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Metformin is the key factor in elevated plasma growth differentiation factor-15 levels in type 2 diabetes : A nested, case–control study

Produced as a tissue defence response to hypoxia and inflammation, growth differentiation factor-15 (GDF-15) is elevated in people receiving metformin treatment. To gain insight into the relationship of GDF-15 with metformin and major cardiovascular risk factors, we analysed the data from the SUMMIT cohort (n = 1438), a four-centre, nested, case–control study aimed at verifying whether biomarkers

Population-Level Analysis to Determine Parameters That Drive Variation in the Plasma Metabolite Profiles

The plasma metabolome is associated with multiple phenotypes and diseases. However, a systematic study investigating clinical determinants that control the metabolome has not yet been conducted. In the present study, therefore, we aimed to identify the major determinants of the plasma metabolite profile. We used ultra-high performance liquid chromatography (UHPLC) coupled to quadrupole time of fli

Metabolically healthy obesity (MHO) in the Malmö diet cancer study - Epidemiology and prospective risks

BACKGROUND/AIMS: Metabolically healthy obesity (MHO) remains controversial, since the underlying mechanisms behind this phenotype remain unclear. We aimed to investigate the characteristics of MHO, as well as prospective risks.METHOD: A cross-sectional analysis was carried out in a subsample of 3812 obese subjects selected from the Malmo diet cancer study (n=28,403). Subjects with MHO (n=1182) wer

Low prevalence of known pathogenic mutations in dominant PD genes : A Swedish multicenter study

Objective: To determine the frequency of mutations known to cause autosomal dominant Parkinson disease (PD) in a series with more than 10% of Sweden's estimated number of PD patients. Methods: The Swedish Parkinson Disease Genetics Network was formed as a national multicenter consortium of clinical researchers who together have access to DNA from a total of 2,206 PD patients; 85.4% were from popul

First Genome-Wide Association Study of Latent Autoimmune Diabetes in Adults Reveals Novel Insights Linking Immune and Metabolic Diabetes

OBJECTIVE: Latent autoimmune diabetes in adults (LADA) shares clinical features with both type 1 and type 2 diabetes; however, there is ongoing debate regarding the precise definition of LADA. Understanding its genetic basis is one potential strategy to gain insight into appropriate classification of this diabetes subtype.RESEARCH DESIGN AND METHODS: We performed the first genome-wide association

Copeptin, B-type natriuretic peptide and cystatin C are associated with incident symptomatic PAD

Purpose: The aim of this study is to evaluate plasma biomarkers as predictors for peripheral arterial disease (PAD). Materials and methods: Prospective longitudinal cohort study of middle-aged individuals from the cardiovascular cohort of the Malmö Diet and Cancer study (MDCS) (n = 5550; 1991–94). Cystatin C, copeptin, N-terminal pro-B-type natriuretic peptide (N-BNP), midregional proatrial natriu

A prediction model for the 40-year risk of knee osteoarthritis in adolescent men

OBJECTIVES: To simplify the previously published Nottingham 12-year risk prediction model for knee osteoarthritis (OA) and examine whether it can be used to predict the 40-year risk of knee OA in young men.METHODS: We included 40 118 men aged 18 undergoing military conscription in Sweden 1969-70. Diagnostic OA codes were obtained from the Swedish National Patient Register 1987-2010. The original N

Stochastic unfolding of nanoconfined DNA : Experiments, model and Bayesian analysis

Nanochannels provide a means for detailed experiments on the effect of confinement on biomacromolecules, such as DNA. Here we introduce a model for the complete unfolding of DNA from the circular to linear configuration. Two main ingredients are the entropic unfolding force and the friction coefficient for the unfolding process, and we describe the associated dynamics by a non-linear Langevin equa

Acoustophoresis for label-free separation and concentration of cancer cells

Here, an acoustophoresis chip is presented that is capable of separating cancer cells from white blood cells (WBCs) and subsequently concentrating the recovered cells in the same chip. The chip utilizes ultrasound standing waves in two dimensions to pre-align, separate and concentrate the cells. 92% of the cancer cells could be recovered while keeping the contamination level of WBCs to only 0.6%.

A phenome-wide comparative analysis of genetic discordance between obesity and type 2 diabetes

Obesity and type 2 diabetes are causally related, yet there is considerable heterogeneity in the consequences of both conditions and the mechanisms of action are poorly defined. Here we show a genetic-driven approach defining two obesity profiles that convey highly concordant and discordant diabetogenic effects. We annotate and then compare association signals for these profiles across clinical an

Insights on Genetic and Environmental Factors in Parkinson's Disease from a Regional Swedish Case-Control Cohort

BACKGROUND: Risk factors for Parkinson's disease (PD) can be more or less relevant to a population due to population-specific genetic architecture, local lifestyle habits, and environmental exposures. Therefore, it is essential to study PD at a local, regional, and continental scale in order to increase the knowledge on disease etiology.OBJECTIVE: We aimed to investigate the contribution of geneti

Artificial intelligence for direct-to-physician reporting of ambulatory electrocardiography

Developments in ambulatory electrocardiogram (ECG) technology have led to vast amounts of ECG data that currently need to be interpreted by human technicians. Here we tested an artificial intelligence (AI) algorithm for direct-to-physician reporting of ambulatory ECGs. Beat-by-beat annotation of 14,606 individual ambulatory ECG recordings (mean duration = 14 ± 10 days) was performed by certified E

The prognostic significance of stress-phenotyping for stroke incidence : the Malmö Diet and Cancer Study

BACKGROUND: Self-reported mental stress is not consistently recognized as a risk factor for stroke. This prompted development of a novel algorithm for stress-phenotype indices to quantify chronic stress prevalence in relation to a modified stroke risk score in a South African cohort. The algorithm is based on biomarkers adrenocorticotrophic hormone, high-density lipoprotein cholesterol, high-sensi

Modern land use changes drive shifts in nutrient cycling and diatom assemblages in the Baltic Sea coastal zone : A millennial perspective with a case study from Gamlebyviken, Swedish east coast

This study aims to investigate and disentangle the impact of land use and climate variability on the Baltic Sea coastal zone from a millennial perspective. To assess the environmental status of the coastal zone we make use of siliceous microfossils (mainly diatoms), stable nitrogen and carbon isotopes, organic carbon accumulation rates, and lithological changes analyzed in a sediment core collecte

Exploring the effect of menstrual loss and dietary habits on iron deficiency in teenagers : A cross-sectional study

Adolescent girls are particularly susceptible to iron deficiency due to increased iron requirements during the pubertal growth spurt, combined with iron loss following menarche. This study aimed to investigate the prevalence of heavy menstrual bleeding in an adolescent population using the SAMANTA questionnaire and to explore its relationship with dietary habits and iron deficiency. This cross-sec

Evaluating cell-specific gene expression using single-cell and single-nuclei RNA-sequencing data from human pancreatic islets of the same donors

Single-cell and single-nuclei RNA-sequencing (scRNA-seq and snRNA-seq) analyze cell-specific transcriptomes. However, only snRNA-seq applies to frozen biobanked samples. For human pancreatic islets, marker genes and reference-based cell type annotation methods are mainly from scRNA-seq datasets and may not be suitable for snRNA-seq. We compared human islet scRNA-seq and snRNA-seq data from the sam

Precision medicine in complex diseases - : Molecular subgrouping for improved prediction and treatment stratification

Complex diseases are caused by a combination of genetic, lifestyle, and environmental factors and comprise common noncommunicable diseases, including allergies, cardiovascular disease, and psychiatric and metabolic disorders. More than 25% of Europeans suffer from a complex disease, and together these diseases account for 70% of all deaths. The use of genomic, molecular, or imaging data to develop

Plaque characteristics and biomarkers predicting regression and progression of carotid atherosclerosis

The factors that influence the atherosclerotic disease process in high-risk individuals remain poorly understood. Here, we used a combination of vascular imaging, risk factor assessment, and biomarkers to identify factors associated with 3-year change in carotid disease severity in a cohort of high-risk subjects treated with preventive therapy (n = 865). The results show that changes in intima-med

The highly expressed calcium-insensitive synaptotagmin-11 and synaptotagmin-13 modulate insulin secretion

AIM: SYT11 and SYT13, two calcium-insensitive synaptotagmins, are downregulated in islets from type-2 diabetic donors, but their function in insulin secretion is unknown. To address this, we investigated the physiological role of these two synaptotagmins in insulin secreting cells.METHODS: Correlations between gene expression levels were performed using previously described RNA-seq data on islets