en  0.001), which was reflected by a task-specific increase in IS MVC (+49%, p = 0.001), but not KE (+1%, p = 0.882). However, no training-induced changes were observed in muscle thickness (p = 0.468) or any evoked responses (p = 0.141). Adjustments in spinal motoneuronal excitability are evident after acute resistance training. After a period of short-term training, there were no changes in the responses to central nervous system stimulation, which suggests that alterations in corticospinal properties of the vastus lateralis might not contribute to increases in strength. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.BACKGROUND High inter-individual variability in therapeutic response to drugs used in the management of Inflammatory Bowel Disease (IBD) leads to high morbidity and high costs. Genetic variants predictive of thiopurine-induced myelosuppression, thiopurine-induced pancreatitis and immunogenicity of Tumour Necrosis Factor alpha (TNFα) antagonists have been identified, but uptake of pre-treatment pharmacogenetic testing into clinical guidelines has been slow. AIM To explore the efficacy of a pharmacogenetic passport for IBD that includes multiple pharmacogenetic predictors of response. METHODS Patients with IBD exposed to thiopurines and/or TNFα antagonists were retrospectively evaluated for the presence of thiopurine toxicity and/or immunogenicity of TNFα antagonists. All patients were genotyped using both whole-exome sequencing and the Illumina Global Screening Array. An in-house-developed computational pipeline translated genetic data into an IBD pharmacogenetic passport that predicted risks for thiopurine toxicity and immunogenicity of TNFα antagonists per patient. Using pharmacogenetic-guided treatment guidelines, we calculated clinical efficacy estimates for pharmacogenetic testing for IBD. RESULTS Among 710 patients with IBD exposed to thiopurines and/or TNFα antagonists, 150 adverse drug responses occurred and our pharmacogenetic passport would have predicted 54 (36%) of these. Using a pharmacogenetic passport for IBD that includes genetic variants predictive of thiopurine-induced myelosuppression, thiopurine-induced pancreatitis, and immunogenicity of TNFα antagonists, 24 patients need to be genotyped to prevent one of these adverse drug responses. CONCLUSIONS This study highlights the clinical efficacy of a pharmacogenetic passport for IBD. Implementation of such a pharmacogenetic passport into clinical management of IBD may contribute to a reduction in adverse drug responses. © 2020 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.AIMS Globally, nearly half of the patients with type 2 diabetes (T2DM) do not successfully achieve target HbA1c with basal insulin, despite meeting fasting plasma glucose (FPG) targets. In this post hoc analysis of the LixiLan-L study, we determined whether iGlarLixi, a fixed-ratio combination of insulin glargine Gla-100 (iGlar) and the glucagon-like peptide-1 receptor agonist lixisenatide (Lixi), addresses the challenge of reducing residual hyperglycemia in patients with T2DM. MATERIALS AND METHODS In LixiLan-L, a randomized, open-label study (NCT02058160), 1018 patients with T2DM on basal insulin for ≥6 months ± oral antidiabetes drugs entered a 6-week run-in period, during which they were switched to and/or optimized for a daily dose of iGlar while continuing only metformin. Post run-in period, 736 patients were then randomized to receive iGlarLixi or were continued on iGlar for 30 weeks ± metformin. Residual hyperglycemia was defined as HbA1c ≥ 7.0% despite an FPG less then 140 mg/dL. RESULTS The proportion of patients with residual hyperglycemia was similar in both treatment arms at screening (~42%), and increased post run-in period (~62%). After 30 weeks, the proportion of patients with residual hyperglycemia declined to 23.8% in the iGlarLixi vs. 47.1% in the iGlar arm (p less then 0.0001). The proportion of patients achieving both HbA1c ( less then 7.0%) and FPG ( less then 140 mg/dL) targets was higher in the iGlarLixi compared with the iGlar arm (50.3% vs. 27.4%, respectively, p less then 0.0001). CONCLUSION iGlarLixi effectively reduces residual hyperglycemia in patients with T2DM on basal insulin therapy. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.Fibroblasts are a key component of the tumor microenvironment (TME) that can serve as a scaffold for tumor cell migration and augment the tumor’s ability to withstand harsh conditions. When activated by external or endogenous stimuli, normal fibroblasts become cancer associated fibroblasts (CAFs), a heterogeneous group of stromal cells in the tumor that are phenotypically and epigenetically different from normal fibroblasts. Dynamic crosstalk between cancer cells, immune cells, and CAFs through chemokines and surface signaling makes the TME conducive to tumor growth. When activated, CAFs promote tumorigenesis and metastasis through several phenomena including regulation of tumor immunity, metabolic reprogramming of the TME, extracellular matrix remodeling and contraction, and induction of therapeutic resistance. Ionizing radiation (radiation theraphy [RT]) is a potent immunological stimulant that has been shown to increase cytotoxic Teff infiltration and IFN-I stimulated genes. RT, however, is unable to overcome the infiltration and activation of immunosuppressive cells which can contribute to tumor progression. Another paradox of RT is that, while very effective at killing cancer cells, it can contribute to the formation of CAFs. This review examines how the interplay between CAFs and immune cells during RT contributes to organ fibrosis, immunosuppression, and tumor growth. We focus on targeting mechanistic pathways of CAF formation as a potentially effective strategy not only for preventing organ fibrosis, but also in hampering tumor progression in response to RT. © 2020 Wiley Periodicals, Inc.Fragment-based lead discovery has become a fundamental approach to identify ligands that efficiently interact with disease-relevant targets. Among the numerous screening techniques, fluorine-detected NMR has gained popularity owing to its high sensitivity, robustness, and ease of use. To effectively explore chemical space, a universal NMR experiment, a rationally designed fragment library, and a sample composition optimized for a maximal number of compounds and minimal measurement time are required. Here, we introduce a comprehensive method that enabled the efficient assembly of a high-quality and diverse library containing nearly 4000 fragments and screening for target-specific binders within days. At the core of the approach is a novel broadband relaxation-edited NMR experiment that covers the entire chemical shift range of drug-like 19F motifs in a single measurement. Our approach facilitates the identification of diverse binders and the fast ligandability assessment of new targets. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.Lithium-chalcogen batteries are an appealing choice for high-energy-storage technology. However, the traditional battery that employs liquid electrolytes suffers irreversible loss and shuttle of the soluble intermediates. New batteries that adopt Li+ -conductive polymer electrolytes to mitigate the shuttle problem are hindered by incomplete discharge of sulfur/selenium. To address the trade-off between energy and cycle life, a new electrolyte is proposed that reconciles the merits of liquid and polymer electrolytes while resolving each of their inferiorities. An in situ interfacial polymerization strategy is developed to create a liquid/polymer hybrid electrolyte between a LiPF6 -coated separator and the cathode. A polymer-gel electrolyte in situ formed on the separator shows high Li+ transfer number to serve as a chemical barrier against the shuttle effect. Between the gel electrolyte and the cathode surface is a thin gradient solidification layer that enables transformation from gel to liquid so that the liquid electrolyte is maintained inside the cathode for rapid Li+ transport and high utilization of active materials. By addressing the dilemma between the shuttle chemistry and incomplete discharge of S/Se, the new electrolyte configuration demonstrates its feasibility to trigger higher capacity retention of the cathodes. As a result, Li-S and Li-Se cells with high energy and long cycle lives are realized, showing promise for practical use. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.BACKGROUND To determine whether discontinuing the Undergraduate Medicine and Health Sciences Admissions Test (UMAT) in 2011 for selection and changes to the South Australian Certificate of Education (SACE) requirements in 2012 when the new Australian Tertiary Admissions Rank (ATAR) was introduced, impacted on students’ accumulative level of achievement and performance in the Bachelor of Oral Health (BOH) program. METHODS Board of Examiner’s course results for end of year performance were collected for BOH cohorts 2006 to 2017 (n=347). Overall performance and achievement level attained were calculated and formed the dependent variables, Performance and Achievement. Group-based trajectory modelling (GBTM) characterised trajectories of yearly academic achievement and the likelihood of each case belonging to the latent group classified as individual group membership. Chi square (or Fischer’s Exact) tests were conducted on groups and selected independent variables, using SAS 9.4. RESULTS A 2-group academic Performance trajectory was selected as Consistent (n=290; (83.6%) and Inconsistent (n=57; 16.4%) and Achievement level (credit number) trajectory as Low (n=154; 44.4%), and High (n=193; 55.6%). Statistically significant findings in relation to achievement level were found; female students, those who enrolled after UMAT was discontinued, students enrolled since SACE changes, and those who nominated BOH as their first career preference, were more likely to achieve higher grades than their counterparts. CONCLUSION Discontinuing the UMAT for selection and SACE changes have shown no adverse changes in students’ level of achievement in the BOH program, although enrolling in a course not their first preference was shown to affect performance level. This article is protected by copyright. All rights reserved.The present work aimed to study the anatomy, histology, cytology and some biochemical parameters (urea, osmolality, haematocrit, serum natrium, serum kalium) of the kidney of Gerbillus tarabuli. The investigated animals (n = 16) were collected from the desert, weighed and transferred alive to the laboratory in separate cages. A blood sample was taken by puncture at the retro-orbital sinus of each animal using a Pasteur-type capillary pipette capillary. They were anaesthetized with urethane injection (25%), after which they were carefully dissected; their organs were taken out and prepared for the histological and cytological studies. Pasteur pipette capillary type the kidney of the Gerbillus tarabuli is subdivided into three regions Cortex (1193.625±60μm), Outer Medulla (1316.72±73μm), Inner Medulla (2525.08±85 μm). Pasteur pipette capillary type the kidney of the Gerbillus tarabuli is subdivided into three regions Cortex (1193.625±60μm), Outer Medulla (1316.72±73μm), Inner Medulla (2525.08±85 μm). The concentration of the biochemical parameters of urea (0.