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Pyruvate dehydrogenase kinase regulates vascular inflammation in atherosclerosis and increases cardiovascular risk
Recent studies have revealed a close connection between cellular metabolism and the chronic inflammatory process of atherosclerosis. While the link between systemic metabolism and atherosclerosis is well established, the implications of altered metabolism in the artery wall are less understood. Pyruvate dehydrogenase kinase (PDK)-dependent inhibition of pyruvate dehydrogenase (PDH) has been identi
An experimental study on lung deposition of inhaled 2 μm particles in relation to lung characteristics and deposition models
Background: The understanding of inhaled particle respiratory tract deposition is a key link to understand the health effects of particles or the efficiency for medical drug delivery via the lung. However, there are few experimental data on particle respiratory tract deposition, and the existing data deviates considerably when comparing results for particles > 1 μm. Methods: We designed an experim
Ambient pressure operando catalytic characterization by combining PM-IRRAS with planar laser-induced fluorescence and surface optical reflectance imaging
We present a combination of optical operando techniques that allow us to bridge the pressure gap in heterogeneous catalysis. By combining Polarization Modulated - InfraRed Reflection Absorption Spectroscopy (PM-IRRAS) with two dimensional-Surface Optical Reflectance (2D-SOR) and Planar Laser Induced Fluorescence (PLIF), we can simultaneously measure the adsorbed species on the catalyst surface, mo
Electrical Conductance and Thermopower of β-Substituted Porphyrin Molecular Junctions─Synthesis and Transport
Molecular junctions offer significant potential for enhancing thermoelectric power generation. Quantum interference effects and associated sharp features in electron transmission are expected to enable the tuning and enhancement of thermoelectric properties in molecular junctions. To systematically explore the effect of quantum interferences, we designed and synthesized two new classes of porphyri
Ventricular–arterial coupling (VAC) in a population-based cohort of middle-aged individuals: The STANISLAS cohort
Background and aimsData exploring normal values of different ventricular–arterial coupling (VAC) parameters and their association with anthropometric and cardiovascular (CV) factors are scarce. We aim to report values of two different methods of VAC assessment according to age and sex and explore their association with CV factors within a large population-based cohort of middle-aged individuals.Me
Second international consensus report on gaps and opportunities for the clinical translation of precision diabetes medicine
Precision medicine is part of the logical evolution of contemporary evidence-based medicine that seeks to reduce errors and optimize outcomes when making medical decisions and health recommendations. Diabetes affects hundreds of millions of people worldwide, many of whom will develop life-threatening complications and die prematurely. Precision medicine can potentially address this enormous proble
Predictive fairness
It has recently been argued that in normal decision circumstances no systematic decision method that predicts the likelihood that individuals possess some property can be fair. Either (i) the decision method correctly identifies the relevant property (e.g. recidivism) more often in one subgroup (e.g. black defendants) than another (e.g. white defendants); or (ii) the decision method systematically
Proteomic characteristics and diagnostic potential of exhaled breath particles in patients with COVID-19
BACKGROUND: SARS-CoV-2 has been shown to predominantly infect the airways and the respiratory tract and too often have an unpredictable and different pathologic pattern compared to other respiratory diseases. Current clinical diagnostical tools in pulmonary medicine expose patients to harmful radiation, are too unspecific or even invasive. Proteomic analysis of exhaled breath particles (EBPs) in c
Reduced risk of serious pneumococcal infections up to 10 years after a dose of pneumococcal conjugate vaccine in established arthritis.
Background: To examine rates of serious pneumococcal infections up to 10 years after vaccination with 7-valent conjugated pneumococcal vaccine (PCV7) in patients with arthritis compared to non-vaccinated arthritis patients.Methods: In total, 595 adult arthritis patients (rheumatoid arthritis; RA = 342, 80 % women and spondylarthropathy; SpA = 253, 45 % women) received one dose of PCV7. Mean age/di
Mepolizumab for Eosinophilic Granulomatosis With Polyangiitis: A European Multicenter Observational Study
ObjectiveMepolizumab proved to be an efficacious treatment for eosinophilic granulomatosis with polyangiitis (EGPA) at a dose of 300 mg every 4 weeks in the randomized, controlled MIRRA trial. In a few recently reported studies, successful real-life experiences with the approved dose for treating severe eosinophilic asthma (100 mg every 4 weeks) were observed. We undertook this study to assess the
Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis
Background: Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery. Results: To expand our understanding of the underlying biological pathways and m
Discovery of drug–omics associations in type 2 diabetes with generative deep-learning models
The application of multiple omics technologies in biomedical cohorts has the potential to reveal patient-level disease characteristics and individualized response to treatment. However, the scale and heterogeneous nature of multi-modal data makes integration and inference a non-trivial task. We developed a deep-learning-based framework, multi-omics variational autoencoders (MOVE), to integrate suc
The contribution of population age-sex structure to the excess mortality estimates of 2020–2021 in Denmark, Finland, Iceland, Norway, and Sweden
The Nordic countries offer an ideal case study of the COVID-19 pandemic due to their comparability, high data quality, and variable mitigations. We investigated the age- and sex-specific mortality patterns during 2020–2021 for the five Nordic countries and analysed the total age- and sex-adjusted excess deaths, ratios of actual to expected death rates, and age-standardized excess death estimates.
3D analysis and grading of calcifications from ex vivo human meniscus
Objective: Meniscal calcifications are associated with the pathogenesis of knee osteoarthritis (OA). We propose a micro-computed tomography (μCT) based 3D analysis of meniscal calcifications ex vivo, including a new grading system. Method: Human medial and lateral menisci were obtained from 10 patients having total knee replacement for medial compartment OA and 10 deceased donors without knee OA (
Circulating Metabolites Associated with Albuminuria in a Hispanic/Latino Population
Background. Albuminuria is associated with metabolic abnormalities, but these relationships are not well understood. We studied the association of metabolites with albuminuria in Hispanics/Latinos, a population with high risk for metabolic disease. Methods. We used data from 3,736 participants from the Hispanic Community Health Study/Study of Latinos, of which 16% had diabetes and 9% had an increa
Stroke genetics informs drug discovery and risk prediction across ancestries
Previous genome-wide association studies (GWASs) of stroke - the second leading cause of death worldwide - were conducted predominantly in populations of European ancestry1,2. Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (6
Assessing the importance of predictors of adherence to a digital self‑management intervention for osteoarthritis
OBJECTIVE: Treatment adherence is suggested to be associated with greater improvement in patient outcomes. Despite the growing use of digital therapeutics in osteoarthritis management, there is limited evidence of person-level factors influencing adherence to these interventions in real-world settings. We aimed to determine the relative importance of factors influencing adherence to a digital self
Heritability of Mitral Regurgitation : Observations From the Framingham Heart Study and Swedish Population
Direct conversion of human fibroblasts to functional excitatory cortical neurons integrating into human neural networks
Background: Human fibroblasts can be directly converted to several subtypes of neurons, but cortical projection neurons have not been generated. Methods: Here we screened for transcription factor combinations that could potentially convert human fibroblasts to functional excitatory cortical neurons. The induced cortical (iCtx) cells were analyzed for cortical neuronal identity using immunocytochem
