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Plasma Folate, Related Genetic Variants, and Colorectal Cancer Risk in EPIC

Background: A potential dual role of folate in colorectal cancer (CRC) is currently subject to debate. We investigate the associations between plasma folate, several relevant folate-related polymorphisms, and CRC risk within the large European Prospective Investigation into Cancer and Nutrition cohort. Methods: In this nested case-control study, 1,367 incident CRC cases were matched to 2,325 contr

Plasma phospholipid fatty acid concentrations and risk of gastric adenocarcinomas in the European Prospective Investigation into Cancer and Nutrition (EPIC-EURGAST)

Background: Epidemiologic data suggest that diet is a risk factor in the etiology of gastric cancer. However, the role of dietary fatty acids, a modifiable risk factor, remains relatively unexplored. Objective: The objective of this study was to determine the association of plasma phospholipid fatty acid concentrations, as biomarkers of exogenous and endogenously derived fatty acids, with the risk

Whole-genome Bisulfite Sequencing of Human Pancreatic Islets Reveals Novel Differentially Methylated Regions in Type 2 Diabetes Pathogenesis

Current knowledge about the role of epigenetics in type 2 diabetes (T2D) remains limited. Only a few studies have investigated DNA methylation of selected candidate genes or a very small fraction of genomic CpG sites in human pancreatic islets, the tissue of primary pathogenic importance for diabetes. Our aim was to characterize the whole-genome DNA methylation landscape in human pancreatic islets

PNPLA3 variant M148 causes resistance to starvation-mediated lipid droplet autophagy in human hepatocytes

The mechanism of how patatin-like phospholipase domain-containing protein 3 (PNPLA3) variant M148 is associated with increased risk of development of hepatic steatosis is still debated. Here, we propose a novel role of PNPLA3 as a key player during autophagosome formation in the process of lipophagy. A human hepatocyte cell line, HepG2 cells, expressing recombinant I148 or 148M, was used to study

Disinformation, Deterrence and the Politics of Attribution

This article unpacks the politics of disinformation attribution as deterrence. Research and policy on disinformation deterrence commonly draw on frameworks inspired by cyber deterrence to address the ‘attribution problem’, thereby overlooking the political aspects underpinning attribution strategies in liberal democracies. Addressing this gap and bringing together disinformation studies and the fo

Intracellular cartilage oligomeric matrix protein augments breast cancer resistance to chemotherapy

Chemotherapy persists as the primary intervention for breast cancer, with chemoresistance posing the principal obstacle to successful treatment. Herein, we show that cartilage oligomeric matrix protein (COMP) expression leads to increased cancer cell survival and attenuated apoptosis under treatment with several chemotherapeutic drugs, anti-HER2 targeted treatment, and endocrine therapy in several

Expression of insulin signalling components in the sensory epithelium of the human saccule.

Several studies have demonstrated a link between diabetes and the dysfunction of the inner ear. Few studies, however, have reported the signalling mechanisms involved in metabolic control in human inner ear cells. Knowledge of the expression and role of the insulin receptor and downstream signalling components in the inner ear is sparce. Our immunohistochemistry approach has shown that the insulin

Salty taste preference, genetic susceptibility, and risk of metabolic dysfunction-associated steatotic liver disease : insights from three prospective cohorts

Background and aims: Animal studies have suggested that high salt intake might increase the risk of metabolic dysfunction-associated steatotic liver disease (MASLD), but results from populations are mixed, in part due to inadequate salt intake measurement. Salty taste preference is the primary factor leading to salt choice and can reflect habitual salt intake. However, no study has investigated t

Network-based insights into miRNA regulation of β-cell insulin secretion in type 2 diabetes

Increasing evidence suggests that microRNAs (miRNAs) contribute to pancreatic β-cell compensation during type 2 diabetes (T2D) pathogenesis. To examine miRNA-mRNA interactions in human islets and their roles in β-cell insulin secretion and T2D, we performed small-RNA sequencing on pancreatic islets from nine individuals with T2D and 52 non-diabetic controls. We identified 70 differentially express

Development of novel neutralizing single-chain fragment variable antibodies against S100A8

S100A8 plays a critical role in the pathogenesis of several inflammatory diseases and multiple types of cancer. Therefore, targeting the S100A8 function may alleviate the pathogenic process in various diseases. Here, specific single-chain variable fragment (scFv) antibodies targeting recombinant S100A8 (rS100A8) were selected by phage display technique and characterized using cDNA sequencing, immu

Association between Life's Simple 7 and life's essential 8 with all-cause and cardiovascular mortality in cardiovascular-kidney-metabolic syndrome population

Aims: This study compares the associations of Life's Simple 7 (LS7) and Life's Essential 8 (LE8) with all-cause and cardiovascular mortality in cardiovascular-kidney-metabolic (CKM) syndrome populations. Methods: This cohort study analyzed 11,487 participants aged ≥20 years with CKM syndrome from NHANES 2005–2018. Participants were categorized into non-advanced (stages 0–2) and advanced (stages 3–

Thirty years of prospective nationwide incidence of childhood type 1 diabetes : the accelerating increase by time tends to level off in Sweden

OBJECTIVE: During the past few decades, a rapidly increasing incidence of childhood type 1 diabetes (T1D) has been reported from many parts of the world. The change over time has been partly explained by changes in lifestyle causing rapid early growth and weight development. The current study models and analyzes the time trend by age, sex, and birth cohort in an exceptionally large study group.RES

Lysine potentiates insulin secretion via AASS-dependent catabolism and regulation of GABA content and signaling

Lysine is an essential amino acid with insulinotropic effects in humans. In vitro, it enhances glucose-stimulated insulin secretion (GSIS) in β-cell lines and rodent islets. While lysine is thought to act via membrane depolarization similar to arginine, the role of its intracellular metabolism in β-cell function remains unexplored. Here, we show that lysine acutely potentiates GSIS and that genes

Time, stress, and control in paratransit services : older passengers’ experiences and strategies

Paratransit services support individuals with limited mobility by providing access to healthcare, errands, and social activities. While designed to be enabling, these services impose temporal demands that require the user’s active engagement, such as booking in time and coordinating with other support services. This study explores how older users experience and manage the temporal dimensions of Sw

Cyclin-dependent kinase 10 controls bone formation and is linked to human skeletal health

BACKGROUND/OBJECTIVE: Bone remodeling is a critical process for skeletal health, and its dysregulation can lead to diseases like osteoporosis. While several Cyclin-Dependent Kinases (CDKs) are known to regulate bone metabolism, the function of CDK10 remains uncharacterized in this context. Human mutations in CDK10 cause the Al Kaissi syndrome, which involves severe skeletal defects, suggesting a

Influence of Preexisting Psychiatric Morbidity on Liothyronine Use in Hypothyroidism : A Swedish Nationwide Cohort Study

Context: Autoimmune hypothyroidism is a common endocrine disorder affecting 1% to 2% of the population in iodine sufficient areas. While levothyroxine is standard treatment, a substantial number of patients report persistent symptoms despite adequate treatment. The use of liothyronine as an adjunct to levothyroxine therapy has increased. The psychiatric characteristics of patients receiving liothy

Cardiovascular-kidney-metabolic syndrome : prevalence, risks, disease trajectories, and early-stage management

Cardiovascular-kidney-metabolic (CKM) syndrome affects approximately 90% of US adults, arising from the convergence of metabolic dysfunction, chronic kidney disease (CKD), and cardiovascular disease (CVD). These conditions create self-reinforcing cycles of multiorgan damage, substantially increasing mortality risk. The American Heart Association’s 2023 staging framework stratifies CKM from stage 0

Freight Transportation Security System

Freight transportation security concerns both public and private actors, however, their interests are often misaligned resulting in conflicting pressure and trade-offs. To understand this, a connection of macro and micro perspectives is required, which is enabled by an institutional lens. Furthermore, there is limited empirical knowledge of how policy design and implementation shape operational co

Joint control of low-density lipoprotein cholesterol, lipoprotein(a), and high-sensitivity C-reactive protein in relation to risk of cardiovascular disease in adults with steatotic liver disease

Background and aims: We examined whether the excess cardiovascular disease (CVD) risk among adults with steatotic liver disease (SLD) subtypes could be reduced or eliminated through joint control of low-density lipoprotein cholesterol (LDL-C), lipoprotein(a) [Lp(a)], and high-sensitivity C-reactive protein (hs-CRP). Methods and results: This prospective cohort study included 291,995 participants f

Expectations and experiences regarding family planning, pregnancy, and motherhood in women with type 1 diabetes – A qualitative study

Background: Optimal treatment and support in family planning for women with type 1 diabetes (T1D) and follow-up during pregnancy are important, however, there is limited knowledge from the women’s perspective on their considerations of family planning, pregnancy, and motherhood. Objectives: To explore expectations and experiences of family planning, pregnancy, and motherhood among women with T1D.