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- Schunk, Stefan J., et al.
(författare)
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Genetically determined NLRP3 inflammasome activation associates with systemic inflammation and cardiovascular mortality
- 2021
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Ingår i: European Heart Journal. - : Oxford University Press. - 0195-668X .- 1522-9645. ; 42:18, s. 1742-1756
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Tidskriftsartikel (refereegranskat)abstract
- AimsInflammation plays an important role in cardiovascular disease (CVD) development. The NOD-like receptor protein-3 (NLRP3) inflammasome contributes to the development of atherosclerosis in animal models. Components of the NLRP3 inflammasome pathway such as interleukin-1β can therapeutically be targeted. Associations of genetically determined inflammasome-mediated systemic inflammation with CVD and mortality in humans are unknown.Methods and resultsWe explored the association of genetic NLRP3 variants with prevalent CVD and cardiovascular mortality in 538 167 subjects on the individual participant level in an explorative gene-centric approach without performing multiple testing. Functional relevance of single-nucleotide polymorphisms on NLRP3 inflammasome activation has been evaluated in monocyte-enriched peripheral blood mononuclear cells (PBMCs). Genetic analyses identified the highly prevalent (minor allele frequency 39.9%) intronic NLRP3 variant rs10754555 to affect NLRP3 gene expression. rs10754555 carriers showed significantly higher C-reactive protein and serum amyloid A plasma levels. Carriers of the G allele showed higher NLRP3 inflammasome activation in isolated human PBMCs. In carriers of the rs10754555 variant, the prevalence of coronary artery disease was significantly higher as compared to non-carriers with a significant interaction between rs10754555 and age. Importantly, rs10754555 carriers had significantly higher risk for cardiovascular mortality during follow-up. Inflammasome inducers (e.g. urate, triglycerides, apolipoprotein C3) modulated the association between rs10754555 and mortality.ConclusionThe NLRP3 intronic variant rs10754555 is associated with increased systemic inflammation, inflammasome activation, prevalent coronary artery disease, and mortality. This study provides evidence for a substantial role of genetically driven systemic inflammation in CVD and highlights the NLRP3 inflammasome as a therapeutic target.
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| 3. |
- Wagenpfeil, Stefan, et al.
(författare)
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Explainable Multimedia Feature Fusion for Medical Applications
- 2022
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Ingår i: JOURNAL OF IMAGING. - : MDPI. - 2313-433X. ; 8:4
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Tidskriftsartikel (refereegranskat)abstract
- Due to the exponential growth of medical information in the form of, e.g., text, images, Electrocardiograms (ECGs), X-ray, and multimedia, the management of a patient's data has become a huge challenge. In particular, the extraction of features from various different formats and their representation in a homogeneous way are areas of interest in medical applications. Multimedia Information Retrieval (MMIR) frameworks, like the Generic Multimedia Analysis Framework (GMAF), can contribute to solving this problem, when adapted to special requirements and modalities of medical applications. In this paper, we demonstrate how typical multimedia processing techniques can be extended and adapted to medical applications and how these applications benefit from employing a Multimedia Feature Graph (MMFG) and specialized, efficient indexing indexing structures in the form of Graph Codes. These Graph Codes are transformed to feature relevant Graph Codes by employing a modified Term Frequency Inverse Document Frequency (TFIDF) algorithm, which further supports value ranges and Boolean operations required in the medical context. On this basis, various metrics for the calculation of similarity, recommendations, and automated inferencing and reasoning can be applied supporting the field of diagnostics. Finally, the presentation of these new facilities in the form of explainability is introduced and demonstrated. Thus, in this paper, we show how Graph Codes contribute new querying options for diagnosis and how Explainable Graph Codes can help to readily understand medical multimedia formats.
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