Association between non-insulin-based insulin resistance indicators and frailty progression: a national cohort study and mendelian randomization analysis.

Background: Insulin resistance (IR) is linked to an increased risk of frailty, yet it remains unclear whether the non-insulin-based IR indicators are associated with frailty trajectories and physical function decline. It aimed to examine the associations of triglyceride-glucose (TyG) index, metabolic score for insulin resistance (METS-IR), estimated glucose disposal rate (eGDR) and with long-term deficit-accumulation frailty trajectories and physical function decline.

Methods: Data from 6722 participants in the China Health and Retirement Longitudinal Study (CHARLS) were analyzed.

Development and maintenance of consensus recommendations on pediatric outpatient antibiotic therapy in Germany: a framework for rational use.

Unlabelled: In pediatric outpatient care, overuse and misuse of antibiotics is linked to a high risk of adverse events and increased antibiotic resistance. In 2019, building upon the work of the Antibiotic Therapy in Bielefeld (AnTiB) project (founded in 2016), a collaboration among the AnTiB, the German Society for Pediatric Infectious Diseases (DGPI), and the Professional Association of Outpatient Pediatricians and Adolescent Physicians (BVKJ) was established to develop consensus recommendations for antibiotic therapy in pediatric outpatient settings in Germany. This working group became the Antibiotic Stewardship in Outpatient Pediatrics (ABSaP).

Mitochondrial protein import stress.

Mitochondria have to import a large number of precursor proteins from the cytosol. Chaperones keep these proteins in a largely unfolded state and guide them to the mitochondrial import sites. Premature folding, mitochondrial stress and import defects can cause clogging of import sites and accumulation of non-imported precursors, representing a critical burden for cellular proteostasis.

The clinical and molecular landscape of diffuse hemispheric glioma, H3 G34-mutant.

Background: Diffuse hemispheric glioma, histone 3 (H3) G34-mutant, has been newly defined in the 2021 WHO classification of central nervous system tumors. Here we sought to define the prognostic roles of clinical, neuroimaging, pathological, and molecular features of these tumors.

Methods: We retrospectively assembled a cohort of 114 patients (median age 22 years) with diffuse hemispheric glioma, H3 G34-mutant, CNS WHO grade 4 and profiled the imaging, histological and molecular landscape of their tumors.

Pancreatic cancer cells infiltrate nerves through TGFbeta1-driven perineural epithelial-to-mesenchymal-like transdifferentiation.

Neural invasion is a prognostic hallmark of pancreatic ductal adenocarcinoma (PDAC), yet the underlying mechanisms behind the disruption of perineural barriers and access of cancer cells into intrapancreatic nerves remain poorly understood. This study aimed to investigate the role of epithelial-mesenchymal transformation (EMT) in perineural epithelial cells during neural invasion.Histopathological analysis of human and murine primary tumors using perineurium-specific GLUT1 antibody revealed a reduction in perineural integrity, which positively correlated with the extent of neural invasion in human PDAC cases.

Perioperative Chemotherapy or Preoperative Chemoradiotherapy in Esophageal Cancer.

Background: The best multimodal approach for resectable locally advanced esophageal adenocarcinoma is unclear. An important question is whether perioperative chemotherapy is preferable to preoperative chemoradiotherapy.

Methods: In this phase 3, multicenter, randomized trial, we assigned in a 1:1 ratio patients with resectable esophageal adenocarcinoma to receive perioperative chemotherapy with FLOT (fluorouracil, leucovorin, oxaliplatin, and docetaxel) plus surgery or preoperative chemoradiotherapy (radiotherapy at a dose of 41.

Unfolding of von Willebrand Factor Type D Like Domains Promotes Mucin Adhesion.

Mucins are the macromolecular key components of mucus. On wet epithelia of mammals, mucin solutions and gels act as powerful biolubricants and reduce friction and wear by generating a sacrificial layer and establishing hydration lubrication. Yet the structure-function relationship of mucin adhesion and lubrication remains elusive.

Depressive Symptoms and Amyloid Pathology.

Importance: Depressive symptoms are associated with cognitive decline in older individuals. Uncertainty about underlying mechanisms hampers diagnostic and therapeutic efforts. This large-scale study aimed to elucidate the association between depressive symptoms and amyloid pathology.

Layer-specific control of inhibition by NDNF interneurons.

Neuronal processing of external sensory input is shaped by internally generated top-down information. In the neocortex, top-down projections primarily target layer 1, which contains NDNF (neuron-derived neurotrophic factor)-expressing interneurons and the dendrites of pyramidal cells. Here, we investigate the hypothesis that NDNF interneurons shape cortical computations in an unconventional, layer-specific way, by exerting presynaptic inhibition on synapses in layer 1 while leaving synapses in deeper layers unaffected.

The neonate respiratory microbiome.

Over the past two decades, it has become clear that against earlier assumptions, the respiratory tract is regularly populated by a variety of microbiota even down to the lowest parts of the lungs. New methods and technologies revealed distinct microbiome compositions and developmental trajectories in the differing parts of the respiratory tract of neonates and infants. In this review, we describe the current understanding of respiratory microbiota development in human neonates and highlight multiple factors that have been identified to impact human respiratory microbiome development including gestational age, mode of delivery, diet, antibiotic treatment, and early infections.

Disentangling Effects of Vegetation Structure and Physiology on Land-Atmosphere Coupling.

Terrestrial vegetation is a key component of the Earth system, regulating the exchange of carbon, water, and energy between land and atmosphere. Vegetation affects soil moisture dynamics by absorbing and transpiring soil water, thus modulating land-atmosphere interactions. Moreover, changes in vegetation structure (e.

SOCS1 deficiency-crossroads of autoimmunity and autoinflammation-two case reports.

Suppressors of cytokine signaling (SOCS) proteins play a critical role in regulating immune signaling pathways. Deficiency of SOCS1 leads to various autoimmune pathologies. We present two unrelated patients with distinct clinical manifestations.

Discrepancy between performance and feedback affects mathematics student teachers' self-efficacy but not their self-assessment accuracy.

Although feedback is of high importance for the professional development of student teachers, the impact of (inadequate) feedback on their self-regulated learning is still unclear. In two studies with mathematics student teachers, we investigated how discrepancies between performance and feedback affected two important aspects of self-regulated learning-self-efficacy and self-assessment accuracy regarding mathematical content knowledge. In the first study,  = 154 student teachers studying mathematics completed a knowledge test on the Pythagorean theorem and received performance feedback that was either correct or manipulated to be more positive or more negative than actual performance.

Spatial and Temporal Relationships Between Roe and Red Deer in an Alpine Area.

Interspecific interactions are important drivers of population dynamics and species distribution. These relationships can increase niche partitioning between sympatric species, which can differentiate space and time use or modify their feeding strategies. Roe deer and red deer are two of the most widespread ungulate species in Europe and show spatial and dietary overlap.

Sulfated Glycosaminoglycans as Inhibitors for Chlamydia Infections: Molecular Weight and Sulfation Dependence.

Glycosaminoglycans (GAGs) play a pivotal role in pathogen attachment and entry into host cells, where the interaction with GAGs is critical for a diverse range of bacteria and viruses. This study focuses on elucidating the specific interactions between sulfated GAGs and the adhesin OmcB (Outer membrane complex protein B) of Chlamydia species, examining how structural characteristics of GAGs, such as sulfation degree and molecular weight, influence their binding affinity and thereby affect bacterial infectivity. A surface-based binding assay is established to determine the binding constants of OmcB with various GAGs.

MaveDB 2024: a curated community database with over seven million variant effects from multiplexed functional assays.

Multiplexed assays of variant effect (MAVEs) are a critical tool for researchers and clinicians to understand genetic variants. Here we describe the 2024 update to MaveDB ( https://www.mavedb.

Evaluating agreement between individual nutrition randomised controlled trials and cohort studies - a meta-epidemiological study.

Background: In nutrition research, randomised controlled trials (RCTs) and cohort studies provide complementary evidence. This meta-epidemiological study aims to evaluate the agreement of effect estimates from individual nutrition RCTs and cohort studies investigating a highly similar research question and to investigate determinants of disagreement.

Methods: MEDLINE, Epistemonikos, and the Cochrane Database of Systematic Reviews were searched from January 2010 to September 2021.

Facing migration under adverse conditions: challenges and resilience in the Colombo-Venezuelan border area.

Background: Internal displacement and cross-country migration are an increasing global phenomenon drawing the attention of politicians and the public. Causes and effects on the migrants and receptor populations are varied and often shaped by immigration laws and how migrants and refugees are being dealt with by local conditions, policy frameworks and by the host population (receptors). The massive influx of Venezuelan migrants into Colombia for more than a decade has characteristics which warrant a systematic analysis to identify contextual and individual factors favouring and hindering the well-being of migrants and their new Colombian neighbours of the receptor population.

The Co-IMPACT Consortium: Integrating Prostate-specific Membrane Antigen Positron Emission Tomography and Radiotherapy in Prostate Cancer Care.

The Co-IMPACT consortium addresses knowledge gaps in prostate-specific membrane antigen positron emission tomography-guided radiotherapy for prostate cancer by establishing a global database (46 centres from 16 countries) to standardise and analyse data across four distinguished clinical scenarios. A collaborative model with the Advanced Prostate Cancer Consensus Conference aligns urgent clinical needs with actionable research insights.

Pearls & Oy-sters: Recurrent Lyme Neuroborreliosis With Seroreversion in a Patient With Multiple Sclerosis on a B-Cell Depleting Therapy.

True seronegativity is extremely rare in Lyme neuroborreliosis (LNB) with reports only in patients with hematological malignancies or under treatment with chemotherapy and B-cell depleting therapies. In these instances, diagnosing LNB can be challenging. We report the case of a 63-year-old patient with 2 independent episodes of LNB.

The Outcomes of Pediatric, Adolescent, and Young Adult Oncology Patients With Non-neutropenic Fever: A Scoping Review of the Literature.

Background: There are established and well-followed guidelines for pediatric oncology patients who have neutropenic fever. However, there are no explicit criteria for this patient group, and over 50% of pediatric oncology patients with fever do not present with neutropenia.

Objective: In this scoping review, we have explored the outcomes of non-neutropenic fever in pediatric, adolescent, and young adult patients with cancer-directed treatment.

Plastics in dermatology: A review and solutions.

Hazards to human and planetary health are present at every stage of the plastic life cycle, yet plastic production is projected to triple by 2060. This review focuses on three key areas: the life cycle of plastic, the impact of microplastics and their associated chemicals, along with recommendations to reduce plastic use. In dermatology, micro- and nanoplastics are especially problematic as they are present in over 90% of personal care products.

The effect of HLA genotype on disease onset and severity in CTLA-4 insufficiency.

Introduction: Human Cytotoxic-T-lymphocyte-antigen-4 (CTLA-4) insufficiency caused by heterozygous germline mutations in is a complex immune dysregulation and immunodeficiency syndrome presenting with reduced penetrance and variable disease expressivity, suggesting the presence of disease modifiers that trigger the disease onset and severity. Various genetic and non-genetic potential triggers have been analyzed in CTLA-4 insufficiency cohorts, however, none of them have revealed a clear association to the disease. Multiple HLA haplotypes have been positively or negatively associated with various autoimmune diseases and inborn errors of immunity (IEI) due to the relevance of MHC in the strength of the T cell responses.

Potential for reduction of radiation dose in the assessment of the lead orientation in directional deep brain stimulation electrodes.

Purpose: Directional deep brain stimulation (dDBS) relies on electrodes steering the stimulation field in a specific direction. Post implantation, however, the intended and real orientation of the lead frequently deviates e.g.