A biomathematical model of SARS-CoV-2 in Syrian hamsters.

When infected with SARS-CoV-2, Syrian hamsters (Mesocricetus auratus) develop moderate disease severity presenting key features of human COVID-19. We here develop a biomathematical model of the disease course by translating known biological mechanisms of virus-host interactions and immune responses into ordinary differential equations. We explicitly describe the dynamics of virus population, affected alveolar epithelial cells, and involved relevant immune cells comprising for example CD4+ T cells, CD8+ T cells, macrophages, natural killer cells and B cells.

Biomarkers troponin and procalcitonin in addition to CRB-65 enhance risk stratification in patients with community-acquired pneumonia.

Background: Community-acquired pneumonia (CAP) remains a leading cause of infectious disease mortality globally, necessitating intensive care unit (ICU) admission for ∼10% of hospitalised patients. Accurate prediction of disease severity facilitates timely therapeutic interventions.

Methods: Our study aimed to enhance the predictive capacity of the clinical CRB-65 score by evaluating eight candidate biomarkers: troponin T high-sensitive (TnT-hs), procalcitonin (PCT), N-terminal pro-brain natriuretic peptide, angiopoietin-2, copeptin, endothelin-1, lipocalin-2 and mid-regional pro-adrenomedullin.

Likelihood of Post-COVID Condition in people with hybrid immunity; data from the German National Cohort (NAKO).

Objectives: The risk of Post-COVID-19 condition (PCC) under hybrid immunity remains unclear.

Methods: Using data from the German National Cohort (NAKO Gesundheitsstudie), we investigated risk factors for self-reported post-infection symptoms (any PCC is defined as having at least one symptom, and high symptom burden PCC as having nine or more symptoms).

Results: Sixty percent of 109,707 participants reported at least one previous SARS-CoV-2 infection; 35% reported having had any symptoms 4-12 months after infection; among them 23% reported nine or more symptoms.

A biomathematical model of atherosclerosis in mice.

Atherosclerosis is one of the leading causes of death worldwide. Biomathematical modelling of the underlying disease and therapy processes might be a useful aid to develop and improve preventive and treatment concepts of atherosclerosis. We here propose a biomathematical model of murine atherosclerosis under different diet and treatment conditions including lipid modulating compound and antibiotics.

Relationship between impaired BMP signalling and clinical risk factors at early-stage vascular injury in the preterm infant.

Introduction: Chronic lung disease, that is, bronchopulmonary dysplasia (BPD) is the most common complication in preterm infants and develops as a consequence of the misguided formation of the gas-exchange area undergoing prenatal and postnatal injury. Subsequent vascular disease and its progression into pulmonary arterial hypertension critically determines long-term outcome in the BPD infant but lacks identification of early, disease-defining changes.

Methods: We link impaired bone morphogenetic protein (BMP) signalling to the earliest onset of vascular pathology in the human preterm lung and delineate the specific effects of the most prevalent prenatal and postnatal clinical risk factors for lung injury mimicking clinically relevant conditions in a multilayered animal model using wild-type and transgenic neonatal mice.

Modelling of human torso shape variation inferred by geometric morphometrics.

Traditional body measurement techniques are commonly used to assess physical health; however, these approaches do not fully represent the complex shape of the human body. Three-dimensional (3D) imaging systems capture rich point cloud data that provides a representation of the surface of 3D objects and have been shown to be a potential anthropometric tool for use within health applications. Previous studies utilising 3D imaging have only assessed body shape based on combinations and relative proportions of traditional body measures, such as lengths, widths and girths.

Genetic Regulation of Cytokine Response in Patients with Acute Community-Acquired Pneumonia.

Background: Community-acquired pneumonia (CAP) is an acute disease condition with a high risk of rapid deteriorations. We analysed the influence of genetics on cytokine regulation to obtain a better understanding of patient's heterogeneity.

Methods: For up to = 389 genotyped participants of the PROGRESS study of hospitalised CAP patients, we performed a genome-wide association study of ten cytokines IL-1β, IL-6, IL-8, IL-10, IL-12, MCP-1 (MCAF), MIP-1α (CCL3), VEGF, VCAM-1, and ICAM-1.

Sex-Specific Causal Relations between Steroid Hormones and Obesity-A Mendelian Randomization Study.

Steroid hormones act as important regulators of physiological processes including gene expression. They provide possible mechanistic explanations of observed sex-dimorphisms in obesity and coronary artery disease (CAD). Here, we aim to unravel causal relationships between steroid hormones, obesity, and CAD in a sex-specific manner.

Krueppel-Like Factor 4 Expression in Phagocytes Regulates Early Inflammatory Response and Disease Severity in Pneumococcal Pneumonia.

The transcription factor Krueppel-like factor (KLF) 4 fosters the pro-inflammatory immune response in macrophages and polymorphonuclear neutrophils (PMNs) when stimulated with , the main causative pathogen of community-acquired pneumonia (CAP). Here, we investigated the impact of KLF4 expression in myeloid cells such as macrophages and PMNs on inflammatory response and disease severity in a pneumococcal pneumonia mouse model and in patients admitted to hospital with CAP. We found that mice with a myeloid-specific knockout of KLF4 mount an insufficient early immune response with reduced levels of pro-inflammatory cytokines and increased levels of the anti-inflammatory cytokine interleukin (IL) 10 in bronchoalveolar lavage fluid and plasma and an impaired bacterial clearance from the lungs 24 hours after infection with .

Verification of immunology-related genetic associations in BPD supports ABCA3 and five other genes.

Background: Inflammatory processes are key drivers of bronchopulmonary dysplasia (BPD), a chronic lung disease in preterm infants. In a large sample, we verify previously reported associations of genetic variants of immunology-related genes with BPD.

Methods: Preterm infants with a gestational age ≤32 weeks from PROGRESS and the German Neonatal Network (GNN) were included.

First genome-wide association study of 99 body measures derived from 3-dimensional body scans.

Body height, body mass index, hip and waist circumference are important risk factors or outcome variables in clinical and epidemiological research with complex underlying genetics. However, these classical anthropometric traits represent only a very limited view on the human body and other traits with potentially higher functional specificity are not yet studied to a larger extent. Participants of LIFE-Adult were assessed by three-dimensional body scanner VITUS XXL determining 99 high-quality anthropometric traits in parallel.

Identification of New, Functionally Relevant Mutations in the Coding Regions of the Human Fos and Jun Proto-Oncogenes in Rheumatoid Arthritis Synovial Tissue.

In rheumatoid arthritis (RA), the expression of many pro-destructive/pro-inflammatory proteins depends on the transcription factor AP-1. Therefore, our aim was to analyze the presence and functional relevance of mutations in the coding regions of the AP-1 subunits of the fos and jun family in peripheral blood (PB) and synovial membranes (SM) of RA and osteoarthritis patients (OA, disease control), as well as normal controls (NC). Using the non-isotopic RNAse cleavage assay, one known polymorphism (T252C: silent; rs1046117; present in RA, OA, and NC) and three novel germline mutations of the cfos gene were detected: (i) C361G/A367G: Gln121Glu/Ile123Val, denoted as "fos121/123"; present only in one OA sample; (ii) G374A: Arg125Lys, "fos125"; and (iii) C217A/G374A: Leu73Met/Arg125Lys, "fos73/125", the latter two exclusively present in RA.

A biomathematical model of immune response and barrier function in mice with pneumococcal lung infection.

Pneumonia is one of the leading causes of death worldwide. The course of the disease is often highly dynamic with unforeseen critical deterioration within hours in a relevant proportion of patients. Besides antibiotic treatment, novel adjunctive therapies are under development.

Dynamics of cytokines, immune cell counts and disease severity in patients with community-acquired pneumonia - Unravelling potential causal relationships.

Background: Community acquired pneumonia (CAP) is a severe and often rapidly deteriorating disease. To better understand its dynamics and potential causal relationships, we analyzed time series data of cytokines, blood and clinical parameters in hospitalized CAP patients.

Methods: Time series data of 10 circulating cytokines, blood counts and clinical parameters were related to baseline characteristics of 403 CAP patients using univariate mixed models.

Molecular analyses of glioblastoma stem-like cells and glioblastoma tissue.

Glioblastoma is a common, malignant brain tumor whose disease incidence increases with age. Glioblastoma stem-like cells (GSCs) are thought to contribute to cancer therapy resistance and to be responsible for tumor initiation, maintenance, and recurrence. This study utilizes both SNP array and gene expression profiling to better understand GSCs and their relation to malignant disease.

[Self-reported infections in the German National Cohort (GNC) in the context of the current research landscape].

Background: Infectious diseases continue to play an important role for disease perception, health-economic considerations and public health in Germany. In recent years, infectious diseases have been linked to the development of non-communicable diseases. Analyses of the German National Cohort (GNC) may provide deeper insights into this issue and pave the way for new targeted approaches in disease prevention.

Markov State Modelling of Disease Courses and Mortality Risks of Patients with Community-Acquired Pneumonia.

Community-acquired pneumonia (CAP) is one of the most frequent infectious diseases worldwide, with high lethality. Risk evaluation is well established at hospital admission, and re-evaluation is advised for patients at higher risk. However, severe disease courses may develop from all levels of severity.

Neutralizing Complement C5a Protects Mice with Pneumococcal Pulmonary Sepsis.

Background: Community-acquired pneumonia and associated sepsis cause high mortality despite antibiotic treatment. Uncontrolled inflammatory host responses contribute to the unfavorable outcome by driving lung and extrapulmonary organ failure. The complement fragment C5a holds significant proinflammatory functions and is associated with tissue damage in various inflammatory conditions.

HLA Class II Allele Analyses Implicate Common Genetic Components in Type 1 and Non-Insulin-Treated Type 2 Diabetes.

Context: Common genetic susceptibility may underlie the frequently observed co-occurrence of type 1 and type 2 diabetes in families. Given the role of HLA class II genes in the pathophysiology of type 1 diabetes, the aim of the present study was to test the association of high density imputed human leukocyte antigen (HLA) genotypes with type 2 diabetes.

Objectives And Design: Three cohorts (Ntotal = 10 413) from Leipzig, Germany were included in this study: LIFE-Adult (N = 4649), LIFE-Heart (N = 4815) and the Sorbs (N = 949) cohort.

Association of proteome and metabolome signatures with severity in patients with community-acquired pneumonia.

A combined OMICS screening approach of human plasma and serum was used to characterize protein and metabolome signatures displaying association to severity of Community-acquired pneumonia (CAP). 240 serum and BD P100 EDTA plasma samples from patients diagnosed with CAP, collected during the day of enrolment to the hospital, were analyzed by a metabolomic and proteomic approach, respectively. Disease severity of CAP patients was stratified using the Sequential Organ Failure Assessment (SOFA) score.

Copy number variants in lipid metabolism genes are associated with gallstones disease in men.

Gallstones Disease (GSD) is one of the most common digestive diseases requiring hospitalization and surgical procedures in the world. GSD has a high prevalence in populations with European or Amerindian ancestry (10-20%) and the influence of genetic factors is broadly acknowledged. However, known genetic variants do not entirely explain the disease heritability suggesting that additional genetic variants remain to be identified.

Central neurocytoma: SNP array analyses, subtel FISH, and review of the literature.

The central neurocytoma (CN) is a rare brain tumor with a frequency of 0.1-0.5% of all brain tumors.

Sequential organ failure assessment score is an excellent operationalization of disease severity of adult patients with hospitalized community acquired pneumonia - results from the prospective observational PROGRESS study.

Background: CAP (Community acquired pneumonia) is frequent, with a high mortality rate and a high burden on health care systems. Development of predictive biomarkers, new therapeutic concepts, and epidemiologic research require a valid, reproducible, and quantitative measure describing CAP severity.

Methods: Using time series data of 1532 patients enrolled in the PROGRESS study, we compared putative measures of CAP severity for their utility as an operationalization.

Association of Human Promoter Variants with the Occurrence of Knee-Osteoarthritis in a Case Control Association Study.

Our aim was to analyse (i) the presence of single nucleotide polymorphisms (SNPs) in the and core promoters in patients with rheumatoid arthritis (RA), knee-osteoarthritis (OA), and normal controls (NC); (ii) their functional influence on / transcription levels; and (iii) their associations with the occurrence of RA or knee-OA. and promoter SNPs were identified in an initial screening population using the Non-Isotopic RNase Cleavage Assay (NIRCA); their functional influence was analysed using reporter gene assays. Genotyping was done in RA ( = 298), knee-OA ( = 277), and NC ( = 484) samples.

Attenuated PDGF signaling drives alveolar and microvascular defects in neonatal chronic lung disease.

Neonatal chronic lung disease (nCLD) affects a significant number of neonates receiving mechanical ventilation with oxygen-rich gas (MV-O). Regardless, the primary molecular driver of the disease remains elusive. We discover significant enrichment for SNPs in the PDGF-Rα gene in preterms with nCLD and directly test the effect of PDGF-Rα haploinsufficiency on the development of nCLD using a preclinical mouse model of MV-O In the context of MV-O, attenuated PDGF signaling independently contributes to defective septation and endothelial cell apoptosis stemming from a PDGF-Rα-dependent reduction in lung VEGF-A.