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Plasma EGF was elevated sixfold (from 4 to 24 pg/mL; P = .02) at 6 hours postdose in the high-risk cohort, in contrast to no peak in plasma EGF in the more severe second-line cohort. After 1 week of uhCG, patients reported a twofold increase in the regulatory T cell to conventional T-cell ratio, suggesting immune modulation despite high-dose steroids. Responding patients reported significantly lower plasma amphiregulin and higher plasma butyrate levels at study completion, suggesting improvement in mucosal damage over time. uhCG is a novel, safe, supportive therapy, proceeding to phase 2 testing at 2000 units/m2 in high-risk aGVHD. This study was registered at www.clinicaltrials.gov as #NCT02525029. https://www.selleckchem.com/products/ptc-209.html © 2020 by The American Society of Hematology.BACKGROUND The German Shepherd Dog (GSD) is one of the most common breeds on earth and has been bred for its utility and intelligence. It is often first choice for police and military work, as well as protection, disability assistance, and search-and-rescue. Yet, GSDs are well known to be susceptible to a range of genetic diseases that can interfere with their training. Such diseases are of particular concern when they occur later in life, and fully trained animals are not able to continue their duties. FINDINGS Here, we provide the draft genome sequence of a healthy German Shepherd female as a reference for future disease and evolutionary studies. We generated this improved canid reference genome (CanFam_GSD) utilizing a combination of Pacific Bioscience, Oxford Nanopore, 10X Genomics, Bionano, and Hi-C technologies. The GSD assembly is ∼80 times as contiguous as the current canid reference genome (20.9 vs 0.267 Mb contig N50), containing far fewer gaps (306 vs 23,876) and fewer scaffolds (429 vs 3,310) than the current canid reference genome CanFamv3.1. Two chromosomes (4 and 35) are assembled into single scaffolds with no gaps. BUSCO analyses of the genome assembly results show that 93.0% of the conserved single-copy genes are complete in the GSD assembly compared with 92.2% for CanFam v3.1. Homology-based gene annotation increases this value to ∼99%. Detailed examination of the evolutionarily important pancreatic amylase region reveals that there are most likely 7 copies of the gene, indicative of a duplication of 4 ancestral copies and the disruption of 1 copy. CONCLUSIONS GSD genome assembly and annotation were produced with major improvement in completeness, continuity, and quality over the existing canid reference. This resource will enable further research related to canine diseases, the evolutionary relationships of canids, and other aspects of canid biology. © The Author(s) 2020. Published by Oxford University Press.BACKGROUND Proteogenomics integrates genomics, transcriptomics, and mass spectrometry (MS)-based proteomics data to identify novel protein sequences arising from gene and transcript sequence variants. Proteogenomic data analysis requires integration of disparate 'omic software tools, as well as customized tools to view and interpret results. The flexible Galaxy platform has proven valuable for proteogenomic data analysis. Here, we describe a novel Multi-omics Visualization Platform (MVP) for organizing, visualizing, and exploring proteogenomic results, adding a critically needed tool for data exploration and interpretation. FINDINGS MVP is built as an HTML Galaxy plug-in, primarily based on JavaScript. Via the Galaxy API, MVP uses SQLite databases as input-a custom data type (mzSQLite) containing MS-based peptide identification information, a variant annotation table, and a coding sequence table. Users can interactively filter identified peptides based on sequence and data quality metrics, view annotated peptide MS data, and visualize protein-level information, along with genomic coordinates. Peptides that pass the user-defined thresholds can be sent back to Galaxy via the API for further analysis; processed data and visualizations can also be saved and shared. MVP leverages the Integrated Genomics Viewer JavaScript framework, enabling interactive visualization of peptides and corresponding transcript and genomic coding information within the MVP interface. CONCLUSIONS MVP provides a powerful, extensible platform for automated, interactive visualization of proteogenomic results within the Galaxy environment, adding a unique and critically needed tool for empowering exploration and interpretation of results. The platform is extensible, providing a basis for further development of new functionalities for proteogenomic data visualization. © The Author(s) 2020. Published by Oxford University Press.BACKGROUND Effective nonpharmacological interventions targeting the enhancement of vascular function and decline of body fatness (BF) in obese individuals are indispensable for the prevention of hypertension and cardiovascular events in young adults. Mat Pilates training (MPT) has gained significant popularity worldwide, yet its effects on vascular function and body composition are understudied. We examined the effects of MPT on vascular function and BF in young obese women with elevated blood pressure (BP). METHODS Twenty-eight young obese women with elevated BP were randomized to an MPT (n = 14) or a nonexercising control (CON, n = 14) group for 12 weeks. Systemic arterial stiffness (brachial-ankle pulse wave velocity (baPWV)), brachial and aortic BP, wave reflection (augmentation index (AIx)), plasma nitric oxide (NO) levels, and BF percentage (BF%) were assessed before and after 12 weeks. RESULTS MPT significantly reduced (P ˂ 0.05) baPWV (-0.7 ± 0.2 m/s), AIx (-4 ± 1%), brachial systolic BP (-5 ± 1 mm Hg), aortic systolic BP (-6 ± 1 mm Hg), and BF% (-2 ± 1%), while significantly increasing plasma NO (6 ± 2 µM) (P ˂ 0.05) compared with CON. MPT improved systemic arterial stiffness, aortic BP, wave reflection, circulating plasma NO, and BF% in young obese women with elevated BP. CONCLUSIONS MPT may be an effective intervention for the improvement of vascular function and BF in young obese women with elevated BP, a population at risk for hypertension and early vascular complications. CLINICAL TRIALS REGISTRATION Trial Number NCT03907384. © American Journal of Hypertension, Ltd 2020. All rights reserved. For Permissions, please email journals.permissions@oup.com.
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