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Background Intestinal dendritic cells (DC) and macrophages drive disease progression in patients with inflammatory bowel disease (IBD). We aimed to characterize the activation and homing profile of human circulating DC and monocyte subsets in healthy control patients (CP) and IBD patients. Methods Eighteen CP and 64 patients with IBD were categorized by diagnoses of Crohn disease (CD) and ulcerative colitis (UC), either endoscopically active (inflamed) or quiescent. Circulating type 1 conventional DC, type 2 conventional DC, plasmacytoid DC, classical monocytes, nonclassical monocytes, and intermediate monocytes were identified by flow cytometry in each individual and characterized for the expression of 18 markers. Association between DC/monocytes and IBD risk was tested by logistic regression. Discriminant canonical analyses were performed to classify the patients in their own endoscopy category considering all markers on each subset. Results CCRL1, CCR3, and CCR5 expression on circulating type 1 DC; CCRL1 expression on nonclassical monocytes; and CCR9 and β7 expression on classical monocytes allowed us to discriminate among the different study groups. Indeed, the same markers (excluding β7) were also associated with IBD when all DC and monocyte subsets were considered at the same time. Conclusions Monitoring the phenotype of human circulating DC and monocyte subsets may provide novel tools as biomarkers for disease diagnosis (CD/UC) or mucosal status (inflamed/noninflamed) in the absence of an invasive colonoscopy.Objective Machine learning (ML) diagnostic tools have significant potential to improve health care. However, methodological pitfalls may affect diagnostic test accuracy studies used to appraise such tools. We aimed to evaluate the prevalence and reporting of design characteristics within the literature. Further, we sought to empirically assess whether design features may be associated with different estimates of diagnostic accuracy. Materials and methods We systematically retrieved 2 × 2 tables (n = 281) describing the performance of ML diagnostic tools, derived from 114 publications in 38 meta-analyses, from PubMed. Data extracted included test performance, sample sizes, and design features. A mixed-effects metaregression was run to quantify the association between design features and diagnostic accuracy. Results Participant ethnicity and blinding in test interpretation was unreported in 90% and 60% of studies, respectively. Reporting was occasionally lacking for rudimentary characteristics such as study design (28% unreported). Internal validation without appropriate safeguards was used in 44% of studies. Several design features were associated with larger estimates of accuracy, including having unreported (relative diagnostic odds ratio [RDOR], 2.11; 95% confidence interval [CI], 1.43-3.1) or case-control study designs (RDOR, 1.27; 95% CI, 0.97-1.66), and recruiting participants for the index test (RDOR, 1.67; 95% CI, 1.08-2.59). Discussion Significant underreporting of experimental details was present. Study design features may affect estimates of diagnostic performance in the ML diagnostic test accuracy literature. Conclusions The present study identifies pitfalls that threaten the validity, generalizability, and clinical value of ML diagnostic tools and provides recommendations for improvement.Aim The impact of sex differences on the clinical outcomes of radiofrequency catheter ablation (RFCA) of atrial fibrillation (AF) is controversial. We investigated the sex differences regarding the efficacy and clinical outcomes of RFCA of AF. Methods and results We conducted a large-scale, prospective, multicentre, observational study (Kansai Plus Atrial Fibrillation Registry). We enrolled 5010 consecutive patients who underwent an initial RFCA of AF at 26 centres (64 ± 10 years; non-paroxysmal AF, 35.7%). The median follow-up duration was 2.9 years. Female patients (n = 1369, 27.3%) were older (female vs. male, 68 ± 9 vs. 63 ± 11 years, P less then 0.0001) with a lower prevalence of non-paroxysmal AF (27.1% vs. 38.9%, P less then 0.0001). Fewer females experienced time-dependent pulmonary vein (PV) reconnections and more females received a non-PV foci ablation than males in the index RFCA. [https://www.selleckchem.com/products/c188-9.html selleck chemical] The 3-year cumulative incidence of AF recurrences in the multivariate analysis after single procedures was significantly higher in females than males (43.3% vs. 39.0%, log rank P = 0.0046). Females remained an independent predictor of AF recurrence (hazard ratio 1.24; 95% confidence interval 1.12-1.38, P less then 0.0001). The AF recurrence rates after multiple procedures were also higher in females, but fewer females experienced PV reconnections during second sessions. More females experienced de novo pacemaker implantations during the long-term follow-up. Females were associated with a higher risk of heart failure hospitalizations and major bleeding after RFCA in the multivariate analysis. Conclusions Females experienced more frequent AF recurrences probably due to non-PV arrhythmogenicity and de novo pacemaker implantations than males during the long-term follow-up after RFCA of AF.Several studies demonstrate that hemolysis and free heme in circulation causes endothelial barrier dysfunction and is associated with severe pathological conditions like acute respiratory distress syndrome, acute chest syndrome, and sepsis. Yet, the precise molecular mechanisms involved in the pathology of heme induced barrier disruption still remains to be elucidated. In this study, we investigated the role of free heme on the endothelial barrier integrity and the mechanisms of heme-mediated intracellular signaling in human lung microvascular endothelial cells (HLMVEC). Heme, in a dose-dependent manner, induced a rapid drop in the endothelial barrier integrity in HLMVEC. An investigation into barrier proteins revealed that heme primarily affects the tight junction proteins, zona occludens-1, claudin-1, and claudin-5, which were significantly reduced after heme exposure. The p38MAPK/HSP27 pathway, involved in the regulation of the endothelial cytoskeleton remodeling, was also significantly altered after heme treatment, both in the HLMVEC and in mice.