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76, 95% CI=1.24-2.51) and high SES groups (OR=2.22, 95% CI=1.37-3.58).

Our study demonstrates that racial disparities in AL among older adults depends on individuals' lifetime SES trajectories, and that older Black Americans receive fewer health benefits for achieving higher SES. These findings underscore the need to evaluate socioeconomic resources across the life course to clarify the extent of racial disparities among aging populations.

Our study demonstrates that racial disparities in AL among older adults depends on individuals' lifetime SES trajectories, and that older Black Americans receive fewer health benefits for achieving higher SES. These findings underscore the need to evaluate socioeconomic resources across the life course to clarify the extent of racial disparities among aging populations.

The PDBe aggregated API is an open-access and open-source RESTful API that provides programmatic access to a wealth of macromolecular structural data and their functional and biophysical annotations through 80+ API endpoints. The API is powered by the PDBe graph database (https//pdbe.org/graph-schema), an open-access integrative knowledge graph that can be used as a discovery tool to answer complex biological questions.

The PDBe aggregated API provides up-to-date access to the PDBe graph database, which has weekly releases with the latest data from the Protein Data Bank, integrated with updated annotations from UniProt, Pfam, CATH, SCOP and the PDBe-KB partner resources. The complete list of all the available API endpoints and their descriptions are available at https//pdbe.org/graph-api. The source code of the Python 3.6+ API application is publicly available at https//gitlab.ebi.ac.uk/pdbe-kb/services/pdbe-graph-api.

Supplementary data are available at Bioinformatics online.

Supplementary data are available at Bioinformatics online.Meiosis produces the haploid gametes required by all sexually-reproducing organisms, occurring in specific temperature ranges in different organisms. However, how meiotic thermotolerance is regulated remains largely unknown. Using the model organism Caenorhabditis elegans, here, we identified the synaptonemal complex (SC) protein SYP-5 as a critical regulator of meiotic thermotolerance. syp-5-null mutants maintained a high percentage of viable progeny at 20 °C but produced significantly fewer viable progeny at 25 °C, a permissive temperature in wild-type worms. Cytological analysis of meiotic events in the mutants revealed that while SC assembly and disassembly as well as DNA double-strand break repair kinetics were not affected by the elevated temperature, crossover designation and bivalent formation were significantly affected. More severe homolog segregation errors were also observed at the elevated temperature. A temperature switching assay revealed that late meiotic prophase events were not temperature-sensitive and that meiotic defects during pachytene stage were responsible for the reduced viability of syp-5 mutants at the elevated temperature. Moreover, SC polycomplex formation and hexanediol sensitivity analysis suggested that SYP-5 was required for the normal properties of the SC, and charge-interacting elements in SC components were involved in regulating meiotic thermotolerance. Together, these findings provide a novel molecular mechanism for meiotic thermotolerance regulation.

In most tissue-based biomedical research, the lack of sufficient pathology training images with well-annotated ground truth inevitably limits the performance of deep learning systems. In this study, we propose a convolutional neural network with foveal blur enriching datasets with multiple local nuclei regions of interest derived from original pathology images. We further propose a human-knowledge boosted deep learning system by inclusion to the convolutional neural network new loss function terms capturing shape prior knowledge and imposing smoothness constraints on the predicted probability maps.

Our proposed system outperforms all state-of-the-art deep learning and non-deep learning methods by Jaccard coefficient, Dice coefficient, Accuracy, and Panoptic Quality in three independent datasets. The high segmentation accuracy and execution speed suggest its promising potential for automating histopathology nuclei segmentation in biomedical research and clinical settings.

The codes, the documentation, and example data are available on an open source at https//github.com/HongyiDuanmu26/FovealBoosted.

Supplementary data are available at Bioinformatics online.

Supplementary data are available at Bioinformatics online.Novel coronavirus disease 2019 (COVID-19) is an emerging, rapidly evolving crisis, and the ability to predict prognosis for individual COVID-19 patient is important for guiding treatment. Laboratory examinations were repeatedly measured during hospitalization for COVID-19 patients, which provide the possibility for the individualized early prediction of prognosis. However, previous studies mainly focused on risk prediction based on laboratory measurements at one time point, ignoring disease progression and changes of biomarkers over time. By using historical regression trees (HTREEs), a novel machine learning method, and joint modeling technique, we modeled the longitudinal trajectories of laboratory biomarkers and made dynamically predictions on individual prognosis for 1997 COVID-19 patients. In the discovery phase, based on 358 COVID-19 patients admitted between 10 January and 18 February 2020 from Tongji Hospital, HTREE model identified a set of important variables including 14 prognostic biomarkers. With the trajectories of those biomarkers through 5-day, 10-day and 15-day, the joint model had a good performance in discriminating the survived and deceased COVID-19 patients (mean AUCs of 88.81, 84.81 and 85.62% for the discovery set). The predictive model was successfully validated in two independent datasets (mean AUCs of 87.61, 87.55 and 87.03% for validation the first dataset including 112 patients, 94.97, 95.78 and 94.63% for the second validation dataset including 1527 patients, respectively). In conclusion, our study identified important biomarkers associated with the prognosis of COVID-19 patients, characterized the time-to-event process and obtained dynamic predictions at the individual level.Annotated genome sequences provide valuable insight into the functional capabilities of members of microbial communities. Nevertheless, most studies on the microbiome in animal guts use metagenomic data, hampering the assignment of genes to specific microbial taxa. Here, we make use of the readily culturable bacterial communities in the gut of the fruit fly Drosophila melanogaster to obtain draft genome sequences for 96 isolates from wild flies. These include 81 new de novo assembled genomes, assigned to three orders (Enterobacterales, Lactobacillales, and Rhodospirillales) with 80% of strains identified to species-level using average nucleotide identity and phylogenomic reconstruction. Based on annotations by the RAST pipeline, among-isolate variation in metabolic function partitioned strongly by bacterial order, particularly by amino acid metabolism (Rhodospirillales), fermentation and nucleotide metabolism (Lactobacillales) and arginine, urea and polyamine metabolism (Enterobacterales). Seven bacterial species, comprising 2-3 species in each order, were well-represented among the isolates and included ≥ 5 strains, permitting analysis of metabolic functions in the accessory genome (i.e. genes not present in every strain). Overall, the metabolic function in the accessory genome partitioned by bacterial order. Two species, Gluconobacter cerinus (Rhodospirillales) and Lactiplantibacillus plantarum (Lactobacillales) had large accessory genomes, and metabolic functions were dominated by amino acid metabolism (G. cerinus) and carbohydrate metabolism (La. plantarum). The patterns of variation in metabolic capabilities at multiple phylogenetic scales provide the basis for future studies of the ecological and evolutionary processes shaping the diversity of microorganisms associated with natural populations of Drosophila.

Poor adherence or persistence to treatment can be a barrier to optimizing clinical practice (real-world) outcomes to intravitreal injection therapy in patients with neovascular age-related macular degeneration (nAMD). Currently, there is a lack of consensus on the definition and classification of adherence specific to this context.

To describe the development and validation of terminology on patient nonadherence and nonpersistence to anti-vascular endothelial growth factor therapy.

Following a systematic review of currently used terminology in the literature, a subcommittee panel of retinal experts developed a set of definitions and classification for validation. Definitions were restricted to use in patients with nAMD requiring intravitreal anti-vascular endothelial growth factor therapy. Validation by the full nAMD Barometer Leadership Coalition was established using a modified Delphi approach, with predetermined mean scores of 7.5 or more signifying consensus. Subsequent endorsement of the definition

This classification system provides a framework for assessing treatment nonadherence and nonpersistence over time and across different health settings in the treatment of nAMD with current intravitreal anti-vascular endothelial growth factor treatments. This may have additional importance, given the potential association of the coronavirus pandemic on adherence to treatment in patients with nAMD.

This classification system provides a framework for assessing treatment nonadherence and nonpersistence over time and across different health settings in the treatment of nAMD with current intravitreal anti-vascular endothelial growth factor treatments. find more This may have additional importance, given the potential association of the coronavirus pandemic on adherence to treatment in patients with nAMD.

POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) syndrome is a rare plasma cell disorder characterized by demyelinating peripheral neuropathy and clonal plasma cell proliferation. Clinical manifestations are believed to be associated with a surge of inflammatory and angiogenic mediators, including interleukins and vascular endothelial growth factor (VEGF), elicited by clonal and polyclonal plasma cells. The clinical manifestations of POEMS syndrome can be debilitating; therefore, early diagnosis is essential. This review discusses several aspects of POEMS syndrome and includes the most recently published findings, with a special emphasis on diagnosis and treatment strategies.

POEMS syndrome may be underdiagnosed because of its rarity, and it can be mistaken for chronic inflammatory demyelinating polyneuropathy; this misdiagnosis may lead to delayed therapy and progressive worsening of symptoms, especially neuropathy. Therefore, in addition to measurement of thein its course; thus, appropriate diagnosis and treatment are important for optimal clinical outcomes.

POEMS syndrome should be considered in the differential diagnosis for patients who have peripheral neuropathy and paraproteinemia among other multisystem manifestations. The syndrome can be debilitating if not recognized early in its course; thus, appropriate diagnosis and treatment are important for optimal clinical outcomes.

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