EDENT1FI Master Protocol for screening of presymptomatic early-stage type 1 diabetes in children and adolescents.

Introduction: The 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.

CIROZ is dispensable in ancestral vertebrates but essential for left-right patterning in humans.

Four genes-DAND5, PKD1L1, MMP21, and CIROP-form a genetic module that has specifically evolved in vertebrate species that harbor motile cilia in their left-right organizer (LRO). We find here that CIROZ (previously known as C1orf127) is also specifically expressed in the LRO of mice, frogs, and fish, where it encodes a protein with a signal peptide followed by 3 zona pellucida N domains, consistent with extracellular localization. We report 16 individuals from 10 families with bi-allelic CIROZ inactivation variants, which cause heterotaxy with congenital heart defects.

EEFSEC deficiency: A selenopathy with early-onset neurodegeneration.

Inborn errors of selenoprotein expression arise from deleterious variants in genes encoding selenoproteins or selenoprotein biosynthetic factors, some of which are associated with neurodegenerative disorders. This study shows that bi-allelic selenocysteine tRNA-specific eukaryotic elongation factor (EEFSEC) variants cause selenoprotein deficiency, leading to progressive neurodegeneration. EEFSEC deficiency, an autosomal recessive disorder, manifests with global developmental delay, progressive spasticity, ataxia, and seizures.

Thalamic deep brain stimulation for central poststroke pain syndrome: an international multicenter study.

Objective: The effectiveness and optimal stimulation site of deep brain stimulation (DBS) for central poststroke pain (CPSP) remain elusive. The objective of this retrospective international multicenter study was to assess clinical as well as neuroimaging-based predictors of long-term outcomes after DBS for CPSP.

Methods: The authors analyzed patient-based clinical and neuroimaging data of previously published and unpublished cohorts from 6 international DBS centers.

An extra pair of eyes: adopting innovative approaches to detect integrity issues in Naunyn-Schmiedeberg's Archives of Pharmacology.

Scientific integrity has been increasingly challenged by scientific misconduct and paper mills, resulting in an increase in retractions. Naunyn-Schmiedeberg's Archives of Pharmacology has been significantly impacted by fraudulent submissions, resulting in numerous retractions. By analyzing retraction notes and utilizing a post-publication surveillance strategy, this editorial discusses how this journal continues to deal with problematic publications, uncovers image- and physiological-related integrity issues, and responds to fraudulent activity.

AI-assisted Total Body Dermoscopic Evaluation of Changes in Melanocytic Nevi during Pregnancy: A Prospective, Comparative Study of 2,799 Nevi.

Pregnancy-associated changes in melanocytic nevi (MN), apart from size increase on the trunk, remain a topic of debate. We conducted the first prospective study to investigate dermoscopic changes in MN comparing pregnant with non-pregnant women on all body parts using a market-approved convolutional neural network (CNN). We included 25 pregnant and 25 non-pregnant women from Basel, Switzerland, who underwent standard skin cancer screenings and whose MN > 2 mm were digitally recorded and analysed by a CNN.

Predicting prosthetic gait and the effects of induced stiff-knee gait.

Prosthetic gait differs considerably from the unimpaired gait. Studying alterations in the gait patterns could help to understand different adaptation mechanisms adopted by these populations. This study investigated the effects of induced stiff-knee gait (SKG) on prosthetic and healthy gait patterns and the capabilities of predictive simulation.

Unveiling Inequities: Racial Disparities in Risk-Reducing Mastectomy for Breast Cancer Prevention.

Background: Risk-reducing mastectomy (RRM) significantly lowers breast cancer risk as a preventive surgery. While racial disparities in breast cancer treatment are well-documented, research on racial differences in the utilization and outcomes of RRM is limited.

Methods: We retrospectively analyzed the American College of Surgeons National Surgical Quality Improvement Program (2008-2022) to identify women who underwent RRM.

Gut microbiota prevents small intestinal tumor formation due to bile acids in gnotobiotic mice.

The gut microbiota is implicated in the development of intestinal tumors. Furthermore, Western diet is a risk factor for colorectal cancer and induces alterations in both the microbiota and bile acid metabolism. Therefore, we aimed to investigate the causal role of Western diet-induced changes in the microbiota and secondary bile acid production, which were linked to disease exacerbation in pigs.

Primary sclerosing cholangitis in children with inflammatory bowel disease: An ESPGHAN position paper from the Hepatology Committee and the IBD Porto group.

Objective: We aimed to provide an evidence-supported approach to diagnose, monitor, and treat children with inflammatory bowel disease (IBD) and primary sclerosing cholangitis (PSC).

Methods: The core group formulated seven PICO-structured clinical questions. A systematic literature search from inception to December 2022 was conducted by a medical librarian using MEDLINE and EMBASE.

Sequential STING and CD40 agonism drives massive expansion of tumor-specific T cells in liposomal peptide vaccines.

The clinical use of cancer vaccines is hampered by the low magnitude of induced T-cell responses and the need for repetitive antigen stimulation. Here, we demonstrate that liposomal formulations with incorporated STING agonists are optimally suited to deliver peptide antigens to dendritic cells in vivo and to activate dendritic cells in secondary lymphoid organs. One week after liposomal priming, systemic administration of peptides and a costimulatory agonistic CD40 antibody enables ultrarapid expansion of T cells, resulting in massive expansion of tumor-specific T cells in the peripheral blood two weeks after priming.

Wilms tumor primary cultures capture phenotypic heterogeneity and facilitate preclinical screening.

Wilms tumors (WT) are characterized by variable contributions of blastemal, epithelial and stromal elements, reflecting their diverse cellular origins and genetic drivers. In vitro models remain rare, despite a growing need to better characterize tumor biology and evaluate new treatments. Using three approaches, we have now established a large collection of long-term cultures that represent this diversity.

Investigation of the Urinary Peptidome to Unravel Collagen Degradation in Health and Kidney Disease.

Naturally occurring fragments of collagen type I alpha 1 chain (COL1A1) have been previously associated with chronic kidney disease (CKD), with some fragments showing positive and others negative associations. Using urinary peptidome data from healthy individuals (n = 1131) and CKD patients (n = 5585) this aspect was investigated in detail. Based on the hypothesis that many collagen peptides are derived not from the full, mature collagen molecule, but from (larger) collagen degradation products, relationships between COL1A1 peptides containing identical sequences were investigated, with the smaller (offspring) peptide being a possible degradation product of the larger (parent) one.

Care for post-COVID-19 condition in Germany from the perspectives of patients, informal caregivers and general practitioners: Study protocol for a mixed methods study.

Background: A large number of individuals suffer from post-COVID-19 condition (PCC), characterised by persistent symptoms following a SARS-CoV-2 infection with an impact on daily personal and professional activities. This study aims at examining which (health) care services are used by PCC patients in the German federal state of Lower Saxony, and how these patients manage their condition. The perspectives of patients, informal caregivers and general practitioners (GPs) will be considered.

The Use of Cannabis-Based Medicine in Selected Neurological Disorders.

Cannabis-based medicine (CBM) is used in a wide variety of different neurological disorders. While the use of CBM in the treatment of pain, AIDS wasting, loss of appetite, and spasticity is well established, CBM application in movement disorders and neurodegenerative disorders is still an emerging topic. The purpose of this chapter is to summarize current evidence behind the use of CBM in selected neurological diseases, mainly movement and neurodegenerative disorders.

Dietary changes following a lifestyle-based intervention for dementia risk reduction - results from the AgeWell.de study.

Purpose: We investigated the effects of a multidomain lifestyle intervention conducted in older adults at increased risk for dementia on participants' diet.

Methods: Secondary analyses of the cluster-randomized AgeWell.de-trial, testing a multidomain intervention (optimization of nutrition and medication, enhancement of physical, social and cognitive activity) in older adults at increased dementia risk.

The paradox of lumbopelvic alignment in anterolateral and posterolateral phenotypes of symptomatic hip dysplasia.

Purpose: The relationship between sagittal lumbopelvic alignment and the bony pathomorphology of hip dysplasia is currently at the forefront of clinical and scientific interest. The aim of this study was to determine whether there is a compensatory lumbopelvic aspect associated with the two major acetabular phenotypes in dysplastic hips.

Methods: From September 2022 to March 2024, a total of 145 patients with symptomatic bilateral hip dysplasia were included in the study.

High-Affinity Lectin Ligands Enable the Detection of Pathogenic Biofilms: Implications for Diagnostics and Therapy.

is a critical priority pathogen and causes life-threatening acute and biofilm-associated chronic infections. The choice of suitable treatment for complicated infections requires lengthy culturing for species identification from swabs or an invasive biopsy. To date, no fast, pathogen-specific diagnostic tools for infections are available.

Frequency, characteristics, and immunological accompaniments of ataxia in anti-NMDAR antibody-associated encephalitis.

Introduction: Very rarely, adult NMDAR antibody-associated encephalitis (NMDAR-E) leads to persistent cerebellar atrophy and ataxia. Transient cerebellar ataxia is common in pediatric NMDAR-E. Immune-mediated cerebellar ataxia may be associated with myelin oligodendrocyte glycoprotein (MOG), aquaporin-4 (AQP-4), kelch-like family member 11 (KLHL11), and glutamate kainate receptor subunit 2 (GluK2) antibodies, all of which may co-occur in NMDAR-E.

Polygenic score distribution differences across European ancestry populations: implications for breast cancer risk prediction.

Background: The 313-variant polygenic risk score (PRS) provides a promising tool for clinical breast cancer risk prediction. However, evaluation of the PRS across different European populations which could influence risk estimation has not been performed.

Methods: We explored the distribution of PRS across European populations using genotype data from 94,072 females without breast cancer diagnosis, of European-ancestry from 21 countries participating in the Breast Cancer Association Consortium (BCAC) and 223,316 females without breast cancer diagnosis from the UK Biobank.

- a large-scale dataset of 3D medical shapes for computer vision.

Objectives: The shape is commonly used to describe the objects. State-of-the-art algorithms in medical imaging are predominantly diverging from computer vision, where voxel grids, meshes, point clouds, and implicit surface models are used. This is seen from the growing popularity of ShapeNet (51,300 models) and Princeton ModelNet (127,915 models).