Objectives/Goals: In neurological animal research, statistical misapplication may lead to overoptimism in a therapy’s potential for successful translation. This pilot study investigated whether human clinical trials that fail have higher prevalence of statistical misapplication in preceding animal experiments, compared to human trials that succeed. Methods/Study Population: Phase 2 clinical trials for 3 neurological conditions were identified on ClinicalTrials.gov and classified as successful or failed based on advancement to Phase 3 and/or preplanned efficacy test results. PRISMA guideline methods were used to systematically search for preclinical animal experiments (same indication and intervention) preceding the start of the human trial. Data were gathered from animal articles by collectors blinded to human trial outcome and included items describing reporting transparency, experimental design and sample sizes, and statistical tests applied. Statistical mistakes were coded based on mismatch between test and design. Rates of mistakes were compared between articles preceding successful and non-successful human trials using weighted point estimates and 95% confidence interval. Results/Anticipated Results: The final sample included 24 trials (16 successful) and 70 associated animal studies. Transparency was poor, with infrequent reporting of group allocation method (39%), sample sizes adequate to evaluate attrition (Discussion/Significance of Impact: Statistical misapplication is common in animal research, and this pilot study has demonstrated that preclinical statistical mistakes may indeed occur more frequently prior to failed human trials. Mistakes and lack of transparency may lead to overoptimism in preclinical experimental findings, with consequences for subsequent human translation.

Objectives/Goals: Our goal is to develop a CRM platform to streamline support for investigators, optimize resource use, and enhance service delivery within a CTSA institution. This platform will measure outcomes, improve transparency, and ensure compliance, creating an efficient, supportive research environment. Methods/Study Population: Beginning with the design concepts and collecting technical requirements, ensuring alignment with the needs of investigators, administrators, and service units. Apply project management methodologies to iteratively design, prototype, and test features. Focus on user-centric interfaces and seamless integration with institutional systems. Incorporate stringent data security protocols in compliance with regulatory standards. Conduct pilot studies to refine functionalities and gather constructive feedback. Facilitate extensive user training programs and offer continuous support. Regularly monitor performance metrics, iterating based on empirical data and user feedback to ensure continuous enhancement and adherence to institutional objectives. Results/Anticipated Results: YCCI successfully designed, developed, and implemented a CRM platform for managing the intake, navigation, consultation, service delivery, and outcomes tracking of the clinical and translational science activities that are supported by and beyond the CTSA-supported infrastructure. The CRM platform has been live in production since roughly July 1, 2024, and YCCI is excited to share data, results, and outcomes with the ACTS community. Discussion/Significance of Impact: YCCI’s CRM platform advances the CTS mission by streamlining PI support, enhancing resource utilization, and fostering inter-team collaboration within the research ops and administration teams. Measuring outcomes and service efficiency enables data-driven decisions, ensuring continuous improvement, and impactful translational science.

Objectives/Goals: This scoping review examines common characteristics of Community Engagement Studios, defined as custom panels bringing together community partners with lived experience around a health issue to provide highly tailored feedback to a research team. The authors also identify health service fields that most commonly use community engagement studios. Methods/Study Population: This scoping review will follow procedures outlined in the Joanna Briggs Institute Manual for Evidence Synthesis. Inclusion criteria are limited to peer reviewed manuscripts published between 2010 and 2024. Key word searches for terms related to Community Engagement Studios will be conducted within Embase, MEDLINE, CINAHL, and Web of Science. Experimental, quasi-experimental, observational studies, process and conceptual manuscripts published in English or Spanish meet inclusion criteria. Two reviewers will reach consensus about article inclusion. Data analysis will include content analysis and descriptive statistics. Results/Anticipated Results: The results for studies that meet inclusion criteria will be summarized through descriptive tables of study characteristics, the number of studies excluded at the full-text review stage, and reasons for the exclusion of any studies that met the initial inclusion criteria. The results will also include a summary of common elements in the design of CE studios, the health disciplines for which CE Studios are most frequently conducted, and the aspect/phase of research design for which CE Studios are most frequently requested. Discussion/Significance of Impact: To date, no work exists examining key elements of Community Engagement Studios and the fields within health services using this valuable research tool. This scoping review is a critical first step to develop guidelines, standards, and best practices around consistent procedures and characteristics to include in the design and conduct of CE Studios.

Objectives/Goals: Research mistrust is well documented. So is community engagement’s potential to foster trust. We share the community engaged development and implementation of informational sessions on research and the protections for participants, aiming at enhancing community members’ knowledge of research. Methods/Study Population: Drawing from a pool of community members who had participated in research projects with a community engaged (CE) research center, we established a four-member Research Partner Committee (RPC) to work with the Center’s research team (CE Team) in the co-creation of materials for an informational session covering two main topics: the fundamentals of biomedical research and of protections for research participants.. The RPC and CE Team also co-developed two sets of pre- and post-tests to evaluate knowledge acquisition at session implementation. Community partners assisted in recruiting their constituents to participate in the sessions and provided convenient sites for the presentations. Results/Anticipated Results: The CE Team and RPC met 7 times to co-create the research and protections presentations (e.g., research definition, importance, inclusion of diverse populations, reasons we have protections, Institutional Review Boards, and informed consent). They also co-developed a 7- and a 9- item pre-post test, respectively. Five informational sessions, implemented by the CE Team with RPC members as observers drew 49 participants (96% African American, 73% female). 55.1% and 75.5% of participants showed a positive change in knowledge after the research and the protections presentations, respectively. 91% agreed to be notified about future research studies at the center. Discussion/Significance of Impact: Engaging community members in dialogue around research and the reasons for mistrust in research encourages relationship development. This engagement equips community members with knowledge to join in conversations around medical studies and make informed decisions about participation in research.

Objectives/Goals: Immune checkpoint inhibitors (IO) have dramatically improved survival outcomes in patients with metastatic melanoma. Still, many patients do not respond these treatments, and others may experience harmful adverse events (irAEs). Thus, there an unmet need for biomarkers for real-time monitoring and management of patients exposed to IO therapies. Methods/Study Population: Serial serum samples were collected from patients with BRAFV600-mutant metastatic melanoma treated with ipilimumab/nivolumab (IO, n = 14) or dabrafenib/trametinib (TT, n = 10). Methylated cell-free DNA (cfDNA) was isolated and sequenced using enzymatic methyl-seq. We develop a robust computational pipeline to identify the top 250 cell-type specific regions of differential methylation (DMRs) across 24 cell-types. Using these differentially methylated regions, a deconvolution tool was developed to determine the abundance of cell type-specific cfDNA in patient serum, and changes in abundance were tracked over treatment time-course to assess response treatment and identify signals of adverse events. Results/Anticipated Results: We demonstrated improved precision in DMR detection evidenced by a higher area under the receiver operator characteristic curve (AUROC) of 0.85 on average. Pathway and functional annotation analysis revealed melanocyte-specific methylation marker regions regulated genes related to melanocyte development and differentiation, including MITF, SOX9/10, and FOXD3. We show these regions are conserved through the transformation to malignant melanoma, indicating melanocyte cfDNA abundance can be used as a marker for tumor burden. We characterize the dynamics of melanocyte-derived cfDNA over the course of treatment in responders and nonresponders to both IO and TT. We observe that changes in concentrations of cfDNA from other cell types correlate with clinically observed irAE-mediated damage to normal tissue. Discussion/Significance of Impact: We demonstrated the utility of decoding the origins of cfDNA fragments obtained from serial liquid biopsy samples. Using cell-specific methylation marks, we identified a signature from the primary melanoma to assess response to treatment, while also obtaining a signal from other tissues throughout the body to monitor immune related adverse events.

Objectives/Goals: Diabetic kidney disease (DKD) affects 40% of diabetic patients, leading to renal failure, yet the molecular drivers remain elusive. MicroRNAs, noncoding regulators of gene expression, may hold the key. This study aims to identify key miRNAs in DKD, providing crucial insights for early intervention. Methods/Study Population: miRNA sequencing was conducted on kidneys from 8-week old male BTBR wild type and BTBR ob/ob mice. BTBR ob/ob mice lack the hormone leptin and spontaneously develop type 2 diabetes, with morphological renal lesions characteristic of human DKD. Total RNA was extracted from whole kidney sections and processed using the QIAseq miRNA library kit. Sequencing was performed on an Illumina NextSeq 550 platform. GeneGlobe analysis was used to identify differentially expressed miRNA functional pathways, while ingenuity pathway analysis (IPA) was employed to predict master regulators and causal networks involved in DKD. Results/Anticipated Results: miRNA sequencing identified significantly differentially expressed miRNAs (p < 0.05) between 8-week-old BTBR WT and BTBR ob/ob male mice, including miR-34a (-6.86 fold), miR-122 (-5.01 fold), miR-129 (-2.23 fold), miR-142a (+2.78 fold), miR-346 (+4.66 fold), miR-547 (-2.49 fold), miR-592 (+11.81 fold), miR-802 (-6.95 fold), and miR-6539 (-7.93 fold). Qiagen GeneGlobe analysis revealed biological processes potentially targeted by these miRNAs, including endocytosis, phagocytosis, hyperglycemia (p = 7.59e-3), and insulin-dependent diabetes (p = 4.32e-4). IPA predicted activation of RRAS, a small GTPase regulating cell growth and signaling (Z-score +2), with miR-34a and miR-122 targeting MYC, PI3K, and TGF-β in DKD progression in BTBR ob/ob mice. Discussion/Significance of Impact: We identified kidney miRNA expression in BTBR ob/ob mice at a pivotal disease stage. miR-34a, miR-122, and RRAS emerged as key drivers in DKD progression, showing remarkable early biomarker potential. These findings lay the groundwork for early detection and innovative therapies to halt DKD and improve patient outcomes.

Objectives/Goals: Investigating the B-cell acute lymphoblastic leukemia (B-ALL)-associated germline SNP rs7090445, located in intron 3 of ARID5B, which is more frequently observed in individuals of Hispanic/Latino descent. Investigating the mechanisms behind this inherited single nucleotide polymorphisms (SNP) that may contribute to the higher incidence of B-ALL in this population. Methods/Study Population: Specific Aim 1: We hypothesize ARID5B SNP rs7090445 disrupts intrinsic enhancer function. Identification of critical DNA looping events impacted by ARID5B variants using Capture C. Affinity purification-mass spectrometry to identify potential ARID5B transcription mediators. Specific Aim 2: We hypothesize the B-ALL-associated SNP leads to a partial human B-cell differentiation block. Utilize Cas9-mediated homology-directed repair to create ARID5B SNP in primary human hematopoietic stem cells. Gene-edited HSCs will be differentiated into B cells using an ex vivo system. Fluorescence-activated cell sorting to sort our pool of cells into stages of B-cell development spectrum. Amplicon sequencing and variant allele frequency of rs7090445 SNP to evaluate its impact on B-cell development. Results/Anticipated Results: This proposal is conceptually innovative as it seeks to understand the mechanism by which the B-ALL-associated SNP rs7090445 in intron 3 of ARID5B disrupts enhancer function and investigates its impact on human B-cell development. Future research will investigate a tumor-suppressive role of ARID5B and whether it constitutes a “first-hit” of leukemogenesis. Discussion/Significance of Impact: Successful completion of this research will elucidate the critical role of the B-ALL-associated ARID5B SNP rs7090445 in human B-cell development and leukemogenesis. As this SNP is more prevalent in Hispanic/Latino populations, it will also provide crucial insights into the genetic factors behind the elevated incidence of B-ALL.

Objectives/Goals: We aimed to discover treatment candidates for uterine fibroids, a common benign tumor with adverse impacts on quality of life. Repurposing already approved medications for fibroids can expedite treatment option expansion. Using genetic proxies, we identified novel fibroid drug candidates and estimated their effect on risk of fibroid diagnosis. Methods/Study Population: We performed a genetically predicted gene expression (GPGE) analysis using S-PrediXcan and GTEx tissue models with multi-ancestry genome-wide association study (GWAS) summary statistics of fibroids (cases  =  74,294, controls  =  465). There were 81 genes significantly associated with fibroid risk. Querying drug–gene interaction databases identified 56 approved medications that target these genes, including two antihypertensives, hydralazine, and spironolactone. Using independent multi-ancestry GWAS summary statistics (N  =  635,969) for systolic (SBP) and diastolic blood pressure (DBP), we conducted GPGE analyses. Blood pressure (exposure) and fibroids (outcome) GPGE summary statistics in the same tissues were used for two-sample Mendelian randomization (MR) analyses to proxy medication effects. Results/Anticipated Results: GPGE analyses identified hydralazine/tumor protein P53 (TP53) activity and spironolactone/thyroid hormone receptor beta (THRB) activity as drug-gene candidate pairs. Both drugs increase gene activity of their paired gene. Increased TP53 expression was associated with SBP in four tissues (exposure). The MR results indicated hydralazine use, proxied by increased TP53 expression, may reduce fibroid risk by 42% per standard deviation of gene expression (odds ratio [OR]  =  0.58, p  =  1.43E-12). Increased THRB expression was associated with DBP in eight tissues and were included in the MR (exposure). The MR results suggest spironolactone use, proxied by increased THRB expression, may reduce fibroid risk by 23% per standard deviation of gene expression (OR  =  0.77, p  = 5.94E-6). Discussion/Significance of Impact: We provide biologically plausible evidence for repurposing hydralazine and spironolactone for reducing risk of fibroid diagnosis. Repurposing these hypertension medications could provide novel preventative treatments for fibroids, particularly for individuals disproportionately affected by both conditions.

Objectives/Goals: The prevalence of type 2 diabetes (T2D) in adolescents is rising, presenting unique challenges for recruitment in clinical research – particularly among adolescents who belong to minoritized race/ethnic backgrounds. The primary aims of our study are to identify and address barriers to recruiting adolescents, particularly around community trust. Methods/Study Population: This study employed a two-phase approach to evaluate recruitment strategies for underrepresented adolescent populations in genomics studies of T2D. After IRB approval, in Phase 1, we utilized the electronic medical record (EMR) system at Children’s of Alabama to prescreen based on inclusion criteria (adolescents aged 12–18 years with T2D). Recruitment efforts were tailored to address barriers unique to underrepresented populations, such as flexibility in scheduling contact times to accommodate family availability. In Phase 2, we are implementing and assessing the effectiveness of a peer recruitment model, wherein adolescents from underrepresented groups are trained to engage peers within their community. Focus groups (6–8 participants per group) will explore facilitators and barriers to recruitment. Results/Anticipated Results: Phase 1 revealed that EMR prescreening effectively identified eligible participants, and direct outreach (phone calls, face-to-face contact during clinical visits) significantly improved recruitment success, especially among underrepresented adolescents. Flexible scheduling and consolidating study appointments enhanced participation, addressing logistical challenges like geographic distance. However, frequent changes in contact information (phone and email information) created barriers. In Phase 2, early focus group results suggest that peer recruitment is promising, with trust and community engagement being key factors. Adolescents recruited by peers were more likely to participate, though logistical hurdles such as transportation and family concerns remain. Discussion/Significance of Impact: Our study demonstrates the value of personalized outreach and prescreening in improving recruitment among adolescents. These strategies can engage communities that include Black, Indigenous, and People of Colored. These findings underscore the need for flexible recruitment strategies to ensure their participation in T2D adolescent research.

Objectives/Goals: Update a 2020 systematic review evaluating comprehensiveness of curricula on community-engaged research (CEnR) principles. Our protocol assesses CEnR training at academic medical centers on inclusion of topics critical in building community-researcher trust, such as self-evaluation of personal traits and understanding power dynamics. Methods/Study Population: Researchers’ well-intentioned interest in CEnR may contribute to mistrust if executed without adequate training in three key domains: 1) community dynamics (e.g., power imbalances, local context), 2) self-evaluation of personal traits (e.g., implicit bias), and 3) dissemination and advocacy. Piasecki et al.’s systematic review found that CEnR trainings at institutions funded by the Clinical and Translational Science Award program inadequately covered these domains. Our protocol builds upon theirs by 1) linking domains to community-researcher trust, as Hallmark et al. recommend; 2) comparing faculty versus community partner CEnR trainings (from CTSA-funded institutions); and 3) including National Cancer Institute-designated cancer centers’ trainings. Results/Anticipated Results: Data collection is underway with analyses to be completed by March 2024. We will determine if programs fortified trainings in Piasecki et al.’s 8 domains (>20% with documented learning objectives, didactic presentations, and experiential learning activities). We will identify exemplar programs to provide recommendations for optimizing curricula. This updated review will gauge progress in the field of CEnR training and guide development of more robust modules, particularly seeking thoughtful, intentional engagement with the target community to cultivate and sustain trust. Strong CEnR training programs are critical for forming inclusive, long-lasting partnerships that benefit researchers and communities alike. Discussion/Significance of Impact: Monitoring and evaluating progress of CEnR training programs ensures the next generation of researchers are prepared to sustain partnerships that benefit individual and community health. Institutional investment in improving CEnR practices is essential to correct historical and prevent future injustices.

Objectives/Goals: Create opportunities for early-stage research apprentices to obtain real-world knowledge expand float pool to meet unmet research staffing needs, and decrease investigator burden Increase operational efficiencies, decrease start-up time, establish metrics, and ensure transparency responsible fiscal stewardship to approach cost neutrality Methods/Study Population: The Research Coordinator Support Service (RCSS) is a pool of research staff available for hire on an hourly basis by Johns Hopkins University (JHU) investigators. RCSS consists of Apprentices we train on the job as well as Coordinators and Senior staff who have completed the apprenticeship program. Started in 2012, RCSS was placed under new management in November 2020. An expansion proposal was submitted to senior leadership for additional financial and human resources. After approval new systems were implemented and additional hires were made. Several efficiencies were introduced in start-up, study assignment, transparency, invoicing, and overall operations to address the waitlist of 25 studies. Senior leadership now required extensive metric reporting to evaluate program success. Results/Anticipated Results: To address the waitlist, current staff was redirected from purely educational to study-related activities and several new hires were made. The waitlist reduced steadily over time and more research occurred. Average hours of research support per month more than doubled from under 500 to over 1,000. When our Administrator left, we implemented an automated hours-based reporting and invoicing tool resulting in substantial cost-savings over rehiring the position. Apprentices, now with rapid onboarding and early study assignments are reporting high satisfaction and many have been promoted to Coordinator positions. Detailed spreadsheets with relevant metrics were created which are accessible, and regularly reported, to senior leadership for decisions on promotions and additional hires. Discussion/Significance of Impact: Budget belt-tightening requires organizations to reduce expenses while continuing to provide the essential services investigators need. This focus has caused RCSS to examine our program and add efficiencies. We hope others looking to build or expand their float pools will benefit from our experiences and the specific efficiencies we implemented.

Objectives/Goals: To assess the attitudes toward social justice of residents and faculty following the didactic series and evaluate the impact of the longitudinal curriculum on resident engagement in social justice activities through community engagements. Methods/Study Population: Data were gathered through questionnaires collected from participating residents and faculty. The session topics were chosen based on “Precepting Toward Social Justice” curriculum from the University of Minnesota Department of Family Medicine and Community Health, including sessions on advocacy, diversity, and implicit bias, among others. The self-assessment questionnaires were specific to the topics of the lecture, assessing knowledge, skills, and attitudes before and after the education sessions. Participants were asked to rate these aptitudes of each topic from “none” to “expert.” Results/Anticipated Results: Out of 22 total participants, 16 returned surveys. Overall, there was a substantial improvement in aptitudes after the lecture. There was an increase in reported above average knowledge of topics: Agency (12.5% to 56.25%), Humility (18.75% to 62.5%), Dignity (12.5% to 62.5%), Partner (18.75% to 50%), Awaken (37.5% to 75%), Place (12.5% to 43.75%), Asset (0% to 37.5%), Sanctuary (6.25% to 50%), Belonging (0% to 37.5%), Whole (0% to 43.75%), Liberation (12.5% to 68.75%), and Heal (37.5% to 75%). 31% reported that the lectures alone had an above average influence on pursuing more social justice activities through community engagement. 44% reported that the lectures had an above average impact on their subsequent patient encounters. 69% stated that this series helped develop their overall social justice skills. Discussion/Significance of Impact: All patients deserve equitable care. Family physicians have a unique role in addressing social justice concerns to eliminate inequalities and drive for better health outcomes. By enforcing social justice in education and implementing it into practice, satisfaction, trust, and well-being of patient and provider will be improved.

Objectives/Goals: We operationalized our evaluation using the RE-AIM framework, by defining its dimensions as nodes within a net effect diagram in the form of radar charts to visually display group variation among nodes. This enhanced our ability to measure the reach, effectiveness, and implementation of our efforts in under-resourced Los Angeles communities. Methods/Study Population: We applied the RE-AIM framework to guide the operationalization of evaluation methods, defining the RE-AIM dimensions generally with a focus on reach, effectiveness, and implementation. We developed and defined a standardized scoring system for metrics that contributed to the RE-AIM dimensions of focus, using data from our activities such as health education workshops targeting diverse, under-resourced populations in Los Angeles. Our standardized scoring system ranged from 1 to 5, reflecting the degree of success within each metric/dimension. Scores were mapped in net effect diagrams in the form of radar charts to enable comparative analysis and visualization, highlighting a variety of grouped variables (i.e., language, locations, and adaptation). Results/Anticipated Results: The operationalized and developed scoring system allowed us to standardize assessment across the RE-AIM dimensions, making it possible to visualize our impact through net effect diagrams. These diagrams illustrated variations in reach, effectiveness, and implementation across different community engagement activities stratified by group variables, providing insights into our impact and areas for adjustment. Preliminary results suggest that the net effect diagram effectively captures both broad and nuanced impacts and serves as a viable application of the RE-AIM framework. The use of standardized scoring enhances data comparability and offers a dynamic visual tool for monitoring ongoing and future initiatives while serving as a tool to display and report our impact. Discussion/Significance of Impact: Operationalizing evaluation with the RE-AIM framework and implementing a standardized scoring system allows us to visualize and monitor effectiveness in real time. This system supports data-driven decision-making for our sustainable, impactful community engagement initiatives ultimately contributing to our goal of improving health equity.

Objectives/Goals: This continuous quality improvement project focuses on the efficiency and effectiveness of social media campaigns for clinical trials and other health research. We analyzed data from 160 studies that recruited via social media campaigns on Meta and used the results to make improvements to MICHR’s Participant Recruitment social media campaigns. Methods/Study Population: Data on 440 ad buys purchased for Meta advertising campaigns designed for 160 studies were collected from U-M’s Research Data Warehouse, Meta, and other administrative sources. MICHR’s participant recruitment team systematically reviewed these data and rated the relevance and effectiveness of the recruitment strategies for each study. Stepwise linear regressions were used to test predictors of the efficiency and effectiveness of social media campaigns on Meta, as measured by the 1) total reach, 2) total clicks, 3) the “click-through rate,” and 4) cost per “click” of the campaign over time. Differences between the impact of campaigns for clinical trials and other clinical and translational research were found. Improvement initiatives informed by these results are underway and their impact is being evaluated. Results/Anticipated Results: 64 clinical trials and 94 non-trials were identified, with an average of $1,635 spent on social media campaigns for trials and $950 spent on non-trials. Across all social media campaigns, an average of 121,500 people were reached at a total cost of $1,220 per campaign, returning 4,288 clicks (4% click through rate) at $0.38 per click. The campaigns for trials reached more people than non-trials (152,998 vs. 101,261) and they attracted a larger number of clicks (6090 vs. 3106). The resulting average click-through rate was higher for clinical trials (4.9% vs. 3.7%), and the cost per click was lower ($0.35 vs. $0.39). Campaigns for clinical trials cost significantly more (Mean  =  $1,635, SD  =  $1,473, p  =  .020) but returned more clicks (Mean  =  6,090, SD  =  5,105, p  =  .007), and higher click-through rates (Mean  =  4.9%, SD  =  2.2%, p  =  .017). Discussion/Significance of Impact: There is great variation in the efficiency and effectiveness of social media advertising campaigns for recruitment into clinical trials and other clinical and translational studies. While the size and cost of these campaigns were found to be higher for clinical trials than for non-trials, the effectiveness of trials’ campaigns can also be greater.

Objectives/Goals: Our research addresses critical gaps by examining the prevalence, blood concentrations, and health implications of xylazine abuse, with a focus on its cardiotoxic effects. We aim to map the geographic distribution of xylazine use across Puerto Rico and characterize its impact on cardiomyocytes at relevant exposure levels. Methods/Study Population: To accurately detect and quantify xylazine in blood samples, we will employ chromatographic techniques coupled with mass spectrometry (UPLC/MS or GC/MS). The xylazine prevalence across the island will be mapped based on health system classifications. Samples will be categorized according to the eight healthcare regions of Puerto Rico, as defined by the “Administración de Seguros de Salud” (ASES), ensuring comprehensive geographic representation. We will investigate the expression profiles of proteins associated with cardiac injury and dysfunction in human cardiomyocytes and in the blood of drug users. Blood samples will be provided by “Iniciativa Comunitaria.” We will assess the xylazine effects on human cardiomyocyte viability and identify key biomarkers of cardiotoxicity induced by xylazine exposure. Results/Anticipated Results: In previous research, we demonstrated that xylazine induces cell death in endothelial cells through both extrinsic and intrinsic pathways. We also observed an increase in reactive oxygen species (ROS) levels after drug exposure, indicating oxidative stress as a potential mechanism of toxicity. Additionally, DNA damage was detected. Given the known relationship between endothelial damage and cardiomyocyte dysfunction in drug-induced cardiotoxicity, we hypothesize that xylazine concentrations vary regionally within Puerto Rico and that chronic xylazine abuse will elevate markers of cardiac injury and dysfunction at common user doses. Discussion/Significance of Impact: The increasing xylazine abuse, particularly in Puerto Rico, represents a critical public health challenge. Our study will fill a knowledge gap by providing crucial data on xylazine’s cardiotoxicity and mapping its geographic prevalence, with the potential to advise healthcare approaches and improve care for drug-using Hispanic populations.

Objectives/Goals: Mayo Clinic’s Clinical Trials Beyond Walls™ (CTBW) program collaborates with study teams to implement decentralized elements in clinical trials, enabling participation from home or local settings. In cancer treatment trials, traditional paper pill diaries are replaced with real-time digital tracking solutions to monitor chemotherapy adherence. Methods/Study Population: The CTBW team developed a solution to deliver electronic pill diaries to research participants using the electronic health record (EHR) system Epic and patient portal MyChart1. The solution includes a portal message to remind participants to take chemotherapy. Medication dose, date taken, and reasons for missed doses (e.g., “I forgot” or “side effects were bothersome”) are captured. An automated in-basket notification system alerts the study team when predefined conditions are met. Configurable medication schedules ensure diaries are sent according to the prescribed frequency. Reports were generated to allow study teams to monitor all participant diaries. Results/Anticipated Results: The CTBW team implemented this digital pill diary in neuro-oncology trial NCT066250472. We anticipate the pill diary in the patient portal will enhance chemotherapy adherence by capturing real-time data in a platform widely used by Mayo Clinic patients. This patient-reported data is stored in the EHR, where it is accessible to providers and study teams. This allows for continuous monitoring, which facilitates a streamlined review of potential adverse events, improved compliance visibility, and timely treatment adjustments compared to paper-based or external solutions. The system also streamlines data entry, reducing human error and eliminating manual transcription. The created language and workflow templates allow the CTBW to scale this approach to future cancer trials Discussion/Significance of Impact: Decentralized clinical trial participants may never visit Mayo Clinic, making digital recording essential. The EHR-based digital pill diary enables continuous monitoring within a familiar system for providers and patients, increasing study team visibility, and allowing for earlier intervention in cases of non-compliance or adverse events.

Objectives/Goals: Discriminatory experiences within healthcare settings significantly hinder equitable health access for sexual minority groups (SMPs) in the USA. These discriminatory experiences can manifest in various forms (e.g., refusal of care). We aimed to explore different types of discrimination encountered by SMPs in the healthcare settings. Methods/Study Population: This study utilized secondary data from the NIH All of Us Research Program. For this analysis, we selected cohorts self-identifying as gay (n  =  9,454), bisexual (n  =  15,284), lesbian (n  =  5,267), and straight (n  =  349,748), enabling robust comparisons across SMPs and straight individuals. We employed analysis of variance and Chi-square analyses to assess group differences in healthcare discrimination, using key indicators from the Discrimination in Medical Settings Scale. These indicators captured experiences such as being treated with less respect or courtesy and feeling ignored by healthcare providers, providing a comprehensive view of discriminatory encounters in healthcare settings for SMPs. Results/Anticipated Results: Our analyses revealed that bisexual individuals reported the highest levels of healthcare discrimination (mean  =  3.64, SD  =  2.45), followed by lesbians (mean  =  3.37, SD  =  2.47), other SMPs (mean  =  3.36, SD  =  2.53), gay (mean  =  2.69, SD  =  2.47), and straight participants (mean  =  2.60, SD  =  2.42). Among the seven discrimination indicators, the most reported experience was feeling like a doctor or nurse was not listening, with 76.8% of bisexual participants, 72.3% of lesbians, 68.8% of other SMPs, and 56.9% of gay participants reporting this experience. This was followed by reports of being treated with less respect and being treated with less courtesy in healthcare settings. These findings highlight the pervasive nature of healthcare discrimination among SMPs, particularly bisexual individuals. Discussion/Significance of Impact: SMPs experience higher levels of discrimination in healthcare settings compared to their straight counterparts. Our results underscore the urgent need to foster respectful, inclusive healthcare environments and ensure that healthcare providers are adequately trained to address the unique health needs and experiences of SMPs.

Objectives/Goals: The impact of the program on alumni students was measured in a 2023 survey, which assessed key factors and student perspectives on motivation to apply/remain in the program, their engagement activities, how they used the skills acquired in RAP upon graduating, and if they were currently serving in a health profession and/or clinical research. Methods/Study Population: Survey questions were based upon specific components of CTSI-RAP that make it unique. Covered topics related to motivation for participation, meaningful experiences, program effectiveness, future use of RAP knowledge/training, and current career roles in the health professions and/or clinical research. The survey was built and analyzed in REDCap and deployed May–July 2023. The study received exempt certification from the IRB. The survey was sent to 123 alumni from the 2013 to 2021 cohorts. Bounced e-mails were followed up on and two reminder e-mails were sent to initial non-responders. Identifiable demographic information was separated from program evaluation questions for analysis. A subanalysis was performed to determine program impact on students who identified as underserved or disadvantaged. Results/Anticipated Results: Respondents included 82/123 (66.7%) alumni. The survey took approximately 15 minutes. Most of the students 64/82 (78.0%) had 1 year or less research experience. The top three motivating factors for joining the RAP program were gaining clinical research experience, exposure to healthcare settings, and interest in pursuing a healthcare related career. Most alumni rated the overall effectiveness of the RAP program as very or somewhat valuable and the majority felt that the program ranked high or very high among their undergraduate experiences. The program was very influential or influential in defining their long-term plans and goals. Just under half felt that their career aspirations were changed or influenced by the program, which was especially true for those who identified as underserved/disadvantaged. Discussion/Significance of Impact: CTSI-RAP alumni highly value their experience in the program. They have benefitted professionally and are motivated to keep their connection to the program alive. With a decade of clinical research excellence and programming, CTSI-RAP’s impact is well established as a proven model benefiting both students and the clinical research infrastructure.

Objectives/Goals: Undergraduate Medical Education (UME) may apply Just-in-Time training (JITT) to provide medical students with learning experiences closely aligned with real-time clinical needs. The purpose of this scoping review is to offer an overview of the implementation of JITT training in UME. Methods/Study Population: Following the five-stage framework by Arksey and O’Malley to methodically collect and analyze studies on JITT in UME, five electronic databases were searched, and a supplemental search for grey literature was conducted. Studies exploring the integration of JITT principles into UME clinical training and their time to follow-up after training were included. Bloom’s Taxonomy was used to assess educational goals of JITT interventions. Results/Anticipated Results: The review yielded 21 studies across 4 countries. The majority were cohort studies (13) and randomized control trials (5). Assessment definitions and use of JITT varied widely. Most studies focused on short-term outcomes, defined by being measured immediately after JITT session (15) or at the end of JITT-based rotation or clerkship (3). Three studies evaluated outcomes at a period longer than 2 weeks after completion of session or clerkship. Attitudes (9), followed by skills (8) were the most common educational goals of intervention. The efficacy and utility of JITT in improving educational goal acquisition was demonstrated in 90% (17/19) of the studies with reported outcomes. Discussion/Significance of Impact: The introduction of JITT in UME has been shown to meet the immediate needs of healthcare environments; however, evidence is limited in the evaluation of longer-term outcomes. Further research to determine the impact of JITT on long-term learning retention and education goal acquisition in UME is merited.

Objectives/Goals: The Clinical and Translational Research (CTR) pathway aims to increase the number of health science professionals participating in CTR in their careers throughout the WWAMI Region (Washington, Wyoming, Alaska, Montana, and Idaho). Methods/Study Population: The first cohort of thirty-one students started in January 2024 and were organized into three groups that met weekly. One in-person group of students in Anchorage, AK; one in-person group in Seattle, WA; and a group of students from across the WWAMI region convened virtually. Students completed a year-long series of elective courses addressing fundamental concepts of designing, conducting, and presenting the results of a research project. Over the summer between year 1 and year 2 of medical school, students dedicated 8 weeks to full-time research activities under the supervision of their research project mentor. In Fall 2024, students prepared and presented research posters at regional poster sessions and abstracts and oral presentations for submission to the Western Medical Research Conference in January 2025. Results/Anticipated Results: The ultimate goal of the CTR pathway is to increase the number of medical providers across the WWAMI region with significant awareness, interest, and experience in research. Many students hesitate to engage in research due to a perceived lack of necessary skills. The CTR pathway addresses this gap by equipping students with the research competencies needed to participate confidently in scientific inquiry. Feedback from the inaugural cohort has been overwhelmingly positive, with many students highlighting how the CTR pathway enhanced their confidence and knowledge, empowering them to execute their proposed research projects successfully. Our second cohort of students joined the CTR pathway in January 2025. Discussion/Significance of Impact: The CTR pathway positions early medical students to engage in research more deeply during their medical training and prepares them to seek additional training opportunities toward a career in research. The majority of students in the first cohort were located at regional sites and many have interest in practicing in rural or underserved areas.