Serum Proteomics Distinguish Subtypes of NMO Spectrum Disorder and MOG Antibody-Associated Disease and Highlight Effects of B-Cell Depletion.

Background And Objectives: AQP4 antibody-positive NMOSD (AQP4-NMOSD), MOG antibody-associated disease (MOGAD), and seronegative NMOSD (SN-NMOSD) are neuroautoimmune conditions that have overlapping clinical manifestations. Yet, important differences exist in these diseases, particularly in B-cell depletion (BCD) efficacy. Yet, the biology driving these differences remains unclear.

Grey Matter Atrophy and its Relationship with White Matter Lesions in Patients with Myelin Oligodendrocyte Glycoprotein Antibody-associated Disease, Aquaporin-4 Antibody-Positive Neuromyelitis Optica Spectrum Disorder, and Multiple Sclerosis.

Objective: To evaluate: (1) the distribution of gray matter (GM) atrophy in myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder (AQP4+NMOSD), and relapsing-remitting multiple sclerosis (RRMS); and (2) the relationship between GM volumes and white matter lesions in various brain regions within each disease.

Methods: A retrospective, multicenter analysis of magnetic resonance imaging data included patients with MOGAD/AQP4+NMOSD/RRMS in non-acute disease stage. Voxel-wise analyses and general linear models were used to evaluate the relevance of regional GM atrophy.

Cardioprotective properties of OMT-28, a synthetic analog of omega-3 epoxyeicosanoids.

OMT-28 is a metabolically robust small molecule developed to mimic the structure and function of omega-3 epoxyeicosanoids. However, it remained unknown to what extent OMT-28 also shares the cardioprotective and anti-inflammatory properties of its natural counterparts. To address this question, we analyzed the ability of OMT-28 to ameliorate hypoxia/reoxygenation (HR)-injury and lipopolysaccharide (LPS)-induced endotoxemia in cultured cardiomyocytes.

Biomarker signatures associated with ageing free of major chronic diseases: results from a population-based sample of the EPIC-Potsdam cohort.

Background: A number of biomarkers denoting various pathophysiological pathways have been implicated in the aetiology and risk of age-related diseases. Hence, the combined impact of multiple biomarkers in relation to ageing free of major chronic diseases, such as cancer, cardiovascular disease and type 2 diabetes, has not been sufficiently explored.

Methods: We measured concentrations of 13 biomarkers in a random subcohort of 2,500 participants in the European Prospective Investigation into Cancer and Nutrition Potsdam study.

The Association of Plasma Leptin, Soluble Leptin Receptor and Total and High-Molecular Weight Adiponectin With the Risk of Perioperative Neurocognitive Disorders.

Background: Perioperative neurocognitive disorders (NCD) are poorly characterized in terms of their risk factor profiles. Leptin and adiponectin are adipose-tissue-derived hormones with a role in inflammation and atherosclerosis whose function in perioperative NCD is unclear. Here, we used a cohort of older adults to examine the association of preoperative plasma concentrations of these biomarkers with the risk of perioperative NCD.

Large-scale assessment of physical activity in a population using high-resolution hip-worn accelerometry: the German National Cohort (NAKO).

Large population-based cohort studies utilizing device-based measures of physical activity are crucial to close important research gaps regarding the potential protective effects of physical activity on chronic diseases. The present study details the quality control processes and the derivation of physical activity metrics from 100 Hz accelerometer data collected in the German National Cohort (NAKO). During the 2014 to 2019 baseline assessment, a subsample of NAKO participants wore a triaxial ActiGraph accelerometer on their right hip for seven consecutive days.

Treatment switches of disease-modifying therapies in people with multiple sclerosis: long-term experience from the German MS Registry.

Background: The spectrum of disease-modifying therapies (DMTs) for people with multiple sclerosis (PwMS) has expanded over years, but data on treatment strategies is largely lacking. DMT switches are common clinical practice.

Objective: To compare switchers and non-switchers, characterize the first DMT switch and identify reasons and predictors for switching the first DMT.

Personality and the use of cancer screenings - Results of the German National Cohort.

Objective: To determine the association between personality characteristics and use of different cancer screenings.

Methods: We used data from the German National Cohort (NAKO; mean age was 53.0 years (SD: 9.

Imaging Markers Derived From MRI-Based Automated Kidney Segmentation—an Analysis of Data From the German National Cohort (NAKO Gesundheitsstudie).

Background: Population-wide research on potential new imaging biomarkers of the kidney depends on accurate automated segmentation of the kidney and its compartments (cortex, medulla, and sinus).

Methods: We developed a robust deep-learning framework for kidney (sub-)segmentation based on a hierarchical, three-dimensional convolutional neural network (CNN) that was optimized for multiscale problems of combined localization and segmentation. We applied the CNN to abdominal magnetic resonance images from the population-based German National Cohort (NAKO) study.

Health Service Use Among Migrants in the German National Cohort-The Role of Birth Region and Language Skills.

To compare health service use (HSU) between migrants and non-migrants in Germany. Using data from the population-based German National Cohort (NAKO), we compared the HSU of general practitioners, medical specialists, and psychologists/psychiatrists between six migrant groups of different origins with the utilization of non-migrants. A latent profile analysis (LPA) with a subsequent multinomial regression analysis was conducted to characterize the HSU of different groups.

Heterozygous missense variant in GLI2 impairs human endocrine pancreas development.

Missense variants are the most common type of coding genetic variants. Their functional assessment is fundamental for defining any implication in human diseases and may also uncover genes that are essential for human organ development. Here, we apply CRISPR-Cas9 gene editing on human iPSCs to study a heterozygous missense variant in GLI2 identified in two siblings with early-onset and insulin-dependent diabetes of unknown cause.

SorLA restricts TNFα release from microglia to shape a glioma-supportive brain microenvironment.

SorLA, encoded by the gene SORL1, is an intracellular sorting receptor of the VPS10P domain receptor gene family. Although SorLA is best recognized for its ability to shuttle target proteins between intracellular compartments in neurons, recent data suggest that also its microglial expression can be of high relevance for the pathogenesis of brain diseases, including glioblastoma (GBM). Here, we interrogated the impact of SorLA on the functional properties of glioma-associated microglia and macrophages (GAMs).

Soluble ACE2 correlates with severe COVID-19 and can impair antibody responses.

Identifying immune modulators that impact neutralizing antibody responses against severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) is of great relevance. We postulated that high serum concentrations of soluble angiotensin-converting enzyme 2 (sACE2) might mask the spike and interfere with antibody maturation toward the SARS-CoV-2-receptor-binding motif (RBM). We tested 717 longitudinal samples from 295 COVID-19 patients and showed a 2- to 10-fold increase of enzymatically active sACE2 (a-sACE2), with up to 1 μg/mL total sACE2 in moderate and severe patients.

Structural disconnectivity in postoperative delirium: A perioperative two-center cohort study in older patients.

Background: Structural disconnectivity was found to precede dementia. Global white matter abnormalities might also be associated with postoperative delirium (POD).

Methods: We recruited older patients (≥65 years) without dementia that were scheduled for major surgery.

Reproducibility assessment of rapid strains in cardiac MRI: Insights and recommendations for clinical application.

Purpose: Studies have shown the incremental value of strain imaging in various cardiac diseases. However, reproducibility and generalizability has remained an issue of concern. To overcome this, simplified algorithms such as rapid atrioventricular strains have been proposed.

Preferences, Adherence, and Satisfaction: Three Years of Treatment Experiences of People with Multiple Sclerosis.

Background: To reduce the risk of long-term disability in people with Multiple Sclerosis (pwMS), an increasing number of disease-modifying immune therapies (DMT) are available, involving diverse mechanisms of action, levels of efficacy, treatment risks, and tolerability aspects. Including patient preferences and expectations in shared decision-making may improve treatment satisfaction, adherence, and persistence.

Purpose: To investigate long-term alignment of individual preferences and expectations of pwMS with their actual DMT and its effect on treatment satisfaction, health-related quality of life (HRQoL), adherence, and treatment discontinuation.

TF-FVIIa PAR2-β-Arrestin Signaling Sustains Organ Dysfunction in Coxsackievirus B3 Infection of Mice.

Background: Accumulating evidence implicates the activation of G-protein-coupled PARs (protease-activated receptors) by coagulation proteases in the regulation of innate immune responses.

Methods: Using mouse models with genetic alterations of the PAR2 signaling platform, we have explored contributions of PAR2 signaling to infection with coxsackievirus B3, a single-stranded RNA virus provoking multiorgan tissue damage, including the heart.

Results: We show that PAR2 activation sustains correlates of severe morbidity-hemodynamic compromise, aggravated hypothermia, and hypoglycemia-despite intact control of the virus.

Clinical Characterization and Ancillary Tests in Susac Syndrome: A Systematic Review.

Susac syndrome (SuS) is an orphan microangiopathic disease characterized by a triad of encephalopathy, visual disturbances due to branch retinal artery occlusions, and sensorineuronal hearing loss. Our previous systematic review on all cases of SuS reported until 2012 allowed for a better understanding of clinical presentation and diagnostic findings. Based on these data, we suggested diagnostic criteria in 2016 to allow early diagnosis and treatment of SuS.

Multiscale networks in multiple sclerosis.

Complex diseases such as Multiple Sclerosis (MS) cover a wide range of biological scales, from genes and proteins to cells and tissues, up to the full organism. In fact, any phenotype for an organism is dictated by the interplay among these scales. We conducted a multilayer network analysis and deep phenotyping with multi-omics data (genomics, phosphoproteomics and cytomics), brain and retinal imaging, and clinical data, obtained from a multicenter prospective cohort of 328 patients and 90 healthy controls.

In vivo monitoring of renal tubule volume fraction using dynamic parametric MRI.

Purpose: The increasing incidence of kidney diseases is a global concern, and current biomarkers and treatments are inadequate. Changes in renal tubule luminal volume fraction (TVF) serve as a rapid biomarker for kidney disease and improve understanding of renal (patho)physiology. This study uses the amplitude of the long T component as a surrogate for TVF in rats, by applying multiexponential analysis of the T-driven signal decay to examine micromorphological changes in renal tissue.

ISG15 blocks cardiac glycolysis and ensures sufficient mitochondrial energy production during Coxsackievirus B3 infection.

Aims: Virus infection triggers inflammation and, may impose nutrient shortage to the heart. Supported by type I interferon (IFN) signalling, cardiomyocytes counteract infection by various effector processes, with the IFN-stimulated gene of 15 kDa (ISG15) system being intensively regulated and protein modification with ISG15 protecting mice Coxsackievirus B3 (CVB3) infection. The underlying molecular aspects how the ISG15 system affects the functional properties of respective protein substrates in the heart are unknown.