Similar deficiencies, different outcomes: succinate dehydrogenase loss in adrenal medulla vs. fibroblast cell culture models of paraganglioma.

Heterozygosity for loss-of-function alleles of the genes encoding the four subunits of succinate dehydrogenase (SDHA, SDHB, SDHC, SDHD), as well as the SDHAF2 assembly factor predispose affected individuals to pheochromocytoma and paraganglioma (PPGL), two rare neuroendocrine tumors that arise from neural crest-derived paraganglia. Tumorigenesis results from loss of the remaining functional SDHx gene copy, leading to a cell with no functional SDH and a defective tricarboxylic acid (TCA) cycle. It is believed that the subsequent accumulation of succinate competitively inhibits multiple dioxygenase enzymes that normally suppress hypoxic signaling and demethylate histones and DNA, ultimately leading to increased expression of genes involved in angiogenesis and cell proliferation.

Analysis of Fluid-Structure Interaction Mechanisms for a Native Aortic Valve, Patient-Specific Ozaki Procedure, and a Bioprosthetic Valve.

The Ozaki procedure is a surgical technique which avoids to implant foreign aortic valve prostheses in human heart, using the patient's own pericardium. Although this approach has well-identified benefits, it is still a topic of debate in the cardiac surgical community, which prevents its larger use to treat valve pathologies. This is linked to the actual lack of knowledge regarding the dynamics of tissue deformations and surrounding blood flow for this autograft pericardial valve.

MAML3-fusions modulate vascular and immune tumour microenvironment and confer high metastatic risk in pheochromocytoma and paraganglioma.

Pheochromocytomas and paragangliomas are rare neuroendocrine tumours. Around 20-25 % of patients develop metastases, for which there is an urgent need of prognostic markers and therapeutic stratification strategies. The presence of a MAML3-fusion is associated with increased metastatic risk, but neither the processes underlying disease progression, nor targetable vulnerabilities have been addressed.

Three-dimensional modelling of aortic leaflet coaptation and load-bearing surfaces: in silico design of aortic valve neocuspidizations.

Objectives: Three-dimensional (3D) modelling of aortic leaflets remains difficult due to insufficient resolution of medical imaging. We aimed to model the coaptation and load-bearing surfaces of the aortic leaflets and adapt this workflow to aid in the design of aortic valve neocuspidizations.

Methods: Geometric morphometrics, using landmarks and semilandmarks, was applied to the geometric determinants of the aortic leaflets from computed tomography, followed by an isogeometric analysis using Non-Uniform Rational Basis Splines (NURBS).