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: Upon diagnosis, patients with acute myeloid leukemia (AML) have significant information needs. Given its recent increase in popularity, patients may use ChatGPT to access information about AML. We will examine the quality, reliability, and readability of information that ChatGPT provides in response to frequently asked questions (FAQs) about AML. Methods/Study Population: From FAQs on the top 3 patient-facing websites about AML, we derived 26 questions, written in lay terms, about AML diagnosis, treatment, prognosis, and functional impact. We queried ChatGPT-4o on 10/14/2024 using a new Google account with no prior history. We asked each question in a separate chat window once, verbatim, and without prompt engineering. After calibration, 5 oncologists independently reviewed ChatGPT responses. We assessed quality via the Global Quality Scale (GQS), scored from 1 (poor) to 5 (excellent) based on flow, topic coverage, and usefulness. For reliability, we assessed whether each response addresses the query and is factually accurate, elaborating on specific inaccuracies. For readability, we assessed Flesch-Kincaid Grade Level, Gunning Fog Index, and Simple Measure of Gobbledygook. Results/Anticipated Results: This will be a descriptive analysis of ChatGPT responses. For quality and reliability assessments, we will report Fleiss’ kappa for inter-rater reliability and expect substantial agreement or greater (≥0.61). Per prior studies in other domains, we hypothesize that ChatGPT responses will have good quality on average (i.e., GQS score near 4). We hypothesize that nearly all responses will address their query and will mostly be accurate; a minority of responses may have partial inaccuracies. Finally, we hypothesize that readability metrics will suggest that a higher educational level (e.g., college-level education) is required for comprehension. Overall, these findings will help elucidate strengths and limitations of ChatGPT for AML and guide discussion of factors patients should be aware of when using ChatGPT. Discussion/Significance of Impact: No prior study has examined the educational quality of ChatGPT for AML. Our study will detail whether patients are receiving trustworthy and meaningful information, identify misinformation, and provide guidance to oncologists when recommending information resources to patients or fielding questions that patients may raise after using ChatGPT.

Objectives/Goals: Although eHealth tools like websites, apps, and wearables are widely available, underserved groups often do not benefit equally. This gap is due to usability challenges and overlooked structural, physical, and psychosocial barriers. Additionally, high costs and licensing issues make these tools hard to sustain and share. Methods/Study Population: This case study presents lessons learned over eight years of designing and disseminating a user-centered educational website on human papillomavirus (HPV) and the HPV vaccine for Hmong parents and teens (Hmong Promoting Vaccines, www.hmonghpv.com [http://www.hmonghpv.com]), a community-based participatory research project. Results/Anticipated Results: Our community-driven approach revealed four key principles for creating and sustaining culturally tailored eHealth tools for underserved groups: * Engage stakeholders like community members, legal teams, and developers early and keep them involved. * Discuss dissemination and sustainability goals from the start. * Explore commercialization options, balancing sustainability with protection for underserved groups. * Identify and use academic resources to discuss commercialization, ownership, copyright, and intellectual property of such eHealth interventions. Discussion/Significance of Impact: The Hmong Promoting Vaccines case study highlights the need for an inclusive approach to designing sustainable eHealth tools for underserved communities. Early stakeholder engagement, careful planning for dissemination, and balancing commercialization with protection can reduce health disparities and create fairer digital solutions.

Objectives/Goals: Conduct an evaluation of the Clinical Research Support Center (CRSC) model using a structured methodology, leverage insights to drive continuous improvement and evolution, and broadly disseminate outcomes to promote knowledge sharing and best practices for similar translational science initiatives. Methods/Study Population: We will utilize a structured case study approach, including adapting a translational science case study evaluation approach to assess impact as well as support practices, barriers, and facilitators that influence research translation. We will collect data from diverse sources. Primary data will come from structured interviews with stakeholders and a survey of a random sample of faculty and research staff. Secondary data includes grant applications, reports, and publications; public stories/media related to research supported by CRSC; scientific publications; and organizational documents. Results/Anticipated Results: The case study will identify the CRSC model’s impact on the research enterprise. Findings will articulate the specific strategies and practices the CRSC implemented to support clinical research; key factors, people, and resources that helped develop, improve, and promote CRSC services; significant milestones in evolution of the CRSC; and specific ways in which support services impact clinical research infrastructure and outcomes. The findings will highlight both strengths and areas for improvement. Early results show historical challenges with operational silos and resource limitations. Findings suggest CRSC facilitators include a team science approach with institutional support. Discussion/Significance of Impact: This case study will provide insights related to benefits, challenges, and facilitators of a translational science support model. Insights will guide the CRSC’s evolution and be broadly disseminated to promote knowledge sharing and best practices for future translational science applications.

Objectives/Goals: The overarching objective of this study is to inform clinicians, patients, and other stakeholders of the level of evidence and the real-world risk-to-benefit profiles associated with older antidepressant drugs that are frequently used off-label. Methods/Study Population: A PubMed literature review was performed to identify clinical trials conducted in the USA between 2013 and 2023 for trazodone and 2000 and 2023 for escitalopram and citalopram. These studies were examined for robustness, due to sample size, study design, and generalizability. Findings were compared with information provided on UpToDate® LexiDrug™, a primary database used by clinicians to inform prescribing practice. To explore risks associated with off-label use, the FDA adverse event reporting system was probed to identify adverse events reported for each drug; results were systematically categorized by reason for use. To compare the volume of on-label to off-label prescriptions, data will be extracted from electronic health records from University of Southern California-affiliated hospitals. Results/Anticipated Results: Studies conducted on off-label prescriptions of these drugs show primarily small sample sizes, pointing to a limitation in generalizability. For citalopram (N = 77) and trazodone (N = 42), over half of their off-label studies had samples of 50 participants or less. These two drugs also showed low evidence rating for off-label prescription on LexiDrug due to limited power studies. Multiple health agencies recommend against off-label prescriptions for trazodone due to insufficient evidence. There is limited data in the US regarding the volume of off-label prescriptions; however, trazodone’s FAERS analysis indicated a large proportion of adverse event reports (1099/7239) come from cases where trazodone was used for insomnia, an off-label indication, compared to depression, the on-label indication (464/7239). Discussion/Significance of Impact: With 1 in 6 Americans taking antidepressants and 40%–80% of these psychiatric prescriptions being employed off-label, there is a serious and present risk for patients regarding the safety and efficacy of these medications. Awareness must be brought to clinicians to protect patients and encourage evidence-based practice.

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: Using k-means clustering, we aimed to identify whether clusters characterized by greater exposure to minority stressors (e.g., experienced/anticipated discrimination) were associated with lower moderate-vigorous physical activity (MVPA) and higher sedentary behavior among sexual and gender minority (SGM; e.g., lesbian/gay, bisexual, transgender) adults. Methods/Study Population: SGM adults face higher risks of inadequate PA due to exposure to minority stressors, which may influence their willingness and ability to engage in PA. An online sample of SGM adults completed daily surveys about experienced and anticipated discrimination and wore wrist accelerometers for 28 days to objectively measure PA. We used k-means clustering to identify clusters based on reports of experienced and anticipated discrimination. We determined the optimal number of clusters using established partition criteria and ran linear regression models (adjusted for demographic factors) to examine the associations of minority stress clusters with MVPA and sedentary time. Results/Anticipated Results: Among 42 SGM adults (mean age 27.0±7.7 years) with 1133 person-days of accelerometry data, we identified four minority stress clusters: low anticipated/low experienced (LALE; reference group), low anticipated/high experienced (LAHE); high anticipated/low experienced (HALE), and high anticipated/high experienced discrimination (HAHE). Participants in the HALE cluster (n = 12) engaged in 202 fewer minutes of MVPA than those in the LALE cluster (n = 7). Participants in the LAHE cluster (n = 10) had 123 fewer minutes of vigorous PA than those in the LALE cluster. No differences were identified for sedentary time. Discussion/Significance of Impact: This is the first study to examine the association of minority stressors with objective PA among SGM adults. Participants in the HALE/LAHE clusters had lower PA than those with low levels of experienced and anticipated discrimination. Interventions to improve PA among SGM adults must target reduction of minority stressors.

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: 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: Unsafe sleep practices contribute to sleep-related infant mortality, a leading cause of preventable sudden unexplained infant death (SUID). Infant illness represents a risk for SUID. However, the mechanism behind this increased risk is unknown. The objective of this study was to measure changes to safe sleep practices during infant illness. Methods/Study Population: We performed a prospective cohort survey study of infants aged 0–12 months presenting to the pediatric emergency department. We assessed sleep practices prior to illness, during illness, and 2 weeks and 1 month following illness. We assessed adherence to American Academy of Pediatrics safe sleep recommendations at each point in time. Wilcoxon sign rank test was used to examine changes between time points. Regression models compared caregivers who reported a change to unsafe sleep practices with those who did not. Results/Anticipated Results: Of enrolled participants (n = 142), 110 (77%) completed all three follow-up surveys. For those with complete follow-up, 62.4% were female, 60.3% were Black, non-Hispanic, 25.7% were White, non-Hispanic. The most common chief complaint was respiratory illness (35.7%), followed by fever (22.7%), and 70.3% of patients were discharged home. Across all sleep behaviors surveyed, caregivers reported, on average, a 12% change to unsafe sleep practices during illness. These changes were sustained at the 2-week and 1-month follow-ups. Factors associated with a change to unsafe sleep practice were parental age. Discussion/Significance of Impact: Over 10% of infants experienced a change to unsafe sleep practices during illness, sustained at 2-week and 1-month follow-ups. This may explain the association of infant illness with SUID. Interventions promoting safe sleep adherence during illness are key to decreasing sleep-related infant mortality.

Objectives/Goals: This study explores strategies to engage minority and vulnerable populations, including individuals with disabilities, in genomics research. It addresses the ethical, legal, and social implications (ELSI) of human research, with emphasis on data management and culturally sensitive return of actionable results. Methods/Study Population: This study will utilize a mixed-methods approach, combining quantitative surveys with qualitative interviews and focus groups to gather data from minority populations and individuals with disabilities in genomics research. Key stakeholders, including community leaders and healthcare providers, will be engaged to ensure the study’s design reflects community needs and values. Data management practices will be evaluated to align with ethical standards and community expectations. Additionally, the study will examine how actionable results can be effectively communicated to participants, considering cultural and individual differences. Results/Anticipated Results: Preliminary findings suggest that a one-size-fits-all approach to community engagement in genomic research is ineffective. This research emphasizes the importance of engaging diverse populations from the very beginning of the study to ensure that their voices are heard, and their concerns are adequately addressed. Preliminary data reveal significant variations in how communities perceive genetic research, highlighting the need for culturally tailored communication strategies. The proposed study also identifies key barriers to participation, such as mistrust of the research process and concerns about data privacy, which must be addressed to enhance community engagement. Discussion/Significance of Impact: Successful community engagement in genomic research requires understanding the cultural and social dynamics of the populations involved. Researchers must adopt flexible, community-centered approaches that address the unique needs of minority and vulnerable groups, improving inclusivity and leading to more equitable health outcomes.

Objectives/Goals: Despite the acknowledgment of post-Ebola syndrome (PES), young EVD survivors have received little attention. The mechanistic drivers and long-term consequences of PES and EVD early in life are unknown. We aim to define PES presentations in pediatric EVD survivors and propose potential mechanistic factors contributing to PES in young people. Methods/Study Population: Here we focus on physical health outcomes in an ongoing cohort study assessing mental and physical health in pediatric EVD survivors (age Results/Anticipated Results: 671 participants were enrolled between 2021 and 2022 (Infected: n = 226, Affected: n = 207, and Control: n = 238). Groups were similar in sex distribution (52.7%, 54.0%, and 53.8% female, respectively) and mean age, although the Infected group was slightly older (14.6 y) than the Affected (13.5 y) and Control groups (14.1 y), a difference unlikely to be clinically significant. Notably, the EVD Infected group exhibited a higher burden of symptoms, with significant findings in cardiac, MSK, ophthalmologic, and “ear, nose, and throat” systems. Principal component analysis showed differential patterns of sequelae across the groups, primarily defined by MSK. Discussion/Significance of Impact: PES is heterogeneous in pediatric EVD survivors. EVD Affected children exhibit a similar yet distinct pattern of clinical sequelae indicating ecological factors impact sequelae and raising questions about the mechanistic drivers of PES in children. Potential mechanisms include inflammation or accelerated aging and immune dysfunction.

Objectives/Goals: As the aging population increases, maintaining cognitive and physical health becomes crucial. Executive functions (EF), including reaction time, sustained attention, and spatial memory, are essential for daily life and independence in older adults but tend to decline with age, especially in Alzheimer’s disease (AD) patients. Methods/Study Population: Physical balance (PB) impairments further exacerbate this decline, affecting the quality of life and independence. Balance training (BT) emerges as a potential non-pharmacological intervention to enhance EF. This study aims to 1) assess the association between PB impairments and EF deterioration in older adults with AD; 2) evaluate the impact of BT on EF enhancement in this population; and 3) explore changes in brain-derived neurotrophic factor (BDNF) biomarkers before and after physical activity related to BT. This pilot study employs a cross-sectional design with older Hispanic adults (>65 years) in Puerto Rico, comparing a control group without BT intervention to an experimental group with BT intervention. Both groups will be assessed for EF and BDNF biomarkers pre- and post-physical activity. Results/Anticipated Results: Expected outcomes include identifying significant correlations between PB impairment and diminished EF, demonstrating measurable EF improvements following BT, and evidencing sustained BDNF release post-BT despite PB impairments. By understanding the biological mechanisms linking BT and cognitive improvements, particularly the role of BDNF, this research could inform future strategies to mitigate cognitive decline in AD patients through targeted physical interventions. Discussion/Significance of Impact: The findings of this study could provide valuable insights into the development of new preventive interventions, enhancing the quality of life and independence for older adults.

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: To support the growing number of clinical research professionals (CRP) working in behavioral and social science contexts, relevant formative assessments of research skills are needed. This study examines the development of an objective formative assessment designed to assess skills relevant to conducting social and behavioral research. Methods/Study Population: A multidisciplinary group at the University of Michigan was convened to develop the assessment. Case studies depicting clinical and translational research conducted in behavioral and social science contexts were used to measure proficiency in seven of the eight ECRPTQ competencies: Scientific Concepts & Research Design, Ethical & Participant Safety Concerns, Clinical Trial Operations (Good Clinical Practice), Study & Site Management, Data Management & Informatics, Leadership & Professionalism, Communication, and Teamwork & Team Science. Three difficulty levels of questions were developed: basic, intermediate, and advanced. To reinforce knowledge and skill development, the assessment was designed to give respondents formative feedback after responding to each question. Results/Anticipated Results: A preliminary “pre-pilot” test was conducted with three postdoctoral scholars to ensure that the assessment items were understandable. The assessment was then pilot tested with a larger group of 40 clinical research professionals (CRP) to test for the clarity and difficulty level of the items. A smaller group of 20 of these CRPs agreed to participate in focus groups to obtain feedback on their user experience. Data regarding years of experience as a CRP, types of studies engaged with, and information regarding professional certification were collected and used in the analyses. Demographic data collected were not connected to user responses. Results of the pilot test and focus groups were used to revise the questions on the final version of the assessment. Discussion/Significance of Impact: To our knowledge, this is the first objective assessment of research skills for CRP working in behavioral and social science contexts. We will discuss how other institutions can use this instrument to evaluate the training needs of their social and behavioral research workforce.

Objectives/Goals: To facilitate engagement between university researchers and Appalachian Kentucky communities, the UK Rural Research Hub (RRH) promotes Community Engaged Research (CEnR) and academic–community partnerships that have the greatest potential to conduct impactful research to improve health and reduce regional health disparities. Methods/Study Population: Through the UK RRH, a wealth of expertise and a range of services sustain successful CEnR. Hub coordinators provide research consultations, accelerate researchers’ engagement with the community, and facilitate the success of studies through study coordination, assistance with participant recruitment, data collection and interventions, and through dissemination back to the community. Results/Anticipated Results: UK RRH coordinators have supported numerous studies across the region. For example, RRH staff facilitated recruitment of and collected data from 40 Appalachian caregivers of patients with Alzheimer’s disease and related dementias (ADRD) in a study to improve home environments for patient well-being. The study provided pilot data for a successful K23 application. Other examples of supported research include studies to improve cancer screening uptake, self-management of diabetes, and cardiovascular disease risk reduction, resulting in improved care in the community and often providing pilot data leading to larger national grants. Discussion/Significance of Impact: Research addressing the complex health issues that burden Appalachian Kentucky requires community engagement to be successful. The UK RRH is at the heart of successful CEnR that benefits researchers and communities alike.

Objectives/Goals: This study aims to explore transcriptional adaptation, where mutations in one gene trigger compensatory changes in related genes, and how this affects the variability in clinical manifestations of ALS. Our findings will provide insights for therapeutic strategies, while we also use gene editing to investigate correcting variants in ALS patients. Methods/Study Population: The presence of a premature termination codon triggers transcriptional activation. Therefore, we utilized CRISPR-Cas9 tool to generate a premature termination codon in CHCHD10 gene in multiple types of cells, including induced pluripotent stem cells derived from patient samples with known CHCHD10 mutations causative for Amyotrophic lateral sclerosis. CRISPR-Cas9 tool was delivered via ribonucleoprotein electroporation and transfected cell’s DNA was sequenced to validate gene editing. To confirm transcriptional adaption, changes in levels of protein and gene expression will be measured via immunoblot and quantification of CHCHD10 and CHCHCD2 from whole cell lysates of the edited cells. Results/Anticipated Results: Utilizing CRISPR-Cas9 tools, we anticipate that CHCHD2 gene can functionally compensate for the loss of function in the CHCHD10 locus through transcriptional adaptation. Additionally, employing single-stranded oligodeoxynucleotides (ssODNs) we aim to accurately correct the genetic aberrations in ALS patient cells, and study the pathomechanisms of aberrant CHCHD10. Discussion/Significance of Impact: The significance of this research lies in its potential to uncover transcriptional adaptation in humans, which could explain why patients with the same genetic variant experience different symptoms. By understanding this mechanism, we could pave the way for novel therapies, especially for CHCHD10-associated ALS.

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: To present an asset-based approach to advance minoritized patients’ participation in clinical research by elevating experienced Black research participants’ motivations and decision-making processes, favorable sociocultural research contexts, and impactful research questions to reduce chronic disease burden and improve quality of life. Methods/Study Population: Data will be extracted from a pilot study to develop an asset-based approach to clinical research with young Black adults living with chronic pain. Participants will be Black patients at an academic medical institution on the West Coast, ages 21 to 44, currently or formerly have chronic pain, and current or previous electronic health record-captured enrollment in a clinical research study. Approximately 25 Black patients will participate in semi-structured focus groups with topics including: motivations for research participation, access to research, preferred research activities, perceived research benefits, favorable structural and cultural contexts, considerations of past ethical and trust violations, and alignment of research questions and patient needs. Data will be collected Fall ‘24 and analyzed in Winter ‘25. Results/Anticipated Results: We will examine experienced Black clinical research participants’ decision-making processes for participating in research, including access to studies, perceived value of research, community support, and alignment of study goals with their personal interests and needs. Results will illuminate the sociocultural, structural, and historical contexts under which Black patients have successfully participated in clinical research, and types of studies they have participated in, and recruitment procedures that have been effective. Also, we will examine the conditions for successful study completion. Investigators will also learn about the types of clinical research questions that minoritized patients believe will have an immediate and long term impact on their lived experienced with chronic illness. Discussion/Significance of Impact: The results will challenge deficit models of minority research participation that focus solely on barriers to participation, previous ethical harms, and violations of trust/trustworthiness by elevating the motivations, favorable contexts, and empirical priorities of experienced Black clinical research participants.

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.