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Interstitial Lung Disease in Antineutrophil Cytoplasmic Antibody–Associated Vasculitis : A European Multicenter Study

Objective: Interstitial lung disease (ILD) can occur in association with antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis (AAV-ILD) or as an isolated entity with positive ANCA (ANCA-ILD). However, data on the epidemiology and outcomes of these conditions remain limited. Methods: A European multicenter retrospective study encompassed patients with AAV-ILD or ANCA-ILD. Baseline and s

Nuclease-NTPase antiphage defence systems use conserved molecular features to control bacterial immunity

Bacteria encode diverse defence systems, including restriction-modification and CRISPR-Cas, that cleave nucleic acid to protect against phage infection. Bioinformatic analyses demonstrate that many recently identified antiphage defence operons comprise a nuclease and NTPase protein, suggesting that additional nucleic acid-targeting systems remain to be understood. Here we develop large-scale compa

Substance Use, Hospitalizations, and Co-Occurring Disorders among Patients Transferred from a Needle Exchange Program to Opioid Maintenance Treatment

Opioid use disorders (OUD) is a relapsing condition with high mortality. Opioid maintenance treatment (OMT) reduces heroin use, and overall morbidity and mortality. The prevalence of psychiatric and substance use disorders, potential baseline predictors for psychiatric hospitalization, and psychiatric diagnoses at follow-up were investigated and may give hints about possible preventative strategie

A self-sustaining layer of early-life-origin B cells drives steady-state IgA responses in the adult gut

The adult immune system consists of cells that emerged at various times during ontogeny. We aimed to define the relationship between developmental origin and composition of the adult B cell pool during unperturbed hematopoiesis. Lineage tracing stratified murine adult B cells based on the timing of output, revealing that a substantial portion originated within a restricted neonatal window. In addi

Quantitative myocardial perfusion during stress using CMR is impaired in healthy Middle Eastern immigrants without CV risk factors

Middle Eastern immigrants constitute a growing proportion of the European population and compared to native Swedes are more insulin resistant, which can contribute to atherosclerosis. Quantitative first pass perfusion (qFPP) using cardiovascular magnetic resonance (CMR) can detect early signs of cardiovascular disease (CVD). The aim was to study if myocardial perfusion differs between healthy male

Intra-Patient Evolution of HIV-2 Molecular Properties

Limited data are available on the pathogenesis of HIV-2, and the evolution of Env molecular properties during disease progression is not fully elucidated. We investigated the intra-patient evolution of molecular properties of HIV-2 Env regions (V1–C3) during the asymptomatic, treatment-naïve phase of the infection in 16 study participants, stratified into faster or slower progressors. Most notably

Direct Reprogramming of Mouse Embryonic Fibroblasts to Conventional Type 1 Dendritic Cells by Enforced Expression of Transcription Factors

Ectopic expression of transcription factor combinations has been recently demonstrated to reprogram differentiated somatic cells towards the dendritic cell (DC) lineage without reversion to a multipotent state. DCs have the ability to induce potent and long-lasting adaptive immune responses. In particular, conventional type 1 DCs (cDC1s) excel on antigen cross-presentation, a critical step for ind

Learning from the past to plan for the future : A scoping review of musculoskeletal clinical research in Sweden 2010-2020

Background: The aims of this study are to 1) determine the scope of musculoskeletal (MSK)-related clinical research in Sweden; 2) collate the amount of first-tier funding received; 3) discuss strategies and infrastructure supporting future MSK clinical trials in Sweden. Methods: A systematic scoping review protocol was applied in PubMed, Scopus, and SweCRIS databases. The articles were examined, a

Single-cell transcriptional and functional analysis of dopaminergic neurons in organoid-like cultures derived from human fetal midbrain

Significant efforts are ongoing to develop refined differentiation protocols to generate midbrain dopamine (DA) neurons from pluripotent stem cells (PSCs) for application in disease modeling, diagnostics, drug screening, and cell-based therapies for Parkinson's Disease (PD). An increased understanding of the timing and molecular mechanisms promoting the generation of distinct subtypes of human mid

Orthostatic blood pressure adaptations, aortic stiffness, and central hemodynamics in the general population: insights from the Malmö Offspring Study (MOS)

PurposeArterial stiffness is independently associated with orthostatic hypotension in older individuals. The relationship between orthostatic blood pressure adaptation and aortic stiffness has not been thoroughly examined in a younger population. We investigated the relationship between orthostatic blood pressure adaptations, central aortic hemodynamics, and aortic stiffness in a cohort of predomi

Silencing of STE20-type kinase STK25 in human aortic endothelial and smooth muscle cells is atheroprotective

Recent studies highlight the importance of lipotoxic damage in aortic cells as the major pathogenetic contributor to atherosclerotic disease. Since the STE20-type kinase STK25 has been shown to exacerbate ectopic lipid storage and associated cell injury in several metabolic organs, we here investigate its role in the main cell types of vasculature. We depleted STK25 by small interfering RNA in hum

A multi-layer functional genomic analysis to understand noncoding genetic variation in lipids

A major challenge of genome-wide association studies (GWASs) is to translate phenotypic associations into biological insights. Here, we integrate a large GWAS on blood lipids involving 1.6 million individuals from five ancestries with a wide array of functional genomic datasets to discover regulatory mechanisms underlying lipid associations. We first prioritize lipid-associated genes with expressi

Genetically Determined Reproductive Aging and Coronary Heart Disease: A Bidirectional 2-sample Mendelian Randomization

Background: Accelerated reproductive aging, in women indicated by early natural menopause, is associated with increased coronary heart disease (CHD) risk in observational studies. Conversely, an adverse CHD risk profile has been suggested to accelerate menopause. Objectives: To study the direction and evidence for causality of the relationship between reproductive aging and (non-)fatal CHD and CHD

How good is the agreement between clinical diagnoses and classification criteria fulfilment in axial spondyloarthritis? Results from the SPARTAKUS cohort

Objectives: To study the agreement between clinical axial spondyloarthritis (axSpA) diagnoses and fulfilment of the Assessment of SpondyloArthritis international Society (ASAS) axSpA and modified New York (mNY) classification criteria, and to compare disease/health status between axSpA subtypes. Method: Patients with prevalent, clinical axSpA attending a rheumatology clinic were enrolled in a cros

Malmö POTS symptom score : Assessing symptom burden in postural orthostatic tachycardia syndrome

BACKGROUND: Postural orthostatic tachycardia syndrome (POTS) is a common cardiovascular autonomic disorder characterized by excessive heart rate (HR) increase on standing and symptoms of orthostatic intolerance, posing significant limitations on functional capacity. No objective tool exists to classify symptom burden in POTS.METHODS: We conducted a case-control study in 62 POTS patients and 50 hea

A somatic mutation in moesin drives progression into acute myeloid leukemia

Acute myeloid leukemia (AML) arises when leukemia-initiating cells, defined by a primary genetic lesion, acquire subsequent molecular changes whose cumulative effects bypass tumor suppression. The changes that underlie AML pathogenesis not only provide insights into the biology of transformation but also reveal novel therapeutic opportunities. However, backtracking these events in transformed huma

Tumor Suppressor Par-4 Regulates Complement Factor C3 and Obesity

Prostate apoptosis response-4 (Par-4) is a tumor suppressor that induces apoptosis in cancer cells. However, the physiological function of Par-4 remains unknown. Here we show that conventional Par-4 knockout (Par-4-/-) mice and adipocyte-specific Par-4 knockout (AKO) mice, but not hepatocyte-specific Par-4 knockout mice, are obese with standard chow diet. Par-4-/- and AKO mice exhibit increased ab

The association between plasma metabolites and future risk of all-cause mortality

Background: Metabolite profiles provide snapshots of the overall effect of numerous exposures accumulated over life courses, which may lead to health outcomes in the future. Objective: We hypothesized that the risk of all-cause mortality is linked to alterations in metabolism earlier in life, which are reflected in plasma metabolite profiles. We aimed to identify plasma metabolites associated with

Genome Editing Using Cas9-gRNA Ribonucleoprotein in Human Pluripotent Stem Cells for Disease Modeling

The discovery that the CRISPR/Cas9 system could be used for genome editing purposes represented a major breakthrough in the field. This advancement has notably facilitated the introduction or correction of disease-specific mutations in healthy or disease stem cell lines respectively; therefore, easing disease modeling studies in combination with differentiation protocols. For many years, variabili