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Sleep disruption within activity problems: experience, treatments as well as difficulties.
Long noncoding RNAs (lncRNAs) have emerged as key coordinators of biological and cellular processes. Characterizing lncRNA expression across cells and tissues is key to understanding their role in determining phenotypes including human diseases. We present here FC-R2, a comprehensive expression atlas across a broadly defined human transcriptome, inclusive of over 109,000 coding and noncoding genes, as described in the FANTOM CAGE-Associated Transcriptome (FANTOM-CAT) study. This atlas greatly extends the gene annotation used in the original recount2 resource. We demonstrate the utility of the FC-R2 atlas by reproducing key findings from published large studies and by generating new results across normal and diseased human samples. In particular, we (a) identify tissue-specific transcription profiles for distinct classes of coding and noncoding genes, (b) perform differential expression analysis across thirteen cancer types, identifying novel noncoding genes potentially involved in tumor pathogenesis and progression, and (c) confirm the prognostic value for several enhancers lncRNAs expression in cancer. Our resource is instrumental for the systematic molecular characterization of lncRNA by the FANTOM6 Consortium. In conclusion, comprised of over 70,000 samples, the FC-R2 atlas will empower other researchers to investigate functions and biological roles of both known coding genes and novel lncRNAs. Published by Cold Spring Harbor Laboratory Press.Immunosuppressive entities in the tumor microenvironment (TME) remain a major impediment to immunotherapeutic approaches for a majority of patients with cancer. While the immunosuppressive role of transforming growth factor-β (TGF-β) in the TME is well known, clinical studies to date with anti-TGF-β agents have led to limited success. The bifunctional agent bintrafusp alfa (previously designated M7824) has been developed in an attempt to address this issue. Bintrafusp alfa consists of an IgG1 targeting programmed death ligand 1 (PD-L1) moiety fused via peptide linkers to the extracellular domain of two TGF-β receptor II molecules designed to 'trap' TGF-β in the TME. This agent is able to bring the TGF-β trap to the TME via its anti-PD-L1 component, thus simultaneously attacking both the immunosuppressive PD-L1 and TGF-β entities. A number of preclinical studies have shown bintrafusp alfa capable of (1) preventing or reverting TGF-β-induced epithelial-mesenchymal transition in human carcinoma cells; this altercommercial re-use. See rights and permissions. Published by BMJ.OBJECTIVES Postnatal thyroid dysfunction is common in preterm infants but the relationship between mild dysfunction and neurodevelopment is unclear. Our aim is to describe the relationship between thyroid function and neurodevelopment. DESIGN Cohort analysis. PATIENTS 1275 infants born under 31 weeks' gestation; there were no exclusion criteria. SETTING The infants were part of a UK daily iodine supplementation trial. MAIN OUTCOMES Thyroid-stimulating hormone, thyroid-binding globulin and total thyroxine levels were measured in dried blood spots on postnatal days 7, 14, 28 and the equivalent of 34 weeks' gestation. Neurodevelopment was measured using the Bayley-III Scales of infant development at 2 years of age. RESULTS No infant was identified as hypothyroid through routine screening. The 3% of infants consistently in the top decile of gestationally age-adjusted thyroid-stimulating hormone levels had a reduction in cognitive score of 7 Bayley units when compared with those not in the top decile (95% CI -13 to -1). A reduction in motor composite score of 6 units (95% CI -12 to less then -0.1) and fine motor score of 1 unit (95% CI -2 to -0.1) was also identified. The 0.7% of infants consistently in the bottom decile of age-adjusted thyroxine levels had a reduction in motor composite score of 14 units (95% CI -25 to -2) and its two subset scores, fine and gross motor, of 2 units (95% CI respectively -4.5 to less then -0.1 and -4.3 to -0.3). CONCLUSIONS Preterm infants with consistent 'mild' thyroid dysfunction score less on neurodevelopmental tests at 2 years of age. Many of these infants will not be detected by current clinical protocols or screening programmes. © Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Apilimod chemical structure Published by BMJ.OBJECTIVE The role of diabetes as a predictor of mortality after stroke remains uncertain, and there are very few data for pre-diabetes. This study investigated the association of pre-diabetes and diabetes with 30-day and 1-year mortality after ischemic stroke (IS) and primary intracerebral hemorrhage (ICH). RESEARCH DESIGN AND METHODS Between 2006 and 2013, 2076 patients with IS and 586 patients with ICH (median age 79) were admitted to hospital within 24 hours after stroke onset and were treated in a stroke unit, where they underwent measurement of glycated hemoglobin (HbA1c). Diabetes was retrospectively defined based on medical history, diagnosis during hospital stay or HbA1c ≥6.5% (48 mmol/mol). Pre-diabetes was defined as HbA1c of 5.7%-6.4% (39-47 mmol/mol). Stroke severity was measured using the National Institutes of Health Stroke Scale (NIHSS). HRs were used to test the association of pre-diabetes and diabetes with 30-day and 1-year mortality after stroke onset. RESULTS Among patients with IS, 830 hatudies. © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.OBJECTIVE Metabolic syndrome (MetS) gains more attention due to high prevalence of obesity, diabetes and hypertension among adults. Although obesity, diabetes and hypertension can certainly compromise health-related quality of life (HRQoL), the correlations of sociodemographic factors, quality of life and MetS remains unclear. This study aims to investigate the association between HRQoL and MetS in an Asian community of the sociodemographic characteristics. RESEARCH DESIGN AND METHODS We performed a cross-sectional study by recruiting 2588 Taiwanese patients aged ≥30 years between August 2015 and August 2017. Sociodemographic data and anthropometric variables were obtained from medical records and physical examination. Meanwhile, HRQoL was assessed by 36-Item Short-Form Health Survey questionnaires. RESULTS The overall prevalence of MetS was 32.8%. Multivariate analysis revealed that age ≥65 years (OR=1.987, p less then 0.001), body mass index (BMI) ≥24 kg/m2 (OR=7.958, p less then 0.001), low educational level (OR=1.
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