Tempo-Express, a CBR Approach to Musical Tempo Transformations

The original publication is available at www.springerlink.comIn this paper, we describe a CBR system for applying musically acceptable tempo transformations to monophonic audio recordings of musical performances. Within the tempo transformation process, the expressivity of the performance is adjusted in such a way that the result sounds natural for the new tempo. A case base of previously performed melodies is used to infer the appropriate expressivity. Tempo transformation is one of the audio post-processing tasks manually done in audiolabs. Automatizing this process may, therefore, be of industrial interest.This research has been partially supported by the Spanish Ministry of Science and Technology under the project TIC 2003-07776-C2-02 "CBR-ProMusic: Content-based Music Processing using CBR" and EU-FEDER funds.Peer reviewe

The mast cell: A Janus in kidney transplants

Mast cells (MCs) are innate immune cells with a versatile set of functionalities, enabling them to orchestrate immune responses in various ways. Aside from their known role in allergy, they also partake in both allograft tolerance and rejection through interaction with regulatory T cells, effector T cells, B cells and degranulation of cytokines and other mediators. MC mediators have both pro- and anti-inflammatory actions, but overall lean towards pro-fibrotic pathways. Paradoxically, they are also seen as having potential protective effects in tissue remodeling post-injury. This manuscript elaborates on current knowledge of the functional diversity of mast cells in kidney transplants, combining theory and practice into a MC model stipulating both protective and harmful capabilities in the kidney transplant setting

Speckle-tracking echocardiography in comparison with ejection fraction for prediction of cardiovascular mortality in patients with end-stage renal disease

Background. Cardiovascular disease is the major cause of death in end-stage renal disease (ESRD). To develop better means to assess cardiovascular risk in these patients, we compared conventional echocardiography-derived left ventricular ejection fraction (EF) with the novel method of 2D speckle-tracking echocardiography to determine cardiac strain.Methods. Predictive performances of conventional EF and speckle-tracking echocardiography-derived global longitudinal strain (GLS) were compared using receiver-operator curve (ROC) analyses and calibration by calibration plots. We also took into account other known cardiovascular risk factors through multivariable logistic regression analysis.Results. The study comprised 171 ESRD patients (mean age 64 years, 64% male) on maintenance dialysis therapy (93% haemodialysis, 7% peritoneal dialysis) for an average period of 39 months. During 2.1 years of follow-up, 42 patients (25%) died from cardiovascular disease. ROC analysis of GLS resulted in an area under the curve of 0.700 [95% confidence interval (CI) 0.603-0.797] compared with an area under the curve of EF of 0.615 (95% CI 0.514-0.716) (P = 0.059 for difference). The total absolute deviation between predicted and observed outcome frequencies obtained by calibration plots were 13.8% for EF compared with only 6.4% for GLS. Best results of ROC analysis (area under the curve = 0.759; P = 0.06), calibration and goodness-of-fit (chi(2) = 28.34, P <= 0.0001, R-2 = 0.25) were achieved for GLS added to a baseline model consisting of known cardiovascular risk factors in a multivariate regression analysis.Conclusions. In summary, in chronic dialysis patients, GLS is a more precise predictor of cardiovascular mortality than conventional echocardiography-derived EF.Clinical epidemiolog

Dexamethasone sensitizes to ferroptosis by glucocorticoid receptor-induced dipeptidase-1 expression and glutathione depletion

Dexamethasone is widely used as an immunosuppressive therapy and recently as COVID-19 treatment. Here, we demonstrate that dexamethasone sensitizes to ferroptosis, a form of iron-catalyzed necrosis, previously suggested to contribute to diseases such as acute kidney injury, myocardial infarction, and stroke, all of which are triggered by glutathione (GSH) depletion. GSH levels were significantly decreased by dexamethasone. Mechanistically, we identified that dexamethasone up-regulated the GSH metabolism regulating protein dipeptidase-1 (DPEP1) in a glucocorticoid receptor (GR)-dependent manner. DPEP1 knockdown reversed the phenotype of dexamethasone-induced ferroptosis sensitization. Ferroptosis inhibitors, the DPEP1 inhibitor cilastatin, or genetic DPEP1 inactivation reversed the dexamethasone-induced increase in tubular necrosis in freshly isolated renal tubules. Our data indicate that dexamethasone sensitizes to ferroptosis by a GR-mediated increase in DPEP1 expression and GSH depletion. Together, we identified a previously unknown mechanism of glucocorticoid-mediated sensitization to ferroptosis bearing clinical and therapeutic implications

Myocardial changes in incident haemodialysis patients over 6-months:an observational cardiac magnetic resonance imaging study

Patients commencing on haemodialysis (HD) have an increased risk of cardiovascular events in the first year after starting HD compared to those patients established on HD longer. Left ventricular (LV) hypertrophy and abnormal myocardial strain predict mortality. There may be changes in the myocardium of incident HD patients over a 6-month period of HD which may explain changes in cardiovascular risk. We used CMR to consider changes in LV mass, myocardial strain and T1 mapping. We examined changes in pre-dialysis highly sensitive troponin T. 33 patients undergoing HD for &#60;12 months were recruited. Participants underwent CMR at baseline and after 6-months of standard care. 6-months of HD was associated with reduction in LV mass index (Baseline: 78.8 g/m2 follow up: 69.9 g/m2, p = &#60;0.001). LV global longitudinal strain also improved (Baseline: −17.9%, follow up: −21.6%, p = &#60;0.001). Change in T1 time was not significant (Baseline septal T1 1277.4 ms, follow up 1271.5 p = 0.504). Highly sensitive troponin T was lower at follow up (Baseline 38.8 pg/L, follow up 30.8 pg/L p = 0.02). In incident HD patients, 6-months of HD was associated with improvements in LV mass, strain and troponin. These findings may reflect improvement in known cardiac tissue abnormalities found in patients over the first year of HD

Human and murine fibroblast single cell transcriptomics reveals fibroblast clusters are differentially affected by ageing, and serum cholesterol

Aims Specific fibroblast markers and in-depth heterogeneity analysis are currently lacking, hindering functional studies in cardiovascular diseases (CVDs). Here, we established cell-type markers and heterogeneity in murine and human arteries and studied the adventitial fibroblast response to CVD and its risk factors hypercholesterolaemia and ageing. Methods and results Murine aorta single-cell RNA-sequencing analysis of adventitial mesenchymal cells identified fibroblast-specific markers. Immunohistochemistry and flow cytometry validated platelet-derived growth factor receptor alpha (PDGFRA) and dipeptidase 1 (DPEP1) across human and murine aorta, carotid, and femoral arteries, whereas traditional markers such as the cluster of differentiation (CD)90 and vimentin also marked transgelin+ vascular smooth muscle cells. Next, pseudotime analysis showed multiple fibroblast clusters differentiating along trajectories. Three trajectories, marked by CD55 (Cd55+), Cxcl chemokine 14 (Cxcl14+), and lysyl oxidase (Lox+), were reproduced in an independent RNA-seq dataset. Gene ontology (GO) analysis showed divergent functional profiles of the three trajectories, related to vascular development, antigen presentation, and/or collagen fibril organization, respectively. Trajectory-specific genes included significantly more genes with known genome-wide associations (GWAS) to CVD than expected by chance, implying a role in CVD. Indeed, differential regulation of fibroblast clusters by CVD risk factors was shown in the adventitia of aged C57BL/6J mice, and mildly hypercholesterolaemic LDLR KO mice on chow by flow cytometry. The expansion of collagen-related CXCL14+ and LOX+ fibroblasts in aged and hypercholesterolaemic aortic adventitia, respectively, coincided with increased adventitial collagen. Immunohistochemistry, bulk, and single-cell transcriptomics of human carotid and aorta specimens emphasized translational value as CD55+, CXCL14+ and LOX+ fibroblasts were observed in healthy and atherosclerotic specimens. Also, trajectory-specific gene sets are differentially correlated with human atherosclerotic plaque traits. Conclusion We provide two adventitial fibroblast-specific markers, PDGFRA and DPEP1, and demonstrate fibroblast heterogeneity in health and CVD in humans and mice. Biological relevance is evident from the regulation of fibroblast clusters by age and hypercholesterolaemia in vivo, associations with human atherosclerotic plaque traits, and enrichment of genes with a GWAS for CVD