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Alternative Complement Pathway in Carotid Atherosclerosis : Low Plasma Properdin Levels Associate With Long-Term Cardiovascular Mortality

BACKGROUND: Complement activation may promote atherosclerosis. Yet, data on the to which extent complement, and more specifically the alternative complement pathway, is activated in patients with carotid atherosclerosis and related to adverse outcome in these patients, are scarce.METHODS AND RESULTS: We measured, by ELISA, plasma levels of factor D, properdin, C3bBbP (C3 convertase), and factor H

Outdoor living environment and cardiovascular disease risk: results from a Swedish cohort

Cardiovascular disease (CVD) is the leading cause of mortality and morbidity worldwide. While sociodemographic, dietary and lifestyle factors have been well documented in relation to CVD, environmental factors have been less studied. However, considering the ongoing biodiversity, climate, and health crises, it is imperative to better understand the interplay between the environment and health. Thi

TARGET-seq: Linking single-cell transcriptomics of human dopaminergic neurons with their target specificity

Dopaminergic (DA) neurons exhibit significant diversity characterized by differences in morphology, anatomical location, axonal projection pattern, and selective vulnerability to disease. More recently, scRNAseq has been used to map DA neuron diversity at the level of gene expression. These studies have revealed a higher than expected molecular diversity in both mouse and human DA neurons. However

Integrating molecular photoswitch memory with nanoscale optoelectronics for neuromorphic computing

Photonic solutions are potentially highly competitive for energy-efficient neuromorphic computing. However, a combination of specialized nanostructures is needed to implement all neuro-biological functionality. Here, we show that donor-acceptor Stenhouse adduct dyes integrated with III-V semiconductor nano-optoelectronics have combined excellent functionality for bio-inspired neural networks. The

Forced LMX1A expression induces dorsal neural fates and disrupts patterning of human embryonic stem cells into ventral midbrain dopaminergic neurons

The differentiation of human pluripotent stem cells into ventral mesencephalic dopaminergic (DA) fate is relevant for the treatment of Parkinson's disease. Shortcuts to obtaining DA cells through direct reprogramming often include forced expression of the transcription factor LMX1A. Although reprogramming with LMX1A can generate tyrosine hydroxylase (TH)-positive cells, their regional identity rem

Serum ARGS-aggrecan in a phase 2 clinical trial targeting osteoarthritis

OBJECTIVE: To monitor serum concentrations of the aggrecan alanine-arginine-glycine-serine (ARGS) neoepitope in a clinical trial of a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-5 inhibition as disease-modifying therapy of knee osteoarthritis, and to investigate relationships between reduction in ARGS and change in cartilage thickness, knee-related pain and function. DESITo monitor serum concentrations of the aggrecan alanine-arginine-glycine-serine (ARGS) neoepitope in a clinical trial of a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-5 inhibition as disease-modifying therapy of knee osteoarthritis, and to investigate relationships between reduction in ARGS and change in cartilage thickness, knee-related pain and function.DesignROCCELLA t

Factors most strongly associated with breathlessness in a population aged 50–64 years

Background: Breathlessness is a troublesome and prevalent symptom in the population, but knowledge of related factors is scarce. The aim of this study was to identify the factors most strongly associated with breathlessness in the general population and to describe the shapes of the associations between the main factors and breathlessness.Methods: a cross-sectional analysis of the multicentre popu

Prior electrocardiograms not useful for machine learning predictions of major adverse cardiac events in emergency department chest pain patients

At the emergency department (ED), it is important to quickly and accurately determine which patients are likely to have a major adverse cardiac event (MACE). Machine learning (ML) models can be used to aid physicians in detecting MACE, and improving the performance of such models is an active area of research. In this study, we sought to determine if ML models can be improved by including a prior

The novel collagen matrikine, endotrophin, is associated with mortality and cardiovascular events in patients with atherosclerosis

Background: Rupture of atherosclerotic plaques is the major cause of acute cardiovascular events. The biomarker PRO-C6 measuring Endotrophin, a matrikine of collagen type VI, may provide valuable information detecting subjects in need of intensified strategies for secondary prevention. Objective: In this study, we evaluate endotrophin in human atherosclerotic plaques and circulating levels of PRO-

Tract-based white matter hyperintensity patterns in patients with systemic lupus erythematosus using an unsupervised machine learning approach

Currently, little is known about the spatial distribution of white matter hyperintensities (WMH) in the brain of patients with Systemic Lupus erythematosus (SLE). Previous lesion markers, such as number and volume, ignore the strategic location of WMH. The goal of this work was to develop a fully-automated method to identify predominant patterns of WMH across WM tracts based on cluster analysis. A

Thrombomodulin (THBD) gene variants and thrombotic risk in a population-based cohort study

Background: The protein C anticoagulant system plays a key role in maintaining the hemostatic balance. Although several studies have identified thrombomodulin gene (THBD) variants among venous thromboembolism (VTE) patients, the role of THBD in relation to VTE in humans remains to be clarified. Objectives: This study aimed to determine the thrombotic risk of rare and common THBD variants in a larg

Associations of Interleukin-5 With Plaque Development and Cardiovascular Events

Experimental studies have suggested an atheroprotective role of interleukin (IL)-5 through the stimulation of natural immunoglobulin M antibody expression. In the present study we show that there are no associations between baseline levels of IL-5 and risk for development of coronary events or stroke during a 15.7 ± 6.3 years follow-up of 696 subjects randomly sampled from the Malmö Diet and Cance

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To mark her 90th birthday on 24 January, MaerzMusik – Festival for Time Issues will devote a special programme to Éliane Radigue, highlighting the many facets of the composer’s work.

Genotoxicity by rapeseed methyl ester and hydrogenated vegetable oil combustion exhaust products in lung epithelial (A549) cells

Biofuel is an attractive substitute for petrodiesel because of its lower environmental footprint. For instance, the polycyclic aromatic hydrocarbons (PAH) emission per fuel energy content is lower for rapeseed methyl ester (RME) than for petrodiesel. The present study assesses genotoxicity by extractable organic matter (EOM) of exhaust particles from combustion of petrodiesel, RME and hydrogenated

PLASMA METABOLOMIC PROFILING PREDICTS AORTIC STIFFNESS AND RISK OF INCIDENT CARDIOVASCULAR DISEASE AND MORTALITY AFTER 16 YEARS OF FOLLOW-UP IN THE GENERAL POPULATION

Objective: The mechanisms and metabolomic profile underlying early vascular ageing have not been explored in the general population. We aimed to investigate the plasma metabolomic profile in aortic stiffness (vascular ageing) and associated risk of incident cardiovascular disease and mortality in the general population.Design and method: We analysed 108 metabolites in plasma of 5172 individuals fr

GATA2 mitotic bookmarking is required for definitive haematopoiesis

In mitosis, most transcription factors detach from chromatin, but some are retained and bookmark genomic sites. Mitotic bookmarking has been implicated in lineage inheritance, pluripotency and reprogramming. However, the biological significance of this mechanism in vivo remains unclear. Here, we address mitotic retention of the hemogenic factors GATA2, GFI1B and FOS during haematopoietic specifica

Proteomic changes to immune and inflammatory processes underlie lung preservation using ex vivo cytokine adsorption.

INTRODUCTION: In recent years, the field of graft preservation has made considerable strides in improving outcomes related to solid organ restoration and regeneration. Ex vivo lung perfusion (EVLP) in line with the related devices and treatments has yielded promising results within preclinical and clinical studies, with the potential to improve graft quality. Its main benefit is to render marginal

Genome-wide RNAi Screen Identifies Cohesin Genes as Modifiers of Renewal and Differentiation in Human HSCs

To gain insights into the regulatory mechanisms of hematopoietic stem cells (HSCs), we employed a genome-wide RNAi screen in human cord-blood derived cells and identified candidate genes whose knockdown maintained the HSC phenotype during culture. A striking finding was the identification of members of the cohesin complex (STAG2, RAD21, STAG1, and SMC3) among the top 20 genes from the screen. Upon

Coding variation in ANGPTL4, LPL, and SVEP1 and the risk of coronary disease

BACKGROUND: The discovery of low-frequency coding variants affecting the risk of coronary artery disease has facilitated the identification of therapeutic targets. METHODS: Through DNA genotyping, we tested 54,003 coding-sequence variants covering 13,715 human genes in up to 72,868 patients with coronary artery disease and 120,770 controls who did not have coronary artery disease. Through DNA sequ