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.

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.

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 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.

Revisiting ascending aortic resection in the elective valve-sparing root replacement: assessing the benefits and necessity of hemiarch replacement at three centres.

Objectives: The aim of this study was to determine the indication and optimal timing for performing a hemiarch procedure in patients undergoing valve-sparing root replacement (VSRR).

Methods: We conducted a retrospective study on 986 patients undergoing VSRR at three tertiary care centres. Inclusion criteria were all patients undergoing elective VSRR.

A Roadmap of Responses to Asymmetry Stress in Lipid Membranes.

The selective insertion of membrane-impermeant amphiphiles such as detergents, (lipo)peptides, drugs, etc. into the leaflet of a membrane causes an imbalance between the intrinsic areas of the and leaflet, referred to as asymmetry stress or differential stress. The literature provides individual mechanisms of how membranes respond to such stress, which are relevant to membrane remodeling processes and leakage phenomena.

Confocal Raman Microscopy with Adaptive Optics.

Confocal Raman microscopy, a highly specific and label-free technique for the microscale study of thick samples, often presents difficulties due to weak Raman signals. Inhomogeneous samples introduce wavefront aberrations that further reduce these signals, requiring even longer acquisition times. In this study, we introduce Adaptive Optics to confocal Raman microscopy for the first time to counteract such aberrations, significantly increasing the Raman signal and image quality.

Thiosemicarbazones as versatile photoswitches with light-controllable supramolecular activity.

Using photoswitchable molecules to manipulate supramolecular interactions under light illumination has driven advancements in numerous fields, allowing for the strategic alteration of molecular systems. However, integrating the moiety responsible for these interactions into the photochromic scaffold can be complex and may hamper the switching efficiency. We thus explored a simple class of organic molecules, namely thiosemicarbazones, featuring both a photoisomerizable C[double bond, length as m-dash]N double bond and a thiourea moiety capable of hydrogen bonding.

Signs of in-vivo aging of zirconia from explanted dental implants with porous coating after several years in function.

The present study investigated the in vivo aging of yttria-stabilized zirconia (YSZ) oral implants (ZiUnite®) removed after 37 to 181 months. These implants featured a porous zirconia surface to enhance osseointegration. They were placed in prospective clinical investigations and had to be explanted due to peri‑implant bone breakdown.