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The spatial distribution of proteome at subcellular levels provides clues for protein functions, thus is important to human biology and medicine. Imaging-based methods are one of the most important approaches for predicting protein subcellular location. Although deep neural networks have shown impressive performance in a number of imaging tasks, its application to protein subcellular localization has not been sufficiently explored. In this study, we developed a deep imaging-based approach to localize the proteins at subcellular levels. Based on deep image features extracted from convolutional neural networks (CNNs), both single-label and multi-label locations can be accurately predicted. Particularly, the multi-label prediction is quite a challenging task. Here we developed a criterion learning strategy to exploit the label-attribute relevancy and label-label relevancy. A criterion that was used to determine the final label set was automatically obtained during the learning procedure. We concluded an optimal CNN architecture that could give the best results. Besides, experiments show that compared with the hand-crafted features, the deep features present more accurate prediction with less features. The implementation for the proposed method is available at https//github.com/RanSuLab/ProteinSubcellularLocation.The Global Mycetoma Working Group (GMWG) was formed in January 2018 in response to the declaration of mycetoma as a neglected tropical disease (NTD) by the World Health Assembly. BLU-945 supplier The aim of the working group is to connect experts and public health practitioners around the world to accelerate mycetoma prevention activities and reduce the impact of mycetoma on patients, healthcare providers and society in the endemic regions. The working group has made tangible contributions to mycetoma programming, awareness and coordination among scientists, clinicians and public health professionals. The group's connectivity has enabled rapid response and review of NTD documents in development, has created a network of public health professionals to provide regional mycetoma expertise and has enabled mycetoma to be represented within broader NTD organizations. The GMWG will continue to serve as a hub for networking and building collaborations for the advancement of mycetoma clinical management and treatment, research and public health programming.Chromatin immunoprecipitation followed by next-generation sequencing (ChIP-seq) is recognized as an extremely powerful tool to study the interaction of numerous transcription factors and other chromatin-associated proteins with DNA. The core problem in the optimization of ChIP-seq protocol and the following computational data analysis is that a 'true' pattern of binding events for a given protein factor is unknown. Computer simulation of the ChIP-seq process based on 'a-priory known binding template' can contribute to a drastically reduce the number of wet lab experiments and finally help achieve radical optimization of the entire processing pipeline. We present a newly developed ChIP-sequencing simulation algorithm implemented in the novel software, in silico ChIP-seq (isChIP). We demonstrate that isChIP closely approximates real ChIP-seq protocols and is able to model data similar to those obtained from experimental sequencing. We validated isChIP using publicly available datasets generated for well-characterized transcription factors Oct4 and Sox2. Although the novel software is compatible with the Illumina protocols by default, it can also successfully perform simulations with a number of alternative sequencing platforms such as Roche454, Ion Torrent and SOLiD as well as model ChIP -Exo. The versatility of isChIP was demonstrated through modelling a wide range of binding events, including those of transcription factors and chromatin modifiers. We also performed a comparative analysis against a few existing ChIP-seq simulators and showed the fundamental superiority of our model. Due to its ability to utilize known binding templates, isChIP can potentially be employed to help investigators choose the most appropriate analytical software through benchmarking of available ChIP-seq programs and optimize the experimental parameters of ChIP-seq protocol. isChIP software is freely available at https//github.com/fnaumenko/isChIP.

Atrial fibrillation (AF) is common in older people and is associated with increased stroke risk that may be reduced by oral anticoagulation (OAC). Frailty also increases with increasing age, yet the extent of OAC prescription in older people according to extent of frailty in people with AF is insufficiently described.

An electronic health records study of 536,955 patients aged ≥65years from ResearchOne in England (384 General Practices), over 15.4months, last follow-up 11th April 2017. OAC prescription for AF with CHA2DS2-Vasc ≥2, adjusted (demographic and treatments) risk of all-cause mortality, and subsequent cerebrovascular disease, bleeding and falls were estimated by electronic frailty index (eFI) category of fit, mild, moderate and severe frailty.

AF prevalence and mean CHA2DS2-Vasc for those with AF increased with increasing eFI category (fit 2.9%, 2.2; mild 11.2%, 3.2; moderate 22.2%, 4.0; and severe 31.5%, 5.0). For AF with CHA2DS2-Vasc ≥2, OAC prescription was higher for mild (53.2%), moderate (55.6%) and severe (53.4%) eFI categories than fit (41.7%). In those with AF and eligible for OAC, frailty was associated with increased risk of death (HR for severe frailty compared with fit 4.09, 95% confidence interval 3.43-4.89), gastrointestinal bleeding (2.17, 1.45-3.25), falls (8.03, 4.60-14.03) and, among women, stroke (3.63, 1.10-12.02).

Among older people in England, AF and stroke risk increased with increasing degree of frailty; however, OAC prescription approximated 50%. Given competing demands of mortality, morbidity and stroke prevention, greater attention to stratified stroke prevention is needed for this group of the population.

Among older people in England, AF and stroke risk increased with increasing degree of frailty; however, OAC prescription approximated 50%. Given competing demands of mortality, morbidity and stroke prevention, greater attention to stratified stroke prevention is needed for this group of the population.

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