Articles: phenotype.
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Cardiac fibrosis occurs following insults to the myocardium and is characterized by the abnormal accumulation of non-compliant extracellular matrix (ECM), which compromises cardiomyocyte contractile activity and eventually leads to heart failure. This phenomenon is driven by the activation of cardiac fibroblasts (cFbs) to myofibroblasts and results in changes in ECM biochemical, structural and mechanical properties. The lack of predictive in vitro models of heart fibrosis has so far hampered the search for innovative treatments, as most of the cellular-based in vitro reductionist models do not take into account the leading role of ECM cues in driving the progression of the pathology. ⋯ Next, we used Mass Spectrometry, nanoindentation, scanning electron and confocal microscopy to unveil the characteristic composition and the visco-elastic properties of the abundant, collagen-rich ECM deposited by cardiac myofibroblasts in vitro. Finally, we demonstrated that the fibrotic ECM activates mechanosensitive pathways in iPSC-derived cardiomyocytes, impacting on their shape, sarcomere assembly, phenotype, and calcium handling properties. We thus propose human bio-inspired decellularized matrices as animal-free, isogenic cardiomyocyte culture substrates recapitulating key pathophysiological changes occurring at the cellular level during cardiac fibrosis.
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Intensive care medicine · Nov 2024
Clinical phenotyping uncovers heterogeneous associations between corticosteroid treatment and survival in critically ill COVID-19 patients.
Disease heterogeneity in coronavirus disease 2019 (COVID-19) may render the current one-size-fits-all treatment approach suboptimal. We aimed to identify and immunologically characterize clinical phenotypes among critically ill COVID-19 patients, and to assess heterogeneity of corticosteroid treatment effect. ⋯ Our multinational study identified three distinct clinical COVID-19 phenotypes, each exhibiting marked differences in demographic, clinical, and immunological features, and in the response to late and short-term corticosteroid treatment.
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The dysfunction of the ABO glycosyltransferase (GT) enzyme, which is caused by mutations in the ABO gene, can lead to weak ABO phenotypes. In this study, we have discovered a novel weak ABO subgroup allele and investigated the underlying mechanism to causing its Aweak phenotype. ⋯ One novel AW allele was identified and the SNP c.424A > G (p.M142V) can cause the Aweak phenotype through damaging the hydrogen bonds and reducing stability of the GTA.
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Sarcoidosis staging primarily has relied on the Scadding chest radiographic system, although chest CT imaging is finding increased clinical use. ⋯ In this study, CT scan features explained additional variability in lung function beyond Scadding stage, with some CT scan features obviating the associations between lung function and Scadding stage. Whether CT scan features, phenotypes, or endotypes could be useful for treating patients with sarcoidosis needs more study.
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To identify whether there is an association between body composition phenotypes and toxicity to chemoradiotherapy in women with cervical cancer. ⋯ Lower SMI was an independent factor for the higher number of adverse events, as it remained a risk factor when analyzed in isolation or in association with adipose tissue. Women with excess adipose tissue associated with lower muscle mass had a risk approximately 4 times higher of delaying or interrupting chemoradiotherapy. Furthermore, for the sum of unfavorable conditions, there was a progressive increase in the risk of TIMT.