome has recently presented in pediatric patients.CASE REPORT: We report a unique case of multisystem inflammatory syndrome in children presenting with characteristic findings in a child who later developed cardiogenic shock requiring venoarterial extracorporeal membrane oxygenation.CONCLUSION: Recognition of these early signs and symptoms facilitates screening and risk stratification of pediatric COVID-19 cas, Severe cardiac dysfunction in a patient with multisystem inflammatory syndrome in children associated with COVID-19: Retrospective diagnosis of a puzzling presentation. A case report.[SEP]Relations: Pneumonia has relations: disease_phenotype_positive with toxic shock syndrome, disease_phenotype_positive with toxic shock syndrome. staphylococcal toxic-shock syndrome has relations: disease_disease with toxic shock syndrome, disease_disease with toxic shock syndrome. Respiratory distress has relations: disease_phenotype_positive with toxic shock syndrome, disease_phenotype_positive with toxic shock syndrome.", "label": "yes"}
{"id": "converted_1570", "sentence1": "Does neuroglobin has neuroprotective properties in the setting of traumatic brain injury?", "sentence2": "Neuroglobin has shown rich neuroprotective effects against cerebral hypoxia, and therefore has the potential to impact outcomes after traumatic brain injury (TBI). , Neuroglobin (Ngb) is proposed to be a neuron-specific, hypoxia-responsive, neuroprotective protein. , CONCLUSION: The increased expression of neuroglobin in traumatic brain injury informed us that neuroglobin had anti-apoptosis action in post-injury neuron. It could protect the neuron from traumatic stress and secondary ischemia and hypoxia insults during ultra-early and acute stages., Neuroglobin-overexpression reduces traumatic brain lesion size in mice., BACKGROUND: Accumulating evidence has demonstrated that over-expression of Neuroglobin (Ngb) is neuroprotective against hypoxic/ischemic brain injuries. , CONCLUSION: Ngb over-expression reduced traumatic lesion volume, which might partially be achieved by decreasing oxidative stress., Neuroglobin upregulation offers neuroprotection in traumatic brain injury., OBJECTIVES: The aim of this study was to investigate rat neuroglobin (rNGB) expression level after traumatic brain injury (TBI) and further study its neuroprotective effects in TBI when it was overexpressed in adenoviral vector., CONCLUSIONS: NGB was upregulated in TBI and overexpressed rNGB had a significant neuroprotection in TBI. , This study suggested that rNGB overexpression may be a new strategy for treating of TBI., Neuroglobin has shown rich neuroprotective effects against cerebral hypoxia, and therefore has the potential to impact outcomes after traumatic brain injury (TBI)., The aim of this study was to investigate rat neuroglobin (rNGB) expression level after traumatic brain injury (TBI) and further study its neuroprotective effects in TBI when it was overexpressed in adenoviral vector., Accumulating evidence has demonstrated that over-expression of Neuroglobin (Ngb) is neuroprotective against hypoxic/ischemic brain injuries., Various studies seem to indicate that neuroglobin is a neuroprotective agent when overexpressed, acting as a potent inhibitor of oxidative and nitrosative stress. [SEP]", "label": "yes"}
{"id": "converted_509", "sentence1": "Is phospholamban a regulatory/inhibitory protein of the Ca ATPase SERCA?", "sentence2": "The membrane protein complex between the sarcoplasmic reticulum Ca(2+)-ATPase (SERCA) and phospholamban (PLN) controls Ca(2+) transport in cardiomyocytes, thereby modulating cardiac contractility. β-Adrenergic-stimulated phosphorylation of PLN at Ser-16 enhances SERCA activity via an unknown mechanism., Phospholamban (PLN) is a type II membrane protein that inhibits the sarcoplasmic reticulum Ca(2+)-ATPase (SERCA), thereby regulating calcium homeostasis in cardiac muscle. In membranes, PLN forms pentamers that have been proposed to function either as a storage for active monomers or as ion channels., Regulation of the SERCA calcium pump by phospholamban (PLB) is largely due to interactions between their respective transmembrane domains. In spite of numerous mutagenesis and kinetic studies, we still do not have a clear mechanistic picture of how PLB influences the calcium transport cycle of SERCA., Calcium transport across the membrane of the sarcoplasmic reticulum (SR) plays an important role in the regulation of heart muscle contraction and relaxation. The sarco(endo)plasmic reticulum Ca(2+) ATPase (SERCA) 2a is responsible for Ca(2+) up-take by this organelle and is inhibited in a reversible manner by phospholamban, another SR membrane protein. Thus, alleviation of phospholamban-mediated inhibition of SERCA2a is a potential therapeutic option for heart failure and cardiomyopathy., Phospholamban has been suggested to be a key regulator of cardiac sarcoplasmic reticulum (SR) Ca cycling and contractility and a potential therapeutic target in restoring the depressed Ca cycling in failing hearts., In larger mammals, a higher fraction of SERCA2a pumps are regulated by phospholamban, and this may influence therapeutic strategies to enhance cardiac contractility and functional cardiac reserve., Phospholamban (PLB) inhibits the sarcoplasmic reticulum (SR) Ca(2+)-ATPase (SERCA), and this inhibition is relieved by Ca(2+) calmodulin-dependent protein kinase II (CaM kinase II) phosphorylation, These findings suggest that PLB is an important modulator of gastric antrum smooth muscle contractility by modulation of SR Ca(2+) release and CaM kinase II activity., The function of the SERCA pump is modulated by the endogenous molecules phospholamban (PLB) and sarcolipin (SLN), expressed in cardiac and skeletal muscles. The mechanism of action of PLB on SERCA is well characterized, whereas that of SLN is only beginning to be understood. ,  Phospholamban (PLB) is an inhibitor of the sarcoplasmic reticulum (SR) Ca2+-ATPase (SERCA)., These results show that alteration of the PLB:SERCA ratio can significantly modulate smooth muscle [Ca2+]i., Phospholamban expressed in cardiac muscle and sarcolipin expressed in skeletal muscle regulate SERCA activity., Phospholamban (PLB) is a 24- to 27-kDa phosphoprotein that modulates activity of the sarco(endo)plasmic reticulum Ca2+ ATPase (SERCA). Expression of PLB is reportedly limited to cardiac, slow-twitch skeletal and smooth muscle in which PLB is an important regulator of [Ca2+]i and contractility in these muscles., Regulation of the sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA 2a) depends on the phosphorylation state of phospholamban (PLB). When PLB is phosphorylated, its inhibitory effect towards SERCA 2a is relieved, leading to an enhanced myocardial performance. ,  Ca(2+) reuptake occurs via sarcoendoplasmic reticulum Ca(2+) ATPase (SERCA) and is regulated by the inhibitory protein phospholamban (PLB) in many cell types., Phospholamban (PLN) is a small integral membrane protein, which binds and inhibits in a yet unknown fashion the Ca(2+)-ATPase (SERCA) in the sarcoplasmic reticulum., Phospholamban (PLN) is the endogenous inhibitor of the sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA), the integral membrane enzyme responsible for 70�% of the removal of Ca(2+) from the cytosol, inducing cardiac muscle relaxation in humans., Phospholamban (PLB) is an integral membrane protein regulating Ca(2+) transport through inhibitory interaction with sarco(endo)plasmic reticulum calcium ATPase (SERCA)., Phosphorylation by protein kinase A and dephosphorylation by protein phosphatase 1 modulate the inhibitory activity of phospholamban (PLN), the endogenous regulator of the sarco(endo)plasmic reticulum calcium Ca(2+) ATPase (SERCA)., Phosphorylation by protein kinase A and dephosphorylation by protein phosphatase 1 modulate the inhibitory activity of phospholamban (PLN), the endogenous regulator of the sarco(endo)plasmic reticulum calcium Ca(2+) ATPase (SERCA), We used EPR spectroscopy to probe directly the interaction between phospholamban (PLB) and its regulatory target, the sarcoplasmic reticulum Ca-ATPase (SERCA)[SEP]", "label": "yes"}
{"id": "converted_163", "sentence1": "Does MicroRNA-21 (miR-21) contribute to cardiovascular disease?", "sentence2": "The synergistic effect of miR-21 and miR-1 were functionally validated for their significant influences on myocardial apoptosis, cardiac hypertrophy and fibrosis., Taken together, we found a novel reciprocal loop between miR-21 and TGFβRIII in cardiac fibrosis caused by myocardial infarction in mice, and targeting this pathway could be a new strategy for the prevention and treatment of myocardial remodeling., It is still controversial whether microRNA-21 (miR-21) participates in the process of cardiac fibrosis., In mice, myocardial miR-21 overexpression is related to cardiac fibrosis elicited by pressure overload. , The myocardial and plasma levels of miR-21 were significantly higher in the AS patients compared with the controls and correlated directly with the echocardiographic mean transvalvular gradients., Our results support the role of miR-21 as a regulator of the fibrotic process that occurs in response to pressure overload in AS patients and underscore the value of circulating miR-21 as a biomarker for myocardial fibrosis., Ad-miR-21 improves LV remodeling and decreases the apoptosis of myocardial cells, suggesting the possible mechanism by which Ad-miR-21 functions in protecting against I/R injury., In the Ad-miR-21 group, LV dimensions, myocardial infarct size, LV/BW, collagen type Ⅰ, type Ⅲ and PCNA positive cells all significantly decreased compared with the Ad-GFP group., While miR-21, -133, -150, -195, and -214 regulate cardiomyocyte hypertrophy, miR-1/-133 and miR-208 have been elucidated to influence myocardial contractile function. In addition, miR-21, -24, -133, -210, -494, and -499 appear to protect myocytes against I/R-induced apoptosis, whereas miR-1, -29, -199a, and -320 promote apoptosis. Myocardial fibrosis can be regulated by the miR-29 family and miR-21., The small regulatory RNA microRNA-21 (miR-21) plays a crucial role in a plethora of biological functions and diseases including development, cancer, cardiovascular diseases and inflammation., During recent years, additional roles of miR-21 in cardiovascular and pulmonary diseases, including cardiac and pulmonary fibrosis as well as myocardial infarction have been described., On the other hand, miR-21, miR-199a, miR-210, and miR-494 have been proven critical for the myocytes' adaptation and survival during hypoxia/ischemia. , Studies have shown that several miRs, including miR-1, miR-133, miR-21, miR-126, miR-320, miR-92a, and miR-199a, are regulated after preconditioning and play an active role in protecting the heart against ischemia/reperfusion injury., Studies using various in vivo, ex vivo, and in vitro models have suggested the possible involvement of miR-1, miR-21, miR-29, miR-92a, miR-133, miR-199a, and miR-320 in ischemia-reperfusion injury and/or remodeling after myocardial infarction., MicroRNA-21 (miR-21) is a highly expressed microRNA (miRNA) in cardiovascular system. Recent studies have revealed that its expression is deregulated in heart and vasculature under cardiovascular disease conditions such as proliferative vascular disease, cardiac hypertrophy and heart failure, and ischemic heart disease. miR-21 is found to play important roles in vascular smooth muscle cell proliferation and apoptosis, cardiac cell growth and death, and cardiac fibroblast functions. Accordingly, miR-21 is proven to be involved in the pathogenesis of the above-mentioned cardiovascular diseases as demonstrated by both loss-of-function and gain-of-function approaches., miR-21 might be a novel therapeutic target in cardiovascular diseases., This review article summarizes the research progress regarding the roles of miR-21 in cardiovascular disease., Remarkably, miR-21 was one of most upregulated miRNAs in hearts after IP. In vivo, IP-mediated cardiac protection against ischaemia/reperfusion injury was inhibited by knockdown of cardiac miR-21. In cultured cardiac myocytes, we identified that miR-21 also had a protective effect on hypoxia/reoxygenation-induced cell apoptosis that was associated with its target gene, programmed cell death 4. The protective effect of miR-21 on cardiac cell apoptosis was further confirmed in rat hearts after ischaemia/reperfusion injury in vivo., Lately, some highlight articles revealed that the altered expression of miRNAs such as miR-1, miR-133, miR-21, miR-208 etc in hearts also contributed to cardiovascular diseases, such as heart ischemia, cardiac hypertrophy, and arrhythmias., Remarkably, miR-21 expression was significantly down-regulated in infarcted areas, but was up-regulated in border areas. The down-regulation of miR-21 in the infarcted areas was inhibited by ischemic preconditioning, a known cardiac protective method. Overexpression of miR-21 via adenovirus expressing miR-21 (Ad-miR-21) decreased myocardial infarct size by 29% at 24 h and decreased the dimension of left ventricles at 2 weeks after AMI. Using both gain-of-function and loss-of-function approaches in cultured cardiac myocytes, we identified that miR-21 had a protective effect on ischemia-induced cell apoptosis that was associated with its target gene programmed cell death 4 and activator protein 1 pathway. The protective effect of miR-21 against ischemia-induced cardiac myocyte damage was further confirmed in vivo by decreased cell apoptosis in the border and infarcted areas of the infarcted rat hearts after treatment with Ad-miR-21. The results suggest that miRNAs such as miR-21 may play critical roles in the early phase of AMI., The results suggest that miR-21 is sensitive to H(2)O(2) stimulation. miR-21 participates in H(2)O(2)-mediated gene regulation and functional modulation in cardiac myocytes. miR-21 might play an essential role in heart diseases related to ROS such as cardiac hypertrophy, heart failure, myocardial infarction, and myocardial ischemia/reperfusion injury., MicroRNA-21 contributes to myocardial disease by stimulating MAP kinase signalling in fibroblasts, Myocardial and circulating levels of microRNA-21 reflect left ventricular fibrosis in aortic stenosis patients, MicroRNA 21 inhibits left ventricular remodeling in the early phase of rat model with ischemia-reperfusion injury by suppressing cell apoptosis, MicroRNA-21 protects against the H(2)O(2)-induced injury on cardiac myocytes via its target gene PDCD4, MicroRNA-21 (miR-21) is a highly expressed microRNA (miRNA) in cardiovascular system., MicroRNA-21 contributes to myocardial disease by stimulating MAP kinase signalling in fibroblasts., MicroRNA-21 (miR-21) is a highly expressed microRNA (miRNA) in cardiovascular system, miR-21 might be a novel therapeutic target in cardiovascular diseases, MicroRNA-21 as therapeutic target in cancer and cardiovascular disease., These findings reveal that microRNAs can contribute to myocardial disease by an effect in cardiac fibroblasts., Our results validate miR-21 as a disease target in heart failure and establish the therapeutic efficacy of microRNA therapeutic intervention in a cardiovascular disease setting.[SEP]", "label": "yes"}
{"id": "converted_2657", "sentence1": "Are AAV vectors considered for the treatment of retinal dystrophies?", "sentence2": " These novel gene vectors aim to more safely and efficiently transduce retinal cells, expand the gene packaging capacity of AAV, and utilize new strategies to correct the varying mechanisms of dysfunction found with inherited retinal dystrophies. [SEP]", "label": "yes"}
{"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_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_4578", "sentence1": "Is the protein HOXA11 associated with endometrial disease?", "sentence2": " Both CD10 and HOXA11 have been implicated in regulation of endometrial homeostasis., Combined expression of HOXA11 and CD10 identifies endometriosis versus normal tissue and tumors., The combination of HOXA11 and CD10 expression profiles provides a useful tool to identify ectopic endometrial tissue and for distinguishing endometriosis from various types of gynecological malignancies and metastases., Downregulation of HOXA11 enhances endometrial cancer malignancy, Low HOXA11 expression may promote the proliferation, migration, invasion of endometrial cancer cells, and increase their resistance to cisplatin through activating PTEN/AKT pathway., Endometrial mRNA and protein expression levels of HOXA10 and HOXA11 were significantly lower in patients with AM than in control patients.[SEP]", "label": "yes"}
{"id": "converted_2184", "sentence1": "Is hydroxyurea usually used to treated infectious disease?", "sentence2": "Hydroxyurea represents the only available disease-modifying therapy for SCA, and has proven safety and efficacy in high-resource countries, In conclusion, the data here presented suggests that hydroxyurea may prevent priapism attacks in sickle cell disease, probably at higher doses than usually prescribed for painful crisis prevention.., Clinical follow-up of hydroxyurea-treated adults with sickle cell disease., t may also attenuate optimal response to hydroxyurea therapy, the only effective and practical treatment option for SCD in sub-Saharan Africa, Hydroxyurea is one of the most successfully used therapies for sickle cell disease, Clinical experience with hydroxyurea for patients with sickle cell disease (SCD) has been accumulating for the past 25 years. The bulk of the current evidence suggests that hydroxyurea is well-tolerated, safe, and efficacious for most patients with SCD[SEP]", "label": "no"}
{"id": "converted_1595", "sentence1": "Does TRIM37 gene mutation causes Mulibrey nanism?", "sentence2": "OBJECTIVE: We studied pubertal development and fecundity in males with Mulibrey nanism (MUL) caused by mutations in the TRIM37 gene., In MUL, mutations in TRIM37 lead to disturbance of sexual maturation, and fertility is severely compromised. , It is caused by recessive mutations in the TRIM37 gene encoding for the peroxisomal TRIM37 protein with ubiquitin-ligase activity. , Mulibrey nanism is an autosomal recessive growth disorder caused by mutations in the TRIM37 gene encoding a protein of unknown function. , Gynecological tumors in Mulibrey nanism and role for RING finger protein TRIM37 in the pathogenesis of ovarian fibrothecomas., To investigate the possible involvement of TRIM37 alterations in the pathogenesis of sporadic fibrothecomas, we analyzed the TRIM37 cDNA for mutations and alternatively spliced transcripts and TRIM37 expression in fibrothecomas of women without Mulibrey nanism. ,  In conclusion, inherited biallelic inactivation of TRIM37 (Mulibrey nanism) predisposes to both mesenchymal and epithelial ovarian tumors and dysregulation of TRIM37 may also be involved in the pathogenesis of sporadic fibrothecomas., A novel splice site mutation in the TRIM37 gene causes mulibrey nanism in a Turkish family with phenotypic heterogeneity., Mulibrey nanism (MUL) is an autosomal recessive disease caused by mutations in the TRIM37 gene encoding the peroxisomal TRIM37 protein of unknown function., Mulibrey nanism (muscle-liver-brain-eye nanism; MUL) is an autosomal recessively transmitted disease characterized by severe growth delays of prenatal onset caused by mutations in the TRIM37 gene., Mutations in the TRIM37 gene underlie mulibrey nanism (muscle-liver-brain-eye nanism), a rare monogenic developmental disorder characterized by severe growth failure, characteristic dysmorphic features, cardiopathy, failure of sexual maturation, and metabolic syndrome., Mulibrey nanism is an autosomal recessive growth disorder caused by mutations in the TRIM37 gene encoding a protein of unknown function., Mulibrey nanism is a rare growth disorder of prenatal onset caused by mutations in the TRIM37 gene, which encodes a RING-B-box-coiled-coil protein., Novel mutations in the TRIM37 gene in Mulibrey Nanism., Five truncating mutations in the TRIM37 gene have previously been reported in Mulibrey nanism patients., Characterisation of the mulibrey nanism-associated TRIM37 gene: transcription initiation, promoter region and alternative splicing., The TRIM37 gene encodes a peroxisomal RING-B-box-coiled-coil protein: classification of mulibrey nanism as a new peroxisomal disorder., A novel splice site mutation in the TRIM37 gene causes mulibrey nanism in a Turkish family with phenotypic heterogeneity, Mulibrey nanism is a rare growth disorder of prenatal onset caused by mutations in the TRIM37 gene, which encodes a RING-B-box-coiled-coil protein, Mulibrey nanism (muscle-liver-brain-eye nanism; MUL) is an autosomal recessively transmitted disease characterized by severe growth delays of prenatal onset caused by mutations in the TRIM37 gene, Mulibrey nanism is an autosomal recessive growth disorder caused by mutations in the TRIM37 gene encoding a protein of unknown function, Mulibrey nanism (MUL) is an autosomal recessive disease caused by mutations in the TRIM37 gene encoding the peroxisomal TRIM37 protein of unknown function, Novel mutations in the TRIM37 gene in Mulibrey Nanism, Five truncating mutations in the TRIM37 gene have previously been reported in Mulibrey nanism patients, Mulibrey nanism (MUL) is a rare autosomal recessive disorder with severe primordial growth retardation and multiorgan involvement, caused by mutations in TRIM37, Refractory congestive heart failure following delayed pericardectomy in a 12-year-old child with Mulibrey nanism due to a novel mutation in TRIM37, A novel mutation in TRIM37 is associated with mulibrey nanism in a Turkish boy, OBJECTIVE: We studied pubertal development and fecundity in males with Mulibrey nanism (MUL) caused by mutations in the TRIM37 gene. , Mulibrey nanism is a rare growth disorder of prenatal onset caused by mutations in the TRIM37 gene, which encodes a RING-B-box-coiled-coil protein. , Mulibrey nanism (muscle-liver-brain-eye nanism; MUL) is an autosomal recessively transmitted disease characterized by severe growth delays of prenatal onset caused by mutations in the TRIM37 gene. , UNLABELLED: Mulibrey nanism (MUL) is a rare autosomal recessive disorder with severe primordial growth retardation and multiorgan involvement, caused by mutations in TRIM37. , Mulibrey nanism (MUL) is an autosomal recessive disease caused by mutations in the TRIM37 gene encoding the peroxisomal TRIM37 protein of unknown function. , Mutations in TRIM37 underlie mulibrey nanism, a rare autosomal recessively inherited disorder with severe growth failure of prenatal onset, constrictive pericardium, hepatomegaly and characteristic dysmorphic features. , Mutations in the TRIM37 gene underlie mulibrey nanism (muscle-liver-brain-eye nanism), a rare monogenic developmental disorder characterized by severe growth failure, characteristic dysmorphic features, cardiopathy, failure of sexual maturation, and metabolic syndrome., A novel mutation in TRIM37 is associated with mulibrey nanism in a Turkish boy., Five truncating mutations in the TRIM37 gene have previously been reported in Mulibrey nanism patients.,  Few monogenic mutations causing human male infertility have been identified to date.  We studied pubertal development and fecundity in males with Mulibrey nanism (MUL) caused by mutations in the TRIM37 gene.,  Mulibrey nanism is a rare growth disorder of prenatal onset caused by mutations in the TRIM37 gene, which encodes a RING-B-box-coiled-coil protein. The pathogenetic mechanisms of mulibrey nanism are unknown.,  Mulibrey nanism is an autosomal recessive growth disorder caused by mutations in the TRIM37 gene encoding a protein of unknown function. More than half of female patients with Mulibrey nanism develop benign mesenchymal tumors of ovarian sex cord-stromal origin., Mulibrey nanism (MUL) is an autosomal recessive disease caused by mutations in the TRIM37 gene encoding the peroxisomal TRIM37 protein of unknown function., Mulibrey nanism (muscle-liver-brain-eye nanism; MUL) is an autosomal recessively transmitted disease characterized by severe growth delays of prenatal onset caused by mutations in the TRIM37 gene., Mulibrey nanism (MUL) is a monogenic disorder with prenatal-onset growth failure, typical clinical characteristics, cardiopathy and tendency for a metabolic syndrome. It is caused by recessive mutations in the TRIM37 gene encoding for the peroxisomal TRIM37 protein with ubiquitin-ligase activity.,  We studied pubertal development and fecundity in males with Mulibrey nanism (MUL) caused by mutations in the TRIM37 gene.  Twenty-eight male MUL patients of the Finnish national cohort aged 8.7 to 50.0 yr (median age, 28.8) at the end of observation were followed for 10 yr beginning from 2000-2001., A novel splice site mutation in the TRIM37 gene causes mulibrey nanism in a Turkish family with phenotypic heterogeneity., We studied pubertal development and fecundity in males with Mulibrey nanism (MUL) caused by mutations in the TRIM37 gene., Mulibrey nanism is an autosomal recessive growth disorder caused by mutations in the TRIM37 gene encoding a protein of unknown function., Mulibrey nanism is a rare growth disorder of prenatal onset caused by mutations in the TRIM37 gene, which encodes a RING-B-box-coiled-coil protein., Novel mutations in the TRIM37 gene in Mulibrey Nanism., Five truncating mutations in the TRIM37 gene have previously been reported in Mulibrey nanism patients., It is caused by recessive mutations in the TRIM37 gene encoding for the peroxisomal TRIM37 protein with ubiquitin-ligase activity., Mulibrey nanism (MUL) is a rare autosomal recessive disorder with severe primordial growth retardation and multiorgan involvement, caused by mutations in TRIM37.[SEP]Relations: metabolic syndrome X has relations: disease_disease with metabolic syndrome, disease_disease with metabolic syndrome. mulibrey nanism has relations: disease_protein with TRIM37, disease_protein with TRIM37.", "label": "yes"}
{"id": "converted_1652", "sentence1": "Is cardiac magnetic resonance imaging indicated in the pre-participation screening of athletes?", "sentence2": "As modern imaging further enhances our understanding of the spectrum of athlete's heart, its role may expand from the assessment of athletes with suspected disease to being part of comprehensive pre-participation screening in apparently healthy athletes., Finally we will address the role of CMR in pre-participation screening.[SEP]", "label": "no"}
{"id": "converted_3183", "sentence1": "Are protamines ubiquitously expressed?", "sentence2": "Protamines are nuclear proteins which are specifically expressed in haploid male germ cells.[SEP]", "label": "no"}
{"id": "converted_2666", "sentence1": "Is sternotomy closure done using either a sternal ZipFix™ implant  or conventional steel wire following cardiac surgery?", "sentence2": "o determine the difference in sternal infection and other infectious events between conventional wire and cable-tie-based closure techniques post-sternotomy in a collective of patients after cardiac surgery., Our study underlines a neutral effect of the sternal ZipFix™ system in patients regarding sternal infection. Postoperative complications are similar in both sternal closure methods. The cable-tie-based system is fast, easy to use, reliable and safe.,  Wire closure still remains the preferred technique despite reasonable disadvantages. Associated complications, such as infection and sternal instability, cause time- and cost-consuming therapies. We present a new tool for sternal closure with its first clinical experience and results.METHODS: The sternal ZipFix(TM) System is based on the cable-tie principle. , In our initial evaluation, the short-term results have shown that the sternal ZipFix(TM) can be used safely and effectively. It is fast, easy to use and serves as a potential alternative for traditional wire closure., To determine the difference in sternal infection and other infectious events between conventional wire and cable-tie-based closure techniques post-sternotomy in a collective of patients after cardiac surgery.[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_2953", "sentence1": "Has ivosidenib been FDA approved for use against acute myeloid leukemia?", "sentence2": "The FDA approved ivosidenib for patients with IDH1-mutant relapsed/refractory acute myeloid leukemia. [SEP]", "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_1139", "sentence1": "Are ACTA1 (alpha actin) and NEB (nebulin) genes related to nemaline myopathy?", "sentence2": "Nemaline myopathy (NM) is a group of congenital myopathies, characterized by the presence of distinct rod-like inclusions \"nemaline bodies\" in the sarcoplasm of skeletal muscle fibers. To date, ACTA1, NEB, TPM3, TPM2, TNNT1, and CFL2 have been found to cause NM., Nemaline myopathy (NM) is the most common congenital myopathy and is caused by mutations in various genes including NEB (nebulin), TPM2 (beta-tropomyosin), TPM3 (gamma-tropomyosin), and ACTA1 (skeletal alpha-actin). 20-25% of NM cases carry ACTA1 defects and these particular mutations usually induce substitutions of single residues in the actin protein. , Nemaline myopathy (NM) is a genetically and clinically heterogenous muscle disorder, which is myopathologically characterized by nemaline bodies. Mutations in six genes have been reported to cause NM: Nebulin (NEB Pelin 1999), alpha-skeletal muscle actin (ACTA1 Nowak 1999), alpha-slow tropomyosin (TPM3 Laing 1995), beta-tropomyosin (TPM2 Donner 2002), slow troponin T (TNNT1 Johnston 2000) and cofilin 2 (CFL2 Agrawal 2007). The majority of cases are due to mutation in NEB and ACTA1. , Nemaline myopathy is a heterogenous form of congenital myopathy characterised by a variable spectrum of clinical features, predominated in the severe form by profound muscle hypotonia and weakness accompanied by respiratory insufficiency. The clinical variability, with differing age of onset and severity of symptoms makes the diagnosis of nemaline myopathy difficult in some cases. Severe forms of nemaline myopathy may be caused by mutation of a number of different genes: skeletal muscle actin (ACTA1), nebulin (NEB) and alpha-tropomyosin (TPM3), all of which encode components of the sarcomeric thin filaments of skeletal muscle. , Most nemaline myopathy patients have mutations in the nebulin (NEB) or skeletal muscle alpha-actin (ACTA1) genes. , We report muscle MRI findings of 10 patients from 8 families with nemaline myopathy. Patients with involvement of the nebulin (NEB) gene showed a consistent pattern of selective muscle involvement corresponding to clinical severity., Patients with nemaline myopathy secondary to mutations in the skeletal muscle alpha-actin (ACTA1) gene showed diffuse involvement of thigh and leg muscles with relative sparing of the gastrocnemii., Congenital myopathies are clinical and genetic heterogeneous disorders characterized by skeletal muscle weakness ranging in severity. Three major forms have been identified: actin myopathy, intranuclear rod myopathy, and nemaline myopathy. Nemaline myopathy is the most common of these myopathies and is further subdivided into seven groups according to severity, progressiveness, and age of onset. At present, five genes have been linked to congenital myopathies. These include alpha-actin (ACTA1), alpha- and beta-tropomyosin (TPM3 and TPM2), troponin T (TNNT1), and nebulin (NEB). , Nemaline myopathy is a structural congenital myopathy which may show both autosomal dominant and autosomal recessive inheritance patterns. Mutations in three different genes have been identified as the cause of nemaline myopathy: the gene for slow alpha-tropomyosin 3 (TPM3) at 1q22-23, the nebulin gene (NEB) at 2q21.1-q22, and the actin gene (ACTA1) at 1q42., Nemaline myopathy is a clinically and genetically heterogeneous condition. The clinical spectrum ranges from severe cases with antenatal or neonatal onset and early death to late onset cases with only slow progression. Three genes are known to cause nemaline myopathy: the genes for nebulin (NEB) on chromosome 2q22, slow alpha-tropomyosin (TPM3) on chromosome 1q21 and skeletal muscle alpha-actin (ACTA1) on chromosome 1q42. , Nemaline myopathy (NM) is the most common congenital myopathy and is caused by mutations in various genes including NEB (nebulin), TPM2 (beta-tropomyosin), TPM3 (gamma-tropomyosin), and ACTA1 (skeletal alpha-actin)., Three genes are known to cause nemaline myopathy: the genes for nebulin (NEB) on chromosome 2q22, slow alpha-tropomyosin (TPM3) on chromosome 1q21 and skeletal muscle alpha-actin (ACTA1) on chromosome 1q42., Five genes have now been associated with nemaline myopathy: alpha-tropomyosin-3 (TPM3), alpha-actin (ACTA1), nebulin (NEB), beta-tropomysin (TPM2) and troponin T (TNNT1)., Most nemaline myopathy patients have mutations in the nebulin (NEB) or skeletal muscle alpha-actin (ACTA1) genes., Severe forms of nemaline myopathy may be caused by mutation of a number of different genes: skeletal muscle actin (ACTA1), nebulin (NEB) and alpha-tropomyosin (TPM3), all of which encode components of the sarcomeric thin filaments of skeletal muscle., Five genes have now been associated with nemaline myopathy: alpha-tropomyosin-3 (TPM3), alpha-actin (ACTA1), nebulin (NEB), beta-tropomysin (TPM2) and troponin T (TNNT1)., Three genes are known to cause nemaline myopathy: the genes for nebulin (NEB) on chromosome 2q22, slow alpha-tropomyosin (TPM3) on chromosome 1q21 and skeletal muscle alpha-actin (ACTA1) on chromosome 1q42., Mutations in three different genes have been identified as the cause of nemaline myopathy: the gene for slow alpha-tropomyosin 3 (TPM3) at 1q22-23, the nebulin gene (NEB) at 2q21.1-q22, and the actin gene (ACTA1) at 1q42., Most nemaline myopathy patients have mutations in the nebulin (NEB) or skeletal muscle alpha-actin (ACTA1) genes, Five genes have now been associated with nemaline myopathy: alpha-tropomyosin-3 (TPM3), alpha-actin (ACTA1), nebulin (NEB), beta-tropomysin (TPM2) and troponin T (TNNT1), Three genes are known to cause nemaline myopathy: the genes for nebulin (NEB) on chromosome 2q22, slow alpha-tropomyosin (TPM3) on chromosome 1q21 and skeletal muscle alpha-actin (ACTA1) on chromosome 1q42, Nemaline myopathy (NM) is the most common congenital myopathy and is caused by mutations in various genes including NEB (nebulin), TPM2 (beta-tropomyosin), TPM3 (gamma-tropomyosin), and ACTA1 (skeletal alpha-actin), Five genes have now been associated with nemaline myopathy: alpha-tropomyosin-3 (TPM3), alpha-actin (ACTA1), nebulin (NEB), beta-tropomysin (TPM2) and troponin T (TNNT1), Nemaline myopathy (NM) is the most common congenital myopathy and is caused by mutations in various genes including NEB (nebulin), TPM2 (beta-tropomyosin), TPM3 (gamma-tropomyosin), and ACTA1 (skeletal alpha-actin), Mutations in three different genes have been identified as the cause of nemaline myopathy: the gene for slow alpha-tropomyosin 3 (TPM3) at 1q22-23, the nebulin gene (NEB) at 2q21.1-q22, and the actin gene (ACTA1) at 1q42, Three genes are known to cause nemaline myopathy: the genes for nebulin (NEB) on chromosome 2q22, slow alpha-tropomyosin (TPM3) on chromosome 1q21 and skeletal muscle alpha-actin (ACTA1) on chromosome 1q42, Most nemaline myopathy patients have mutations in the nebulin (NEB) or skeletal muscle alpha-actin (ACTA1) genes, Severe forms of nemaline myopathy may be caused by mutation of a number of different genes: skeletal muscle actin (ACTA1), nebulin (NEB) and alpha-tropomyosin (TPM3), all of which encode components of the sarcomeric thin filaments of skeletal muscle[SEP]Relations: congenital myopathy has relations: disease_protein with TPM3, disease_disease with nemaline myopathy, disease_protein with TPM3, disease_disease with nemaline myopathy. muscle tissue has relations: anatomy_protein_present with TPM3, anatomy_protein_present with TNNT1, anatomy_protein_present with NEB, anatomy_protein_present with TPM3, anatomy_protein_present with TNNT1, anatomy_protein_present with NEB. nemaline myopathy has relations: disease_protein with NEB, disease_disease with congenital myopathy, disease_protein with TNNT1, disease_protein with TPM3, disease_protein with NEB, disease_disease with congenital myopathy, disease_protein with TNNT1, disease_protein with TPM3. alpha-actinopathy has relations: disease_disease with nemaline myopathy, disease_disease with congenital myopathy, disease_disease with nemaline myopathy, disease_disease with congenital myopathy. Myopathy has relations: disease_phenotype_positive with nemaline myopathy, disease_phenotype_positive with nemaline myopathy. Respiratory insufficiency has relations: disease_phenotype_positive with nemaline myopathy, disease_phenotype_positive with nemaline myopathy. TNNT1 has relations: protein_protein with TPM3, disease_protein with nemaline myopathy, protein_protein with TPM3, disease_protein with nemaline myopathy.", "label": "yes"}
{"id": "converted_3186", "sentence1": "Are there any anti-amyloid antibody approved as drug for Alzheimer's disease treatment?", "sentence2": "Treatment with memantine, a noncompetitive NMDA receptor antagonist which is an approved drug for treatment of Alzheimer's disease, rescued protein phosphatase-2A activity by decreasing its demethylation at Leu309 selectively and attenuated Alzheimer's disease-like pathology and cognitive impairment in adeno-associated virus vector-1-I1PP2A rats. , anti-Amyloid agents (13.30%), no new drugs have been approved during the past 15 years; and the available medications are not cost-effective. [SEP]", "label": "no"}
{"id": "converted_46", "sentence1": "Are there web based self management strategies for chronic pain ?", "sentence2": "Fibromyalgia Symptom Reduction by Online Behavioral Self-monitoring, , This study aimed to evaluate effects of a web-based, self-monitoring and symptom management system (SMARTLog) that analyzes personal self-monitoring data and delivers data-based feedback over time., Moderate use (3 times weekly x 3 months) increased likelihood of clinically significant improvements in pain, memory, gastrointestinal problems, depression, fatigue, and concentration; heavy use (4.5 times weekly x five months) produced the above plus improvement in stiffness and sleep difficulties., Results suggest that the tailored online chronic pain management program showed promising effects on pain at 1 and 6 months posttreatment and quality of life at 6 months posttreatment in this naturalistic study., Results suggest the potential value of self-management for chronic pain patients and the potential acceptability of web-based delivery of intervention content., Patient involvement can be fostered by web-based applications combining health information with decision support or behaviour change support. These so-called Interactive Health Communication Applications (IHCAs) can reach great numbers of patients at low financial cost and provide information and support at the time, place and learning speed patients prefer., Web-based interventions may also be effective in enhancing self-management for individuals with chronic pain, but little is known about long-term effects. Research on Web-based interventions to support self-management following participation in pain management programs is limited. OBJECTIVE: The aim is to examine the long-term effects of a 4-week smartphone-intervention [SEP]", "label": "yes"}
{"id": "converted_2562", "sentence1": "Is subacute sclerosing panencephalitis caused by the Measles vaccine?", "sentence2": "Subacute sclerosing panencephalitis (SSPE) is a potentially fatal complication of measles. , Subacute sclerosing panencephalitis (SSPE) is a fatal complication of measles. We reviewed California cases from 1998-2015 to understand risk f, Subacute sclerosing panencephalitis should be eliminated by measles vaccination, The mean interval between measles infection and onset of subacute sclerosing panencephalitis was 6.5 years (range = 3-11 years)., Active surveillance of subacute sclerosing panencephalitis for those with measles infection during the 1988 outbreak is necessary to conduct multicenter drug trials for this devastating disease.<br>, There has been an increasing trend of subacute sclerosing panencephalitis in southern China after the measles outbreak in 1988., The prevalence rate of subacute sclerosing panencephalitis in Hong Kong and Macau in 2002 was 1 per million total population or 5.5 per million children., Because a positive correlation was found between the prevalence of measles and the onset of subacute sclerosing panencephalitis, particularly among children infected at an early age, it is vital to eradicate measles infection by vaccination.<br>, Incidence of subacute sclerosing panencephalitis following measles and measles vaccination in Japan., UNLABELLED Subacute sclerosing panencephalitis (SSPE), in the majority of cases, is caused by the wild measles virus, although there are some reports relating SSPE to vaccination., Subacute sclerosing panencephalitis (SSPE) is a progressive neurodegenerative disease caused by the measles (rubeola) virus and is most often seen in children., There was no indication that measles vaccine can induce SSPE., Subacute Sclerosing Panencephalitis (SSPE), a rare lethal disease of children and young adults due to persistence of measles virus (MeV) in the brain, is caused by wild type (wt) MeV., Subacute sclerosing panencephalitis (SSPE) is a progressive neurological disorder of childhood and early adolescence caused by persistent defective measles virus., Subacute sclerosing panencephalitis (SSPE) is a devastating disease of the central nervous system (CNS) caused by persistent mutant measles virus infection., Subacute sclerosing panencephalitis (SSPE) caused by persistent defective measles virus strains, is a progressive neurological disorder of children and adolescents., Subacute sclerosing panencephalitis (SSPE), in the majority of cases, is caused by the wild measles virus, although there are some reports relating SSPE to vaccination., Measles can persist in the central nervous system and cause subacute sclerosing panencephalitis (SSPE), a progressive disease that is almost always fatal., However, because of the median 8-year interval between measles and onset of SSPE,, The prevention of endemic circulation of measles virus in England and Wales through the high coverage achieved with MMR vaccine, together with the measles/rubella vaccination campaign of 1994, has resulted in the near elimination of SSPE., We applied the polymerase chain reaction (PCR) to detect the measles virus genome in specimens from a 12-year-old boy with SSPE who had received measles vaccine 10 years before and had no history of apparent natural measles. The oligonucleotide primers for PCR were prepared based on the nucleotide sequence of the F and NP genes of the measles virus Edmonston strain.RESULTS: F and NP genes were detected in both the cerebrospinal fluid and peripheral blood lymphocytes. Nucleotide and deduced amino acid sequence analysis of the F gene showed that the patient's virus was different from that of the vaccine strain. Judging from these results, it was likely that the SSPE-associated strain in this case was derived from the wild-type rather than the vaccine strain, subacute sclerosing panencephalitis (SSPE) is a late, rare and usually fatal complication of measles infection., Subacute sclerosing panencephalitis (SSPE) is a chronic central nervous (CNS) system infection caused by measles virus,  Epidemiological and virological data suggest that measles vaccine does not cause SSPE., Subacute sclerosing panencephalitis, a rare, progressive, fatal central nervous system disease of children, is caused by measles virus., Subacute sclerosing panencephalitis is a form of chronic persistent measles encephalitis in childhood which rarely manifests after wild virus infection., Subacute sclerosing panencephalitis is a fatal infectious disease of childhood caused by persistence of the measles virus in the brain. , Subacute sclerosing panencephalitis (SSPE) is a fatal encephalitis manifesting a number of years after a primary measles infection. , Subacute sclerosing panencephalitis (SSPE) is a fatal complication of measles infection., In 2015, the Oregon Health Authority was notified of the death of a boy with subacute sclerosing panencephalitis (SSPE), a rare and fatal complication of measles., Subacute sclerosing panencephalitis (SSPE) is a rare progressive neurological disorder of early adolescence caused by persistent infection of the measles virus, which remains prevalent worldwide despite an effective vaccine. , Subacute Sclerosing Panencephalitis (SSPE) is a debilitating disorder associated with the measles infection in childhood.[SEP]Relations: subacute sclerosing panencephalitis has relations: disease_disease with encephalitis, disease_disease with encephalitis. Nipah virus disease has relations: disease_disease with encephalitis, disease_disease with encephalitis. inherited neurodegenerative disorder has relations: disease_disease with neurodegenerative disease, disease_disease with neurodegenerative disease.", "label": "no"}
{"id": "converted_905", "sentence1": "Are viruses involved in the etiology of human subacute thyroiditis?", "sentence2": "he etiology of subacute (de Quervain's) thyroiditis (SAT) is uncertain, although it probably represents a nonspecific inflammatory response by the thyroid to a variety of viruses., Subacute thyroiditis is an inflammatory disorder of the thyroid caused probably by viruses. I, We believe that the etiologic agent was the Epstein-Barr virus because heterophile and Epstein-Barr virus-specific antibodies were positive., ltogether, these results indicate that the mechanism of inhibition of Spumavirinae infection by interferon differs from that described for the other Retroviridae, and particularly for types B, C and D viruses. Our data is of therapeutic interest since Spumavirinae have been linked to pathological processes such as de Quervain thyroiditis.[SEP]", "label": "yes"}
{"id": "converted_3777", "sentence1": "Does protein ALEX1 contain armadillo repeats?", "sentence2": "ALEX1 (Arm protein lost in epithelial cancers, on chromosome X), contains two armadillo repeats domains, is expressed different in normal and carcinomas tissues., Arm protein lost in epithelial cancers, on chromosome X 1 (ALEX1) is a novel member of the Armadillo family which has two Armadillo repeats as opposed to more than six repeats in the classical Armadillo family members.[SEP]", "label": "yes"}
{"id": "converted_2428", "sentence1": "Is autosomal dominant inheritanced form of Osteogenesis imperfecta caused by mutations in the genes associated with collagen production?", "sentence2": "steogenesis imperfecta (OI) is a heterogeneous bone disorder characterized by recurrent fractures. Although most cases of OI have heterozygous mutations inCOL1A1orCOL1A2and show autosomal dominant inheritance,, Osteogenesis imperfecta (OI) is a group of hereditary disorders characterized by decreased bone mass and increased fracture risk. The majority of OI cases have an autosomal dominant pattern of inheritance and are usually caused by mutations in genes encoding type I collagen,  Osteogenesis imperfecta (OI) is a group of hereditary disorders characterized by low bone mass and recurrent fractures. Most OI cases follow an autosomal dominant pattern of inheritance and are attributed to mutations in genes encoding type I collagen (COL1A1/COL1A2). , Osteogenesis imperfecta (OI) is a genetic disorder characterised by low bone mineral density resulting in fractures. 85-90% of patients with OI carry a variant in the type 1 collagen genes, COL1A1 and COL1A2, which follows an autosomal dominant pattern of inheritance., Osteogenesis imperfecta (OI) comprises a heterogeneous group of disorders that are characterized by susceptibility to bone fractures, and range in severity from a subtle increase in fracture frequency to death in the perinatal period. Most patients have defects in type I collagen biosynthesis with autosomal-dominant inheritance, but many autosomal-recessive genes have been reported., To investigate mutation of COL1A1 gene and analyze the relationship between genotype and clinical phenotype in a family with osteogenesis imperfecta, Dominant inheritance of osteogenesis imperfecta (OI) is caused by mutations in COL1A1 or COL1A2, the genes that encode type I collagen,, Osteogenesis imperfecta (OI) is a heterogeneous group of inherited disorders of bone formation, resulting in low bone mass and an increased propensity to fracture. It exhibits a broad spectrum of clinical severity, ranging from multiple fractures in utero and perinatal death, to normal adult stature and low fracture incidence. Extra-skeletal features of OI include blue sclera, hearing loss, skin hyperlaxity, joint hyperextensibility, and dentinogenesis imperfecta. The proα1(I) and proα2(I) chains of collagen 1 are encoded by the COL1A1 and COL1A2 genes, respectively; quantitative or qualitative defects in type I collagen synthesis usually manifest as types of OI or some sub-types of EDS. The majority of patients (about 90%) with a clinical diagnosis of OI have a mutation in the COL1A1 or COL1A2, Osteogenesis imperfecta (OI) type I is characterized by bone fragility without significant deformity, osteopenia, normal stature, blue sclerae, and autosomal dominant inheritance. Dermal fibroblasts from most affected individuals produce about half the expected amount of type I collagen, suggesting that the OI type I phenotype results from a variety of mutations which alter the apparent expression of either COL1A1 or COL1A2, the genes encoding the chains of type I collagen., Autosomal dominant osteogenesis imperfecta is caused by mutations in the COL1A2 and COL1A1 genes of type I collagen. , Osteogenesis imperfecta is caused by dominant autosomal mutations in the type I collagen coding genes (COL1A1 and COL1A2) in about 85% of individuals, affecting collagen quantity or structure., Osteogenesis imperfecta (OI) is a heterogeneous group of disorders of connective tissue, mainly caused by mutations in the collagen type I genes (COL1A1 and COL1A2)., Autosomal dominant osteogenesis imperfecta (OI) is caused by mutations in the genes (COL1A1 or COL1A2) encoding the chains of type I collagen., In approximately 90% of individuals with osteogenesis imperfecta, mutations in either of the genes encoding the pro-alpha1 or pro-alpha2 chains of type I collagen (COL1A1 or COL1A2) can be identified., Autosomal dominant OI is caused by mutations in the genes (COL1A1 or COL1A2) encoding the chains of type I collagen., ext-generation sequencing technology was used to screen a panel of known OI genes.RESULTS: In 41 probands, we identified 28 different disease-causing variants of 9 different known OI genes. Eleven of the variants are novel. Ten of the 28 variants are located in COL1A1, five in COL1A2, three in BMP1, three in FKBP10, two in TMEM38B, two in P3H1, and one each in CRTAP, SERPINF1, and SERPINH1. , Osteogenesis imperfecta (OI) is a clinically and genetically heterogeneous disorder associated with bone fragility and susceptibility to fractures after minimal trauma. OI type V has an autosomal-dominant pattern of inheritance and is not caused by mutations in the type I collagen genes COL1A1 and COL1A2. , Detection of a high frequency RsaI polymorphism in the human pro alpha 2(I) collagen gene which is linked to an autosomal dominant form of osteogenesis imperfecta., Osteogenesis imperfecta due to recurrent point mutations at CpG dinucleotides in the COL1A1 gene of type I collagen., Osteogenesis imperfecta (OI), commonly known as \"brittle bone disease\", is a dominant autosomal disorder characterized by bone fragility and abnormalities of connective tissue. Biochemical and molecular genetic studies have shown that the vast majority of affected individuals have mutations in either the COL1A1 or COL1A2 genes that encode the chains of type I procollagen. , Osteogenesis imperfecta is normally caused by an autosomal dominant mutation in the type I collagen genes COL1A1 and COL1A2.[SEP]Relations: collagen type I trimer has relations: cellcomp_protein with COL1A2, cellcomp_protein with COL1A1, cellcomp_protein with COL1A2, cellcomp_protein with COL1A1, cellcomp_protein with COL1A2, cellcomp_protein with COL1A1, cellcomp_protein with COL1A2, cellcomp_protein with COL1A1. Hearing impairment has relations: disease_phenotype_positive with dentinogenesis imperfecta, disease_phenotype_positive with dentinogenesis imperfecta. COL1A1 has relations: anatomy_protein_present with connective tissue, protein_protein with COL1A2, anatomy_protein_present with connective tissue, protein_protein with COL1A2. Autosomal dominant inheritance has relations: disease_phenotype_positive with dentinogenesis imperfecta, disease_phenotype_positive with dentinogenesis imperfecta. osteogenesis imperfecta has relations: disease_protein with COL1A2, disease_protein with SERPINH1, disease_protein with SERPINF1, disease_protein with TMEM38B, disease_protein with COL1A1, disease_protein with BMP1, disease_protein with COL1A2, disease_protein with SERPINH1, disease_protein with SERPINF1, disease_protein with TMEM38B, disease_protein with COL1A1, disease_protein with BMP1, disease_protein with COL1A2, disease_protein with SERPINH1, disease_protein with SERPINF1, disease_protein with TMEM38B, disease_protein with COL1A1, disease_protein with BMP1, disease_protein with COL1A2, disease_protein with SERPINH1, disease_protein with SERPINF1, disease_protein with TMEM38B, disease_protein with COL1A1, disease_protein with BMP1. TMEM38B has relations: anatomy_protein_present with connective tissue, anatomy_protein_present with connective tissue. SERPINF1 has relations: anatomy_protein_present with connective tissue, anatomy_protein_present with connective tissue. connective tissue has relations: anatomy_protein_present with COL1A1, anatomy_protein_present with COL1A2, anatomy_protein_present with SERPINH1, anatomy_protein_present with TMEM38B, anatomy_protein_present with BMP1, anatomy_protein_present with SERPINF1, anatomy_protein_present with COL1A1, anatomy_protein_present with COL1A2, anatomy_protein_present with SERPINH1, anatomy_protein_present with TMEM38B, anatomy_protein_present with BMP1, anatomy_protein_present with SERPINF1. Hyperextensibility at elbow has relations: disease_phenotype_positive with dentinogenesis imperfecta, disease_phenotype_positive with dentinogenesis imperfecta. Blue sclerae has relations: disease_phenotype_positive with dentinogenesis imperfecta, disease_phenotype_positive with dentinogenesis imperfecta. SERPINH1 has relations: anatomy_protein_present with connective tissue, anatomy_protein_present with connective tissue.", "label": "yes"}
{"id": "converted_3856", "sentence1": "Does an antiphlogistic promotes inflammation?", "sentence2": "The therapeutic effect of olipiphate was demonstrated for chronic inflammation of advanced arthritis and concanavalin A-related acute edema. The best systemic effect was obtained with 50 mg/kg, symptomatic--100 mg/kg. Skin wounds treated with 5% olipiphate (26 + 2) healed faster than those treated with 2% solcoseryl (30 + 0.8) or in control (33 + 0.6). It was shown histologically that the proliferative and antiphlogistic effect of olipiphate involved no scars., Moreover, we observed an in vitro-inhibition of human neutrophil elastase, a protease involved in the inflammatory process, by extracts and fractions from yarrow, which suggests additional mechanisms of antiphlogistic action., Blood 5-HT in adrenalectomized rats with inflammationadrenalectomized rats 42 days and 3 months old with inflammation after injection of phenylbutazone an increase of 5-HT was observed, but in 18-month-old animals in which antiphlogistic action is highest a decrease of 5-HT was observed., These results indicate that methotrexate is a nonsteroidal antiinflammatory agent, the antiphlogistic action of which is due to increased adenosine release at inflamed sites., The antiphlogistic Ibuprofen incorporated in liposomes caused a decrease of the inflammatory edema induced by Carrageenan in the distal part of the rat's hind leg after both the intramuscular and percutaneous administration., Enhancement of the immunoreactivity inhibition caused by the drugs was not proportional to the increase in their antiphlogistic effects determined by the Selye model of inflammation., Antiinflammatory agents: new series of N-substituted amino acids with complex pyrimidine structures endowed with antiphlogistic activity.,  investigate whether the antiphlogistic ingredient may suppress the inflammatory response to ultraviolet (UV) irradiation, the SPF was determined in vivo. F, Antiphlogistics were found to enhance the membrane viscosity both in control and under inflammation., e in vivo determination of the SPF. Evidence of anti-inflammatory activity of the sunscreen antiphlogistics bisabolol and panthenol was also not apparent in the UV model over a time course of 48 h. Conlusion: The antiphlogistic ingredients panthenol and bisabolol incorporated in the tested sunscreen formula do not interfere with erythema reddening and thus , nts was analyzed in vitro. To investigate whether the antiphlogistic ingredient may suppress the inflammatory response to ultraviolet (UV) irradiation, the , The aim of this study was to analyze the formation of the most relevant inflammation mediators including proteins and lipids in human fibroblasts upon inflammatory stimulation and subsequent treatment with dexamethasone, a powerful antiphlogistic drug.[SEP]Relations: Methotrexate has relations: drug_drug with Ibuprofen, drug_drug with Ibuprofen. Dexamethasone has relations: drug_drug with Ibuprofen, drug_drug with Ibuprofen. Erythema has relations: drug_effect with Ibuprofen, drug_effect with Ibuprofen. Dexpanthenol has relations: drug_drug with Ibuprofen, drug_drug with Ibuprofen. Phenylbutazone has relations: drug_drug with Ibuprofen, drug_drug with Ibuprofen.", "label": "no"}
{"id": "converted_2571", "sentence1": "Can gas vesicles be detected by ultrasound?", "sentence2": "Gas vesicles-genetically encoded protein nanostructures isolated from buoyant photosynthetic microbes-have recently been identified as nanoscale reporters for ultrasound., Here, we demonstrate that genetic engineering of gas vesicles results in nanostructures with new mechanical, acoustic, surface, and functional properties to enable harmonic, multiplexed, and multimodal ultrasound imaging as well as cell-specific molecular targeting. [SEP]", "label": "yes"}
{"id": "converted_2176", "sentence1": "Is dexamethasone recommended for treatment of intracerebral hemorrhage?", "sentence2": "Dexamethasone and other glucocorticoids should be avoided. , During the third interim analysis, the death rate at the 21st day was identical in the two groups (dexamethasone vs. placebo, 21 of 46 vs. 21 of 47; chi-square = 0.01, P = 0.93). In contrast, the rate of complications (mostly infections and complications of diabetes) was much higher in the dexamethasone group (chi-square = 10.89, P less than 0.001), leading to early termination of the study. In the light of the absence of a demonstrable beneficial effect and the presence of a significant harmful effect, current practices of using dexamethasone for treatment of primary supratentorial hemorrhage should be reconsidered., In the light of the absence of a demonstrable beneficial effect and the presence of a significant harmful effect, current practices of using dexamethasone for treatment of primary supratentorial hemorrhage should be reconsidered.[SEP]", "label": "no"}
{"id": "converted_1414", "sentence1": "Are genes symmetrically distributed between leading and lagging DNA strand in bacteria?", "sentence2": "Genomic DNA is used as the template for both replication and transcription, whose machineries may collide and result in mutagenesis, among other damages. Because head-on collisions are more deleterious than codirectional collisions, genes should be preferentially encoded on the leading strand to avoid head-on collisions, as is observed in most bacterial genomes examined., Most genes in bacteria are encoded on the leading strand of replication. This presumably avoids the potentially detrimental head-on collisions that occur between the replication and transcription machineries when genes are encoded on the lagging strand., The majority of bacterial genes are located on the leading strand, genes of some functional categories such as ribosome have higher preferences to be on the leading strands, genes of some functional categories such as transcription factor have higher preferences on the lagging strands, essential genes are more preferentially situated at the leading strand than at the lagging strand, remarkable strand-bias of the distribution of essential genes, Head-on encounters between the replication and transcription machineries on the lagging DNA strand can lead to replication fork arrest and genomic instability. To avoid head-on encounters, most genes, especially essential and highly transcribed genes, are encoded on the leading strand such that transcription and replication are co-directional., Replication-associated purine asymmetry may contribute to strand-biased gene distribution., strand-biased gene distribution (SGD), SGD correlates not only with polC, but also with purine asymmetry (PAS), In bacteria, most genes are on the leading strand of replication, a phenomenon attributed to collisions between the DNA and RNA polymerases., genes whose expression is important for fitness are selected to the leading strand because this reduces the duration of these interruptions, Among prokaryotic genomes, the distribution of genes on the leading and lagging strands of the replication fork is known to be biased. , We show that the evidence they provided is invalid and that the existence of lagging strand encoded genes is explainable by a balance between deleterious mutations that bring genes from the leading to the lagging strand and purifying selection purging such mutants., Based on those experimentally determined for 10 bacteria, we find that essential genes are more preferentially situated at the leading strand than at the lagging strand, for all the 10 genomes studied, confirming previous findings based on either smaller datasets or putatively assigned ones by homology search., The majority of bacterial genes are located on the leading strand, and the percentage of such genes has a large variation across different bacteria., Most genes in bacteria are encoded on the leading strand of replication., This paradox could be explained by assuming that the stronger mutation pressure and selection after inversion preferentially eliminate genes transferred from the leading to the lagging DNA strand., We have shown that the relative number of translocations which have switched positions of genes from the leading to the lagging DNA strand is lower than the number of translocations which have transferred genes from the lagging strand to the leading strand of prokaryotic genomes., Most genes in bacteria are encoded on the leading strand of replication, The majority of bacterial genes are located on the leading strand, and the percentage of such genes has a large variation across different bacteria, We have shown that the relative number of translocations which have switched positions of genes from the leading to the lagging DNA strand is lower than the number of translocations which have transferred genes from the lagging strand to the leading strand of prokaryotic genomes, Using Monte Carlo methods, we have simulated, under experimentally determined directional mutation pressure, the divergence rate and the elimination rate of genes depending on their location in respect to the leading/lagging DNA strands in the asymmetric prokaryotic genome[SEP]", "label": "no"}
{"id": "converted_2430", "sentence1": "Are splicing speckles associated with transcription?", "sentence2": "We show here that RNA splicing speckled domains (splicing speckles) fluctuate in constrained nuclear volumes and remodel their shapes., We present a model where recycling splicing factors return as part of small sub-speckles from distal sites of RNA processing to larger splicing speckles by a directed ATP-driven mechanism through interchromatin spaces., Analysis of a HeLa cell line stably expressing EYFP-NHPX showed that the nucleolar accumulation of NHPX was preceded by its transient accumulation in splicing speckles., In vivo analysis of NHPX reveals a novel nucleolar localization pathway involving a transient accumulation in splicing speckles., \"Splicing speckles\" are major nuclear domains rich in components of the splicing machinery and polyA(+) RNA. Although speckles contain little detectable transcriptional activity, they are found preferentially associated with specific mRNA-coding genes and gene-rich R bands, and they accumulate some unspliced pre-mRNAs, RNA polymerase II transcribes mRNAs and is required for splicing, with some reports suggesting that the inactive complexes are stored in splicing speckle, In normal cell growth conditions GFPeIF4A-III was mainly nucleoplasmic, but in hypoxia stress conditions it moved to the nucleolus and splicing speckles., Localization of eIF4A-III in the nucleolus and splicing speckles is an indicator of plant stress.,  Using antibodies raised against mouse RBM6 to immunostain mammalian cell lines we found that the endogenous protein was both distributed diffusely in the nucleus and concentrated in a small number of nuclear foci that corresponded to splicing speckles/interchromatin granule clusters (IGCs, Subnuclear targeting of the RNA-binding motif protein RBM6 to splicing speckles and nascent transcripts.[SEP]", "label": "no"}
{"id": "converted_3115", "sentence1": "Is lactotransferrin a tumour suppressor?", "sentence2": "LTF (lactotransferrin, or lactoferrin) plays important role in innate immunity, and its anti-tumor function has also been reported in multiple cancers., We previously reported that LTF is significantly down-regulated in nasopharyngeal carcinoma (NPC) and acts as a tumor suppressor by suppressing AKT signaling., The tumor suppressor function of lactotransferrin (LTF) has been reported in a variety of tumors, including GC, nasopharyngeal carcinoma (NPC) and prostate cancer., Lactotransferrin (LTF) has been confirmed to act as a tumor suppressor in multiple cancers, Lactotransferrin acts as a tumor suppressor in nasopharyngeal carcinoma by repressing AKT through multiple mechanisms., LTF is likely to be a candidate tumor suppressor and downregulates the development of NPC by inhibiting NPC proliferation through induction of cell cycle arrest and modulation of the MAPK signaling pathway.[SEP]", "label": "yes"}
{"id": "converted_147", "sentence1": "Has the protein TIEG1 been associated with apoptosis?", "sentence2": "TGF-beta) inducible early gene 1 (TIEG1) is known to induce apoptosis in TGF-beta sensitive pancreatic cancer cells, yet its effect on TGF-beta resistant cancer cells remains unclear, overexpression of TIEG1, protected ALL cells against chemotherapy-induced cell death,  TIEG1 might be involved in mediating this effect from the microenvironment onto the leukemia cells, We also demonstrate that TIEG-1 ectopic expression in CGNPs induces cell cycle arrest that can lead to apoptosis but fails to promote differentiation, TIEG1 acts as an inducer or repressor of gene transcription to enhance the TGFbeta/Smad pathway, as well at other signaling pathways, to regulate cell proliferation, differentiation, and apoptosis., TGFbeta inducible early gene (TIEG1) mimics TGFbeta action and induces apoptosis, the transforming growth factor-beta- (TGF-beta-) inducible early response 1 gene (TIEG1), which plays a pivotal role in TGF-beta-regulated cell growth control and apoptosis, Induction of mRNA for Smad4 and the TGF-beta1-regulated apoptosis-inducing transcription factor TGF-beta1-inducible early gene (TIEG1) was detected within the first 6 h of doxazosin treatmen, TIEG1 (TGF-beta inducible early gene) is a recently characterized transcription factor regulated by TGF-beta that induces apoptosis when overexpressed in pancreatic adenocarcinoma cell lines, Influence of TIEG1 on apoptosis, the influence of TIEG1 on apoptosis of HL-60 cells and the expression of Bcl-2/Bax, The expression of genes involved in insulin resistance (PDK4, AHSG) is increased, together with expression of TIEG1, a transcription factor that can induce apoptosis via the mitochondrial pathway, the overexpression of TIEG1 mediated growth inhibition and apoptosis in TGF-β1-resistant HCC cell lines,, On the other hand, KLF10 deficient keratinocytes showed increased proliferation and apoptosis, LF10, transforming growth factor-β-inducible early gene 1, IEG1 can induce apoptosis of cancer cells, TGF-β inducible early gene 1) plays a significant role in regulating cell proliferation and apoptosis, TIEG1) is a Krüppel-like transcription factor (KLF10) that was originally cloned from human osteoblasts as an early response gene to TGF-β treatment, Adenoviral delivery of TIEG1 (AdTIEG1) to TIEG1(-/-) cells reversed the RANKL-induced NFATc1 signaling defect in TIEG1(-/-) precursors and eliminated the differentiation and apoptosis defects, (TGF)-β inducible early gene (TIEG)-1 is implicated in the control of cell proliferation, differentiation, and apoptosis in some cell types, TIEG1 has been shown to mimic the effects of TGF-beta in various carcinoma cells and plays a critical role in the apoptotic cascade, (TIEG) is a family of primary response genes induced by TGF-beta, which are well recognized in regulating cellular proliferation and apoptosis, In human and murine tissues it has been shown that TIEG1 and TIEG2 induce apoptosis and inhibit cell growth, overexpression of TIEG1 in OLI-neu cells induced apoptosis, (TGF-beta(1))-inducible transcription factors have recently elicited interest because of their critical role in the regulation of cell proliferation, differentiation, and apoptosis, ectopic overexpression of TIEG is sufficient to trigger the apoptotic cell program in these cells[SEP]", "label": "yes"}
{"id": "converted_2533", "sentence1": "Are paralog genes co-regulated?", "sentence2": "Co-regulation of paralog genes in the three-dimensional chromatin architecture., Consequently, paralogs show correlation in gene expression whereby the mechanisms of co-regulation remain unclear. In eukaryotes, genes are regulated in part by distal enhancer elements through looping interactions with gene promoters. These looping interactions can be measured by genome-wide chromatin conformation capture (Hi-C) experiments, which revealed self-interacting regions called topologically associating domains (TADs). We hypothesize that paralogs share common regulatory mechanisms to enable coordinated expression according to TADs. To test this hypothesis, we integrated paralogy annotations with human gene expression data in diverse tissues, genome-wide enhancer-promoter associations and Hi-C experiments in human, mouse and dog genomes. We show that paralog gene pairs are enriched for co-localization in the same TAD, share more often common enhancer elements than expected and have increased contact frequencies over large genomic distances. Combined, our results indicate that paralogs share common regulatory mechanisms and cluster not only in the linear genome but also in the three-dimensional chromatin architecture. This enables concerted expression of paralogs over diverse cell-types and indicate evolutionary constraints in functional genome organization., Paralog genes arise from gene duplication events during evolution, which often lead to similar proteins that cooperate in common pathways and in protein complexes. Consequently, paralogs show correlation in gene expression, We hypothesize that paralogs share common regulatory mechanisms to enable coordinated expression according to TADs., Further, interspecific changes in testis bias of expression are generally correlated within the co-regulated pairs and are anti-correlated within the anti-regulated pairs, suggesting coordinated regulation within both types of paralogous gene pairs., Analysis of the Drosophila melanogaster testes transcriptome reveals coordinate regulation of paralogous genes., Further, interspecific changes in testis bias of expression are generally correlated within the co-regulated pairs and are anti-correlated within the anti-regulated pairs, suggesting coordinated regulation within both types of paralogous gene pairs.<br>, Consequently, paralogs show correlation in gene expression whereby the mechanisms of co-regulation remain unclear., Co-regulation of paralog genes in the three-dimensional chromatin architecture., Further, interspecific changes in testis bias of expression are generally correlated within the co-regulated pairs and are anti-correlated within the anti-regulated pairs, suggesting coordinated regulation within both types of paralogous gene pairs.., We show that paralog gene pairs are enriched for co-localization in the same TAD, share more often common enhancer elements than expected and have increased contact frequencies over large genomic distances. , MiRNA genes are often subject to co-evolutionary changes together with their target transcripts, which may be reflected by differences between paralog mouse and primate miRNA/mRNA pairs., We characterize the collapse over time through the distribution of runs of reduced paralog pairs in duplicated segments., In addition, we identified 81 co-regulated regions on the human genome (RIDGEs) by using expression data from all cancers. Some RIDGEs (28%) consist of paralog genes while another subset (30%) are specifically dysregulated in tumors but not in normal tissues., We conclude that the similarity of hoxb3a/Hoxa3 regulatory mechanisms reflect the shared descent of both genes from a single ancestral paralog group 3 gene., Conserved co-regulation and promoter sharing of hoxb3a and hoxb4a in zebrafish., By analyzing paralogs of testis-biased genes, we identified \"co-regulated\" paralogous pairs in which both genes are testis biased, \"anti-regulated\" pairs in which one paralog is testis biased and the other downregulated in testes, and \"neutral\" pairs in which one paralog is testis biased and the other constitutively expressed.[SEP]", "label": "yes"}
{"id": "converted_1333", "sentence1": "Can cognitive behavioral therapy improve fatigue in cancer patients?", "sentence2": "Physical activity, educational interventions, and cognitive-behavioral therapy have the most supportive data and can be recommended to patients with confidence. , For women undergoing radiotherapy (3 RCTs), hypnosis combined with cognitive-behavioral therapy improved distress and fatigue., Patients in the CBT group reported a significantly larger decrease in fatigue scores than patients in the waiting list group., However, relative to VCBT-I, PCBT-I was associated with significantly greater improvements of insomnia severity, early morning awakenings, depression, fatigue, and dysfunctional beliefs about sleep. , CBT-I may also improve mood, fatigue, and overall quality of life, and can be successfully delivered through a variety of treatment modalities, making it possible to reach a broader range of patients who may not have access to more traditional programs. , No group differences in improvement were noted relative to QOL, fatigue, or mood. , In case of persistent fatigue, personalized cognitive behavioral therapy can be considered., ONCLUSION: The results support CBTH as an evidence-based intervention to control fatigue in patients undergoing radiotherapy for breast cancer. , Severe fatigue after cancer treatment can be treated effectively with cognitive behavioral therapy (CBT), but it is unclear whether CBT has an effect on cognitive functioning., CONCLUSION: CBT for post-cancer fatigue has already been shown to be an effective therapy. , Frequently reported side effects include cancer-related fatigue, peripheral neuropathy, and psychological distress. Exercise and cognitive behavioral therapy interventions have counteracted such adverse effects in other cancer populations. , There is evidence from methodologically rigorous controlled trials that exercise, psycho-educational interventions, and cognitive-behavioral therapy for insomnia are effective in the treatment of CRF, and a wide range of pharmacologic and nonpharmacologic interventions has shown initial promise in single-arm pilot studies with small, heterogeneous samples. , CONCLUSIONS: Physical training combined with cognitive-behavioral therapy and physical training alone had significant and beneficial effects on fatigue compared with no intervention. Physical training was equally effective as or more effective than physical training combined with cognitive-behavioral therapy in reducing cancer-related fatigue, suggesting that cognitive-behavioral therapy did not have additional beneficial effects beyond the benefits of physical training., RESULTS: Imagery/hypnosis and CBT/CST interventions have produced improvement in all the three cancer-related symptoms individually: pain, fatigue, and sleep disturbance., RESULTS: Multilevel modeling indicated that for weekly FACIT fatigue data, there was a significant effect of the CBTH intervention on the rate of change in fatigue (p < .05), such that on average, CBTH participants' fatigue did not increase over the course of treatment, whereas control group participants' fatigue increased linearly., ONCLUSION: The results suggest that CBTH is an effective means for controlling and potentially preventing fatigue in breast cancer radiotherapy patients., Results were consistent with the view that CBTH was effective in managing fatigue and skin discomfort, and increasing relaxation., RESULTS: Participants in the Internet group showed significant improvements at post-assessment compared with those in the control group in overall insomnia severity (F(1,26) = 22.8; p<0.001), sleep efficiency (F(1,24) = 11.45; P = 0.002), sleep onset latency (F(1,24) = 5.18; P = 0.03), soundness of sleep (F(1,24) = 9.34; P = 0.005), restored feeling upon awakening (F(1,24) = 11.95; P = 0.002), and general fatigue (F(1,26) = 13.88; P = 0.001). , Cognitive-behavior therapy (CBT) has alleviated fatigue and improved QOL of cancer patients; however, little is known about the effects of nurse-led CBT on breast cancer patients undergoing radiotherapy., Physical training was equally effective as or more effective than physical training combined with cognitive-behavioral therapy in reducing cancer-related fatigue, suggesting that cognitive-behavioral therapy did not have additional beneficial effects beyond the benefits of physical training., Cognitive-behavior therapy (CBT) has alleviated fatigue and improved QOL of cancer patients; however, little is known about the effects of nurse-led CBT on breast cancer patients undergoing radiotherapy., Physical training was equally effective as or more effective than physical training combined with cognitive-behavioral therapy in reducing cancer-related fatigue, suggesting that cognitive-behavioral therapy did not have additional beneficial effects beyond the benefits of physical training., The positive effects of cognitive behavioral therapy in adolescents with chronic fatigue syndrome are sustained after cognitive behavioral therapy[SEP]Relations: peripheral nervous system disease has relations: disease_disease with peripheral neuropathy, disease_disease with peripheral neuropathy.", "label": "yes"}
{"id": "converted_1563", "sentence1": "Are cyclophilins ubiquitously expressed?", "sentence2": "Cyclophilin from Leishmania donovani (LdCyp) is a ubiquitous peptidyl-prolyl cis-trans isomerase, Cyclophilins (CYPs) and FK506-binding proteins (FKBPs) are ubiquitous proteins belonging to the peptidyl-prolyl cis/trans isomerase (PPIase) family.,  However, their wide distribution and ubiquitous nature signifies their fundamental importance in plant survival., Cyclophilins (Cyps) are ubiquitous proteins that effect the cis-trans isomerization of Pro amide bonds, and are thus crucial to protein folding., FK506 binding proteins (FKBPs) and cyclophilins (CYPs) are abundant and ubiquitous proteins belonging to the peptidyl-prolyl cis/trans isomerase (PPIase) superfamily, which regulate much of metabolism through a chaperone or an isomerization of proline residues during protein folding., Cyclophilin is a ubiquitous peptidyl prolyl cis/trans isomerase that plays critical roles in many biological processes., The receptor for cyclosporin is the protein cyclophilin, which is a ubiquitous peptidylprolyl isomerase. , Cyps (cyclophilins) are ubiquitous proteins of the immunophilin superfamily with proposed functions in protein folding, protein degradation, stress response and signal transduction. , Cyclophilins are folding helper enzymes belonging to the class of peptidyl-prolyl cis-trans isomerases (PPIases; EC 5.2.1.8) that catalyze the cis-trans isomerization of peptidyl-prolyl bonds in proteins. They are ubiquitous proteins present in almost all living organisms analyzed to date, with extremely rare exceptions., Immunophilins are ubiquitous enzymes responsible for proline isomerisation during protein synthesis and for the chaperoning of several membrane proteins., Cyclophilins (CyPs) are a large class of highly conserved ubiquitous peptidyl-prolyl cis-trans isomerases., Cyclophilins belong to the family of peptidyl-prolyl cis/trans isomerases (PPIases), which are ubiquitous and highly conserved enzymes capable of cis/trans isomerizing Xaa-Pro peptide bonds. , Originally identified as the cellular targets of immunosuppressant drugs, the immunophilins encompass two ubiquitous protein families: the FK-506 binding proteins or FKBPs, and the cyclosporin-binding proteins or cyclophilins.[SEP]", "label": "yes"}
{"id": "converted_4559", "sentence1": "Is there an association between pyostomatitis vegetans and Crohn's disease?", "sentence2": "Among the main oral manifestations of IBD are cobblestoning of the oral mucosa, labial swellings with vertical fissures, pyostomatitis vegetans, angular cheilitis, perioral erythema, and glossitis. , Pyostomatitis Vegetans: A Clue for Diagnosis of Silent Crohn's Disease., We present a case of Pyostomatitis vegetans involving gingiva and oral mucosa with no skin lesion which led to the diagnosis of Crohn's disease to emphasize important role of dentists in diagnosis of rare oral lesions and management of patients' systemic disease., Moreover, in both CD and UC, there occur several other inflammatory skin conditions such as erythema nodosum, pyoderma gangrenosum, hidradenitis suppurativa, chronic oral aphthous disease, Sweet syndrome, pyostomatitis vegetans, and bowel-associated dermatosis-arthritis syndrome. , Diffuse mucosal swelling, cobblestone mucosa, localised mucogingivitis, deep linear ulceration, fibrous tissue tags, polyps, nodules, pyostomatitis vegetans, and aphthous-like ulcers have been described in Crohn's disease. , Aphthous stomatitis and pyostomatitis vegetans are among non-specific oral manifestations of IBD., Pyostomatitis vegetans (PV) is a rare, chronic mucocutaneous disorder associated with inflammatory bowel disease (IBD). Oral lesions of PV are distinct and present as multiple white or yellow pustules with an erythematous base that coalesce and undergo necrosis to form a typical \"snail tracks\" appearance. Two cases of PV associated with IBD--one with Crohn's disease (CD) and the other with ulcerative colitis (UC) are reported.,  Oral involvement during IBD includes several types of lesions: the most common are aphthae; uncommon lesions include, among others, pyostomatitis vegetans and granulomatous lesions of CD. , Pyostomatitis vegetans (PV) is a rare condition characterized by pustules that affect the oral mucosa. It is a highly specific marker for inflammatory bowel disease and its correct recognition may lead to the diagnosis of ulcerative colitis or Crohn's disease. , matitis and pyostomatitis vegetans are among non-specific oral manifestations of IBD. In differe, on-specific manifestations, such as aphthous stomatitis and angular cheilitis, occur in both diseases, while pyostomatitis vegetans is more pronounced in patients with UC. Non-specific lesio, ment during IBD includes several types of lesions: the most common are aphthae; uncommon lesions include, among others, pyostomatitis vegetans and granulomatous lesions of CD. Starting wit, s ulcers, pyostomatitis vegetans, cobblestoning and gingivitis are important oral findings frequently observed in IBD patients. Their p, e main oral manifestations of IBD are cobblestoning of the oral mucosa, labial swellings with vertical fissures, pyostomatitis vegetans, angular cheilitis, perioral erythema, and glossitis. In this sen, Pyostomatitis vegetans is frequently associated with chronic inflammatory bowel diseases and can, thus, give a diagnostic hint at an existing ulcerative colitis or Crohn’s disease., Oral Crohn's disease and pyostomatitis vegetans. An unusual association., [Pyostomatitis vegetans and Crohn's disease. A specific association of 2 diseases]., osis of Crohn's disease. Clinical manifestations improved dramatically with prednisone.DISCUSSION: This case of pyostomatitis-pyodermatitis vegetans involved several aspects rarely reported in the literature: a) the cutaneomucosal signs were inaugural; b) the association with Crohn's disease; c) the presence of lesions to the genital mucosa; d) the unusual localization , Pyostomatitis vegetans is a specific marker for ulcerative colitis and Crohn's disease., The pathogenetic interrelationship between pyostomatitis vegetans and Crohn's disease is discussed., Successful treatment with infliximab and methotrexate of pyostomatitis vegetans associated with Crohn's disease., Infliximab and methotrexate may be a promising treatment for the rare cases of pyostomatitis vegetans associated with Crohn's disease., INTRODUCTION: Pyostomatitis vegetan (PV) is often associated with chronic inflammatory bowel disease (IBD).OBSERVATION: Tw[SEP]Relations: Methotrexate has relations: contraindication with inflammatory bowel disease, contraindication with inflammatory bowel disease. inflammatory bowel disease has relations: disease_phenotype_positive with Crohn's disease, disease_phenotype_positive with Crohn's disease, disease_phenotype_positive with Crohn's disease, disease_phenotype_positive with Crohn's disease. Pustule has relations: disease_phenotype_positive with pyoderma gangrenosum, disease_phenotype_positive with pyoderma gangrenosum. Oral ulcer has relations: disease_phenotype_positive with inflammatory bowel disease, disease_phenotype_positive with inflammatory bowel disease.", "label": "yes"}
{"id": "converted_2970", "sentence1": "Does allele phasing improve the phylogenetic utility of ultraconserved elements?", "sentence2": "Allele Phasing Greatly Improves the Phylogenetic Utility of Ultraconserved Elements., Our empirical analyses of Ultraconserved Element (UCE) locus data collected from the South American hummingbird genus Topaza demonstrate that phased allele sequences carry sufficient phylogenetic information to infer the genetic structure, lineage divergence, and biogeographic history of a genus that diversified during the last three million years. The phylogenetic results support the recognition of two species, and suggest a high rate of gene flow across large distances of rainforest habitats but rare admixture across the Amazon River. Our simulations provide evidence that analyzing allele sequences leads to more accurate estimates of tree topology and divergence times than the more common approach of using contig sequences., Allele Phasing Greatly Improves the Phylogenetic Utility of Ultraconserved Elements.Advances in high-throughput sequencing techniques now allow relatively easy and affordable sequencing of large portions of the genome, even for nonmodel organisms. [SEP]", "label": "yes"}
{"id": "converted_2792", "sentence1": "Is celecoxib effective for treatment of amyotrophic lateral sclerosis?", "sentence2": "NTERPRETATION: At the dosage studied, celecoxib did not have a beneficial effect on research subjects with ALS, and it was safe. A biological effect of celecoxib was not demonstrated in the cerebrospinal fluid. Further studies of celecoxib at a dosage of 800 mg/day in ALS are not warranted., Prostaglandin E(2) levels in cerebrospinal fluid were not elevated at baseline and did not decline with treatment.<br><b>INTERPRETATION</b>: At the dosage studied, celecoxib did not have a beneficial effect on research subjects with ALS, and it was safe.[SEP]", "label": "no"}
{"id": "converted_874", "sentence1": "Is cystatin C or cystatin 3 used as a biomarker of kidney function?", "sentence2": "to explore the effect of ageing on renal function with cystatin C as the marker of glomerular filtration rate (GFR) in the general population without vascular disease or diabetes., Cystatin C, a more specific kidney function biomarker, was also elevated at 24 h after CLP., This study evaluated FGF-23 as well as traditional markers of kidney disease, namely urine albumin-to-creatinine ratio (UACR) and creatinine-cystatin C estimated GFR (eGFRCrCyC), as risk factors for AKI in elderly individuals. , he primary predictor was estimated GFR (eGFR) calculated using serum cystatin C (eGFR(cys))., A number of recent reports have suggested that the cystatin C/creatinine (CysC/Cr) ratio might be a useful biomarker of renal function in pediatric patients., The CKD-EPI equation using cystatin C was the most precise method of renal function evaluation in patients with neurogenic bladder., Serum cystatin C (CysC) is an endogenous marker of kidney function., The urinary content of CysC reflects tubular epithelial dysfunction whereas that of NGAL also characterizes tubular atrophy., Estimated kidney function based on serum cystatin C , : Several formulas for glomerular filtration rate (GFR) estimation, based on serum creatinine or cystatin C, have been proposed. , he highest and lowest eGFR levels corresponded to the cystatin C-based and MDRD-4 equations, respectively. , The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) recently proposed an equation to estimate GFR in subjects without cirrhosis using both serum creatinine and cystatin C levels., Emerging evidence has shown that cystatin C may improve classification of glomerular filtration rate for defining chronic kidney disease in certain clinical populations and assist in understanding the complications of chronic kidney disease, Beta-trace protein (BTP) and cystatin C (CysC) are novel biomarkers of renal function. , Cystatin C could improve chronic kidney disease (CKD) classification in HIV-infected women relative to serum creatinine.,  Iohexol clearance and cystatin C formulae identify a greater proportion of patients with a GFR <60 mL/min/1.73 m(2), which also predicts the development of AKI.,  Cystatin C was recently reported to be an endogenous surrogate of kidney function, and a high level of cystatin C is reported to be a strong predictor of CVD;, Studies that have simultaneously compared measured GFR and estimated GFR (using endogenous filtration markers such as creatinine, or newer ones such as cystatin C or β-trace protein)[SEP]", "label": "yes"}
{"id": "converted_2486", "sentence1": "Is vorinostat effective for glioblastoma?", "sentence2": "Conclusions: Vorinostat combined with standard chemoradiation had acceptable tolerability in newly diagnosed glioblastoma. Although the primary efficacy endpoint was not met, vorinostat sensitivity and resistance signatures could facilitate patient selection in future trials., LESSONS LEARNED: Combination regimen with bevacizumab (BEV) and vorinostat is well tolerated in patients with recurrent glioblastoma., CONCLUSION: Combination treatment of BEV and VOR was well tolerated. This combination therapy for this study population did not improve PFS6 or median OS when compared with BEV monotherapy., We present two patients with glioblastoma multiforme who developed severe hemolytic anemia shortly after initiating therapy with vorinostat, a pan-active histone deacetylase inhibitor, while on prophylactic dapsone., Vorinostat is the most advanced HDAC inhibitor that entered clinical trials in glioblastoma, showing activity in recurrent disease. Multiple phase II trials with vorinostat in combination with targeted agents, temozolomide and radiotherapy are currently recruiting. , . On the basis of the results of this phase II study, further evaluation of the vorinostat-bortezomib combination in GBM patients in this dose and schedule is not recommended., ith the increased toxicities associated with CPT-11 coupled with its unclear clinical significance, investigating the efficacy of vorinostat combined with bevacizumab alone may represent a more promising strategy to evaluate in the context of a phase II clinical trial., CONCLUSION: Vorinostat in combination with temozolomide is well tolerated in patients with HGG. A phase I/II trial of vorinostat with radiotherapy and concomitant TMZ in newly diagnosed glioblastoma is underway.[SEP]Relations: Temozolomide has relations: drug_drug with Vorinostat, drug_drug with Vorinostat. Bevacizumab has relations: drug_drug with Vorinostat, drug_drug with Vorinostat.", "label": "no"}
{"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_745", "sentence1": "Is rivaroxaban metabolized in kidneys?", "sentence2": "The novel oral anticoagulants (i.e., dabigatran, apixaban, rivaroxaban) all undergo renal metabolism to varying degrees, and hence dosing, efficacy, and safety require special consideration in CKD patients., The new oral anticoagulants have relatively little data in patients with severe renal impairment, and all have an element of renal excretion., Now new anticoagulant drugs(dabigatran and rivaroxaban) can become available. Therefore, we have to learn how to use those drugs. They have to carefully be used because they discharge from kidney and old aged patients have potential renal dysfunction. , In the everyday practice it will be necessary to be very cautious in patients with impaired renal function, as all these drugs are eliminated by kidneys., Dabigatran etexilate and rivaroxaban carry the highest risk due to a high degree of renal excretion, whereas the risk for apixaban, edoxaban and betrixaban seems lower., However, all these agents undergo renal clearance to varying degrees, and hence dosing, efficacy, and safety require special consideration in patients with CKD. , Rivaroxaban being excreted via kidney and liver, some precautions should apply in case of liver insufficiency. , Rivaroxaban elimination is mainly renal, but also through faecal matter and by hepatic metabolism. [SEP]Relations: Rivaroxaban has relations: drug_drug with Dabigatran etexilate, drug_drug with Dabigatran etexilate. Edoxaban has relations: drug_drug with Dabigatran etexilate, drug_drug with Dabigatran etexilate. Apixaban has relations: drug_drug with Dabigatran etexilate, drug_drug with Dabigatran etexilate. Dabigatran has relations: drug_drug with Dabigatran etexilate, drug_drug with Dabigatran etexilate. Betrixaban has relations: drug_drug with Dabigatran etexilate, drug_drug with Dabigatran etexilate.", "label": "yes"}
{"id": "converted_1739", "sentence1": "Is there a relationship between thyroid hormone altered metabolism and coronary artery disease?", "sentence2": "The results showed that higher levels of TSH within the reference range were independently associated with the presence of CAD only among subjects less than or equal to 65 years old, suggesting age might influence the relationship., FT3 levels within the normal range were inversely correlated with the presence and severity of CAD. Moreover, lower FT3 concentrations were correlated with the Gensini score and independently predicted the presence and severity of CAD., High TSH within the reference range was associated with increased risk of coronary death in women (P(trend) 0·005), but not in men. The risk of coronary death was also increased among women with subclinical hypothyroidism or subclinical hyperthyroidism, compared to women with TSH of 0·50-1·4 mU/l. ,  Prevalence of CHD was more common in hypothyroid and moderate SCH patients., The angiographic results were as follows: significant coronary disease (SH 28.1% vs. non-SH 43.8%; p=0.087); three-vessel disease (9.4% vs. 9.9%; p=0.919); two-vessel disease (12.5% vs. 13.4%; p=0.892); single-vessel disease (6.3% vs. 29.5%; p=0.051); minimal lesions (9.4% vs. 10.9%; p=0.794); and no coronary disease (62.4% vs, 45.3%; p=0.064)., Lower fT3 levels were predictive of both single-vessel (p = 0.012) and multivessel (p = 0.009) CAD. Through a multivariate logistic regression analysis, fT3 was still linked to the presence of CAD (hazard ratio [HR]: 0.48, 95% confidence interval [CI]: 0.34-0.68, p < 0.001)., Our study showed that FT(4) levels were associated with the presence and the severity of CAD. Also, this study suggests that elevated serum FT(4) levels even within normal range could be a risk factor for CAD. , The present meta-analysis indicates that sub-clinical hypothyroidism is associated with both, a significant risk of CHD at baseline and at follow-up., The incidence of multi-vessel disease was higher in patients with high TSH level (p=0.026). TSH level showed a significant correlation with age (r=0.109, p=0.044) and Gensini's score (r=0.117, p=0.045). The multivariate analysis revealed that age (OR 2.39, p=0.001), diabetes (OR 3.74, p=0.001), creatinine (OR 2.06, p=0.008), and smoking (OR 1.85, p=0.045) were independent predictors for significant coronary artery disease, but TSH level did not predict coronary artery stenosis., These data in patients referred for coronary angiography suggest that variation of thyroid function within the statistical normal range may influence the presence and severity of coronary atherosclerosis.[SEP]Relations: coronary stenosis has relations: disease_disease with coronary artery disease, disease_disease with coronary artery disease.", "label": "yes"}
{"id": "converted_3788", "sentence1": "Is Semagacestat effective for Alzheimer's Disease?", "sentence2": "However, a large phase 3 trial of semagacestat, a potential non-transition state analog (non-TSA) GSI, in patients with Alzheimer's disease (AD) was terminated due to unexpected aggravation of cognitive deficits and side effects. , BACKGROUND: In a recent report, 76 weeks' treatment with a gamma-secretase inhibitor (semagacestat) was associated with poorer cognitive outcomes in Alzheimer's disease (AD)., CONCLUSION: In participants with mild to moderate AD, high dose semagacestat treatment was associated with greater severity and faster worsening of NPS in a pattern resembling an agitated depression. , INTRODUCTION: The negative efficacy study examining the γ-secretase inhibitor semagacestat in mild to moderate Alzheimer's disease (AD) included a number of biomarkers of the disease as well as safety outcomes., A clinical trial with the wide-spectrum γ-secretase inhibitor semagacestat has, however, demonstrated that global inhibition of all γ-secretases causes serious toxicity. , ESULTS: Semagacestat treatment was associated with increased reporting of suspected Notch-related adverse events (gastrointestinal, infection, and skin cancer related). Other relevant safety findings associated with semagacestat treatment included cognitive and functional worsening, skin-related TEAEs, renal and hepatic changes, increased QT interval, and weight loss. , CONCLUSIONS: As compared with placebo, semagacestat did not improve cognitive status, and patients receiving the higher dose had significant worsening of functional ability., RESULTS: The trial was terminated before completion on the basis of a recommendation by the data and safety monitoring board., The ADAS-cog scores worsened in all three groups (mean change, 6.4 points in the placebo group, 7.5 points in the group receiving 100 mg of the study drug, and 7.8 points in the group receiving 140 mg; P=0.15 and P=0.07, respectively, for the comparison with placebo). The ADCS-ADL scores also worsened in all groups (mean change at week 76, -9.0 points in the placebo group, -10.5 points in the 100-mg group, and -12.6 points in the 140-mg group; P=0.14 and P<0.001, respectively, for the comparison with placebo). Patients treated with semagacestat lost more weight and had more skin cancers and infections, treatment discontinuations due to adverse events, and serious adverse events (P<0.001 for all comparisons with placebo). , Recently disclosed Phase III findings on semagacestat indicated that Alzheimer's disease (AD) patients on this drug showed significantly worsened cognitive function compared to those treated with placebo., The recent failure of semagacestat in two large Phase III studies questions the value of γ-secretase inhibitors in treating Alzheimer's disease., ntly disclosed Phase III findings on semagacestat indicated that Alzheimer's disease (AD) patients on this drug showed significantly worsened cognitive function compared to those treated with placebo. Since, ts from Phase III studies showed that semagacestat failed to slow disease progression, and it was associated with worsening of clinical measures of cognition and the ability to perform activities of daily living. Furthermore, sem, rge Phase III clinical trials of semagacestat in mild-to-moderate AD patients were prematurely interrupted because of the observation of a detrimental cognitive and functional effect of the drug. These detrimental ef, BACKGROUND: In a recent report, 76 weeks' treatment with a gamma-secretase inhibitor (semagacestat) was associated with poorer cognitive outcomes in Alzheimer's d, However, a large phase 3 trial of semagacestat, a potential non-transition state analog (non-TSA) GSI, in patients with Alzheimer's disease (AD) was terminated due to unexpected aggravation of cognitive deficits and side effects., However, the preliminary equivocal cognitive results obtained with bapineuzumab as well as the detrimental cognitive effects observed with semagacestat, a potent γ-secretase inhibitor, raise the possibility that targeting Aβ may not be clinically efficacious in AD.[SEP]", "label": "no"}
{"id": "converted_2159", "sentence1": "Is autophagy the process where bacteria ingest viral particles?", "sentence2": "Autophagy, a cellular degradation process, Autophagy, a form of lysosomal degradation capable of eliminating dysfunctional proteins and organelles, is a cellular process associated with homeostasis., Autophagy, a programmed process in which cell contents are delivered to lysosomes for degradation, appears to have both tumor-suppressive and tumor-promoting functions; both stimulation and inhibition of autophagy have been reported to induce cancer cell death, and particular genes and proteins have been associated both positively and negatively with autophagy, Autophagy is a lysosome-mediated catabolic process involving the degradation of intracellular contents (e.g., proteins and organelles) as well as invading microbes (e.g., parasites, bacteria and viruses)., Autophagy is a cellular process that targets proteins, lipids and organelles to lysosomes for degradation, but it has also been shown to combat infection with various pathogenic bacteria., Autophagy, an intracellular degradation process highly conserved from yeast to humans, is viewed as an important defence mechanism to clear intracellular bacteria., Autophagy has intracellular anti-viral and anti-bacterial functions, and plays a role in the initiation of innate and adaptive immune system responses to viral and bacterial infections., documented abundant autophagy within VZV-infected cells throughout the infectious cycle but also demonstrated that VZV-induced autophagy facilitated VZV glycoprotein biosynthesis and processing., Autophagy is a highly conserved process by which cells can recycle organelles and proteins by degrading them in the lysosomes.[SEP]", "label": "yes"}
{"id": "converted_4606", "sentence1": "Is REGN5458 a single-targeted antibody?", "sentence2": "CD3-engaging bispecific antibodies (bsAbs) and chimeric antigen receptor (CAR) T cells are potent therapeutic approaches for redirecting patient T cells to recognize and kill tumors. Here we describe a fully human bsAb (REGN5458) that binds to B-cell maturation antigen (BCMA) and CD3, and compare its antitumor activities vs those of anti-BCMA CAR T cells to identify differences in efficacy and mechanism of action. [SEP]", "label": "no"}
{"id": "converted_724", "sentence1": "Are there any clinical trials of the effect of evening primrose oil on postmenopausal symptoms ?", "sentence2": "To analyze whether the time (morning/evening) of administration of a compound containing 60 mg of dry soy seed extract (glycine max) with 40% of total isoflavones, primrose oil and α-tocopherol modifies the effect on the climacteric syndrome., The object of this study was to evaluate the effect of different doses of a compound containing isoflavones 60 mg, primrose oil 440 mg and vitamin E 10 mg. (IOVE) on menopausal complaints. This was an open, multicentre, randomised, group comparative, efficacy and safety trial., Emphasis was placed on randomized, double-blind, placebo-controlled clinical trials, as these provide the best efficacy and safety data, Nonprescription therapies reviewed include black cohosh, dong quai, evening primrose oil, physical activity, phytoestrogens, and red clover, The effect of oral evening primrose oil on menopausal hot flashes: a randomized clinical trial., The aim of this study was to compare the efficacy of evening primrose with placebo in improvement of menopausal hot flashes. ,  The application of oral evening primrose oil compared with placebo for controlling hot flashes may decrease more the intensity of attacks , Our search identified 58 randomised controlled trials of which 11 involved the use of clonidine, six for SSRIs, four for gabapentin, seven for black cohosh, seven for red clover, 18 for phytoestrogens, two for ginseng, one for evening primrose,, Single clinical trials have found no benefit for dong quai, evening primrose oil,, Single clinical trials have found that dong quai, evening primrose oil,, To evaluate the efficacy of gamolenic acid provided by evening primrose oil in treating hot flushes and sweating associated with the menopause. DESIGN: Randomised, double blind, placebo controlled study.[SEP]", "label": "yes"}
{"id": "converted_2887", "sentence1": "Is the enzyme ERAP2 associated with the disease birdshot chorioretinopathy?", "sentence2": "Allele-specific Alterations in the Peptidome Underlie the Joint Association of HLA-A*29:02 and Endoplasmic Reticulum Aminopeptidase 2 (ERAP2) with Birdshot Chorioretinopathy., BSCR is also associated with endoplasmic reticulum aminopeptidase 2 (ERAP2), an enzyme involved in processing HLA class I ligands, thus implicating the A*29:02 peptidome in this disease. , A genome-wide association study identifies a functional ERAP2 haplotype associated with birdshot chorioretinopathy.[SEP]Relations: ERAP1 has relations: protein_protein with ERAP2, protein_protein with ERAP2.", "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_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_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_3037", "sentence1": "Are there graph kernel libraries available implemented in JAVA?", "sentence2": "graphkernels: R and Python packages for graph comparison., Measuring the similarity of graphs is a fundamental step in the analysis of graph-structured data, which is omnipresent in computational biology. Graph kernels have been proposed as a powerful and efficient approach to this problem of graph comparison. Here we provide graphkernels, the first R and Python graph kernel libraries including baseline kernels such as label histogram based kernels, classic graph kernels such as random walk based kernels, and the state-of-the-art Weisfeiler-Lehman graph kernel. The core of all graph kernels is implemented in C ++ for efficiency. Using the kernel matrices computed by the package, we can easily perform tasks such as classification, regression and clustering on graph-structured samples.[SEP]", "label": "no"}
{"id": "converted_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_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_3042", "sentence1": "Is Semagacestat effective for treatment of Alzheimer's disease?", "sentence2": "However, a large phase 3 trial of semagacestat, a potential non-transition state analog (non-TSA) GSI, in patients with Alzheimer's disease (AD) was terminated due to unexpected aggravation of cognitive deficits and side effects., BACKGROUND: In a recent report, 76 weeks' treatment with a gamma-secretase inhibitor (semagacestat) was associated with poorer cognitive outcomes in Alzheimer's disease (AD)., A clinical trial with the wide-spectrum γ-secretase inhibitor semagacestat has, however, demonstrated that global inhibition of all γ-secretases causes serious toxicity. , OBJECTIVE: Semagacestat, a γ-secretase inhibitor, demonstrated an unfavorable risk-benefit profile in a Phase 3 study of patients with Alzheimer's disease (IDENTITY trials), and clinical development was halted. , CONCLUSIONS: As compared with placebo, semagacestat did not improve cognitive status, and patients receiving the higher dose had significant worsening of functional ability. Semagacestat was associated with more adverse events, including skin cancers and infections., BACKGROUND\nIn a recent report, 76 weeks' treatment with a gamma-secretase inhibitor (semagacestat) was associated with poorer cognitive outcomes in Alzheimer's disease (AD)., Semagacestat was associated with more adverse events, including skin cancers and infections., CONCLUSIONS\nAs compared with placebo, semagacestat did not improve cognitive status, and patients receiving the higher dose had significant worsening of functional ability., OBJECTIVE\nSemagacestat, a γ-secretase inhibitor, demonstrated an unfavorable risk-benefit profile in a Phase 3 study of patients with Alzheimer's disease (IDENTITY trials), and clinical development was halted., Recently disclosed Phase III findings on semagacestat indicated that Alzheimer's disease (AD) patients on this drug showed significantly worsened cognitive function compared to those treated with placebo., The recent failure of semagacestat in two large Phase III studies questions the value of γ-secretase inhibitors in treating Alzheimer's disease., A phase 3 trial of semagacestat for treatment of Alzheimer's disease.As compared with placebo, semagacestat did not improve cognitive status, and patients receiving the higher dose had significant worsening of functional ability. , Preliminary results from Phase III studies showed that semagacestat failed to slow disease progression, and it was associated with worsening of clinical measures of cognition and the ability to perform activities of daily living. , Changes in Neuropsychiatric Inventory Associated with Semagacestat Treatment of Alzheimer's Disease.In participants with mild to moderate AD, high dose semagacestat treatment was associated with greater severity and faster worsening of NPS in a pattern resembling an agitated depression. , Patients treated with semagacestat lost more weight and had more skin cancers and infections, treatment discontinuations due to adverse events, and serious adverse events (P<0.001 for all comparisons with placebo)., <b>OBJECTIVE</b>: Semagacestat, a γ-secretase inhibitor, demonstrated an unfavorable risk-benefit profile in a Phase 3 study of patients with Alzheimer's disease (IDENTITY trials), and clinical development was halted., Other relevant safety findings associated with semagacestat treatment included cognitive and functional worsening, skin-related TEAEs, renal and hepatic changes, increased QT interval, and weight loss., Patients treated with semagacestat lost more weight and had more skin cancers and infections, treatment discontinuations due to adverse events, and serious adverse events (P&lt;0.001 for all comparisons with placebo)., Semagacestat, a γ-secretase inhibitor, demonstrated an unfavorable risk-benefit profile in a Phase 3 study of patients with Alzheimer's disease (IDENTITY trials), and clinical development was halted.[SEP]", "label": "no"}
{"id": "converted_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_4221", "sentence1": "Does a comet assay measure radiation induced mutations?", "sentence2": "Evaluation of primary DNA-damage is one way to identify potential genotoxic agents and for this purpose the Comet assay has, for the last decades, been used to monitor DNA single strand and double strand breaks in individual cells, DNA strand-break frequency was examined by means of the comet assay i, . The comet assay (as this method was subsequently named) was able to measure, for the first time, the fraction of radiobiologically hypoxic cells in mouse and human tumors. It was used to determine that the rate of rejoining of DNA breaks was relatively homogenous within an irradiated population of cells, The comet assay is frequently used to measure DNA damage in individual cells. , Thus a complete repair of DNA damage induced by gamma-irradiation and measurable by the Comet assay was observed, whereas the yield of somatic mutations increased in relation to the radiation dose., xanthi) mutagenicity assay is the ability to analyze and compare on the same plants under identical treatment conditions both the induced acute DNA damage in somatic cells as measured by the Comet assay and the yield of induced leaf somatic mutations., The present study reveals that gamma radiation induces single strand breaks in DNA as measured by alkaline comet assay in bivalves and comet assay serves as a sensitive and rapid method to detect genotoxicity of gamma radiation., The present study is aimed (a) to know the genotoxic effect of gamma radiation on aquatic fauna employing two species of selected bivalves, (b) to evaluate the possible use of 'Comet assay' for detecting genetic damage in haemocytes of bivalves as a biomarker for environmental biomonitoring and also (c) to compare the relative sensitivity of two species of bivalves viz., The single cell gel electrophoresis (SCGE) assay, more commonly known as the comet assay, due to the \"comet-like\" appearance of the cells, was originally developed as a technique to measure the presence of DNA single-strand breaks., BACKGROUND: The neutral comet assay was devised to measure double-stranded DNA breaks, but it has also been used to measure apoptosis based on its characteristic DNA fragmentation patterns., 2, 4, 6, 8 and 10 Gy) of gamma radiation and their genotoxic effects on the haemocytes were studied using the comet assay., PURPOSE: The Deoxyribonucleic Acid (DNA) Comet assay, being a quick, simple, sensitive, reliable and fairly inexpensive method for measuring DNA strand breaks, has been used to assess DNA damage caused by gamma radiation in developmental stages of maize weevil Sitophilus zeamais Motschulsky., This paper attempts a correlation between the induction and repair of DNA damage measured in the comet assay and the clinical observed reaction in order to evaluate the suitability of the comet assay for prediction of radiation sensitivity., gle cell gel electrophoresis (e.g., Comet Assay) and immunofluoresence microscopy to detect the presence of gamma-H2AX foci, we find that Cr[VI] induces DNA double-strand breaks similar to ionizing radiation (IR). We also demo, ir of DNA damage induced by gamma-irradiation and measurable by the Comet assay was observed, whereas the yield of somatic mutations increased in relation to the radiation dose. Data on the kinetic, eased yield of somatic mutations was highly correlated (r = 0.996) with the increased DNA damage measured by the Comet assay immediately after irradiation. With inc, rther assess potential co-mutagenic effects of FA, we exposed A549 human lung cells to FA in combination with various mutagens and measured the induction and removal of DNA damage by the comet assay and the production of chromosomal mutations by the cytokinesis-block micronucleus assay (CBMN assay). The , DNA effects were analysed in leukocytes using the alkaline Comet assay, gene mutations and chromosome aberrations were measured in erythrocytes using the flow cytometric Pig-a gene mutation assay and the micronucleus test (applying both microscopic and flow cytometric evaluation), respectively., A wide variety of mutagens have been shown to cause DNA alterations detectable with the comet assay, but it is not yet clear whether a relationship exists between the DNA effects and the induction of mutations., The transgenerational changes in mutation rates were attributed to the presence of a persistent subset of endogenous DNA lesions (double- and single-strand breaks), measured by the phosphorylated form of histone H2AX (gamma-H2AX) and alkaline Comet assays., The single-cell electrophoresis (comet) assay is an established method for measuring radiation-induced strand breaks in DNA., The COMET assay is recognized as a rapid and sensitive method in quantifying radiation induced DNA damage., The relationship between cellular radiosensitivity and radiation-induced DNA damage measured by the comet assay., Reliable Comet assay measurements for detecting DNA damage induced by ionising radiation and chemicals., Radiation sensitivity of lymphocytes from healthy individuals and cancer patients as measured by the comet assay., The comet assay is a potential tool for use in neutron therapy, as well as a method for the rapid screening of samples from individuals accidentally exposed to radiation., Induction and repair of DNA damage as measured by the Comet assay and the yield of somatic mutations in gamma-irradiated tobacco seedlings., The increased yield of somatic mutations was highly correlated (r = 0.996) with the increased DNA damage measured by the Comet assay immediately after irradiation., The alkaline version of single cell gel electrophoresis (comet) assay is widely used for evaluating DNA damage at the individual cell level., Induction (2 and 5 Gy) of gamma-ray-induced DNA damage and its repair (during 60 min after irradiation) was measured with the alkaline and neutral comet assay., The alkaline single-cell gel electrophoresis (SCGE or Comet) assay appears to be a promising tool for measuring DNA damage at the individual cell level in both in vitro and in vivo studies., Considering our previous studies showing significant increases in the frequency of cytogenetic damage (when measured as micronuclei) in patients treated with relatively low doses of 131I, the results obtained in the present work by using the Comet assay could indicate that 1 week after the exposure most of the radioiodine-induced DNA lesions, that can be detected with this assay, have already been repaired., Hence, we are using the single-cell gel electrophoresis (comet assay) to detect mouse mutants that display a genetic susceptibility to ionizing radiation., We have established the analysis parameters in the comet assay which are currently used to detect radiation-sensitive mouse mutants and to control the variance within the mouse population in the ENU screen., Comet assay as a tool to screen for mouse models with inherited radiation sensitivity.[SEP]", "label": "yes"}
{"id": "converted_2791", "sentence1": "Is erythropoietin effective for treatment of amyotrophic lateral sclerosis?", "sentence2": "This study was performed to validate the ALS-MITOS as a 6-month proxy of survival in 200 ALS patients followed up to 18 months.METHODS: Analyses were performed on data from the recombinant human erythropoietin RCT that failed to demonstrate differences between groups for both primary and secondary outcomes., CONCLUSIONS: RhEPO 40,000 IU fortnightly did not change the course of ALS., At 12 months, the annualised rate of death (rhEPO 0.11, 95% CI 0.06 to 0.20; placebo: 0.08, CI 0.04 to 0.17), tracheotomy or >23 h NIV (rhEPO 0.16, CI 0.10 to 0.27; placebo 0.18, CI 0.11 to 0.30) did not differ between groups, also after stratification by onset and ALSFRS-R at baseline.[SEP]", "label": "no"}
{"id": "converted_2096", "sentence1": "Is Cryptococcus neoformans a frequent cause of isolated skin infections in immunocompromised individuals", "sentence2": " Cryptococcus is an opportunistic yeast with a worldwide distribution that primarily causes significant infections in immunocompromised individuals, generally by affecting the respiratory tract. But primary cutaneous cryptococcosis (PCC) without systemic infection is rare. , Cryptococcus is a ubiquitous fungus and is known for causing meningitis and cutaneous infections in immunocompromised individuals., Cryptococcus neoformans is an encapsulated yeast that can cause primary pulmonary infections or disseminate and cause infections of the central nervous system, meninges, skin, and bone in the immunocompromised host., The authors report a male patient, a seller with no detected immunosuppression, with an extensive ulcerated skin lesion localized on the left forearm, caused by Cryptococcus neoformans var.[SEP]", "label": "no"}
{"id": "converted_4481", "sentence1": "Can Isradipine slow progression of Early Parkinson Disease?", "sentence2": "Adjusted least-squares mean changes in total UPDRS score in the antiparkinson medication ON state over 36 months for isradipine and placebo recipients were 2.99 (95% CI, 0.95 to 5.03) points versus 3.26 (CI, 1.25 to 5.26) points, respectively, with a treatment effect of -0.27 (CI, -3.02 to 2.48) point (P = 0.85)., Conclusion: Long-term treatment with immediate-release isradipine did not slow the clinical progression of early-stage PD., ONS: These results are consistent with the recent secondary analysis of the STEADY-PD III clinical trial-suggesting that clinically attainable brain exposure to isradipine may slow early-stage PD progression. © 2021 , These findings suggest that greater exposure to isradipine might slow disease progression., erm treatment with immediate-release isradipine did not slow the clinical progression of early-stage PD.Primary Funding So, BACKGROUND: Recent examination of the STEADY-PD III isradipine clinical trial data concluded that early-stage Parkinson's disease (PD) participants who had longer exposure to isradipine had a significant delay in their need for symptomatic medication, as well as a lower medication burden at the end of t, RESULTS: Isradipine exposures did not correlate with the primary clinical outcome, changes in the antiparkinson therapy-adjusted Unified Parkinson's Disease Rating Scale parts I-III score over 36 months (Spearman rank correlation coefficient, rs : ,  These findings suggest that greater exposure to isradipine might slow disease progressio, Conclusion: Long-term treatment with immediate-release isradipine did not slow the clinical progression of early-stage P, However, in a recently completed phase 3 clinical trial, the dihydropyridine (DHP) LTCC inhibitor isradipine failed to slow disease progression in early PD patients, questioning the feasibility of DHPs for PD therapy., BACKGROUND: Recent examination of the STEADY-PD III isradipine clinical trial data concluded that early-stage Parkinson's disease (PD) participants who had longer exposure to isradipine had a significant delay in their need for symptomatic medication, as well as a lower medication burden at the end o[SEP]", "label": "no"}
{"id": "converted_4165", "sentence1": "Is belimumab effective for the lupus nephritis?", "sentence2": "Long-term effects of combined B-cell immunomodulation with rituximab and belimumab in severe, refractory systemic lupus erythematosus: 2-year results., CONCLUSIONS: Combined B-cell targeted therapy with RTX and BLM prevented full B-cell repopulation including DN B cells, with concomitant specific reduction of SLE-relevant autoantibodies. , Clinical Efficacy of Routinely Administered Belimumab on Proteinuria and Neuropsychiatric Lupus., Conclusions: In our series, BEL led to a decrease of proteinuria in patients with proteinuria of more than 1,000 mg/g creatinine despite standard of care treatment, and led to a marked clinical improvement in one patient with NPSLE. No adverse events were observed. Routinely administered BEL shows clinical efficacy on non-approved manifestations, but careful patient selection is warranted., Phase II Randomized Trial of Rituximab Plus Cyclophosphamide Followed by Belimumab for the Treatment of Lupus Nephritis., OBJECTIVE: To assess the safety, mechanism of action, and preliminary efficacy of rituximab followed by belimumab in the treatment of refractory lupus nephritis (LN)., CONCLUSION: The addition of belimumab to a treatment regimen with rituximab and CYC was safe in patients with refractory LN., RECENT FINDINGS: Recently, the Belimumab in Subjects with Systemic Lupus Erythematosus - Lupus Nephritis trial tested belimumab, an inhibitor of B-cell activating factor, as an add-on therapy to steroids and either mycophenolate mofetil (MMF) or cyclophosphamide when given IV monthly over a period of 104 weeks at an effect size of 11% for a Primary Efficacy Renal Response. , Case report: successful treatment of membranous lupus nephritis with belimumab in an African female immigrant., Recently introduced into the market, belimumab (Benlysta) is a monoclonal antibody that has potential clinically efficacious applications for the treatment of lupus nephritis., Successful treatment of a mycophenolate mofetil-refractory proliferative lupus nephritis with Belimumab in a 19-year-old woman., Following treatment with belimumab, proteinuria rapidly improved to almost normal levels and clinical remission lasted. Belimumab might hold promise for this indication.[SEP]Relations: Belimumab has relations: drug_drug with Cyclophosphamide, drug_drug with Cyclophosphamide. Bloom syndrome has relations: disease_protein with BLM, disease_protein with BLM. Rituximab has relations: drug_drug with Cyclophosphamide, drug_drug with Cyclophosphamide. Mycophenolate mofetil has relations: drug_drug with Cyclophosphamide, drug_drug with Cyclophosphamide, drug_drug with Cyclophosphamide, drug_drug with Cyclophosphamide.", "label": "yes"}
{"id": "converted_282", "sentence1": "Is the Wnt protein modified by notum?", "sentence2": "Notum deacylates Wnt proteins to suppress signalling activity., Kinetic and mass spectrometric analyses of human proteins show that Notum is a carboxylesterase that removes an essential palmitoleate moiety from Wnt proteins and thus constitutes the first known extracellular protein deacylase., the Wnt inhibitor notum, the WNT-inhibitor notum.[SEP]", "label": "yes"}
{"id": "converted_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_4125", "sentence1": "Is vocimagene amiretrorepvec effective for glioblastoma?", "sentence2": "CONCLUSIONS: These results support an immune-related mechanism of action for Toca 511 and Toca FC, and suggest that molecular and immunologic signatures are related to clinical benefit from treatment., The median OS was 11.10 months for the Toca 511/FC group and 12.22 months for the control group (hazard ratio, 1.06; 95% CI 0.83, 1.35; P = .62). The secondary end points did not demonstrate statistically significant differences. The rates of adverse events were similar in the Toca 511/FC group and the SOC control group.Conclusions and Relevance: Among patients who underwent tumor resection for first or second recurrence of glioblastoma or anaplastic astrocytoma, administration of Toca 511 and Toca FC, compared with SOC, did not improve overall survival or other efficacy end points.[SEP]", "label": "no"}
{"id": "converted_860", "sentence1": "Is hypersensitivity to DNA crosslinking agents a hallmark of Fanconi anemia?", "sentence2": "The Fanconi anemia (FA) core complex plays a central role in the DNA damage response network, FAAP100-deficient cells display hallmark features of FA cells, including defective FANCD2 monoubiquitination, hypersensitivity to DNA crosslinking agents, and genomic instability., Fanconi anemia (FA) is a rare genetic disorder characterized by aplastic anemia, cancer/leukemia susceptibility and cellular hypersensitivity to DNA crosslinking agents, such as cisplatin., Fanconi anemia (FA) is an inherited chromosomal recessive syndrome characterized by cellular hypersensitivity to DNA crosslinking agents and bone marrow failure, which cause aplastic anemia, and an increased incidence of malignancy., Features of chromosomal aberrations, hypersensitivity to DNA crosslinking agents, and predisposition to malignancy have suggested a fundamental anomaly of DNA repair in Fanconi anemia., Fanconi anemia (FA) is one of several genetic diseases with characteristic cellular hypersensitivity to DNA crosslinking agents which suggest that FA proteins may function as part of DNA repair processes., Fanconi anemia (FA) is characterized by cellular hypersensitivity to DNA crosslinking agents, but how the Fanconi pathway protects cells from DNA crosslinks and whether FA proteins act directly on crosslinks remain unclear., Fanconi Anemia (FA) is a rare genetic disorder associated with a bone-marrow failure, cancer predisposition and hypersensitivity to DNA crosslinking agents., Fanconi anemia (FA) is a heterogeneous disease associated with a bone marrow failure, cancer predisposition and hypersensitivity to DNA crosslinking agents., Fanconi anemia (FA) is an inherited disorder characterized by defective DNA repair and cellular sensitivity to DNA crosslinking agents., Fanconi anemia (FA) is an inherited disease characterized by bone marrow failure, increased cancer risk and hypersensitivity to DNA cross-linking agents, implying a role for this pathway in the maintenance of genomic stability., Genetic or epigenetic inactivation of the pathway formed by the Fanconi Anemia (FA) proteins occurs in several cancer types, including head and neck squamous cell carcinomas (HNSCC), rendering the affected tumors potentially hypersensitive to DNA crosslinking agents., Fanconi Anemia (FA) is a rare autosomic recessive and X-linked disease with chromosomal instability after exposure to crosslinking agents as the hallmark., Fanconi Anemia (FA) is an autosomal recessive disease characterized by chromosome instability, cellular hypersensitivity to DNA cross-linking agents, and increased predisposition to malignancies., The Bloom protein (BLM) and Topoisomerase IIIalpha are found in association with proteins of the Fanconi anemia (FA) pathway, a disorder manifesting increased cellular sensitivity to DNA crosslinking agents., Using siRNA depletion and gene knockout techniques, we show that FAAP100-deficient cells display hallmark features of FA cells, including defective FANCD2 monoubiquitination, hypersensitivity to DNA crosslinking agents, and genomic instability., Fanconi anemia (FA) is a recessive human cancer prone syndrome featuring bone marrow failure, developmental abnormalities and hypersensitivity to DNA crosslinking agents exposure., FA is a chromosome instability syndrome characterized by childhood-onset aplastic anemia, cancer or leukemia susceptibility, and cellular hypersensitivity to DNA crosslinking agents., Functional defects in the Fanconi pathway can result in a marked hypersensitivity to interstrand crosslinking agents, such as mitomycin C., At the cellular level, hypersensitivity to DNA interstrand crosslinks is the defining feature in Fanconi anemia., DNA crosslinking agents may led to DNA cross-linking lesion, and Fanconi anemia pathway plays a key role in repairing its cross-linking., Fanconi anemia (FA), an autosomal recessive disorder of children, is characterized by congenital or childhood aplastic anemia, multiple developmental anomalies, increased incidence of myeloid leukemia, increased spontaneous chromosome breakage, and cellular and chromosomal hypersensitivity to DNA bifunctional crosslinking and alkylating agents., elegans provides an excellent model system for the study of the Fanconi Anemia (FA), one of the hallmarks of which is sensitivity to interstrand crosslinking agents, Using siRNA depletion and gene knockout techniques, we show that FAAP100-deficient cells display hallmark features of FA cells, including defective FANCD2 monoubiquitination, hypersensitivity to DNA crosslinking agents, and genomic instability, One of the hallmark phenotypes of FA is cellular hypersensitivity to agents that induce DNA interstrand crosslinks (ICLs), such as mitomycin C (MMC), Furthermore, the cytological hallmark of FA, the DNA crosslink-induced radial chromosome formation, exemplifies an innate impairment in the repair of these particularly cytotoxic DNA lesions [A.D, Fanconi anemia (FA) is characterized by cellular hypersensitivity to DNA crosslinking agents, but how the Fanconi pathway protects cells from DNA crosslinks and whether FA proteins act directly on crosslinks remain unclear, Features of chromosomal aberrations, hypersensitivity to DNA crosslinking agents, and predisposition to malignancy have suggested a fundamental anomaly of DNA repair in Fanconi anemia, Fanconi anemia (FA) is an inherited chromosomal recessive syndrome characterized by cellular hypersensitivity to DNA crosslinking agents and bone marrow failure, which cause aplastic anemia, and an increased incidence of malignancy, Genetic or epigenetic inactivation of the pathway formed by the Fanconi Anemia (FA) proteins occurs in several cancer types, including head and neck squamous cell carcinomas (HNSCC), rendering the affected tumors potentially hypersensitive to DNA crosslinking agents, Fanconi anemia (FA) is a human autosomal disorder characterized by cancer susceptibility and cellular sensitivity to DNA crosslinking agents such as mitomycin C and diepoxybutane, The Fanconi anemia pathway promotes DNA glycosylase-dependent excision of interstrand DNA crosslinks., DNA crosslinking agents may led to DNA cross-linking lesion, and Fanconi anemia pathway plays a key role in repairing its cross-linking, FA is a chromosome instability syndrome characterized by childhood-onset aplastic anemia, cancer or leukemia susceptibility, and cellular hypersensitivity to DNA crosslinking agents, The disease is manifested by defects in DNA repair, hypersensitivity to DNA crosslinking agents, and a high degree of chromosomal aberrations[SEP]Relations: chromosome has relations: cellcomp_protein with BLM, cellcomp_protein with BLM. Bloom syndrome has relations: disease_protein with BLM, disease_protein with BLM. Fanconi anemia complementation group has relations: disease_protein with FANCD2, disease_disease with Fanconi anemia, disease_protein with FANCD2, disease_disease with Fanconi anemia, disease_protein with FANCD2, disease_disease with Fanconi anemia, disease_protein with FANCD2, disease_disease with Fanconi anemia.", "label": "yes"}
{"id": "converted_1669", "sentence1": "Does ghrelin play a role in ischemic stroke?", "sentence2": "Recent evidence suggests that ghrelin may also be neuroprotective after injury in animal models of cerebral ischemia., Overall, these experiments point to a neurodegenerative but antiapoptotic effect of endogenous ghrelin in this model of global ischemia, highlighting that further research is essential before we can apply ghrelin treatments to neurodegenerative insults in the clinic.,  The serum ghrelin level was higher in the MCAO group when compared with the control group (P < 0.05). , Our results showed that higher level of serum ghrelin decreased gastrointestinal motility and damage to the intestinal mucosa existed in rats with MCAO., Leptin, adiponectin and ghrelin, new potential mediators of ischemic stroke., RESULTS: Significantly higher levels of leptin and lower levels of adiponectin and ghrelin were confirmed in the stroke group., Ghrelin levels correlated mildly with triglyceride levels, and were dominant in men with cardioembolic stroke., CONCLUSIONS: Adipokines and ghrelin play an important role in ischemic stroke, but their function in stroke subtypes seems to be different and sex influenced., Ghrelin suppresses inflammation and neuronal nitric oxide synthase in focal cerebral ischemia via the vagus nerve., Compared with vehicle treatment, human ghrelin treatment in vagus nerve-intact rats after MCAO showed marked reduction in neurological deficit by 57% and infarct size by 25%. , Human ghrelin treatment in vagus nerve-intact rats significantly decreased the above measurements. Human ghrelin treatment also improved 7-day survival and significantly decreased neurological deficit over the entire 7 days after MCAO in vagus nerve-intact rats compared with vehicle. , Human ghrelin is thus a neuroprotective agent that inhibits inflammation, nNOS activity, and apoptosis in focal cerebral ischemia through a vagal pathway., Ghrelin is known to promote neuronal defense and survival against ischemic injury by inhibiting apoptotic processes. , Our data indicate that des-acyl ghrelin, as well as ghrelin, protect cortical neurons against ischemic injury through the inhibition of Par-4 expression and apoptotic molecules in mitochondrial pathway., In conclusion, it is considered that ghrelin as well as S-100B can be a useful marker for the prediction of stoke after CPB. , Adipokines and ghrelin play an important role in ischemic stroke, but their function in stroke subtypes seems to be different and sex influenced., In this review we discuss pre-clinical evidence suggesting ghrelin may be a useful therapeutic in protecting the brain against injury after ischemic stroke., Both ghrelin and des-acyl ghrelin protected cortical neurons from ischemic injury., Our data indicate that des-acyl ghrelin, as well as ghrelin, protect cortical neurons against ischemic injury through the inhibition of Par-4 expression and apoptotic molecules in mitochondrial pathway., Adipokines and ghrelin play an important role in ischemic stroke, but their function in stroke subtypes seems to be different and sex influenced., In this review we discuss pre-clinical evidence suggesting ghrelin may be a useful therapeutic in protecting the brain against injury after ischemic stroke, Human ghrelin is thus a neuroprotective agent that inhibits inflammation, nNOS activity, and apoptosis in focal cerebral ischemia through a vagal pathway, Both ghrelin and des-acyl ghrelin protected cortical neurons from ischemic injury, Overall, these experiments point to a neurodegenerative but antiapoptotic effect of endogenous ghrelin in this model of global ischemia, highlighting that further research is essential before we can apply ghrelin treatments to neurodegenerative insults in the clinic, In the present study, we investigated the role of prostate apoptosis response-4 (Par-4), a proapoptotic gene the expression of which is increased after ischemic injury, in ghrelin-mediated neuroprotection during middle cerebral artery occlusion (MCAO), Adipokines and ghrelin play an important role in ischemic stroke, but their function in stroke subtypes seems to be different and sex influenced[SEP]", "label": "yes"}
{"id": "converted_3566", "sentence1": "Has LB-100 been tested in clinical trials?", "sentence2": "To determine the MTD and to assess the safety, tolerability, and potential activity of LB-100, a first-in-class small-molecule inhibitor of protein phosphatase 2A (PP2A) in adult patients with progressive solid tumors., Safety, Tolerability, and Preliminary Activity of LB-100, an Inhibitor of Protein Phosphatase 2A, in Patients with Relapsed Solid Tumors: An Open-Label, Dose Escalation, First-in-Human, Phase I Trial.[SEP]", "label": "yes"}
{"id": "converted_3273", "sentence1": "Has the drug Afrezza been approved by the FDA?", "sentence2": "In contrary, MannKind Corporation started developing its ultra-rapid-acting insulin Afrezza in a bold bid, probably by managing the issues in which Exubera was not successful. Afrezza has been marketed since February, 2015 by Sanofi after getting FDA approval in June 2014.[SEP]", "label": "yes"}
{"id": "converted_3359", "sentence1": "Is the FIP virus thought to be a mutated strain for the Feline enteric Coronavirus?", "sentence2": "Feline infectious peritonitis (FIP) results from mutations in the viral genome during a common feline enteric coronavirus (FECV) infection., It is caused by FIP virus (FIPV), a virulent mutant strain of Feline Enteric Coronavirus (FECV)., Feline infectious peritonitis virus (FIPV) was presumed to arise from mutations in the 3c of a ubiquitous and largely nonpathogenic feline enteric coronavirus (FECV)., Feline enteric coronavirus (FECV) causes inapparent or mild enteritis in cats, but a highly fatal disease, called feline infectious peritonitis (FIP), can arise through mutation of FECV to FIP virus (FIPV)., Feline infectious peritonitis (FIP) is a lethal systemic disease caused by FIP virus (FIPV), a virulent mutant of apathogenic feline enteric coronavirus (FECV)., Feline infectious peritonitis (FIP) is an almost invariably fatal feline coronavirus (FCoV)-induced disease thought to arise from a combination of viral mutations and an overexuberant immune response., BACKGROUND\n\nFeline Infectious Peritonitis (FIP) is a lethal systemic disease, caused by the FIP Virus (FIPV); a virulent mutant of Feline Enteric Coronavirus (FECV)., BACKGROUND Feline Infectious Peritonitis (FIP) is a lethal systemic disease, caused by the FIP Virus (FIPV); a virulent mutant of Feline Enteric Coronavirus (FECV)., This coronavirus is a virulent mutant of the harmless, ubiquitous feline enteric coronavirus (FECV)., Feline infectious peritonitis virus (FIPV) was presumed to arise from mutations in the 3c of a ubiquitous and largely nonpathogenic feline enteric coronavirus (FECV)., Whilst intact in all FECVs, the 3c gene was mutated in the majority (71.4 %) of FIPVs, but not in all, implying that mutation in 3c is not the (single) cause of FIP.[SEP]", "label": "yes"}
{"id": "converted_831", "sentence1": "Have 5q35 microdeletions been implicated in Sotos syndrome development?", "sentence2": "Loss-of-function mutations of NSD1 and 5q35 microdeletions encompassing NSD1 are a major cause of Sotos syndrome (Sos), which is characterized by overgrowth, macrocephaly, characteristic facies, and variable intellectual disability (ID), We observed a novel 3.5 Mb 5q subtelomeric deletion in a 3-year-old girl with developmental delay, hypotonia and multiple minor anomalies. Comparison of her phenotype with the few published patients with terminal 5q35 deletions revealed several overlapping features, but also showed remarkable differences such as shortness of stature versus macrosomia. After the report of 5q35.3 microdeletions in Sotos syndrome we integrated the published BACs into the public draft sequence and exactly mapped the deletion size in our patient by FISH analysis with 15 BAC probes. We demonstrated that the deletion in our patient is immediately adjacent to the reported Sotos syndrome deletion site, Switch in FGFR3 and -4 expression profile during human renal development may account for transient hypercalcemia in patients with Sotos syndrome due to 5q35 microdeletions., Multiple mechanisms are implicated in the generation of 5q35 microdeletions in Sotos syndrome., After the report of 5q35.3 microdeletions in Sotos syndrome we integrated the published BACs into the public draft sequence and exactly mapped the deletion size in our patient by FISH analysis with 15 BAC probes., Clinical and genetic spectrum of 18 unrelated Korean patients with Sotos syndrome: frequent 5q35 microdeletion and identification of four novel NSD1 mutations., Here we describe a new case of Sotos syndrome with a 5q35 microdeletion, affecting the fibroblast growth factor receptor 4 (FGFR4) gene, presenting with infantile hypercalcemia., Microdeletions at 5q35.3, encompassing NSD1, are responsible for approximately 10% of non-Japanese cases of Sotos., Alu-related 5q35 microdeletions in Sotos syndrome., Most cases of Sotos syndrome are caused by intragenic NSD1 mutations or 5q35 microdeletions., Multiple mechanisms are implicated in the generation of 5q35 microdeletions in Sotos syndrome, Clinical and genetic spectrum of 18 unrelated Korean patients with Sotos syndrome: frequent 5q35 microdeletion and identification of four novel NSD1 mutations, Microdeletions at 5q35.3, encompassing NSD1, are responsible for approximately 10% of non-Japanese cases of Sotos, A case of Sotos syndrome with 5q35 microdeletion and novel clinical findings., Here we describe a new case of Sotos syndrome with a 5q35 microdeletion, affecting the fibroblast growth factor receptor 4 (FGFR4) gene, presenting with infantile hypercalcemia. , There are two types of mutations that cause NSD1 haploinsufficiency: mutations within the NSD1 gene (mutation type) and a 5q35 submicroscopic deletion encompassing the entire NSD1 gene (deletion type). , aCGH and metaphase FISH are useful for rapid diagnosis of 5q35 microdeletion associated with Sotos syndrome., Multiple mechanisms are implicated in the generation of 5q35 microdeletions in Sotos syndrome., Switch in FGFR3 and -4 expression profile during human renal development may account for transient hypercalcemia in patients with Sotos syndrome due to 5q35 microdeletions., A case of Sotos syndrome with 5q35 microdeletion and novel clinical findings., Most cases of Sotos syndrome are caused by intragenic NSD1 mutations or 5q35 microdeletions., aCGH and metaphase FISH are useful for rapid diagnosis of 5q35 microdeletion associated with Sotos syndrome., Alu-related 5q35 microdeletions in Sotos syndrome.[SEP]Relations: Abnormality of the dentition has relations: disease_phenotype_positive with Sotos syndrome, disease_phenotype_positive with Sotos syndrome. Macrocephaly has relations: disease_phenotype_positive with Sotos syndrome, disease_phenotype_positive with Sotos syndrome. Sotos syndrome has relations: disease_protein with NSD1, disease_protein with NSD1. Intellectual disability has relations: disease_phenotype_positive with Sotos syndrome, disease_phenotype_positive with Sotos syndrome.", "label": "yes"}
{"id": "converted_1513", "sentence1": "Is thrombophilia related to increased risk of miscarriage?", "sentence2": "Thrombophilia does hardly increase the risk of IUGR/PMPC or if so, it can be prevented by LMWH, for illustrative purposes, a patient presenting with combined thrombophilia--both genetic and acquired--will be discussed. This patient had suffered severe gestational complications that led to devastating obstetrical outcome, Thrombophilias have been implicated in complications related to ischemic placental disease including recurrent pregnancy loss, intrauterine fetal demise, preeclampsia, fetal growth restriction, placental abruption, and preterm delivery, Further information about the combined risk of aPC resistance and pregnancy is needed before guidance on the management of affected women can be formulated., Thrombotic risk during pregnancy and the puerperium is higher in asymptomatic women with than without thrombophilia, Further studies are required to assess the thrombotic risk in women with preeclampsia as well as early or late recurrent pregnancy loss., Risk of pregnancy-related venous thrombosis in carriers of severe inherited thrombophilia, In conclusion, homozygous carriers of factor V Leiden and, to a lesser extent, double heterozygous carriers of factor V Leiden and of the prothrombin mutation have an increased risk of venous thrombosis during pregnancy, particularly high during the postpartum period, Careful diagnosis, observation and monitoring can add significant benefit to LMWH therapy during pregnancy, Pregnancy in healthy women is accompanied by hypercoagulable changes that may interact with thrombophilia risk factors and threaten pregnancy., Fifty-three (13 %) women had antiphospholipid antibodies (lupus anticoagulant and/or anti-beta2-glycoprotein 1 antibodies) mainly associated with the risk of spontaneous abortion during the first trimester, thrombophilia was found to be considerably more common in women with pregnancy-associated complications in comparison with the general population, and most frequently in conjunction with venous thromboembolism during pregnancy and the postpartum period, When counseling white women with a history of preeclampsia, screening for thrombophilia can be useful for preconceptional counseling and pregnancy management., knowledge combined with the appropriate use of thromboprophylaxis and treatment in women who have objectively confirmed VTE continue to improve maternal and perinatal outcomes, The risk of having thrombophilia is doubled in men who have fathered pregnancies which ended in perinatal death as well as in the mothers of such pregnancies., The prevalence of thrombophilic variants is of possible public health significance for other morbidity; but perhaps not in relation to preeclampsia, This study suggests that thrombophilia \"mediates\" in lowering of cardiovascular risk factors in women with a history of preeclampsia[SEP]", "label": "yes"}
{"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_785", "sentence1": "Is flibanserin effetive for Hypoactive Sexual Desire Disorder? ", "sentence2": "Mechanism of action of flibanserin, a multifunctional serotonin agonist and antagonist (MSAA), in hypoactive sexual desire disorder., Flibanserin is a novel multifunctional serotonin agonist and antagonist (MSAA) that improves sexual functioning in premenopausal women who suffer from reduced sexual interest and desire., Flibanserin is a novel, non-hormonal drug for the treatment of HSDD in pre- and postmenopausal women, although the application submitted to the U.S. Food and Drug Administration by Sprout Pharmaceuticals is only for premenopausal women., CONCLUSIONS: In naturally postmenopausal women with HSDD, flibanserin, compared with placebo, has been associated with improvement in sexual desire, improvement in the number of SSEs, and reduced distress associated with low sexual desire, and is well tolerated., INTRODUCTION: Flibanserin is a mixed 5-HT1A agonist/5-HT2A antagonist that has been developed for the treatment of hypoactive sexual desire disorder in women, BACKGROUND: Flibanserin, a novel serotonin (5-HT)(1A) agonist and 5-HT(2A) antagonist, has been shown to increase sexual desire and reduce distress in women with Hypoactive Sexual Desire Disorder (HSDD). , Hypoactive sexual desire disorder (HSDD) is the most commonly described form of female sexual dysfunction. There is currently no pharmacological therapy approved to treat HSDD, and therefore, there is an unmet medical need for the development of efficacious treatment alternatives. Flibanserin is a novel, non-hormonal drug for the treatment of HSDD in pre- and postmenopausal women, although the application submitted to the U.S. , Sexual function adverse events across flibanserin groups were generally comparable to placebo.Although these studies were not designed or powered to compare sexual function outcomes, results suggested a potential benefit of flibanserin on sexual function, particularly on female sexual desire, and provided a rationale to evaluate the efficacy of flibanserin as a treatment for female hypoactive sexual desire disorder.[SEP]", "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_3482", "sentence1": "Is PF-05190457 an inverse agonist of the ghrelin receptor?", "sentence2": "Pharmacokinetics and pharmacodynamics of PF-05190457: The first oral ghrelin receptor inverse agonist to be profiled in healthy subjects., To evaluate safety, tolerability and pharmacokinetics of oral PF-05190457, an oral ghrelin receptor inverse agonist, in healthy adults.,  PF-05190457 is a well-tolerated first-in-class ghrelin receptor inverse agonist with acceptable pharmacokinetics for oral daily dosing.[SEP]", "label": "yes"}
{"id": "converted_360", "sentence1": "Have thyronamines  effects on fat tissue?", "sentence2": "In conclusion, trace amines and thyronamines are negative inotropic agents., Their in vivo administration induces effects opposite to those induced by thyroid hormone, including lowering of body temperature.[SEP]", "label": "no"}
{"id": "converted_3531", "sentence1": "Is Huntington's disease is caused by expansion of a CTG repeat in the HTT gene on Chromosome 4?", "sentence2": "Huntington's disease (HD) is caused by a CAG repeat expansion that encodes a polyglutamine (polyQ) expansion in the HD disease protein, huntingtin (HTT)., Huntington disease (HD) is a dominantly inherited disorder caused by a CAG expansion mutation in the huntingtin (HTT) gene, which results in the HTT protein that contains an expanded polyglutamine tract., In Huntington's disease (HD), expansion of CAG codons in the huntingtin gene (HTT) leads to the aberrant formation of protein aggregates and the differential degeneration of striatal medium spiny neurons (MSNs)., Huntington disease (HD) is a progressive autosomal dominant neurodegenerative disorder, characterized by abnormal movements, cognitive decline, and psychiatric symptoms, caused by a CAG repeat expansion in the huntingtin (HTT) gene on chromosome 4p., Huntington's disease (HD) is a polyglutamine disorder caused by a CAG expansion in the Huntingtin (HTT) gene exon 1., IMPORTANCE\n\nHuntington disease (HD), a prototypic monogenic disease, is caused by an expanded CAG repeat in the HTT gene exceeding 35 units., Huntington's disease (HD) is an autosomal dominantly inherited disorder caused by the expansion of CAG repeats in the Huntingtin (HTT) gene., Huntington's disease (HD) is a neurodegenerative disorder caused by a CAG trinucleotide repeat expansion in the huntingtin (HTT) gene., BACKGROUND Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT., Huntington's disease (HD) is an inherited neurodegenerative disease caused by an expanded CAG repeat in the HTT gene., IMPORTANCE Huntington disease (HD), a prototypic monogenic disease, is caused by an expanded CAG repeat in the HTT gene exceeding 35 units., Huntington 's disease ( HD ) is an inherited neurodegenerative disorder caused by a CAG repeat expansion within exon 1 of the huntingtin ( HTT ) gene. , Huntington 's disease ( HD) , a dominantly inherited neurodegenerative disease , is defined by its genetic cause , a CAG-repeat expansion in the HTT gene , its motor and psychiatric symptomology and primary loss of striatal medium spiny neurons ( MSNs) . , Huntington 's disease ( HD ) is an incurable neurodegenerative disorder caused by a CAG repeat expansion in exon 1 of the Huntingtin ( HTT ) gene. , Huntington 's disease ( HD ) is a progressive neurodegenerative disorder caused by a CAG trinucleotide repeat expansion in the huntingtin ( HTT ) gene , which encodes a polyglutamine tract in the HTT protein . , Huntington 's disease ( HD ) is an autosomal progressive neurodegenerative disorder caused by the expansion of CAG repeats in the HTT gene. , Huntington 's disease ( HD ) is an autosomal dominant neurodegenerative disease caused by the expansion of a CAG trinucleotide repeat in exon 1 of the huntingtin ( htt ) gene. , Huntington 's disease ( HD) , caused by a CAG repeat expansion in the huntingtin ( HTT ) gene , is characterized by abnormal protein aggregates and motor and cognitive dysfunction . , Huntington 's disease ( HD ) is a neurodegenerative disease caused by the expansion of a CAG trinucleotide repeat in exon 1 of the huntingtin ( HTT ) gene. , Huntington 's disease ( HD ) is an autosomal disease caused by a CAG repeat expansion in the huntingtin ( HTT ) gene. , BACKGROUND\nHuntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT., Huntington's disease (HD) is an autosomal dominant disorder caused by an expansion in the trinucleotide CAG repeat in exon-1 in the huntingtin gene, located on chromosome 4., HD is caused by expansion of the CAG trinucleotide repeat region in exon 1 of the Huntingtin gene (HTT), leading to the formation of mutant HTT transcripts (muHTT)., Huntington's disease (HD) is a neurodegenerative disorder characterized by involuntary choreic movements, cognitive impairment, and behavioral changes, caused by the expansion of an unstable CAG repeat in HTT., Huntington disease (HD), the most common inherited cause of chorea, is an autosomal dominant disorder, caused by an expanded trinucleotide CAG repeat (>39) in the HTT gene on chromosome 4p16.3., Huntington's disease (HD) is an inherited neurodegenerative disease caused by an expanded CAG repeat in the huntingtin (HTT) gene.[SEP]", "label": "no"}
{"id": "converted_3010", "sentence1": "In clinical trials, the H3 R antagonist CEP-26401 has a positive effect on cognition, yes or no?", "sentence2": "CEP-26401 is a novel orally active, brain-penetrant, high-affinity histamine H3 receptor (H3R) antagonist, with potential therapeutic utility in cognition enhancement, hese results demonstrate potent behavioral effects of CEP-26401 in rodent models and suggest that this novel H₃R antagonist may have therapeutic utility in the treatment of cognitive and attentional disorders, CEP-26401 is a novel orally active, brain-penetrant, high-affinity histamine H3 receptor (H3R) antagonist, with potential therapeutic utility in cognition enhancement., CEP-26401 (irdabisant), a potent and selective histamine H₃ receptor antagonist/inverse agonist with cognition-enhancing and wake-promoting activities., However, although a number of clinical studies examining the efficacy of H3 receptor antagonists for a variety of cognitive disorders are currently underway, no clinical proof of concept for an H3 receptor antagonist has been reported to date., Further clinical studies are required to establish the potential of low-dose CEP-26401 in cognition enhancement.<br>[SEP]", "label": "yes"}
{"id": "converted_443", "sentence1": "Can we detect DNA strand asymmetries using dinucleotide relative abundance \"genomic signatures\"?", "sentence2": "comparing the heterogeneities of bacterial genomes with respect to strand-independent first- and second-order features, (i) G + C content and (ii) dinucleotide relative abundance,, the concept of a genomic signature was introduced with the observation of species-type specific Dinucleotide Relative Abundance Profiles (DRAPs); dinucleotides were identified as the subsequences with the greatest bias in representation in a majority of genomes., dinucleotide relative abundance values (the genomic signature), The dinucleotide relative abundance profile can be regarded as a genomic signature because, despite diversity between species, it varies little between 50 kilobase or longer windows on a given genome., The profile is computed from the base step \"odds ratios\" that compare dinucleotide frequencies to those expected under the assumption of stochastic equilibrium (thorough shuffling). , The genome signatures (dinucleotide relative abundance values), Early biochemical experiments measuring nearest neighbor frequencies established that the set of dinucleotide relative abundance values (dinucleotide biases) is a remarkably stable property of the DNA of an organism., the set of dinucleotide biases constitutes a 'genomic signature' that can discriminate sequences from different organisms., the set of dinucleotide odds ratio (relative abundance) values constitute a signature of each DNA genome, Dinucleotide relative abundance extremes: a genomic signature., The dinucleotide relative abundance profile can be regarded as a genomic signature because, despite diversity between species, it varies little between 50 kilobase or longer windows on a given genome., Previously, the concept of a genomic signature was introduced with the observation of species-type specific Dinucleotide Relative Abundance Profiles (DRAPs); dinucleotides were identified as the subsequences with the greatest bias in representation in a majority of genomes., Comparisons within and between species sample sequences are based on the profile of dinucleotide relative abundance values (The profile is rho*XY = f*XY/f*Xf*Y for all XY, where f*X denotes the frequency of the nucleotide X and f*XY denotes the frequency of the dinucleotide XY, both computed from the sequence concatenated with its inverted complement)., Dinucleotide relative abundances (i.e., dinucleotide representations normalized by the component nucleotide frequencies) are consonant with respect to the leading and lagging strands[SEP]", "label": "no"}
{"id": "converted_2244", "sentence1": "Does RNA polymerase II have RNA cleavage activity?", "sentence2": "In addition to RNA synthesis, multisubunit RNA polymerases (msRNAPs) support enzymatic reactions such as intrinsic transcript cleavage., msRNAP active sites from different species appear to exhibit differential intrinsic transcript cleavage efficiency and have likely evolved to allow fine-tuning of the transcription process., Here we show that a single amino-acid substitution in the trigger loop (TL) of Saccharomyces RNAP II, Rpb1 H1085Y, engenders a gain of intrinsic cleavage activity where the substituted tyrosine appears to participate in acid-base chemistry at alkaline pH for both intrinsic cleavage and nucleotidyl transfer. , The eukaryotic transcription factor TFIIS enhances elongation and nascent transcript cleavage activities of RNA polymerase II in a stalled elongation complex., The transcription factor TFIIS zinc ribbon dipeptide Asp-Glu is critical for stimulation of elongation and RNA cleavage by RNA polymerase II, By site-directed mutagenesis, we have demonstrated that invariant residues Asp-261 and Glu-262 of the nucleic acid-binding TFIIS Zn ribbon are critical for stimulation of both elongation and RNA cleavage activities of RNA polymerase II., Complexes of yeast RNA polymerase II and RNA are substrates for TFIIS-induced RNA cleavage., RNA in such RNA-RNA polymerase complexes undergoes reactions previously thought to be unique to nascent RNA in ternary complexes with DNA, including TFIIS-dependent cleavage and elongation by 3'-terminal addition of NMP from NTP., Nascent RNA cleavage by arrested RNA polymerase II does not require upstream translocation of the elongation complex on DNA., Here we show that in the presence of SII and nucleotides, transcript cleavage is detected during SII-dependent elongation but not during SII-independent transcription. , under typical transcription conditions, SII is necessary but insufficient to activate RNA cleavage. RNA cleavage could serve to move RNA polymerase II away from the transcriptional impediment and/or permit RNA polymerase II multiple attempts at RNA elongation., SII is an RNA polymerase II-binding protein that stimulates transcription elongation and also activates nascent transcript cleavage by RNA polymerase II in elongation complexes in vitro, The RNA polymerase II elongation complex. Factor-dependent transcription elongation involves nascent RNA cleavage., Cleavage was not restricted to an elongation complex arrested at this particular site, showing that nascent RNA hydrolysis is a general property of RNA polymerase II elongation complexes., Elongation factor SII (also known as TFIIS) is an RNA polymerase II binding protein that allows bypass of template arrest sites by activating a nascent RNA cleavage reaction., During gene transcription, the RNA polymerase (Pol) active center can catalyze RNA cleavage., During gene transcription, the RNA polymerase (Pol) active center can catalyze RNA cleavage., The eukaryotic transcription factor TFIIS enhances elongation and nascent transcript cleavage activities of RNA polymerase II in a stalled elongation complex., Rpb9, a small subunit of RNA polymerase II, enhances the cleavage stimulation activity of S-II., These results suggest that both S-II and Rpb9 maintain transcriptional fidelity by stimulating the cleavage activity intrinsic to RNA polymerase II., It is also possible that the transcript cleavage activity of RNA polymerase II represents a proofreading function of the enzyme.., Nascent RNA cleavage by arrested RNA polymerase II does not require upstream translocation of the elongation complex on DNA., Intrinsic transcript cleavage in yeast RNA polymerase II elongation complexes.[SEP]", "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_3056", "sentence1": "As of Feb 2019, are major brain gangliosides a target for the treatment of Alzheimer's disease?", "sentence2": "An understanding of the mechanism on the interaction of GM1 and Aβs in AD may contribute to the development of new neuroregenerative therapies for this disorder., Abnormal ganglioside metabolism also may occur in AD brains, Continuous intraventricular infusion of GM1 has recently been shown to have a significant beneficial effect in Alzheimer disease of early onset (AD Type I)., Gangliosides--a new therapeutic agent against stroke and Alzheimer's disease., Gangliosides--a new therapeutic agent against stroke and Alzheimer's disease.Gangliosides are glycosphingolipids localized to the outer leaflet of the plasma membrane of vertebrate cells. , Continuous intraventricular infusion of GM1 has recently been shown to have a significant beneficial effect in Alzheimer disease of early onset (AD Type I).<br>[SEP]Relations: familial Alzheimer disease has relations: disease_disease with Alzheimer disease, disease_disease with Alzheimer disease.", "label": "yes"}
{"id": "converted_3754", "sentence1": "Glucoraphanin from broccoli can help reduce obesity , yes or no?", "sentence2": "Glucoraphanin: a broccoli sprout extract that ameliorates obesity-induced inflammation and insulin resistance., A recent study demonstrated that glucoraphanin, a precursor of the Nrf2 activator sulforaphane, ameliorates obesity by enhancing energy expenditure and browning of white adipose tissue, and attenuates obesity-related inflammation and insulin resistance by polarizing M2 macrophages and reducing metabolic endotoxemia., Thus, this review focuses on the efficiency and safety of glucoraphanin in alleviating obesity, insulin resistance, and NAFLD., Glucoraphanin: a broccoli sprout extract that ameliorates obesity-induced inflammation and insulin resistance, tudy demonstrated that glucoraphanin, a precursor of the Nrf2 activator sulforaphane, ameliorates obesity by enhancing energy expenditure and browning of white adipose tissue, and attenuates obesity-related inflammation and insulin resistance by polarizing M2 macrophages and reducing metabolic endotoxemia. Thus, this , iew focuses on the efficiency and safety of glucoraphanin in alleviating obesity, insulin resistance, and NAFLD. Abbreviations: [SEP]", "label": "yes"}
{"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_4696", "sentence1": "Do Afamin bind Vitamin E?", "sentence2": "The plasma glycoprotein afamin has been previously identified as an alternative carrier protein for vitamin E in extravascular fluids such as plasma and cerebrospinal, ovarian follicular, and seminal fluids., afamin, a vitamin E-binding protein in human plasma, the human vitamin E-binding protein afamin, Afamin is a plasma vitamin E-binding glycoprotein, The human vitamin E-binding glycoprotein afamin is primarily expressed in the liver and has been associated with prevalent and incident metabolic syndrome[SEP]Relations: metabolic syndrome X has relations: disease_disease with metabolic syndrome, disease_disease with metabolic syndrome.", "label": "yes"}
{"id": "converted_1502", "sentence1": "Can Alzheimer's disease related miRNAs be detected in patients' blood?", "sentence2": "miRNAs are aberrantly expressed in AD, and these have been implicated in the regulation of amyloid-β (Aβ) peptide, tau, inflammation, cell death, and other aspects which are the main pathomechanisms of AD. In addition, regulation of miRNAs varies in blood, and cerebral spinal fluid may indicate alterations in AD., miRNA microarray analysis was carried out on blood of rats at 1 week and 2 months after injection. RESULTS: Many up- and downregulated miRNAs were detected., Blood miRNAs could be useful as biomarkers for exposure to nanoparticles. miR-298 regulates β-amyloid (Aβ) precursor protein-converting enzyme-1 (BACE1) in Alzheimer's disease.,  We previously studied microRNAs (miRNAs) in AD autopsy brain samples and reported a connection between miR-137, -181c, -9, -29a/b and AD, through the regulation of ceramides. In this study, the potential role of these miRNAs as diagnostic markers for AD was investigated. We identified that these miRNAs were down-regulated in the blood serum of probable AD patients. , 287 with Alzheimer disease (AD) as compared with 344 age- and gender-matched controls. In addition, we evaluated expression levels of hnRNP-A1 and its regulatory microRNA (miR)-590-3p in blood cells from patients and controls., Decreased relative expression levels of hsa-miR-590-3p was observed in patients with AD versus controls (0.685 ± 0.080 versus 0.931 ± 0.111, p = 0.079), and correlated negatively with hnRNP-A1 mRNA levels (r = -0.615, p = 0.0237)., expression analysis of Sp1 and its regulatory microRNAs (hsa-miR-29b and hsa-miR-375) has been performed in peripheral blood mononuclear cells (PBMCs), together with Sp1 protein analysis., Significantly decreased relative expression levels of hsa-miR-29b, but not of hsa-miR-375, were observed in AD patients, Sp1 and its regulatory hsa-miR-29b are deregulated in AD patients, possibly leading to aberrant production of downstream target genes involved in the pathogenesis. , We previously observed that miR-137, -181c, -9, and 29a/b post-transcriptionally regulate SPT levels, and the corresponding miRNA levels in the blood sera are potential diagnostic biomarkers for AD. Here, we observe a negative correlation between cortical Aβ42 and sera Aβ42, and a positive correlation between cortical miRNA levels and sera miRNA levels suggesting their potential as noninvasive diagnostic biomarkers.[SEP]Relations: Alzheimer disease has relations: disease_protein with BACE1, disease_protein with BACE1. familial Alzheimer disease has relations: disease_disease with Alzheimer disease, disease_disease with Alzheimer disease. adrenal cortex has relations: anatomy_protein_present with BACE1, anatomy_protein_present with BACE1.", "label": "yes"}
{"id": "converted_4717", "sentence1": "Can parasite infections by Schistosoma japonicum prevent or improve asthma?", "sentence2": "Helminths and their products can shape immune responses by modulating immune cells, which are dysfunctional in inflammatory diseases such as asthm, Schistosoma japonicum peptide SJMHE1 suppresses airway inflammation of allergic asthma in mice., Schistosoma japonicum infection downregulates house dust mite-induced allergic airway inflammation in mice., To our knowledge, it is the first study to reveal the impact of S. japonicum infection on house dust mite induced severe asthma. More in depth investigation is need to elucidate the underlying mechanisms, Novel T-cell epitopes on Schistosoma japonicum SjP40 protein and their preventive effect on allergic asthma in mice., hese results reveal a novel form of immune protective mechanism, which may play an important role in the modulating effect of helminth infection on allergic asthmatic reactions., Using a panel of overlapping peptides, we identified T-cell epitopes on SjP40 protein of Schistosoma japonicum, which can induce Th1 cytokine and inhibit the production of Th2 cytokines and airway inflammation in a mouse model of allergic asthma., Helminths and their products can regulate immune response and offer new strategies to control and alleviate inflammation, including asthma., SJMHE1 Peptide from Schistosoma japonicum Inhibits Asthma in Mice by Regulating Th17/Treg Cell Balance via miR-155., We previously found that a peptide named as SJMHE1 from Schistosoma japonicum can suppress asthma in mice, el of overlapping peptides, we identified T-cell epitopes on SjP40 protein of Schistosoma japonicum, which can induce Th1 cytokine and inhibit the production of Th2 cytokines and airway inflammation in a mouse model of allergic asthma. These resul, has been shown that helminth infections including Schistosoma mansoni may modulate atopic diseases including asthma. I, Schistosoma japonicum infection downregulates house dust mite-induced allergic airway inflammation in mice, it is the first study to reveal the impact of S. japonicum infection on house dust mite induced severe asthma. More in depth inv, s study, we investigated the impact of Schistosoma japonicum infection on the allergic airway inflammation induced by repeated intracheal inoculations of house dust mites (HDM), which is a Th17 and neutrophils dominant murine asthma model, mimicking severe asthma. We found, Schistosoma japonicum infection showed protective effects against allergic airway inflammation (AAI)., Therefore, we hypothesize that Schistosoma japonicum egg antigens, a type of native antigen, can induce production of CD4(+) CD25(+) T cells with regulatory activity, modulating airway inflammation and inhibiting asthma development., Schistosoma japonicum infection modulates the development of allergen-induced airway inflammation in mice., It has been shown that helminth infections including Schistosoma mansoni may modulate atopic diseases including asthma., Schistosoma japonicum egg antigens stimulate CD4 CD25 T cells and modulate airway inflammation in a murine model of asthma., Most previous studies focused on understanding the preventive effect of S. japonicum infection on asthma (infection before allergen sensitization), whereas the protective effects of S. japonicum infection (allergen sensitization before infection) on asthma were rarely investigated., In conclusion, our data showed that lung-stage S. japonicum infection could relieve OVA-induced asthma in a mouse model., In this study, we investigated the protective effects of S. japonicum infection on AAI using a mouse model of OVA-induced asthma.,  prior to OVA immunization. These results suggest that both bisexual and male S. japonicum infections may modulate the development of allergic asthma., aponicum, which can induce Th1 cytokine and inhibit the production of Th2 cytokines and airway inflammation in a mouse model of allergic asthma. These, ve found that Schistosoma infection or Schistosoma related products can improve or prevent some immune and inflammatory diseases, such as severe asthm, Our findings indicated that S. japonicum infection was able to effectively inhibit host's allergic airway inflammation, which may be related to the upregulated Treg cells upon infection., These results suggest that both bisexual and male S. japonicum infections may modulate the development of allergic asthma., We found that lung-stage S. japonicum infection significantly ameliorated OVA-induced AAI, whereas post-lung-stage infection did not., In a murine model of asthma, S. japonicum egg antigens decreased the expression of Th2 cytokines, relieved antigen-induced airway inflammation, and inhibited asthma development., We found that S. japonicum infection downregulated airway hyperresponsiveness., However, in recent years, studies have found that Schistosoma infection or Schistosoma related products can improve or prevent some immune and inflammatory diseases, such as severe asthma, inflammatory bowel disease, diabetes and so on., In areas where schistosomiasis is endemic, a negative correlation is observed between atopy and helminth infection, associated with a low prevalence of asthma.[SEP]Relations: helminthiasis has relations: disease_disease with schistosomiasis, disease_disease with schistosomiasis. allergic asthma has relations: disease_disease with asthma, disease_disease with asthma. Schistosoma mansoni infectious disease has relations: disease_disease with schistosomiasis, disease_disease with schistosomiasis. asthma has relations: disease_disease with allergic asthma, disease_disease with allergic asthma. Schistosoma japonicum infectious disease has relations: disease_disease with schistosomiasis, disease_disease with schistosomiasis.", "label": "yes"}
{"id": "converted_790", "sentence1": "Is recommended the use of perioperative treatment with thyroid hormone therapy in patients undergoing coronary artery bypass grafting?", "sentence2": "Short duration postoperative iv T(3) therapy increases cardiac index and does not alter mortality., We conclude that although widespread interest has been shown on the use of thyroid hormones in the perioperative period, and the effect of cardiopulmonary bypass on thyroid hormone metabolism widely studied, there is no substantial evidence to justify routine use of thyroid hormones in patients undergoing coronary artery bypass grafting., There is no clear evidence at this point to support thyroid hormone replacement in the latter patients, and it may be potentially harmful. Rather, we hold that T3 treatment of various surgical and other patients with nonthyroidal illness should be deferred until proof of its therapeutic efficacy is demonstrated., Perioperative administration of triiodothyronine increased cardiac output slightly and decreased systemic vascular resistance, but it had no effect on operative outcome. Routine use after coronary surgery is thus not recommended., Although mild effects on myocardial performance may exist, we cannot recommend at this time the routine use of intravenous T(3) as an inotropic agent in patients undergoing coronary artery bypass graft surgery., Raising serum triiodothyronine concentrations in patients undergoing coronary-artery bypass surgery increases cardiac output and lowers systemic vascular resistance, but does not change outcome or alter the need for standard postoperative therapy., Thus, there seems to be no sound justification for a routine use of T3 in patients undergoing open-heart procedures.[SEP]", "label": "no"}
{"id": "converted_2934", "sentence1": "Have machine learning methods been used to predict the severity of major depressive disorder(MDD)?", "sentence2": "Here, we conduct a meta-review to identify predictors of response to antidepressant therapy in order to select robust input features for machine learning models of treatment response. , machine learning framework involving EEG-based functional connectivity to diagnose major depressive disorder (MDD)., Identification of risk factors of treatment resistance may be useful to guide treatment selection, avoid inefficient trial-and-error, and improve major depressive disorder (MDD) care. We extended the work in predictive modeling of treatment resistant depression (TRD) via partition of the data from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) cohort into a training and a testing dataset., persistence and severity of major depressive disorder from baseline self-reports,  These results confirm that clinically useful MDD risk-stratification models can be generated from baseline patient self-reports and that ML methods improve on conventional methods in developing such models, Furthermore, machine learning weighting factors may reflect an objective biomarker of major depressive disorder illness severity, based on abnormalities of brain structure., Notably, while the only information provided for training the classifiers was T(1)-weighted scans plus a categorical label (major depressive disorder versus controls), both relevance vector machine and support vector machine 'weighting factors' (used for making predictions) correlated strongly with subjective ratings of illness severity., BACKGROUND\nAlthough variation in the long-term course of major depressive disorder (MDD) is not strongly predicted by existing symptom subtype distinctions, recent research suggests that prediction can be improved by using machine learning methods., BACKGROUND Although variation in the long-term course of major depressive disorder (MDD) is not strongly predicted by existing symptom subtype distinctions, recent research suggests that prediction can be improved by using machine learning methods., BACKGROUND Growing evidence documents the potential of machine learning for developing brain based diagnostic methods for major depressive disorder (MDD)., OBJECTIVE We aimed to integrate neural data and an advanced machine learning technique to predict individual major depressive disorder (MDD) patient severity., Furthermore, machine learning weighting factors may reflect an objective biomarker of major depressive disorder illness severity, based on abnormalities of brain structure., <b>BACKGROUND</b>: Although variation in the long-term course of major depressive disorder (MDD) is not strongly predicted by existing symptom subtype distinctions, recent research suggests that prediction can be improved by using machine learning methods.[SEP]", "label": "yes"}
{"id": "converted_1953", "sentence1": "Is ABCE1 involved in ribosomal recycling?", "sentence2": "Ribosome recycling orchestrated by the ATP binding cassette (ABC) protein ABCE1 can be considered as the final-or the first-step within the cyclic process of protein synthesis, connecting translation termination and mRNA surveillance with re-initiation.,  Recent studies have identified ABCE1 as a ribosome-recycling factor important for translation termination in mammalian cells, yeast and also archaea., d a termination/prerecycling complex containing eRF1-ABCE1, ABCE1, a eukaryotic ribosome recycling factor[SEP]", "label": "yes"}
{"id": "converted_2166", "sentence1": "Is intraoperative radiotherapy used for treatment of glioblastoma?", "sentence2": " 1) Intraoperative radiotherapy ( IOR , 1,000-2,000 rad) was applied in 13 cases; the 2-year survival was 41.6%. , The median survival time after IORT was 12 months for 9 patients with glioblastoma or anaplastic astrocytoma, while it was 51 months for 8 patients with less infiltrative tumors (ependymoma, anaplastic ependymoma, and anaplastic oligodendroglioma). , It is concluded that IORT combined with extensive tumor removal has an acceptable toxicity in previously irradiated patients and can be effective for selected recurrent malignant brain tumors., CONCLUSIONS: The results of this study indicate that IORT can contribute to successful tumor treatment while neither increasing peri-operative morbidity nor subacute sequelae., This review compiles preclinical and clinical evidence for a dedicated treatment of both residual cancer cells and regional microenvironment using intraoperative radiotherapy (IORT).,  Intraoperative radiotherapy (IORT) is a pragmatic and effective approach to sterilize the margins from persistent tumor cells, abrogate post-injury proliferative stimuli and to bridge the therapeutic gap between surgery and radiochemotherapy. , [Surgical treatment and radiation therapy for glioblastoma multiforme, with special reference to intraoperative radiotherapy]., Rationale for intraoperative radiotherapy in glioblastoma., Intraoperative radiotherapy (IORT) was performed in 20 of 36 patients with glioma; 11 glioblastomas, 7 malignant astrocytomas, 2 benign astrocytomas., [Surgical treatment and radiation therapy for glioblastoma multiforme, with special reference to intraoperative radiotherapy], INTRAGO: intraoperative radiotherapy in glioblastoma multiforme—a phase I/II dose escalation study, Intraoperative cobalt-60 treatment of glioblastoma multiforme, An intraoperative remote afterloading endocurietherapy (ECT) technique with high-activity 60cobalt (60Co) for the treatment of glioblastoma multiforme (GM) is described, [Surgical treatment and radiation therapy for glioblastoma multiforme, with special reference to intraoperative radiotherapy]., Rationale for intraoperative radiotherapy in glioblastoma., Intraoperative cobalt-60 treatment of glioblastoma multiforme., INTRAGO: intraoperative radiotherapy in glioblastoma multiforme—a phase I/II dose escalation study., Intraoperative remote afterloading endocurietherapy with high-activity 60cobalt for treatment of glioblastoma multiforme., Combining intraoperative carmustine wafers and Stupp regimen in multimodal first-line treatment of primary glioblastomas., The intraoperative use of carmustine wafers in combination with Stupp regimen is a viable first-line treatment option of glioblastomas., An intraoperative remote afterloading endocurietherapy (ECT) technique with high-activity 60cobalt (60Co) for the treatment of glioblastoma multiforme (GM) is described., The study investigated if intraoperative use of carmustine wafers, particularly in combination with Stupp regimen, is a viable and safe first-line treatment option of glioblastomas.[SEP]", "label": "no"}
{"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_897", "sentence1": "Does magnesium sulfate improve outcomes of subarachnoid hemorrhage patients?", "sentence2": "CONCLUSION: Patients assigned a higher serum magnesium concentration had a reduced incidence of vasospasm as seen by angiography, but the difference was not statistically significant. Clinically significant outcomes were not different between groups., 158 patients (26·2%) had poor outcome in the magnesium group compared with 151 (25·3%) in the placebo group (risk ratio [RR] 1·03, 95% CI 0·85-1·25). Our updated meta-analysis of seven randomised trials involving 2047 patients shows that magnesium is not superior to placebo for reduction of poor outcome after aneurysmal subarachnoid haemorrhage (RR 0·96, 95% CI 0·86-1·08). INTERPRETATION: Intravenous magnesium sulphate does not improve clinical outcome after aneurysmal subarachnoid haemorrhage, therefore routine administration of magnesium cannot be recommended. , There is a tendency in the magnesium group to have better outcomes. , Due to inconsistently reported benefits and the occurrence of side effects, phase II data suggested that intravenous magnesium for SAH provided either no overall net benefit or uncertain trade-offs. Benefit was likewise not supported in the single phase III clinical trial., tatistically significant clinical benefits could not be demonstrated for the other drugs (clazosentan, statins, and magnesium). CONCLUSIONS: Insufficient evidence is available to support the use of the triple-H therapy, clazosentan, statins, or magnesium sulfate for the prevention of cerebral vasospasm following subarachnoid hemorrhage. , Magnesium sulfate decreased the rate of cerebral infarction, but not of DCI or poor functional outcome. Regarding outcome, a beneficial effect of magnesium sulfate on outcome can not be ruled out because of sample size limitations., CONCLUSIONS: The present findings do not lend support to a beneficial effect of magnesium sulphate infusion on delayed cerebral infarction. The reduction in DCI and improvement in the clinical outcomes of aneurysmal SAH patients following magnesium sulphate infusion observed in previous pilot studies are not confirmed, although a beneficial effect cannot be ruled out because of sample size limitation., Favorable outcome (Good recovery and moderate disability, as defined by Glasgow Outcome Scale) was achieved in 20 of 30 (67%) patients receiving magnesium sulfate infusion and 16 of 30 (53%) patients receiving placebo treatment, p = 0.292, odds ratio 1.750, 95% CI 0.616-4.974., Similarly, the pooled odds ratio for favorable outcome is 1.598, 95% CI 1.074-2.377, statistically significant. , RESULTS: The worst clinical outcomes at 6 months were seen in MgSO(4) group patients, with mean plasma magnesium concentrations in the fourth quartile, and in placebo group patients, with mean such concentrations in the third and fourth quartiles. CONCLUSIONS: No evidence was found to suggest that a higher mean plasma magnesium concentration improves clinical outcomes. On the contrary, we found an association between high plasma magnesium concentration and worse clinical outcomes., The proportions of patients with a favorable outcome at 6 months (Extended Glasgow Outcome Scale 5 to 8) were similar, 64% in the magnesium sulfate group and 63% in the saline group (OR, 1.0; 95% CI, 0.7 to 1.6). Secondary outcome analyses (modified Rankin Scale, Barthel Index, Short Form 36, and clinical vasospasm) also showed no significant differences between the 2 groups. , CONCLUSIONS: The results do not support a clinical benefit of intravenous magnesium sulfate infusion over placebo infusion in patients with acute aneurysmal subarachnoid hemorrhage., Magnesium infusion reduced the risk of poor outcome and delayed cerebral ischemia (DCI): the relative risk was 0.62 (95% confidence interval (CI) 0.46-0.83) and 0.73 (95% CI 0.53-1.00), respectively. , CONCLUSION: The meta-analysis suggests that intravenous magnesium therapy reduces the risk of DCI and poor outcome after aneurysmal SAH. , The incidence of delayed ischemic infarction was significantly lower in magnesium-treated patients (22% vs. 51%; p = .002); 34 of 54 magnesium patients and 27 of 53 control patients reached good outcome (p = .209)., BACKGROUND: A meta-analysis of current data suggests that magnesium sulfate infusion improves the outcome after aneurysmal subarachnoid hemorrhage through a reduction in delayed ischemic neurological deficit. , These data imply that intravenous magnesium therapy, besides a supposed beneficial effect on outcome, also provides pain relief for SAH patients, for whom it might also improve functional outcome., Preliminary evidence has suggested that magnesium sulfate infusion reduces delayed ischemic neurological deficit and improves clinical outcome after aneurysmal subarachnoid hemorrhage. , In a phase II randomized clinical trial of 283 patients, magnesium treatment reduced the risk of DCI by 34% and of poor outcome by 23%., BACKGROUND: Recent studies suggest that high-dose MgSO4 therapy is safe and reduces the incidence of DIND and subsequent poor outcome after SAH. , On-treatment analysis showed a significantly better outcome after 3 months (P = .017) and a trend toward better outcome after 1 year (P = .083). ,  CONCLUSIONS: High-dose MgSO4 therapy might be efficient as a prophylactic adjacent therapy after SAH to reduce the risk for poor outcome. , There was no significant difference in mortality rate at discharge (p = 0.328). A trend toward improved outcome as measured by the modifed Rankin Scale (p = 0.084), but not the Glasgow Outcome Scale (p = 1.0), was seen in the MgSO4 treated group. CONCLUSIONS: Analysis of the results suggests that MgSO4 infusion may have a role in cerebral vasospasm prophylaxis if therapy is initiated within 48 hours of aneurysm rupture., There was, however, no difference between groups in functional recovery or Glasgow Outcome Scale score. , Patients receiving MgSO4 tended to have fewer neurological deficits, better functional recovery and an improved score in GOS. , CONCLUSIONS: MgSO4 infusion after aneurysmal SAH is well tolerated and may be useful in producing better outcome., CONCLUSION: Magnesium did not seem to interfere in vasospasm frequency but apparently acted favorably in decreasing morbidity and length of hospital stay., None of the patients died; no CT evidence of ischemic infarction was present; and most had good outcomes (GOS 5 in 10 patients; GOS 4 in 8 patients)., At that time, 18 patients in the treatment group and 6 in the placebo group had an excellent outcome (risk ratio, 3.4; 95% CI, 1.3 to 8.9). CONCLUSIONS: This study suggests that magnesium reduces DCI and subsequent poor outcome, but the results are not yet definitive. , We observed a trend in which a higher percentage of patients obtained GOS scores of 4 or 5 in the group treated with MgSO4, but the trend did not reach a statistically significant level. , Magnesium sulfate treatment improves outcome in patients with subarachnoid hemorrhage: a meta-analysis study., BACKGROUND AND PURPOSE: Pilot clinical trials using magnesium sulfate in patients with acute aneurysmal subarachnoid hemorrhage have reported trends toward improvement in clinical outcomes., Preliminary evidence has suggested that magnesium sulfate infusion reduces delayed ischemic neurological deficit and improves clinical outcome after aneurysmal subarachnoid hemorrhage., Our results indicate that although there was reduced likelihood of a poor outcome for patients treated with magnesium sulfate after SAH, patient mortality was not improved., CONCLUSION: Administration of intra-arterial magnesium sulfate in combination with nicardipine was well tolerated in patients with subarachnoid hemorrhage and cerebral vasospasm without a significant change in MAP and ICP., Current evidence does not support the prophylactic use of magnesium sulfate in aneurysmal subarachnoid hemorrhage, Preliminary evidence has suggested that magnesium sulfate infusion reduces delayed ischemic neurological deficit and improves clinical outcome after aneurysmal subarachnoid hemorrhage, A meta-analysis of current data suggests that magnesium sulfate infusion improves the outcome after aneurysmal subarachnoid hemorrhage through a reduction in delayed ischemic neurological deficit, Despite the publication of several randomized controlled studies, there is still much debate on whether magnesium sulfate improves outcome in patients with aneurysmal subarachnoid hemorrhage, Magnesium sulphate is a neuroprotective agent that might improve outcome after aneurysmal subarachnoid haemorrhage by reducing the occurrence or improving the outcome of delayed cerebral ischaemia[SEP]Relations: Magnesium sulfate has relations: drug_drug with Magnesium, drug_drug with Magnesium. Nicardipine has relations: contraindication with cerebral infarction, drug_drug with Magnesium, contraindication with cerebral infarction, drug_drug with Magnesium.", "label": "no"}
{"id": "converted_4038", "sentence1": "Is the process of DNA loop-extrusion independent of ATP?", "sentence2": "The DNA-organizing mechanism of condensin depends on the energy of ATP hydrolysis but how this activity specifically promotes proper compaction and segregation of chromosomes during mitosis remains poorly understood., We suggest that loading and translocation are mediated by conformational changes in cohesin's hinge driven by cycles of ATP hydrolysis., Using ultra-deep Hi-C, we show that loop domains form by a process that requires cohesin ATPases., Strikingly, without ATP, we observe the emergence of hundreds of CTCF-independent loops that link regulatory DNA. , Each TAD emerges from multiple loops dynamically formed through extrusion, contrary to typical illustrations of single static loops. , However, the model requires a motor to generate the loops, and although cohesin is a strong candidate for the extruding factor, a suitable motor protein (or a motor activity in cohesin itself) has yet to be found. Here we explore a new hypothesis: that there is no motor, and thermal motion within the nucleus drives extrusion., We observed that a single condensin complex is able to extrude tens of kilobase pairs of DNA at a force-dependent speed of up to 1500 base pairs per second, using the energy of adenosine triphosphate hydrolysis, Our model explains what can be the driving force of chromatin loop extrusion and how it can be ensured that loops grow quickly and in a good direction. In addition, the supercoiling-driven loop extrusion mechanism is consistent with earlier explanations proposing why TADs flanked by convergent CTCF binding sites form more stable chromatin loops than TADs flanked by divergent CTCF binding sites., Oligomerization and ATP stimulate condensin-mediated DNA compaction., Strikingly, without ATP, we observe the emergence of hundreds of CTCF-independent loops that link regulatory DNA., DNA compaction by cohesin requires adenosine triphosphate (ATP) hydrolysis and is force sensitive., The identification and quantification of further initiation steps--ATP binding and extrusion of an initial DNA loop--allowed us to deduce a complete kinetic reinitiation scheme., In support of this model, single-molecule imaging experiments indicate that Saccharomyces cerevisiae condensin complexes can extrude DNA loops in an ATP-hydrolysis-dependent manner in vitro., These structures depend on cohesin, a ring-shaped DNA-entrapping adenosine triphosphatase (ATPase) complex that has been proposed to form loops by extrusion., Loop formation and maintenance depend on cohesin's ATPase activity and on NIPBL-MAU2, but not on topological entrapment of DNA by cohesin.[SEP]", "label": "yes"}
{"id": "converted_4", "sentence1": "Is RANKL secreted from the cells?", "sentence2": "Osteoprotegerin (OPG) is a soluble secreted factor that acts as a decoy receptor for receptor activator of NF-κB ligand (RANKL) , Osteoprotegerin (OPG) is a secreted glycoprotein and a member of the tumor necrosis factor receptor superfamily. It usually functions in bone remodeling, by inhibiting osteoclastogenesis through interaction with a receptor activator of the nuclear factor κB (RANKL)., e RANKL/OPG ratio secreted by osteoblasts increased and RANK expression by osteoclasts increased, leading to increased osteoclastogenesis, Osteoprotegerin (OPG) is an essential secreted protein in bone turnover due to its role as a decoy receptor for the Receptor Activator of Nuclear Factor-kB ligand (RANKL) in the osteoclasts, thus inhibiting their differentiation, We identify a TNFSF11 transcript variant that extends the originally identified transcript encoding secreted RANKL., Activated human T cells express alternative mRNA transcripts encoding a secreted form of RANKL., OPG, on the other hand, is secreted by osteoblast as a decoy receptor for RANKL, prevents RANKL from binding to RANK and thus prevents bone resorption, Receptor activator of nuclear factor κB ligand (RANKL) and osteoprotegerin (OPG) are cytokines predominantly secreted by osteoblasts and play a central role in differentiation and functional activation of osteoclasts, Although B. abortus-activated T cells actively secreted the pro-osteoclastogenic cytokines RANKL and IL-17, osteoclastogenesis depended on IL-17, because osteoclast generation induced by Brucella-activated T cells was completely abrogated when these cells were cultured with BMMs from IL-17 receptor knockout mice. ,  osteoclastogenesis and bone destruction in autoimmune arthritis. We isolated human fibroblasts from RA, pyrophosphate arthropathy (PPA) and osteoarthritis (OA) patients and analyzed their RANKL/OPG expression profile and the capacity of their secreted factors to induce osteoclastogenesis., Osteoprotegerin (OPG) and receptor activator of nuclear factor κB ligand (RANKL) are cytokines predominantly secreted by osteoblasts and play critical roles in the differentiation and function of osteoclasts. [SEP]Relations: tumor necrosis factor receptor binding has relations: molfunc_protein with TNFSF11, molfunc_protein with TNFSF11, molfunc_protein with TNFSF11, molfunc_protein with TNFSF11. osteoarthritis susceptibility has relations: disease_disease with osteoarthritis, disease_disease with osteoarthritis.", "label": "yes"}
{"id": "converted_3193", "sentence1": "Is the Philadelphia chromosome a fusion between parts of chromosomes 1 and 9?", "sentence2": " The Philadelphia chromosome, t(9;22)(q34;q11), is present in 95% of CML patients, resulting in constitutive tyrosine kinase activity; however, ~5% of CML patients possess a Philadelphia variant. , Chronic Myeloid Leukemia (CML) is myeloproliferative neoplasm characterized by Philadelphia chromosome which is a balanced translocation between chromosome 9 and 22 in 90% of cases., Chronic myeloid leukemia is a stem cell disease with the presence of Philadelphia chromosome generated through reciprocal translocation of chromosome 9 and 22. [SEP]", "label": "no"}
{"id": "converted_1278", "sentence1": "Is there evidence for de novo genesis of enhancers in vertebrates?", "sentence2": "De novo genesis of enhancers in vertebrates., Evolutionary innovation relies partially on changes in gene regulation. While a growing body of evidence demonstrates that such innovation is generated by functional changes or translocation of regulatory elements via mobile genetic elements, the de novo generation of enhancers from non-regulatory/non-mobile sequences has, to our knowledge, not previously been demonstrated. Here we show evidence for the de novo genesis of enhancers in vertebrates. For this, we took advantage of the massive gene loss following the last whole genome duplication in teleosts to systematically identify regions that have lost their coding capacity but retain sequence conservation with mammals. We found that these regions show enhancer activity while the orthologous coding regions have no regulatory activity. These results demonstrate that these enhancers have been de novo generated in fish. By revealing that minor changes in non-regulatory sequences are sufficient to generate new enhancers, our study highlights an important playground for creating new regulatory variability and evolutionary innovation., Here we show evidence for the de novo genesis of enhancers in vertebrates., While a growing body of evidence demonstrates that such innovation is generated by functional changes or translocation of regulatory elements via mobile genetic elements, the de novo generation of enhancers from non-regulatory/non-mobile sequences has, to our knowledge, not previously been demonstrated., While a growing body of evidence demonstrates that such innovation is generated by functional changes or translocation of regulatory elements via mobile genetic elements, the de novo generation of enhancers from non-regulatory/non-mobile sequences has, to our knowledge, not previously been demonstrated, While a growing body of evidence demonstrates that such innovation is generated by functional changes or translocation of regulatory elements via mobile genetic elements, the de novo generation of enhancers from non-regulatory/non-mobile sequences has, to our knowledge, not previously been demonstrated. Here we show evidence for the de novo genesis of enhancers in vertebrates. For this, we took advantage of the massive gene loss following the last whole genome duplication in teleosts to systematically identify regions that have lost their coding capacity but retain sequence conservation with mammals. , Here we show evidence for the de novo genesis of enhancers in vertebrates. , While a growing body of evidence demonstrates that such innovation is generated by functional changes or translocation of regulatory elements via mobile genetic elements, the de novo generation of enhancers from non-regulatory/non-mobile sequences has, to our knowledge, not previously been demonstrated. Here we show evidence for the de novo genesis of enhancers in vertebrates.[SEP]", "label": "yes"}
{"id": "converted_1340", "sentence1": "Are there enhancer RNAs (eRNAs)?", "sentence2": "active enhancers are transcribed, producing a class of noncoding RNAs called enhancer RNAs (eRNAs). eRNAs are distinct from long noncoding RNAs (lncRNAs), but these two species of noncoding RNAs may share a similar role in the activation of mRNA transcription,  eRNAs may then facilitate enhancer-promoter interaction or activate promoter-driven transcription, Enhancer RNAs: a class of long noncoding RNAs synthesized at enhancers, Enhancer RNAs and regulated transcriptional programs, enhancers have been found to be broadly transcribed, resulting in the production of enhancer-derived RNAs, or eRNAs, The emerging roles of eRNAs in transcriptional regulatory networks, we found certain enhancer RNAs (eRNAs) regulate chromatin accessibility of the transcriptional machinery at loci encoding master regulators of myogenesis (i.e., MyoD/MyoG), thus suggesting their significance and site-specific impact in cellular programming, Enhancer RNAs: the new molecules of transcription,  the discovery that distal regulatory elements known as enhancers are transcribed and such enhancer-derived transcripts (eRNAs) serve a critical function in transcriptional activation has added a new dimension to transcriptional regulation, eRNAs reach the heart of transcription, Recent studies have disclosed the function of enhancer RNAs (eRNAs), which are long non-coding RNAs transcribed from gene enhancer regions, in transcriptional regulation., Since the discovery that many transcriptional enhancers are transcribed into long noncoding RNAs termed \"enhancer RNAs\" (eRNAs), their putative role in enhancer function has been debated., Recent studies have revealed that active enhancers are transcribed, producing a class of noncoding RNAs called enhancer RNAs (eRNAs)., Enhancer RNAs (eRNAs) are a class of long noncoding RNAs (lncRNA) expressed from active enhancers, whose function and action mechanism are yet to be firmly established., In addition to widespread transcription of long non-coding RNAs (lncRNAs) in mammalian cells, bidirectional ncRNAs are transcribed on enhancers, and are thus referred to as enhancer RNAs (eRNAs)., In addition to widespread transcription of long non-coding RNAs (lncRNAs) in mammalian cells, bidirectional ncRNAs are transcribed on enhancers, and are thus referred to as enhancer RNAs (eRNAs). , A subset of enhancers are occupied by RNA polymerase II (RNAP II) and transcribed to produce long non-coding RNAs termed eRNAs. , Very recent evidence has indicted that some eRNAs play a role in initiating or activating transcription, possibly by helping recruit and/or stabilize binding of the general transcription machinery to the proximal promoter of their target genes. , In addition to widespread transcription of long non-coding RNAs (lncRNAs) in mammalian cells, bidirectional ncRNAs are transcribed on enhancers, and are thus referred to as enhancer RNAs (eRNAs). However, it has remained unclear whether these eRNAs are functional or merely a reflection of enhancer activation. , Notably, RNAPII at enhancers transcribes bi-directionally a novel class of enhancer RNAs (eRNAs) within enhancer domains defined by the presence of histone H3 monomethylated at lysine 4. The level of eRNA expression at neuronal enhancers positively correlates with the level of messenger RNA synthesis at nearby genes, suggesting that eRNA synthesis occurs specifically at enhancers that are actively engaged in promoting mRNA synthesis., A function of CBP at enhancers may be to recruit RNA polymerase II (RNAPII), as we also observed activity-regulated RNAPII binding to thousands of enhancers. Notably, RNAPII at enhancers transcribes bi-directionally a novel class of enhancer RNAs (eRNAs) within enhancer domains defined by the presence of histone H3 monomethylated at lysine 4.,  Enhancer RNAs (eRNAs) are a class of long noncoding RNAs (lncRNA) expressed from active enhancers, whose function and action mechanism are yet to be firmly established. Here we show that eRNAs facilitate the transition of paused RNA polymerase II (RNAPII) into productive elongation by acting as a decoy for the negative elongation factor (NELF) complex upon induction of immediate early genes (IEGs) in neurons., Recent studies have disclosed the function of enhancer RNAs (eRNAs), which are long non-coding RNAs transcribed from gene enhancer regions, in transcriptional regulation., Recent studies have revealed that active enhancers are transcribed, producing a class of noncoding RNAs called enhancer RNAs (eRNAs). eRNAs are distinct from long noncoding RNAs (lncRNAs), but these two species of noncoding RNAs may share a similar role in the activation of mRNA transcription., Enhancer RNAs (eRNAs) are a class of long noncoding RNAs (lncRNA) expressed from active enhancers,, In addition to widespread transcription of long non-coding RNAs (lncRNAs) in mammalian cells, bidirectional ncRNAs are transcribed on enhancers, and are thus referred to as enhancer RNAs (eRNAs). However, it has remained unclear whether these eRNAs are functional or merely a reflection of enhancer activation.,  Recent studies have revealed that active enhancers are transcribed, producing a class of noncoding RNAs called enhancer RNAs (eRNAs). eRNAs are distinct from long noncoding RNAs (lncRNAs), but these two species of noncoding RNAs may share a similar role in the activation of mRNA transcription.[SEP]", "label": "yes"}
{"id": "converted_2", "sentence1": "Is the protein Papilin secreted?", "sentence2": "Using expression analysis, we identify three genes that are transcriptionally regulated by HLH-2: the protocadherin cdh-3, and two genes encoding secreted extracellular matrix proteins, mig-6/papilin and him-4/hemicentin. , We found that mig-6 encodes long (MIG-6L) and short (MIG-6S) isoforms of the extracellular matrix protein papilin, each required for distinct aspects of DTC migration. Both MIG-6 isoforms have a predicted N-terminal papilin cassette, apilins are homologous, secreted extracellular matrix proteins which share a common order of protein domains. , The TSR superfamily is a diverse family of extracellular matrix and transmembrane proteins, many of which have functions related to regulating matrix organization, cell-cell interactions and cell guidance. This review samples some of the contemporary literature regarding TSR superfamily members (e.g. F-spondin, UNC-5, ADAMTS, papilin, and TRAP) where specific functions are assigned to the TSR domains., Papilins are extracellular matrix proteins , Papilin is an extracellular matrix glycoprotein ,  Collagen IV, laminin, glutactin, papilin, and other extracellular matrix proteins were made primarily by hemocytes and were secreted into the medium. , A sulfated glycoprotein was isolated from the culture media of Drosophila Kc cells and named papilin.[SEP]Relations: ADAMTS4 has relations: cellcomp_protein with extracellular matrix, cellcomp_protein with extracellular matrix.", "label": "yes"}
{"id": "converted_1543", "sentence1": "Is there a mouse model for Fanconi anemia?", "sentence2": "Cyclophosphamide promotes engraftment of gene-modified cells in a mouse model of Fanconi anemia without causing cytogenetic abnormalities, We compared Cy preconditioning with fludarabine (Flu) or cytarabine (AraC) or no conditioning as a control in fanca ( -/- ) mutant mice receiving gene-modified bone marrow cells, We conclude that Cy is an effective and superior preparative regimen with respect to engraftment of lentivirus-transduced cells and functional correction in fanca ( -/- ) mice, To study whether there is a causal relationship between FA pathway defects and tumour development, we have generated a mouse model with a targeted disruption of the FA core complex gene Fancf, Fancf-deficient mouse embryonic fibroblasts displayed a phenotype typical for FA cells: they showed an aberrant response to DNA cross-linking agents as manifested by G(2) arrest, chromosomal aberrations, reduced survival, and an inability to monoubiquitinate FANCD2, Fancf homozygous mice were viable, born following a normal Mendelian distribution, and showed no growth retardation or developmental abnormalities. The gonads of Fancf mutant mice functioned abnormally, showing compromised follicle development and spermatogenesis as has been observed in other FA mouse models and in FA patients, In a cohort of Fancf-deficient mice, we observed decreased overall survival and increased tumour incidence, To provide further experimental access to the FA-M complementation group we have generated Fancm-deficient mice by deleting exon 2, FANCM deficiency caused hypogonadism in mice and hypersensitivity to cross-linking agents in mouse embryonic fibroblasts (MEFs), thus phenocopying other FA mouse models, Fancm(Delta2/Delta2) mice also showed unique features atypical for FA mice, including underrepresentation of female Fancm(Delta2/Delta2) mice and decreased overall and tumor-free survival, Fancm-deficient mice reveal unique features of Fanconi anemia complementation group M, Fancf-deficient mice are prone to develop ovarian tumours, In vivo proliferation advantage of genetically corrected hematopoietic stem cells in a mouse model of Fanconi anemia FA-D1, Using an FA mouse model with a marked hematopoietic phenotype, the FA-D1 (Brca2(Delta27/Delta27)) mice, we demonstrate that the lentivirus-mediated gene therapy of FA HSCs results in the progressive expansion of genetically corrected clones in mild-conditioned FA-D1 recipients, Consistent with these data, hematopoietic progenitors from FA recipients progressively became mitomycin C resistant and their chromosomal instability was reverted, Hematopoietic dysfunction in a mouse model for Fanconi anemia group D1, We have investigated the hematopoietic phenotype of mice with a hypomorphic mutation in the Brca2/Fancd1 gene (Brca2(Delta27/Delta27) mutation), Conventional BM competition experiments showed a marked repopulation defect in Brca2(Delta27/Delta27) hematopoietic stem cells (HSCs), compared to wild-type HSCs, Moreover, we have observed for the first time in a DNA repair disease model a very significant proliferation defect in Brca2(Delta27/Delta27) HSCs maintained in their natural physiological environment, The hematopoietic phenotype associated with the Brca2(Delta27/Delta27) mutation suggests that this FA-D1 mouse model will constitute an important tool for the development of new therapies for FA, including gene therapy, In vitro phenotypic correction of hematopoietic progenitors from Fanconi anemia group A knockout mice, In this study we characterized the hematopoietic phenotype of a Fanca knockout mouse model and corrected the main phenotypic characteristics of the bone marrow (BM) progenitors using retroviral vectors, The hematopoiesis of these animals was characterized by a modest though significant thrombocytopenia, consistent with reduced numbers of BM megakaryocyte progenitors, As observed in other FA models, the hematopoietic progenitors from Fanca(-/-) mice were highly sensitive to mitomycin C (MMC), Aiming to correct the phenotype of Fanca(-/-) progenitors, purified Lin(-)Sca-1(+) cells were transduced with retroviral vectors encoding the enhanced green fluorescent protein (EGFP) gene and human FANCA genes. Lin(-)Sca-1(+) cells from Fanca(-/-) mice were transduced with an efficiency similar to that of samples from wild-type mice. More significantly, transductions with FANCA vectors corrected both the MMC hypersensitivity as well as the impaired ex vivo expansion ability that characterized the BM progenitors of Fanca(-/-) mice,  The Btbd12 knockout mouse therefore establishes a disease model for Fanconi anemia and genetically links a regulator of nuclease incision complexes to the Fanconi anemia DNA crosslink repair pathway., Hematopoietic dysfunction in a mouse model for Fanconi anemia group D1., Bone marrow failure in the Fanconi anemia group C mouse model after DNA damage., In vivo proliferation advantage of genetically corrected hematopoietic stem cells in a mouse model of Fanconi anemia FA-D1., Assessment of the flexed-tail mouse as a possible model for Fanconi anemia: analysis of mitomycin C-induced micronuclei., The Btbd12 knockout mouse therefore establishes a disease model for Fanconi anemia and genetically links a regulator of nuclease incision complexes to the Fanconi anemia DNA crosslink repair pathway., Cyclophosphamide promotes engraftment of gene-modified cells in a mouse model of Fanconi anemia without causing cytogenetic abnormalities., Mouse models of Fanconi anemia., Five of these genes have been deleted or mutated in the mouse, as well as a sixth key regulatory gene, to create mouse models of Fanconi anemia., This review summarizes the phenotype of each of the Fanconi anemia mouse models and highlights how genetic and interventional studies using the strains have yielded novel insight into therapeutic strategies for Fanconi anemia and into how the Fanconi anemia pathway protects against genomic instability., To study FA complementation group A using the mouse as a model system, we cloned and characterized the mouse homolog of the human FANCA cDNA., Here we describe the phenotype of the Btbd12 knockout mouse, the mouse ortholog of SLX4, which recapitulates many key features of the human genetic illness Fanconi anemia., Five of these genes have been deleted or mutated in the mouse, as well as a sixth key regulatory gene, to create mouse models of Fanconi anemia, In contrast to observations made in other Fanconi anemia (FA) mouse models, low numbers of hematopoietic colony-forming cells (CFCs) were noted in Brca2(Delta27/Delta27) mice, either young or adult, Fanconi anemia group A and C double-mutant mice: functional evidence for a multi-protein Fanconi anemia complex., In addition, mouse models are also useful for testing treatments for FA., Development and characterization of immortalized fibroblastoid cell lines from an FA(C) mouse model., These mouse models display the characteristic FA feature of cellular hypersensitivity to DNA cross-linking agents[SEP]Relations: Cytarabine has relations: drug_drug with Cyclophosphamide, drug_drug with Cyclophosphamide. Fanconi anemia complementation group has relations: disease_protein with FANCD2, disease_disease with Fanconi anemia, disease_protein with FANCD2, disease_disease with Fanconi anemia, disease_protein with FANCD2, disease_disease with Fanconi anemia, disease_protein with FANCD2, disease_disease with Fanconi anemia, disease_protein with FANCD2, disease_disease with Fanconi anemia, disease_protein with FANCD2, disease_disease with Fanconi anemia. Mitomycin has relations: drug_drug with Cyclophosphamide, drug_drug with Cyclophosphamide, drug_drug with Cyclophosphamide, drug_drug with Cyclophosphamide. Hypogonadism has relations: disease_phenotype_positive with Fanconi anemia, disease_phenotype_positive with Fanconi anemia.", "label": "yes"}
{"id": "converted_3563", "sentence1": "Are genes that escape X-chromosome inactivation related to mental impairment?", "sentence2": "Mutation screening of the MECP2 gene in a large cohort of 613 fragile-X negative patients with mental retardation., The first one, the double nucleotide substitution c.1162_1163delinsTA leading to a premature stop codon (p.Pro388X) was found in a female patient with random X-inactivation, presenting with borderline mental impairment without any features of Rett syndrome. , the c.679C>G substitution, changing a glutamine to a glutamate in the transcriptional repression functional domain (p.Gln227Glu), was found in a female patient with a moderately biased X-chromosome inactivation profile and presenting with mild intellectual delay and minor psychotic features, Genes that escape X-inactivation in humans have high intraspecific variability in expression, are associated with mental impairment but are not slow evolving.,  The newly described escape genes cluster on the X chromosome in the same chromosomal regions as the previously known escapees. There is an excess of escaping genes associated with mental retardation, consistent with this being a common phenotype of polyX phenotypes.[SEP]Relations: MECP2 has relations: disease_protein with Rett syndrome, disease_protein with Rett syndrome.", "label": "yes"}
{"id": "converted_62", "sentence1": "Is pregnancy an additional risk during during H1N1 infection?", "sentence2": "H1N1 influenza in pregnancy can be associated with severe complications, This case series confirms a high number of complications in pregnant women due to pandemic H1N1/09., Pregnant women might be at increased risk for complications from pandemic H1N1 virus infection., Pregnant women are at increased risk for complications from pandemic influenza H1N1 virus infection. , Vaccination of pregnant women against influenza A (H1N1) by Russian subunit formulation (MonoGrippol plus) showed reactogenicity comparable to control group by the level of influence on general metabolic and immunologic homeostasis and on the course of pregnancy, which is an evidence of its safety, Pregnancy was identified as a major risk factor for increased mortality and morbidity due to H1N1 influenza in the pandemic of 2009 to 2010, While it is not possible to ascertain retrospectively if myocarditis was caused by either infection with H1N1 virus or as a result of pregnancy (in the absence of endomyocardial biopsies), the significant association with myocardial involvement in both women demonstrates the increased risk of exposure to H1N1 influenza virus in pregnant women., Although limited in size, the fully prospective nature of the safety follow-up of these women vaccinated during pregnancy is unique and offers an important degree of reassurance for the use of the AS03 adjuvanted H1N1 (2009) vaccine in this high risk group for H1N1 infection., During the H1N1 2009 pandemic, pregnant women constituted one of the priority groups for vaccination in many countries, creating a need for close monitoring of the safety of the vaccine in pregnant women, Emerging data suggest that pregnancy conveys high risk for severe complications from the 2009 pandemic influenza A virus (2009 H1N1) infection, Pregnant women have been identified as a group at risk, both for respiratory complications than for the admissions to the Intensive Care Unit (ICU) during the 2009 H1N1 influenza pandemic, This report mitigates substantially the presumed severity of pandemic H1N1/09 influenza infection during pregnancy, The results of our study do not indicate a risk for the pregnant woman and the developing embryo/fetus after H1N1 vaccination, This large cohort study found no evidence of an increased risk of fetal death associated with exposure to an adjuvanted pandemic A/H1N1 2009 influenza vaccine during pregnancy, Our results suggest that second- or third-trimester H1N1 vaccination was associated with improved fetal and neonatal outcomes during the recent pandemic, Pregnant women might thus be at increased risk of complications from pandemic H1N1 virus infection, and illness may progress rapidly, Pregnant women with H1N1 infection seem to benefit from antiviral therapy., arly identification and treatment were the most important factors in different countries and areas examined., The vaccine and antiviral drugs that have been the most efficient means to control the novel virus appear to be safe but require more extensive study, However, there were significant differences between the two groups in relation to mean age, treatment with oseltamivir, schooling, and presence of other risk factors, To investigate whether exposure to an adjuvanted influenza A(H1N1)pdm09 vaccine during pregnancy was associated with increased risk of adverse fetal outcomes., In this Danish cohort, exposure to an adjuvanted influenza A(H1N1)pdm09 vaccine during pregnancy was not associated with a significantly increased risk of major birth defects, preterm birth, or fetal growth restriction, Most people affected by the virus, including pregnant women, suffer a mild viral illness, and make a full recovery, Pregnant women, because of their altered immunity and physiological adaptations, are at higher risk of developing pulmonary complications, especially in the second and third trimesters, The pregnancy outcomes were also poor for women who were affected by the virus with a fivefold increase in the perinatal mortality rate and threefold increase in the preterm delivery rate, regnant women were at increased risk for serious outcomes of 2009 pandemic influenza A virus subtype H1N1 (influenza A[H1N1]pdm09) infection, but little is known about the overall impact of the pandemic on neonatal and maternal outcomes, In this large, geographically diverse population, A(H1N1)pdm09 infection increased the risk for hospitalization during pregnancy, Vaccination during pregnancy with Pandemrix(®) appeared to have no ill effects on the pregnancy. On the contrary, the rate of preterm birth and low birthweight was lower than expected, which agrees with some previous results, During the influenza A(H1N1)pmd09 pandemic, although many cases occurred in younger adults, the risk factors identified for severe infections and complications were similar to those for seasonal influenza, including chronic respiratory, renal, liver, and heart diseases., In terms of pregnancy, the studies have shown contradictory results due to variations in methodology and medical care., However, it seems that pregnancy, particularly during the third trimester, increases the risk of complications, and that early antiviral treatment is associated with improved outcomes., Pregnant women with mild clinical illness secondary to 2009 H1N1 were not at a greater risk of adverse pregnancy outcomes, However, severely infected women were more likely to deliver SGA infants, Gestational age is associated with the risk of developing critical infection. The risk increases with increasing weeks of gestation.,  Following the start of winter in Liaoning province in China, the number of pregnant women infected with influenza increased significantly, regnancy, with or without additional complications, constitutes a high-risk condition for complications of influenza infection and warrants early intervention with neuraminidase inhibitors such as oseltamivir, if influenza is suspected[SEP]", "label": "yes"}
{"id": "converted_3900", "sentence1": "Are Toll-like receptors (TLRs) induced by microbes?", "sentence2": "The C-type lectin receptor CLEC4E and Toll-like receptor TLR4 expressed by host cells are among the first line of defense in encountering pathogens., Gram-negative bacteria and endogenous molecules coordinate to trigger inflammatory cascades via Toll-like receptor 4 to induce excessive expression of cytokines such as tumor necrosis factor-α and to activate NLRP3 inflammasome, a multiprotein complex that processes pro-interleukin-1β into its mature form. , During viral infection, viral nucleic acids are detected by virus sensor proteins including toll-like receptor 3 or retinoic acid-inducible gene I-like receptors (RLRs) in mammalian cells. , Toll-like receptor 9 (TLR9) activation is attributed to delivery of bacterial DNA, We determine that HBCs have the capacity to play a defensive role, where they are responsive to Toll-like receptor stimulation and are microbicidal.[SEP]", "label": "yes"}
{"id": "converted_2056", "sentence1": "Is PUVA therapy indicated for eczema treatment?", "sentence2": "With bath PUVA treatment, the best results were found in patients with hyperkeratotic eczema (17/22; 77% good clinical response) followed by patients with palmoplantar psoriasis (26/41; 63%) and patients with dyshidrotic eczema (8/16; 50%). , Oral vs. bath PUVA using 8-methoxypsoralen for chronic palmoplantar eczema., Both oral and bath PUVA with 8-methoxypsoralen (8-MOP) have been shown to be effective in the treatment of chronic palmoplantar eczema. , Oral PUVA is preferable for patients with hyperkeratotic eczema and bath PUVA for patients with dyshidrotic eczema., Treatment of hand eczema is dominated by the administration of topical glucocorticosteriods. If topical treatment fails, the best second-line option is ultraviolet (UV) therapy alone or as combination therapy. UVB and PUVA (psoralen plus UVA) therapy is effective and has relatively few side effects. , Although local PUVA has been proven to be effective in the treatment of chronic hand eczema, little is known about the efficacy and safety of local narrowband UVB (TL-01) for this condition., Local narrowband UVB phototherapy regimen is as effective as paint-PUVA therapy in patients with chronic hand eczema of dry and dyshidrotic types., Smoking is likely to be a reason for the failure of bath-PUVA therapy in the treatment of chronic palmoplantar eczema, in particular regarding smokers with eczema of the dyshidrotic type where no complete remission was achieved., Treatment of chronic palmoplantar eczema with local bath-PUVA therapy., Bath-PUVA therapy has been described as successful treatment for palmoplantar eczema., Systemic PUVA therapy may be useful in the treatment of chronic palmoplantar eczema., A new psoralen-containing gel for topical PUVA therapy: development, and treatment results in patients with palmoplantar and plaque-type psoriasis, and hyperkeratotic eczema., These results indicate that topical PUVA therapy with psoralen in aqueous gel is a useful therapeutic modality for treatment of psoriasis patients, and patients with recalcitrant dermatoses such as palmoplantar psoriasis and hyperkeratotic eczema., In order to evaluate environmental influences possibly having an impact on the efficacy of this therapy, smokers and non-smokers suffering from palmoplantar eczema treated with bath-PUVA therapy were compared., Does smoking influence the efficacy of bath-PUVA therapy in chronic palmoplantar eczema?, PUVA therapy caused acute aggravation of the eczema., Hyperkeratotic eczema cleared significantly better with oral than with bath PUVA (P=0.03).CONCLUSION: Oral PUVA is preferable for patients with hyperkeratotic eczema and bath PUVA for patients with dyshidrotic eczema., BACKGROUND: Systemic PUVA therapy may be useful in the treatment of chronic palmoplantar eczema., These results indicate that topical PUVA therapy with psoralen in aqueous gel is a useful therapeutic modality for treatment of psoriasis patients, and patients with recalcitrant dermatoses such as palmoplantar psoriasis and hyperkeratotic eczema., Vitiligo (60.9%) was the commonest skin disorder treated with PUVA, followed by psoriasis (20.9%), endogenous eczema (11.3%), mycosis fungoides (3.5%), lichen amyloidosis (2.6%) and prurigo nodularis (0.9%)., bath PUVA using 8-methoxypsoralen for chronic palmoplantar eczema., A 36-year-old female patient was treated with PUVA for dyshidrotic eczema that had not shown sufficient response to topical therapy over the previous months., BACKGROUND: Both oral and bath PUVA with 8-methoxypsoralen (8-MOP) have been shown to be effective in the treatment of chronic palmoplantar eczema., One patient with hand eczema consistently had detectable 8-MOP levels 1 hour after topical PUVA treatments.CONCLUSION: This report indicates that there is minimal, if any, systemic absorption of 8-MOP after topical PUVA treatment of patients with palmoplantar psoriasis., In the narrowband UVB-treated side, the tolerance of all the patients to the treatment was good all patients well-tolerated the treatment with the exception of mild xerosis that responded to topical emollients.Local narrowband UVB phototherapy regimen is as effective as paint-PUVA therapy in patients with chronic hand eczema of dry and dyshidrotic types, Bath-PUVA therapy has been described as successful treatment for palmoplantar eczema, Smoking is likely to be a reason for the failure of bath-PUVA therapy in the treatment of chronic palmoplantar eczema, in particular regarding smokers with eczema of the dyshidrotic type where no complete remission was achieved, Systemic PUVA therapy may be useful in the treatment of chronic palmoplantar eczema, However, few data are available on the effectiveness of local bath-PUVA therapy in palmoplantar eczema.Our purpose was to assess the effectiveness of local bath-PUVA therapy in 28 patients with chronic palmar or plantar eczema or both who were resistant to conventional topical treatment.After fungal or bacterial infection had been excluded in all patients, hands or feet or both were soaked for 15 minutes in warm water containing 1 mg/L 8-methoxypsoralen, No phototoxic reactions were observed.Local bath-PUVA therapy is of value in the management of chronic palmoplantar eczema resistant to standard modes of topical treatment, Treatment of chronic palmoplantar eczema with local bath-PUVA therapy, Bath-PUVA therapy has been described as successful treatment for palmoplantar eczema. , Smoking is likely to be a reason for the failure of bath-PUVA therapy in the treatment of chronic palmoplantar eczema, in particular regarding smokers with eczema of the dyshidrotic type where no complete remission was achieved., OBJECTIVE: Our purpose was to assess the effectiveness of local bath-PUVA therapy in 28 patients with chronic palmar or plantar eczema or both who were resistant to conventional topical treatment. , CONCLUSION: Local bath-PUVA therapy is of value in the management of chronic palmoplantar eczema resistant to standard modes of topical treatment. , Topical PUVA therapy for chronic hand eczema., However, few data are available on the effectiveness of local bath-PUVA therapy in palmoplantar eczema.Our purpose was to assess the effectiveness of local bath-PUVA therapy in 28 patients with chronic palmar or plantar eczema or both who were resistant to conventional topical treatment.After fungal or bacterial infection had been excluded in all patients, hands or feet or both were soaked for 15 minutes in warm water containing 1 mg/L 8-methoxypsoralen., No phototoxic reactions were observed.Local bath-PUVA therapy is of value in the management of chronic palmoplantar eczema resistant to standard modes of topical treatment., Smoking is likely to be a reason for the failure of bath-PUVA therapy in the treatment of chronic palmoplantar eczema, in particular regarding smokers with eczema of the dyshidrotic type where no complete remission was achieved., However, our own observations showed that patients with palmoplantar eczema of the dyshidrotic or hyperkeratotic type responded only partially to bath-PUVA therapy., In the narrowband UVB-treated side, the tolerance of all the patients to the treatment was good all patients well-tolerated the treatment with the exception of mild xerosis that responded to topical emollients.Local narrowband UVB phototherapy regimen is as effective as paint-PUVA therapy in patients with chronic hand eczema of dry and dyshidrotic types., Comparison of localized high-dose UVA1 irradiation versus topical cream psoralen-UVA for treatment of chronic vesicular dyshidrotic eczema., No phototoxic reactions were observed.CONCLUSION: Local bath-PUVA therapy is of value in the management of chronic palmoplantar eczema resistant to standard modes of topical treatment., These results indicate that topical PUVA therapy with psoralen in aqueous gel is a useful therapeutic modality for treatment of psoriasis patients, and patients with recalcitrant dermatoses such as palmoplantar psoriasis and hyperkeratotic eczema.., Treatment of chronic palmoplantar eczema with local bath-PUVA therapy., Oral PUVA is preferable for patients with hyperkeratotic eczema and bath PUVA for patients with dyshidrotic eczema.., Does smoking influence the efficacy of bath-PUVA therapy in chronic palmoplantar eczema?, Local bath-PUVA therapy is of value in the management of chronic palmoplantar eczema resistant to standard modes of topical treatment., However, few data are available on the effectiveness of local bath-PUVA therapy in palmoplantar eczema., A new psoralen-containing gel for topical PUVA therapy: development, and treatment results in patients with palmoplantar and plaque-type psoriasis, and hyperkeratotic eczema., Smoking is likely to be a reason for the failure of bath-PUVA therapy in the treatment of chronic palmoplantar eczema, in particular regarding smokers with eczema of the dyshidrotic type where no complete remission was achieved.., In order to investigate the effectiveness of topical PUVA-bath therapy (PUVA-soak therapy) on chronic palmoplantar dermatoses, 30 patients with plaque-type psoriasis, pustular psoriasis, endogenous eczema, dyshidrotic eczema and hyperkeratotic dermatitis of the palms and soles were treated over 8 weeks with PUVA-soak using 8-MOP., Our purpose was to assess the effectiveness of local bath-PUVA therapy in 28 patients with chronic palmar or plantar eczema or both who were resistant to conventional topical treatment.[SEP]Relations: vitiligo-associated multiple autoimmune disease susceptibility 1 has relations: disease_phenotype_positive with Vitiligo, disease_phenotype_positive with Vitiligo. primary cutaneous amyloidosis has relations: disease_disease with lichen amyloidosis, disease_disease with lichen amyloidosis.", "label": "yes"}
{"id": "converted_4119", "sentence1": "Can propofol cause green urine?", "sentence2": "Reasons for discontinuing propofol are signs of rhabdomyolysis (92.9%), green urine, elevated liver enzymes (71.4% each) and elevated triglycerides (57.1%)., Propofol-Induced Green Urine in a Patient with Refractory Status Epilepticus., We present the case of a 52-year-old man, who developed green urine following propofol coma therapy for status epilepticus., The green discoloration of urine is a rare and benign condition, which occurs when clearance of propofol exceeds the hepatic and extrahepatic elimination., Green discolouration of urine following propofol infusion in a dog.,  During mechanical ventilation, anaesthesia was maintained using a propofol target-controlled infusion system and, subsequently, the dog produced bright green urine in the urine collection system. Although previously documented in humans, this appears to be the first report of green urine in a dog following propofol use., Green urine is also caused by medications such as propofol and infections such as pseudomonas., Although it is assumed that the phenolic derivatives of propofol can cause green discoloration of the urine, the actual origin remains unknown., An uncommon adverse effect of propofol is green discoloration of the urine, which has been reported not only under general anesthesia but also with sedation., Antibiotics were avoided when propofol was recognized as a rare and benign potential cause of the green urine., Green Urine Due to Propofol: A Case Report with Review of Literature., Herein, we present a case of 62-year-old postoperative lady, noticed to be passing green coloured urine believed to be due to intravenous Propofol administration for induction of general anaesthesia., Green urine is rare indeed and it is a benign potential side effect of propofol; this phenomenon is related to the metabolism of propofol., Clinical significance of rare and benign side effects: propofol and green urine., Green urine in a patient who received a continuous infusion of propofol: A case report., This phenomenon is due to metabolism of propofol which may lead to a phenolic green chromophore which is conjugated in the liver and excreted in the urine., Green Urine Discoloration due to Propofol Infusion: A Case Report., An analysis of green discoloration of urine caused by propofol infusion., We experienced green urine from a long-term anesthetized patient who received a continuous infusion of propofol., We present a 19-year-old man who excreted green urine after propofol infusion., green colour of urine due to Propofol occurs when clearance of Propofol exceeds hepatic elimination, and extrahepatic elimination of Propofol occurs. Thi, Green urine from propofol infusion is a benign and rare side effect, Grass-green urine from propofol infusion, Propofol-Induced Green Urine in a Patient with Refractory Status Epilepticus, sedation. An uncommon adverse effect of propofol is green discoloration of the urine, which has been reported not only under general anesthesia but also with, erein, we present a case of 62-year-old postoperative lady, noticed to be passing green coloured urine believed to be due to intravenous Propofol administration for induction of general anaesthesia. T, en urine is rare indeed and it is a benign potential side effect of propofol; this phenomenon is related to the metabolism of propofol. W, Green urine is also caused by medications such as propofol and infections such as pseudomonas, Green Urine Due to Propofol: A Case Report with Review of Literature, LUSION: We experienced a case of a patient with green discoloration of the urine after general anesthesia using propofol. Al, After starting continuous infusion of propofol for postoperative sedation, his urine became dark green., We believe that the green discoloration of the urine was caused by propofol infusion and was related to impaired enterohepatic circulation and extrahepatic glucuronidation in the kidneys., WHAT IS KNOWN AND OBJECTIVE: Propofol, a commonly used sedative, has on rare occasions, been reported to discolour urine green,  IS NEW AND CONCLUSION: Green discoloration of the urine from propofol infusion is dose dependent. It,  We report on a patient who produced dark green discoloration of urine from prolonged propofol infusion, administered for intractable epilepsy, Dark green discoloration of the urine after prolonged propofol infusion: a case report.,  experienced a case of a patient with green discoloration of the urine after general anesthesia using propofol. A, On the third day of propofol infusion his urine was dark green., Green urine from propofol infusion is a benign and rare side effect., The green colour of urine due to Propofol occurs when clearance of Propofol exceeds hepatic elimination, and extrahepatic elimination of Propofol occurs., ur change is dose dependent. We report on a patient who produced dark green discoloration of urine from prolonged propofol infusion, administered for intractable epilepsy.CASE SUMMARY: The colour intensity of the patient's uri, Several substances in literature have been associated with green urine including propofol, biliverdin, metoclopramide, methylene blue, indigo blue, amitriptyline, methocarbamol, indomethacin, promethazine, cimetidine and food colourings. , We discuss a case of a benign cause of green discoloration of urine caused by propofol infusion, which reversed following its discontinuation., The patient's urine subsequently showed a green discoloration. Urine discoloration was completely reversible upon discontinuation of propofol., Two days after admittance, we observed a green discoloration of the urine. This is a rare and benign side effect of propofol., We describe a 58-year-old man who developed green urine after operation on a pressure ulcer. The discolouration disappeared gradually after two days. We think that the use of methylene blue dye during the revision of the wounds and the use of the sedative propofol could have caused it.[SEP]Relations: Indomethacin has relations: drug_drug with Propofol, drug_drug with Propofol. Amitriptyline has relations: drug_drug with Propofol, drug_drug with Propofol. Cimetidine has relations: drug_drug with Propofol, drug_drug with Propofol. Methylene blue has relations: drug_drug with Propofol, drug_drug with Propofol. Metoclopramide has relations: drug_drug with Propofol, drug_drug with Propofol. Promethazine has relations: drug_drug with Propofol, drug_drug with Propofol.", "label": "yes"}
{"id": "converted_3711", "sentence1": "Was vivotif licensed in Europe and the US at the same time?", "sentence2": "Vivotif® is an oral live attenuated vaccine which contains a mutated strain of Salmonella (Ty21a) and reproduces the natural infection. The vaccine was first licensed in Europe in 1983 and in the US in 1989, and over the years it has proved efficacious and safe.[SEP]", "label": "no"}
{"id": "converted_2637", "sentence1": "Is there a disease or condition called Exploding Head Syndrome?", "sentence2": "This case report describes the first-ever diagnosis of exploding head syndrome in a patient with longstanding epilepsy and novel nocturnal events. , Exploding head syndrome (EHS) is characterized by loud noises or a sense of explosion in the head during sleep transitions., Exploding head syndrome is characterized by the perception of loud noises during sleep-wake or wake-sleep transitions. , Exploding head syndrome (EHS) is characterized by attacks of a sudden noise or explosive feeling experienced in the head occurring during the transition from wake to sleep or from sleep to wake., Exploding head syndrome is characterized by the perception of abrupt, loud noises when going to sleep or waking up., xploding head syndrome (EHS) is a rare parasomnia in which affected individuals awaken from sleep with the sensation of a loud bang. , Contrary to some earlier theorizing, exploding head syndrome was found to be a relatively common experience in younger individuals., Exploding head syndrome is characterized by the perception of loud noises during sleep-wake or wake-sleep transitions., Fifty patients suffering from the \"exploding head syndrome\" are described., In spite of the fact that its characteristic symptomatology was first described approximately 150 y ago, exploding head syndrome has received relatively little empirical and clinical attention., After first discussing the history, prevalence, and associated features, the available polysomnography data and five main etiological theories for exploding head syndrome are summarized., Exploding head syndrome: six new cases and review of the literature., Exploding Head Syndrome in the Epilepsy Monitoring Unit: Case Report and Literature Review., Exploding head syndrome: a case report., Exploding head syndrome is common in college students., Exploding head syndrome episodes were accompanied by clinically significant levels of fear, and a minority (2.80%) experienced it to such a degree that it was associated with clinically significant distress and/or impairment., Attention has recently been drawn to a condition termed the exploding head syndrome, which is characterized by unpleasant, even terrifying sensations of flashing lights and/or sounds during reported sleep., Exploding head syndrome is a rare phenomenon but can be a significant disruption to quality of life., The rare headache disorder hypnic headache and the exploding head syndrome are also discussed., This case report describes the first-ever diagnosis of exploding head syndrome in a patient with longstanding epilepsy and novel nocturnal events., BACKGROUND Exploding head syndrome (EHS) is characterized by attacks of a sudden noise or explosive feeling experienced in the head occurring during the transition from wake to sleep or from sleep to wake., INTRODUCTION Exploding head syndrome (EHS) is a rare parasomnia in which affected individuals awaken from sleep with the sensation of a loud bang., Contrary to some earlier theorizing, exploding head syndrome was found to be a relatively common experience in younger individuals., This hitherto unreported syndrome is characterised by a sense of an explosive noise in the head usually in the twilight stage of sleep., EHS is a well-defined disease entity with a benign nature., Exploding head syndrome: a case report., Clinical features of the exploding head syndrome., Exploding head syndrome is common in college students., The exploding head syndrome: polysomnographic recordings and therapeutic suggestions., This article reviews the features of an uncommon malady termed \"the exploding head syndrome.\" Sufferers describe terrorizing attacks of a painless explosion within their head, The case is reported of a 47-year old female suffering from the exploding head syndrome. This syndrome consists of a sudden awakening due to a loud noise shortly after falling asleep, sometimes accompanied by a flash of light.[SEP]", "label": "yes"}
{"id": "converted_2072", "sentence1": "Is vemurafenib used for thyroid cancer?", "sentence2": "Vemurafenib in patients with BRAF(V600E)-positive metastatic or unresectable papillary thyroid cancer refractory to radioactive iodine: a non-randomised, multicentre, open-label, phase 2 trial., Vemurafenib, an oncogenic BRAF kinase inhibitor approved for BRAF-positive melanoma, showed clinical benefit in three patients with BRAF(V600E)-positive papillary thyroid cancer in a phase 1 trial., INTERPRETATION: Vemurafenib showed antitumour activity in patients with progressive, BRAF(V600E)-positive papillary thyroid cancer refractory to radioactive iodine who had never been treated with a multikinase inhibitor. , CONTEXT: Vemurafenib, a selective BRAF inhibitor, appears to have promising clinical activity in patients with papillary thyroid cancer (PTC) harboring the BRAF(V600E) mutation., Efficacy and tolerability of vemurafenib in patients with BRAF(V600E) -positive papillary thyroid cancer: M.D. Anderson Cancer Center off label experience., CONCLUSIONS: Vemurafenib is a potentially effective and well-tolerated treatment strategy in patients with advanced PTC harboring the BRAF(V600E) mutation., The US Food and Drug Administration-approved BRAF inhibitors, vemurafenib and dabrafenib, have demonstrated superior efficacy in patients with BRAF-mutant melanomas but have limited efficacy in BRAF-mutant colorectal cancer. Little is known at this time regarding BRAF inhibitors in thyroid cancer. Initial reports in patients with progressive, radioactive iodine-refractory BRAF-mutant papillary thyroid cancer suggest response rates of approximately 30-40%., Use of vemurafenib in anaplastic thyroid carcinoma: a case report., Finally, we found that propranolol can amplify the cytotoxicity of vemurafenib and sensitize thyroid cancer cells to cytotoxic effect of vemurafenib., CONTEXT: Vemurafenib, a selective BRAF inhibitor, appears to have promising clinical activity in patients with papillary thyroid cancer (PTC) harboring the BRAF(V600E) mutation.OBJECTIVE: To determine the efficacy and safety of vemurafenib when used outside of a clinical trial.DESIGN: A retrospective review at MD Anderson Cancer Center.METHODS: The best responses were evaluated using RECIST v1.1., Vemurafenib, a selective BRAF inhibitor, appears to have promising clinical activity in patients with papillary thyroid cancer (PTC) harboring the BRAF(V600E) mutation.To determine the efficacy and safety of vemurafenib when used outside of a clinical trial.A retrospective review at MD Anderson Cancer Center.The best responses were evaluated using RECIST v1.1, CONTEXT: Vemurafenib, a selective BRAF inhibitor, appears to have promising clinical activity in patients with papillary thyroid cancer (PTC) harboring the BRAF(V600E) mutation.OBJECTIVE: To determine the efficacy and safety of vemurafenib when used outside of a clinical trial.DESIGN: A retrospective review at MD Anderson Cancer Center.METHODS: The best responses were evaluated using RECIST v1.1. , Finally, we found that propranolol can amplify the cytotoxicity of vemurafenib and sensitize thyroid cancer cells to cytotoxic effect of vemurafenib., Metformin or rapamycin adjuvant treatment may provide clinical benefits with minimal side effects to BRAFV600E-positive advanced thyroid cancer patients treated with vemurafenib., Vemurafenib, a selective BRAF inhibitor, appears to have promising clinical activity in patients with papillary thyroid cancer (PTC) harboring the BRAF(V600E) mutation.To determine the efficacy and safety of vemurafenib when used outside of a clinical trial.A retrospective review at MD Anderson Cancer Center.The best responses were evaluated using RECIST v1.1., Our data demonstrate that vemurafenib induces ER stress response-mediated autophagy in thyroid cancer and autophagy inhibition may be a beneficial strategy to sensitize BRAF-mutant thyroid cancer to vemurafenib.., Combination of vemurafenib and metformin decreased cell viability and increased apoptosis in both BCPAP papillary thyroid cancer cells and 8505c anaplastic thyroid cancer cells., Targeting autophagy sensitizes BRAF-mutant thyroid cancer to vemurafenib., Propranolol sensitizes thyroid cancer cells to cytotoxic effect of vemurafenib., mTOR inhibitors sensitize thyroid cancer cells to cytotoxic effect of vemurafenib., Vemurafenib induced a high level of autophagy in BRAF-mutant thyroid cancer cells.[SEP]Relations: 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_4210", "sentence1": "Is the zelda transcription factor a chromatin remodeller?", "sentence2": "ncreasing the number of Zelda binding sites accelerates the kinetics of nuclei transcriptional activation regardless of their transcriptional past, Zelda facilitates transcriptional activation by accumulating in microenvironments where it could accelerate the duration of multiple pre-initiation steps., Zelda acts through specific chromatin patterns of histone modifications to mark developmental enhancers and active promoters, Zelda overcomes the high intrinsic nucleosome barrier at enhancers during Drosophila zygotic genome activation., The Drosophila genome activator Vielfaltig (Vfl), also known as Zelda (Zld), is thought to prime enhancers for activation by patterning transcription factors (TFs). Such priming is accompanied by increased chromatin accessibility, early enhancers are characterized by an intrinsically high nucleosome barrier. Zld tackles this nucleosome barrier through local depletion of nucleosomes with the effect being dependent on the number and position of Zld motifs., Zelda is differentially required for chromatin accessibility, transcription factor binding, and gene expression in the early Drosophila embryo, Open chromatin is associated with Zelda-bound loci, as well as more generally with regions of active transcriptio, During this developmental transition, the zygotic genome is largely transcriptionally quiescent and undergoes significant chromatin remodeling. In Drosophila, the DNA-binding protein Zelda (also known as Vielfaltig) is required for this transition and for transcriptional activation of the zygotic genome., Zld facilitates binding of Dl to regulatory DNA, and that this is associated with increased chromatin accessibility., Importantly, the change in chromatin accessibility is strongly correlated with the change in Zld binding, Zelda is differentially required for chromatin accessibility, transcription factor binding, and gene expression in the early Drosophila embryo., We propose that both Zelda and GAGA factor function to specify sites of open chromatin and together facilitate the remodeling of the early embryonic genome., is analysis highlighted a strong and specific enrichment of predicted ZGA-associated CRMs for Zelda, CBP, Trl binding sites, as well as for histone marks associated with active enhancers (H3K4me1) and for open chromatin regions.CO, We demonstrate that Zelda is essential for hundreds of regions of open chromatin., Intriguingly, some Zelda sites still maintain these chromatin patterns in Drosophila embryos lacking maternal Zelda protein., Zelda potentiates morphogen activity by increasing chromatin accessibility., Zelda binds cis-regulatory elements (TAGteam heptamers), making chromatin accessible for gene transcription., zinc-finger TF zelda (zld) is essential for the maternal-to-zygotic transition (MZT) in Drosophila melanogaster, where it directly binds over thousand cis-regulatory modules to regulate chromatin accessibility. D. mela, This Zelda-mediated chromatin accessibility facilitates transcription-factor recruitment and early gene expression., While analyzing chromatin immunoprecipitation data sets from 21 sequence-specific transcription factors active in the Drosophila embryo, we found that binding of all factors exhibits a dose-dependent relationship with \"TAGteam\" sequence motifs bound by the zinc finger protein Vielfaltig, also known as Zelda, a recently discovered activator of the zygotic genome., These different timing classes each associate with binding sites for two transcription factors, GAGA-factor and Zelda, previously implicated in controlling chromatin accessibility at ZGA., Together this reveals a distinct requirement for a chromatin remodeller in promoting the activity of the pioneer factor OCT4 and regulating the pluripotency network., Chromatin accessibility at OCT4-bound sites requires the chromatin remodeller BRG1, which is recruited to these sites by OCT4 to support additional transcription factor binding and expression of the pluripotency-associated transcriptome., The pioneer factor OCT4 requires the chromatin remodeller BRG1 to support gene regulatory element function in mouse embryonic stem cells., Pioneer transcription factors recognise and bind their target sequences in inaccessible chromatin to establish new transcriptional networks throughout development and cellular reprogramming., During this process, pioneer factors establish an accessible chromatin state to facilitate additional transcription factor binding, yet it remains unclear how different pioneer factors achieve this., Here, we discover that the pluripotency-associated pioneer factor OCT4 binds chromatin to shape accessibility, transcription factor co-binding, and regulatory element function in mouse embryonic stem cells., Open chromatin is associated with Zelda-bound loci, as well as more generally with regions of active transcription., Unexpectedly, chromatin at a large subset of Zelda-bound regions remains open even in the absence of Zelda., During this developmental transition, the zygotic genome is largely transcriptionally quiescent and undergoes significant chromatin remodeling., Here we used formaldehyde-assisted isolation of regulatory elements to determine the role of Zelda in regulating regions of open chromatin in the early embryo., Pioneer transcription factors can engage nucleosomal DNA, which leads to local chromatin remodeling and to the establishment of transcriptional competence., Recently, we showed that Zelda acts through specific chromatin patterns of histone modifications to mark developmental enhancers and active promoters., The zinc-finger TF zelda (zld) is essential for the maternal-to-zygotic transition (MZT) in Drosophila melanogaster, where it directly binds over thousand cis-regulatory modules to regulate chromatin accessibility., Nonetheless, the extent to which Zelda influences chromatin accessibility across the genome is largely unknown., We present evidence that Zld facilitates binding of Dl to regulatory DNA, and that this is associated with increased chromatin accessibility., ZRF1 facilitates the remodeling of multiprotein complexes at chromatin and lies at the heart of signaling processes that occur at DNA damage sites and during transcriptional activation., We postulate that ZRF1 operates in conjunction with cellular remodeling machines and suggest that on-site remodeling might be a hallmark of many chromatin-associated signaling pathways., Reconstituted transcription reactions established that the Brahma (BRM) chromatin-remodeling complex is essential for Zeste-directed activation on nucleosomal templates.[SEP]Relations: DNAJC2 has relations: anatomy_protein_present with heart, anatomy_protein_present with heart.", "label": "yes"}
{"id": "converted_1010", "sentence1": "Is it possible to purify pseudopodia to be used for proteomic analysis?", "sentence2": "we developed an approach to biochemically isolate the pseudopodium from the cell body using 3.0-micrometer porous filters for large-scale quantitative proteomic and phosphoproteomic analysis., Recent work using unique subcellular fractionation methodologies combined with spatial genomic, proteomic, and phosphoproteomic profiling has provided insight into the invadopodiome and pseudopodiome signaling networks , ere, we purified the pseudopodial proteomes, tumor cells were placed on a fibronectin-coated porous membrane to form pseudopodia. According to the motile potentials of the cells, the cells formed pseudopodial microprocesses in the pores. An excimer laser, which was used for ophthalmic refractive surgeries, horizontally ablated cells at the membrane surface to remove the cell body. , we describe methods for the immunoaffinity purification of phosphotyrosine proteins (pY) from pseudopodia that have been isolated from migratory cells. These methods are compatible with current mass spectrometry-based protein identification technologies and can be utilized for the large-scale identification of the pseudopodium pY proteome in various migratory cell lines, including primary and cancer cells.[SEP]", "label": "yes"}
{"id": "converted_3349", "sentence1": "The LINCS L1000 data set contains gene expression data for drug treated human cells, yes or no?", "sentence2": " Library of Integrated Network-based Cellular Signatures (LINCS) L1000 dataset that measured changes in GE before and after treatment of human cells with over 20 000 small-molecule compounds including most of the FDA-approved drugs., The Library of Integrated Network-based Cellular Signatures (LINCS) L1000 big data provide gene expression profiles induced by over 10 000 compounds, shRNAs, and kinase inhibitors using the L1000 platform., The Library of Integrated Cellular Signatures (LINCS) project provides comprehensive transcriptome profiling of human cell lines before and after chemical and genetic perturbations.,  Recently, resources such as the Library of Integrated Network-Based Cellular Signatures (LINCS) L1000 database provide gene expression profiles induced by various chemical and genetic perturbations, The library of integrated network-based cellular signatures (LINCS) L1000 data set currently comprises of over a million gene expression profiles of chemically perturbed human cell lines., The LINCS L1000 data repository contains almost two million gene expression profiles for thousands of small molecules and drugs., The GE data is from the Library of Integrated Network-based Cellular Signatures (LINCS) L1000 dataset that measured changes in GE before and after treatment of human cells with over 20 000 small-molecule compounds including most of the FDA-approved drugs.[SEP]", "label": "yes"}
{"id": "converted_4691", "sentence1": "Is HYDIN (Hydrocephalus-inducing protein homolog) an axonemal protein?", "sentence2": "Hydin was recently identified as an axonemal protein; however, its function is as yet unknown., precise axonemal location of hydin, a protein that, when mutated, causes hydrocephalus, and defined a unique role for hydin in ciliary motility.[SEP]", "label": "yes"}
{"id": "converted_2889", "sentence1": "Does Panitumumab prolong survival of biliary tract cancer patients?", "sentence2": "Panitumumab in combination with gemcitabine and oxaliplatin does not prolong survival in wild-type KRAS advanced biliary tract cancer: A randomized phase 2 trial (Vecti-BIL study)., CONCLUSIONS: Panitumumab in combination with chemotherapy does not improve ORR, PFS and OS in patients with KRAS wild-type, advanced biliary cancer. , No survival differences were observed: the median overall survival was 9.9 months in arm A and 10.2 months in arm B (P = .42). In a subgroup analysis, no differences in PFS according to the site of the primary tumor were observed; patients with intrahepatic cholangiocarcinoma treated with panitumumab may have had a survival benefit in comparison with the control group (15.1 vs 11.8 months, P = .13). , CONCLUSIONS\nPanitumumab in combination with chemotherapy does not improve ORR, PFS and OS in patients with KRAS wild-type, advanced biliary cancer., CONCLUSIONS Panitumumab in combination with chemotherapy does not improve ORR, PFS and OS in patients with KRAS wild-type, advanced biliary cancer., Despite many clinical trials being conducted with molecular targeted agents including erlotinib, cetuximab, panitumumab, bevacizumab, sorafenib, cediranib, trametinib and vandetanib, no agent has shown to be effective for advanced biliary tract cancer., Adding panitumumab to standard protocols does not prolong survival but provokes additional adverse effects.[SEP]Relations: Bevacizumab has relations: drug_drug with Panitumumab, drug_drug with Panitumumab. Cetuximab has relations: drug_drug with Panitumumab, drug_drug with Panitumumab.", "label": "no"}
{"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_3498", "sentence1": "Has ProSavin undergone phase IV clinical trials by 2018?", "sentence2": "Long-term safety and tolerability of ProSavin, a lentiviral vector-based gene therapy for Parkinson's disease: a dose escalation, open-label, phase 1/2 trial., We undertook a phase 1/2 open-label trial with 12-month follow-up at two study sites (France and UK) to assess the safety and efficacy of ProSavin after bilateral injection into the putamen of patients with Parkinson's disease. [SEP]", "label": "no"}
{"id": "converted_191", "sentence1": "Are thyroid hormone receptor alpha1 mutations implicated in thyroid hormone resistance syndrome?", "sentence2": "This study reports the consequences of LT4 treatment over a prolonged period of time in 2 of the first patients with a heterozygous mutation in TRα1., Here we show that the dysregulation of the pituitary-thyroid axis was worsened by the lack of TR alpha1 in TR betaPV mice, and severe impairment of postnatal growth was manifested in TR betaPV mice deficient in TR alpha1., Heterozygous 2- to 3-week- old mice exhibit a severe retardation of post-natal development and growth, but only a minor reduction in serum thyroxine levels. , The data demonstrate a novel array of effects mediated by a dominant negative TRalpha1, and may provide important clues for identification of a potentially unrecognized human disorder and its treatment., No mutations in DNA- and hormone-binding-domains of TRbeta1 and TRalpha1 genes were found in proband, suggesting that the defect could be due to an unknown mutation in either the TR gene or a post receptor abnormality, These results demonstrate that the lack of TR alpha1 exacerbates the manifestation of RTH in TR betaPV mice. Therefore, TR alpha1 could play a compensatory role in mediating the functions of T3 in heterozygous patients with RTH. [SEP]", "label": "yes"}
{"id": "converted_3217", "sentence1": "Is ustekinumab a polyclonal antibody?", "sentence2": "Ustekinumab, a human monoclonal IgG1 antibody targeting the p40-subunit shared by interleukin (IL)12 and IL-23, represents a potential treatment for atopic dermatitis (AD).[SEP]", "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_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_166", "sentence1": "Are there any statistical methods for normalizing and identifying differential regions in histone modification ChIP-seq data?", "sentence2": "ChIPnorm: a statistical method for normalizing and identifying differential regions in histone modification ChIP-seq libraries., In this paper we propose a two-stage statistical method, called ChIPnorm, to normalize ChIP-seq data, and to find differential regions in the genome, given two libraries of histone modifications of different cell types. We show that the ChIPnorm method removes most of the noise and bias in the data and outperforms other normalization methods. We correlate the histone marks with gene expression data and confirm that histone modifications H3K27me3 and H3K4me3 act as respectively a repressor and an activator of genes. Compared to what was previously reported in the literature, we find that a substantially higher fraction of bivalent marks in ES cells for H3K27me3 and H3K4me3 move into a K27-only state. We find that most of the promoter regions in protein-coding genes have differential histone-modification sites., In this paper we propose a two-stage statistical method, called ChIPnorm, to normalize ChIP-seq data, and to find differential regions in the genome, given two libraries of histone modifications of different cell types., In this paper we propose a two-stage statistical method, called ChIPnorm, to normalize ChIP-seq data, and to find differential regions in the genome, given two libraries of histone modifications of different cell types. , In this paper we propose a two-stage statistical method, called ChIPnorm, to normalize ChIP-seq data, and to find differential regions in the genome, given two libraries of histone modifications of different cell types. We show that the ChIPnorm method removes most of the noise and bias in the data and outperforms other normalization methods. , In this paper we propose a two-stage statistical method, called ChIPnorm, to normalize ChIP-seq data, and to find differential regions in the genome, given two libraries of histone modifications of different cell types., In this paper we propose a two-stage statistical method, called ChIPnorm, to normalize ChIP-seq data, and to find differential regions in the genome, given two libraries of histone modifications of different cell types. We show that the ChIPnorm method removes most of the noise and bias in the data and outperforms other normalization methods., This problem turns out to be surprisingly difficult, even in simple pairwise comparisons, because of the significant level of noise in ChIP-seq data. In this paper we propose a two-stage statistical method, called ChIPnorm, to normalize ChIP-seq data, and to find differential regions in the genome, given two libraries of histone modifications of different cell types., In this paper we propose a two-stage statistical method, called ChIPnorm, to normalize ChIP-seq data, and to find differential regions in the genome, given two libraries of histone modifications of different cell types.[SEP]", "label": "yes"}
{"id": "converted_1226", "sentence1": "Are there interactomes available for POU5F1 and SOX2?", "sentence2": "The interactomes of POU5F1 and SOX2 enhancers in human embryonic stem cells., We assayed long-range chromosomal interactions on putative enhancers of POU5F1 and SOX2 genes in human embryonic stem cells (hESCs) using 4C-Seq technique. We discovered that their frequent interacting regions mainly overlap with early DNA replication domains. The interactomes are associated with active histone marks and enriched with 5-hydroxymethylcytosine sites. In hESCs, genes within the interactomes have elevated expression. Additionally, some genes associated with the POU5F1 enhancer contribute to pluripotency. Binding sites for multiple DNA binding proteins, including ATF3, CTCF, GABPA, JUND, NANOG, RAD21 and YY1, are enriched in both interactomes.[SEP]Relations: NANOG has relations: protein_protein with POU5F1, protein_protein with SOX2, protein_protein with POU5F1, protein_protein with SOX2.", "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_488", "sentence1": "Can exosomes be detected in urine?", "sentence2": "Exosomes are nanovesicles secreted into the extracellular environment upon internal vesicle fusion with the plasma membrane. The molecular content of exosomes is a fingerprint of the releasing cell type and of its status. For this reason, and because they are released in easily accessible body fluids such as blood and urine, they represent a precious biomedical tool. , Exosomes are vesicles that are released from the kidney into urine., Quantification of human urinary exosomes by nanoparticle tracking analysis., Urinary extracellular vesicles (uEVs) are released by cells throughout the nephron and contain biomolecules from their cells of origin., Urinary exosomes have been proposed as potential diagnostic tools., Urinary exosomes as a source of kidney dysfunction biomarker in renal transplantation, . Here we sought to optimize the methodologies for the isolation and quantification of urinary exosomal microRNA as a prelude to biomarker discovery studies. , Exosomes are small (30-150 nm) vesicles containing unique RNA and protein cargo, secreted by all cell types in culture. They are also found in abundance in body fluids including blood, saliva, and urine. , Urinary exosome-like vesicles (ELVs) are a heterogenous mixture (diameter 40-200 nm) containing vesicles shed from all segments of the nephron including glomerular podocytes, Exosomes are cytoplasm containing vesicles released by many cells that can be found in several biological fluids including urine., Proteomic analysis of urinary exosomes in cardiovascular and associated kidney diseases by two-dimensional electrophoresis and LC-MS/MS[SEP]", "label": "yes"}
{"id": "converted_1242", "sentence1": "Is nimodipine recommended for prevention of vasospasm in aneurysmal subarachnoid hemorrhage patients?", "sentence2": "This article discusses some of these unresolved issues, including the use of medications such as nimodipine, antifibrinolytics, statins, and magnesium; coiling or clipping for aneurysm securement; and the prevention and treatment of potential complications., The results of this study were as follows: nimodipine demonstrated benefit following aneurysmal SAH; other calcium channel blockers, including nicardipine, do not provide unequivocal benefit; triple-H therapy, fasudil, transluminal balloon angioplasty, thrombolytics, endothelin receptor antagonists, magnesium, statins, and miscellaneous therapies such as free radical scavengers and antifibrinolytics require additional study., The present results suggest that fasudil is equally or more effective than nimodipine for the prevention of cerebral vasospasm and subsequent ischemic injury in patients undergoing surgery for SAH., Three studies (2 meta-analyses and 1 randomized controlled trial) demonstrated that nimodipine use confers benefits (reduced morbidity and mortality) for patients with aneurysmatic subarachnoid hemorrhage., Nimodipine is the only preventative treatment that can be recommended., Nimodipine (Nimotop), HMG Co-A reductase inhibitor (statins) and enoxaparin (Lovenox) were the only drugs with level-1 evidence available for the treatment of vasospasm from aneurysmal subarachnoid hemorrhage as defined by the US Preventative Services Task Force., The calcium antagonist nimodipine has been shown to reduce the incidence of ischemic complications following aneurysmal subarachnoid hemorrhage (SAH)., There was no significant difference in the incidence of DINDs (28 vs 30% in the peroral and intravenous groups, respectively) or middle cerebral artery blood flow velocities (> 120 cm/second, 50 vs 45%, respectively)., Clinical outcome according to the Glasgow Outcome Scale was the same in both groups, and there was no difference in the number of patients with new infarctions on MR imaging., The results suggest that there is no clinically relevant difference in efficacy between peroral and intravenous administration of nimodipine in preventing DINDs or cerebral vasospasm following SAH., the risk of delayed cerebral ischemia is reduced with nimodipine and avoiding hypovolemia, A recommendations (standard) for the prophylaxis and treatment of cerebral vasospasm with oral Nimodipine in good grade patients., Of the 75 patients initially considered for active treatment, 83% underwent surgery within 48 hours of rupture, all received nimodipine, 16% received tissue plasminogen activator to lyse subarachnoid or intraventricular clots, 40% underwent hypertensive treatment, and 7% underwent transluminal balloon angioplasty for vasospasm., All patients with aneurysmal SAH should be treated with the calcium antagonist nimodipine, and in certain circumstances patients should receive anticonvulsants., The following review gives an account of pathophysiological mechanisms; the importance of treatment with calcium antagonists, hypervolaemic haemodilution, and induced arterial hypertension is discussed in light of the current literature., Seven placebo-controlled clinical studies have shown that nimodipine improves the outcome of patients with severe neurological damage due to cerebral vasospasm., In a series of 100 individuals with a ruptured supratentorial aneurysm, who were subjected to aneurysm operation in the acute stage and who subsequently received intravenous treatment with the calcium channel blocker nimodipine, the occurrence of DID with FND was reduced to 5%., There are many possible successful treatment options for preventing vasospasm, delayed ischemic neurologic deficits, and poor neurologic outcome following aneurysmal subarachnoid hemorrhage; however, further multicenter RCTs need to be performed to determine if there is a significant benefit from their use. Nimodipine is the only treatment that provided a significant benefit across multiple studies., Absence of symptomatic vasospasm, occurrence of low density areas associated with vasospasm on CT, and occurrence of adverse events were similar between the two groups. The clinical outcomes were more favorable in the fasudil group than in the nimodipine group (p = 0.040). The proportion of patients with good clinical outcome was 74.5% (41/55) in the fasudil group and 61.7% (37/60) in the nimodipine group., Cerebral vasospasm is the classic cause of delayed neurological deterioration leading to cerebral ischemia and infarction, and thus, poor outcome and occasionally death, after aneurysmal subarachnoid hemorrhage (SAH). Advances in diagnosis and treatment, principally nimodipine, intensive care management, hemodynamic manipulations, and endovascular neuroradiology procedures, have improved the prospects for these patients, but outcomes remain disappointing., Cerebral vasospasm is the classic cause of delayed neurological deterioration after aneurysmal subarachnoid hemorrhage, leading to cerebral ischemia and infarction, and thus to poor outcome and occasionally death. Advances in diagnosis and treatment-principally the use of nimodipine, intensive care management, hemodynamic manipulations and endovascular neuroradiology procedures-have improved the prospects for these patients, but outcomes remain disappointing., Cerebral vasospasm and delayed cerebral ischemia remain common complications of aneurysmal subarachnoid hemorrhage (SAH), and yet therapies for cerebral vasospasm are limited. Despite a large number of clinical trials, only calcium antagonists have strong evidence supporting their effectiveness., The only proven therapy for vasospasm is nimodipine., nimodipine is indicated after SAH and tirilazad is not effective., Fasudil hydrochloride and nimodipine both showed inhibitory effects on cerebral vasospasm. The incidence of symptomatic vasospasm was five of 33 patients in the fasudil group and nine of 32 patients in the nimodipine group. Good recovery evaluated by the Glasgow Outcome Scale was achieved by 23 of 33 patients in the fasudil group and 19 of 34 patients in the nimodipine group. Both drugs significantly improved consciousness levels and neurological deficits such as aphasia. However, fasudil hydrochloride improved motor disturbance more than nimodipine.[SEP]Relations: Hydrochlorothiazide has relations: drug_drug with Nimodipine, drug_drug with Nimodipine. Fasudil has relations: drug_drug with Nimodipine, drug_drug with Nimodipine. Nicardipine has relations: drug_drug with Nimodipine, drug_drug with Nimodipine. Enoxaparin has relations: drug_drug with Nimodipine, drug_drug with Nimodipine.", "label": "yes"}
{"id": "converted_1131", "sentence1": "Do conserved noncoding elements co-occur with matrix-attachment regions?", "sentence2": "We hypothesized that some of these regions might be matrix-scaffold attachment regions, MARs (or S/MARs). MARs comprise one of the few classes of eukaryotic noncoding DNA with an experimentally characterized function, being involved in the attachment of chromatin to the nuclear matrix, chromatin remodeling and transcription regulation. To test our hypothesis, we analyzed the co-occurrence of predicted MARs with highly conserved noncoding DNA regions in human-mouse genomic alignments. We found that 11% of the conserved noncoding DNA consists of predicted MARs. Conversely, more than half of the predicted MARs co-occur with one or more independently identified conserved sequence blocks. An excess of conserved predicted MARs is seen in intergenic regions preceding 5' ends of genes, suggesting that these MARs are primarily involved in transcriptional control, A significant fraction of conserved noncoding DNA in human and mouse consists of predicted matrix attachment regions., To test our hypothesis, we analyzed the co-occurrence of predicted MARs with highly conserved noncoding DNA regions in human-mouse genomic alignments., To test our hypothesis, we analyzed the co-occurrence of predicted MARs with highly conserved noncoding DNA regions in human-mouse genomic alignments[SEP]", "label": "yes"}
{"id": "converted_1030", "sentence1": "Are DNA helicases involved in progeroid syndromes?", "sentence2": "Among these syndromes, relevant advances have recently been made in Werner syndrome, one of several progeroid syndromes characterized by defective DNA helicases,, Progeroid syndromes (PSs) constitute a group of disorders characterized by clinical features mimicking physiological aging at an early age., However, all the characterized PSs enter in the field of rare monogenic disorders and several causative genes have been identified. These can be separated in subcategories corresponding to (i) genes encoding DNA repair factors, in particular, DNA helicases, and (ii) genes affecting the structure or post-translational maturation of lamin A, a major nuclear component., None of the known progerias represents true precocious ageing. Some of them, including Werner (WS), Bloom (BS), and Rothmund-Thomson syndromes (RTS) as well as combined xeroderma pigmentosa-Cockayne syndrome (XP-CS) are characterised by features resembling precocious ageing and the increased risk of malignant disease. Such phenotypes result from the mutations of the genes encoding proteins involved in the maintenance of genomic integrity, in most cases DNA helicases., Single-gene mutations can produce human progeroid syndromes--phenotypes that mimic usual or \"normative\" aging., The prototypic example of the former is the Werner syndrome, a condition caused by mutations of the RecQ family of DNA helicases., Progeria and progeroid syndromes are characterized by the earlier onset of complex senescent phenotypes. WRN was originally identified as a gene responsible for Werner syndrome (WS; \"Progeria of Adults\"). The WRN gene product has RecQ-type helicase domains in the central region of the protein.[SEP]Relations: Werner syndrome has relations: disease_protein with WRN, disease_protein with WRN.", "label": "yes"}
{"id": "converted_604", "sentence1": "Has the fungus Ashbya gossypii got many nuclei that share cytoplasm?", "sentence2": "multinucleated Ashbya gossypii cells., multinucleated Ashbya gossypii fungal cells, Nuclei in the filamentous, multinucleated fungus Ashbya gossypii divide asynchronously. , multinucleated Ashbya gossypii cells, We analyzed a unique asynchronous nuclear division cycle in a multinucleated filamentous fungus, Ashbya gossypii.,  multinucleated hyphae in Ashbya gossypii., We have followed the migration of GFP-labelled nuclei in multinucleate hyphae of Ashbya gossypii, multinucleate fungus Ashbya gossypii, Ashbya gossypii grows as multinucleated and constantly elongating hyphae, multinucleated hyphae of Ashbya gossypii., We report the mechanistic basis guiding the migration pattern of multiple nuclei in hyphae of Ashbya gossypii. , multinucleate fungal cells, multinucleate Ashbya gossypii cells relies on a minimal network of genes, Clustering of nuclei in multinucleated hyphae is prevented by dynein-driven bidirectional nuclear movements and microtubule growth control in Ashbya gossypii., In the multinucleate fungus Ashbya gossypii, cytoplasmic microtubules (cMTs) emerge from the spindle pole body outer plaque (OP) in perpendicular and tangential directions., multinucleated hyphae of Ashbya gossypii., multiple nuclei in Ashbya gossypii hyphae, Ashbya gossypii has a budding yeast-like genome but grows exclusively as multinucleated hyphae.[SEP]", "label": "yes"}
{"id": "converted_3714", "sentence1": "Is deletion at 6q24.2-26 associated with shorter survival for ovarian cancer patients?", "sentence2": "Deletion at 6q24.2-26 predicts longer survival of high-grade serous epithelial ovarian cancer patients., Standard treatments for advanced high-grade serous ovarian carcinomas (HGSOCs) show significant side-effects and provide only short-term survival benefits due to disease recurrence. Thus, identification of novel prognostic and predictive biomarkers is urgently needed. We have used 42 paraffin-embedded HGSOCs, to evaluate the utility of DNA copy number alterations, as potential predictors of clinical outcome. Copy number-based unsupervised clustering stratified HGSOCs into two clusters of different immunohistopathological features and survival outcome (HR = 0.15, 95%CI = 0.03-0.81; Padj = 0.03). We found that loss at 6q24.2-26 was significantly associated with the cluster of longer survival independently from other confounding factors (HR = 0.06, 95%CI = 0.01-0.43, Padj = 0.005). The prognostic value of this deletion was validated in two independent series, one consisting of 36 HGSOCs analyzed by fluorescent in situ hybridization (P = 0.04) and another comprised of 411 HGSOCs from the Cancer Genome Atlas study (TCGA) (HR = 0.67, 95%CI = 0.48-0.93, Padj = 0.019). In addition, we confirmed the association of low expression of the genes from the region with longer survival in 799 HGSOCs (HR = 0.74, 95%CI = 0.61-0.90, log-rank P = 0.002) and 675 high-FIGO stage HGSOCs (HR = 0.76, 95%CI = 0.61-0.96, log-rank P = 0.02) available from the online tool KM-plotter. Finally, by integrating copy number, RNAseq and survival data of 296 HGSOCs from TCGA we propose a few candidate genes that can potentially explain the association. Altogether our findings indicate that the 6q24.2-26 deletion is an independent marker of favorable outcome in HGSOCs with potential clinical value as it can be analyzed by FISH on tumor sections and guide the selection of patients towards more conservative therapeutic strategies in order to reduce side-effects and improve quality of life., We found that loss at 6q24.2-26 was significantly associated with the cluster of longer survival independently from other confounding factors (HR = 0.06, 95%CI = 0.01-0.43, Padj = 0.005)., OBJECTIVE\n\nWe aimed to evaluate the prognostic and predictive value of the nucleotide excision repair-related gene GTF2H5, which is localized at the 6q24.2-26 deletion previously reported by our group to predict longer survival of high-grade serous ovarian cancer patients., We found that loss at 6q24.2-26 was significantly associated with the cluster of longer survival independently from other confounding factors (HR = 0.06, 95%CI = 0.01-0.43, Padj = 0.005)., OBJECTIVE\nWe aimed to evaluate the prognostic and predictive value of the nucleotide excision repair-related gene GTF2H5, which is localized at the 6q24.2-26 deletion previously reported by our group to predict longer survival of high-grade serous ovarian cancer patients., OBJECTIVE: We aimed to evaluate the prognostic and predictive value of the nucleotide excision repair-related gene GTF2H5, which is localized at the 6q24.2-26 deletion previously reported by our group to predict longer survival of high-grade serous ovarian cancer patients., We aimed to evaluate the prognostic and predictive value of the nucleotide excision repair-related gene GTF2H5, which is localized at the 6q24.2-26 deletion previously reported by our group to predict longer survival of high-grade serous ovarian cancer patients.[SEP]", "label": "no"}
{"id": "converted_4025", "sentence1": "Is Lanabecestat effective for Alzheimer's disease?", "sentence2": "INTRODUCTION: The APECS and AMARANTH trials showed that beta-secretase (BACE) inhibitors verubecestat and lanabecestat failed to slow cognitive and functional decline in individuals with prodromal or early Alzheimer's disease. , Conclusions and Relevance: Treatment with lanabecestat was well tolerated and did not slow cognitive or functional decline., INTRODUCTION: The APECS and AMARANTH trials showed that beta-secretase (BACE) inhibitors verubecestat and lanabecestat failed to slow cognitive and functional decline in individuals with prodromal or early Alzheimer's disease., INTRODUCTION: The APECS and AMARANTH trials showed that beta-secretase (BACE) inhibitors verubecestat and lanabecestat failed to slow cognitive and functional decline in individuals with prodromal or early Alzheime, INTRODUCTION: The APECS and AMARANTH trials showed that beta-secretase (BACE) inhibitors verubecestat and lanabecestat failed to slow cognitive and functional decline in individuals with prodromal or early Alzhei[SEP]", "label": "no"}
{"id": "converted_146", "sentence1": "Is SLC22A3 expressed in the brain?", "sentence2": "The organic cation transporter (OCT) 3 is widely expressed in various organs in humans, and involved in the disposition of many exogenous and endogenous compounds. Several lines of evidence have suggested that OCT3 expressed in the brain plays an important role in the regulation of neurotransmission. , The organic cation transporter 3 (OCT3; synonymous: extraneuronal monoamine transporter, EMT, Slc22a3) encodes an isoform of the organic cation transporters and is expressed widely across the whole brain., In agreement with this distribution, OCT3/Slc22a3-deficient mice show evidence of altered monoamine neurotransmission in the brain, with decreased intracellular content and increased turnover of aminergic transmitters., CRT, taurine transporter (TauT/SLC6A6) and organic cation transporter (OCT3/SLC22A3) expressed at the BCSFB are involved in guanidinoacetic acid or creatinine efflux transport from CSF., The organic cation transporter 3 (OCT3; synonymous: extraneuronal monoamine transporter, EMT, Slc22a3) encodes an isoform of the organic cation transporters and is expressed widely across the whole brain, The organic cation transporter 3 (OCT3; synonymous: extraneuronal monoamine transporter, EMT, Slc22a3) encodes an isoform of the organic cation transporters and is expressed widely across the whole brain. , CRT may be a key factor facilitating blood-to-brain guanidinoacetate transport in patients deficient in S-adenosylmethionine:guanidinoacetate N-methyltransferase, the creatine biosynthetic enzyme, resulting in cerebral accumulation of guanidinoacetate. CRT, taurine transporter (TauT/SLC6A6) and organic cation transporter (OCT3/SLC22A3) expressed at the BCSFB are involved in guanidinoacetic acid or creatinine efflux transport from CSF., Slc22a3) encodes an isoform of the organic cation transporters and is expressed widely across the whole brain., CRT, taurine transporter (TauT/SLC6A6) and organic cation transporter (OCT3/SLC22A3) expressed at the BCSFB are involved in guanidinoacetic acid or creatinine efflux transport from CSF. Interestingly, BBB efflux transport of GCs, including guanidinoacetate and creatinine, is negligible, though the BBB has a variety of efflux transport systems for synthetic precursors of GCs, such as amino acids and neurotransmitters.,  The organic cation transporter (OCT) 3 is widely expressed in various organs in humans, and involved in the disposition of many exogenous and endogenous compounds. Several lines of evidence have suggested that OCT3 expressed in the brain plays an important role in the regulation of neurotransmission., CRT, taurine transporter (TauT/SLC6A6) and organic cation transporter (OCT3/SLC22A3) expressed at the BCSFB are involved in guanidinoacetic acid or creatinine efflux transport from CSF., Several lines of evidence have suggested that OCT3 expressed in the brain plays an important role in the regulation of neurotransmission., The organic cation transporter 3 (OCT3; synonymous: extraneuronal monoamine transporter, EMT, Slc22a3) encodes an isoform of the organic cation transporters and is expressed widely across the whole brain., OCT2-OCT-3 display differential tissue distribution: OCT1 is predominantly found in liver of humans, and liver and kidney in rodents; OCT2 is most strongly expressed in both human and rodent kidney, whereas is OCT3 primarily expressed in placenta, but also more widely detected in various tissues, including brain and lung.[SEP]Relations: POU2F2 has relations: anatomy_protein_present with placenta, anatomy_protein_present with placenta. placenta has relations: anatomy_protein_present with SLC22A3, anatomy_protein_present with SLC22A3. SLC6A6 has relations: anatomy_protein_present with placenta, anatomy_protein_present with placenta. SLC22A3 has relations: anatomy_protein_present with placenta, anatomy_protein_present with placenta.", "label": "yes"}
{"id": "converted_3211", "sentence1": "Can antisense threapy be used for Huntington's disease?", "sentence2": "In this issue of Neuron, Kordasiewicz et al. (2012) show the benefit of transient antisense oligonucleotide (ASO) therapy to degrade Huntingtin mRNA and elicit sustained therapeutic benefit in HD mice., \"Huntingtin holiday\": progress toward an antisense therapy for Huntington's disease.[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_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_4177", "sentence1": "Should cerebrolysin be used for aneurysmal subarachnoid hemorrhage?", "sentence2": "No significant difference was detected in the proportion of patients with favorable six-month GOSE in either study group (odds ratio (OR): 1.49; 95% confidence interval (CI): 0.43-5.17). Secondary functional outcome measures for favorable six-month recovery i.e. a mRS of 0 to 3 (OR: 3.45; 95% CI 0.79-15.01) were comparable for both groups. Similarly, there was no difference in MOCA neurocognitive performance (p-value: 0.75) and in the incidence of DCI (OR: 0.85 95% CI: 0.28-2.59).CONCLUSIONS: Use of Cerebrolysin in addition to standard-of-care management of aneurysmal SAH is safe, well tolerated and feasible. However, the neutral results of this trial suggest that it does not improve the six-month global functional performance of patients., CONCLUSION: Cerebrolysin injection during the acute period of SAH appeared to reduce the mortality rate, especially in poor-grade patients. This study suggests the potential of Cerebrolysin for treating aneurysmal SAH. Further studies are needed to confirm our results.[SEP]", "label": "no"}
{"id": "converted_1236", "sentence1": "Is there any cross-talk between the Wnt and the Akt pathways?", "sentence2": "Our data demonstrate that engaging Wnt signaling at the receptor level by this method leads to necessary crosstalk between multiple signaling pathways including activation of Akt, mTOR, Wnt/β-catenin, PKA/CREB, and inhibition of RhoA/ROCK that substantially increase human β-cell proliferation while maintaining the β-cell phenotype., The cross-talk role of Wnt/β-catenin and PI3K/Akt signaling pathway, with GSK-3β as the key enzyme bridging these pathways, may contribute to the inhibition of cholangiocarcinoma cells by hUC-MSCs., We find that Wnt stimulation leads to phosphorylation of insulin signaling key mediators, including Akt, GSK3β, and ERK1/2, although with a lower fold stimulation and slower time course than observed for insulin., Wnt induces phosphorylation of Akt, ERK1/2, and GSK3β, and this is dependent on insulin/IGF-1 receptors., Pharmacologic inhibition of PI3K resulted in the downregulation of several members of the β-catenin pathway, including Fra-1, c-Myc, and cyclin D1., Similar results were observed in vivo, as intratumoral injection of LY294002 downregulated the expression of the components of the β-catenin pathway and delayed tumor growth in nude mice harboring subcutaneous LN229 xenografts., These results suggest that the PI3K/AKT signaling pathway regulates glioma cell proliferation, in part via repression of the Wnt/β-catenin pathway., Small-molecule inhibitors of phosphatidylinositol 3-kinase/Akt signaling inhibit Wnt/beta-catenin pathway cross-talk and suppress medulloblastoma growth, Small-molecule inhibitors targeting the PI3K/Akt signaling pathway affected beta-catenin signaling by activation [corrected] of GSK-3beta, [corrected] resulting in cytoplasmic retention of beta-catenin and reduced expression of its target genes cyclin D1 and c-Myc., These findings demonstrate the importance of cross-talk between the PI3K/Akt and beta-catenin pathways in medulloblastoma and rationalize the PI3K/Akt signaling pathway as a therapeutic target in treatment of this disease., Western blot analyses revealed that the recombinant Wnt ligand Wnt-3A increased phosphorylation of AKT and the downstream kinase glycogen synthase kinase (GSK)-3beta as well as accumulation of activated, nuclear beta-catenin., Chemical inhibition of PI3K abolished Wnt-dependent phosphorylation of AKT and GSK-3beta and trophoblast motility but did not affect appearance of activated beta-catenin or Wnt/TCF reporter activity., The data suggest that Wnt-3A may activate canonical Wnt signaling and PI3K/AKT through distinct receptors., Mutational activation of the phosphatidylinositol 3-kinase (PI3K) pathway occurs in a wide variety of tumors, whereas activating Wnt pathway mutants are predominantly found in colon cancer. Because GSK3 is a key component of both pathways, it is widely assumed that active PI3K signaling feeds positively into the Wnt pathway by protein kinase B (PKB)-mediatefd inhibition of GSK3., n addition, PKB has been proposed to modulate the canonical Wnt signaling through direct stabilization and nuclear localization of beta-catenin., Here, we show that compartmentalization by Axin of GSK3 prohibits cross-talk between the PI3K and Wnt pathways and that Wnt-mediated transcriptional activity is not modulated by activation of the PI3K/PKB pathway., Our recent study revealed a second mechanism for Cby-mediated beta-catenin inhibition in which Cby cooperates with 14-3-3 adaptor proteins to facilitate nuclear export of beta-catenin, following phosphorylation of Cby by Akt kinase., Therefore, our findings unravel a novel molecular mechanism regulating the dynamic nucleo-cytoplasmic trafficking of beta-catenin and provide new insights into the cross-talk between the Wnt and Akt signaling pathways., Here, we review recent literature concerning Cby function and discuss our current understanding of the relationship between Wnt and Akt signaling., As inappropriate activation of WNT/CTNNB1 signaling causes late-onset GCT development and cross talk between the PI3K/AKT and WNT/CTNNB1 pathways has been reported, we tested whether these pathways could synergize in GCT., This explains why prostate tumors subjected to androgen ablation experience an increase in Akt phosphorylation, and suggest that the tumor compensates for the loss of one pathway with another. Different modes of interaction between the two pathways, including direct interaction, or regulation via downstream intermediates, such as the wnt/GSK-3beta/beta-catenin pathway, NF-kappaB, and the FOXO family of transcription factors, will be discussed., FGF signals are transduced through FGF receptor to the FRS2-GRB2-GAB1-PI3K-AKT signaling cascade to downregulate GSK3beta activity depending on Ser 9 phosphorylation. Because GSK3beta-dependent phosphorylation of beta-catenin and SNAIL leads to FBXW1 (betaTRCP)-mediated ubiquitination and degradation, GSK3beta downregulation results in the stabilization and the nuclear accumulation of beta-catenin and SNAIL., Bridging the BMP and Wnt pathways by PI3 kinase/Akt and 14-3-3zeta, Concurrently, PTEN, an inhibitor of PI3K/Akt pathway, is also primarily inactivated in the ISCs, leading to activation of Akt. Thus, Akt may contribute to activation of beta-catenin in ISCs in coordination with Wnt signaling., Thus, we propose that BMP signaling plays a role in inhibition of ISC self-renewal through suppression of Wnt/beta-catenin signaling in ISC, and this cross-talk is bridged, at least in part, through the PTEN/Akt pathway and further enforced by 14-3-3zeta., In MC3T3-E1 osteoblast-like cultures, dexamethasone (DEX) activates glycogen synthase kinase-3beta (GSK3beta) and inhibits a differentiation-related cell cycle that occurs at a commitment stage immediately after confluence., Here we show that DEX inhibition of the differentiation-related cell cycle is associated with a decrease in beta-catenin levels and inhibition of LEF/TCF-mediated transcription., These inhibitory activities are no longer observed in the presence of lithium, a GSK3beta inhibitor., DEX decreased the serum-responsive phosphorylation of protein kinase B/Akt-Ser(473) within minutes, and this inhibition was also observed after 12 h. When the phosphatidylinositol 3-kinase (PI3K)/Akt pathway was inhibited by wortmannin, DEX no longer inhibited beta-catenin levels., Furthermore, DEX-mediated inhibition of LEF/TCF transcriptional activity was attenuated in the presence of dominant negative forms of either PI3K or protein kinase B/Akt. These results suggest cross-talk between the PI3K/Akt and Wnt signaling pathways., These results suggest that inhibition of a PI3K/Akt/GSK3beta/beta-catenin/LEF axis and stimulation of HDAC1 cooperate to mediate the inhibitory effect of DEX on Wnt signaling and the osteoblast differentiation-related cell cycle., WISP-1 (Wnt-1-induced secreted protein) was identified as an oncogene regulated by the Wnt-1-beta-catenin pathway., Here it is shown that WISP-1 can activate the antiapoptotic Akt/PKB signaling pathway. , Our results show that both TGFβ1 and Wnt3a lead to increased accumulation of β-catenin, phosphorylation of AKT and p44/42 MAPK.[SEP]Relations: Medulloblastoma has relations: disease_phenotype_positive with medulloblastoma, disease_phenotype_positive with medulloblastoma. CTNNB1 has relations: disease_protein with medulloblastoma, protein_protein with PTEN, disease_protein with medulloblastoma, protein_protein with PTEN. cytoplasm has relations: cellcomp_protein with PTEN, cellcomp_protein with PTEN.", "label": "yes"}
{"id": "converted_2130", "sentence1": "Have studies shown that there is no link between DNA methylation patterns and Post Traumatic Stress Disorder?", "sentence2": "Using pre-deployment SKA2 methylation levels and childhood trauma exposure, we found that the previously published suicide prediction rule significantly predicted post-deployment PTSD symptoms (AUC=0.66, 95% CI: 0.53-0.79) with an optimal sensitivity of 0.81 and specificity of 0.91. Permutation analysis using random methylation loci supported these findings. Together, these data establish the importance of SKA2 for cortisol stress responsivity and the development of PTSD and provide further evidence that SKA2 is a promising biomarker for stress-related disorders including PTSD.,  Results provide novel support for PTSD-related accelerated aging in DNAm and extend the evidence base of known DNAm age correlates to the domains of neural integrity and cognition., We investigated serum DNA methylation patterns in genomic repetitive elements, LINE-1 and Alu, for post-traumatic stress disorder (PTSD) cases and controls who were US military service members recently deployed to Afghanistan or Iraq., In light of its role in glucocorticoid receptor transactivation, we investigated whether SKA2 DNA methylation influences cortisol stress reactivity and is involved in the development of post-traumatic stress disorder (PTSD)., These results suggest that alterations in global methylation pattern are involved in behavioural adaptation to environmental stress and pinpoint Dlgap2 as a possible target in PTSD., Here we examined whether there was a link between an established rat model of post-traumatic stress disorder (PTSD) and Bdnf DNA methylation, We investigated serum DNA methylation patterns in genomic repetitive elements, LINE-1 and Alu, for post-traumatic stress disorder (PTSD) cases and controls who were US military service members recently deployed to Afghanistan or Iraq.Cases (n = 75) had a postdeployment diagnosis of PTSD, DNA methylation in repetitive elements and post-traumatic stress disorder: a case-control study of US military service members, Here we examined whether there was a link between an established rat model of post-traumatic stress disorder (PTSD) and Bdnf DNA methylation. , DNA methylation in repetitive elements and post-traumatic stress disorder: a case-control study of US military service members., AIM: We investigated serum DNA methylation patterns in genomic repetitive elements, LINE-1 and Alu, for post-traumatic stress disorder (PTSD) cases and controls who were US military service members recently deployed to Afghanistan or Iraq. , Together, these results suggest that psychosocial stress may alter global and gene-specific DNA methylation patterns potentially associated with peripheral immune dysregulation., DNA methylation in vulnerability to post-traumatic stress in rats: evidence for the role of the post-synaptic density protein Dlgap2., Subjects with PTSD showed a higher DNA methylation of four CpG sites at the BDNF promoter compared with those without PTSD, Cumulatively, the data suggest that epigenetic variation at SKA2 mediates vulnerability to suicidal behaviors and PTSD through dysregulation of the HPA axis in response to stress.[SEP]", "label": "no"}
{"id": "converted_47", "sentence1": "Is Weaver syndrome similar to Sotos?", "sentence2": "Overgrowth conditions are a heterogeneous group of disorders characterised by increased growth and variable features, including macrocephaly, distinctive facial appearance and various degrees of learning difficulties and intellectual disability. Among them, Sotos and Weaver syndromes are clinically well defined and due to heterozygous mutations in NSD1 and EZH2, respectively. NSD1 and EZH2 are both histone-modifying enzymes, NSD1 and EZH2 are SET domain-containing histone methyltransferases that play key roles in the regulation of transcription through histone modification and chromatin modeling: NSD1 preferentially methylates lysine residue 36 of histone 3 (H3K36) and is primarily associated with active transcription, while EZH2 shows specificity for lysine residue 27 (H3K27) and is associated with transcriptional repression, Constitutional NSD1 and EZH2 mutations cause Sotos and Weaver syndromes respectively, overgrowth syndromes with considerable phenotypic overlap, Clinically, Weaver syndrome is closely related to Sotos syndrome, which is frequently caused by mutations in NSD1, Overgrowth syndromes such as Beckwith-Wiedemann syndrome, Sotos syndrome, and Weaver syndrome have an increased risk of neoplasia., Thus, it is not surprising that prenatal overgrowth occurs in several syndromes, including the Sotos and Weaver syndromes., NSD1 mutations are the major cause of Sotos syndrome and occur in some cases of Weaver syndrome but are rare in other overgrowth phenotypes., We conclude therefore that NSD1 mutations account for most cases of Sotos syndrome and a significant number of Weaver syndrome cases in our series., We conclude that intragenic mutations of NSD1 are the major cause of Sotos syndrome and account for some Weaver syndrome cases but rarely occur in other childhood overgrowth phenotypes., Overgrowth syndromes such as Beckwith-Wiedemann syndrome, Sotos syndrome, and Weaver syndrome have an increased risk of neoplasia, NSD1 mutations are the major cause of Sotos syndrome and occur in some cases of Weaver syndrome but are rare in other overgrowth phenotypes, We conclude that intragenic mutations of NSD1 are the major cause of Sotos syndrome and account for some Weaver syndrome cases but rarely occur in other childhood overgrowth phenotypes, Considerable phenotypic overlap between Sotos and Weaver syndromes is also evident. , Considerable phenotypic overlap between Sotos and Weaver syndromes is also evident. The identification of an EZH2 mutation can therefore provide an objective means of confirming a subtle presentation of Weaver syndrome and/or distinguishing Weaver and Sotos syndromes.,  Overgrowth syndromes such as Beckwith-Wiedemann syndrome, Sotos syndrome, and Weaver syndrome have an increased risk of neoplasia. Two previous cases of neuroblastoma have been reported in children with Weaver syndrome., Weaver syndrome is closely related to Sotos syndrome,, Overgrowth syndromes such as Beckwith-Wiedemann syndrome, Sotos syndrome, and Weaver syndrome have an increased risk of neoplasia., Considerable phenotypic overlap between Sotos and Weaver syndromes is also evident., Clinically, Weaver syndrome is closely related to Sotos syndrome, which is frequently caused by mutations in NSD1.[SEP]Relations: Neuroblastoma has relations: disease_phenotype_positive with Beckwith-Wiedemann syndrome, disease_phenotype_positive with Sotos syndrome, disease_phenotype_positive with Beckwith-Wiedemann syndrome, disease_phenotype_positive with Sotos syndrome. Beckwith-Wiedemann syndrome has relations: disease_protein with NSD1, disease_protein with NSD1. Feeding difficulties has relations: disease_phenotype_positive with Sotos syndrome, disease_phenotype_positive with Sotos syndrome. Weaver syndrome has relations: disease_protein with EZH2, disease_protein with NSD1, disease_protein with EZH2, disease_protein with NSD1. Macrocephaly has relations: disease_phenotype_positive with Sotos syndrome, disease_phenotype_positive with Weaver syndrome, disease_phenotype_positive with Sotos syndrome, disease_phenotype_positive with Weaver syndrome. Sotos syndrome has relations: disease_protein with NSD1, disease_protein with NSD1. Intellectual disability has relations: disease_phenotype_positive with Weaver syndrome, disease_phenotype_positive with Sotos syndrome, disease_phenotype_positive with Weaver syndrome, disease_phenotype_positive with Sotos syndrome.", "label": "yes"}
{"id": "converted_3904", "sentence1": "Is Ixodes a species of tick?", "sentence2": "ixodid ticks, ixodid ticks ,  ixodid ticks, tick, Ixodes ricinus, hard ticks (family Ixodidae), The two enzootic tick vectors, Ixodes affinis and Ixodes minor, rarely bite humans but are more important than the human biting \"bridge\" vector, Ixodes scapularis, in maintaining the enzootic spirochete cycle in nature., is more common in coastal habitats, where a greater diversity of Ixodes species ticks are found feeding on small mammal hosts (four species when compared with only I. pacificus in other sampled habitats)., We found three of five previously reported tick species as well as a tick resembling the eastern North American tick Ixodes minor Neumann (which we here designate Ixodes \"Mojave morphotype\") on isolated Amargosa voles and Owens Valley voles (Microtus californicus vallicola Bailey) in Inyo County in 2012 and 2014., THODS: We focused on the well-studied tick genus Ixodes from which many species are known to transmit zoonotic diseases to humans. W, Ectoparasites of Microtus californicus and Possible Emergence of an Exotic Ixodes Species Tick in California., Since 2007, non-native tick species have been documented in the state every year, including Amblyomma americanum, Dermacentor andersoni, Dermacentor occidentalis, Dermacentor variabilis, Ixodes pacificus, Ixodes ricinus, Ixodes scapularis, Ixodes texanus, and Rhipicephalus sanguineus sensu lato (s.l.)., in 1.5% of Ixodes species ticks and 3.6% of small mammals., Data-driven predictions and novel hypotheses about zoonotic tick vectors from the genus Ixodes., spirochetes and transmitted by Ixodes species ticks., In this study, cutaneous bite-site lesions were analyzed using Affymetrix mouse genome 430A 2.0 arrays and histopathology at 1, 3, 6, and 12 hours after uninfected Ixodes scapularis nymphal tick attachment., The minimally vegetated, extremely arid desert surrounding the pools is essentially uninhabitable for Ixodes species ticks., Biology of Ixodes species ticks in relation to tick-borne zoonoses., Borrelia miyamotoi is a newly described emerging pathogen transmitted to people by Ixodes species ticks and found in temperate regions of North America, Europe, and Asia., Rickettsia conorii was found in virtually all non- Ixodes tick species from Albania and Turkey., Ixodes anatis is a species of endophilic (nidicolous) tick species parasitizing brown kiwi (Apteryx mantelli). Even, Ixodes ariadnae is a tick species of bats so far reported only in Central Europe, with its description based on the female and nymph. Th, BACKGROUND: Ixodes collaris Hornok, 2016 is a recently discovered tick species associated with bats, Ixodes holocyclus (Acarina: Ixodidae) and Ixodes cornuatus (Acarina: Ixodidae) are two tick species found in the more densely populated areas of Australia and are known to be the cause of the neurotoxic disease tick paralysis in humans and mammals. Borre, Ixodes affinis Neumann (Acari: Ixodidae) is a hard-bodied tick species distributed throughout much of the southeastern United States. Alt, ixodid tick fauna consists of 241 species in the genus Ixodes and 442 species in the genera Amblyomma, Anomalohimalaya, Bothriocroton, Cosmiomma, Dermacentor, Haemaphysalis, Hyalomma, Margaropus, Nosomma, Rhipicentor and Rhipicephalus in the family Ixodidae, with the genus Boophilus becoming a subgenus of the genus Rhipicephalus. The family Nutt, e following 16 ixodid tick species were identified: Ixodes fuscipes, Amblyomma auricularium, Amblyomma coelebs, Amblyomma dubitatum, Amblyomma geayi, Amblyomma humerale, Amblyomma latepunctatum, Amblyomma longirostre, Amblyomma naponense, Amblyomma nodosum, Amblyomma oblongoguttatum, Amblyomma ovale, Amblyomma romitii, Amblyomma rotundatum, Amblyomma scalpturatum, and Amblyomma varium. From these, A. aur, In 2014, a new tick species, Ixodes inopinatus, was described, which is closely related to Ixodes ricinus. So fa, ontinent. Zoonotic Babesia is vectored by Ixodes ticks and is commonly transmitted in North America by Ixodes scapularis, the tick species responsible for transmitting the pathogens that also cause Lyme disease, Powassan virus, and anaplasmosis in hu, In addition to identifying novel, testable hypotheses about intrinsic features driving vectorial capacity across Ixodes tick species, our model identifies particular Ixodes species with the highest probability of carrying zoonotic diseases, offering specific targets for increased zoonotic investigation and surveillance., To date, the tick fauna of this area consists of 117 species in the following families: Argasidae-Argas (7 species), Carios (4 species) and Ornithodoros (2 species); Ixodidae-Amblyomma (8 species), Anomalohimalaya (2 species), Dermacentor (12 species), Haemaphysalis (44 species), Hyalomma (6 species), Ixodes (24 species) and Rhipicephalus (8 species)., During a 3-yr comprehensive study, 196 ixodid ticks (9 species) were collected from 89 passerine birds (32 species) from 25 localities across Canada to determine the distribution of avian-associated tick species and endogenous Lyme disease spirochetes, Borrelia burgdorferi Johnson, Schmid, Hyde, Steigerwalt, and Brenner., In the Polish fauna there are 19 species of ticks (Ixodida) recognized as existing permanently in our country: Argas reflexus, Argas polonicus, Carios vespertilionis, Ixodes trianguliceps, Ixodes arboricola, Ixodes crenulatus, Ixodes hexagonus, Ixodes lividus, Ixodes rugicollis, Ixodes caledonicus, Ixodes frontalis, Ixodes simplex, Ixodes vespertilionis, Ixodes apronophorus, Ixodes persulcatus, Ixodes ricinus, Haemaphysalis punctata, Haemaphysalis concinna, Dermacentor reticulatus., Occasionally, alien species of ticks transferred to the territory of Poland are recorded: Amblyomma sphenodonti, Amblyomma exornatum, Amblyomma flavomaculatum, Amblyomma latum, Amblyomma nuttalli, Amblyomma quadricavum, Amblyomma transversale, Amblyomma varanensis, Amblyomma spp., Dermacentor marginatus, Hyalomma aegyptium, Hyalomma marginatum, Ixodes eldaricus, Ixodes festai, Rhipicephalus rossicus, Rhipicephalus sanguineus., Haemaphysalis leporispalustris (Packard) (one nymph, 14 larvae); the bird tick Ixodes brunneus Koch (two larvae); the American dog tick, Dermacentor variabilis (Say) (one nymph); and Ixodes affinis Neumann (one larva)., Four members of the Ixodes ricinus species complex, Ixodes pacificus, Ixodes persulcatus, Ixodes ricinus and Ixodes scapularis, have, between them, a worldwide distribution within the northern hemisphere., Diapause in ticks of the medically important Ixodes ricinus species complex., Herein, we report these ticks to represent three different species: Ixodes catarinensis n. sp., We found that 430 endemic ticks were from 3 Ixodes species: Ixodes pacificus, Ixodes spinipalpis, and Ixodes angustus, whereas Ixodes scapularis (n = 111) was the most common species among the 119 nonendemic ticks., In total, 549 human-biting Ixodes ticks were submitted comprising both endemic and nonendemic species., Human-Biting Ixodes Ticks and Pathogen Prevalence from California, Oregon, and Washington., In this study, we show that many nonendemic Ixodes ticks (119/549) are most likely acquired from travel to a different geographic region., The Ixodes ricinus species complex is a group of ticks distributed in almost all geographic regions of the world., We report a tick associated with the enhancement of mammalian meat anaphylaxis after tick bite which is novel for both Australia and the world and establishes Ixodes (Endopalpiger) australiensis as a second tick species associated with mammalian meat allergy in Australia., Among the various species of hard ticks, Ixodes ricinus is the most frequently found tick throughout Europe.,  in humans. We aimed to identify intrinsic traits that predict which Ixodes tick species are confirmed or strongly suspected to be vectors of zoonotic pathogens.METHODS: We focused on the well-studied tick genus Ixodes from which many species are known to transmit zoonoti, A list of the 70 species of Australian ticks; diagnostic guides to and species accounts of Ixodes holocyclus (paralysis tick), Ixodes cornuatus (southern paralysis tick) and Rhipicephalus australis (Australian cattle tick); and consideration of the place of Australia in the evolution of ticks with comments on four controversial ideas., Differentiation of medically important Euro-Asian tick species Ixodes ricinus, Ixodes persulcatus, Ixodes hexagonus, and Dermacentor reticulatus by polymerase chain reaction., All these I. granulatus ticks collected from Taiwan and Japan were genetically affiliated to a monophyletic group with highly homogeneous sequences (95.8-99.5% similarity), and can be discriminated from other species and subgenera of Ixodes ticks with a sequence divergence ranging from 13.6% to 62.9%., The phylogenetic relationships were analyzed by comparing the sequences of mitochondrial 16S ribosomal DNA gene obtained from 19 strains of ticks representing seven species of Ixodes and two outgroup species (Rhipicephalus sanguineus and Haemaphysalis inermis)., e, I. woyliei n. sp. was only found on two I. o. fusciventer.CONCLUSIONS: Morphological and molecular data have confirmed the first new Australian Ixodes tick species described in ov, More than 800 tick species have been reported world-wide however only about 30 tick species feed on humans, among them Ixodes ricinus, which is the most frequent tick species biting humans in Europe., Description of a new tick species, Ixodes collaris n. sp. (Acari: Ixodidae), from bats (Chiroptera: Hipposideridae, Rhinolophidae) in Vietnam.[SEP]", "label": "yes"}
{"id": "converted_3928", "sentence1": "Is the Apis mellifera genome available?", "sentence2": " Mining Apis mellifera sequences made it possible to identify the honey bee subspecies both at the mitochondrial and nuclear genome levels., Honey bee research is believed to be influenced dramatically by colony collapse disorder (CCD) and the sequenced genome release in 2006, but this assertion has never been tested.,  The genome release and CCD had quantitively only minor effects, mainly on honey bee health-related topics post-2006. , We show that the honeybee genome is structured with respect to plasticity; genes that respond to an environmental trigger are colocated in the honeybee genome in a series of gene clusters, many of which have been assembled in the last 80 My during the evolution of the Apidae. , we have mined histone methyltransferases and demethylases from the whole genome sequence of Aedes aegypti (Diptera), the pea aphid Acyrthosiphon pisum, the triatomid bug Rhodnius prolixus (Hemiptera), the honeybee Apis mellifera (Hymenoptera),[SEP]", "label": "yes"}
{"id": "converted_888", "sentence1": "Does replication timing affect the rate of somatic mutations?", "sentence2": "Here we observe that mutation rate, as reflected in recent evolutionary divergence and human nucleotide diversity, is markedly increased in later-replicating regions of the human genome, ll classes of substitutions are affected, suggesting a generalized mechanism involving replication time-dependent DNA damage, We show that mutation rate varies 6-fold across a single chromosome, that this variation is correlated with replication timing, and we propose a model to explain this variation that relies on the temporal separation of two processes for replicating past damaged DNA: error-free DNA damage tolerance and translesion synthesis., Recent studies revealed a long suspected replication-timing effect on mutation rate, but the mechanisms that regulate the increase in mutation rate as the genome is replicated remain unclear. , DNA repair systems, in general, are less efficient in late replicating heterochromatic regions compared to early replicating euchromatic regions of the genome., The mutational profile of the yeast genome is shaped by replication, the mutation rate increases with the replication timing by more than 30% between the earliest and the latest replicating regions., Thus, we show that the leading replicating strands present an excess of C over G and of A over T in the genome of S. cerevisiae (reciprocally an excess of G + T over C + A in lagging strands), Late-replicating domains have higher divergence and diversity in Drosophila melanogaster, Recent evidence also suggests that late replication is associated with high mutability in yeast., Limited evidence from one chromosome arm in Drosophila melanogaster suggests the opposite pattern, with regions overlapping early-firing origins showing increased levels of diversity and divergence, The mutation rate for DNA mismatch repair null strains was approximately 1 mutation per genome per generation, 225-fold greater than the wild-type rate. The mutations were distributed randomly throughout the genome, independent of replication timing., Many single-nucleotide substitutions in cancer genomes arise because of errors in DNA replication, which is spatio-temporally stratified., Here we propose that DNA replication patterns help shape the mutational landscapes of normal and cancer genomes, Using data on five fully sequenced cancer types and two personal genomes, we determined that the frequency of intergenic single-nucleotide substitution is significantly higher in late DNA replication timing regions, even after controlling for a number of genomic features, we found that genomic regions in close spatial proximity to late-replicating domains display similar mutation spectra as the late-replicating regions themselves, In addition, certain chromosome rearrangements found in cancer cells and in cells exposed to ionizing radiation display a significant delay in replication timing of >3 hours that affects the entire chromosome(2,3). Recent work from our lab indicates that disruption of discrete cis-acting autosomal loci result in an extremely late replicating phenotype that affects the entire chromosome(4)., A conservative estimate is that at least 1-2% of new deleterious mutations affect some aspect of DNA replication, repair, or chromosome segregation. Since deleterious mutations can have an effect even as heterozygotes, this mutation accumulation can create an inherited background of late-acting mutations that themselves enhance mutation rate., Drake calculates that lytic RNA viruses display spontaneous mutation rates of approximately one per genome while most have mutation rates that are approximately 0.1 per genome (Drake 1993). This constancy of germline mutation rates among microbial species need not necessarily mean constancy of the somatic mutation rates., A recent flurry of reports correlates replication timing (RT) with mutation rates during both evolution and cancer., DNA replication timing, genome stability and cancer: late and/or delayed DNA replication timing is associated with increased genomic instability., Since deleterious mutations can have an effect even as heterozygotes, this mutation accumulation can create an inherited background of late-acting mutations that themselves enhance mutation rate., In addition, this method allows for the unambiguous identification of chromosomal rearrangements that correlate with changes in replication timing that affect the entire chromosome.[SEP]Relations: malignant giant cell tumor has relations: disease_disease with cancer, disease_disease with cancer.", "label": "yes"}
{"id": "converted_317", "sentence1": "Have mutations in the Polycomb group been found in human diseases?", "sentence2": "We identify a novel mutation in PHC1, a human orthologue of the Drosophila polyhomeotic member of polycomb group (PcG), which significantly decreases PHC1 protein expression, increases Geminin protein level and markedly abolishes the capacity to ubiquitinate histone H2A in patient cells., In clinical specimens of head and neck cancer, we found that coamplification of BMI1 and AURKA correlated with poorer prognosis., Mutations of EZH2, RUNX1, TP53, and ASXL1 were associated with shorter overall survival independent of the LR-PSS., In this study, we show the high frequency of spontaneous γδ T-cell leukemia (T-ALL) occurrence in mice with biallelic deletion of enhancer of zeste homolog 2 (Ezh2)., Subsequently, analysis of deletion profiles of other PRC2 members revealed frequent losses of genes such as EZH2, AEBP2, and SUZ12; however, the deletions targeting these genes were large. We also identified two patients with homozygous losses of JARID2 and AEBP2. We observed frequent codeletion of AEBP2 and ETV6, and similarly, SUZ12 and NF1., A total of 25 different EZH2 mutations were detected in 5.9% of PMF, 1.2% of PPV-MF, and 9.4% of PET-MF patients; most were exonic heterozygous missense changes., In the present investigation we have focused on the candidate region in 6p23, a region that have been found linked to CL/P in several investigations, in the attempt to find out the susceptibility gene provisionally named OFC1. Gene expression experiments in mice embryo of positional candidate genes revealed that JARID2 was highly and specifically expressed in epithelial cells in merging palatal shelves., High expression of EZH2 and amplification of EZH2 was found in 54.1% and 12.0% of ESCCs, respectively., We also observed that HOXA9 levels were significantly inversely correlated with survival and that BMI-1 was overexpressed in cases with 11q23 rearrangements, suggesting that p19(ARF) suppression may be involved in MLL-associated leukemia., We demonstrate that in multiple experimental models of metastatic prostate cancer both BMI1 and Ezh2 genes are amplified and gene amplification is associated with increased expression of corresponding mRNAs and proteins., he EZH2 gene amplification was significantly (P < 0.05) associated with increased EZH2 protein expression., The third tumor showed a t(6p;10q;10p) as the sole karyotypic abnormality, leading to the fusion of PHF1 with another partner, the enhancer of polycomb (EPC1) gene from 10p11; EPC1 has hitherto not been associated with neoplasia.[SEP]Relations: neurofibromatosis has relations: disease_protein with NF1, disease_protein with NF1. precursor lymphoblastic lymphoma/leukemia has relations: disease_protein with RUNX1, disease_protein with RUNX1. head and neck neoplasm has relations: disease_disease with head and neck cancer, disease_disease with head and neck cancer. EZH2 has relations: protein_protein with PHF1, protein_protein with BMI1, protein_protein with ASXL1, protein_protein with EPC1, protein_protein with AEBP2, protein_protein with PHF1, protein_protein with BMI1, protein_protein with ASXL1, protein_protein with EPC1, protein_protein with AEBP2.", "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_2669", "sentence1": "Is CXCL7 a chemokine?", "sentence2": "CXCL7, a chemokine highly expressed in platelets, , Chemokine CXCL7 Heterodimers[SEP]", "label": "yes"}
{"id": "converted_352", "sentence1": "Are there studies representing the involvement of Notch mutations in neurodegenerative diseases such as Down syndrome, Pick's and Prion's disease, and cadasil syndrome?", "sentence2": "he Notch signaling pathway plays a critical role in maintaining the balance between cell proliferation, differentiation and apoptosis, and is a highly conserved signaling pathway that regulates normal development in a context- and dose-dependent manner. Dysregulation of Notch signaling has been suggested to be key events in a variety of hematological malignancies. Notch1 signaling appears to be the central oncogenic trigger in T cell acute lymphoblastic leukemia (T-ALL), in which the majority of human malignancies have acquired mutations that lead to constitutive activation of Notch1 signaling., In a forward genetic screen for mutations that alter intracellular Notch receptor trafficking in Drosophila melanogaster, we recovered mutants that disrupt genes encoding serine palmitoyltransferase and acetyl-CoA carboxylase., Signaling pathways have become a major source of targets for novel therapies in hepatocellular carcinoma (HCC). Survival benefits achieved with sorafenib, a multikinase inhibitor, are unprecedented and underscore the importance of improving our understanding of how signaling networks interact in transformed cells., Notch-1 immunoexpression is increased in Alzheimer's and Pick's disease, (PSEN1) is the major locus for mutations causing familial Alzheimer's disease (FAD) and is also mutated in Pick disease of brain, familial acne inversa and dilated cardiomyopathy. It is a critical facilitator of Notch signalling and many other signalling pathways and protein cleavage events including production of the Amyloidβ (Aβ) peptide from the AMYLOID BETA A4 PRECURSOR PROTEIN (APP, As beta-APP and Notch are both processed by gamma-secretase, we analyzed expression of the Notch signaling pathway in the adult DS brain and in a model system for DS, human trisomy 21 fibroblasts by quantitative PCR. In adult DS cortex we found that Notch1, Dll1 and Hes1 expression is up-regulated. Moreover, DS fibroblasts and Alzheimer disease cortex also show overexpression of Notch1 and Dll1, indicating that enhanced beta-APP processing found in both DS and AD could be instrumental in these changes, A systems biology approach to Down syndrome: identification of Notch/Wnt dysregulation in a model of stem cells aging, Notch3 gene has been recently identified as a causative gene for cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)[SEP]Relations: gamma-secretase complex has relations: cellcomp_protein with PSEN1, cellcomp_protein with PSEN1. dilated cardiomyopathy has relations: disease_protein with PSEN1, disease_protein with PSEN1. NOTCH3 has relations: protein_protein with PSEN1, disease_protein with hepatocellular carcinoma, protein_protein with PSEN1, disease_protein with hepatocellular carcinoma.", "label": "yes"}
{"id": "converted_2561", "sentence1": "Has intepirdine been evaluated in clinical trials? (November 2017)", "sentence2": "Using small molecules blocking 5-HT6serotonin receptor (intepirdine), inhibiting BACE activity (E2609, AZD3293, and verubecestat), or reducing tau aggregation (TRx0237) are also currently in Phase III clinical trials.[SEP]", "label": "yes"}
{"id": "converted_79", "sentence1": "Are there any urine biomarkers for chronic kidney disease?", "sentence2": "Kidney and urine proteomic biomarkers are considered as promising diagnostic tools to predict CKD progression early in diabetic nephropathy, facilitating timely and selective intervention that may reduce the related health-care expenditures., Both blood and urine biomarkers are reviewed in this paper and offer a considerable opportunity to enhance the understanding of the pathophysiology and known epidemiology of these recently defined syndromes., Cardiorenal syndromes (CRS) have been subclassified as five defined entities which represent clinical circumstances in which both the heart and the kidney are involved in a bidirectional injury and dysfunction via a final common pathway of cell-to-cell death and accelerated apoptosis mediated by oxidative stress., There is a strong association between both acute and chronic dysfunction of the heart and kidneys with respect to morbidity and mortality., Both blood and urine biomarkers, including the assessment of catalytic iron, a critical element to the generation of oxygen-free radicals and oxidative stress, are reviewed in this paper., Identification of urine biomarkers has proven to be beneficial in recent years because of ease of handling, stability, and the ability to standardize the various markers to creatinine or other peptides generally already present in the urine. Recent markers such as neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), and podocin have garnered a lot of attention. The emergence of these and other biomarkers is largely because of the evolution of novel genomic and proteomic applications in investigations of acute kidney injury and chronic kidney disease.[SEP]Relations: diabetic nephropathy has relations: disease_disease with chronic kidney disease, disease_disease with chronic kidney disease.", "label": "yes"}
{"id": "converted_2274", "sentence1": "Is autophagy modulated in a circadian fashion?", "sentence2": "TOR signaling pathway and autophagy are involved in the regulation of circadian rhythms in behavior and plasticity of L2 interneurons in the brain of Drosophila melanogaster.,  Our results indicate that the TOR signaling pathway and autophagy are involved in the regulation of circadian rhythms in the behavior and plasticity of neurons in the brain of adult flies., the pathways of autophagy, mTOR, SIRT1, and Wnt that control mammalian circadian rhythm, Metabolic pathways, bile acid synthesis, and autophagic and immune/inflammatory processes are driven by the biological clock. , our findings suggest that the clock geneBmal1is a positive regulator of autophagy through the mTOR signaling pathway and protects cardiomyocytes against high-glucose toxicity., Autophagy is a highly conserved intracellular degradation system, and recently was shown to display circadian rhythms in mice. [SEP]", "label": "yes"}
{"id": "converted_2620", "sentence1": "Is DNA polymerase θ involved in DNA repair?", "sentence2": "DNA polymerase θ (Pol θ) is implicated in various cellular processes including double-strand break repair and apurinic/apyrimidinic site bypass.,  Pol θ is the defining enzyme for a pathway of DSB repair termed \"alternative end-joining\" (altEJ) or \"theta-mediated end-joining.\", DNA polymerase θ is a key player in PARP-mediated DNA damage repair and essential for the survival of cancer cells where homologous recombination is compromised. , DNA polymerase θ protects against genomic instability via an alternative end-joining repair pathway for DNA double-strand breaks.[SEP]", "label": "yes"}
{"id": "converted_2210", "sentence1": "Is dupilumab an antibody targeting the IL-1 receptor?", "sentence2": "Atopic dermatitis (AD) is characterized by type 2 helper T (Th2) cell-driven inflammation. Dupilumab is a fully human monoclonal antibody directed against the IL-4 receptor α subunit that blocks the signaling of IL-4 and IL-13, both key cytokines in Th2-mediated pathways., Dupilumab, a humanized monoclonal antibody to the interteukin-4R is the first antibody (i.e. 'biological') with published efficacy shown in controlled prospective studies in atopic dermatitis. , Dupilumab, a human monoclonal antibody against interleukin-4 receptor alpha, inhibits signaling of interleukin-4 and interleukin-13, type 2 cytokines that may be important drivers of atopic or allergic diseases such as atopic dermatitis., Best evidence of the clinical efficacy of novel immunologic approaches using biological agents in patients with AD is available for the anti-IL-4 receptor α-chain antibody dupilumab, but a number of studies are currently ongoing with other specific antagonists to immune system players.,  Dupilumab, a fully human anti-interleukin-4 receptor α monoclonal antibody, inhibits interleukin-4 and interleukin-13 signalling, key drivers of type-2-mediated inflammation. , Dupilumab was also introduced as a possible treatment for patients with severe pemphigus. It can directly inhibit IL-4 by targeting IL-4 α-chain receptor., We evaluated the efficacy and safety of dupilumab (SAR231893/REGN668), a fully human monoclonal antibody to the alpha subunit of the interleukin-4 receptor[SEP]Relations: Eczema has relations: phenotype_phenotype with Atopic dermatitis, phenotype_phenotype with Atopic dermatitis. dermatitis, atopic has relations: disease_phenotype_positive with Atopic dermatitis, disease_phenotype_positive with Atopic dermatitis.", "label": "no"}
{"id": "converted_2848", "sentence1": "Is inositol effective for trichotillomania?", "sentence2": "Patients assigned to inositol failed to show significantly greater reductions on primary or secondary outcomes measures compared with placebo (all P>0.05)., This is the first study assessing the efficacy of inositol in the treatment of trichotillomania, but found no differences in symptom reductions between inositol and placebo., At study endpoint, 42.1% of patients were 'much or very much improved' on inositol compared with 35.3% on placebo., Conclusions • The review indicates that yoga, aerobic exercise, acupuncture, biofeedback, hypnosis, and inositol and N-acetylcysteine all show promise in the treatment of excoriation disorder and other body-focused repetitive behaviors, such as trichotillomania., Future studies should examine whether inositol may be beneficial in controlling pulling behavior in a subgroup of individuals with trichotillomania.[SEP]", "label": "no"}
{"id": "converted_1176", "sentence1": "Is there an association between serum interleukin-6 concentrations and outcomes of stroke patients?", "sentence2": " In addition, IL-6 concentrations affect clinical outcomes in ischemic stroke., After appropriate adjustment, the odds ratios for the association of markers and poor outcome (comparing the upper and the lower third) were interleukin-6, 3.1 (95% CI: 1.9-5.0); C-reactive protein, 1.9 (95% CI: 1.2-3.1); fibrinogen, 1.5 (95% CI: 1.0-2.36); white cell count, 2.1 (95% CI: 1.3-3.4); and glucose 1.3 (95% CI: 0.8-2.1). The results for interleukin-6 were similar to other studies. , -6 and IL-10 levels were higher in patients with poor outcome. On logistic regression analysis, higher values of IL-6 were significantly associated with clinical outcome at 1 month (odds ratio [OR], 1.25; 95% confidence interval [CI], 1.02-1.54). , In hemorrhagic stroke, high levels of IL-6 in the early phase indicated a poor neurological outcome., Initially elevated levels of hs-IL-6 at presentation further correlated with unfavorable clinical outcomes (by NIHSS and mRs) at both time points. Analysis of variance in the different quartiles identified an hs-IL-6 gradient-dependent correlation at both time points, such that the higher the initial hs-IL-6 concentration, the higher the elevation in inflammatory biomarkers and the poorer the neurological state at both time points (p<0.001 for NIHSS and p=0.001 for mRs, for trend across quartiles). CONCLUSIONS: This study demonstrates the potential of employing hs-IL-6 as an early stage biomarker for the prognosis of acute ischemic stroke. , Another negative correlation was found between IL-6 and CNS scores (r = -0.451, p = 0.000)., In addition, increased levels of IL-6 and reduced levels of protein C and protein S may play a role in acute ischemic stroke severity., Variables that are predictors of adverse stroke outcome include erythrocyte sedimentation rate, and levels of C-reactive protein (CRP), interleukin-6, tumour necrosis factor-alpha and intercellular adhesion molecule-1. [SEP]", "label": "yes"}
{"id": "converted_529", "sentence1": "Is TALEN being used on stem cells?", "sentence2": "Precise correction of the dystrophin gene in duchenne muscular dystrophy patient induced pluripotent stem cells by TALEN and CRISPR-Cas9., Genetic correction of patient-derived induced pluripotent stem cells (iPSCs) by TALENs or CRISPR-Cas9 holds promise for DMD gene therapy; however, the safety of such nuclease treatment must be determined., We generated helper-dependent, capsid-modified adenovirus (HD-Ad5/35) vectors for zinc-finger nuclease (ZFN)- or transcription activator-like effector nuclease (TALEN)-mediated genome editing in human CD34+ hematopoietic stem cells (HSCs) from mobilized adult donors. , We used transcription activator-like effector nuclease (TALEN)-mediated gene editing in mouse embryonic stem cells (mESCs) to produce mice with targeted gene disruptions and insertions in two Y-linked genes--Sry and Uty., Transcription activator-like effector nuclease (TALEN)-mediated gene correction in integration-free β-thalassemia induced pluripotent stem cells., A TALEN genome-editing system for generating human stem cell-based disease models., Low incidence of off-target mutations in individual CRISPR-Cas9 and TALEN targeted human stem cell clones detected by whole-genome sequencing., Using CRISPR-Cas9 and TALEN targeted human pluripotent stem cell clones, we performed whole-genome sequencing at high coverage in order to assess the degree of mutagenesis across the entire genome., A modified TALEN-based system for robust generation of knock-out human pluripotent stem cell lines and disease models., In this study, we utilized a cell-penetrating peptide-based system for ZFN and TALEN delivery., At all loci tested we obtained human embryonic stem cell (ESC) and induced pluripotent stem cell (iPSC) clones carrying transgenic cassettes solely at the TALEN-specified location., We report here the use of TALENs to rapidly and efficiently generate mutant alleles of 15 genes in cultured somatic cells or human pluripotent stem cells, the latter for which we differentiated both the targeted lines and isogenic control lines into various metabolic cell types., Zinc-finger nucleases (ZFNs) and transcription activator-like effector nucleases (TALENs) have been successfully used to knock out endogenous genes in stem cell research., Here we report different methods to efficiently perform TALEN-mediated gene integration and inactivation in different mammalian cell systems including induced pluripotent stem cells and delineate experimental examples associated with these approaches, Together, our results demonstrate that TALE-based transcriptional repressor and TALENs are two promising approaches for loss-of-function studies of microRNA clusters in somatic cells and pluripotent stem cells, We report here the use of TALENs to rapidly and efficiently generate mutant alleles of 15 genes in cultured somatic cells or human pluripotent stem cells, the latter for which we differentiated both the targeted lines and isogenic control lines into various metabolic cell types, TALEN-mediated generation and genetic correction of disease-specific human induced pluripotent stem cells., Baculoviral transduction facilitates TALEN-mediated targeted transgene integration and Cre/LoxP cassette exchange in human-induced pluripotent stem cells., We used transcription activator-like effector nuclease (TALEN)-mediated gene editing in mouse embryonic stem cells (mESCs) to produce mice with targeted gene disruptions and insertions in two Y-linked genes--Sry and Uty. , Using CRISPR-Cas9 and TALEN targeted human pluripotent stem cell clones, we performed whole-genome sequencing at high coverage in order to assess the degree of mutagenesis across the entire genome. , A 5% modification rate was observed in human induced pluripotent stem cells (hiPSCs) treated with TAT-TALEN as measured by the Surveyor assay.  TAT-TALEN protein-mediated gene disruption was applicable in hiPSCs and represents a promising technique for gene knockout in stem cells., Here we engineered transcription activator-like effector nucleases (TALENs) for five distinct genomic loci. At all loci tested we obtained human embryonic stem cell (ESC) and induced pluripotent stem cell (iPSC) clones carrying transgenic cassettes solely at the TALEN-specified location., Seamless correction of the sickle cell disease mutation of the HBB gene in human induced pluripotent stem cells using TALENs., At all loci tested we obtained human embryonic stem cell (ESC) and induced pluripotent stem cell (iPSC) clones carrying transgenic cassettes solely at the TALEN-specified location. Our data suggest that TALENs employing the specific architectures described here mediate site-specific genome modification in human pluripotent cells with similar efficiency and precision as do zinc-finger nucleases (ZFNs).[SEP]", "label": "yes"}
{"id": "converted_1766", "sentence1": "Is ocrelizumab effective for treatment of multiple sclerosis?", "sentence2": " Advances made in immunomodulation are driving the progress being made in the treatment of MS. Ocrelizumab is the first treatment with positive results in the primarily progressive forms and tocilizumab, a drug product for rheumatoid arthritis, stands out as a potential candidate for the treatment of neuromyelitis optica.,  Expert commentary: The recent encouraging results of the ocrelizumab trial in PP MS, the first to reach the primary disability endpoint, indicate B cells as a promising therapeutic target to prevent disease progression. , Ocrelizumab also shows efficacy in the primary progressive form of multiple sclerosis., Ocrelizumab for the treatment of relapsing-remitting multiple sclerosis., Expert commentary: The topline results of two phase-III randomized clinical trials demonstrate superiority of ocrelizumab over interferon beta in RRMS patients with regards to clinical and paraclinical outcome parameters. , The efficacy of three of them, rituximab, ocrelizumab and ofatumumab in MS has been confirmed by placebo-controlled clinical trials demonstrating a significant reduction of the annualized relapsing rate (ARR), new gadolinium-enhancing (GdE) and T2 lesions. , Ongoing PMS trials are currently being conducted with the phosphodiesterase inhibitor ibudilast, S1P modulator siponimod and anti-B-cell therapy ocrelizumab. , RECENT FINDINGS: Novel and imminently emerging DMTs for the treatment of RRMS include alemtuzumab, daclizumab, ocrelizumab, pegylated interferon-β-1a, and three times weekly glatiramer acetate. , To summarize mechanisms of action, efficacy, and safety of novel and imminently emerging disease-modifying treatments (DMTs) intended to be used in relapsing-remitting multiple sclerosis (RRMS).Novel and imminently emerging DMTs for the treatment of RRMS include alemtuzumab, daclizumab, ocrelizumab, pegylated interferon-β-1a, and three times weekly glatiramer acetate, Ocrelizumab in relapsing-remitting multiple sclerosis: a phase 2, randomised, placebo-controlled, multicentre trial., We aimed to assess efficacy and safety of two dose regimens of the humanised anti-CD20 monoclonal antibody ocrelizumab in patients with relapsing-remitting multiple sclerosis. , In multiple sclerosis (MS), B cell-depleting therapy using monoclonal anti-CD20 Abs, including rituximab (RTX) and ocrelizumab, effectively reduces disease activity. , Ocrelizumab also shows efficacy in the primary progressive form of multiple sclerosis.Most of the presented cell-depleting and myeloablative therapies are highly effective treatment options but are also accompanied by significant risks., The armamentarium of approved disease-modifying therapies in MS and those in development include: (1) the first approved, moderately effective, injectable interferon-β and glatiramer acetate; (2) oral drugs (fingolimod, laquinimod, teriflunomide, dimethyl fumarate); (3) monoclonal antibodies (rituximab, ocrelizumab, ofatumumab, daclizumab, alemtuzumab); and (4) immunosuppressive agents (e.g. mitoxantrone)., BACKGROUND: B lymphocytes are implicated in the pathogenesis of multiple sclerosis. We aimed to assess efficacy and safety of two dose regimens of the humanised anti-CD20 monoclonal antibody ocrelizumab in patients with relapsing-remitting multiple sclerosis.METHODS: We did a multicentre, randomised, parallel, double-blind, placebo-controlled study involving 79 centres in 20 countries. Patients aged 18-55 years with relapsing-remitting multiple sclerosis were randomly assigned (1:1:1:1) via an interactive voice response system to receive either placebo, low-dose (600 mg) or high-dose (2000 mg) ocrelizumab in two doses on days 1 and 15, or intramuscular interferon beta-1a (30 ìg) once a week., Ocrelizumab for the treatment of relapsing-remitting multiple sclerosis., The potential role for ocrelizumab in the treatment of multiple sclerosis: current evidence and future prospects., Ocrelizumab in relapsing-remitting multiple sclerosis: a phase 2, randomised, placebo-controlled, multicentre trial., Ocrelizumab also shows efficacy in the primary progressive form of multiple sclerosis.[SEP]Relations: Rheumatoid arthritis has relations: disease_phenotype_positive with rheumatoid arthritis, disease_phenotype_positive with rheumatoid arthritis. relapsing-remitting multiple sclerosis has relations: disease_disease with multiple sclerosis, disease_disease with multiple sclerosis. multiple sclerosis has relations: disease_disease with relapsing-remitting multiple sclerosis, disease_disease with relapsing-remitting multiple sclerosis.", "label": "yes"}
{"id": "converted_3146", "sentence1": "Is L-4F an apoE mimetic peptide?", "sentence2": "Apolipoprotein A-I mimetic peptide 4F suppresses tumor-associated macrophages and pancreatic cancer progression., L-4F, an Apolipoprotein A-I (ApoA-I) mimetic peptide, is engineered to mimic the anti-inflammatory and anti-oxidative functionalities of ApoA-I.[SEP]", "label": "no"}
{"id": "converted_450", "sentence1": "Can SUMO affect calcium homeostasis?", "sentence2": "Increasing SUMOylation levels correlated inversely with calcium influx in sensory neurons., CRMP2 deSUMOylation by SUMO proteases SENP1 and SENP2 normalized calcium influx to those in the CRMP2AAA mutant., Thus, our results identify a novel role for SUMO modification in CRMP2/CaV2.2 signaling pathway, Moreover, SUMO1 overexpression in isolated cardiomyocytes augmented contractility and accelerated Ca(2+) decay.,  RIM1α SUMOylation at lysine residue K502 facilitates the clustering of CaV2.1 calcium channels and enhances the Ca(2+) influx necessary for vesicular release, whereas non-SUMOylated RIM1α participates in the docking/priming of synaptic vesicles and maintenance of active zone structure. , Identification and characterization of a SUMO-1 conjugation system that modifies neuronal calcium/calmodulin-dependent protein kinase II in Drosophila melanogaster.[SEP]", "label": "yes"}
{"id": "converted_4570", "sentence1": "Is AGO2 related to cytokinesis?", "sentence2": "AGO2 localizes to cytokinetic protrusions in a p38-dependent manner and is needed for accurate cell division., We suggest that AGO2 is part of a regulatory mechanism triggered by cytokinetic stress to generate the appropriate micro-environment for local transcript homeostasis.[SEP]", "label": "yes"}
{"id": "converted_2407", "sentence1": "Has the proteome of mice hippocampus been analysed?", "sentence2": "We employed a discovery-based proteomic approach in subcellular fractions of hippocampal tissue from chronic intermittent alcohol (CIE)-exposed C57Bl/6J mice to gain insight into alcohol-induced changes in GluN2B signaling complexes. ,  We employed shotgun liquid chromatography-mass spectrometry (LC-MS) proteomic and metabonomic profiling approaches on prefrontal cortex (PFC) and hippocampal (HPC) tissue from Df(16)A+/-mice, a model of the 22q11.2 deletion syndrome. ,  Molecular alterations in the frontal cortex and hippocampus ofTsc1+/-and control mice, with or without rapamycin treatment, were investigated. A quantitative mass spectrometry-based shotgun proteomic approach (LC-MSE) was employed as an unbiased method to detect changes in protein levels., This dataset reports on the analysis of mouse hippocampus by LC-MS/MS, from mice fed a diet that was either deficient in n-3 FA (n-3 Def) or sufficient in n-3 FA (n-3 Adq). , Using isobaric tags for relative and absolute quantitation (iTRAQ) and proteomic methods, here we identified learning-induced changes in the hippocampal proteome of non-transgenic (NonTg) and 3 × Tg-AD mice, a widely used animal model of AD. [SEP]Relations: DiGeorge syndrome has relations: disease_disease with 22q11.2 deletion syndrome, disease_disease with 22q11.2 deletion syndrome.", "label": "yes"}
{"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_704", "sentence1": "Are CD44 variants (CD44v) associated with poor prognosis of metastasis?", "sentence2": "CD44 variants and prognosis, The CD44 variant (CD44v) isoforms have been noted as markers for tumour metastasis and prognosis in several adenocarcinomas., Positive CD44v3 expression was associated with more advanced pathological stage and poorer prognosis than negative CD44v3 expression, CD44v6 expression in the adenocarcinoma component may directly affect the behavior of carcinoma and the prognosis of patients, D44 variant 6 in endometrioid carcinoma of the uterus: its expression in the adenocarcinoma component is an independent prognostic marker, CD44v5 expression is independently positively correlated with the aggressiveness of thymic epithelial tumors. The expression of CD44v5 may be a potential trigger of tumor invasion in thymomas, analysis of CD44v expression provides indications of biological and clinical relevance also in low grade lymphoproliferative disorders, clinical relevance of CD44 variant isoform expression on B-cell chronic lymphocytic leukemia, CD44 variants and its association with survival in pancreatic cancer, CD44 variant 6(v6) molecule has been noted as a marker for tumor metastasis and prognosis in several tumors, CD44v2 and CD44v6 may be useful markers for poor prognosis in curatively resected primary pancreatic cancer, CD44v8-10 may play an important role in the adhesion of tumor cells to the capillaries of distant organs in the metastatic process, and that immunohistochemical detection of CD44v8-10 may be a biologic marker of prognostic significance., combined expression of CD44v8-10 and SLX may be a biologic marker of prognostic significance, variant isoforms (CD44v) are expressed on different malignant cells and tissues. Their upregulation has been implicated, in the progression and metastasis of malignomas., expression of the CD44 variant exon 6 is associated with lymph node metastasis in non-small cell lung cancer, a number of variant forms of CD44 are frequently expressed, although these variants are infrequently expressed in normal lung tissue, and that the expression of CD44v6 is particularly associated with lymph node metastasis in NSCLC, Expression of CD44v6 may suggest an increased risk for local lymph node metastasis in NSCLCs, different CD44 isoforms are found in human skin cancers and are modulated during carcinogenesis, D44 isoforms correlate with cellular differentiation but not with prognosis in human breast cancer, Correlations between prognosis and expression of CD44v have been reported for gastric and colon carcinoma, for non-Hodgkin's lymphoma, and recently for breast carcinoma, Certain splice variants (CD44v) can promote the metastatic behaviour of cancer cells. In human colon and breast cancer the presence of epitopes encoded by exon v6 on primary resected tumour material indicates poor prognosis, In human mammary carcinomas and colorectal carcinomas, the expression of CD44v has also been correlated with more progressed tumor stages.[SEP]Relations: colorectal carcinoma has relations: disease_disease with colon carcinoma, disease_disease with colon carcinoma. adenocarcinoma has relations: disease_disease with carcinoma, disease_disease with carcinoma. endometrioid adenocarcinoma has relations: disease_disease with adenocarcinoma, disease_disease with adenocarcinoma. carcinoma has relations: disease_disease with adenocarcinoma, disease_disease with breast carcinoma, disease_disease with adenocarcinoma, disease_disease with breast carcinoma.", "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_3480", "sentence1": "Does nintedanib hold promise for lung disease associated with systemic sclerosis?", "sentence2": "The patient developed progressive lung fibrosis under several immunosuppressants and was started on nintedanib, with clinical and functional stabilization. Nintedanib is a tyrosine-kinase inhibitor that blocks several profibrotic pathways, inhibiting proliferation and migration of fibroblasts and decreasing the synthesis of extracellular matrix proteins. It is approved for idiopathic lung fibrosis and has demonstrated good results in inhibiting migration and proliferation of systemic sclerosis dermal fibroblasts, constituting a promising agent for systemic sclerosis-associated lung fibrosis., BACKGROUND: Nintedanib is an inhibitor targeting platelet-derived growth factor receptor, fibroblast growth factor receptor and vascular endothelial growth factor receptor tyrosine kinases that has recently been approved for the treatment of idiopathic pulmonary fibrosis. , CONCLUSION: Nintedanib targets core features of SSc in Fra2-transgenic mice and ameliorates histological features of pulmonary arterial hypertension, destructive microangiopathy and pulmonary and dermal fibrosis. These data might have direct implications for the ongoing phase III clinical trial with nintedanib in SSc-associated interstitial lung disease., In light of the ongoing advances in our understanding of the pathogenic mechanisms underlying interstitial lung disease in systemic sclerosis, this review also summarizes novel treatment approaches, presenting clinical and preclinical evidence for rituximab, tocilizumab, pirfenidone, and nintedanib, as well as hematopoietic stem cell transplantation and lung transplantation., Pirfenidone and nintedanib are emerging agents that exert pleiotropic effects, reflective of the multiple mechanistic pathways of IPF. , Design of a randomised, placebo-controlled clinical trial of nintedanib in patients with systemic sclerosis-associated interstitial lung disease (SENSCIS™)., The SENSCIS™ trial is a randomised, placebo-controlled Phase III trial that will evaluate the efficacy and safety of nintedanib in patients with SSc-ILD (NCT02597933)., CONCLUSIONS: This trial will assess the efficacy and safety of nintedanib in patients with SSc-ILD., Nintedanib for Systemic Sclerosis-Associated Interstitial Lung Disease., Nintedanib, a tyrosine kinase inhibitor, has been shown to have antifibrotic and antiinflammatory effects in preclinical models of systemic sclerosis and ILD., METHODS\n\nWe conducted a randomized, double-blind, placebo-controlled trial to investigate the efficacy and safety of nintedanib in patients with ILD associated with systemic sclerosis., CONCLUSIONS\n\nAmong patients with ILD associated with systemic sclerosis, the annual rate of decline in FVC was lower with nintedanib than with placebo; no clinical benefit of nintedanib was observed for other manifestations of systemic sclerosis., Potential of Nintedanib in Treatment of Progressive Fibrosing Interstitial Lung Diseases., Anti-fibrotic nintedanib-a new opportunity for systemic sclerosis patients?, Newer agents with anti-fibrotic properties, such as pirfenidone or nintedanib, might hold promise also for the pulmonary fibrosis seen in sarcoidosis., This suggests that nintedanib inhibits fundamental processes in the pathogenesis of fibrosis., This suggests that nintedanib and pirfenidone , drugs known to slow disease progression in patients with idiopathic pulmonary fibrosis , may also slow the progression of ILD associated with systemic autoimmune diseases, In the SENSCIS® trial , nintedanib reduced the rate of ILD progression in patients with systemic sclerosis-associated ILD, Nintedanib, a tyrosine kinase inhibitor, has been shown to have antifibrotic and antiinflammatory effects in preclinical models of systemic sclerosis and ILD., The goal of the present study was to determine the effects of nintedanib on a cellular model of SSc-associated interstitial lung disease (ILD)., OBJECTIVES\nNintedanib is approved for the treatment of idiopathic pulmonary fibrosis (IPF) and was demonstrated to slow disease progression in patients with IPF by reducing decline in forced vital capacity by 50%., Nintedanib: new indication for systemic sclerosis-associated interstitial lung disease., Nintedanib (Ofev™), an oral triple kinase inhibitor targeting pro-fibrotic pathways, has been used for treatment of idiopathic pulmonary fibrosis (IPF)., These data might have direct implications for the ongoing phase III clinical trial with nintedanib in SSc-associated interstitial lung disease., Based on positive results from phase III, placebo-controlled, randomized comparative clinical trial conducted in patients with systemic sclerosis-associated interstitial lung disease (SSc-ILD), nintedanib received marketing approval in the United States and Japan for the treatment of SSc-ILD., Nintedanib is an intracellular inhibitor of tyrosine kinases that has been approved for treatment of IPF and has recently been shown to reduce the rate of lung function decline in patients with ILD associated with systemic sclerosis (SSc-ILD).[SEP]Relations: interstitial lung disease has relations: disease_disease with lung disease, disease_disease with lung disease. Rituximab has relations: drug_drug with Pirfenidone, drug_drug with Pirfenidone. Nintedanib has relations: drug_drug with Pirfenidone, drug_drug with Pirfenidone. sarcoidosis, susceptibility to has relations: disease_disease with sarcoidosis, disease_disease with sarcoidosis. Tocilizumab has relations: drug_drug with Pirfenidone, drug_drug with Pirfenidone.", "label": "yes"}
{"id": "converted_4566", "sentence1": "Is Otolin-1 a matrix protein?", "sentence2": "otoconia matrix protein, otolin-1, Otolin-1 is a collagen-like protein expressed in the inner ear of vertebrates. , Mammalian Otolin: a multimeric glycoprotein specific to the inner ear that interacts with otoconial matrix protein Otoconin-90 and Cerebellin-1, binds to otolin-1 and forming matrix protein architectures[SEP]", "label": "yes"}
{"id": "converted_1491", "sentence1": "Is there any research that relates the function of Notch Signaling with Alzheimer Disease?", "sentence2": "RIP regulates signaling pathways by abrogating or releasing signaling molecules. Since the discovery, already >15 years ago, of its catalytic component, presenilin, and even much earlier with the identification of amyloid precursor protein as its first substrate, γ-secretase has been commonly associated with Alzheimer's disease. However, starting with Notch and thereafter a continuously increasing number of novel substrates, γ-secretase is becoming linked to an equally broader range of biological processes., In the last decade, increasing evidence has pointed out an important role of this pathway beyond embryonic development, indicating that Notch also displays a critical function in the mature brain of vertebrates and invertebrates. This pathway appears to be involved in neural progenitor regulation, neuronal connectivity, synaptic plasticity and learning/memory. In addition, Notch appears to be aberrantly regulated in neurodegenerative diseases, including Alzheimer's disease and ischemic injury, Along with β-secretase, this enzyme produces the amyloid β-protein of Alzheimer's disease (AD) from the amyloid β-protein precursor. Because of its key role in the pathogenesis of AD, γ-secretase has been a prime target for drug discovery, and many inhibitors of this protease have been developed. The therapeutic potential of these inhibitors is virtually negated by the fact that γ-secretase is an essential part of the Notch signaling pathway, rendering the compounds unacceptably toxic upon chronic exposure, High physiological concentrations of Aβ monomer induced angiogenesis by a conserved mechanism that blocks γ-secretase processing of a Notch intermediate, NEXT, and reduces the expression of downstream Notch target genes. Our findings allude to an integration of signaling pathways that utilize γ-secretase activity, which may have significant implications for our understanding of Alzheimer's pathogenesis vis-à-vis vascular changes that set the stage for ensuing neurodegeneration., Aggregated forms of Aβ have a pathogenic role in Alzheimer disease and, thus, reducing the Aβ levels by inhibiting γ-secretase is a possible treatment strategy for Alzheimer disease. Regrettably, clinical trials have shown that inhibition of γ-secretase results in Notch-related side effects. Therefore, it is of great importance to find ways to inhibit amyloid precursor protein (APP) processing without disturbing vital signaling pathways such as Notch. Nicastrin (Nct) is part of the γ-secretase complex and has been proposed to be involved in substrate recognition and selection[SEP]Relations: NCSTN has relations: disease_protein with Alzheimer disease, disease_protein with Alzheimer disease. inherited neurodegenerative disorder has relations: disease_disease with Alzheimer disease, disease_disease with Alzheimer disease. familial Alzheimer disease has relations: disease_disease with Alzheimer disease, disease_disease with Alzheimer disease.", "label": "yes"}
{"id": "converted_2187", "sentence1": "Is edema a symptom of nephrotic syndrome?", "sentence2": "Nephrotic syndrome (NS) is a common clinical disease with four main clinical manifestations: hypoalbuminemia (<30 g/L), macro-proteinuria (>3.5 g/24 h), edema, and hyperlipidemia. , Nephrotic syndrome is an unusual manifestation of IgA Nephropathy (IgAN)., Twelve patients with IgAN with steroid-responsive nephrotic syndrome were evaluated and followed up. All patients presented with generalized edema. , The clinical features of sudden onset of generalized edema, initial heavy proteinuria and initial severe hypoalbuminemia might help identify the subset of patients, especially in low grade IgAN., Most patients presented within 3 months duration (61.4%) and the most common symptom was puffiness of face (98.45%) followed by pedal edema (91%). , We analyzed medical records of 290 patients with diagnosis of nephrotic syndrome as defined by International Study of Kidney Disease in Children (ISKDC), between January 1987 and December 2000, at the Sher-I-Kashmir Institute of Medical Sciences, Soura, Srinagar. , He was admitted because of systemic edema and dyspnea on effort Laboratory data revealed renal failure and nephrotic syndrome, whereas there was no symptom of diabetic retinopathy., Nephrotic syndrome: more than just oedema., Oedema is the commonest presenting symptom and sign in nephrotic syndrome. , One of these five clinical syndromes is the nephrotic syndrome, which is characterized by proteinuria > 3.5 g/day accompanied by hypalbuminemia, hyperlipoproteinemia and pronounced edema, Tolvaptan therapy for massive edema in a patient with nephrotic syndrome, Nephrotic syndrome (NS) is characterized by water and sodium retention, which leads to edema, The non-osmotic stimulation of arginine vasopressin release from the pituitary gland has been implicated as one of the important factors in abnormal water retention in patients with NS.We present the initial description of a patient with massive edema caused by refractory nephrotic syndrome, which was effectively treated with tolvaptan, a selective oral vasopressin V2 receptor antagonist.Tolvaptan is effective for the treatment of massive edema caused by NS, We report a child with steroid-resistant nephrotic syndrome with diuretic-resistant nephrotic edema treated successfully using acute peritoneal dialysis as a means of UF, Albumin and Furosemide Combination for Management of Edema in Nephrotic Syndrome: A Review of Clinical Studies, The treatment of edema in patients with nephrotic syndrome is generally managed by dietary sodium restriction and loop diuretics, Nine months after introduction of tiopronin, the boy manifested generalized edema, oliguria, and biochemical indices of nephrotic syndrome, Blessed were the days when it all made sense and the apparent mechanism for edema formation in nephrotic syndrome was straightforward: the kidneys lost protein in the urine, which lowered the plasma oncotic pressure, The nephrotic syndrome is characterized by a combination of pathological lab values and clinical symptoms, i. e. pronounced proteinuria (usually more than 3 - 3,5 g protein/24 h), hypoalbuminemia, edema and hyperlipidemia., The patient was admitted with edema of both legs, and the nephrotic syndrome was discovered, leading to the diagnosis of AA amyloidosis on kidney biopsy., Linear regression to relate measures.Other signs and symptoms of nephrotic syndrome at baseline (serum albumin < 3.5 g/dL, serum total cholesterol > 260 mg/dL or use of a statin, and edema or use of a loop diuretic); progression of chronic kidney disease during follow-up (doubling of baseline serum creatinine level or requirement for dialysis or kidney transplantation)., A case of interstitial shadows associated with oral cyclophosphamide therapy in a 32-month-old girl with steroid-resistant nephrotic syndrome, who was admitted to the Nishi-Kobe Medical Center with systemic edema, is reported., Nephrotic syndrome represents a constellation of symptoms including hyperalbuminuria, hypoalbuminemia, edema formation, hypercholesterolemia, hypertension, hypercoagulopathy, and increased infection risk., Pathophysiology of edema formation in children with nephrotic syndrome not due to minimal change disease., To study the evidence-based therapy of edema in nephrotic syndrome by analyzing the literatures systematically., Edema is the prominent feature of nephrotic syndrome and initially develops around the eyes and legs., Intussusception should be considered in the differential diagnosis of abdominal pain in patients with nephrotic syndrome, especially in patients exhibiting prolonged edema., Oedema is the commonest presenting symptom and sign in nephrotic syndrome., Other signs and symptoms of nephrotic syndrome at baseline (serum albumin < 3.5 g/dL, serum total cholesterol > 260 mg/dL or use of a statin, and edema or use of a loop diuretic); progression of chronic kidney disease during follow-up (doubling of baseline serum creatinine level or requirement for dialysis or kidney transplantation).[SEP]Relations: Steroid-sensitive nephrotic syndrome has relations: phenotype_phenotype with Nephrotic syndrome, phenotype_phenotype with Nephrotic syndrome. Tolvaptan has relations: drug_drug with Furosemide, drug_drug with Furosemide. Tiopronin has relations: contraindication with proteinuria, contraindication with nephrotic syndrome, drug_drug with Furosemide, contraindication with proteinuria, contraindication with nephrotic syndrome, drug_drug with Furosemide. Chronic kidney disease has relations: disease_phenotype_positive with AA amyloidosis, disease_phenotype_positive with AA amyloidosis. steroid-resistant nephrotic syndrome has relations: disease_disease with nephrotic syndrome, disease_disease with nephrotic syndrome. Proteinuria has relations: disease_phenotype_positive with AA amyloidosis, disease_phenotype_positive with AA amyloidosis. AA amyloidosis has relations: disease_phenotype_positive with Nephrotic syndrome, disease_phenotype_positive with Nephrotic syndrome. Abdominal pain has relations: drug_effect with Furosemide, disease_phenotype_positive with AA amyloidosis, drug_effect with Furosemide, disease_phenotype_positive with AA amyloidosis. Hypercholesterolemia has relations: disease_phenotype_positive with hyperlipoproteinemia, disease_phenotype_positive with hyperlipoproteinemia. Nephrotic syndrome has relations: disease_phenotype_positive with AA amyloidosis, disease_phenotype_positive with AA amyloidosis.", "label": "yes"}
{"id": "converted_4017", "sentence1": "Is eptinezumab a small molecule?", "sentence2": "Eptinezumab-jjmr (referred to as eptinezumab hereafter; Vyepti™) is a humanised monoclonal antibody that binds to calcitonin gene-related peptide (CGRP) and blocks its binding to the receptor. [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_1992", "sentence1": "Is there a role of proton beam therapy in medulloblastoma treatment?", "sentence2": "All papers directly compared outcomes from protons with photons, five papers included medulloblastoma, four papers each included craniopharyngioma and low grade gliomas and three papers included ependymoma., There are many indications of protontherapy for paediatric brain tumours in curative intent, either for localized treatment of ependymomas, germ-cell tumours, craniopharyngiomas, low-grade gliomas; or panventricular irradiation of pure non-secreting germinoma; or craniospinal irradiation of medulloblastomas and metastatic pure germinomas., Cost-effectiveness analysis of cochlear dose reduction by proton beam therapy for medulloblastoma in childhood., BACKGROUND: The aim of this study is to evaluate the cost-effectiveness of proton beam therapy with cochlear dose reduction compared with conventional X-ray radiotherapy for medulloblastoma in childhood.METHODS: We developed a Markov model to describe health states of 6-year-old children with medulloblastoma after treatment with proton or X-ray radiotherapy., Evaluation of permanent alopecia in pediatric medulloblastoma patients treated with proton radiation., BACKGROUND: To precisely calculate skin dose and thus to evaluate the relationship between the skin dose and permanent alopecia for pediatric medulloblastoma patients treated with proton beams., CONCLUSIONS: Our results based on 12 patients provide a relationship between the skin dose and permanent alopecia for pediatric medulloblastoma patients treated with protons. , Proton beam craniospinal irradiation reduces acute toxicity for adults with medulloblastoma., PURPOSE: Efficacy and acute toxicity of proton craniospinal irradiation (p-CSI) were compared with conventional photon CSI (x-CSI) for adults with medulloblastoma., CONCLUSIONS: This report is the first analysis of clinical outcomes for adult medulloblastoma patients treated with p-CSI. , Dilemmas concerning dose distribution and the influence of relative biological effect in proton beam therapy of medulloblastoma., OBJECTIVE: To improve medulloblastoma proton therapy., The aim of this study is to evaluate the cost-effectiveness of proton beam therapy with cochlear dose reduction compared with conventional X-ray radiotherapy for medulloblastoma in childhood., The aim of this study is to evaluate the cost-effectiveness of proton beam therapy with cochlear dose reduction compared with conventional X-ray radiotherapy for medulloblastoma in childhood.We developed a Markov model to describe health states of 6-year-old children with medulloblastoma after treatment with proton or X-ray radiotherapy, All patients completed therapy without interruption.Our proton-beam technique for craniospinal irradiation of pediatric medulloblastoma has successfully reduced normal-tissue doses and acute treatment-related sequelae, Potential role of proton therapy in the treatment of pediatric medulloblastoma/primitive neuro-ectodermal tumors: spinal theca irradiation, For 6 MV x-rays > 60% of the dose prescribed to the target was delivered to 44% of the heart volume, while the proton beam was able to completely avoid the heart, the liver, and in all likelihood the thyroid and gonads as well.The present study demonstrates a potential role of proton therapy in decreasing the dose (and toxicity) to the critical structures in the irradiation of the spinal neuraxis in medulloblastoma/PNET, Potential role of proton therapy in the treatment of pediatric medulloblastoma/primitive neuroectodermal tumors: reduction of the supratentorial target volume, This review describes the role of radiation in general and proton therapy in particular for the treatment of medulloblastoma, central nervous system primitive neuroectodermal tumors, atypical teratoid/rhabdoid tumors, and the recently described embryonal tumor with multilayered rosettes, Reducing toxicity from craniospinal irradiation: using proton beams to treat medulloblastoma in young children., Intensity-modulated radiotherapy did show more bladder dose reduction than the other techniques in pelvic sarcoma irradiation.CONCLUSIONS: In the diseases studied, using various techniques of 3D-CRT, electrons, IMRT, and protons, protons are most optimal in treating retinoblastomas, medulloblastomas (posterior fossa and craniospinal), and pelvic sarcomas., For 6 MV x-rays>60% of the dose prescribed to the target was delivered to 44% of the heart volume, while the proton beam was able to completely avoid the heart, the liver, and in all likelihood the thyroid and gonads as well.CONCLUSION: The present study demonstrates a potential role of proton therapy in decreasing the dose (and toxicity) to the critical structures in the irradiation of the spinal neuraxis in medulloblastoma/PNET., In medulloblastoma, three posterior fossa irradiation techniques were analyzed: 3D-CRT, IMRT, and protons., Potential role of proton therapy in the treatment of pediatric medulloblastoma/primitive neuro-ectodermal tumors: spinal theca irradiation., Potential role of proton therapy in the treatment of pediatric medulloblastoma/primitive neuroectodermal tumors: reduction of the supratentorial target volume., The present study demonstrates a potential role of proton therapy in decreasing the dose (and toxicity) to the critical structures in the irradiation of the spinal neuraxis in medulloblastoma/PNET., Cost-effectiveness analysis of cochlear dose reduction by proton beam therapy for medulloblastoma in childhood., Dilemmas concerning dose distribution and the influence of relative biological effect in proton beam therapy of medulloblastoma., To improve medulloblastoma proton therapy., Our proton-beam technique for craniospinal irradiation of pediatric medulloblastoma has successfully reduced normal-tissue doses and acute treatment-related sequelae., Treatment planning with protons for pediatric retinoblastoma, medulloblastoma, and pelvic sarcoma: how do protons compare with other conformal techniques?[SEP]Relations: Medulloblastoma has relations: disease_phenotype_positive with medulloblastoma, disease_phenotype_positive with medulloblastoma.", "label": "yes"}
{"id": "converted_4291", "sentence1": "Is histone variant H3.3K27M associated with gliomas?", "sentence2": "Reciprocal H3.3 gene editing identifies K27M and G34R mechanisms in pediatric glioma including NOTCH signaling., Well-known oncohistones, with mutations on both H3.1 and H3.3, include H3K36M in chondroblastoma, H3K27M in glioma, Diffuse intrinsic pontine gliomas (DIPG) are the most aggressive brain tumors in children with 5-year survival rates of only 2%. About 85% of all DIPG are characterized by a lysine-to-methionine substitution in histone 3, which leads to global H3K27 hypomethylation accompanied by H3K27 hyperacetylation. [SEP]", "label": "yes"}
{"id": "converted_160", "sentence1": "Is there any software for automated analysis of FISH images?", "sentence2": "he study demonstrated the feasibility of automated FISH signal analysis that applying a CAD scheme to the automated generated 2-D projection images., A color imaging technique, multiplex fluorescent in situ hybridization (M-FISH), has been developed to ease the analysis of the process. Using an M-FISH technique each chromosome class (1,2, …,22,X,Y) is stained with a unique color. However, significant variations between images are observed due to a number of factors such as uneven hybridization and spectral overlap among channels. These types of variations influence the pixel classification accuracy of image classification methods which are supervised and require a set of annotated images for training. In this paper, we present a fully unsupervised M-FISH chromosome image classification methodology. Our main contributions are 1) the assumption that the intensity of a chromosome pixel is sampled from multiple Gaussian components [Gaussian mixture model (GMM)] such that each component corresponds to one chromosome class, and 2) the initialization of the GMM model using the emission information of each chromosome class. This is feasible since prior to the M-FISH image acquirement, we already know which chromosome class is emitting to each of the five M-FISH image channels. The method has been tested on a large number of M-FISH images and an overall accuracy of 89.85% is reported. Our method is unsupervised and presents higher classification accuracy even when it is compared with common supervised based methods., hybridization (FISH) tests provide promising molecular imaging biomarkers to more accurately and reliably detect and diagnose cancers and genetic disorders. Since current manual FISH signal analysis is low-efficient and inconsistent, which limits its clinical utility, developing automated FISH image scanning systems and computer-aided detection (CAD) schemes has been attracting research interests. To acquire high-resolution FISH images in a multi-spectral scanning mode, a huge amount of image data with the stack of the multiple three-dimensional (3-D) image slices is generated from a single specimen. Automated preprocessing these scanned images to eliminate the non-useful and redundant data is important to make the automated FISH tests acceptable in clinical applications. In this study, a dual-detector fluorescence image scanning system was applied to scan four specimen slides with FISH-probed chromosome X. A CAD scheme was developed to detect analyzable interphase cells and map the multiple imaging slices recorded FISH-probed signals into the 2-D projection images. CAD scheme was then applied to each projection image to detect analyzable interphase cells using an adaptive multiple-threshold algorithm, identify FISH-probed signals using a top-hat transform, and compute the ratios between the normal and abnormal cells. To assess CAD performance, the FISH-probed signals were also independently visually detected by an observer. The Kappa coefficients for agreement between CAD and observer ranged from 0.69 to 1.0 in detecting/counting FISH signal spots in four testing samples.,  In this paper we developed a sparse representation-based classification (SRC) algorithm based on L1-norm minimization for classifying chromosomes from multicolor fluorescence in situ hybridization (M-FISH) images. The algorithm has been tested on a comprehensive M-FISH database that we established, demonstrating improved performance in classification. When compared with other pixel-wise M-FISH image classifiers such as fuzzy c-means (FCM) clustering algorithms and adaptive fuzzy c-means (AFCM) clustering algorithms that we proposed earlier the current method gave the lowest classification error. In order to evaluate the performance of different SRC for M-FISH imaging analysis, three different sparse representation methods, namely, Homotopy method, Orthogonal Matching Pursuit (OMP), and Least Angle Regression (LARS), were tested and compared. Results from our statistical analysis have shown that Homotopy based method is significantly better than the other two methods. , Fluorescence in situ hybridization (FISH) is used to study the organization and the positioning of specific DNA sequences within the cell nucleus. Analyzing the data from FISH images is a tedious process that invokes an element of subjectivity. Automated FISH image analysis offers savings in time as well as gaining the benefit of objective data analysis. While several FISH image analysis software tools have been developed, they often use a threshold-based segmentation algorithm for nucleus segmentation. As fluorescence signal intensities can vary significantly from experiment to experiment, from cell to cell, and within a cell, threshold-based segmentation is inflexible and often insufficient for automatic image analysis, leading to additional manual segmentation and potential subjective bias. To overcome these problems, we developed a graphical software tool called FISH Finder to automatically analyze FISH images that vary significantly. By posing the nucleus segmentation as a classification problem, compound Bayesian classifier is employed so that contextual information is utilized, resulting in reliable classification and boundary extraction. This makes it possible to analyze FISH images efficiently and objectively without adjustment of input parameters. Additionally, FISH Finder was designed to analyze the distances between differentially stained FISH probes., The simultaneous detection of protein expression and gene copy number changes in patient samples, like paraffin-embedded tissue sections, is challenging since the procedures of immunohistochemistry (IHC) and Fluorescence in situ Hybridization (FISH) negatively influence each other which often results in suboptimal staining. Therefore, we developed a novel automated algorithm based on relocation which allows subsequent detection of protein content and gene copy number changes within the same cell. METHODS: Paraffin-embedded tissue sections of colorectal cancers were stained for CD133 expression. IHC images were acquired and image coordinates recorded. Slides were subsequently hybridized with fluorescently labeled DNA probes. FISH images were taken at the previously recorded positions allowing for direct comparison of protein expression and gene copy number signals within the same cells/tissue areas. Relocation, acquisition of the IHC and FISH images, and enumeration of FISH signals in the immunophenotyped tumour areas were done in an automated fashion. RESULTS: Automated FISH analysis was performed on 13 different colon cancer samples that had been stained for CD133; each sample was scored for MYC, ZNF217 and Chromosome 6 in CD133 positive and negative glands. From the 13 cases four (31%) showed amplification for the MYC oncogene and seven of 13 (54%) cases were amplified for ZNF217., The simultaneous detection of protein expression and gene copy number changes in patient samples, like paraffin-embedded tissue sections, is challenging since the procedures of immunohistochemistry (IHC) and Fluorescence in situ Hybridization (FISH) negatively influence each other which often results in suboptimal staining.Therefore, we developed a novel automated algorithm based on relocation which allows subsequent detection of protein content and gene copy number changes within the same cell. METHODS: Paraffin-embedded tissue sections of colorectal cancers were stained for CD133 expression. IHC images were acquired and image coordinates recorded. Slides were subsequently hybridized with fluorescently labeled DNA probes. FISH images were taken at the previously recorded positions allowing for direct comparison of protein expression and gene copy number signals within the same cells/tissue areas. Relocation, acquisition of the IHC and FISH images, and enumeration of FISH signals in the immunophenotyped tumour areas were done in an automated fashion. RESULTS: Automated FISH analysis was performed on 13 different colon cancer samples that had been stained for CD133; each sample was scored for MYC, ZNF217 and Chromosome 6 in CD133 positive and negative glands. From the 13 cases four (31%) showed amplification for the MYC oncogene and seven of 13 (54%) cases were amplified for ZNF217. There was no significant difference between CD133 positive tumour and CD133 negative tumour cells. , The simultaneous detection of protein expression and gene copy number changes in patient samples, like paraffin-embedded tissue sections, is challenging since the procedures of immunohistochemistry (IHC) and Fluorescence in situ Hybridization (FISH) negatively influence each other which often results in suboptimal staining.Therefore, we developed a novel automated algorithm based on relocation which allows subsequent detection of protein content and gene copy number changes within the same cell.Methods: Paraffin-embedded tissue sections of colorectal cancers were stained for CD133 expression. IHC images were acquired and image coordinates recorded. Slides were subsequently hybridized with fluorescently labeled DNA probes. FISH images were taken at the previously recorded positions allowing for direct comparison of protein expression and gene copy number signals within the same cells/tissue areas. Relocation, acquisition of the IHC and FISH images, and enumeration of FISH signals in the immunophenotyped tumour areas were done in an automated fashion.Results: Automated FISH analysis was performed on 13 different colon cancer samples that had been stained for CD133; each sample was scored for MYC, ZNF217 and Chromosome 6 in CD133 positive and negative glands. From the 13 cases four (31%) showed amplification for the MYC oncogene and seven of 13 (54%) cases were amplified for ZNF217. There was no significant difference between CD133 positive tumour and CD133 negative tumour cells.[SEP]Relations: colorectal carcinoma has relations: disease_protein with ZNF217, disease_protein with SRC, disease_protein with MYC, disease_protein with ZNF217, disease_protein with SRC, disease_protein with MYC.", "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_300", "sentence1": "Is alternative splicing of apoptotic genes playing a role in the response to DNA or mitochondrial damage?", "sentence2": "Apoptosis promoted by UV in cells lacking p53 is prevented when the change in AS of the apoptotic gene bcl-x is reverted, confirming the relevance of this mechanism., We demonstrate that E2F1 requires SC35 to switch the alternative splicing profile of various apoptotic genes such as c-flip, caspases-8 and -9 and Bcl-x, towards the expression of pro-apoptotic splice variants. Finally, we provide evidence that E2F1 upregulates SC35 in response to DNA-damaging agents and show that SC35 is required for apoptosis in response to these drugs., This analysis revealed that DNA damage resulted in changes in splicing activity that modified the splicing pattern of Fas, a key pro-apoptotic, p53-inducible death receptor., Bortezomib induces mitochondrial damage in native cells and also activates the UPR by splicing of Xbp-1 and induction of CHOP, which is significantly reduced by silencing of MUC4., The tumour-suppressor protein p53 is an important activator of apoptosis. Although p53-deficient cancer cells are less responsive to chemotherapy, their resistance is not complete, which suggests that other apoptotic pathways may exist. A p53-related gene, p73, which encodes several proteins as a result of alternative splicing, can also induce apoptosis., Induction of apoptosis was significantly reduced in P388/SPR cells, as indicated by minimal DNA fragmentation. Analysis of oncogenes regulating apoptotic cell death revealed a marked decrease of bcl-2 in combination with a moderate reduction of bax protein, but a striking overexpression of the long form of the bcl-X protein.[SEP]Relations: Protein S human has relations: drug_drug with Bortezomib, drug_drug with Bortezomib, drug_drug with Bortezomib, drug_drug with Bortezomib, drug_drug with Bortezomib, drug_drug with Bortezomib, drug_drug with Bortezomib, drug_drug with Bortezomib. Protein C has relations: drug_drug with Bortezomib, drug_drug with Bortezomib.", "label": "yes"}
{"id": "converted_2060", "sentence1": "Do brown fat cells produce heat?", "sentence2": "WAT and BAT are both involved in energy balance. WAT is mainly involved in the storage and mobilization of energy in the form of triglycerides, whereas BAT specializes in dissipating energy as heat during cold- or diet-induced thermogenesis., Because brown adipose tissue (BAT) dissipates energy in the form of heat, increasing energy expenditure by augmenting BAT-mediated thermogenesis may represent an approach to counter obesity and its complications., Classic brown fat and inducible beige fat both dissipate chemical energy in the form of heat through the actions of mitochondrial uncoupling protein 1. This nonshivering thermogenesis is crucial for mammals as a defense against cold and obesity/diabetes., Mitochondrial uncoupling protein 1 in brown fat cells produces heat by dissipating the energy generated by fatty acid and glucose oxidation., Brown fat biology and thermogenesis., Brown fat (brown adipose tissue, BAT) primary function is to produce heat. , Brown fat cells were classified into 6 types: Type 1 cells are fat-depleted cells filled with granular cytoplasm and are believed to be produced after oxidation of fat for heat production., Calorimetric measurements from cell suspensions showed that ATP increased basal heat production of isolated brown fat cells by approximately 40% but had no effect on the greater than fivefold increase in heat production seen with maximal adrenergic stimulation., Classic brown fat and inducible beige fat both dissipate chemical energy in the form of heat through the actions of mitochondrial uncoupling protein 1., Brown adipocytes oxidize fatty acids to produce heat in response to cold or to excessive energy intake; stimulation of brown fat development and function may thus counteract obesity., The occurrence of Types 1 and/or 6 cells that has been revealed in 65 out of the total 180 samples (36%), suggests that the oxidation of fat for the thermogenesis proceeds in the brown fat tissue and that brown fat cells partially undergo fat depletion., Brown fat cells were classified into 6 types: Type 1 cells are fat-depleted cells filled with granular cytoplasm and are believed to be produced after oxidation of fat for heat production., In response to cold, both classical brown fat and the newly identified \"beige\" or \"brite\" cells are activated by β-adrenergic signaling and catabolize stored lipids and carbohydrates to produce heat via UCP1, The ability of brown adipocytes (fat cells) to dissipate energy as heat shows great promise for the treatment of obesity and other metabolic disorders, Inappropriate heat dissipation ignites brown fat thermogenesis in mice with a mutant thyroid hormone receptor α1, Brown fat and vascular heat dissipation: The new cautionary tail, Brown adipose produces heat as a defense against hypothermia and obesity, and the appearance of brown-like adipocytes within white adipose tissue depots is associated with improved metabolic phenotypes. , In the same manner, marked ability to produce a considerable amount of heat was evidenced in  brown fat tissue of children and teenagers. , Brown fat cells were classified into 6 types: Type 1 cells are fat-depleted cells filled with granular cytoplasm and are believed to be produced after oxidation of fat for heat production. , It is inferred that brown-adipose-tissue heat production is reduced during (and probably also some time after) anesthesia. , Parallel measurements of heat production and thermogenin content in brown fat cells during cold acclimation of rats., The classical white adipose tissue builds up energy in the form of triglycerides and is useful for preventing fatigue during periods of low caloric intake and the brown adipose tissue instead of inducing fat accumulation can produce energy as heat., In response to cold, both classical brown fat and the newly identified \"beige\" or \"brite\" cells are activated by β-adrenergic signaling and catabolize stored lipids and carbohydrates to produce heat via UCP1., White adipose tissue stores energy reserves as fat, whereas the metabolic function of brown adipose tissue is lipid oxidation to produce heat., The main function of brown adipose tissue (BAT) is to produce heat in response to cold., Brown adipocytes oxidize fatty acids to produce heat in response to cold or caloric overfeeding., Brown fat (brown adipose tissue, BAT) primary function is to produce heat., Adipose tissue plays an active role in energy balance because it is not only a lipid storing and mobilizing tissue but consists of functionally specialized tissues able to produce heat (in brown adipose tissue) and to produce or release a vast number of so called adipokines or adipocytokines., Brown adipose tissue (BAT), a specialized fat that dissipates energy to produce heat, plays an important role in the regulation of energy balance., Brown adipose cells are specialized to dissipate chemical energy in the form of heat, as a physiological defence against cold and obesity., In the present study, the thermogenesis of human brown fat tissue was suggested chiefly with regard to the occurrence of Types 1 and/or 6 cells., In the same manner, marked ability to produce a considerable amount of heat was evidenced in  brown fat tissue of children and teenagers., Adult humans have heat-producing and energy-consuming brown adipose tissue in the clavicular region of the neck., Brown and beige adipocytes expend chemical energy to produce heat and are therefore important in regulating body temperature and body weight., In human perirenal brown fat tissue, darkly stained fat-depleted cells (D) occupy, with other cell types (CR, CR'), an important part in the reversible heat production cycle of the brown fat tissue., Brown fat is a specialized fat depot that can increase energy expenditure and produce heat.[SEP]", "label": "yes"}
{"id": "converted_550", "sentence1": "Does d-tubocurarine (d-TC) induces irreversible inhibition of nicotinic acetylcholine receptor (nAChR) at the neuromuscular junction?", "sentence2": "An integrated model describing the interaction of nondepolarizing neuromuscular blocking agents with reversible anticholinesterase agents is derived and compared with a naive model using experimental data obtained from four anesthetized dogs. Three consecutive but separate steady-state d-tubocurarine blocks (approximately 50, 70, and 90%) were induced in each of the four dogs and reversed by short edrophonium infusions., The ability of hexamethonium (C6) to reverse the neuromuscular blocking action of tubocurarine (Tc), Volatile anesthetics enhance the neuromuscular blockade produced by nondepolarizing muscle relaxants (NDMRs). The neuromuscular junction is a postulated site of this interaction. We tested the hypothesis that volatile anesthetic enhancement of muscle relaxation is the result of combined drug effects on the nicotinic acetylcholine receptor., Concentration-effect curves for the inhibition of acetylcholine-induced currents were established for vecuronium, d-tubocurarine, isoflurane, and sevoflurane. Subsequently, inhibitory effects of NDMRs were studied in the presence of the volatile anesthetics at a concentration equivalent to half the concentration producing a 50% inhibition alone. All individually tested compounds produced rapid and readily reversible concentration-dependent inhibition., The pharmacological diversity of the different isoforms of the nicotinic acetylcholine receptor arises from the diversity of the subunits that assemble to form the native receptors. The aim of this study was to investigate the actions of the muscle relaxants d-tubocurarine, pancuronium and vecuronium on different isoforms of nicotinic acetylcholine receptors, At all three receptor types, d-tubocurarine and pancuronium blocked the responses elicited by acetylcholine in a reversible manner. , As further evidence of anticholinesterase activity, methamidophos (1-100 microM) was able to reverse the blockade by d-tubocurarine, There was an initial partial reversal of the neuromuscular inhibition caused by tubocurarine, Isoflurane and sevoflurane enhance the receptor blocking effects of nondepolarizing muscle relaxants on nicotinic acetylcholine receptors., Because other purinergic 2X (P2X) receptor antagonists, NF023 and NF279, do not have the reverse effects on the neuromuscular blockade of d-TC, the effect of NF449 seems irrelevant to inhibition of P2X receptors., The association rate constant for Tc binding to sites on the nicotinic acetylcholine receptor appears to be very fast (k+D = 8.9 x 10(8) M-1 s-1) and comparable to that for acetylcholine (ACh)., The aim of this study was to investigate the mechanism for the reversal effect of NF449 (a suramin analogue) on the neuromuscular block induced by d-tubocurarine (d-TC)., Study of the reversal effect of NF449 on neuromuscular blockade induced by d-tubocurarine.[SEP]Relations: Tubocurarine has relations: drug_drug with Isoflurane, drug_drug with Isoflurane. Hexamethonium has relations: drug_drug with Isoflurane, drug_drug with Isoflurane. Vecuronium has relations: drug_drug with Isoflurane, drug_drug with Isoflurane. Pancuronium has relations: drug_drug with Isoflurane, drug_drug with Isoflurane. Edrophonium has relations: drug_drug with Isoflurane, drug_drug with Isoflurane. muscle tissue has relations: anatomy_protein_present with C6, anatomy_protein_present with C6. Sevoflurane has relations: drug_drug with Isoflurane, drug_drug with Isoflurane.", "label": "no"}
{"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_3336", "sentence1": "Are genomic regulatory blocks (GRBs) any different than TADs?", "sentence2": "Topologically associating domains are ancient features that coincide with Metazoan clusters of extreme noncoding conservation., Clusters of CNEs define the span of regulatory inputs for many important developmental regulators and have been described previously as genomic regulatory blocks (GRBs). Their function and distribution around important regulatory genes raises the question of how they relate to 3D conformation of these loci. Here, we show that clusters of CNEs strongly coincide with topological organisation, predicting the boundaries of hundreds of topologically associating domains (TADs) in human and Drosophila. The set of TADs that are associated with high levels of noncoding conservation exhibit distinct properties compared to TADs devoid of extreme noncoding conservation. The close correspondence between extreme noncoding conservation and TADs suggests that these TADs are ancient, revealing a regulatory architecture conserved over hundreds of millions of years.Metazoan genomes contain many clusters of conserved noncoding elements. Here, the authors provide evidence that these clusters coincide with distinct topologically associating domains in humans and Drosophila, revealing a conserved regulatory genomic architecture.[SEP]", "label": "no"}
{"id": "converted_3130", "sentence1": "Are apoE mimetics being considered as a treatment against Alzheimer's disease?", "sentence2": "The apolipoprotein-E-mimetic COG112 protects amyloid precursor protein intracellular domain-overexpressing animals from Alzheimer's disease-like pathological features., Studies show that administration of apolipoprotein E (apoE) and apoE-derived small peptide mimetics protect AD mouse models against these AD-like features.[SEP]", "label": "yes"}
{"id": "converted_847", "sentence1": "Is transcription-associated mutagenesis (TAM) related to gene expression levels?", "sentence2": "These mutations were frequent in plasmid-borne lacS expressed at a high level but not in single-copy lacS in the chromosome or at lower levels of expression in a plasmid., The results suggest that important DNA repair or replication fidelity functions are impaired or overwhelmed in pJlacS, with results analogous to those of the \"transcription-associated mutagenesis\" seen in bacteria and eukaryotes., the rate of point mutation in a gene increases with the expression level of the gene. Transcription induces mutagenesis on both DNA strands, indicating simultaneous actions of several TAM mechanisms., High-levels of transcription through a gene stimulate spontaneous mutation rate, a phenomenon termed transcription-associated mutation (TAM)., High levels of transcription in Saccharomyces cerevisiae are associated with increased genetic instability, which has been linked to DNA damage. Here, we describe a pGAL-CAN1 forward mutation assay for studying transcription-associated mutagenesis (TAM) in yeast., The acquisition of mutations was directly correlated to the level of transcription, Our results demonstrate that the level of Leu(+) reversions increased significantly in parallel with the induced increase in transcription levels., Transcription-associated mutagenesis in yeast is directly proportional to the level of gene expression, spontaneous mutation rate is directly proportional to the transcription level, suggesting that movement of RNA polymerase through the target initiates a mutagenic process(es), High transcription is associated with genetic instability, notably increased spontaneous mutation rates, which is a phenomenon termed Transcription-Associated-Mutagenesis (TAM)., Using this system, we also investigated two hypotheses that have been proposed to explain transcription-associated mutagenesis (TAM): (1) transcription impairs replication fork progression in a directional manner and (2) DNA lesions accumulate under high-transcription conditions., Transcription-associated mutagenesis in yeast is directly proportional to the level of gene expression and influenced by the direction of DNA replication., High levels of transcription in Saccharomyces cerevisiae are associated with increased genetic instability, which has been linked to DNA damage., Using this system, we also investigated two hypotheses that have been proposed to explain transcription-associated mutagenesis (TAM): (1) transcription impairs replication fork progression in a directional manner and (2) DNA lesions accumulate under high-transcription conditions., Using comparative genomics of related species as well as mutation accumulation lines, we show in yeast that the rate of point mutation in a gene increases with the expression level of the gene, High transcription is associated with genetic instability, notably increased spontaneous mutation rates, which is a phenomenon termed Transcription-Associated-Mutagenesis (TAM), Using this system, we also investigated two hypotheses that have been proposed to explain transcription-associated mutagenesis (TAM): (1) transcription impairs replication fork progression in a directional manner and (2) DNA lesions accumulate under high-transcription conditions, High-levels of transcription through a gene stimulate spontaneous mutation rate, a phenomenon termed transcription-associated mutation (TAM)[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_2661", "sentence1": "Has rituximab been considered as a treatment for chronic fatigues syndrome? (November 2017)", "sentence2": " The use of rintatolimod and rituximab as well as counselling, behavioural and rehabilitation therapy programs may be of benefit for CFS/ME, but the evidence of their effectiveness is still limited. [SEP]", "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"}