58 research outputs found

    Novel Loci for Adiponectin Levels and Their Influence on Type 2 Diabetes and Metabolic Traits : A Multi-Ethnic Meta-Analysis of 45,891 Individuals

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    J. Kaprio, S. Ripatti ja M.-L. Lokki työryhmien jäseniä.Peer reviewe

    The Physics of the B Factories

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    Whole-genome sequencing reveals host factors underlying critical COVID-19

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    Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

    Case study challenge: surgery

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    Latent patient profile modelling and applications with mixed-variate restricted Boltzmann machine

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    Efficient management of chronic diseases is critical in modern health care. We consider diabetes mellitus, and our ongoing goal is to examine how machine learning can deliver information for clinical efficiency. The challenge is to aggregate highly heterogeneous sources including demographics, diagnoses, pathologies and treatments, and extract similar groups so that care plans can be designed. To this end, we extend our recent model, the mixed-variate restricted Boltzmann machine (MV.RBM), as it seamlessly integrates multiple data types for each patient aggregated over time and outputs a homogeneous representation called "latent profile" that can be used for patient clustering, visualisation, disease correlation analysis and prediction. We demonstrate that the method outperforms all baselines on these tasks - the primary characteristics of patients in the same groups are able to be identified and the good result can be achieved for the diagnosis codes prediction

    The effect of vitamin A supplementation on serum retinol and retinol binding protein levels

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    A randomised double blind controlled trial was conduced to see whether vitamin A supplementation in the form of retinyl palmitate would increase the concentrations of serum retinol and retinol binding protein. A total of 376 people were studied and were allocated to one of 7 regimens covering doses of vitamin A from 0 (placebo) to 36,000 IU daily. Supplementation continued for 6 months and blood samples were collected immediately before the start of supplementation, after 3 months and after 6 months. There was a small but statistically significant increase in serum retinol levels associated with supplementation, but no significant increase in serum retinol binding protein. The extent of the increase in serum retinol was related to the extent of the supplementation. On average, for every 10,000 IU of retinyl palmitate per day, the serum retinol concentration increased by 13 μg/l after 3 months (an increase of 2%) and 12 μg/l after 6 months of supplementation (2% increase). All the regimens used showed no evidence of toxicity other than minor symptomatic and physical changes affecting the skin and mucous membranes
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