The Monarch Initiative in 2024: an analytic platform integrating phenotypes, genes and diseases across species.

Bridging the gap between genetic variations, environmental determinants, and phenotypic outcomes is critical for supporting clinical diagnosis and understanding mechanisms of diseases. It requires integrating open data at a global scale. The Monarch Initiative advances these goals by developing open ontologies, semantic data models, and knowledge graphs for translational research. The Monarch App is an integrated platform combining data about genes, phenotypes, and diseases across species. Monarch\u27s APIs enable access to carefully curated datasets and advanced analysis tools that support the understanding and diagnosis of disease for diverse applications such as variant prioritization, deep phenotyping, and patient profile-matching. We have migrated our system into a scalable, cloud-based infrastructure; simplified Monarch\u27s data ingestion and knowledge graph integration systems; enhanced data mapping and integration standards; and developed a new user interface with novel search and graph navigation features. Furthermore, we advanced Monarch\u27s analytic tools by developing a customized plugin for OpenAI\u27s ChatGPT to increase the reliability of its responses about phenotypic data, allowing us to interrogate the knowledge in the Monarch graph using state-of-the-art Large Language Models. The resources of the Monarch Initiative can be found at monarchinitiative.org and its corresponding code repository at github.com/monarch-initiative/monarch-app

Potential for in situ Bioremediation of a Low-pH, High-Nitrate Uranium-Contaminated Groundwater

The potential for stimulating microbial U(VI) reduction as an in situ bioremediation strategy for uranium-contaminated groundwater was evaluated in uranium-contaminated sediment from the FRC, Oak Ridge, TN. Sediment was at low pH (pH 4) and contained high (55 mM) concentrations of nitrate. The addition of organic electron donors resulted in a slow removal of ca. 20% of the nitrate over 120 days with a concurrent increase in pH. Uranium precipitated during nitrate reduction. This precipitation of U(VI) was not due to its reduction to U(IV) because over 90% of the uranium in the sediments remained as U(VI). Studies in which the pH of the sediments was artificially raised suggested that an increase in pH alone could not account for the precipitation of the U(VI) during nitrate reduction. Metal-reducing bacteria were recovered from the sediments in enrichment cultures, but molecular analysis of the sediment demonstrated that the addition of electron donors did not stimulate the growth of these metal reducers. Thus, although U(VI) was precipitated from the groundwater with the simple addition of electron donors, most of the uranium in the sediments was in the form of U(VI), and thus was not effectively immobilized

Using differences between perceptions of importance and competence to identify teaching needs of primary care preceptors

BACKGROUND: An important goal of a comprehensive faculty development plan is to improve teaching. This is especially important for clinical preceptors. PURPOSE: This study used a novel approach to assessing the teaching needs of preceptors, an essential and often neglected first step in faculty development. Measurement focused on discrepancies between importance and current performance related to a rich variety of teaching behaviors. This study also considered differences in perceived teaching needs among primary care specialties. METHOD: Twenty-six clerkship directors from 13 participating medical schools in the Northeast United States invited randomly selected family medicine, internal medicine, and pediatric preceptors to complete a teaching needs survey. One hundred five preceptors responded. RESULT: Findings revealed that preceptors most need to develop general teaching skills that will help them save time such as selecting appropriate teaching behaviors, assessing learners\u27 needs and providing appropriate feedback, and helping learners learn independently. On the other hand, preceptors expressed less need to improve teaching related to cost containment, disease prevention, clinical decision making, office management, and using computers to aid teaching. Family practice preceptors rated their current teaching performance significantly higher than pediatric preceptors despite no differences in previous faculty development experience. CONCLUSION: Faculty development for preceptors should focus on general teaching skills relative to teaching skills tied to specific medical areas. Novel approaches to teaching while practicing medicine that increase efficiency should be explored. Faculty developers should consider differences in confidence among preceptors from different specialties

Development and implementation of an objective structured teaching exercise (OSTE) to evaluate improvement in feedback skills following a faculty development workshop

BACKGROUND: Faculty development programs focusing on teaching have become widespread. PURPOSE: Despite the popularity of such programs, evidence as to their effectiveness is limited. This article reports on the development of an objective structured teaching exercise (OSTE) and its pilot implementation in an evaluation of a faculty development program module. A written test intended to measure feedback skills was also developed and pilot tested. METHODS: A separate-sample, pretest-posttest design was used to pilot test both instruments. RESULTS: The results showed some evidence of significant differences between groups tested preworkshop and postworkshop. Higher scores were observed for the posttest group compared to the pretest group only for OSTE items focusing on prioritizing and limiting the amount of feedback given at one time and on action planning. CONCLUSIONS: Results suggest that an OSTE may be sensitive to changes in preceptor skill level for skills that are relatively easy to incorporate immediately into practice. Lack of differences in other skill areas may be due to lack of sensitivity of the measure or to need for practice and reflection before changes in performance on other feedback skills are evident

A Functional riboSNitch in the 3\u27 Untranslated Region of

Previous studies have shown that common variants of the gene coding for FK506-binding protein 51 (FKBP5), a critical regulator of glucocorticoid sensitivity, affect vulnerability to stress-related disorders. In a previous report, FKBP5 rs1360780 was identified as a functional variant because of its effect on gene methylation. Here we report evidence for a novel functional FKBP5 allele, rs3800373. This study assessed the association between rs3800373 and post-traumatic chronic pain in 1607 women and men from two ethnically diverse human cohorts. The molecular mechanism through which rs3800373 affects adverse outcomes was established via in silico, in vivo, and in vitro analyses. The rs3800373 minor allele predicted worse adverse outcomes after trauma exposure, such that individuals with the minor (risk) allele developed more severe post-traumatic chronic musculoskeletal pain. Among these individuals, peritraumatic circulating FKBP5 expression levels increased as cortisol and glucocorticoid receptor (NR3C1) mRNA levels increased, consistent with increased glucocorticoid resistance. Bioinformatic, in vitro, and mutational analyses indicate that the rs3800373 minor allele reduces the binding of a stress- and pain-associated microRNA, miR-320a, to FKBP5 via altering the FKBP5 mRNA 3′UTR secondary structure (i.e., is a riboSNitch). This results in relatively greater FKBP5 translation, unchecked by miR-320a. Overall, these results identify an important gene–miRNA interaction influencing chronic pain risk in vulnerable individuals and suggest that exogenous methods to achieve targeted reduction in poststress FKBP5 mRNA expression may constitute useful therapeutic strategies