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nt vaccine development. Copyright © 2020 American Society for Microbiology.Vibralactone, a hybrid compound derived from phenols and a prenyl group, is a strong pancreatic lipase inhibitor with a rare fused bicyclic β-lactone skeleton. Recently, researcher reported a vibralactone derivative (compound C1) that caused inhibition of pancreatic lipase with a half-maximal inhibitory concentration of 14 nM determined by structure-based optimization, suggesting a potential candidate as a new anti-obesity treatment. In the present study, we sought to identify the main gene encoding prenyltransferase in Stereum vibrans, which is responsible for the prenylation of phenol leading to vibralactone synthesis. Two RNA silencing transformants of identified gene (vib-PT) were obtained through Agrobacterium tumefaciens-mediated transformation. Compared to wild-type strains, the transformants showed a decrease in vib-PT expression ranging from 11.0% to 56.0% at 5, 10, and 15 days in reverse transcription-quantitative PCR (RT-qPCR) analysis and along with a reduction in primary vibralactone production oin a basidiomycetes species that is responsible for the synthesis of vibralactone. The identified gene, vib-PT, was expressed in E. coli to obtain a soluble and enzymatically active fusion Vib-PT protein. In vitro characterization of the enzyme demonstrated the catalytic mechanism of prenylation and broad substrate range for different aromatic acceptors and prenyl donors. These characteristics highlight the possibility of Vib-PT to generate prenylated derivatives of aromatics and other compounds as improved bioactive agents or potential prodrugs. this website Copyright © 2020 American Society for Microbiology.BACKGROUND AND OBJECTIVES Cancer survival is improving along with an increase in the potential for adverse kidney effects from antineoplastic treatments or nephrectomy. We sought to describe recent trends in the incidence of kidney failure related to antineoplastic treatments and urinary tract cancers and evaluate patient survival and kidney transplantation access. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS We used the French Renal Epidemiology and Information Network registry to identify patients with kidney failure related to antineoplastic treatments or urinary tract cancer from 2003 to 2015. We identified 287 and 1157 cases with nephrotoxin- and urinary tract cancer-related kidney failure, respectively. The main study outcomes were death and kidney transplantation. After matching cases to two to ten controls (n=11,678) with other kidney failure causes for age, sex, year of dialysis initiation, and diabetes status, we estimated subdistribution hazard ratios (SHR) of each outcome separately for patients ffer significantly between cases and controls. CONCLUSIONS Cancer-related kidney failure is slowly but steadily increasing. Mortality does not appear to be increased among patients without active malignancy at dialysis start, but their access to kidney transplant remains limited. Copyright © 2020 by the American Society of Nephrology.BACKGROUND AND OBJECTIVES Walking while talking is a dual cognitive-motor task that predicts frailty, falls, and cognitive decline in the general elderly population. Adults with CKD have gait abnormalities during usual walking. It is unknown whether they have greater gait abnormalities and cognitive-motor interference during walking while talking. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Community-dwelling, nondisabled adults (n=330) ≥65 years of age underwent quantitative gait analysis, including walking while talking. Differences in walking while talking performance by CKD status were evaluated, and relative changes between walking while talking and walking alone performance were computed to quantify cognitive-motor interference (dual-task cost). Associations were tested using multivariable linear spline regression models, and independent gait domains were derived using factor analysis. CKD was defined as an eGFR less then 60 ml/min per 1.73 m2. RESULTS CKD was present in 134 (41%) participants. Particr 1.73 m2 lower eGFR was associated with a poorer performance of 0.2 SD (95% confidence interval, 0.1 to 0.3) for walking while talking and 0.2 SD (95% confidence interval, 0.03 to 0.3) for dual-task cost. CONCLUSIONS During walking while talking, CKD is associated with gait abnormalities, possibly due to increased cognitive-motor interference. Copyright © 2020 by the American Society of Nephrology.Low-dose adjuvant epigenetic therapy (AET) reduced metastasis and promoted survival in mouse models. ©2020 American Association for Cancer Research.Mismatch repair (MMR)-deficient tumors exhibit proteome-wide protein instability and aggregation. ©2020 American Association for Cancer Research.The MaMTH-DS assay detected inhibitors of mutant EGFR in non-small cell lung cancer cells. ©2020 American Association for Cancer Research.OBJECTIVE To produce a single 'growth-chart-style' blood pressure (BP) chart with clear diagnostic thresholds to assist paediatricians to make prompt and accurate diagnoses of hypertension. DESIGN The well-established but complex published data on normal BP ranges in prepubertal children were identified and analysed to determine if it was possible to produce a single, user-friendly, colour-coded chart, showing diagnostic hypertension thresholds for systolic and diastolic BP without losing clinically important information. RESULTS There were sufficient published normative childhood BP data available to define systolic and diastolic BP centiles from term onwards but only sufficient to determine systolic BP centiles from 28 weeks of gestation to term. Up to 13 years of age, it was possible to combine boys' and girls' data without loss of precision and to define the threshold between stage 1 and stage 2 (severe) hypertension as the 95th centile +12 mm Hg. This allowed the production of single colour-coded charts for systolic and diastolic BP and to advise on making simple adjustments for the impact of stature on individual children's results. CONCLUSIONS A simplified, integrated BP chart with colour-coded diagnostic thresholds was produced to assist the prompt diagnosis of hypertension in prepubertal children. This information could be included into a Paediatric Early Warning System score. © Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.PURPOSE Patient safety failures are recognised as a global threat to public health, yet remain a leading cause of death internationally. Vulnerable children are inversely more in need of high-quality primary health and social-care but little is known about the quality of care received. Using national patient safety data, this study aimed to characterise primary care-related safety incidents among vulnerable children. METHODS This was a cross-sectional mixed methods study of a national database of patient safety incident reports occurring in primary care settings. Free-text incident reports were coded to describe incident types, contributory factors, harm severity and incident outcomes. Subsequent thematic analyses of a purposive sample of reports was undertaken to understand factors underpinning problem areas. RESULTS Of 1183 reports identified, 572 (48%) described harm to vulnerable children. Sociodemographic analysis showed that included children had child protection-related (517, 44%); social (353, 30%); psychological (189, 16%) or physical (124, 11%) vulnerabilities. Priority safety issues included poor recognition of needs and subsequent provision of adequate care; insufficient provider access to accurate information about vulnerable children, and delayed referrals between providers. CONCLUSION This is the first national study using incident report data to explore unsafe care amongst vulnerable children. Several system failures affecting vulnerable children are highlighted, many of which pose internationally recognised challenges to providers aiming to deliver safe care to this at-risk cohort. We encourage healthcare organisations globally to build on our findings and explore the safety and reliability of their healthcare systems, in order to sustainably mitigate harm to vulnerable children. © Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.OBJECTIVE To determine the safety of ceftriaxone in paediatric patients and systematically evaluate the categories and incidences of adverse drug reactions (ADRs) of ceftriaxone in paediatric patients. METHODS We performed a systematic search in Medline, PubMed, Cochrane Central Register of Controlled Trials, EMBASE, CINAHL, International Pharmaceutical Abstracts and bibliographies of relevant articles up to December 2018 for all types of studies that assessed the safety of ceftriaxone in paediatric patients aged ≤18 years. RESULTS 112 studies met the inclusion criteria involving 5717 paediatric patients who received ceftriaxone and reported 1136 ADRs. The most frequent ADRs reported in prospective studies were gastrointestinal (GI) disorders (37.4 %, 292/780), followed by hepatobiliary disorders (24.6%, 192/780). Serious ADRs leading to withdrawal or discontinuation of ceftriaxone were reported in 86 paediatric patients. Immune haemolytic anaemia (34.9%, 30/86) and biliary pseudolithiasis (26.7%, 23/86) were the two major causes. Haemolytic anaemia following intravenous ceftriaxone led to death in 11 children whose primary disease was sickle cell disease. Almost all biliary pseudolithiasis are reversible. However, the incidence was high affecting one in five paediatric patients (20.7%). CONCLUSIONS GI ADRs are the most common toxicity of ceftriaxone in paediatric patients. Immune haemolytic anaemia and biliary pseudolithiasis are the most serious ADRs and the major reasons for discontinuation of ceftriaxone. Immune haemolytic anaemia is more likely in children with sickle cell disease and may cause death. Ceftriaxone should be used with caution in children with sickle cell disease. TRIAL REGISTRATION NUMBER CRD42017055428. © 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.A major challenge in modern biology is to understand how naturally occurring variation in DNA sequences affects complex organismal traits through networks of intermediate molecular phenotypes. This question is best addressed in a genetic mapping population in which all molecular polymorphisms are known and for which molecular endophenotypes and complex traits are assessed on the same genotypes. Here, we performed deep RNA sequencing of 200 Drosophila Genetic Reference Panel inbred lines with complete genome sequences and for which phenotypes of many quantitative traits have been evaluated. We mapped expression quantitative trait loci for annotated genes, novel transcribed regions, transposable elements, and microbial species. We identified host variants that affect expression of transposable elements, independent of their copy number, as well as microbiome composition. We constructed sex-specific expression quantitative trait locus regulatory networks. These networks are enriched for novel transcribed regions and target genes in heterochromatin and euchromatic regions of reduced recombination, as well as genes regulating transposable element expression.