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Orticumab : the potential to harness oxidized LDL to reduce coronary inflammation with plaque-targeted therapy

Purpose of review Myocardial infarction survivors are at a high risk of a recurrent event despite receiving guideline preventive therapy. There is accumulated evidence that persistent atherosclerotic plaque inflammation contributes to this risk. Oxidized low-density lipoprotein (LDL) is widely recognized as a key factor in plaque inflammation and instability; however, no therapies that directly ta

Size-selective glomerular filtration as a hallmark of premature kidney ageing in nondiabetic individuals

Background During the last decade, evidence has emerged on selective glomerular hypofiltration syndromes (SGHS), defined by selectively reduced filtration of middle-sized molecules irrespective of kidney function and resulting in a low ratio between cystatin C- and creatinine-based estimated glomerular filtration rates (eGFRcys/eGFRcr). We aimed to examine whether SGHS is a hallmark of premature k

Sugar-sweetened beverage intake associations with fasting glucose and insulin concentrations are not modified by selected genetic variants in a ChREBP-FGF21 pathway : a meta-analysis

Aims/hypothesis: Sugar-sweetened beverages (SSBs) are a major dietary contributor to fructose intake. A molecular pathway involving the carbohydrate responsive element-binding protein (ChREBP) and the metabolic hormone fibroblast growth factor 21 (FGF21) may influence sugar metabolism and, thereby, contribute to fructose-induced metabolic disease. We hypothesise that common variants in 11 genes in

Autoantibodies against aldehyde-modified collagen type IV are associated with risk of development of myocardial infarction

Background: Oxidation of LDL particles entrapped in the extracellular matrix of the arterial wall is a key factor in the development of atherosclerosis. Lipid oxidation products, such as malondialdehyde (MDA), react with surrounding extracellular matrix proteins and cause modifications that are recognized by the immune system. MDA modification of collagen type IV is increased in carotid lesions fr

Dietary folate intake and pancreatic cancer risk : Results from the European prospective investigation into cancer and nutrition

Pancreatic cancer (PC) has an exceptionally low survival rate and primary prevention strategies are limited. Folate plays an important role in one-carbon metabolism and has been associated with the risk of several cancers, but not consistently with PC risk. We aimed to investigate the association between dietary folate intake and PC risk, using the standardised folate database across 10 European c

Monogenic diabetes : From genetic insights to population-based precision in care. reflections from a diabetes care editors’ expert forum

Individualization of therapy based on a person’s specific type of diabetes is one key element of a “precision medicine” approach to diabetes care. However, applying such an approach remains difficult because of barriers such as disease heterogeneity, difficulties in accurately diagnosing different types of diabetes, multiple genetic influences, incomplete understanding of pathophysiology, limitati

Whole blood co-expression modules associate with metabolic traits and type 2 diabetes: an IMI-DIRECT study

Background: The rising prevalence of type 2 diabetes (T2D) poses a major global challenge. It remains unresolved to what extent transcriptomic signatures of metabolic dysregulation and T2D can be observed in easily accessible tissues such as blood. Additionally, large-scale human studies are required to further our understanding of the putative inflammatory component of insulin resistance and T2D.

Co-benefits from sustainable dietary shifts for population and environmental health : an assessment from a large European cohort study

Background: Unhealthy diets, the rise of non-communicable diseases, and the declining health of the planet are highly intertwined, where food production and consumption are major drivers of increases in greenhouse gas emissions, substantial land use, and adverse health such as cancer and mortality. To assess the potential co-benefits from shifting to more sustainable diets, we aimed to investigate

Validation of the classification for type 2 diabetes into five subgroups : a report from the ORIGIN trial

Aims/hypothesis: Data analyses from Swedish individuals with newly diagnosed diabetes have suggested that diabetes could be classified into five subtypes that differ with respect to the progression of dysglycaemia and the incidence of diabetes consequences. We assessed this classification in a multiethnic cohort of participants with established and newly diagnosed diabetes, randomly allocated to i

Ensemble of Deep Convolutional Neural Networks with Monte Carlo Dropout Sampling for Automated Image Segmentation Quality Control and Robust Deep Learning Using Small Datasets

Recent progress on deep learning (DL)-based medical image segmentation can enable fast extraction of clinical parameters for efficient clinical workflows. However, current DL methods can still fail and require manual visual inspection of outputs, which is time-consuming and diminishes the advantages of automation. For clinical applications, it is essential to develop DL approaches that can not onl

Cardiovascular Proteomics : A Post Hoc Analysis from a Phase II Randomized Clinical Trial Comparing GnRH Antagonist vs GnRH Agonist among Men with Advanced Prostate Cancer

PURPOSE: Recent studies demonstrated reduced cardiovascular (CV) risk with gonadotropin-releasing hormone (GnRH) antagonist, yet the underlying mechanism remains undetermined. The objective of this study was to examine longitudinal changes over time in established CV related proteins among men treated with GnRH agonists vs GnRH antagonist. MATERIALS AND METHODS: We performed a proteomics analysis

Attributes and predictors of long COVID

Reports of long-lasting coronavirus disease 2019 (COVID-19) symptoms, the so-called ‘long COVID’, are rising but little is known about prevalence, risk factors or whether it is possible to predict a protracted course early in the disease. We analyzed data from 4,182 incident cases of COVID-19 in which individuals self-reported their symptoms prospectively in the COVID Symptom Study app1. A total o

Glucocorticoid induced TNF receptor family-related protein (GITR) – A novel driver of atherosclerosis

Atherosclerosis is a lipid-driven, chronic inflammatory disease. In spite of efficient lipid lowering treatments, such as statins and PCSK9 inhibitors, patients, especially those with elevated inflammatory biomarkers, still have a significant residual cardiovascular disease risk. Novel drugs targeting inflammatory mediators are needed to further reduce this residual risk. Agonistic immune checkpoi

Cell-specific and divergent roles of the CD40L-CD40 axis in atherosclerotic vascular disease

Atherosclerosis is a major underlying cause of cardiovascular disease. Previous studies showed that inhibition of the co-stimulatory CD40 ligand (CD40L)-CD40 signaling axis profoundly attenuates atherosclerosis. As CD40L exerts multiple functions depending on the cell-cell interactions involved, we sought to investigate the function of the most relevant CD40L-expressing cell types in atheroscleros

Factors associated with serum ferritin levels and iron excess : results from the EPIC-EurGast study

Purpose: Excess iron is involved in the development of non-communicable diseases such as cancer, type 2 diabetes and cardiovascular conditions. We aimed to describe the prevalence of excess iron and its determinants in healthy European adults. Methods: Sociodemographic, lifestyle, iron status, dietary information, and HFE genotyping were obtained from controls from the nested case–control study EP

Mitochondrial clearance of calcium facilitated by MICU2 controls insulin secretion

Objective: Transport of Ca2+ into pancreatic β cell mitochondria facilitates nutrient-mediated insulin secretion. However, the underlying mechanism is unclear. Recent establishment of the molecular identity of the mitochondrial Ca2+ uniporter (MCU) and associated proteins allows modification of mitochondrial Ca2+ transport in intact cells. We examined the consequences of deficiency of the accessor

Consumption of ultra-processed foods associated with weight gain and obesity in adults : A multi-national cohort study

BACKGROUND: There is a worldwide shift towards increased consumption of ultra-processed foods (UPF) with concurrent rising prevalence of obesity. We examined the relationship between the consumption of UPF and weight gain and risk of obesity.METHODS: This prospective cohort included 348 748 men and women aged 25-70 years. Participants were recruited between 1992 and 2000 from 9 European countries

Hyponatremia in the Emergency Department: Could Biomarkers Help in Diagnosis and Treatment?

Objective: Hyponatremia is the most common electrolyte imbalance. The initial treatment decision is based on clinical evaluation of patient volume status but an accurate assessment is difficult, particularly differentiating mild hypovolemia from euvolemia. The aim of this study is to examine if biomarkers are valuable in the early determination of volume status and SIADH diagnosis. Methods: Blood

Cardiovascular risk assessment in south and middle-east asians living in the western countries

Nearly a quarter of the world population lives in the South Asian region (India, Pakistan, Bangladesh, Sri Lanka, Nepal, Bhutan, and the Maldives). Due to rapid demographic and epidemiological transition in these countries, the burden of non-communicable diseases is growing, which is a serious public health concern. Particularly, the prevalence of pre-diabetes, diabetes and atherosclerotic cardiov