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Estimating the Direct Effect between Dietary Macronutrients and Cardiometabolic Disease, Accounting for Mediation by Adiposity and Physical Activity

Assessing the causal effects of individual dietary macronutrients and cardiometabolic disease is challenging owing to the complexity to distinguish direct effects from those mediated or confounded by other factors. To estimate these effects, intake of protein, carbohydrate, sugar, fat, and its subtypes were obtained using food frequency data derived from a Swedish population-based cohort (n~60,000

Four groups of type 2 diabetes contribute to the etiological and clinical heterogeneity in newly diagnosed individuals: An IMI DIRECT study

The presentation and underlying pathophysiology of type 2 diabetes (T2D) is complex and heterogeneous. Recent studies attempted to stratify T2D into distinct subgroups using data-driven approaches, but their clinical utility may be limited if categorical representations of complex phenotypes are suboptimal. We apply a soft-clustering (archetype) method to characterize newly diagnosed T2D based on

What makes children learn how to swim? – health, lifestyle and environmental factors associated with swimming ability among children in the city of Malmö, Sweden

Background: Swimming ability among children in the city of Malmö, Sweden is strongly affected by socioeconomic differences. We investigated to what extent mediating health and lifestyle factors, such as children’s eating, sleeping and physical activity habits, as well as the characteristics of the social and working environment at both school and home, could explain the socioeconomic gradient in s

Exposome-wide ranking of modifiable risk factors for cardiometabolic disease traits

The present study assessed the temporal associations of ~ 300 lifestyle exposures with nine cardiometabolic traits to identify exposures/exposure groups that might inform lifestyle interventions for the reduction of cardiometabolic disease risk. The analyses were undertaken in a longitudinal sample comprising > 31,000 adults living in northern Sweden. Linear mixed models were used to assess the av

International Society for Heart and Lung Transplantation Guidelines for the Evaluation and Care of Cardiac Transplant Candidates-2024

The "International Society for Heart and Lung Transplantation Guidelines for the Evaluation and Care of Cardiac Transplant Candidates-2024" updates and replaces the "Listing Criteria for Heart Transplantation: International Society for Heart and Lung Transplantation Guidelines for the Care of Cardiac Transplant Candidates-2006" and the "2016 International Society for Heart Lung Transplantation Lis

Critical time window of neuronal cholesterol synthesis during neurite outgrowth

Cholesterol is an essential membrane component enriched in plasma membranes, growth cones, and synapses. The brain normally synthesizes all cholesterol locally, but the contribution of individual cell types to brain cholesterol metabolism is unknown. To investigate whether cortical projection neurons in vivo essentially require cholesterol biosynthesis and which cell types support neurons, we have

Unanswered questions in prostate cancer — findings of an international multi-stakeholder consensus by the PIONEER consortium

PIONEER is a European network of excellence for big data in prostate cancer consisting of 37 private and public stakeholders from 9 countries across Europe. Many progresses have been done in prostate cancer management, but unanswered questions in the field still exist, and big data could help to answer these questions. The PIONEER consortium conducted a two-round modified Delphi survey aiming at b

Identification of Genetic Variation Influencing Metformin Response in a Multiancestry Genome-Wide Association Study in the Diabetes Prevention Program (DPP)

Genome-wide significant loci for metformin response in type 2 diabetes reported elsewhere have not been repli-cated in the Diabetes Prevention Program (DPP). To as-sess pharmacogenetic interactions in prediabetes, we conducted a genome-wide association study (GWAS) in the DPP. Cox proportional hazards models tested associations with diabetes incidence in the metformin (MET; n = 876) and placebo (P

Unconventional Charge-Density-Wave Gap in Monolayer NbS2

Using scanning tunneling microscopy and spectroscopy, for a monolayer of transition metal dichalcogenide H-NbS2 grown by molecular beam epitaxy on graphene, we provide unambiguous evidence for a charge density wave (CDW) with a 3 × 3 superstructure, which is not present in bulk NbS2. Local spectroscopy displays a pronounced gap on the order of 20 meV at the Fermi level. Within the gap, low-energy

Precision medicine for cardiometabolic disease : a framework for clinical translation

Cardiometabolic disease is a major threat to global health. Precision medicine has great potential to help to reduce the burden of this common and complex disease cluster, and to enhance contemporary evidence-based medicine. Its key pillars are diagnostics; prediction (of the primary disease); prevention (of the primary disease); prognosis (prediction of complications of the primary disease); trea

Research Protocol for an Observational Health Data Analysis on the Adverse Events of Systemic Treatment in Patients with Metastatic Hormone-sensitive Prostate Cancer : Big Data Analytics Using the PIONEER Platform

Combination therapies in metastatic hormone-sensitive prostate cancer (mHSPC), which include the addition of an androgen receptor signaling inhibitor and/or docetaxel to androgen deprivation therapy, have been a game changer in the management of this disease stage. However, these therapies come with their fair share of toxicities and side effects. The goal of this observational study is to report

Nb3Cl8 : a prototypical layered Mott-Hubbard insulator

Despite its simplicity and relevance for the description of electronic correlations in solids, the Hubbard model is seldom inarguably realized in real materials. Here, we show that monolayer Nb3Cl8 is an ideal candidate to be described within a single-orbital Hubbard model, constructed within a “molecular” rather than atomic basis set using ab initio constrained random phase approximation calculat

Ab initio electron-lattice downfolding : Potential energy landscapes, anharmonicity, and molecular dynamics in charge density wave materials

The interplay of electronic and nuclear degrees of freedom presents an outstanding problem in condensed matter physics and chemistry. Computational challenges arise especially for large systems, long time scales, in nonequilibrium, or in systems with strong correlations. In this work, we show how downfolding approaches facilitate complexity reduction on the electronic side and thereby boost the si

A Fecal Metabolite Signature of Impaired Fasting Glucose : Results From Two Independent Population-Based Cohorts

Prediabetes is a metabolic condition associated with gut mi-crobiome composition, although mechanisms remain elu-sive. We searched for fecal metabolites, a readout of gut microbiome function, associated with impaired fasting glucose (IFG) in 142 individuals with IFG and 1,105 healthy individuals from the UK Adult Twin Registry (TwinsUK). We used the Cooperative Health Research in the Region of Aug

The case for precision medicine in the prevention, diagnosis, and treatment of cardiometabolic diseases in low-income and middle-income countries

Cardiometabolic diseases are the leading preventable causes of death in most geographies. The causes, clinical presentations, and pathogenesis of cardiometabolic diseases vary greatly worldwide, as do the resources and strategies needed to prevent and treat them. Therefore, there is no single solution and health care should be optimised, if not to the individual (ie, personalised health care), the

Understanding diabetes heterogeneity : key steps towards precision medicine in diabetes

Diabetes is a highly heterogeneous condition; yet, it is diagnosed by measuring a single blood-borne metabolite, glucose, irrespective of aetiology. Although pragmatically helpful, disease classification can become complex and limit advances in research and medical care. Here, we describe diabetes heterogeneity, highlighting recent approaches that could facilitate management by integrating three d

Acoustic enrichment of heterogenous circulating tumor cells and clusters from patients with metastatic prostate cancer

BACKGROUND: There are important unmet clinical needs to develop cell enrichment technologies to enable unbiased label-free isolation of both single cell and clusters of circulating tumor cells (CTCs) manifesting heterogeneous lineage specificity. Here, we report a pilot study based on microfluidic acoustophoresis enrichment of CTCs using the CellSearch CTC assay as a reference modality.METHODS: Ac