Targeting the Type I Interferon Pathway in Glomerular Kidney Disease: Rationale and Therapeutic Opportunities.

Type I interferons (IFNs) are immunostimulatory molecules that can activate the innate and adaptive immune systems. In cases of immune dysfunction, prolonged activation of the type I IFN pathway has been correlated with kidney tissue damage in a wide range of kidney disorders, such as lupus nephritis (LN) and focal segmental glomerulosclerosis (FSGS). Genetic mutations, such as risk variants in conjunction with elevated type I IFN expression, are also associated with higher rates of chronic kidney disease in patients with LN and collapsing FSGS.

Nanocarrier imaging at single-cell resolution across entire mouse bodies with deep learning.

Efficient and accurate nanocarrier development for targeted drug delivery is hindered by a lack of methods to analyze its cell-level biodistribution across whole organisms. Here we present Single Cell Precision Nanocarrier Identification (SCP-Nano), an integrated experimental and deep learning pipeline to comprehensively quantify the targeting of nanocarriers throughout the whole mouse body at single-cell resolution. SCP-Nano reveals the tissue distribution patterns of lipid nanoparticles (LNPs) after different injection routes at doses as low as 0.

A truncated variant of the ribosome-associated trigger factor specifically contributes to plant chloroplast ribosome biogenesis.

Molecular chaperones are essential throughout a protein's life and act already during protein synthesis. Bacteria and chloroplasts of plant cells share the ribosome-associated chaperone trigger factor (Tig1 in plastids), facilitating maturation of emerging nascent polypeptides. While typical trigger factor chaperones employ three domains for their task, the here described truncated form, Tig2, contains just the ribosome binding domain.

Microcomputed tomographic analysis of the trabecular and cortical architecture of the proximal femur and hip bone of cats and small breed dogs.

This study aims to provide an initial database to gain more detailed knowledge of the trabecular and cortical bone structure of pelvic and femur bones in cats and smaller dogs. Additionally, the bony microarchitecture between cats and smaller dogs was compared to identify possible differences between those species. These findings could potentially improve the development of non-cemented total hip replacement (THR).

Neuropathology, pathomechanism, and transmission in zoonotic Borna disease virus 1 infection: a systematic review.

Borna disease, which is a severe encephalitis that primarily affects horses and sheep, has been recognised for over two centuries. Borna disease virus 1 (BoDV-1) has been identified as a cause of a predominantly fatal encephalitis in humans. Little scientific data exist regarding the virus' transmission, entry portal, and excretion routes.

Twins with at least one with CHD and their immunisation status in direct comparison-are both twins complying with the German immunisation recommendations?

Background: Patients with congenital heart defects (CHDs) are at higher risk for infectious diseases. This may partly be due to frequent hospital stays and the associated exposure to pathogens. This study aims to provide a comprehensive overview of immunisation coverage among twins in which at least one twin has CHD.

Intravitreal enzyme replacement therapy slows retinopathy in late infantile ceroid lipofuscinosis type 2.

Ceroid lipofuscinosis type 2 (CLN2) is caused by biallelic pathogenic variants in the TPP1 gene, encoding lysosomal tripeptidyl peptidase 1 (TPP1). The classical late-infantile phenotype has an age of onset between 2 and 4 years and is characterized by psychomotor regression, myoclonus, ataxia, blindness, and shortened life expectancy. Vision loss occurs due to retinal degeneration, usually when severe neurological symptoms are already evident.

Conceptual foundations of a REFRAME-based approach to discriminate across total knee implant designs based on the positions of functional centres of rotation.

In modern knee arthroplasty, surgeons increasingly aim for individualised implant selection based on data-driven decisions to improve patient satisfaction rates. The identification of an implant design that optimally fits to a patient's native kinematic patterns and functional requirements could provide a basis towards subject-specific phenotyping. The goal of this study was to achieve a first step towards identifying easily accessible and intuitive features that allow for discrimination between implant designs based on kinematic data.

Translation, adaptation, and validation of the Care Coordination Instrument for cancer patients.

Background: Cancer requires interdisciplinary intersectoral care. The Care Coordination Instrument (CCI) captures patients' perspectives on cancer care coordination. We aimed to translate, adapt, and validate the CCI for Germany (CCI German version).

Satiety-enhancing placebo intervention decreases selective attention to food cues.

Background: As placebo interventions could influence appetite and satiety in first studies, they are a promising tool for the future treatment of obesity. Furthermore, individuals with heightened body weight show increased selective attention for food cues. This study aimed to investigate whether placebo induced changes of appetite and satiety can affect attention allocation and to examine correlating factors.

Targeting pleuro-alveolar junctions reverses lung fibrosis in mice.

Lung fibrosis development utilizes alveolar macrophages, with mechanisms that are incompletely understood. Here, we fate map connective tissue during mouse lung fibrosis and observe disassembly and transfer of connective tissue macromolecules from pleuro-alveolar junctions (PAJs) into deep lung tissue, to activate fibroblasts and fibrosis. Disassembly and transfer of PAJ macromolecules into deep lung tissue occurs by alveolar macrophages, activating cysteine-type proteolysis on pleural mesothelium.

Long-term persistence of glycemic dysregulation in patients with a history of pheochromocytoma/paraganglioma.

Context: Pheochromocytomas and paragangliomas (PPGLs) are rare endocrine tumors that frequently produce catecholamines. Catecholamine-induced cardiometabolic complications substantially contribute to increased morbidity and mortality in PPGL patients prior to surgical resection.

Objective: To determine whether markers of elevated cardiometabolic risk persist in patients following PPGL resection.

CDK5 interacts with MST2 and modulates the Hippo signalling pathway.

MST2 (STK3) is a major upstream kinase in the Hippo signalling pathway, an evolutionary conserved pathway in regulation of organ size, self-renewal and tissue homeostasis. Its downstream effectors are the transcriptional regulators YAP and TAZ. This pathway is regulated by a variety of factors, such as substrate stiffness or cell-cell contacts.

Real-world multicentre cohort study on choices and effectiveness of immunotherapies in NMOSD and MOGAD.

Background: Recurrent attacks in neuromyelitis optica spectrum disorders (NMOSDs) or myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) can lead to severe disability. We aimed to analyse the real-world use of immunotherapies in patients with NMOSD and MOGAD, focusing on changes in treatment strategies, effects on attack rates (ARR) and risk factors for attacks.

Methods: This longitudinal registry-based cohort study included 493 patients (320 with aquaporin-4 immunoglobulin G (AQP4-IgG) seropositive NMOSD (65%), 44 with AQP4-IgG seronegative NMOSD (9%) and 129 MOGAD (26%)) with 1247 treatments from 19 German and one Austrian centre from the registry of the neuromyelitis optica study group (NEMOS).

Establishment of Stable Knockdown of MACC1 Oncogene in Patient-Derived Ovarian Cancer Organoids.

High-grade serous ovarian cancer (HGSOC) remains the most lethal gynecological malignancy, and there is still an unmet medical need to deepen basic research on its origins and mechanisms of progression. Patient-derived organoids of high-grade serous ovarian cancer (HGSOC-PDO) are a powerful model to study the complexity of ovarian cancer as they maintain, in vitro, the mutational profile and cellular architecture of the cancer tissue. Genetic modifications by lentiviral transduction allow novel insights into signaling pathways and the potential identification of biomarkers regarding the evolution of drug resistance.

Why are we still in need for novel anti-obesity medications?

From the pioneering moment in 1987 when the insulinotropic effect of glucagon-like peptide 1 (GLP-1) was first demonstrated in humans, to today's pharmaceutical gold rush for GLP-1-based treatments of obesity, the journey of GLP-1 pharmacology has been nothing short of extraordinary. The sequential conceptual developments of long-acting GLP-1 receptor (GLP-1R) mono-agonists, GLP-1R/glucose-dependent insulinotropic polypeptide receptor (GIPR) dual-agonists, and GLP-1R/GIPR/glucagon receptor (GcgR) triple agonists, have led to profound body weight-lowering capacities, with benefits that extend past obesity and towards obesity-associated diseases. The GLP-1R/GIPR dual-agonist tirzepatide has demonstrated a remarkable 23% body weight reduction in individuals with obesity over 72 weeks, eclipsing the average result achieved by certain types of bariatric surgery.

Targeting T cell exhaustion: emerging strategies in non-small cell lung cancer.

Lung cancer continues to be a major contributor to cancer-related deaths globally. Recent advances in immunotherapy have introduced promising treatments targeting T cell functionality. Central to the efficacy of these therapies is the role of T cells, which are often rendered dysfunctional due to continuous antigenic stimulation in the tumor microenvironment-a condition referred to as T cell exhaustion.

Long-term patient-reported outcomes following congenital heart surgery in adults.

Objective: To investigate the long-term impact of cardiac surgery on the quality of life in adults with congenital heart disease (ACHDs).

Methods: Patients who had undergone cardiac surgery for congenital heart disease (CHD) at the age of 18 years or more were recruited in a single-center, cross-sectional study. The enrolled subjects completed online questionnaires to assess patient-reported outcomes: perceived health status and life satisfaction, psychological functioning, health behaviors, and illness perception.

1924-2024: First centennial of EEG.

On July 6th of 1924 Hans Berger -a German psychiatrist- first recorded electric signals from the human brainvia scalp electrodes. This date marks the beginning of Electroencephalography. In this review a representative panel of past and present Officers of the International Federation of Clinical Neurophysiology (IFCN) and of its Official Journal briefly summarizes the past, present and future of Electroencephalographic and related neurophysiological techniques' impact and the role of the IFCN in global collaboration, education, standardization, research innovation, and clinical practice.

Crosstalk between periodontitis and cardiovascular risk.

Recent demographic developments resulted in an aged society with a rising disease burden of systemic and non-communicable diseases (NCDs). In cardiovascular disease (CVD), a NCD with high morbidity and mortality, recent preventive strategies include the investigation of comorbidities to reduce its significant economic burden. Periodontal disease, an oral bacterial-induced inflammatory disease of tooth-supporting tissue, is regulated in its prevalence and severity by the individual host response to a dysbiotic oral microbiota.

BMIgap: a new tool to quantify transdiagnostic brain signatures of current and future weight.

Understanding the neurobiological underpinnings of weight gain could reduce excess mortality and improve long-term trajectories of psychiatric disorders. We used support-vector machines and whole-brain voxel-wise grey matter volume to generate and validate a BMI predictor in healthy individuals (N = 1504) and applied it to individuals with schizophrenia (SCZ,N = 146), clinical high-risk states for psychosis (CHR,N = 213) and recent-onset depression (ROD,N = 200). We computed BMIgap (BMI-BMI), interrogated its brain-level overlaps with SCZ and explored whether BMIgap predicted weight gain at 1- and 2-year follow-up.

Optimal Medical Therapy for Heart Failure and Integrated Care in Patients With Atrial Fibrillation: A Report From the ESC-EHRA EORP Atrial Fibrillation Long-Term General Registry.

Background: Heart failure (HF) often occurs in patients with atrial fibrillation (AF), with a major impact on prognosis. Few data are available on the effect of integrated treatment strategies to improve prognosis in patients with AF. We aimed to evaluate the association between HF (according to left ventricular ejection fraction [LVEF]), HF optimal medical therapy and adherence to the Atrial Fibrillation Better Care pathway, and major outcomes in patients with AF.