Thorsenortega4984

Producing findable, accessible, interoperable and reusable (FAIR) data cannot be accomplished solely by data curators in all disciplines. In biology, we have shown that phenotypic data curation is not only costly, but it is burdened with inter-curator variation. We intend to propose a software platform that would enable all data producers, including authors of scientific publications, to produce ontologized data at the time of publication. Working toward this goal, we need to identify ontology construction methods that are preferred by end users. Here, we employ two usability studies to evaluate effectiveness, efficiency and user satisfaction with a set of four methods that allow an end user to add terms and their relations to an ontology. Thirty-three participants took part in a controlled experiment where they evaluated the four methods (Quick Form, Wizard, WebProtégé and Wikidata) after watching demonstration videos and completing a hands-on task. Another think-aloud study was conducted with three professional botanists. The efficiency effectiveness and user confidence in the methods are clearly revealed through statistical and content analyses of participants' comments. Quick Form, Wizard and WebProtégé offer distinct strengths that would benefit our author-driven FAIR data generation system. Features preferred by the participants will guide the design of future iterations.Enhancers are cis-regulatory elements that play essential roles in tissue-specific gene expression during development. Sotorasib Enhancer function in the expression of developmental genes requires precise regulation, while deregulation of enhancer function could be the main cause of tissue-specific cancer development. MLL3/KMT2C and MLL4/KMT2D are two paralogous histone modifiers that belong to the SET1/MLL (also named COMPASS) family of lysine methyltransferases and play critical roles in enhancer-regulated gene activation. Importantly, large-scale DNA sequencing studies have revealed that they are amongst the most frequently mutated genes associated with human cancers. MLL3 and MLL4 form identical multi-protein complexes for modifying mono-methylation of histone H3 lysine 4 (H3K4) at enhancers, which together with the p300/CBP-mediated H3K27 acetylation can generate an active enhancer landscape for long-range target gene activation. Recent studies have provided a better understanding of the possible mechanisms underlying the roles of MLL3/MLL4 complexes in enhancer regulation. Moreover, accumulating studies offer new insights into our knowledge of the potential role of MLL3/MLL4 in cancer development. In this review, we summarize recent evidence on the molecular mechanisms of MLL3/MLL4 in the regulation of active enhancer landscape and long-range gene expression, and discuss their clinical implications in human cancers.

Immunosuppressant exposure is associated with risk for Clostridioides difficile infection (CDI), however it is unknown whether this risk is shared equally across immunosuppressant classes.

This was a retrospective study. Adults were included if they were tested for community acquired CDI (CA-CDI) by stool PCR within 72 hours of hospital admission from 2010 to 2019. The primary outcome was CA-CDI requiring hospitalization, defined as a positive stool PCR test. The primary exposure was immunosuppressant class, at any dose or duration, defined based on the medication reconciliation performed at hospital admission and categorized as systemic steroids, calcineurin inhibitors, antimetabolites, anti-TNFα agents, anti-CD20 antibody, and all others.

10,992 hospitalized patients met criteria for the study including 1,793 (16%) with CA-CDI. 23% used one or more class of immunosuppressant. The most common class was systemic steroids (16%), followed by calcineurin inhibitors (14%) and antimetabolites (10%). Among those using any immunosuppressant, 27% tested positive for CA-CDI compared to 22% among those who did not use any immunosuppressant (P<0.01). After adjusting for baseline patient characteristics, only calcineurin inhibitors (aOR 1.19, 95% CI 1.01-1.44) were associated with increased risk for CA-CDI. Risk for CA-CDI rose with multiple classes of immunosuppressant aOR 1.22, aOR 1.53, and aOR 2.40 for two, three, and four classes respectively.

Calcineurin inhibitors were associated with a modest but significantly increased risk of CA-CDI. The greatest risk was observed among patients using multiple classes of immunosuppressants. Future studies should recognize that CDI risk differs based on immunosuppressant class.

Calcineurin inhibitors were associated with a modest but significantly increased risk of CA-CDI. The greatest risk was observed among patients using multiple classes of immunosuppressants. Future studies should recognize that CDI risk differs based on immunosuppressant class.

Gait speed is a powerful indicator of health with aging. Potential genetic contributions to gait speed and its decline with aging are not well defined. We determined the heritability of and potential genetic regions underlying change in gait speed using longitudinal data from 2379 individuals belonging to 509 families in the Long Life Family Study (mean age 64±12, range 30-110 years; 45% men).

Gait-speed was measured over 4 meters at baseline and follow up (7±1 years). Quantitative trait linkage analyses were completed using pedigree-based maximum-likelihood methods with logarithm of the odds (LOD) scores >3.0 indicating genome-wide significance. We also performed linkage analysis in the top 10% of families contributing to LOD scores to allow for heterogeneity among families (HLOD). Data were adjusted for age, sex, height, and field center.

At baseline, 26.9% of individuals had "slow" gait-speed <1.0 m/s (mean 1.1±0.2 m/s) and gait speed declined at a rate of -0.02±0.03 m/s per year (p<0.0001). Baseline and change in gait-speed were significantly heritable (h 2 = 0.24-0.32, p<0.05). We did not find significant evidence for linkage for baseline gait speed; however, we identified a significant locus for change in gait speed on chromosome 16p (LOD=4.2). A subset of 21 families contributed to this linkage peak (HLOD = 6.83). Association analyses on chromosome 16 showed that the strongest variant resides within the ADCY9 gene.

Further analysis of the chromosome 16 region, and ADCY9 gene, may yield new insight on the biology of mobility decline with aging.

Further analysis of the chromosome 16 region, and ADCY9 gene, may yield new insight on the biology of mobility decline with aging.