Identifying the functional microbes in spontaneous food fermentation is important to improve food quality. To identify key flavor producer in Chinese liquor fermentation, we proposed a novel quantitative microbiome profiling method that used indigenous internal standards to normalize high-throughput amplicon sequencing results. We screened Lactobacillus acetotolerans and Lactobacillus jinshani as indigenous internal standards by their high distribution frequencies and relative abundances. After determining the absolute abundance of indigenous internal standards using quantitative PCR with their species-specific primers, the liquor fermented bacterial community and its dynamics were better characterized by internal standards normalization. Based on quantitative microbiome profiling, we identified that Lactobacillus was a key flavor producer that was correlated with eight flavor compounds. Metatranscriptomic analysis indicated that Lactobacillus was active in transcribing genes involving the biosynthesis of flaation. Copyright © 2020 American Society for Microbiology.Communities of gut bacteria (microbiota) are known to play roles in resistance to pathogen infection and optimal weight gain in turkey flocks. However, knowledge of turkey respiratory microbiota and its link to gut microbiota is lacking. This study presents a 16S rRNA gene-based census of the turkey respiratory microbiota (nasal cavity and trachea) alongside gut microbiota (cecum and ileum) in two identical commercial Hybrid Converter turkey flocks raised in parallel under typical field commercial conditions. The flocks were housed in adjacent barns during the brood stage and in geographically separated farms during the grow-out stage. Several bacterial taxa that were acquired in the respiratory tract at the beginning of the brood stage persisted throughout the flock cycle, primarily Staphylococcus Late-emerging predominant taxa in the respiratory tract included Deinococcus and Corynebacterium Tracheal and nasal microbiota of turkeys were identifiably distinct from one another and from gut microbiota. Neverthtory microbiota in turkeys are entirely unexplored. This study has elucidated the microbiota of respiratory tracts of turkeys from two commercial flocks raised in parallel throughout a normal flock cycle. Further, the study suggests that bacteria originating in the gut or in poultry house environments may influence respiratory communities; and consequently, induce poor performance, either directly or indirectly. Future attempts to develop microbiome-based interventions for turkey health should delimit the contributions of respiratory microbiota and aim to limit disturbances to those communities. Copyright © 2020 American Society for Microbiology.Cross-feeding based on the metabolite 1,2-propanediol has been proposed to have an important role in the establishment of trophic interactions among gut symbionts, but its ecological importance has not been empirically established. Here, we show that in vitro growth of Lactobacillus reuteri ATCC PTA 6475 is enhanced through 1,2-propanediol produced by Bifidobacterium breve UCC2003 and Escherichia coli MG1655 from the metabolization of fucose and rhamnose, respectively. Work with isogenic mutants showed that the tropic interaction is dependent on the pduCDE operon in L. reuteri, which encodes for the ability to use 1,2-propanediol, and the L-fucose permease (fucP) gene in B. breve, which is required for 1,2-propanediol formation from fucose. Experiments in gnotobiotic mice revealed that, although the pduCDE operon bestows a fitness burden on L. reuteri ATCC PTA 6475 in the mouse digestive tract, the ecological performance of the strain was enhanced in the presence of B. breve UCC2003 and the mucus-degrading spgut ecosystems, which could employ mixtures of bacterial strains that establish trophic interactions or a personalized approach based on the ability of a resident microbiota to provide resources for the incoming microbe. Copyright © 2020 American Society for Microbiology.Bacillus thuringiensis (Bt) is the most widely used active ingredient for biological insecticides. The composition of δ-endotoxins (Cry and Cyt proteins) in the parasporal crystal determines the toxicity profile of each Bt strain. However, a reliable method for their identification and quantification has not been available, due to the high sequence identity of the genes that encode the δ-endotoxins and the toxins themselves. Here we have developed an accurate and reproducible mass spectrometry-based method (LC-MS/MS-MRM), using isotopically-labelled proteotypic peptides for each protein in a particular mixture, to determine the relative proportion of each δ-endotoxin within the crystal. To validate the method, artificial mixtures containing Cry1Aa, Cry2Aa and Cry6Aa were analyzed. Determination of the relative abundance of proteins (in molarity) with our method was in good agreement with the expected values. This method was then applied to the most common commercial Bt-based products DiPel® DF, Xentari® GD, Vhe production of Bt-based insecticides is its quality control. By specifically quantifying the relative proportion of each of the toxins that make up the crystal, our method represents the most consistent and repeatable evaluation procedure in the quality control of different batches produced in successive fermentations. This method can also contribute to the design of specific culture media and fermentation conditions that optimize Bt crystal composition across a range of Bt strains that target different pestiferous insects. Quantitative information on crystal composition should also prove valuable to phytosanitary product registration authorities that oversee the safety and efficacy of crop protection products. Copyright © 2020 American Society for Microbiology.OBJECTIVES Children born very preterm (VPT) are at an increased risk of developing mental health (MH) disorders. Our aim for this study was to assess rates of MH disorders in children born VPT and term at 13 years of age and stability of MH disorders between ages 7 and 13 years by using a diagnostic measure. METHODS Participants were from the Victorian Infant Brain Study longitudinal cohort and included 125 children born VPT ( less then 30 weeks’ gestational age and/or less then 1250 g) and 49 children born term (≥37 weeks’ gestational age) and their families. Participants were followed-up at both 7 and 13 years, and the Development and Well-Being Assessment was administered to assess for MH disorders. RESULTS Compared with term peers, 13-year-olds born VPT were more likely to meet criteria for any MH disorder (odds ratio 5.9; 95% confidence interval 1.71-20.03). Anxiety was the most common disorder in both groups (VPT = 14%; term = 4%), whereas attention-deficit/hyperactivity disorder carried the greatest differential elevated risk (odds ratio 5.6; 95% confidence interval 0.71-43.80). Overall rates of MH disorders remained stable between 7 and 13 years, although at an individual level, many participants shifted in or out of diagnostic categories over time. CONCLUSIONS Children born VPT show higher rates of MH disorders than their term peers, with changing trajectories over time. Findings highlight the importance of early identification and ongoing assessment to support those with MH disorders in this population. Copyright © 2020 by the American Academy of Pediatrics.OBJECTIVE High-risk opioid prescribing practices in workers’ compensation (WC) settings are associated with excess opioid-related morbidity, longer work disability and higher costs. This study characterises the burden of prescription opioid-related hospitalisations among injured workers. METHODS Hospital discharge data for eight states (Arizona, Colorado, Michigan, New Jersey, New York, South Carolina, Utah and Washington) were obtained from the State Inpatient Databases, Healthcare Cost and Utilization Project, Agency for Healthcare Research and Quality. We calculated 5-year (2010-2014) average annual rates of prescription opioid overdose/adverse effect (AE) hospitalisations. Injured workers were identified using payer (WC) and external cause codes. RESULTS State-level average annual prescription opioid overdose/AE hospitalisation rates ranged from 0.3 to 1.2 per 100 000 employed workers. Rates for workers aged ≥65 years old were two to six times the overall rates. Among those hospitalised with prescription opioid overdose/AEs, injured workers were more likely than other inpatients to have a low back disorder diagnosis, and less likely to have an opioid dependence/abuse or cancer diagnosis, or a fatal outcome. Averaged across states, WC was the primary expected payer for less then 1% of prescription opioid overdose/AE hospitalisations vs 6% of injury hospitalisations. CONCLUSIONS Population-based estimates of prescription opioid morbidity are almost nonexistent for injured workers; this study begins to fill that gap. Rates for injured workers increased markedly with age but were low relative to inpatients overall. Research is needed to assess whether WC as payer adequately identifies work-related opioid morbidity for surveillance purposes, and to further quantify the burden of prescription opioid-related morbidity. © Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.INTRODUCTION Humeral shaft fractures can lead to radial nerve injury and may require surgery and rehabilitation. We determined the causative events of humeral fracture, including arm wrestling, in young Korean soldiers and examined whether humeral fracture is related to demographic characteristics and the presence of radial nerve palsy. METHODS We reviewed 7.5 years (July 2012 to June 2019) of medical records covering patients who had experienced a humeral shaft fracture after entering military service and had received surgery for open reduction and internal fixation. Data were obtained on basic demographics, initial event provoking the fracture, presence of radial nerve palsy, initial and follow-up severity of the weakness, and any discharge from military service because of prolonged radial nerve palsy. RESULTS Of 123 cases, arm wrestling was the leading cause (52.8%). A high energy injury, such as falling from a height (11.4%), and sports related slips (10.6%) were other causes. All humeral shaft fractures J.Tissue-resident macrophages (TRMs) maintain tissue homeostasis, but they can also provide a replicative niche for intracellular pathogens such as Leishmania How dermal TRMs proliferate and maintain their M2 properties even in the strong TH1 environment of the L. major infected dermis is not clear. Here, we show that, in infected mice lacking IL-4/13 from eosinophils, dermal TRMs shifted to a proinflammatory state, their numbers declined, and disease was attenuated. Intravital microscopy revealed a rapid infiltration of eosinophils followed by their tight interaction with dermal TRMs. IL-4-stimulated dermal TRMs, in concert with IL-10, produced a large amount of CCL24, which functioned to amplify eosinophil influx and their interaction with dermal TRMs. An intraperitoneal helminth infection model also demonstrated a requirement for eosinophil-derived IL-4 to maintain tissue macrophages through a CCL24-mediated amplification loop. CCL24 secretion was confined to resident macrophages in other tissues, implicating eosinophil-TRM cooperative interactions in diverse inflammatory settings. Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.Intestinal mononuclear phagocytes (MPs) are composed of heterogeneous dendritic cell (DC) and macrophage subsets necessary for the initiation of immune response and control of inflammation. Although MPs in the normal intestine have been extensively studied, the heterogeneity and function of inflammatory MPs remain poorly defined. We performed phenotypical, transcriptional, and functional analyses of inflammatory MPs in infectious Salmonella colitis and identified CX3CR1+ MPs as the most prevalent inflammatory cell type. CX3CR1+ MPs were further divided into three distinct populations, namely, Nos2 +CX3CR1lo, Ccr7 +CX3CR1int (lymph migratory), and Cxcl13 +CX3CR1hi (mucosa resident), all of which were transcriptionally aligned with macrophages and derived from monocytes. In follow-up experiments in vivo, intestinal CX3CR1+ macrophages were superior to conventional DC1 (cDC1) and cDC2 in inducing Salmonella-specific mucosal IgA. We next examined spatial organization of the immune response induced by CX3CR1+ macr.To identify genetic variants for risk of squamous cell carcinoma of the head and neck (SCCHN), we conducted a two-phase genome-wide association study consisting of 7,858,089 SNPs in 2,171 cases and 4,493 controls of non-Hispanic white, of which 434,839 typed and 7,423,250 imputed SNPs as the discovery. SNPs with P less then 1×10-3 were further validated in the OncoArray study of oral and pharynx cancer (5,205 cases and 3,232 controls of European ancestry) from dbGaP. Meta-analysis of the discovery and replication studies identified one novel locus 6p22.1 (P = 2.96×10-9 for the leading rs259919) and two cancer susceptibility loci 6p21.32 (rs3135001, HLA-DQB1) and 6p21.33 (rs1265081, CCHCR1) associated with SCCHN risk. Further stratification by tumor site revealed four known cancer loci (5p15.33, 6p21.32, 6p21.33, and 2p23.1) associated with oral cavity cancer risk and oropharyngeal cancer risk, respectively. In addition, one novel locus 18q22.2 (P = 2.54×10-9 for the leading SNP rs142021700) was identified for hypo-pharynx and larynx cancer risk. For SNPs in those reported or novel loci, we also performed functional annotations by bioinformatics prediction and eQTL analysis. Collectively, our identification of four reported loci (2p23.1, 5p15.33, 6p21.32, and 6p21.33) and two novel loci (6p22.1 and 18q22.2) for SCCHN risk highlight the importance of HLA loci for oropharyngeal cancer risk, suggesting that immunologic mechanisms are implicated in the etiology of this subset of SCCHN. Copyright ©2020, American Association for Cancer Research.GRP78, an endoplasmic reticulum (ER) chaperone, is a master regulator of the ER stress. A number of studies revealed that high levels of GRP78 protein in cancer cells confer multidrug resistance (MDR) to therapeutic treatment. Therefore, drug candidate that reduces GRP78 may represent a novel approach to eliminate MDR cancer cells. Our earlier studies showed that a set of 4H-chromene derivatives induce selective cytotoxicity in MDR cancer cells. In the present study, we elucidated its selective mechanism in four MDR cancer cell lines with one lead candidate (CXL146). Cytotoxicity results confirmed the selective cytotoxicity of CXL146 towards the MDR cancer cell lines. We noted significant overexpression of GRP78 in all four MDR cell lines compared to the parental cell lines. Unexpectedly, CXL146 treatment rapidly and dose-dependently reduced GRP78 protein in MDR cancer cell lines. Using HL60/MX2 cell line as the model, we demonstrated that CXL146 treatment activated the unfolded protein response (UPR) as evidpeutics.Growing evidence indicates that oxidative and endoplasmic reticular stress, which trigger changes in ion channels and inflammatory pathways that may undermine cellular homeostasis and survival, are critical determinants of injury in the diabetic kidney. Cells are normally able to mitigate these cellular stresses by maintaining high levels of autophagy, an intracellular lysosome-dependent degradative pathway that clears the cytoplasm of dysfunctional organelles. However, the capacity for autophagy in both podocytes and renal tubular cells is markedly impaired in type 2 diabetes, and this deficiency contributes importantly to the intensity of renal injury. The primary drivers of autophagy in states of nutrient and oxygen deprivation-sirtuin-1 (SIRT1), AMP-activated protein kinase (AMPK), and hypoxia-inducible factors (HIF-1α and HIF-2α)-can exert renoprotective effects by promoting autophagic flux and by exerting direct effects on sodium transport and inflammasome activation. Type 2 diabetes is characterized bylar function and reduce the risk of ESKD in large-scale randomized clinical trials of patients with type 2 diabetes. Copyright © 2020 by the American Society of Nephrology.It has been hypothesized that androgens respond to the social interactions as a way to adjust the behaviour of individuals to the challenges of the social environment in an adaptive manner. Therefore, it is expected that transient changes in circulating androgen levels within physiological scope should impact the state of the brain network that regulates social behavior, which should translate into adaptive behavioural changes. Here, we examined the effect that a transient peak in androgen circulating levels, which mimics socially driven changes in androgen levels, has on the forebrain state, which harbors most nuclei of the social decision-making network. For this purpose, we successfully induced transient changes in circulating androgen levels in an African cichlid fish (Mozambique tilapia, Oreochromis mossambicus) commonly used as a model in behavioral neuroendocrinology by injecting 11-ketotestosterone or testosterone, and compared the forebrain transcriptome of these individuals to control fish injected with vehicle. Forebrain samples were collected 30 min and 60 min after injection and analyzed using RNAseq. Our results showed that a transient peak in 11-ketotestosterone drives more accentuated changes in forebrain transcriptome than testosterone, and that transcriptomic impact was greater at the 30 min than at the 60 min post-androgen administration. Several genes involved in the regulation of translation, steroid metabolism, ion channel membrane receptors, and genes involved in epigenetic mechanisms were differentially expressed after 11-ketotestosterone or testosterone injection. In summary, this study identified specific candidate genes that may regulate socially driven changes in behavioural flexibility mediated by androgens. Copyright © The Author(s) 2020. Published by the Genetics Society of America.FUS is a nucleic acid binding protein that, when mutated, cause a subset of familial amyotrophic lateral sclerosis (ALS). Expression of FUS in yeast recapitulates several pathological features of the disease-causing mutant proteins, including nuclear to cytoplasmic translocation, formation of cytoplasmic inclusions, and cytotoxicity. Genetic screens using the yeast model of FUS have identified yeast genes and their corresponding human homologs suppressing FUS induced toxicity in yeast, neurons and animal models. To expand the search for human suppressor genes of FUS induced toxicity, we carried out a genome-scale genetic screen using a newly constructed library containing 13570 human genes cloned in an inducible yeast-expression vector. Through multiple rounds of verification, we found 37 human genes that, when overexpressed, suppress FUS induced toxicity in yeast. Human genes with DNA or RNA binding functions are overrepresented among the identified suppressor genes, supporting that perturbations of RNA metabolism is a key underlying mechanism of FUS toxicity. Copyright © The Author(s) 2020. Published by the Genetics Society of America.Novel pathogens can cause massive declines in populations, and even extirpation of hosts. But disease can also act as a selective pressure on survivors, driving the evolution of resistance or tolerance. Bat white-nose syndrome (WNS) is a rapidly spreading wildlife disease in North America. The fungus causing the disease invades skin tissues of hibernating bats, resulting in disruption of hibernation behavior, premature energy depletion, and subsequent death. We used whole-genome sequencing to investigate changes in allele frequencies within a population of Myotis lucifugus in eastern North America to search for genetic resistance to WNS. Our results show low FST values within the population across time, i.e. prior to WNS (Pre-WNS) compared to the population that has survived WNS (Post-WNS). However, when dividing the population with a geographical cut-off between the states of Pennsylvania and New York, a sharp increase in values on scaffold GL429776 is evident in the Post-WNS samples. Genes present in the diverged area are associated with thermoregulation and promotion of brown fat production. Thus, although WNS may not have subjected the entire M. lucifugus population to selective pressure, it may have selected for specific alleles in Pennsylvania through decreased gene flow within the population. However, the persistence of remnant sub-populations in the aftermath of WNS is likely due to multiple factors in bat life history. Copyright © The Author(s) 2020. Published by the Genetics Society of America.INTRODUCTION Hypertension is one of the most common medical conditions and represents a major risk factor for heart attack, stroke, kidney disease and mortality. The risk of progression to hypertension depends on several factors, and combining these risk factors into a multivariable model for risk stratification would help to identify high-risk individuals who should be targeted for healthy behavioural changes and/or medical treatment to prevent the development of hypertension. The risk prediction models can be further improved in terms of accuracy by using a metamodel updating technique where existing hypertension prediction models can be updated by combining information available in existing models with new data. A systematic review and meta-analysis will be performed of hypertension prediction models in order to identify known risk factors for high blood pressure and to summarise the magnitude of their association with hypertension. METHODS AND ANALYSIS MEDLINE, Embase, Web of Science, Scopus and grey literature will be systematically searched for studies predicting the risk of hypertension among the general population. The search will be based on two key concepts hypertension and risk prediction. The summary statistics from the individual studies will be the regression coefficients of the hypertension risk prediction models, and random-effect meta-analysis will be used to obtain pooled estimates. Heterogeneity and publication bias will be assessed, along with study quality, which will be assessed using the Prediction Model Risk of Bias Assessment Tool checklist. ETHICS AND DISSEMINATION Ethics approval is not required for this systematic review and meta-analysis. We plan to disseminate the results of our review through journal publications and presentations at applicable platforms. © 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 To evaluate the association between socioeconomic status (SES) and referral to cardiac rehabilitation (CR) after incident acute coronary syndrome (ACS) by dividing the referral process into three phases (1) informed about CR, (2) willingness to participate in CR, (3) and assigned CR setting. DESIGN Cross-sectional study. SETTING Department of Cardiology at a Danish University Hospital from 1 January 2011 to 31 December 2014. PARTICIPANTS A total of 1229 patients assessed for CR during hospitalisation with ACS were prospectively registered in the Rehab-North Register from 2011 to 2014. SES was assessed using data from national registers, concerning personal income, occupational status, educational level and civil status. Patients were excluded if one of the following criteria was fulfilled (1) missing data on SES, or (2) acceptable reason for not informing patients about CR (treatment with coronary artery bypass grafting, transfer to another hospital, still under treatment or death). MAIN OUTCOME MEAs) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.OBJECTIVES Symptom Screening in Pediatrics Tool (SSPedi) is a validated approach to measuring bothersome symptoms for English-speaking and Spanish-speaking children with cancer and paediatric haematopoietic stem cell transplantation (HSCT) recipients. Objectives were to translate SSPedi into French, and among French-speaking children receiving cancer treatments, to evaluate understandability and cultural relevance. METHODS We conducted a multiphase, descriptive study to translate SSPedi into French. Forward translation was performed by four medical translators. After confirming that back translation was satisfactory, we enrolled French-speaking children with cancer and paediatric HSCT recipients at four centres in France and Canada. PRIMARY AND SECONDARY OUTCOME MEASURES Understandability was evaluated by children themselves who self-reported degree of difficulty, and by two adjudicators who rated incorrectness. Assessment of cultural relevance was qualitative. Participants were enrolled in cohorts of 10. RESULTS There were 30 children enrolled. Participants were enrolled from Marseille (n=10, 33%), Ottawa (n=1, 3%), Quebec City (n=11, 37%) and Toronto (n=8, 27%). No child reported that it was hard or very hard to complete French SSPedi in the last cohort of 10 participants. Changes to the instrument itself were not required. After enrolment of 30 respondents, the French translation of SSPedi was considered finalised based on self-reported difficulty with understanding, adjudicated incorrect understanding and cultural relevance. CONCLUSIONS We translated and finalised SSPedi for use by French-speaking children and adolescents receiving cancer treatments. Future work should begin to use the translated version to conduct research and to facilitate clinical care. © 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.INTRODUCTION Hypertensive disorders of pregnancy (HDP), one of the most common obstetrical complications, has been reported to have a controversial relationship with the increased risk of asthma in offspring. No systematic review of this topic has been performed. The aim of this systematic review will be to summarise the available evidence examining the association between HDP and the risk of asthma in offspring. METHODS AND ANALYSIS We will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Meta-analysis of Observational Studies in Epidemiology guidelines. A systematic search of the PubMed, Embase, Cochrane and Web of Science databases will be performed using a detailed search strategy from database inception through 31 December 2019. Cohort, case-control and cross-sectional studies that report a diagnosis of maternal HDP and asthma in offspring will be included. Studies will be limited to the English language and include only human participants. Two independent reviewers will review will be based on published data. It is anticipated that the dissemination of results will take place at conferences and through publication in a peer-reviewed journal. © 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.INTRODUCTION Non-communicable diseases (NCDs) are the leading cause of death worldwide, including in Korea; thus, customised techniques for chronic disease management for the prevention, early diagnosis and treatment of NCDs are crucial. The Korean Medicine Daejeon Citizen Cohort (KDCC) study has been tasked with developing precise health promotion model for preventing and managing chronic diseases that considers individual traits, lifestyle factors and clinical data based on traditional Korean medicine. METHODS AND ANALYSIS The KDCC study is a prospective cohort study of the community-based population in Korea. This study will sample 2000 adults aged 30-55 years in Daejeon area using stratified cluster sampling. The baseline survey began in 2017 and was completed in 2019, and follow-up surveys will be conducted three times every 2 years until 2025. In follow-ups, factors related to cardiovascular disease, metabolic syndrome and relevant diseases, as well as respondents’ health status information, will be examined via questionnaire surveys and health examinations. DISCUSSION The KDCC study will investigate the effects of an interaction of Korean medicine type with genome based, lifestyle and various clinical information on chronic diseases and individuals’ health status using longitudinal epidemiological data. These findings are expected to inform the development of tailored health promotion programmes based on precision Korean medicine. TRIAL REGISTRATION NUMBER KCT0004297. © 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.INTRODUCTION Development of a support system for families caring for people with schizophrenia in routine psychiatric care settings is an important issue worldwide. Regional mental health systems are inadequate for delivering effective services to such family members. Despite evidence that family psychoeducation (FPE) alleviates the burden of schizophrenia on families, its dissemination in routine clinical practice remains insufficient, suggesting the need for developing an effective and implementable intervention for family caregivers in the existing mental health system setting. In Japan, the visiting nurse service system would be a practical way of providing family services. Visiting nurses in local communities are involved in the everyday lives of people with schizophrenia and their families. Accordingly, visiting nurses understand their needs and are able to provide family support as a service covered by national health insurance. The purpose of this study is to discover whether a brief FPE programme proo, Japan (No 2019065NI) approved this study. The results will be published in a scientific peer-reviewed journal. TRIAL REGISTRATION NUMBER UMIN000038044. © 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.OBJECTIVES Clinicians are facing increasing demands on their time, exacerbated by fiscal constraints and increasing patient complexity. Volunteers are an essential part of the many healthcare systems, and are one resource to support improved patient experience and a mechanism through which to address unmet needs. Hospitals rely on volunteers for a variety of tasks and services, but there are varying perceptions about volunteers’ place within the healthcare team. This study aimed to understand the role of volunteers in stroke rehabilitation, as well as the barriers to volunteer engagement. DESIGN A qualitative case study was conducted to understand the engagement of volunteers in stroke rehabilitation services within a complex rehabilitation and continuing care hospital in Ontario, Canada. PARTICIPANTS 28 clinicians, 10 hospital administrators and 22 volunteers participated in concurrent focus groups and interviews. Organisational documents pertaining to volunteer management were retrieved and analysed. RESULTS While there was support for volunteer engagement, with a wide range of potential activities for volunteers, several barriers to volunteer engagement were identified. These barriers relate to paid workforce/unionisation, patient safety and confidentiality, volunteer attendance and lack of collaboration between clinical and volunteer resource departments. CONCLUSIONS An interprofessional approach, specifically emphasising and addressing issues related to key role clarity, may mediate these barriers. Clarity regarding the role of volunteers in hospital settings could support workforce planning and administration. © 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.OBJECTIVES National guidelines for the management of irritable bowel syndrome (IBS) recommend that psychological therapies should be considered, but their relative efficacy is unknown, because there have been few head-to-head trials. We performed a systematic review and network meta-analysis to try to resolve this uncertainty. DESIGN We searched the medical literature through January 2020 for randomised controlled trials (RCTs) assessing efficacy of psychological therapies for adults with IBS, compared with each other, or a control intervention. Trials reported a dichotomous assessment of symptom status after completion of therapy. We pooled data using a random effects model. Efficacy was reported as a pooled relative risk (RR) of remaining symptomatic, with a 95% CI to summarise efficacy of each comparison tested, and ranked by therapy according to P score. RESULTS We identified 41 eligible RCTs, containing 4072 participants. After completion of therapy, the psychological interventions with the largest numbend were the most efficacious long term. TRIAL REGISTRATION NUMBER The study protocol was published on the PROSPERO international prospective register of systematic reviews (registration number CRD 42020163246). © Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.Every month, DTB scans sources of information on treatments, disease management and other healthcare topics for key items to bring to our readers’ attention and help them keep up to date. To do this, we produce succinct, contextualised summaries of the information concerned. © BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.BACKGROUND Patients undergoing chemotherapy are known to be at risk for infection from myelosuppression by cytotoxic agents (CTAs) or immunosuppressive effects from mTOR inhibitors. The infection risk of newly developed anticancer agents has not been fully evaluated. It remains unknown how T-cell activation induced by immune checkpoint inhibitors (ICIs) relates to infection. METHODS We retrospectively examined infection risk in patients with cancer treated with investigational agents in a phase I study. The investigational agents were classified into four groups CTA, phosphatidylinositol 3 kinase/Akt/mammalian target of rapamycin inhibitor (PAM), molecular targeted agent (MTA) and ICI. All infection-related adverse events (AEs) during treatment were recorded. We compared the CTA, PAM and ICI with MTA, because MTA are already considered low risk and were used in the largest number of patients. RESULTS A total of 641 patients were enrolled 35 CTAs (5.5%), 61 PAMs (9.5%), 445 MTAs (69.4%) and 100 ICIs (15.6%). Aty for Medical Oncology.Individuals with dialysis-dependent kidney failure experience considerable disease- and treatment-related decline in functional status and overall wellbeing. Despite these experiences, there have been few substantive technological advances in KRT in decades. As such, new federal initiatives seek to accelerate innovation. Historically, integration of patient perspectives into KRT product development has been limited. However, the US Food and Drug Administration recognizes the importance of incorporating patient perspectives into the total product life cycle (i.e., from product conception to postmarket surveillance) and encourages the consideration of patient-reported outcomes in regulatory-focused clinical trials when appropriate. Recognizing the significance of identifying patient-reported outcome measures (PROMs) that capture contemporary patient priorities, the Kidney Health Initiative, a public-private partnership between the American Society of Nephrology and US Food and Drug Administration, convened a workgroup to (1) develop a conceptual framework for a health-related quality of life PROM; (2) identify and map existing PROMs to the conceptual framework, prioritizing them on the basis of their supporting evidence for use in the regulatory environment; and (3) describe next steps for identifying PROMs for use in regulatory clinical trials of transformative KRT devices. This paper summarizes the proposed health-related quality-of-life PROM conceptual framework, maps and prioritizes PROMs, and identifies gaps and future needs to advance the development of rigorous, meaningful PROMS for use in clinical trials of transformative KRT devices. Copyright © 2020 by the American Society of Nephrology.The Kidney Disease Improving Global Outcomes (KDIGO) 2017 „Clinical Practice Guideline on the Evaluation and Care of Living Kidney Donors” was developed to assist medical professionals who evaluate living kidney donor candidates and provide care before, during, and after donation. This guideline Work Group concluded that a comprehensive approach to donor candidate risk assessment should replace eligibility decisions on the basis of assessments of single risk factors in isolation. To address all issues important to living donors in a pragmatic and comprehensive guideline, many of the guideline recommendations were on the basis of expert consensus opinion even when no direct evidence was available. To advance available evidence, original data analyses were also undertaken to produce a „proof-of-concept” risk projection model for kidney failure. This was done to illustrate how the community can advance a new quantitative framework of risk that considers each candidate’s profile of demographic and health characteristics. A public review by stakeholders and subject matter experts as well as industry and professional organizations informed the final formulation of the guideline. This review highlights the guideline framework, key concepts, and recommendations, and uses five patient scenarios and 12 guideline statements to illustrate how the guideline can be applied to support living donor evaluation and care in clinical practice. Copyright © 2020 by the American Society of Nephrology.Some brain cancer patients show extremely short survival post-radiochemotherapy treatment for unknown reasons. Recent work shows that this is closely linked to encephalopathy associated with reactivation of latent cytomegalovirus in the host. Importantly, survival can be enhanced by treatment with anti-viral drugs. Copyright ©2020, American Association for Cancer Research.OBJECTIVE There is recent evidence that demonstrates worse oncologic outcomes associated with minimally invasive radical hysterectomy when compared with open radical hysterectomy, particularly in patients with tumors >2 cm. The aim of our study was to retrospectively evaluate the oncological outcomes between laparoscopic and open radical hysterectomy in International Federation of Gynecology and Obstetrics(FIGO) 2009 stage IB1 (FIGO 2009) cervical cancer patients with tumor size ≤2 cm. METHODS A retrospective review of medical records was performed to identify patients who underwent either laparoscopic or open radical hysterectomy during January 2010 and December 2018. Inclusion criteria were (1) histologically confirmed cervical cancer including all histological types; (2) FIGO 2009 stage IB1; (3) tumor size ≤2 cm (determined by pelvic examination, magnetic resonance imaging or transvaginal ultrasound); (4) had undergone radical hysterectomy (type II or III) with pelvic and/or para-aortic lymphadenectomy as ry was associated with lower disease-free survival compared with open surgery (adjusted hazard ratio 4.64, 95% CI 1.26 to 17.06; p=0.02). In patients with non-squamous cell carcinoma or with grade II-III, laparoscopic surgery had a significantly worse 5 year disease-free survival compared with the open surgery group (74% vs 100%, p=0.01, and 88.8% vs 98.0%, p=0.02, respectively). CONCLUSION Laparoscopic radical hysterectomy was associated with worse disease-free survival for stage IB1 (FIGO 2009) cervical cancer patients with tumor size ≤2 cm compared with open radical hysterectomy. Further studies may shed additional light on the impact of minimally invasive surgery in this low-risk patient population. © IGCS and ESGO 2020. No commercial re-use. See rights and permissions. Published by BMJ.INTRODUCTION Despite renewed treatment options for advanced epithelial ovarian cancer, survival remains poor. The Patient Association and the Gynecological Oncology Working Party in the Netherlands have identified a need for a tool to improve shared decision-making. The aim of this study was to develop an evidence-based online decision aid for patients with advanced epithelial ovarian cancer and their medical team. METHODS First, we identified the patients’ and clinicians’ needs using surveys and in-depth interviews. Second, we conducted multidisciplinary face-to-face meetings with representatives from all stakeholders (clinicians and patient representatives) to determine the content of the decision aid. Third, we developed the decision aid using standardized criteria and national guidelines. Finally, we tested the usability of the tool with patients and clinicians who participated in the needs assessment. RESULTS Patients and clinicians indicated the need for more sources of reliable information that include, based on a confirmed need for more extensive information sources. The decision aid is currently under assessment in a multicenter implementation trial. © IGCS and ESGO 2020. No commercial re-use. See rights and permissions. Published by BMJ.OBJECTIVE The aim of this study was to compare the clinical outcomes of chemoradiotherapy with or without bevacizumab in patients with newly diagnosed International Federation of Gynecology and Obstetrics (FIGO) stage IVB cervical cancer. METHODS 41 patients with stage IVB cervical cancer who underwent chemoradiotherapy between August 2015 and December 2017 were retrospectively analyzed. This study included 11 patients who received bevacizumab before or after radiotherapy (group A) and 30 patients who received conventional chemoradiotherapy without bevacizumab (group B). We excluded the following patients those with dual primary cancers; those whose pathologic diagnosis was neither squamous cell carcinoma nor adenocarcinoma; those who did not undergo radiotherapy; or those from whom follow-up data could not be collected. We analyzed the treatment responses, toxicities, progression-free survival, and overall survival rates. RESULTS A total of 41 patients were included in the analysis. The median follow-up was experienced more bowel toxicities. Bevacizumab did not improve progression-free survival among patients with node-only metastasis. © IGCS and ESGO 2020. No commercial re-use. See rights and permissions. Published by BMJ.OBJECTIVE The aim of this systematic review and meta-analysis was to review evidence supporting the use of prophylactic human papillomavirus (HPV) vaccines to influence the risk of recurrence of cervical intraepithelial neoplasia after surgical treatment. METHODS A systematic literature search was performed for publications reporting risk of recurrence of cervical intraepithelial neoplasia after surgical treatment in patients receiving HPV vaccination (either in the prophylactic or adjuvant setting). Comprehensive searches of six electronic databases (MEDLINE, Embase, Web of Science, PubMed, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, and references of identified studies) from their inceptions were performed (English language only), and hand search reference lists were performed. Two independent reviewers applied inclusion and exclusion criteria to select manuscripts, with differences discussed and agreed by consensus. The literature search was performed using PRISvant to surgical treatment. © IGCS and ESGO 2020. No commercial re-use. See rights and permissions. Published by BMJ.OBJECTIVE Most studies evaluating the oncologic safety of minimally invasive surgery for endometrial cancer focus on patients with stage I disease. The aim of this study was to investigate the outcomes of minimally invasive surgery for patients with endometrial carcinoma involving the cervix. METHODS Patients diagnosed between January 2010 and December 2015, with clinical stage II endometrial carcinoma, who underwent hysterectomy with lymphadenectomy, were drawn from the National Cancer Database. Inclusion criteria were clinical International Federation of Gynecology and Obstetrics (FIGO 2009) stage II, patients who underwent hysterectomy with lymphadenectomy, and known route of surgery (open or minimally invasive). Patients who received radiation therapy prior to surgery, those who had subtotal/supracervical hysterectomy, or unknown type of hysterectomy were excluded. The exposure of interest was performance of minimally invasive surgery either laparoscopic or robotic-assisted. Overall survival (primary endpof extensive lymphadenectomy, presence of positive lymph nodes, tumor histology, presence of lymphovascular space invasion, tumor size, and administration of radiotherapy, performance of minimally invasive surgery was not associated with worse survival (HR 0.90, 95% CI 0.73 to 1.11). CONCLUSIONS In this retrospective analysis, minimally invasive surgery in patients with stage II endometrial carcinoma was associated with superior short-term peri-operative outcomes and improved 3-year overall survival. © IGCS and ESGO 2020. No commercial re-use. See rights and permissions. Published by BMJ.Poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi) have transformed the treatment landscape in front-line and recurrent high-grade serous ovarian cancer. Maintenance strategies with PARPi have been assessed in randomized phase III trials in ovarian cancer; switch maintenance in the case of olaparib, niraparib, and rucaparib; and concurrent followed by continuation maintenance with veliparib. These studies have shown progression-free survival advantage with PARPi maintenance, with no major adverse changes in the quality of life; however, overall survival data remain immature to date. PARPi have also been incorporated in clinical practice as a single-agent treatment strategy in high-grade serous ovarian cancer, mainly in women who harbor alterations in the BRCA1/2 genes or have alterations in the homologous recombination deficiency (HRD) pathway. Contemporary studies are looking into potentially synergistic combination strategies with anti-angiogenics and immune checkpoint inhibitors, among others. The expansion of PARPi treatment has not been limited to ovarian cancer; talazoparib is licensed in patients with HER2-negative breast cancer with germline BRCA mutations (BRCAm), and front-line olaparib maintenance in patients with pancreatic cancer with germline BRCAm. Numerous studies assessing PARPi either in monotherapy or in combination with other agents are ongoing in multiple tumors, including prostate, endometrial, brain, and gastric cancers. Many patients are being treated with PARPi, some for prolonged periods of time. As a result, a thorough knowledge of the potential short- and long-term adverse events and their management is warranted to improve patient safety, treatment efficacy, and towards maintaining an appropriate dose intensity. © IGCS and ESGO 2020. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ.BACKGROUND The need for radical surgery followed by adjuvant chemoradiation may be reduced by abandoning radical surgery in patients in whom lymph node involvement is detected intra-operatively. OBJECTIVES To analyze, in a retrospective cohort study, the efficacy of the algorithm using intra-operative pathological assessment of sentinel lymph nodes. METHODS A retrospective single-institution study was carried out, which analyzed data from all consecutive patients with cervical cancer who were referred for primary surgical treatment between May 2005 and December 2015. Inclusion criteria were as follows (1) TNM stage T1a1 with lymphovascular space invasion, T1a2, T1b, T2a, and selected T2b with incipient parametrial invasion; (2) adenocarcinoma, squamous cell carcinoma, or adenosquamous carcinoma; (3) no evidence of enlarged suspicious nodes or distant metastases on pre-operative imaging; (4) primary surgery with curative intent; (5) successful detection of sentinel lymph node, at least, unilaterally. All patie © IGCS and ESGO 2020. No commercial re-use. See rights and permissions. Published by BMJ.INTRODUCTION Venous thromboembolism prevention during the perioperative period requires comprehensive risk-level assessment. The aim of this study was to evaluate the incidence of deep vein thrombosis and to assess the cut-off levels of serum D-dimer as a screening strategy for deep vein thrombosis during the perioperative period. METHODS A total of 205 patients (ovarian cancer 68, endometrial cancer 76, cervical cancer 61) who underwent gynecological surgery, including retroperitoneal lymph node dissection, were enrolled. We retrospectively analyzed the data on the cut-off value of D-dimer assessed using area under the receiver operating characteristic curve preoperatively, and 2 or 3 months, postoperatively. All patients underwent leg vein ultrasonography regardless of the serum D-dimer level. Furthermore, CT scans were performed to evaluate both disease status and venous thromboembolism, including pulmonary thromboembolism. Statistical analyzes were performed using the Mann-Whitney U-test (D-dimer values oD-dimer at 2 or 3 months postoperatively was higher than preoperative value. © IGCS and ESGO 2020. No commercial re-use. See rights and permissions. Published by BMJ.Cysteine depletion caused ferroptosis in human pancreatic cancer cells and improved survival in mice. ©2020 American Association for Cancer Research.Amid concerns over the spread of COVID-19, oncology practices have „gone virtual,” with video appointments scheduled for any service that does not require diagnostic testing or treatment. ©2020 American Association for Cancer Research.TMPRSS2 is both the most frequently altered gene in primary prostate cancer and a critical factor enabling cellular infection by coronaviruses, including SARS-CoV-2. The modulation of its expression by sex steroids could contribute to the male predominance of severe infections, and given that TMPRSS2 has no known indispensable functions, and inhibitors are available, it is an appealing target for prevention or treatment of respiratory viral infections. ©2020 American Association for Cancer Research.Germline loss-of-function ELP1 variants were found in pediatric Sonic Hedgehog medulloblastomas. ©2020 American Association for Cancer Research.Lurbinectedin produced responses in 35.2% of 105 patients with relapsed small-cell lung cancer. ©2020 American Association for Cancer Research.PARP1 inhibitors that clash with a specific helix in the helical domain prevent release from DNA. ©2020 American Association for Cancer Research.