Explore the vast range of titles available.

Objectives To determine the impact of the COVID-19 pandemic on the incidence rates of infection and islet autoimmunity in children at risk for type 1 diabetes. Methods 1050 children aged 4 to 7 months with an elevated genetic risk for type 1 diabetes were recruited from Germany, Poland, Sweden, Belgium and the UK. Reported infection episodes and islet autoantibody development were monitored until age 40 months from February 2018 to February 2023. Results The overall infection rate was 311 (95% Confidence Interval [CI], 304–318) per 100 person years. Infection rates differed by age, country, family history of type 1 diabetes, and period relative to the pandemic. Total infection rates were 321 per 100 person-years (95% CI 304–338) in the pre-pandemic period (until February 2020), 160 (95% CI 148–173) per 100 person-years in the first pandemic year (March 2020—February 2021; P  < 0.001) and 337 (95% CI 315–363) per 100 person-years in subsequent years. Similar trends were observed for respiratory and gastrointestinal infections. Islet autoantibody incidence rates were 1.6 (95% CI 1.0–2.4) per 100 person-years in the pre-pandemic period, 1.2 (95% CI 0.8–1.9) per 100 person-years in the first pandemic year ( P  = 0.46), and 3.4 (95% CI 2.3–4.8) per 100 person-years in subsequent years ( P  = 0.005 vs. pre-pandemic year; P  < 0.001 vs. first pandemic year). Conclusions The COVID-19 pandemic was associated with significantly altered infection patterns. Islet autoantibody incidence rates increased two-fold when infection rates returned to pre-pandemic levels.

IntroductionThe Global Platform for the Prevention of Autoimmune Diabetes-SINT1A Study is designed as a randomised, placebo-controlled, double-blind, multicentre, multinational, primary prevention study aiming to assess whether daily administration of Bifidobacterium infantis from age 7 days to 6 weeks until age 12 months to children with elevated genetic risk for type 1 diabetes reduces the cumulative incidence of beta-cell autoantibodies in childhood.Methods and analysisInfants aged 7 days to 6 weeks from Germany, Poland, Belgium, UK and Sweden are eligible for study participation if they have a >10.0% expected risk for developing multiple beta-cell autoantibodies by age 6 years as determined by genetic risk score or family history and HLA genotype. Infants are randomised 1:1 to daily administration of B. infantis EVC001 or placebo until age 12 months and followed for a maximum of 5.5 years thereafter. The primary outcome is the development of persistent confirmed multiple beta-cell autoantibodies. Secondary outcomes are (1) Any persistent confirmed beta-cell autoantibody, defined as at least one confirmed autoantibody in two consecutive samples, including insulin autoantibodies, glutamic acid decarboxylase, islet tyrosine phosphatase 2 or zinc transporter 8, (2) Diabetes, (3) Transglutaminase autoantibodies associated with coeliac disease, (4) Respiratory infection rate in first year of life during supplementation and (5) Safety. Exploratory outcomes include allergy, antibody response to vaccines, alterations of the gut microbiome or blood metabolome, stool pH and calprotectin.Ethics and disseminationThe study was approved by the local ethical committees of the Technical University Munich, Medical Faculty, the Technische Universität Dresden, the Medizinische Hochschule Hannover, the Medical University of Warsaw, EC Research UZ Leuven and the Swedish ethical review authority. The results will be disseminated through peer-reviewed journals and conference presentations and will be openly shared after completion of the study.Trial registration numberNCT04769037.

IntroductionThe identification of type 1 diabetes at an early presymptomatic stage has clinical benefits. These include a reduced risk of diabetic ketoacidosis (DKA) at the clinical manifestation of the disease and a significant reduction in clinical symptoms. The European action for the Diagnosis of Early Non-clinical Type 1 diabetes For disease Interception (EDENT1FI) represents a pioneering effort to advance early detection of type 1 diabetes through public health screening. With the EDENT1FI Master Protocol, the project aims to harmonise and standardise screening for early-stage type 1 diabetes and care.Methods and analysisPublic health islet autoantibody screening is conducted in the Czech Republic, Denmark, Germany, Italy, Poland, Portugal, Sweden and the UK. Between November 2023 (start date) and October 2028 (planned end date), an estimated number of 200 000 children and adolescents aged 1–17 years are expected to be screened. Screening is performed in capillary blood, examining different islet autoantibodies (autoantibodies against insulin, glutamic acid decarboxylase-65, insulinoma-associated antigen-2 and/or zinc transporter-8). Positive screening results undergo confirmation through a second antibody method. A second (venous) blood sample is requested if at least two autoantibodies are detected, to confirm the autoantibody status. Children and adolescents with confirmed two or more autoantibodies are invited to metabolic staging (oral glucose tolerance test, haemoglobin A1c (HbA1c), random glucose, optionally continuous glucose monitoring); an educational programme and recommendations for monitoring are provided. The feasibility and acceptability of screening are evaluated by feedback questionnaires. Pseudonymised data is collated in the EDENT1FI Registry. Study outcomes include country-specific screening rates, prevalences of stage 1 and stage 2 type 1 diabetes, number in EDENT1FI Registry, proportion with DKA and symptoms at clinical diagnosis and median HbA1c.Ethics and disseminationFollowing the EDENT1FI Master Protocol, site-specific protocols are developed and approved by local ethics committees (Technical University of Munich, Medical Faculty, Nr. 70/14; Medizinische Hochschule Hannover, Nr. 9588_BO_S_2021; Technische Universität Dresden, Nr. BO-EK-356082020; Center for Sundhed Region Hovedstaden, Nr. H-22053116; Swedish Ethical Review Authority, Nr. 2023-00312-01; National Health Service Health Research Authority and Health Care Research Wales, IRAS (Integrated Research Application System) project ID 309252; Italian National Institute of Health, National ethics committee for clinical trials of public research bodies (EPR) and other national public institutions, Prot. PRE BIO CE Nr. 0059835; Charles University in Prague, Ethics Committee for Multi-Centric Clinical Trials of the University Hopital Motol and 2nd Faculty of Medicine, Nr. 1271/23; Bioethics Committee at the Medical University of Warsaw, Nr. 21/2024 and KB/6/R/2024; Associação Protectora dos Diabéticos de Portugal, Nr. 211/2024). Results are disseminated through peer-reviewed journals and conference presentations and will be shared openly.

Very few B cells in germinal centers (GCs) and extrafollicular (EF) regions of lymph nodes express CD30. Their specific features and relationship to CD30-expressing Hodgkin and Reed/Sternberg (HRS) cells of Hodgkin lymphoma are unclear but highly relevant, because numerous patients with lymphoma are currently treated with an anti-CD30 immunotoxin. We performed a comprehensive analysis of human CD30+ B cells. Phenotypic and IgV gene analyses indicated that CD30+ GC B lymphocytes represent typical GC B cells, and that CD30+ EF B cells are mostly post-GC B cells. The transcriptomes of CD30+ GC and EF B cells largely overlapped, sharing a strong MYC signature, but were strikingly different from conventional GC B cells and memory B and plasma cells, respectively. CD30+ GC B cells represent MYC+ centrocytes redifferentiating into centroblasts; CD30+ EF B cells represent active, proliferating memory B cells. HRS cells shared typical transcriptome patterns with CD30+ B cells, suggesting that they originate from these lymphocytes or acquire their characteristic features during lymphomagenesis. By comparing HRS to normal CD30+ B cells we redefined aberrant and disease-specific features of HRS cells. A remarkable downregulation of genes regulating genomic stability and cytokinesis in HRS cells may explain their genomic instability and multinuclearity.

Very few B cells in germinal centers (GCs) and extrafollicular (EF) regions of lymph nodes express CD30. Their specific features and relationship to [CD30.sup.-]expressing Hodgkin and Reed/Sternberg (HRS) cells of Hodgkin lymphoma are unclear but highly relevant, because numerous patients with lymphoma are currently treated with an anti-CD30 immunotoxin. We performed a comprehensive analysis of human [CD30.sup.+] B cells. Phenotypic and IgV gene analyses indicated that [CD30.sup.+] GC B lymphocytes represent typical GC B cells, and that [CD30.sup.+] EF B cells are mostly post-GC B cells. The transcriptomes of [CD30.sup.+] GC and EF B cells largely overlapped, sharing a strong MYC signature, but were strikingly different from conventional GC B cells and memory B and plasma cells, respectively. [CD30.sup.+] GC B cells represent [MYC.sup.+] centrocytes redifferentiating into centroblasts; [CD30.sup.+] EF B cells represent active, proliferating memory B cells. HRS cells shared typical transcriptome patterns with [CD30.sup.+] B cells, suggesting that they originate from these lymphocytes or acquire their characteristic features during lymphomagenesis. By comparing HRS to normal [CD30.sup.+] B cells we redefined aberrant and disease-specific features of HRS cells. A remarkable downregulation of genes regulating genomic stability and cytokinesis in HRS cells may explain their genomic instability and multinuclearity.