The EpiGraphDB platform is openly available at https//epigraphdb.org. Code for replicating case study results is available at https//github.com/MRCIEU/epigraphdb as Jupyter notebooks using the API, and https//mrcieu.github.io/epigraphdb-r using the R package.

Supplementary data are available at Bioinformatics online.

Supplementary data are available at Bioinformatics online.

Early COVID-19 diagnosis prior to laboratory testing results is crucial for infection control in hospitals. Models exist predicting COVID-19 diagnosis, but significant concerns exist regarding methodology and generalisability.

To generate the first COVID-19 diagnosis risk score for use at the time of hospital admission using the TRIPOD (transparent reporting of a multivariable prediction model for individual prognosis or diagnosis) checklist.

A multivariable diagnostic prediction model for COVID-19 using the TRIPOD checklist applied to a large single-centre retrospective observational study of patients with suspected COVID-19.

581 individuals were admitted with suspected COVID-19; the majority had laboratory-confirmed COVID-19 (420/581, 72.2%). Retrospective collection was performed of electronic clinical records and pathology data.

The final multivariable model demonstrated AUC 0.8535 (95% confidence interval (0.8121-0.8950). The final model used 6 clinical variables that are routinely available inuld be used by any healthcare worker to support hospital infection control prior to laboratory testing results.

We present a high-performance software integrating shotgun with top-down proteomic data. The tool can deal with multiple experiments and search engines.

Enable rapid and easy visualization, manual validation, and comparison of the identified proteoform sequences including the PTM characterization.

We demonstrate the effectiveness of our approach on a large-scale E. coli dataset; ProteoCombiner unambiguously shortlisted proteoforms among those identified by the multiple search engines.

ProteoCombiner, a demonstration video and user tutorial are freely available at https//proteocombiner.pasteur.fr, for academic use; all data are thus available from the ProteomeXchange consortium (identifier PXD017618).

Supplementary material is available at Bioinformatics online.

Supplementary material is available at Bioinformatics online.

The cost of drug development has dramatically increased in the last decades, with the number new drugs approved per billion US dollars spent on R&D halving every year or less. The selection and prioritization of targets is one the the most influential decisions in drug discovery. Here we present a Gaussian Process model for the prioritization of drug targets cast as a problem of learning with only positive and unlabeled examples.

Since the absence of negative samples does not allow standard methods for automatic selection of hyperparameters, we propose a novel approach for hyperparameter selection of the kernel in One Class Gaussian Processes. We compare our methods with state-of-the-art approaches on benchmark datasets and then show its application to druggability prediction of oncology drugs. Our score reaches an AUC 0.90 on a set of clinical trial targets starting from a small training set of 102 validated oncology targets. Our score recovers the majority of known drug targets and can be used to identify novel set of proteins as drug target candidates.

Source code implemented in Python is freely available for download at https//github.com/AntonioDeFalco/Adaptive-OCGP.

Supplementary data are available at Bioinformatics online.

Supplementary data are available at Bioinformatics online.

Nocturnal hypertension is an important phenotype of abnormal diurnal blood pressure (BP) variability and a known risk marker for target organ damage and cardiovascular events. This study aimed to assess the differential BP-lowering effects of esaxerenone vs. eplerenone on nocturnal BP in hypertensive patients with different nocturnal dipping patterns.

This was a post hoc analysis of the „Esaxerenone (CS-3150) Compared to Eplerenone in Patients with Essential Hypertension” study (NCT02890173), which was a phase 3, multicenter, randomized, controlled, double-blind, parallel-group clinical study conducted in Japan. Ambulatory BP monitoring data were collected.

Patients (n = 1,001) were randomized to esaxerenone 2.5 mg/day (n = 331) or 5 mg/day (n = 338), or eplerenone 50 mg/day (n = 332). Reductions in nighttime systolic BP (95% confidence interval) were significantly greater with 2.5 and 5 mg/day esaxerenone vs. eplerenone (-2.6 [-5.0, -0.2] and -6.4 mm Hg [-8.8, -4.0], respectively). Esaxerenone significantly reduced nighttime BP from baseline compared with eplerenone in non-dippers with previously uncontrolled BP. In addition, esaxerenone did not markedly alter nighttime BP in extreme dipper patients. In the esaxerenone 5 mg/day group, esaxerenone-induced decreases in nighttime BP were greater than eplerenone-induced decreases in older patients.

Esaxerenone may be an effective treatment option for nocturnal hypertension, especially in older patients and those with a non-dipper pattern of nocturnal BP.

Esaxerenone may be an effective treatment option for nocturnal hypertension, especially in older patients and those with a non-dipper pattern of nocturnal BP.

There are limited data on how vedolizumab (VDZ) impacts extraintestinal manifestations (EIMs) in inflammatory bowel disease (IBD). The aim of this study was to determine the clinical outcomes of EIMs after initiation of VDZ for patients with IBD.

A multicenter retrospective study of patients with IBD who received at least 1 dose of VDZ between January 1, 2014 and August 1, 2019 was conducted. The primary outcome was the rate of worsening EIMs after VDZ. Secondary outcomes were factors associated with worsening EIMs and peripheral arthritis (PA) specifically after VDZ.

A total of 201 patients with IBD (72.6% with Crohn disease; median age 38.4 years (interquartile range, 29-52.4 years); 62.2% female) with EIMs before VDZ treatment were included. The most common type of EIM before VDZ was peripheral arthritis (PA) (68.2%). Worsening of EIMs after VDZ occurred in 34.8% of patients. There were no statistically significant differences between the worsened EIM (n = 70) and the stable EIM (n = 131) groups in term of age, IBD subtype, or previous and current medical therapy. We found that PA was significantly more common in the worsening EIM group (84.3% vs 59.6%; P < 0.01). Worsening of EIMs was associated with a higher rate of discontinuation of VDZ during study follow-up when compared with the stable EIM group (61.4% vs 44%; P = 0.02). Treatment using VDZ was discontinued specifically because of EIMs in 9.5% of patients.

Almost one-third of patients had worsening EIMs after VDZ, which resulted in VDZ discontinuation in approximately 10% of patients. Previous biologic use or concurrent immunosuppressant or corticosteroid therapy did not predict EIM course after VDZ.

Almost one-third of patients had worsening EIMs after VDZ, which resulted in VDZ discontinuation in approximately 10% of patients. Previous biologic use or concurrent immunosuppressant or corticosteroid therapy did not predict EIM course after VDZ.

There is strong evidence that social support-particularly perceived social support-functions as a protective factor for health. Few studies have investigated how medical students perceive the types of social support they experience.

To determine how osteopathic medical students perceive social support, understand the factors that influence their perceptions, and explore how group participation in a cocurricular, academic program could affect student perceptions.

In this cross-sectional study of 983 medical students at a multicampus osteopathic medical school in the Midwest, potential respondents were invited by email in March 2018 to participate in a self-reported evaluation of their perceived social support using a 40-question Interpersonal Support Evaluation List (ISEL). The demographic variables included gender, race, age, current phase in medical school, Hispanic heritage, campus assignment, and hometown population type. A total score for each type of social support and a summative score for overall it. Longitudinal studies following medical students over time would contribute to a more complete understanding of social support in medical students as they move from preclinical to the clinical phases of medical school.

It is critical to understand the ways medical students experience social support and the factors that contribute to it. Longitudinal studies following medical students over time would contribute to a more complete understanding of social support in medical students as they move from preclinical to the clinical phases of medical school.Hydathodes are typically found at leaf teeth in vascular plants and are involved in water release to the outside. Although morphological and physiological analysis of hydathodes has been performed in various plants, little is known about the genes involved in hydathode function. In this study, we performed fluorescent protein-based imaging and tissue-specific RNA-seq analysis in Arabidopsis hydathodes. We used the enhancer trap line E325, which has been reported to express green fluorescent protein (GFP) at its hydathodes. We found that E325-GFP was expressed in small cells found inside the hydathodes (named E cells) that were distributed between the water pores and xylem ends. No fluorescence of the phloem markers pSUC2GFP and pSEOR1SEOR1-YFP was observed in the hydathodes. These observations indicate that Arabidopsis hydathodes are composed of three major components water pores, xylem ends, and E cells. In addition, we performed transcriptome analysis of the hydathode using the E325-GFP line. Microsamples were collected from GFP-positive or -negative regions of E325 leaf margins with a needle-based device (~130 µm in diameter). RNA-seq was performed with each single microsample using a high-throughput library preparation method called Lasy-Seq. We identified 72 differentially expressed genes. Among them, 68 genes showed significantly higher and four genes showed significantly lower expression in the hydathode. Our results provide new insights into the molecular basis for hydathode physiology and development.

We report results of Years 2 and 3 of consecutive cluster-randomized controlled trials of trivalent inactivated influenza vaccine (IIV3) in Senegal.

We cluster-randomized (11) 20 villages to annual vaccination with IIV3 or inactivated poliovirus vaccine (IPV) of age-eligible residents (6 months – 10 years). The primary outcome was total vaccine effectiveness against laboratory-confirmed influenza illness (LCI) among age-eligible children (modified-intention-to-treat population [mITT]). Secondary outcomes were indirect (herd protection) and population (overall community) vaccine effectiveness.

We vaccinated 74% of 12,408 age-eligible children in Year 2 (June 2010-April 11) and 74% of 11,988 age-eligible children in Year 3 (April 2011-December 2011) with study vaccines. Annual cumulative incidence of LCI was 4.7 (Year 2) and 4.2 (Year 3) per 100 mITT child vaccinees of IPV villages. In Year 2, IIV3 matched circulating influenza strains. The total effectiveness was 52.8% (95% CI 32.3%-67.0%), and the population effectiveness was 36.