Objectives/Goals: This study assesses the feasibility of a human-to-swine lung transplant model for the evaluation of bioengineered organs. Given the critical organ shortage, this research explores bioengineered organs as a potential solution by evaluating early lung function, immune responses, and technical aspects to develop a model for bioengineered lungs. Methods/Study Population: The study employs a non-survival human-to-swine left lung transplant model in an immunosuppressed Yorkshire swine. A combination of cobra venom factor pretreated with methylprednisolone and Benadryl with scheduled dosing of tacrolimus and mycophenolate over a 24-hour period will be administered. The transplanted human lung is assessed over a 24-hour post-transplant period, with hourly pulmonary vein gas sampling and lung tissue resections. The proposed model will assess the immunological response of swine to human lung tissue as well as the efficacy of the immunosuppression model. Tissue samples are taken at intervals to evaluate for signs of rejection, cellular damage, and the overall function of the transplanted lung. All tissues are preserved in formaldehyde for subsequent immunohistology evaluation. Results/Anticipated Results: We anticipate a successful non-survival swine transplant model with pulmonary function sustained for the full 24-hour study using our proposed immunosuppression regimen. Initial testing with a standard human lung will lay the groundwork to assess the effectiveness of the human-to-swine transplant model. Hourly pulmonary vein gas analyses and tissue biopsies are expected to show minimal immune rejection, supported by the preoperative immunosuppression regimen. Early data indicate that the swine tolerates both the surgical procedure and immunosuppressive therapy well, with manageable hemodynamic stability. This model is expected to yield critical insights into lung viability and will identify areas for optimization for long-term survival studies to test the efficacy of bioengineered organs. Discussion/Significance of Impact: This non-survival swine model offers valuable insights into the acute-phase immune response and functional viability of human-to-swine lung transplant model. The findings will support the development of long-term survival models that will allow the evaluation of bioengineered organs based solely on their functionality as engineered organs.

Objectives/Goals: Biomedical researchers must understand disease pathology mechanisms and participate in the translation of laboratory findings, research dissemination, and discovery implementation to improve health outcomes. Also, they need experience engaging diverse stakeholders. This requires intentional training as a translational scientist. Methods/Study Population: Our T32, pre-doctoral Translational Biomedical Sciences (TBS) Training Program addresses the 7 characteristics of a translational scientist: domain expert, boundary crosser, team player, process innovator, skilled communicator, systems thinker, and rigorous researcher. Core curriculum components include a clinical practicum where trainees shadow a clinical researcher; community-engaged research training with community member interactions to apply learned principles; a translational research informatics class with informatics, bioinformatics, and natural language processing training; a research seminar providing practical research dissemination and implementation experience; and a team science course where trainees learn to participate on/lead research teams. Trainees tailor the courses to their research areas. Results/Anticipated Results: Using the 7 characteristics of a translational scientist as a guiding framework, we developed five, one-semester courses (described above) integral to the development of the TBS trainees. The initial cohort of trainees are taking the classes, and they will evaluate the courses using Kirkpatrick’s Model, assessing reaction, learning, behavior, and results. The trainees will complete follow-up surveys annually throughout the doctoral program to evaluate ongoing changes in behavior and results. At semester end, trainees will also participate in focus groups to provide feedback about the courses, their relevance to the characteristics of a translational scientist, and barriers and facilitators to the development of the 7 characteristics. Iterative changes will be made to the courses based on trainees’ feedback. Discussion/Significance of Impact: The TBS Program will provide a comprehensive educational experience that prepares trainees for successful, independent research careers in the broad area of translational science as well as equipping them with the confidence to work across disciplines with diverse stakeholders to design, disseminate, and implement their research.

Objectives/Goals: This project provides a framework for collaborative design of a health technology intervention. We aim to provide guidance for those seeking to incorporate community-informed insights into their intervention development, particularly within the context of a large randomized controlled trial. Methods/Study Population: As part of the patient engagement arm of the Championing Hypertension Remote Monitoring for Equity and Dissemination study, we designed patient-facing intervention components for a home hypertension monitoring system. In the design process, we convened patient consultants via regular meetings, one-on-one interviews, and focus groups, and then subsequently analyzed meeting recordings, audio transcripts, and stakeholder notes. All design sessions were offered in either English or Spanish, and sixteen participants were involved. An inductive thematic analysis is being performed utilizing two coders, and Dedoose has been used to organize and refine the data. Results/Anticipated Results: The randomized trial will begin late 2024, with overall design findings incorporated into the intervention. A more detailed qualitative analysis will map these design findings to overarching theory from the Technology Acceptance Model. These qualitative themes will provide a model of patient involvement in study design in a large randomized controlled trial, potentially guiding future improvements in technology-based healthcare delivery interventions. Discussion/Significance of Impact: As technology becomes integral to healthcare, involving patients in intervention design and rollout can improve efficacy and utilization. By offering a framework for patient involvement in intervention design, we aim to create a replicable model to enhance the translation of research into practice.

Objectives/Goals: The objective of this project was to develop electronic health record-based algorithms, or computational phenotypes, for carbapenem-resistant Enterobacterales (CRE) and extended-spectrum beta-lactamase-producing Enterobacterales (ESBL) infections based on public health surveillance case definitions. Methods/Study Population: We analyzed electronic health records (EHR) from a retrospective cohort of patients within the University of Colorado Health System. We detected CRE and ESBL infections using a set of string-matching algorithms for bacterial organism, specimen source, and antibiotic susceptibility test results. Infections were limited to the first case of each organism per patient in a 30-day period. We conducted manual chart review on a subset of cases and non-cases for validation purposes. We then performed a descriptive analysis to examine demographic characteristics of patients with CRE and ESBL infections including sex, age, infection type, and organism. All analyses were conducted using R statistical software. Results/Anticipated Results: There were 634 CRE infections from 2013 to 2023, with the majority from urine (n = 448, 70.7%) or blood specimens (n = 56, 8.8%). Over half of CRE case-patients were female (n =  362, 57.1%). The mean age was 65.0 years. Most isolates were identified as Enterobacter cloacae complex species (n = 353, 55.6%). There was a total of 4,363 ESBL infections from 2019 to 2023, and most were urine (n = 3,550, 81.4%) or blood specimens (n = 457, 10.5%). Most ESBL case-patients were female (n = 3,030, 69.4%) with a mean age of 61.2 years. The majority of isolates were identified as Escherichia coli (n = 2,932, 67.2%), followed by Klebsiella pneumoniae (n = 368, 8.4%). Validation results are pending, including sensitivity and specificity of the algorithms. Discussion/Significance of Impact: Demographic characteristics of CRE and ESBL case-patients were similar to findings from traditional public health surveillance. The algorithms will supplement traditional surveillance methods, inform future epidemiological research using EHR data, as well as contribute to the development of standardized EHR-based definitions for CRE and ESBL.

Objectives/Goals: Collaborations between Academic Medical Centers (AMCs) and Historically Black Colleges & Universities (HBCUs) are critical to addressing health disparities and building research capacity. Herein, we examine the Duke-NCCU Collaborative Translational Research pilot funding program [2018–2023] to identify opportunities, challenges, and lessons learned from querying key stakeholders. Methods/Study Population: The Duke-NCCU collaborative pilot funding program was launched to support new inter-institutional collaborations that aim to accelerate research discoveries into testing in clinical or population settings. Eight one-year, $50,000 collaborative grants were awarded. Each funded team was assigned a CTSI Project Leader (PL) for project management support. To evaluate the program, we developed surveys targeting principal investigators (PI) and PLs. Questions covered collaboration motivation, goals, outcomes, operational processes, project management support, institutional differences, and challenges. Qualitative analysis will be employed to evaluate the responses and identify common themes. Results/Anticipated Results: The PI survey examines aspects of inter-institutional collaborations, focusing on common themes, such as authorship, definition of success, and institutional culture. The PL survey prompts feedback on managing inter-institutional teams, expectations, and challenges. Select questions were shared between both surveys to capture both perspectives. Surveys were reviewed by members of the Duke CTSI evaluation and team science teams. The PI survey will be disseminated to 16 investigators, while the PL survey will reach 5 project leaders. Built on Qualtrics, each survey takes 20–30 minutes to complete. To encourage participation, incentives will be offered as two $100 gift card drawings. Respondents can choose to complete the survey on Qualtrics or through a recorded and transcribed Zoom session. Discussion/Significance of Impact: AMC-HBCU inter-institutional collaborations drive innovation, workforce development, and equitable dissemination of outcomes. This study exemplifies collaboration, offering insights into translational research collaborations critical to advance equitable healthcare and improving population health.

Objectives/Goals: 1) Discuss process of pilot integration of Community Health Worker (CHW) services as a component of patient-centered healthcare service delivery in 3 clinic models. 2) Summarize profiles of patients who self-select to utilize CHW services. 3) Discuss social determinants of health impacts of underserved and historically marginalized populations. Methods/Study Population: The priority population consists of individuals living in Mobile AL at or below poverty level. USA Health Center for Healthy Communities (CHC) piloted the integration of CHW services at USA Health Stanton Road Clinic (SRC), at USA Student Run Free Clinic (SRFC), and as part of a Medi Hub Outreach Clinic with the historically underserved MOWA Choctaw native American population. SRC is a high-utilization clinic for uninsured or underinsured patients across the breadth of the Gulf Coast. The other 2 sites serve similar clientele. Social determinants of health (SDOH) screenings at intake facilitate CHW referral for a clients’ unique needs for support at healthcare or social care agencies. Referral summaries can then be used to guide planning, community collaborating partner intervention, and clinical quality certification, Results/Anticipated Results: Results include identification of referrals process by which CHWs are able to provide culturally competent support to persons accessing healthcare services at the 3 clinic models identified. Identification of top SDOH needs that preclude access to care among the patients served during a 24-month pilot period, e.g., (i) housing insecurity, (ii) food insecurity, (iii) transportation, (iv) health Ins, and (v) pharmacy access and payment assistance. Discussion of beneficial impacts for health care service delivery with other members of the multidisciplinary clinical teams as recorded referrals can be used to guide planning, clinic certification efforts Discussion/Significance of Impact: Patient utilization of CHW services though self-selective offers opportunities for equity in access to care services from direct SDOH impacts, where CHWs act as responsive resource coordinators within the multi-disciplinary service delivery team.

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 study’s overarching goal is to characterize the relationship between water transfer rate (Kw) across the blood–brain barrier (BBB) as measured by diffusion prepared (DP) and multi-echo (ME) ASL in two cohorts that have been shown to have regionally different water transfer rates due to underlying changes in BBB physiology. Methods/Study Population: Ten young, healthy participants (aged 21–30 years, 4f) and 12 elderly participants (aged 66–84 years, 8f) underwent MRI scans on a 3T Siemens Prisma scanner. Structural scans, along with DP and ME ASL, were acquired from each of the participants. The order of the DP and ME ASL sequences was reversed in half the participants to account for ordinal bias. FreeSurfer was used to segment the structural image into respective gray matter, white matter, and deep cortical gray regions to perform region of interest (ROI) analysis. Results/Anticipated Results: We are still in the project’s analysis phase. The anticipated result is that we will see different water transfer rate (Kw) patterns between the old and young groups and between the two sequence groups. Discussion/Significance of Impact: The significance of the results is that we can answer two questions: 1) if there are any differences between water transfer rates in the two age groups and 2) whether there are any variations in performance differences between the sequences.

Objectives/Goals: Children with chronic respiratory technology needs (CRTN) are becoming a dominant patient group in pediatric intensive care units (ICUs). However, little is known about patient-level, long-term outcomes in this population. The lack of such knowledge may lead to inadequate ICU therapies, interventions, or follow-up care. Methods/Study Population: This project will deploy a set of ecological momentary assessment (EMA) modules measuring real-time functioning as well as standardized instruments to measure child and family outcomes including health care utilization, physical functioning, and health-related quality of life following pediatric critical illness in children with CRTN. EMA has particular strength in assessing conditions where individual-level characteristics vary over time, as after critical illness. EMA’s recurrent measurements allow for evaluation of the variables’ temporal course and limit the potential for bias associated with recall surveys. Pulmonary function in children with CRTN in this study will be monitored over time using standardized pulmonary metrics and information from home respiratory machines. Results/Anticipated Results: This work tests the central hypothesis that long-term functional outcomes in children with CRTN are predicted by multimodal data obtained during and shortly after critical illness. To date, 17 families (of a planned 70) have been enrolled. Adherence to EMA modules is high, with 80% completion. Following serial data collection at 3, 6, and 9 months after hospital discharge, phenotypes of recovery (including improvement, stability, or deterioration) will be described. This will include 1) describing the patient demographic and clinical features associated with each long-term outcome trajectory and 2) identifying subgroups with similar outcome trajectories using patient demographics, features of the clinical illness, and EMA data using both traditional biostatistical and causal analysis techniques. Discussion/Significance of Impact: This project will provide important insights into the long-term outcomes following critical illness of children with CRTN while utilizing an innovative methodology. This proposal will provide the necessary information to drive future clinical trials assessing potential interventions at a number of different points to improve outcomes.

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 primary objectives of this project were to create a user-friendly website that • Shares details of ongoing studies in an easily searchable and filterable format. • Provides lay summaries of study results. • Highlights our volunteer registry. • Offers a platform for community engagement and feedback on research interests. Methods/Study Population: The website, developed using DRUPAL 10 and launched in June 2024, was created with input from faculty, staff, research participants, and community partners. It targets potential participants, community members, providers, and other Academic Medical Centers. The development process included focus groups to identify design and feature needs, design iterations and usability testing, and an external accessibility review. Study information is automatically updated from the Study Information Portal (SIP) in OnCore and a custom REDCap survey. Features include a research volunteer registry, study results in lay terms, educational content about research, and multiple ways for community engagement. The site supports English and Spanish and follows best practices for accessibility. Results/Anticipated Results: Community feedback on the site has been very positive, with positive comments about ease of navigation and the improved appearance of the website. It is still early, but we have seen a notable increase in enrollment in the Volunteer Registry since the launch of the website. We track referral sources for the registry, and to date, we have seen 98 individuals enrolled who were directed to us through the website since it launched. This equates to an average of 5 people a week, more than any other referral source. This rate increases to almost 7 per week if we look solely at the period since we started the promotion of the website in early August. As the site awareness expands, we will also be getting feedback from individual studies and are tracking email communication generated from the site as well. Discussion/Significance of Impact: The development of this website represents a significant step toward improving community engagement in clinical research at Duke. By providing a centralized platform for study information, results, and community feedback, we aim to foster a more informed and involved participant base, ultimately enhancing the impact and reach of our research.

Objectives/Goals: Research participants are not representative of our communities. To determine research perceptions, we are recruiting individuals who have and have not participated in studies. We aim to identify trends, capturing motivating factors, access barriers, and participants’ concerns to inform best practices to engage participants. Methods/Study Population: We developed a 25-item survey with a goal of engaging 500 individuals. Survey questions were developed based on published literature of research motivations and barriers, as well as focus groups conducted in our central Pennsylvania community. Survey questions consist of Likert-scale, multiple choice, and free text, with administration through REDCap. Potential survey participants will be recruited from the Penn State Volunteer Repository and through partnering clinical networks, including federally qualified health centers. We will also recruit individuals who have never participated in research to engage underrepresented groups via the Penn State Clinical and Translational Science Institute’s community partner network. Analyses will include Chi-squared tests and binomial logistic regression. Results/Anticipated Results: The primary dependent variable will be past participation in research, while the primary independent variables will be binary responses to questions relating to motivators and barriers to participation in research. Secondary analysis will stratify these comparisons by race or rurality with a subgroup analysis using the same methods as the primary analysis. Based on these analyses, we anticipate that those who have never participated in research will face greater and different barriers than those who have participated in research. We also anticipate that motivators will be similar between to the two groups. We anticipate finding differences in motivators and barriers among different races as well as differences when examining rurality versus non-rurality. Survey results will be available in January. Discussion/Significance of Impact: This will be one of the few studies in the literature focused on uncovering motivators and barriers to research participation. Understanding what motivates and prevents individuals from participating in research is one of the first steps to enhancing the research process so that people want, and are able, to participate in studies.

Objectives/Goals: In recent years, there has been growing interest in the development of air pollution prediction models, particularly in low- and middle-income countries that are disproportionately impacted by the effects of air pollution. Recent methodological advancements, particularly in machine learning, provide novel opportunities for modeling efforts. Methods/Study Population: We estimate daily ground-level fine particulate matter (PM2.5) concentrations in the Mexico City Metropolitan Area at 1-km2 grids from 2005 to 2023 using a multistage approach. Spatial and temporal predictor variables include data from the moderate resolution imaging spectroradiometer (MODIS), Copernicus Atmosphere Monitoring Service (CAMS), and additional meteorological and land use variables. We employed machine-learning-based approaches (random forest and gradient boosting algorithms) to downscale satellite measurements and incorporate local sources, then utilized a generalized additive model (GAM) to geographically weight predictions from the initial models. Model performance was evaluated using 10-fold cross-validation. Results/Anticipated Results: On average, the random forest, gradient boosting, and GAM models explained 75, 82, and 83% of variations measured in PM2.5 concentrations. PM2.5 levels were generally higher in densely populated urban centers and lower in suburban and rural areas. Important predictors of ground-level PM2.5 included wind (both u and v components), 2-meter mean air temperature, elevation, and the normalized difference vegetation index (NDVI). Discussion/Significance of Impact: Using novel machine learning-based approaches, we developed robust models with fine-scale spatial (1-km2) and temporal (daily) variations of PM2.5 in Mexico City from 2005 to 2023. The predicted PM2.5 concentrations can further advance public health research on air pollution in Mexico City and beyond.

Objectives/Goals: SARS-CoV-2 infection has been shown to impact multiple organ systems, including the brain, and is associated with increased cognitive decline in vulnerable populations. The gut microbiome may play a significant role in modulating these effects, as shifts in microbiota composition have been linked to inflammation and systemic disease processes. Methods/Study Population: To explore these interactions, we conducted an acute COVID-19 study using 12-week-old C57 mice intranasally inoculated with 1x10^4 PFU of the Mouse Adapted 10 (MA-10) strain of SARS-CoV-2. On day 5 postinfection, we performed 16S ribosomal RNA sequencing on fecal samples, analyzed using QIIME2 and DeSeq2, to assess microbiome alterations and identify changes in metabolic pathways associated with inflammatory responses. Results/Anticipated Results: Analysis revealed notable shifts in the gut microbiome during the acute phase of COVID-19 infection, with significant alterations in metabolic pathways related to inflammation and immune regulation. These changes suggest that early gut microbiome disruptions may contribute to the host response in acute COVID-19. Discussion/Significance of Impact: Our findings indicate that acute SARS-CoV-2 infection leads to rapid alterations in the gut microbiome, which could underlie inflammatory and immune pathways impacting disease progression. These insights highlight the potential for microbiome-targeted therapies to mitigate acute COVID-19 morbidity and warrant further investigation.

Objectives/Goals: Early childhood obesity is a major concern for Latin American children in the U.S., with gut barrier dysfunction as a key risk factor. Diet plays a role in gut development, but few studies have focused on Latin American infants. Our objective is to identify culturally relevant introductory foods that promote in vitro gut barrier development and function. Methods/Study Population: Pooled human milk (2.5 mL) from 6-month postpartum Hispanic mothers was combined with fruit and vegetable baby food products (2.5 g) and subjected to a 3-phase in vitro digestion system that simulates oral, gastric, and intestinal digestion. Digesta products were then anaerobically fermented for 24-hours using human stool inoculum, centrifuged, and filter sterilized. Intestinal epithelial cells (Caco-2, ATCC) were grown to confluence on 0.4 μm polystyrene transwell inserts using a DMEM + 10% FBS medium and allowed to differentiate for 21-days. Highly differentiated monolayers were treated with a 1:4 dilution of fermenta with medium in triplicate. The cell experiment was conducted twice. Cell layer integrity was measured using transepithelial electrical resistance (TEER) 24- and 48-hours after treatment. Results/Anticipated Results: Dietary intake data from the What We Eat in America database indicated that the top 3 fruit and vegetable exposures for infants with Mexican or Hispanic ethnicity were banana, apple, and carrot. Commercial baby food purees of these fruits and vegetables, in addition to baby foods with blueberry and spinach (Natural for Baby, Gerber Products Company) were acquired for digestion and fermentation experiments. Caco-2 cell experiments with these foods are ongoing. We expect Caco-2 monolayer incubated with fermenta from human milk and fruit or vegetables will have greater TEER values due to increased integrity of the cell layer as compared to those with breast milk alone. We also expect that exposure to fruit and vegetable fermenta will increase gene expression of tight junctions compared to exposure to media and human milk. Discussion/Significance of Impact: Using an in vitro digestion and fermentation system coupled with cell culture studies, we are identifying cellular mechanisms that link individual fruits and vegetables to gut barrier function. This will support translational work focused on mitigating obesity development in vulnerable populations.

Objectives/Goals: Injury to the medial knee ligaments (sMCL, dMCL, POL) and anterior cruciate ligament (ACL) can cause anteromedial rotatory instability (AMRI). AMRI can cause knee instability and ACL graft failure, but it is unclear how the sMCL, dMCL, POL, and ACL resist AMRI. We aimed to characterize the in-situ forces of the sMCL, dMCL, POL, and ACL under loading conditions involved with AMRI. Methods/Study Population: We characterized the in situ forces of the sMCL, dMCL, POL, and ACL under 1) isolated external tibial rotation torque (ER), 2) isolated anterior tibial force (Ant), and 3) combined ER+Ant loading. Twenty-eight human cadaveric knees (18 male; mean age, 48±13; 21–65 years) were tested on a robotic manipulator with force sensing. Tibiofemoral kinematics were recorded under isolated ER (4Nm, 0–90°), isolated Ant (134N at 0–90°), and combined ER+Ant (4Nm+100N at 15, 30, 90°). The sMCL, dMCL, POL, and ACL were dissected in random order. The in situ force (N) in the sMCL, dMCL, POL, and ACL at the peak applied load for each loading condition was calculated using superposition and compared with Kruskal–Wallis tests with post hoc pairwise testing using a Bonferroni–Holm correction for multiple comparisons (α = 0.05). Results/Anticipated Results: Under isolated ER, the force in the sMCL (32–52N) from 0°-90° exceeded that of the ACL, dMCL, and POL at each flexion angle (p0.05). Force in the ACL was the second highest (26–6N from 0°-90°). Force in the dMCL and POL was low (≤12N). Under isolated Ant, the ACL carried the highest force at all flexion angles (≥113N) (p0.05), but at 90° the sMCL carried the highest force of all ligaments (p0.05). At 90°, force in the dMCL diminished (Discussion/Significance of Impact: We show that the sMCL is the major stabilizer to external rotation torques and combined anterior and external loading conditions related to anteromedial rotatory instability across the arc of knee flexion, while the dMCL, POL, and ACL play a less prominent role, with the exception of the ACL and dMCL near full extension.

Objectives/Goals: The University of Utah (U of U) CTSI has partnered with the Salt Lake Center for Science Education (SLCSE), a Title I school serving grades 7–12. Goals of this partnership are to 1) bridge the gap between K12 classroom learning and real-world applications and 2) better prepare students from underrepresented populations to enter the STEM workforce. Methods/Study Population: To cultivate science self-efficacy in grade 7–12 students, experiences included interviewing a scientist for 7th graders, model organism lab visits for 11th graders, and summer research internships for rising seniors. Additional engagements on the SLCSE campus included U of U guest speakers, U of U faculty and student participation in afterschool STEM clubs, U of U graduate students’ mentorship of high school science fair projects, and U of U faculty support in establishing a zebrafish lab for biology students. All students were surveyed at the start and end of the academic year using DEVISE evaluation tools developed by the Cornell Lab of Ornithology. Students participating in the summer internship program also completed the mentoring competency assessment before and after their ten-week internship experience. Results/Anticipated Results: During the first year of a seven-year longitudinal study, 380 SLCSE students engaged in at least one science experience through the Utah CTSI-SLCSE partnership named BEES (Boosting Engagement through Experiences in Science). Pearson product-moment correlations were used in preliminary studies to examine relationships between experience type and student motivation and interest in STEM. Field trips to U of U STEM labs and of U graduate students’ mentorship of high school science fair projects were significantly correlated with student motivation and interest, while the interview-a-scientist experience was significantly correlated with motivation only. The Utah CTSI-SLCSE BEES Program’s impact on student STEM success continues to be assessed using surveys and student reflections. Discussion/Significance of Impact: Access to science for underserved K-12 students is a critical issue in addressing educational equity and improving pathways into STEM fields. Many students attending SLCSE are low-income minority students with limited access to role models in STEM. The BEES partnership provides impactful opportunities for students to gain access to STEM.

Objectives/Goals: Poor visual memory and perceptual organization task performance predicts cognitive decline and is sensitive to dementia severity. No genome-wide association study (GWAS) has assessed the genomic basis of cognitive visual-spatial phenotypes. We aimed to identify common genetic variants associated with visual memory and spatial organization. Methods/Study Population: We included dementia- and stroke-free participants aged 45 years or older from up to seven cohorts in the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, who performed cognitive tasks assessing delayed visual memory (e.g., Benton Visual Retention Test (BVRT, n = 10,934) and visual reproductions (VR, n = 5,527)) or spatial organization (i.e., Hooper Visual Organization Test (HVOT, n = 5,024)). Each cohort used linear regression models to relate common genetic variants imputed to the 1000 Genomes panel to each cognitive phenotype, adjusting for age, sex, population stratification, and education. Summary statistics for the BVRT were meta-analyzed using METAL. Combined GWAS was used for a joint analysis of all traits. Results/Anticipated Results: We identified a genome-wide significant variant related to BVRT performance located near the TSHZ3 gene (rs10425277, p = 6.76×10–9). TSHZ3 is important for the development and function of cortical projecting neurons and may be implicated in Alzheimer’s disease progression by repressing CASP4 transcription. Multitrait analyses, including BVRT, VR, and HVOT, identified two additional variants of interest in SMYD3 gene (rs10802275, p = 5.58×10–7) and near ZFPM2 (rs2957459, p = 2.03×10–7), both of which are overexpressed in the brain and have important implications for neurodevelopment. SMYD3 may be directly involved in synaptic dysfunction and has been shown to be upregulated in the prefrontal cortex of Alzheimer’s disease patients. Discussion/Significance of Impact: Our findings suggest that variants related to visual memory and spatial organization are involved in neurodevelopmental and degenerative pathways. This GWAS adds to the growing body of GWAS literature on the genetic basis of cognitive function. Additional analyses are underway to replicate these findings and extend functional annotation.

Objectives/Goals: To assess the impact of UCLA’s Clinical and Translational Science Institute Research Associates Program (CTSI-RAP), a student-led undergraduate clinical research initiative, on current members’ career interests and development. Methods/Study Population: To evaluate CTSI-RAP’s impact, we surveyed students using the REDCap platform between May and June 2023. The survey captured data on demographics, academic background, motivations for joining, and engagement in clinical research activities. Students also provided self-assessments of how the program influenced their career interests. Both descriptive and qualitative analyses were then used to assess key factors influencing students’ experiences, including the program’s impact on career decisions in healthcare and clinical research. Results/Anticipated Results: Out of 43 students surveyed, 40 responded (93%). Before entering, 84.2% of students had less than one year of research experience, and most students (73.6%) did not have family members in healthcare or research professions. Top reasons for joining were gaining clinical research exposure, healthcare setting experience, and pursuing healthcare careers. Overall, 97% of students stated CTSI-RAP “definitely” or “most probably” confirmed their interest in medicine and 76% of students reported CTSI-RAP has “definitely” or “most probably” solidified their interest in clinical research. 100% of students who have applied for a job, professional school, scholarship, or internship included CTSI-RAP as a meaningful experience, reflecting the program’s mission to provide motivations for a career in medicine and science. Discussion/Significance of Impact: Since its establishment in 2013, CTSI-RAP has expanded from 15 students to more than 50 annually, providing hands-on clinical research and professional development opportunities. The program’s peer-mentorship and student-led approach have proven effective in preparing students for diverse healthcare and research pathways.

Objectives/Goals: Our objective is to examine patient and community perspectives on hospital actions that signify accountability to healthcare equity; part of our overall goal is to identify equity measure concepts representative of community perspectives and priorities for future hospital accountability programs. Methods/Study Population: We conducted a qualitative thematic analysis of secondary data – 32 focus group transcripts from our hospital’s Community Health Needs Assessment (CHNA). A tri-annual CHNA is required of nonprofit hospitals to maintain tax exemption. Diverse participants were recruited from our hospital’s large catchment area. Coding focused on responses to 6 pertinent questions. We adapted the National Committee for Quality Assurance, “Health Equity Measurement Framework for Medicaid Accountability” which consists of 5 domains (access, clinical, experience, structure, and social) to guide the development of our a priori coding tree and subsequent analysis. Two coders double-coded 25% of transcripts. The multidisciplinary research team, including community partners, met iteratively to extract and refine themes. Results/Anticipated Results: We organized our analysis by our conceptual framework’s 5 measurement domains. The “access” and “experience” domains were the most salient for participants. We defined “access” by four sub-domains: financial access, physical access, communication access, and navigability; and “experience” by two subdomains: inclusivity and accomodation. Beyond discussing concepts within these measurement domains, participants debated the “scope” of the hospital’s role with regard to healthcare equity. While some did not think “it was the hospitals” responsibility to give people access to good jobs or fair pay, education…, “other participants felt that healthcare involves not just addressing peoples’ physical health but. their housing… because how can someone take care of their health when they are homeless?” Discussion/Significance of Impact: When asked about hospital accountability to healthcare equity, “access” and “experiences” of care are the most salient measurement domains for patients and communities. The “scope” of the hospital’s role is debated. Policy and health system leaders can apply these perspectives to equity measurement initiatives.