Sex dimorphism in kidney health and disease: mechanistic insights and clinical implication.

Sex is a key variable in the regulation of human physiology and pathology. Many diseases disproportionately affect one sex: autoimmune diseases, such as systemic lupus erythematosus, are more common in women but more severe in men, whereas the incidence of other disorders such as gouty arthritis and malignant cancers is higher in men. Besides the pathophysiology, sex may also influence the efficacy of therapeutics; participants in clinical trials are still predominately men, and the side effects of drugs are more common in women than in men.

Making the effect visible - OX40 targeting nanobodies for imaging of activated T cells.

Purpose: Human OX40 (hOX40/CD134), a member of the TNF receptor superfamily, is mainly expressed on activated T lymphocytes. Triggered by its ligand OX40L (CD252), it provides costimulatory signals that support the differentiation, proliferation and long-term survival of T cells. Besides being a relevant therapeutic target, hOX40 is also an important biomarker for monitoring the presence or infiltration of activated T cells within the tumor microenvironment (TME), the inflammatory microenvironment (IME) in immune-mediated diseases (IMIDs) and the lymphatic organs.

Evaluation of variation in preclinical electroencephalographic (EEG) spectral power across multiple laboratories and experiments: An EQIPD study.

The European Quality In Preclinical Data (EQIPD) consortium was born from the fact that publications report challenges with the robustness, rigor, and/or validity of research data, which may impact decisions about whether to proceed with further preclinical testing or to advance to clinical testing, as well as draw conclusions on the predictability of preclinical models. To address this, a consortium including multiple research laboratories from academia and industry participated in a series of electroencephalography (EEG) experiments in mice aimed to detect sources of variance and to gauge how protocol harmonisation and data analytics impact such variance. Ultimately, the goal of this first ever between-laboratory comparison of EEG recordings and analyses was to validate the principles that supposedly increase data quality, robustness, and comparability.

Combined Assessment of Function and Survival to Demonstrate the Effect of Treatment on Progressive Supranuclear Palsy.

Background: Progressive supranuclear palsy (PSP) is a rare and fatal neurodegenerative disorder for which there are currently no disease-modifying treatments. Recent trials of potential therapies had durations of 12 months, which may be insufficient because of nonrandom missingness due to death. Longer durations, incorporating PSP Rating Scale and survival, can reduce the potential for type II error.

Subphenotypes of adult-onset diabetes: Data-driven clustering in the population-based KORA cohort.

Aims: A data-driven cluster analysis in a cohort of European individuals with type 2 diabetes (T2D) has previously identified four subgroups based on clinical characteristics. In the current study, we performed a comprehensive statistical assessment to (1) replicate the above-mentioned original clusters; (2) derive de novo T2D subphenotypes in the Kooperative Gesundheitsforschung in der Region Augsburg (KORA) cohort and (3) describe underlying genetic risk and diabetes complications.

Methods: We used data from n = 301 individuals with T2D from KORA FF4 study (Southern Germany).

Stimulation of the withdrawal reflex in gait training after stroke: A systematic review and meta-analysis.

Background: After a stroke many people experience hemiparesis, resulting in walking difficulties which affects independence, mobility, and participation in activities of daily living. Activating the nociceptive withdrawal reflex (NWR) during gait training aims to support the initiation and facilitation of the swing phase of the paretic leg. The aim of this review is to investigate the orthotic and therapeutic effects of a NWR stimulation intervention to improve gait in patients after a stroke.

Physiologists as medical scientists: An early warning from the German academic system.

"Medical scientists" are postgraduate investigators who are engaged in biomedical research, and either hold a biomedical PhD or are qualified in medicine but do not participate in patient care. Medical scientists constitute ~40% of staff at medical faculties and >90% at nonuniversity medical research institutions in Germany. However, medical scientists in Germany face limited long-term career prospects and a lack of dedicated training and support programmes.

Efficiency of multivariate tests in trials in progressive supranuclear palsy.

Measuring disease progression in clinical trials for testing novel treatments for multifaceted diseases as progressive supranuclear palsy (PSP), remains challenging. In this study we assess a range of statistical approaches to compare outcomes as measured by the items of the progressive supranuclear palsy rating scale (PSPRS). We consider several statistical approaches, including sum scores, a modified PSPRS rating scale that had been recommended by FDA in a pre-IND meeting, multivariate tests, and analysis approaches based on multiple comparisons of the individual items.

Successful non-invasive imaging of the coronary artery IMT in pediatric patients with Kawasaki disease using high-resolution echocardiography.

Kawasaki Disease (KD) is a multisystemic vasculitis of medium- and small-sized arteries. Abnormal intimal thickening may develop in the involved arterial area after regression of coronary artery aneurysm (CAA). Intimal dysfunction may induce local stenosis or arteriosclerosis in the future.

Monitoring of Respiratory Disease Patterns in a Multimicrobially Infected Pig Population Using Artificial Intelligence and Aggregate Samples.

A 24/7 AI sound-based coughing monitoring system was applied in combination with oral fluids (OFs) and bioaerosol (AS)-based screening for respiratory pathogens in a conventional pig nursery. The objective was to assess the additional value of the AI to identify disease patterns in association with molecular diagnostics to gain information on the etiology of respiratory distress in a multimicrobially infected pig population. Respiratory distress was measured 24/7 by the AI and compared to human observations.

2-Pyridylmetallocenes, Part IX. Sulphur-Substituted 2-Pyridylferrocene: Synthesis and Reactivity towards Pt(II) and Hg(II).

Thio-substituted 2-pyridylferrocenes [CpFe{CH(X)(CHN)}] (X = SOTol, ; SMe, ) were prepared from [CpFe(CHR)] (R = SOTol, ; 2-CHN, ) in moderate yields. The reactions of and with [PtCl(DMSO)] yielded the binuclear N, S chelated complexes [CpFe{CH(X)(CHN)}-(к-N,S)-PtCl] (X= SOTol, , SMe, ), while the reaction of with Hg(OAc)/LiCl led to cyclomercuration with generation of [CpFe{CH(SMe)(CHN)(HgCl)}], . The crystal structures of ·CHCl and were determined.

Prognostic Value of Speckle Tracking Echocardiography-Derived Strain in Unmasking Risk for Arrhythmias in Children with Myocarditis.

Risk assessment in pediatric myocarditis is challenging, particularly when left ventricular ejection fraction (LVEF) is preserved. This study aimed to evaluate LV myocardial deformation using speckle-tracking echocardiography (STE)-derived longitudinal +strain (LS) and assessed its diagnostic and prognostic value in children with myocarditis. Retrospective STE-derived layer-specific LV LS analysis was performed on echocardiograms from patients within the multicenter, prospective registry for pediatric myocarditis "MYKKE".

Implementation of an Immunoassay Based on the MVA-T7pol-Expression System for Rapid Identification of Immunogenic SARS-CoV-2 Antigens: A Proof-of-Concept Study.

The emergence of hitherto unknown viral pathogens presents a great challenge for researchers to develop effective therapeutics and vaccines within a short time to avoid an uncontrolled global spread, as seen during the coronavirus disease 2019 (COVID-19) pandemic. Therefore, rapid and simple methods to identify immunogenic antigens as potential therapeutical targets are urgently needed for a better pandemic preparedness. To address this problem, we chose the well-characterized Modified Vaccinia virus Ankara (MVA)-T7pol expression system to establish a workflow to identify immunogens when a new pathogen emerges, generate candidate vaccines, and test their immunogenicity in an animal model.

Immunoglobulin secretion influences the composition of chicken caecal microbiota.

The chicken caecum is colonised by hundreds of different bacterial species. Which of these are targeted by immunoglobulins and how immunoglobulin expression shapes chicken caecal microbiota has been addressed in this study. Using cell sorting followed by sequencing of V3/V4 variable region of 16S rRNA, bacterial species with increased or decreased immunoglobulin coating were determined.

A reproducible representation of healthy tibiofemoral kinematics during stair descent using REFRAME - Part II: Exploring optimisation criteria and inter-subject differences.

Kinematic analysis is a central component of movement biomechanics, describing the relative motion of joint segments during different activities, in different subject cohorts, and at different timepoints. Establishing whether two sets of kinematic signals represent fundamentally similar or different underlying motion patterns is especially challenging, given 1) the lack of consensus around reference frame and joint axis definition, and 2) the substantial effect that minimal variations in frame position and orientation are known to have on signal magnitude and characteristics. As such, enormous variability in the reporting of tibiofemoral kinematics has resulted in joint movement patterns that remain controversially discussed.

Self-supervised learning for accurately modelling hierarchical evolutionary patterns of cerebrovasculature.

Cerebrovascular abnormalities are critical indicators of stroke and neurodegenerative diseases like Alzheimer's disease (AD). Understanding the normal evolution of brain vessels is essential for detecting early deviations and enabling timely interventions. Here, for the first time, we proposed a pipeline exploring the joint evolution of cortical volumes (CVs) and arterial volumes (AVs) in a large cohort of 2841 individuals.

Oxidation of a zirconium nitride multilayer-covered knee implant after two years in clinical use.

The surface composition and microstructure of an up to 5 µm thick multilayer on a knee implant were investigated. When the implant was explanted after approximately two years of clinical use due to failure from aseptic loosening, the topmost ZrN layer was found to be oxidized. Interestingly, only the non-articulating area was visibly oxidized (color change).

Machine learning-based new classification for immune infiltration of gliomas.

Background: Glioma is a highly heterogeneous and poorly immunogenic malignant tumor, with limited efficacy of immunotherapy. The characteristics of the immunosuppressive tumor microenvironment (TME) are one of the important factors hindering the effectiveness of immunotherapy. Therefore, this study aims to reveal the immune microenvironment (IME) characteristics of glioma and predict different immune subtypes using machine learning methods, providing guidance for immune therapy in glioma.

Balance Assessment on a Modified Posturomed Platform in Healthy Dogs.

Reliable, standardized balance tests for dogs are not available yet. The purpose of this study was to investigate the reliability of static and dynamic posturography in healthy dogs. Healthy dogs ( = 20) were positioned with four paws longitudinally and with the forepaws only transversely on a modified pressure-sensitive balance platform (Posturomed-FDM-JS, Zebris, Isny, Germany).