Dysregulation of MMP2-dependent TGF-ß2 activation impairs fibrous cap formation in type 2 diabetes-associated atherosclerosis.

Type 2 diabetes is associated with cardiovascular disease, possibly due to impaired vascular fibrous repair. Yet, the mechanisms are elusive. Here, we investigate alterations in the fibrous repair processes in type 2 diabetes atherosclerotic plaque extracellular matrix by combining multi-omics from the human Carotid Plaque Imaging Project cohort and functional studies.

Robust, credible, and interpretable AI-based histopathological prostate cancer grading.

Background: Prostate cancer (PCa) is among the most common cancers in men and its diagnosis requires the histopathological evaluation of biopsies by human experts. While several recent artificial intelligence-based (AI) approaches have reached human expert-level PCa grading, they often display significantly reduced performance on external datasets. This reduced performance can be caused by variations in sample preparation, for instance the staining protocol, section thickness, or scanner used.

Interleukin-1 receptor accessory protein blockade limits the development of atherosclerosis and reduces plaque inflammation.

Aims: The interleukin-1 receptor accessory protein (IL1RAP) is a co-receptor required for signalling through the IL-1, IL-33, and IL-36 receptors. Using a novel anti-IL1RAP-blocking antibody, we investigated the role of IL1RAP in atherosclerosis.

Methods And Results: Single-cell RNA sequencing data from human atherosclerotic plaques revealed the expression of IL1RAP and several IL1RAP-related cytokines and receptors, including IL1B and IL33.

Invariant natural killer T cells and incidence of first-time coronary events: a nested case-control study.

Aims: Invariant natural killer T (iNKT) cells, a T cell subset that is CD1d-restricted and expresses a semi-invariant T cell receptor, have been proposed to contribute to dyslipidaemia-driven cardiovascular disease due to their ability to specifically recognize lipid antigens. Studies in mice have attributed pro-atherogenic properties to iNKT cells, but studies in humans investigating associations of iNKT cells with incident coronary events (CE) are lacking.

Methods And Results: Here, we used flow cytometry to enumerate circulating iNKT cells (CD3 CD1d-PBS57-Tetramer) in a case-control cohort nested within the prospective population-based Malmö Diet and Cancer Study ( = 416) to explore associations with incident first-time CE during a median follow-up of 14 years.

Observational study of diagnosis and management in adult primary hypothyroidism in southwest of Sweden.

Objective: The objective was to explore the management of newly diagnosed hypothyroidism in adults regarding laboratory diagnostics and treatment in Region Halland (RH). In addition, to investigate whether current recommendations were followed regarding diagnostics.

Design: Retrospective observational study.

Transforming growth factor-β2 is associated with atherosclerotic plaque stability and lower risk for cardiovascular events.

Aims: Transforming growth factor-beta (TGF-β) exists in three isoforms TGF-β1, -β2, and -β3. TGF-β1 has been suggested to be important for maintaining plaque stability, yet the role of TGF-β2 and -β3 in atherosclerosis remains to be investigated.This study explores the association of the three isoforms of TGF-β with plaque stability in the human atherosclerotic disease.

Plasma levels of CCL21, but not CCL19, independently predict future coronary events in a prospective population-based cohort.

Background And Aims: The homeostatic chemokines CCL21 and CCL19 have been explored as biomarkers in cardiovascular disease prediction in patients with established cardiovascular disease, but associations between these chemokines and first-time coronary event incidence have not been investigated before. Here, we explored associations between CCL21 or CCL19 and first-time incident coronary events in the general population-based Malmö Diet and Cancer cohort with two decades of follow-up.

Methods: CCL21 and CCL19 levels in plasma were analysed with ELISA and proximity extension assay and associations with disease incidence were explored with conditional logistic regression in a nested case-control cohort (CCL21; n = 676) and with Cox regression in a population-based cohort (CCL19; n = 4636).

AI-based prostate analysis system trained without human supervision to predict patient outcome from tissue samples.

In order to plan the best treatment for prostate cancer patients, the aggressiveness of the tumor is graded based on visual assessment of tissue biopsies according to the Gleason scale. Recently, a number of AI models have been developed that can be trained to do this grading as well as human pathologists. But the accuracy of the AI grading will be limited by the accuracy of the subjective "ground truth" Gleason grades used for the training.

Neuronal Sprouting and Reorganization in Bone Tissue Infiltrated by Human Breast Cancer Cells.

Background: Pain is a common complication for patients with metastatic bone disease. Animal models suggest that the pain, in part, is driven by pathological sprouting and reorganization of the nerve fibers innervating the bone. Here, we investigate how these findings translate to humans.

Digging deep into a GAC filter - Temporal and spatial profiling of adsorbed organic micropollutants.

A large pilot-scale granular activated carbon (GAC) filter was operated downstream in a full-scale wastewater treatment plant to remove organic micropollutants. To describe the spatial and temporal developments of micropollutant adsorption profiles in the GAC filter, micropollutants were extracted from GAC media taken at various filter depths and number of treated bed volumes. At a low number of treated bed volumes (2600 BVs), most micropollutants were adsorbed in the top layers of the filter.

Osteomodulin attenuates smooth muscle cell osteogenic transition in vascular calcification.

Rationale: Vascular calcification is a prominent feature of late-stage diabetes, renal and cardiovascular disease (CVD), and has been linked to adverse events. Recent studies in patients reported that plasma levels of osteomodulin (OMD), a proteoglycan involved in bone mineralisation, associate with diabetes and CVD. We hypothesised that OMD could be implicated in these diseases via vascular calcification as a common underlying factor and aimed to investigate its role in this context.

Osteomodulin Gene Expression Is Associated With Plaque Calcification, Stability, and Fewer Cardiovascular Events in the CPIP Cohort.

Background: Stable atherosclerotic plaques are characterized by thick fibrous caps of smooth muscle cells, collagen, and macrocalcifications. Identifying factors of plaque stability is necessary to design drugs to prevent plaque rupture and symptoms. Osteomodulin, originally identified in bones, is expressed by bone synthesizing osteoblasts and involved in mineralization.

Soluble CD40 Levels in Plasma Are Associated with Cardiovascular Disease and in Carotid Plaques with a Vulnerable Phenotype.

Background And Purpose: CD40 and CD40 ligand (CD40L) are costimulatory molecules of the tumor necrosis factor receptor superfamily and well known for their involvement in inflammatory diseases: atherosclerotic mouse models with disrupted CD40 signalling develop lesions of reduced size with a more stable plaque profile. This study investigated the potential of plasma and intraplaque levels of CD40 and CD40L as markers for cardiovascular disease (CVD) in humans and their association with plaque stability.

Methods: Soluble CD40 and CD40L (sCD40L) were measured in plasma in 1,437 subjects from The SUrrogate markers for Micro- and Macro-vascular hard endpoints for Innovative diabetes Tools (SUMMIT) cohort.

High levels of autoantibodies against apoB100 p210 are associated with lower incidence of atrial fibrillation in women.

Background And Objectives: Atrial fibrillation (AF) is associated with inflammation, both systemically and in the atrial tissue. Oxidized low-density lipoprotein (LDL) is increased in patients with AF and is suggested to be one of the molecules that drives inflammation. Autoantibodies against oxidized LDL and apolipoprotein B100, the protein component of LDL, are linked to atherosclerotic disease.

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-C6 in patients with atherosclerosis, to determine the predictive potential of the biomarker.

Antibodies against apoB100 peptide 210 inhibit atherosclerosis in apoE mice.

Atherosclerotic plaques are characterized by an accumulation and subsequent oxidation of LDL, resulting in adaptive immune responses against formed or exposed neoepitopes of the LDL particle. Autoantibodies against native p210, the 3136-3155 amino acid sequence of the LDL protein apolipoprotein B-100 (apoB100) are common in humans and have been associated with less severe atherosclerosis and decreased risk for cardiovascular events in clinical studies. However, whether apoB100 native p210 autoantibodies play a functional role in atherosclerosis is not known.

Autoantibodies Against Methylglyoxal-Modified Apolipoprotein B100 and ApoB100 Peptide Are Associated With Less Coronary Artery Atherosclerosis and Retinopathy in Long-Term Type 1 Diabetes.

Objective: Methylglyoxal (MGO), a reactive aldehyde forming advanced glycation end products (AGEs), is increased in diabetes and recognized by the immune system, resulting in anti-AGE-specific autoantibodies. The association of these immune responses with macro- and microvascular complications in type 1 diabetes remains unclarified. We investigated associations between MGO-modified apolipoprotein B100 (apoB100) and apoB100 peptide 5 (MGO-p5) autoantibodies and coronary atherosclerosis and retinopathy in type 1 diabetes.

Reduced oxidized LDL in T2D plaques is associated with a greater statin usage but not with future cardiovascular events.

Background: Type 2 diabetes (T2D) patients are at a greater risk of cardiovascular events due to aggravated atherosclerosis. Oxidized LDL (oxLDL) has been shown to be increased in T2D plaques and suggested to contribute to plaque ruptures. Despite intensified statin treatment during the last decade the higher risk for events remains.

The proteoglycan mimecan is associated with carotid plaque vulnerability and increased risk of future cardiovascular death.

Background And Aims: A vulnerable plaque is an atherosclerotic plaque that is rupture-prone with a higher risk to cause cardiovascular symptoms such as myocardial infarction or stroke. Mimecan or osteoglycin is a small leucine-rich proteoglycan, important for collagen fibrillogenesis, that has been implicated in atherosclerotic disease, yet the role of mimecan in human atherosclerotic disease remains unknown.

Methods: 196 human atherosclerotic carotid plaques were immunostained for mimecan.

CD163+ macrophages are associated with a vulnerable plaque phenotype in human carotid plaques.

Macrophages are a functionally heterogeneous group of immune cells abundant in atherosclerotic plaques. Macrophages expressing CD163 are associated with intraplaque hemorrhage and have previously been considered atheroprotective. However, in a recent study CD163-deficient atherosclerotic ApoE mice exhibited smaller and less complex plaques, suggesting a proatherogenic role of CD163.

Interventions to reduce dehydration related to defunctioning loop ileostomy after low anterior resection in rectal cancer: a prospective cohort study.

Background: Defunctioning loop ileostomy (DLI) in low anterior resection (LAR) in rectal cancer patients reduces the morbidity of anastomotic leakages. In our previous study, 30% of patients developed dehydration due to DLI, mostly during the first 6 weeks. This interventional study aimed to reduce these figures by establishing a surveillance programme.

Lipoprotein ability to exchange and remove lipids from model membranes as a function of fatty acid saturation and presence of cholesterol.

Lipoproteins play a central role in the development of atherosclerosis. High and low-density lipoproteins (HDL and LDL), known as 'good' and 'bad' cholesterol, respectively, remove and/or deposit lipids into the artery wall. Hence, insight into lipid exchange processes between lipoproteins and cell membranes is of particular importance in understanding the onset and development of cardiovascular disease.

Low Levels of CD4CD28 T Cells at Baseline Are Associated With First-Time Coronary Events in a Prospective Population-Based Case-Control Cohort.

Objective: CD4CD28 T cells have been shown to be associated with recurrent coronary events and suggested as potential biomarker and therapeutic target. It is unknown whether CD4CD28 T cells associate with first-time cardiovascular events. We examined CD4CD28 T cells in a prospective population-based cohort and in patients with advanced atherosclerosis.