Knowledge graphs have become a common approach for knowledge representation. Yet, the application of graph methodology is elusive due to the sheer number and complexity of knowledge sources. In addition, semantic incompatibilities hinder efforts to harmonize and integrate across these diverse sources. As part of The Biomedical Translator Consortium, we have developed a knowledge graph–based question-answering system designed to augment human reasoning and accelerate translational scientific discovery: the Translator system. We have applied the Translator system to answer biomedical questions in the context of a broad array of diseases and syndromes, including Fanconi anemia, primary ciliary dyskinesia, multiple sclerosis, and others. A variety of collaborative approaches have been used to research and develop the Translator system. One recent approach involved the establishment of a monthly “Question-of-the-Month (QotM) Challenge” series. Herein, we describe the structure of the QotM Challenge; the six challenges that have been conducted to date on drug-induced liver injury, cannabidiol toxicity, coronavirus infection, diabetes, psoriatic arthritis, and ATP1A3-related phenotypes; the scientific insights that have been gleaned during the challenges; and the technical issues that were identified over the course of the challenges and that can now be addressed to foster further development of the prototype Translator system. We close with a discussion on Large Language Models such as ChatGPT and highlight differences between those models and the Translator system.

Co-design is seen as crucial for designing solutions for resource-constrained people living in developing countries. To best understand their needs, user engagement and co-design strategies need to first be developed. In this Design Practice Brief, a process of co-design was created and used to understand ways telecommunication engineers could engage with rural communities in Uganda. It reports and reflects on (i) the experience of co-designing with nondesigners and (ii) creating a co-design structure and developing co-design methods of engaging with community members living in developing countries. In doing so, it offers a format and case study for future practitioners facilitating and conducting co-design with nondesigners and contributes to a knowledge gap in the reporting and reflection of co-design practice. This case study is unique as the co-design practice was achieved remotely (online), crossed disciplines (designers and telecommunication engineers) and cultural boundaries (European and African). It finds that in co-designing with nondesigners, preparation and structure are key, with acknowledgement and management of cultural and discipline differences.

Justice-involved youth (JIY) have high rates of behavioral health disorders, but few can access, much less complete, treatment in the community. Behavioral health treatment completion among JIY is poorly understood, even within treatment studies. Measurement, reporting, and rates of treatment completion vary across studies. This systematic review and meta-analysis synthesizes the literature on rates of treatment completion among JIY enrolled in research studies and identifies potential moderators. After systematically searching 6 electronic databases, data from 13 studies of 20 individual treatment groups were abstracted and coded. A meta-analysis examined individual prevalence estimates of treatment completion in research studies as well as moderator analyses. Prevalence effect sizes revealed high rates of treatment completion (pr = 82.6). However, analysis suggests a high likelihood that publication bias affected the results. Treatment groups that utilized family- or group-based treatment (pr = 87.8) were associated with higher rates of treatment completion compared to treatment groups utilizing individual treatment (pr = 61.1). Findings suggest that it is possible to achieve high rates of treatment completion for JIY, particularly within the context of family- and group-based interventions. However, these findings are limited by concerns about reporting of treatment completion and publication bias.

The Expanded Program for Immunization Consortium – Human Immunology Project Consortium study aims to employ systems biology to identify and characterize vaccine-induced biomarkers that predict immunogenicity in newborns. Key to this effort is the establishment of the Data Management Core (DMC) to provide reliable data and bioinformatic infrastructure for centralized curation, storage, and analysis of multiple de-identified “omic” datasets. The DMC established a cloud-based architecture using Amazon Web Services to track, store, and share data according to National Institutes of Health standards. The DMC tracks biological samples during collection, shipping, and processing while capturing sample metadata and associated clinical data. Multi-omic datasets are stored in access-controlled Amazon Simple Storage Service (S3) for data security and file version control. All data undergo quality control processes at the generating site followed by DMC validation for quality assurance. The DMC maintains a controlled computing environment for data analysis and integration. Upon publication, the DMC deposits finalized datasets to public repositories. The DMC architecture provides resources and scientific expertise to accelerate translational discovery. Robust operations allow rapid sharing of results across the project team. Maintenance of data quality standards and public data deposition will further benefit the scientific community.

OBJECTIVES/GOALS: We aim to identify and characterize anti-Sox2-specific CD8+ T cell responses in stable MUGS patients expressing HLA class I alleles-A*02:01 and /or -B*07:02. METHODS/STUDY POPULATION: Cross sectional study of patients with stable MGUS defined as stable serum paraprotein for ≥ 12 months from the MM Research Clinic at the Abramson Cancer Institute. Sox2 T cell reactivity will be assessed by IFN-γ ELISPOT assays. Rested PBMC will be pulsed with candidate Sox2-derived peptides predicted to display high affinity to HLA class I alleles and known to be processed and presented as determined by “targeted MS/MS” (mass spectrometry). The presence of anti-Sox2-specific CD8+ T cells will be confirmed in peptide/HLA multimer assays using flow cytometry. Anti-Sox2-specific CD8+ T cells will be characterized for HLA restriction and TCR αβ composition. RESULTS/ANTICIPATED RESULTS: Our work is still in progress. From Aug to Dec 2019, 22 MGUS subjects have been analyzed, 11 of which were found to have the HLA of interest. Positive Sox-2 reactivity by ELISpot was found in 3 subjects. DISCUSSION/SIGNIFICANCE OF IMPACT: Anti-Sox2 immune responses may maintain MGUS in a clinical indolent state by eliminating Sox2-expressing clonogenic MM cells. A detailed characterization of anti-Sox2 T cells followed by in-vivo assessment of their anti-myeloma activity could provide the foundation for a Sox2 based immunotherapy approach in MM.

The European Commission is an increasingly important source of funding for international research projects and is due to announce its Framework 5 program early in 1999. The Outcomes of Depression International Network (ODIN), funded from the current EC Biomed 2 program, is a case study in European academic co-operation. Its organization has three key elements. First, engaging the principal investigators: this has involved identifying potential partners, ensuring reciprocity of interests, effective co-ordination, `dividing the spoils' in advance, and setting up good personal and electronic communication systems. Second, an esprit de corps has been created amongst the researchers, maintaining contact and consistency, and promoting higher degrees. Third, ongoing problems including difficulties in negotiations with the EC, divergence of detailed study methods, and isolation and demoralization amongst researchers, have been addressed. ODIN may provide a useful model for researchers wishing to set up international collaborative groups.

This study investigated the attitudes of medical students towards psychiatry, both as a subject on the medical curriculum and as a career choice. Three separate questionnaires previously validated on medical student populations were administered prior to and immediately following an 8-week clinical training programme. The results indicate that the perception of psychiatry was positive prior to clerkship and became even more so on completion of training. On completion of the clerkship, there was a rise in the proportion of students who indicated that they might choose a career in psychiatry. Attitudes toward psychiatry correlated positively with the psychiatry examination results. Those that intended to specialise in psychiatry achieved significantly higher examination scores in the psychiatry examination.

Deriving glacier outlines from satellite data has become increasingly popular in the past decade. In particular when glacier outlines are used as a base for change assessment, it is important to know how accurate they are. Calculating the accuracy correctly is challenging, as appropriate reference data (e.g. from higher-resolution sensors) are seldom available. Moreover, after the required manual correction of the raw outlines (e.g. for debris cover), such a comparison would only reveal the accuracy of the analyst rather than of the algorithm applied. Here we compare outlines for clean and debris-covered glaciers, as derived from single and multiple digitizing by different or the same analysts on very high- (1 m) and medium-resolution (30 m) remote-sensing data, against each other and to glacier outlines derived from automated classification of Landsat Thematic Mapper data. Results show a high variability in the interpretation of debris-covered glacier parts, largely independent of the spatial resolution (area differences were up to 30%), and an overall good agreement for clean ice with sufficient contrast to the surrounding terrain (differences ∼5%). The differences of the automatically derived outlines from a reference value are as small as the standard deviation of the manual digitizations from several analysts. Based on these results, we conclude that automated mapping of clean ice is preferable to manual digitization and recommend using the latter method only for required corrections of incorrectly mapped glacier parts (e.g. debris cover, shadow).

A few studies have examined the association between vitamin D and telomere length, and fewer still have examined the relationship in black or male populations. We investigated the cross-sectional association between the vitamin D metabolite 25-hydroxyvitamin D (25(OH)D) concentration in plasma and relative leucocyte telomere length (LTL) in 1154 US radiologic technologists who were 48–93 years old (373 white females, 278 white males, 338 black females, 165 black males). Plasma 25(OH)D concentration was measured by the chemiluminescence immunoassay, and relative LTL was measured by quantitative PCR. Logistic regression was used to obtain OR and 95 % CI for long v. short (based on median) LTL in relation to continuous 25(OH)D, quartiles of 25(OH)D and 25(OH)D deficiency. We found no significant association between continuous 25(OH)D and long LTL in all participants (Ptrend=0·440), nor in white females (Ptrend=0·845), white males (Ptrend=0·636), black females (Ptrend=0·967) or black males (Ptrend=0·484). Vitamin D deficiency (defined as 25(OH)D<30 nmol/l), however, was significantly associated with short LTL in whites (P=0·024), but not in other groups. In this population, we found little evidence to support associations between 25(OH)D and long LTL over the entire range of 25(OH)D in the overall study population or by sex and race.