Genomic investigations of unexplained acute hepatitis in children

Since its first identification in Scotland, over 1,000 cases of unexplained paediatric hepatitis in children have been reported worldwide, including 278 cases in the UK1. Here we report an investigation of 38 cases, 66 age-matched immunocompetent controls and 21 immunocompromised comparator participants, using a combination of genomic, transcriptomic, proteomic and immunohistochemical methods. We detected high levels of adeno-associated virus 2 (AAV2) DNA in the liver, blood, plasma or stool from 27 of 28 cases. We found low levels of adenovirus (HAdV) and human herpesvirus 6B (HHV-6B) in 23 of 31 and 16 of 23, respectively, of the cases tested. By contrast, AAV2 was infrequently detected and at low titre in the blood or the liver from control children with HAdV, even when profoundly immunosuppressed. AAV2, HAdV and HHV-6 phylogeny excluded the emergence of novel strains in cases. Histological analyses of explanted livers showed enrichment for T cells and B lineage cells. Proteomic comparison of liver tissue from cases and healthy controls identified increased expression of HLA class 2, immunoglobulin variable regions and complement proteins. HAdV and AAV2 proteins were not detected in the livers. Instead, we identified AAV2 DNA complexes reflecting both HAdV-mediated and HHV-6B-mediated replication. We hypothesize that high levels of abnormal AAV2 replication products aided by HAdV and, in severe cases, HHV-6B may have triggered immune-mediated hepatic disease in genetically and immunologically predisposed children

Adaptive Multimedia Retrieval: Identifying, Summarizing, and Recommending Image and Music

International audienc

Blockchain and smart contracts : Technologies, research issues and applications

This position paper analyzes blockchain technology from a scientific and application-oriented perspective of the Fraunhofer-Gesellschaft. It examines relevant technical aspects and related research questions. This shows that the technology still has fundamental research and development challenges in all areas. These include, for example, the modularization of individual blockchain concepts as well as their combination and integration for application-specific blockchain solutions. The investigation of fields of application and industries that can best benefit from the new technology shows that different properties of the blockchain are relevant for a field of application are. While the automation potential associated with smart contracts is essential for the Internet of Things, it is the irreversibility of the transactions managed for applications in the areas of supply chain, digital media or for guarantees of origin. However, the decisive aspect is that the blockchain is of great relevance for many different areas of application outside of the financial sector and, above all, independent of cryptocurrencies. The paper provides a list of criteria to identify applications that are suitable for using a blockchain. that the blockchain is of great relevance for many different areas of application outside of the financial sector and, above all, independent of cryptocurrencies. The paper provides a list of criteria to identify applications that are suitable for the use of a blockchain. that the blockchain is of great relevance for many different areas of application outside of the financial sector and, above all, independent of cryptocurrencies. The paper provides a list of criteria to identify applications that are suitable for using a blockchain

Blockchain and smart contracts: Technologies, research issues and applications

This position paper analyzes blockchain technology from the scientific and application-oriented perspective of the Fraunhofer-Gesellschaft. It examines relevant technical aspects and related research questions. It shows that technology still has fundamental research and development challenges in all areas. These include, for example, the modularization of individual blockchain concepts as well as their combination and integration for application-specific blockchain solutions

Animal models and animal-free innovations for cardiovascular research: current status and routes to be explored. Consensus document of the ESC Working Group on Myocardial Function and the ESC Working Group on Cellular Biology of the Heart

Cardiovascular diseases represent a major cause of morbidity and mortality, necessitating research to improve diagnostics, and to discover and test novel preventive and curative therapies, all of which warrant experimental models that recapitulate human disease. The translation of basic science results to clinical practice is a challenging task, in particular for complex conditions such as cardiovascular diseases, which often result from multiple risk factors and comorbidities. This difficulty might lead some individuals to question the value of animal research, citing the translational 'valley of death', which largely reflects the fact that studies in rodents are difficult to translate to humans. This is also influenced by the fact that new, human-derived in vitro models can recapitulate aspects of disease processes. However, it would be a mistake to think that animal models do not represent a vital step in the translational pathway as they do provide important pathophysiological insights into disease mechanisms particularly on an organ and systemic level. While stem cell-derived human models have the potential to become key in testing toxicity and effectiveness of new drugs, we need to be realistic, and carefully validate all new human-like disease models. In this position paper, we highlight recent advances in trying to reduce the number of animals for cardiovascular research ranging from stem cell-derived models to in situ modelling of heart properties, bioinformatic models based on large datasets, and state-of-the-art animal models, which show clinically relevant characteristics observed in patients with a cardiovascular disease. We aim to provide a guide to help researchers in their experimental design to translate bench findings to clinical routine taking the replacement, reduction, and refinement (3R) as a guiding concept