Label-Free Proteomics Approach Characterizes Plasma Protein Signature of Donor Brain Death

Purpose Despite recent advances in donation after circulatory death, transplants from brain-dead donors remain the sole source in heart transplantation (HTx) worldwide. Due to organ shortage, marginal donors are increasingly used and the utilization of transplants becomes markedly more challenging. They undergo invariably brain death that induces a systemic cytokine and catecholamine storm that lead to systemic inflammation, labile hemodynamics, and organ hypoperfusion. Together, these can damage the heart and aggravate later occurring graft injury, and ultimately, compromise graft function. However, the effect of donor brain death on allografts is not well understood. Methods In a separate prospective, blinded single-center trial, we collected donor plasma samples and relevant clinical patient data from 50 HTx brain-dead donors and as controls plasma samples from age- and gender-matched 23 healthy volunteers. Quantitative label-free proteomics in high definition MSE mode (HDMSE) was carried out on the samples. Various statistical analyses were performed on quantitative proteomics data to obtain the most reliably distinguishing proteins, which classify the donors vs controls. Results With two or more unique proteins per identification, 463 proteins were quantified in our pilot study. A complete separation between donors and controls based on a set of 278 proteins (p-valuePeer reviewe

Symbolic Melodic Similarity: State of the Art and Future Challenges

Fostered by the introduction of the Music Information Retrieval Evaluation eXchange (MIREX) competition, the number of systems which calculate Symbolic Melodic Similarity has recently increased considerably. In order to understand the state of the art, we provide a comparative analysis of existing algorithms. The analysis is based on eight criteria that help characterising the systems, and highlighting strengths and weaknesses. We also propose a taxonomy which classifies algorithms based on their approach. Both taxonomy and criteria are fruitfully exploited for providing input for new forthcoming research in the area

Effect of Donor Simvastatin Treatment on Gene Expression Profiles in Human Cardiac Allografts during Ischemia-Reperfusion Injury

Purpose Numerous studies have shown that statin therapy initiated early after heart transplantation has beneficial effects on the development of cardiac allograft vasculopathy. Recently, we were able to show in a randomized clinical trial that simvastatin treatment of brain-dead donors conditions the heart transplant to withstand ischemia-reperfusion injury and to reduce the need for rejection treatments early after transplantation. In this study, we analyzed myocardial gene expression profiles in cardiac allografts after donor simvastatin treatment. Methods 84 heart transplant donors received 80 mg of simvastatin via nasogastric tube (n=42), or no treatment (n=42) in a prospective, double-blinded randomized controlled trial. Transmural Tru-Cut biopsies were taken from the apex of left ventricle of the donor heart immediately before reperfusion and 1 hour after reperfusion. 20 heart biopsies from donors without treatment and 20 heart biopsies from donors with simvastatin treatment will be analyzed with RNA sequencing. Results The preliminary analysis of RNA sequencing data from myocardial biopsies revealed altogether 137 significantly differentially expressed genes in all pairwise comparisons. The overall biological functions of these genes were related to gene ontology terms such as response to toxic substance, leukocyte migration, neutrophil mediated immunity, response to lipopolysaccharide, and response to oxidative stress. At the KEGG pathway level, our results indicated alterations in IL-17, TNF, MAPK and the AGE-RAGE signaling pathways. Conclusion We have shown in previous studies that donor simvastatin treatment induces protective effects against IRI in heart transplant recipients. In this study, we were able to detect significantly differentially expressed genes related to effects of simvastatin treatment. In order to single out genes that show beneficial effects of simvastatin treatment, further analysis will be conducted by exploring gene expression changes in specific biological functional categories, such as interleukin signaling and neutrophil degranulation. The complete analysis will be presented at the ISHLT 2019 congress.Peer reviewe

Heart Transplantation for Early-Onset Anthracycline-Induced Cardiomyopathy Within 5 Months of Chemotherapy Completion

Publisher Copyright: © 2021 The AuthorsA 9-year-old boy developed progressive anthracycline-induced cardiomyopathy three months after completion of chemotherapy for osteosarcoma. Five months after completion of chemotherapy, at the age of 10 years, heart transplantation was performed. At 29 months since transplantation, the patient remains free of rejection and recurrence of osteosarcoma. (Level of Difficulty: Intermediate.)Peer reviewe

Compression-based Modelling of Musical Similarity Perception

Similarity is an important concept in music cognition research since the similarity between (parts of) musical pieces determines perception of stylistic categories and structural relationships between parts of musical works. The purpose of the present research is to develop and test models of musical similarity perception inspired by a transformational approach which conceives of similarity between two perceptual objects in terms of the complexity of the cognitive operations required to transform the representation of the first object into that of the second, a process which has been formulated in informationtheoretic terms. Specifically, computational simulations are developed based on compression distance in which a probabilistic model is trained on one piece of music and then used to predict, or compress, the notes in a second piece. The more predictable the second piece according to the model, the more efficiently it can be encoded and the greater the similarity between the two pieces. The present research extends an existing information-theoretic model of auditory expectation (IDyOM) to compute compression distances varying in symmetry and normalisation using high-level symbolic features representing aspects of pitch and rhythmic structure. Comparing these compression distances with listeners’ similarity ratings between pairs of melodies collected in three experiments demonstrates that the compression-based model provides a good fit to the data and allows the identification of representations, model parameters and compression-based metrics that best account for musical similarity perception. The compression-based model also shows comparable performance to the best-performing algorithms on the MIREX 2005 melodic similarity task