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To compare the effectiveness and safety of off-label underdosed apixaban with on-label standard dose apixaban in Asian patients with atrial fibrillation (AF).<br /><br /> Using the Korean nationwide claims database, we identified patients who were prescribed apixaban and did not fulfil the dose reduction criteria for apixaban between January 2015 and December 2017. A multivariable Cox hazard regression model was performed, and hazard ratios (HRs) for ischemic stroke, major bleeding (MB), all-cause death, and composite outcome were analysed. Compared to patients prescribed on-label standard dose apixaban (n = 4,194), patients prescribed off-label underdosed apixaban (n = 2,890) showed a higher risk of ischemic stroke (adjusted HR [aHR], 1.38; 95% confidence interval [CI], 1.06-1.81), all-cause death (aHR, 1.19; 95% CI, 1.01-1.39), and the composite outcome (aHR, 1.17; 95% CI, 1.03-1.34), but with no significant differences in MB between the two groups. Among the patients who did not meet any dose reduction criteria, o clinical outcomes for Asian patients with AF.CD4 expression identifies a subset of mature T cells primarily assisting the germinal center reaction and contributing to CD8+ T-cell and B-cell activation, functions, and longevity. Herein, we present a family in which a novel variant disrupting the translation-initiation codon of the CD4 gene resulted in complete loss of membrane and plasma soluble CD4 in peripheral blood, lymph node, bone marrow, skin, and ileum of a homozygous proband. This inherited CD4 knockout disease illustrates the clinical and immunological features of a complete deficiency of any functional component of CD4 and its similarities and differences with other clinical models of primary or acquired loss of CD4+ T cells. The first inherited loss of any functional component of CD4, including soluble CD4, is clinically distinct from any other congenital or acquired CD4 T-cell defect and characterized by compensatory changes in T-cell subsets and functional impairment of B cells, monocytes, and natural killer cells.<br /><br /> Systemic sclerosis (SSc) is an autoimmune disease characterized by peripheral vasculopathy and skin and internal organ fibrosis. Accumulating evidence underlines a close association between a metabolic reprogramming of activated fibroblasts and fibrosis. This prompted us to determine the metabolism of SSc dermal fibroblasts and the effect on the vasculopathy characterizing the disease.<br /><br /> Seahorse XF96 Extracellular Flux Analyzer was exploited to evaluate SSc fibroblast metabolism. In vitro invasion and capillary morphogenesis assays were used to determine the angiogenic ability of endothelial cells (EC). Immunofluorescence, flow cytometer and real time PCR techniques provided evidence of the molecular mechanism behind the impaired vascularization that characterizes SSc patients.<br /><br /> SSc fibroblasts, compared with control, showed a boosted glycolytic metabolism with increased lactic acid release and subsequent extracellular acidification, that in turn was found to impair EC invasion and organization in capillary-like networks without altering cell viability. A molecular link between extracellular acidosis and endothelial dysfunction was identified as acidic EC up-regulated MMP-12 which cleaves and inactivates uPAR, impairing angiogenesis in SSc. [https://www.selleckchem.com/products/FK-506-(Tacrolimus).html selleck products] Moreover, the acidic environment was found to induce the loss of endothelial markers and the acquisition of mesenchymal-like features in EC, thus promoting the endothelial-to-mesenchymal transition (EndoMT) process that contributes to both capillary rarefaction and tissue fibrosis in SSc.<br /><br /> This study disclosed a liaison among the metabolic reprogramming of SSc dermal fibroblasts, extracellular acidosis and endothelial dysfunction that may contribute to the impairment and loss of peripheral capillary networks in SSc disease.<br /><br />This study disclosed a liaison among the metabolic reprogramming of SSc dermal fibroblasts, extracellular acidosis and endothelial dysfunction that may contribute to the impairment and loss of peripheral capillary networks in SSc disease.<br /><br /> To analyse the available evidence about the use of rituximab (RTX) and other biologic agents in eosinophilic granulomatosis with polyangiitis (EGPA) patients and to provide useful findings to inform the design of future, reliable clinical trials.<br /><br /> A systematic review was performed. A systematic search was conducted in PubMed/MEDLINE, Scopus, Web of Science and the Cochrane library databases on RTX, and an extensive literature search was conducted on other biologic agents.<br /><br /> Forty-five papers pertinent to our questions were found 16 retrospective cohort studies, 8 case series, 3 prospective cohort studies and 18 single case reports, for a total of 368 EGPA patients. More than 80% of evaluable patients achieved complete or partial remission with a tendency towards a higher rate of complete response in the pANCA-positive subgroup.<br /><br /> Although the majority of the evaluable EGPA patients treated with RTX appears to achieve complete remission, we strongly believe that a number of sources of heterogeneity impair a clear interpretation of results and limit their transferability in clinical practice. Differences in design, enrolment criteria, outcome definition and measurement make a comparison among data obtained from studies on RTX and other biologic agents unreliable.<br /><br />Although the majority of the evaluable EGPA patients treated with RTX appears to achieve complete remission, we strongly believe that a number of sources of heterogeneity impair a clear interpretation of results and limit their transferability in clinical practice. Differences in design, enrolment criteria, outcome definition and measurement make a comparison among data obtained from studies on RTX and other biologic agents unreliable.<br /><br /> Metagenomics has revolutionized microbiome research by enabling researchers to characterize the composition of complex microbial communities. Taxonomic profiling is one of the critical steps in metagenomic analyses. Marker genes, which are single-copy and universally found across Bacteria and Archaea, can provide accurate estimates of taxon abundances in the sample.<br /><br /> We present TIPP2, a marker gene-based abundance profiling method, that combines phylogenetic placement with statistical techniques to control classification precision and recall. TIPP2 includes an updated set of reference packages and several algorithmic improvements over the original TIPP method. We find that TIPP2 provides comparable or better estimates of abundance than other profiling methods (including Bracken, mOTUsv2, and MetaPhlAn2), and strictly dominates other methods when there are under-represented (novel) genomes present in the dataset.<br /><br /> The code for our method is freely available in open source form at https//github.com/smirarab/sepp/blob/tipp2/README.