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Importance Inflammation is a key driver of malnutrition during illness and is often accompanied by metabolic effects, including insulin resistance and reduction of appetite. However, it still remains unclear if inflammation influences the response to nutritional support among patients with disease-related malnutrition. Objective To examine whether patients' baseline inflammatory status is associated with the effect of nutritional support on 30-day mortality. Design, Setting, and Participants This is a secondary analysis of the Effect of Early Nutritional Support on Frailty, Functional Outcomes, and Recovery of Malnourished Medical Inpatients Trial (EFFORT), a randomized clinical trial conducted in 8 Swiss hospitals from April 2014 to February 2018. A total of 1950 participants who had C-reactive protein measurements at the time of admission were included in this secondary analysis. Data analysis was conducted between June and July 2019. Interventions Hospitalized patients at risk for malnutrition were randoml2.50; P = .39), providing evidence that inflammation has a significant modifying association (P for interaction = .005). Conclusions and Relevance Based on this secondary analysis of a multicenter randomized trial, a patient's admission inflammatory status was associated with their response to nutritional support. If validated in future clinical trials, nutritional support may need to be individualized based on a patient's initial presentation and markers of inflammation. These results may also help to explain some of the heterogeneity in treatment effects of nutrition seen in previous critical care trials. Trial Registration ClinicalTrials.gov Identifier NCT02517476.Importance Mortality, morbidity, and health-related quality of life (HRQoL) are patient-relevant end points generally considered in the early benefit assessments of new cancer treatments. Progression-related end points, such as time to progression or progression-free survival, are not included, although patients and physicians testify to the detrimental association of disease progression with HRQoL. Objective To examine the association of disease progression and HRQoL in 4 prevalent solid-cancer entities in routine clinical practice. [https://www.selleckchem.com/products/mln2480.html learn more] Design, Setting, and Participants This cohort study evaluated data from 4 prospective, nonintervention, multicenter registries collected between 2011 and 2018 in 203 centers in Germany. Patients' HRQoL was assessed regularly for up to 5 years. The change in HRQoL scores after disease progression was examined with linear mixed models, adjusting for demographic and clinical covariates. Patients with metastatic breast, pancreatic, lung, and colorectal cancer were recruited at the stst pronounced in lung cancer (6.7 points [95% CI, 3.5-9.9 points]; P  less then  .001) and pancreatic cancer (5.4 points [95% CI, 3.3-7.5 points]; P  less then  .001) and less in colorectal cancer (3.5 points [95% CI, 1.3-5.7 points]; P = .002) and breast cancer (2.4 points [95% CI, 1.0-3.9 points]; P = .001). The second progression was associated with an even larger decrease in HRQoL. Conclusions and Relevance These findings suggest that disease progression is associated with a deterioration in HRQoL among patients with metastatic breast, pancreatic, lung, and colorectal cancer. This evidence highlights the importance of progression-related end points, such as time to progression and progression-free survival, as additional patient-relevant end points when evaluating the benefit of new treatments for patients with metastatic cancer.BACKGROUND Sleep and circadian rhythm disturbances in schizophrenia are common, but incompletely characterized. We aimed to describe and compare the magnitude and heterogeneity of sleep-circadian alterations in remitted schizophrenia and compare them with those in interepisode bipolar disorder. METHODS EMBASE, Medline, and PsycINFO were searched for case-control studies reporting actigraphic parameters in remitted schizophrenia or bipolar disorder. Standardized and absolute mean differences between patients and controls were quantified using Hedges' g, and patient-control differences in variability were quantified using the mean-scaled coefficient of variation ratio (CVR). A wald-type test compared effect sizes between disorders. RESULTS Thirty studies reporting on 967 patients and 803 controls were included. Compared with controls, both schizophrenia and bipolar groups had significantly longer total sleep time (mean difference [minutes] [95% confidence interval CI] = 99.9 [66.8, 133.1] and 31.1 [19.3, 42.9], respectively), time in bed (mean difference = 77.8 [13.7, 142.0] and 50.3 [20.3, 80.3]), but also greater sleep latency (16.5 [6.1, 27.0] and 2.6 [0.5, 4.6]) and reduced motor activity (standardized mean difference [95% CI] = -0.86 [-1.22, -0.51] and -0.75 [-1.20, -0.29]). Effect sizes were significantly greater in schizophrenia compared with the bipolar disorder group for total sleep time, sleep latency, and wake after sleep onset. CVR was significantly elevated in both diagnoses for total sleep time, time in bed, and relative amplitude. CONCLUSIONS In both disorders, longer overall sleep duration, but also disturbed initiation, continuity, and reduced motor activity were found. Common, modifiable factors may be associated with these sleep-circadian phenotypes and advocate for further development of transdiagnostic interventions that target them. © The Author(s) 2020. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.AIMS The prevalence and prognostic implications of left atrial appendage (LAA) thrombus (LAAT) in patients considered for transcatheter aortic valve replacement (TAVR) are incompletely defined. We, therefore, studied pre-procedural cardiac computed tomography angiography (CCTA) scans of TAVR candidates to determine the prevalence of LAAT and its association with late outcomes. METHODS AND RESULTS Baseline clinical variables and CCTA findings from a prospective TAVR registry were analysed for the prevalence of pre-procedural LAAT and its impact on in-hospital outcomes and late mortality. LAAT was differentiated from LAA filling defects (LAAFD) reflecting stasis without clot. Patients (n = 561) with complete in-hospital and late mortality data were included in the study (median follow-up 31.6 months). LAAT and LAAFD were evidenced on pre-procedural CCTA in 24 (4.3%) and 26 (4.6%) patients, respectively. One hundred fourteen (20.3%) patients died during the study period. Though in-hospital adverse event rates (including stroke) did not differ among groups, mortality at long-term follow-up was higher among LAAT patients compared with those with or without LAAFD (58.3% vs. 11.5% vs. 19.0%, respectively; P  less then  0.003). By multivariable analysis, LAAT (but not LAAFD) was independently associated with all-cause mortality [hazard ratio (HR) = 3.33 (1.83-6.00), P  less then  0.001]. In patients with LAAT, oral anticoagulation at discharge was associated with lower mortality risk, independently of atrial fibrillation status. CONCLUSIONS LAAT visualized by pre-procedural CCTA is an independent predictor of late mortality following TAVR, but not peri-procedural stroke. When reporting TAVR-CCTA, particular note should be made of LAA features and presence of LAAT which may have prognostic and management implications. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email journals.permissions@oup.com.MYB-bHLH-WDR transcription factor (TF) complexes (MBWs) regulate Arabidopsis seed coat development including mucilage and tannin biosynthesis. The R2R3 MYBs MYB5, MYB23 and TRANSPARENT TESTA2 (TT2) participate in the MBW complexes with the WD-repeat protein TRANSPARENT TESTA GLABRA1 (TTG1). These complexes regulate GLABRA2 (GL2) and TTG2 expression in developing seeds. Microarray transcriptome analysis of ttg1-1 and wild-type (Ler) developing seeds identified 246 TTG1-regulated genes which include all known metabolic genes of the tannin biosynthetic pathway. The first detailed TTG1-dependent metabolic pathways could be proposed for the biosynthesis of mucilage, jasmonic acid and cuticle including wax ester in developing seeds. We also assigned many known and previously uncharacterized genes to the activation/inactivation of hormones, plant immunity and nutrient transport. The promoters of six cuticle pathway genes were active in developing seeds. Expression of 11 genes was determined in the developing seeds of the combinatorial mutants of MYB5, MYB23 and TT2, and in the combinatorial mutants of GL2, HOMEODOMAIN GLABROUS2 (HDG2) and TTG2. These six TFs positively co-regulated the expression of four repressor genes while three of the six TFs repressed the wax biosynthesis genes examined, suggesting that the three TFs up-regulate the expression of these repressor genes which in turn repress the wax biosynthesis genes. Chromatin immunoprecipitation analysis identified 21 genes directly regulated by MYB5 including GL2, HDG2, TTG2, four repressor genes and various metabolic genes. We propose a multi-tiered regulatory mechanism by which MBWs regulate tannin, mucilage, jasmonic acid and cuticle biosynthetic pathways. © The Author(s) 2020. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email journals.permissions@oup.com.Eukaryotic chromatin is tightly packed into hierarchical structures, allowing appropriate gene transcription in response to environmental and developmental cues. Here, we provide a chromosome-scale de novo genome assembly of sesame with a total length of 292.3 Mb and scaffold N50 of 20.5 Mb, containing estimated 28,406 coding genes using PacBio long-reads combined with a genome-wide chromosome conformation capture (Hi-C) approach. Based on this high-quality reference genome, we detected changes of chromatin architectures between normally growth and dark treated sesame seedlings. Gene expression level was significantly higher in "A" compartment and TAD boundary regions than in "B" compartment and TAD interior regions, which is coincident with enrichment of H4K3me3 modification in these regions. Moreover, differentially expressed genes induced by dark treated were enriched in the changed TAD-related regions and genomic differential contact regions. Go enrichment analysis of differentially expressed genes showed that genes related to "Response to stress" and "Photosynthesis" functional categories were enriched which corresponds to dark treatment. These results suggested that chromatin organization is associated with gene transcription in response to dark treatment in sesame. Our results will facilitate understanding of regulatory mechanisms in response to environmental cues in plants. © The Author(s) 2020. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email journals.permissions@oup.com.Disrespect and abuse during childbirth are violations of women's human rights and an indicator of poor-quality care. Disrespect and abuse during childbirth are widespread, yet data on providers' perspectives on the topic are limited. We examined providers' perspectives on the frequency and drivers of disrespect and abuse during facility-based childbirth in a rural county in Kenya. We used data from a mixed-methods study in a rural county in Western Kenya with 49 maternity providers (32 clinical and 17 non-clinical) in 2016. Providers were asked structured questions on disrespect and abuse, followed by open-ended questions on why certain behaviours were exhibited (or not). Most providers reported that women were often treated with dignity and respect. However, 53% of providers reported ever observing other providers verbally abuse women and 45% reported doing so themselves. Observation of physical abuse was reported by 37% of providers while 35% reported doing so themselves. Drivers of disrespect and abuse included perceptions of women being difficult, stress and burnout, facility culture and lack of accountability, poor facility infrastructure and lack of medicines and supplies, and provider attitudes.