Diastereoselective synthesis of tetrahydropyrrolo[1,2-]oxadiazoles from functionalized Δ-pyrrolines and generated nitrile oxides.

Tetrahydropyrrolo[1,2-]oxadiazoles have been synthesized in good-to-excellent yields the cycloaddition of nitrile oxides ( generated from aldoximes) to readily accessible functionalized Δ-pyrrolines. The reaction proceeds smoothly at room temperature in a two-phase system in the presence of sodium hypochloride as an oxidant to diastereoselectively afford pharmaceutically prospective 1,2,4-oxadiazolines fused with a five-membered ring. The reaction tolerates a broad range of substrates, including those with oxidant-sensitive functional groups and competitive reaction sites.

Evaporative loss and environmental impact of covers on water storages: A review.

Commercial products to reduce evaporation from water storages have been developed since the 1960s. Categorised as suspended and floating continuous covers, floating modular covers, and monomolecular (monolayer) and multimolecular chemical films, product adoption by agricultural water managers is low. The role of evaporation reduction in improving water use efficiency is well established, but information on the suitability of product categories for farm water storages is lacking.

Aging-associated augmentation of gut microbiome virulence capability drives sepsis severity.

Unlabelled: Prior research has focused on host factors as mediators of exaggerated sepsis-associated morbidity and mortality in older adults. This focus on the host, however, has failed to identify therapies that improve sepsis outcomes in the elderly. We hypothesized that the increased susceptibility of the aging population to sepsis is not only a function of the host, but also reflects longevity-associated changes in the virulence of gut pathobionts.

Truchet-tile structure of a topologically aperiodic metal-organic framework.

When tiles decorated to lower their symmetry are joined together, they can form aperiodic and labyrinthine patterns. Such Truchet tilings offer an efficient mechanism of visual data storage related to that used in barcodes and QR codes. We show that the crystalline metal-organic framework [OZn][1,3-benzenedicarboxylate] (TRUMOF-1) is an atomic-scale realization of a complex three-dimensional Truchet tiling.

Phase 1, open-label, dose-escalation study on the safety, pharmacokinetics, and preliminary efficacy of intravenous Coxsackievirus A21 (V937), with or without pembrolizumab, in patients with advanced solid tumors.

Background: Oncolytic virus V937 showed activity and safety with intratumoral administration. This phase 1 study evaluated intravenous V937±pembrolizumab in patients with advanced solid tumors.

Methods: Patients had advanced non-small cell lung cancer (NSCLC), urothelial cancer, metastatic castration-resistant prostate cancer, or melanoma in part A (V937 monotherapy), and metastatic NSCLC or urothelial cancer in part B (V937+pembrolizumab).

["That One Can See How it is Supposed to be." Conception, Piloting and Evaluation of an Interprofessional Rehabilitation-Related Module for the Training Courses in Medicine, Nursing, and Physiotherapy].

Background: Considering the growing rehabilitative care requirements, good interprofessional cooperation is of central relevance for health care professions and is increasingly demanded. Interprofessional cooperation does not yet play a significant role in health professions' education, despite the fact that it is considered an important element of success in outcome- and patient-centered health care. The field of rehabilitation lacks interprofessional teaching concepts and material.

Thioredoxin reductase 1 regulates hepatic inflammation and macrophage activation during acute cholestatic liver injury.

Background And Aims: Cholestatic liver diseases, including primary sclerosing cholangitis, are characterized by periportal inflammation with progression to hepatic fibrosis and ultimately cirrhosis. We recently reported that the thioredoxin antioxidant response is dysregulated during primary sclerosing cholangitis. The objective of this study was to examine the impact of genetic and pharmacological targeting of thioredoxin reductase 1 (TrxR1) on hepatic inflammation and liver injury during acute cholestatic injury.

Characteristics Associated With Refractory Course, Blindness, and Treatment Strategy-Related Outcomes in Patients With Mucous Membrane Pemphigoid.

Importance: Mucous membrane pemphigoid (MMP) is a rare and heterogeneous subepithelial autoimmune bullous disease with predominant mucosal involvement. Characteristics associated with the disease course and complications are yet to be delineated.

Objectives: To evaluate characteristics associated with refractory disease course and blindness among patients with MMP and to estimate the association of different treatment strategies with the prognostic outcome.

[Fracture sequelae type 2 of the proximal humerus-clinical results after arthroplasty].

Locked dislocations of the glenohumeral joint are rare but often painful and are associated with limited range of motion in the shoulder. In patients of advanced age, arthroplasty is increasingly indicated as a surgical treatment option. Preoperatively, the direction of dislocation, the presence and extent of a glenoid defect, and the soft tissue situation (rotator cuff status, joint capsule) should be analyzed in a differentiated manner.

Apremilast prevents blistering in human epidermis and stabilizes keratinocyte adhesion in pemphigus.

Pemphigus vulgaris is a life-threatening blistering skin disease caused by autoantibodies destabilizing desmosomal adhesion. Current therapies focus on suppression of autoantibody formation and thus treatments directly stabilizing keratinocyte adhesion would fulfill an unmet medical need. We here demonstrate that apremilast, a phosphodiesterase 4 inhibitor used in psoriasis, prevents skin blistering in pemphigus vulgaris.

A Phase Ib/II Study of Lenvatinib and Pembrolizumab in Advanced Endometrial Carcinoma (Study 111/KEYNOTE-146): Long-Term Efficacy and Safety Update.

JCO The open-label phase Ib/II Study 111/KEYNOTE-146 of daily lenvatinib 20 mg plus pembrolizumab 200 mg once every 3 weeks showed promising efficacy and tolerable safety in patients with previously treated advanced endometrial carcinoma (EC; primary data cutoff date: January 10, 2019). This updated analysis reports long-term follow-up efficacy and safety data from 108 patients with previously treated EC included in the primary analysis. End points included objective response rate, duration of response, progression-free survival, overall survival, and safety.

Overview of stab injuries in Far North Queensland: A new insight into the demographics, injury patterns and management.

Background: Cairns Hospital is the northernmost tertiary referral hospital in Far North Queensland (FNQ) and manages trauma from a large catchment area. A large burden of stab injuries occurs in at-risk patient groups, such as Indigenous and mental health patients, in this region. This research aims to present an overview of the demographics, injury patterns, management and outcomes for stabbings injuries in FNQ.

Meeting report - Desmosome dysfunction and disease: Alpine desmosome disease meeting.

Desmosome diseases are caused by dysfunction of desmosomes, which anchor intermediate filaments (IFs) at sites of cell-cell adhesion. For many decades, the focus of attention has been on the role of actin filament-associated adherens junctions in development and disease, especially cancer. However, interference with the function of desmosomes, their molecular constituents or their attachments to IFs has now emerged as a major contributor to a variety of diseases affecting different tissues and organs including skin, heart and the digestive tract.

Intake of marine and plant-derived n-3 fatty acids and development of atherosclerotic cardiovascular disease in the Danish Diet, Cancer and Health cohort.

Purpose: The objective of this study was to investigate the association between intake of seafood and plant-derived n-3 polyunsaturated fatty acids (PUFA) and development of total atherosclerotic cardiovascular disease (ASCVD) and acute major ischemic events.

Methods: A total of 53,909 men and women were enrolled between 1993 and 1997 into the Danish Diet, Cancer and Health cohort and followed through nationwide Danish registries for development of total ASCVD defined as a first registration of myocardial infarction, peripheral artery disease, or ischemic stroke due to large artery atherosclerosis or small-vessel occlusion. At recruitment, the intake of the major marine n-3 PUFA, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and the plant-derived n-3 PUFA, alpha-linolenic acid (ALA), was assessed using a validated food frequency questionnaire.

The acoustic realization of contrastive focus by 6-year-old Australian English-speaking children.

Children as young as five have some ability to produce contrastive focus [Wells et al. (2004) J. Child Lang.

Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.

Background: Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery.

Results: To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches.

Abnormalities of the Eyelashes in Turner's Syndrome.

Turner's syndrome (TS) is a sex chromosome disorder caused by a partial loss, complete absence or structural abnormality of one X chromosome in females. Special ocular features are often found. Some of the abnormalities are only cosmetic, such as the abnormalities of the eyelashes.

Part one: abuse liability of Vuse Solo (G2) electronic nicotine delivery system relative to combustible cigarettes and nicotine gum.

Abuse liability (AL) of electronic nicotine delivery systems (ENDS) is relevant as the category increases in popularity as a potentially less-harmful alternative to cigarette smoking. AL assessments are important to the FDA in determining if a new product is appropriate for the protection of public health. This paper reports the results for Vuse Solo (G2 cartridge design) compared to high and low AL-comparators evaluated in an open-label, randomized crossover confinement AL study.

Evaluating the impact of alternative intervention strategies in accelerating onchocerciasis elimination in an area of persistent transmission in the West Region of Cameroon.

Background: Alternative strategies are recommended to accelerate onchocerciasis elimination in problematic areas including areas where annual ivermectin (IVM) distributions are unable to interrupt transmission. The aim of this study was to accelerate progress towards elimination in the Massangam health district, West Region of Cameroon where impact evaluations demonstrated ongoing transmission of onchocerciasis infection and high microfilaria (mf) prevalence despite more than 20 years of annual IVM distribution.

Methodology/principal Findings: Parasitological, entomological, and breeding site surveys were conducted in 2015 delineating a focus of high transmission and identified three communities with high mf prevalence.

Corrigendum: Cutaneous kinase activity correlates with treatment outcomes following PI3K delta inhibition in mice with experimental pemphigoid diseases.

[This corrects the article DOI: 10.3389/fimmu.2022.

Analysis of T cell repertoires of CD45RO CD4 T cells in cohorts of patients with bullous pemphigoid: A pilot study.

Autoimmune diseases develop over years - starting from a subclinical phenotype to clinically manifest autoimmune disease. The factors that drive this transition are ill-defined. To predict the turning point towards clinical disease and to intervene in the progress of autoimmune-mediated dysfunction, the establishment of new biomarkers is needed.