Objectives/Goals: To evaluate the impact and perceived value of a structured coaching and leadership program for trainees in KL2 and T32 programs. Methods/Study Population: This qualitative evaluation included individualized coaching and group workshops incorporating leadership development and the DISC behavioral communication model (Dominance, Influence, Steadiness, and Conscientiousness). Semi-structured interviews were conducted with twelve KL2 and T32 trainees between July and August 2025. Transcripts were analyzed using descriptive content analysis and inductive coding by two analysts in MAXQDA Results/Anticipated Results: Five key themes emerged: 1) both T and K trainees consistently described coaching as a broadly positive and beneficial experience; 2) coaching helped trainees build concrete organizational strategies, particularly around time management and logistical processes; 3) the curriculum helped build trainees’ confidence and professional identity, especially around communication with mentors, bosses, or their team; 4) coaching was perceived as complementary and well integrated within KL2 and T32 training, particularly by addressing “soft skills” missing elsewhere; and 5) participants recommended stronger orientation, more opportunities for practical skill-building during sessions, and offering greater diversity and choice in coaches. Discussion/Significance of Impact: Individualized coaching complements training for early career translational researchers. Trainees gained practical tools for team management and strategic planning, while benefiting from a confidential space for professional growth. Findings suggest coaching is valuable to training programs for developing translational research leaders.

Objectives/Goals: Our goal is to characterize how peripheral immune cells from people with HIV (HIV+) and control (HIV-) donors respond to stimulation with lipopolysaccharide from Porphyromonas gingivalis (Pg-LPS) and lipoteichoic acid from Staphylococcus aureus (Sa-LTA) and differentiate how these affect signaling in brain organoids. Methods/Study Population: To characterize peripheral blood mononuclear cells (PBMCs) response to microbial products, HIV+ and HIV– PBMCs were exposed to Pg-LPS or Sa-LTA for 24 or 48 hours. iNOS expression was assessed by western blot. IL-6 was quantified by ELISA, while TNF-α and IL-10 were measured via Ella multiplex. To differentiate how bacterial products directly affect neurons, human brain organoids (hBOs) were stimulated with Pg-LPS or Sa-LTA for 24 hours. To differentiate how bacterial products indirectly affect neurons, hBOs were co-cultured with PBMCs previously exposed to microbial products (primed). TNF-α, IL-6, and IL-10 levels were quantified by ELISA and multiplex. Neural function and reactivity were analyzed by measuring PSD95, synaptophysin, vGLUT1, pERK/tERK, and GFAP expression with western blot. Results/Anticipated Results: Pg-LPS increased TNF-α in HIV– PBMCs only at 48 h (p=0.033); in HIV+ PBMCs, TNF-α increased at 24 h (p=0.026) but declined by 48 h (p=0.011). HIV+ PBMCs secreted IL-6 at 24 h, which decreased by 48 h (p=0.025). IL-10 secretion remained stable in HIV– PBMCs but was elevated at 24 h versus 48 h in HIV+ PBMCs (p=0.006). No changes in iNOS expression were detected. Sa-LTA did not induce notable effects. In hBOs, direct stimulation with Pg-LPS or Sa-LTA did not alter TNF-α and IL-10 levels, nor neuronal markers. IL-6 was undetectable in Pg-LPS-treated hBOs and decreased in Sa-LTA-treated hBOs. Interestingly, hBOs co-cultured with primed PBMCs had higher astrocyte reactivity (p=0.034) than hBOs directly exposed to Pg-LPS 24h, while hBOs co-cultured with untreated PBMCs showed higher levels of neuronal markers. Discussion/Significance of Impact: HIV+ PBMCs exhibit a pro-inflammatory response to Pg-LPS at 24h, counterbalanced by an anti-inflammatory modulation. Oral pathogen products may be driving distinct immune activation dynamics in PWH and in the brain, potentially contributing to neuroinflammatory mechanisms that trigger neuronal dysfunction and cognitive impairment.

Objectives/Goals: Hepatocellular carcinoma (HCC) is a therapeutic challenge due to poor tumor immunogenicity, low endogenous T cell response, and a complex tumor microenvironment (TME). We propose an immunotherapeutic strategy leveraging widespread antiviral immunity – particularly memory T cells against SARS-CoV-2 spike (SPIKE) – to redirect T cells into tumors. Methods/Study Population: By engineering oncolytic viruses (OV) to express SPIKE, the approach aims to recruit virus-specific T cells and re-activate them through viral boosting, enhancing tumor clearance. This has been successfully shown in a B-16 melanoma model, another solid tumor system. We will also develop a dual-specific CAR T cell platform against SPIKE and GPC3, the most common HCC tumor-associated antigen (TAA), enabling antitumor targeting which can also benefit from OV readministration. The experimental plan includes purification and titration of a single-cycle adenovirus expressing SPIKE (SC-Ad-SPIKE), infection of murine and human HCC cell lines to validate SPIKE expression and replication, and in vivo treatment of subcutaneous or orthotopic murine tumors in pre-immunized or naïve mice using OV. Results/Anticipated Results: This strategy offers a translatable platform to re-focus existing antiviral memory toward otherwise weakly immunogenic tumors like HCC, potentially enhancing clinical efficacy through oncolytic virotherapy and CAR T cell engineering. We should see better average tumor clearance and survival in the groups treated with the OV and CAR T against SPIKE than controls with only GPC3 given the lack of reliance on tumor-GPC3 expression. Discussion/Significance of Impact: Our approach could be crucial for patients given how varied current responses are to available therapies. The combination of a generalized OV therapy and a more targeted CAR T provides a promising new solution to the current unmet need of many HCC patients globally.

Objectives/Goals: To (1) determine concordance (matched clinical and pathological AD diagnoses) and discordance (mismatched) between clinical and neuropathological findings in AD and (2) determine whether educational attainment differentiates individuals with concordant versus discordant AD profiles. Methods/Study Population: Secondary analyses will use data from the National Alzheimer’s Coordinating Center (NACC), which include baseline and follow-up cognitive assessments, educational history, and postmortem neuropathological evaluations. Participants will be classified into four clinico-pathological groups: two concordant groups – (1) true AD (both clinically and pathologically confirmed AD) and (2) true healthy (no clinical or pathological evidence of AD); and two discordant groups – (3) resilient (pathologically confirmed AD without clinical symptoms) and (4) symptomatic without pathology (clinical AD with absent or minimal pathological confirmation). Multinomial logistic regression will be used to examine associations between educational attainment and group classification. Results/Anticipated Results: We hypothesize that higher educational attainment will be associated with an increased likelihood of clinico-pathological discordance. Specifically, individuals with higher education are expected to be overrepresented in the resilient group (high pathology, no clinical AD) compared to the true AD group (both clinical and pathological AD). Conversely, lower education levels may be more common in the true AD and symptomatic without pathology groups, reflecting reduced cognitive reserve or potential diagnostic misclassification. We further anticipate that within the discordant groups, higher education will correlate with better baseline and follow-up cognitive performance despite comparable levels of neuropathological burden. Discussion/Significance of Impact: Findings would suggest that education enhances cognitive reserve, mitigating the clinical effects of AD pathology and helping explain why some individuals remain cognitively intact despite significant disease. Recognizing this role highlights the need to integrate neuropathological and reserve-related factors in AD research and diagnosis.

Objectives/Goals: Clozapine is the most effective treatment for people with treatment-resistant schizophrenia but is underutilized. Black patients are less likely to receive clozapine than White patients. Given limited data on the efficacy of clozapine in this population, we assessed clinical response in a large clinical trial of clozapine in Black patients. Methods/Study Population: This secondary analysis of a 6-month prospective, open-label clinical trial of clozapine in Black patients with schizophrenia spectrum disorders included 221 participants, 103 from Maryland, and 118 from Nigeria. The primary outcome was reduction in symptom severity as measured by total Brief Psychiatric Rating Scale (BPRS) over time on clozapine and modeled by a linear mixed effects model adjusted for age, sex, location, marital status, diagnosis, smoking status, Duffy null (ACKR-1 CC) genotype, clozapine dose, and clozapine level. We also assessed (i) changes in BPRS subscales over time, (ii) predictors of 20% improvement in BPRS, (iii) time to 20% BPRS improvement, and (v) the burden of clozapine side effects and the association of side effects and clinical improvement. Results/Anticipated Results: The average age was 40.2 years; 63% were male, 78% had schizophrenia, and 20% had schizoaffective disorder. BPRS total scores improved by 10.94 points (p < 0.001), adjusting for age, sex, and clozapine dose. Participants showed significant improvement in positive, resistance, affective, and activation, but not negative subscale scores. Nigerian participants were 21.5 times more likely to demonstrate 20% BPRS improvement compared to Maryland participants (p <0.001) and showed improvement more quickly, with most of the improvement in the first 4 weeks in Nigerian participants and 12 weeks for those in Maryland. 44.1% of participants had weight gain of at least 5% from baseline to endpoint. Improvement in tardive dyskinesia (p = 0.008) and weight gain (p < 0.001) were associated with BPRS improvement. Discussion/Significance of Impact: This study demonstrates clozapine’s efficacy in Black patients with schizophrenia spectrum disorders. Greater improvement in Nigerian participants may reflect differences in treatment resistance, social support, or expectation bias across groups. Further research is needed to improve utilization of clozapine in Black patients.

Objectives/Goals: RF-DASH trains first responders with agricultural health and safety knowledge to prevent farm accidents and improve emergency preparedness in rural communities. We used a collaborative instructional design approach to develop an online version of this in-person, in-demand, highly effective training to increase its reach and enhance its impact. Methods/Study Population: The RF-DASH project team engaged e-learning specialists to develop learning objectives and outcomes, establish course structure, curate elements of the RF-DASH in-person curriculum into e-learning materials, and design interactive course content. We then conducted user testing including an initial content review by expert RF-DASH trainers, two rounds of user testing with agricultural safety professionals and first responders. Feedback from user testing was integrated into the final version of the online training and helped inform the evaluation plan that was developed prior to the online training launch in October 2025. Results/Anticipated Results: The RF-DASH Online Course uses interactive learning techniques, including 360° virtual tours of actual farms, animated videos, and knowledge checks. The virtual tours were deemed critical by reviewers for translating the in-person training to an online format while maintaining the real-life applicability that makes the intervention effective and appealing. The co-design approach required flexibility and humility among all actors, which resulted in a stronger product and deep learning for all. The opportunity to “learn what you don’t know you don’t know” was crucial and is not always supported by funders, timelines, or team capacity. For translational science to achieve the breadth and depth of its potential for impact, these challenges should be met with support rather than reluctance whenever possible. Discussion/Significance of Impact: The collaborative co-design process used to create the online version of the training was critical to the quality and relevance of the final product, and the learning that resulted on behalf of the RF-DASH team speaks to the utility of conducting a needs assessment at the outset of adapting any intervention for new audiences and aims.

Objectives/Goals: This study addresses mobility disability in the aging Deep South population by: 1) identifying protective movement patterns against obesity-related decline and 2) providing clinicians evidence-based, comprehensive exercise recommendations to combat the region’s disproportionate burden of mobility disability. Methods/Study Population: We will recruit 60 participants: young adults (n=20, 18–35 years), older sedentary adults (n=20, 65+ years), and older lifelong runners (n=20, 65+ years, 10+ years consistent activity). Participants will undergo 3D gait analysis using motion capture and force plates across multiple walking speeds and dual-task conditions. We will measure novel speed-invariant collision dynamics (H1/K1 joint powers) alongside traditional propulsive measures (A2/H3). This approach eliminates speed confounds that have plagued aging research, allowing true assessment of whether lifelong exercise preserves youthful movement patterns and cognitive-motor integration. Novel, quantitative measures like this are critical for helping populations facing high obesity rates and manual labor demands. Results/Anticipated Results: We hypothesize older runners will demonstrate 1) smaller dual-task costs during cognitive challenge, suggesting maintained cognitive-motor integration and 2) more efficient ankle–hip power distribution, reflecting preservation of energy-efficient movement strategies. These findings will establish which biomechanical qualities are most protective against age-related decline and may reveal relationships between superior movement patterns and overall health status. Given the Deep South’s unique convergence of obesity, chronic disease, and limited healthcare access, identifying sustainable interventions like running that preserve mobility is critical for reducing regional health disparities. Discussion/Significance of Impact: Speed-invariant biomarkers enable early detection of movement dysfunction before disability manifests and understanding how biomechanical health relates to common comorbidities allows more comprehensive, targeted interventions addressing the region’s obesity and chronic disease burden.

Objectives/Goals: The purpose of this project is to generate a model identifying environmental and behavioral predictors on STI diagnosis. Using the fitted model, we examined how the effects of these predictor variables vary as a function of age. Understanding age-dependent correlates of STIs can allow us to be more precise when identifying intervention strategies. Methods/Study Population: We examined surveys and EHRs using the All of Us Researcher Workbench. We created two cohorts (STI diagnosis vs. No-STI diagnosis) matched on self-reported demographic variables. We also extracted survey-derived participant environmental indicators such as alcohol use and annual income. Most participants (60%) were classified as White, majority (94%) had health insurance, 53% were employed for wages or self-employed, and 82% went to or graduated from college (N=5873). We conducted a random forest analysis to predict STI diagnosis given the identified variables. To explain machine learning predictions for complex models, like random forests, we used SHAP values. Using this technique, we further explored the relationship between the variables identified as significant to the model and age at STI diagnosis. Results/Anticipated Results: Results of the random forest showed that the internal estimate of prediction was 51.64% accurate, indicating a low accuracy. The mean decreased Gini values for the top 5 contributors to the model were as follows: annual income (276.74943), limited social contact (196.94722), education (166.86742), safety dynamics in the neighborhood (142.62170), and community safety concerns (141.37972). The results of the SHAP analysis suggested that the relationship between low-earning participants and STI diagnosis has a negative relationship with age at diagnosis; in other words, the relationship between income and STI diagnosis decreases with age. Discussion/Significance of Impact: Our environment plays an important role in our health. This project demonstrates that participant-reported environmental variables were associated with STI outcomes in the model. Furthermore, some of these effects are found to be age-dependent. Future research could explore how modifying behavioral or contextual factors may influence STI risk.

Objectives/Goals: To describe how the Ivy Tech Community College and Indiana CTSI partnership creates early entry points into translational science, expands access for community college students, and strengthens the biomedical research workforce. Methods/Study Population: The Indiana CTSI partnered with Ivy Tech, a community college system that has campuses throughout the state, to launch a Research Scholars Program. This is a 10-week summer immersion experience introducing community college students to biomedical and health sciences. Students are matched with research teams at Indiana University, Purdue University, or Notre Dame (depending on where the student lives), engaging in 35 hours per week in research activities and professional development. Students receive a stipend and may be provided a laptop if needed. Recruitment is supported through collaboration with Ivy Tech faculty and staff, including classroom outreach, referrals, and information sessions. Results/Anticipated Results: Across two cohorts, the program achieved 17 completions by community college students from multiple Ivy Tech campuses, including one #_msocom_1who returned for a second summer. Students gained hands-on research skills, professional development, and communication training, presenting their findings at program-end symposia and a virtual presentation connecting participants across campuses. Outcomes include poster presentations at regional meetings, transfers to four-year institutions, and pursuit of health and biomedical careers. Several students have continued working with mentors, and one was hired part-time by their lab, underscoring the program’s statewide impact through partnerships with IU, Purdue, and Notre Dame. -------------------------------------------------------------------------------- #_msoanchor_1 Discussion/Significance of Impact: This program highlights how the Indiana CTSI–Ivy Tech partnership expands access to translational science for learners within community college settings. Statewide collaboration, sustained mentoring, and student outcomes together provide a scalable model for workforce development.

Objectives/Goals: The University of Illinois Chicago’s CTSA is developing dynamic dashboards to track K awardee outcomes. Integrating data on grants, publications, and milestones, the dashboard illustrates scholars’ research journeys while highlighting the role of the K program in advancing their careers. Methods/Study Population: Since 2007, CCTS has supported over 60 KL2 scholars and affiliates. To track scholar outcomes, the evaluation program has developed Power BI dashboards that visualize scholars’ career trajectories. These dashboards draw on several sources, including publicly available data, institutional records, and FlightTracker. They highlight key career outcomes such as grant awards and peer-reviewed publications since program entry, providing an overview of scholars’ careers while illustrating how they advanced after the program. The dashboards shown continue to evolve. Our current efforts are focused on incorporating impacts from the TSBM and streamlining data collection. Results/Anticipated Results: The dashboards provide a comprehensive and interactive view of KL2 scholars’ career trajectories, illustrating how the K program contributes to research productivity and career advancement. They reveal trends in grant funding, publications, and other key career milestones over time. The dashboards enable us to more easily identify patterns across cohorts, explore individual scholar achievements, and assess broader program impact. Continued refinement of processes in collecting and displaying data, including AI-supported data collection and incorporation of TSBM outcomes, is expected to ensure a more complete picture of the translational impact of K award support. Discussion/Significance of Impact: The dashboards enhance tracking of K awardees by providing a clear, data-driven view of scholar and affiliate outcomes. They can inform program improvements and highlight broad impacts on career development and translational science. This approach may be adopted by other CTSA hubs.

Objectives/Goals: The UIC Center for Clinical and Translational Science offers a robust training infrastructure for research staff including a certificate that can be completed in ~18 months. New staff, however, needed a concentrated experience with hands-on training and institution-specific content. We developed an in-person bootcamp in response. Methods/Study Population: Research Essentials Playbook was a 1.5 day bootcamp-style workshop targeting research staff with up to 2 years of experience at UIC. Topics were based on stakeholder input and the ACRP Entry Level CRC Competency Development and Assessment Roadmap divided into Day 1 in the morning: Didactic sessions (e.g., Project management, safety and ethics, and promoting respect for participants); Day 1 in the afternoon: choice of two hands-on sessions (e.g., clinical research lab, informed consent – practical skills, recruiting participants made easy); Day 2 in the morning: UIC-specific policies. Before and after the workshop, participants indicated their agreement with the statements “I am confident in my knowledge, skills and abilities as a research staff at UIC.” and “I feel like a part of UIC research community.” Results/Anticipated Results: 38 people registered and 34 attended at least one day. Participants were primarily from the College of Medicine but represented all health colleges. 20 participants had 0-2 years of experience at UIC; 6 people had 3–5 years of experience at UIC, 6 people had 5–10 years of experience at UIC, and 6 people had 10+ years of experience at UIC. While most participants had job titles that are typically associated with research staff, 5 participants held faculty titles. After the workshop, in response to the questions about confidence and belonging, respectively, 94% and 88% of participants agreed or strongly agreed, 89% of participants agreed or strongly agreed that the hands-on sessions were helpful, and 100% agreed the content was relevant to their job responsibilities and the workshops fulfilled their expectations. Discussion/Significance of Impact: This in-person bootcamp succeeded at its training and community-building goals and helped us identify candidates for a new Research Coordinator Mentorship program. Research Essentials Playbook will be offered at least once a year for newly hired staff and adapted for inclusion in new faculty orientation and onboarding activities.

Objectives/Goals: Medical therapies to halt progression of aortic stenosis (AS) are now being studied; however, the sensitivity of transthoracic echocardiography (TTE) measures to detect disease progression remain unclear. We will evaluate alternative TTE-derived measures of AS severity as potential markers of disease progression to improve trial efficiency. Methods/Study Population: We will conduct a retrospective cohort study of adults with mild or moderate aortic stenosis who had TTE imaging at Tufts Medical Center from 2012 to 2024. Two cohorts will be examined: 1) a reproducibility cohort of patients with studies less than 2 months apart to assess measurement consistency; and 2) a progression cohort with studies more than 6 months apart to evaluate disease progression over time. Echocardiographic parameters including peak velocity, mean pressure gradient, and aortic valve area will be used. We will use recurrent quantitative measurements to evaluate reproducibility, variability, and signal-to-noise characteristics and to model implications for efficient clinical trial design. Analysis will use RStudio. Results/Anticipated Results: Overall there are 2,668 patients with progressive AS. Median age at first TTE is 76 (68–83) years. 1,120 (42%) are female. The reproducibility cohort includes 991 patients (1,728 paired TTEs, median 10 days (0–16) apart), and the progression cohort includes 323 patients (323 paired TTEs, median 504 days (394–750) apart). Additional demographic and comorbidity data will be obtained. Recurrent measurements will quantify reproducibility, variability, and signal-to-noise characteristics. Anticipated results include 1) identification of the most reliable measures for tracking progression, 2) characterization of measurement variability, and 3) modeling of implications for efficient clinical trial design and evidence-based patient management. Discussion/Significance of Impact: Interest in therapies to halt aortic stenosis progression is growing. Establishing consensus on the most reproducible and practical imaging endpoints is essential. By quantifying real-world variability, we aim to optimize trial design so that effective treatments can be studied and improve outcomes.

Objectives/Goals: Sleep is a useful intervention target to improve mental and physical health. Yet, the contextual factors that impact sleep in real-life settings are poorly understood. We assessed how psychological and socioenvironmental factors influence self-reported sleep in a large, US sample (Study 1) and sleep physiology in a prospective cohort (Study 2). Methods/Study Population: Study 1: 13,483 participants (63% males, mean age 46, 24% non-White) completed on-demand blood pressure (BP), self-reported stress, physical health, and sleep duration assessments for 3 weeks. Study 2: 42 Black adults (23% males, mean age 42) completed up to six ambulatory sleep recordings at home for 2 weeks. Stage durations for rapid eye movement (REM) and non-REM Stages 1, 2, and 3 were determined. Daily self-reports of stress and physical health were also gathered. For both studies, residence zip codes were linked to a national database to quantify neighborhood factors (i.e., built environment, poverty, social cohesion, etc.). Multiple linear regressions and mixed-effect models assessed whether neighborhood factors, demographics, health indices, and stress could predict sleep durations. Results/Anticipated Results: In Study 1, neighborhood disadvantage, perceived stress, and systolic BP were associated with shorter sleep durations. Better self-reported health predicted longer sleep durations. Black, Native, Latino/as, and Pacific Islander participants had shorter sleep durations, whereas White participants had longer sleep durations. An interaction between perceived stress intensity and health indicated that better health (+1SD) protected sleep from increasing stress. Preliminary analyses in 26 participants from Study 2 revealed that neighborhood disadvantage and self-reported poor health are associated with shorter Stage 2 sleep durations. However, daily stress did not predict stage durations, and no interactions emerged. Discussion/Significance of Impact: Neighborhood disadvantage led to short sleep in two studies, with novel findings indicating that Stage 2 durations may be most sensitive to structural disadvantage. Interventions that invest in material resources to reduce neighborhood inequities may be an innovative approach to protect sleep and mitigate related illness.

Objectives/Goals: People experiencing homelessness (PEH) face disproportionate cervical cancer burden and screening barriers. Our goal was to design a tailored intervention involving community health worker (CHW)-led education and delivery of context-appropriate screening options in two homeless shelters in Indiana. Methods/Study Population: Guided by a community advisory board and following a human-centered design (HCD) framework, interviews with 30 PEH were conducted in the inspiration phase to explore experiences, knowledge, and attitudes toward cervical cancer screening, including human papillomavirus (HPV) self-sampling, a novel approach where patients collect their own vaginal swab. Rapid qualitative analysis informed an HCD session with 12 PEH in the ideation phase to further explore screening motivators and key messages to encourage uptake of HPV self-sampling. Data were synthesized into an educational flipbook and iteratively refined with participant feedback. Results/Anticipated Results: Findings from interviews and the HCD session highlighted a strong desire to be screened and the need for clear information, access to a trusted CHW, and choice in screening options. The final intervention consisted of an individual cervical cancer education session with a CHW utilizing the educational flipbook, followed by optional screening through HPV self-sampling at the shelter and/or navigation to a clinic. To date, a total of 200 participants have enrolled in the education session. Preliminary results show significant knowledge gains and retention and positive shifts in attitudes toward screening. After an education flipbook redesign, HPV self-sampling uptake significantly increased. Discussion/Significance of Impact: Applying a HCD approach enabled meaningful engagement to iteratively develop and refine an intervention that addressed community needs, increased HPV self-sampling uptake, and expanded cervical cancer screening access for people experiencing homelessness in Indiana.

Objectives/Goals: Outline researchers’ perspectives on an “Aim 0” approach of engaging with people connected to the research topic to leverage their perspective when developing research questions. Worked with researchers at varying levels of career stage to understand their thoughts and concerns of this work. Methods/Study Population: Used human-centered design (HCD) methods to conduct nine semi-structured interviews with researchers at varying levels of career stage (early to senior level researchers). Interviews lasted 30–60 minutes while participants answered questions using collage cards, journey maps, and card sorting HCD methods. Questions related to communication dynamics between investigators and their population, how communication could be more population-centered, a research project journey including decisions on who and when to engage populations, and barriers and facilitators of engaging populations earlier in the research process to incorporate their voice in the development of research questions. Results/Anticipated Results: An HCD analysis approach will be conducted to outline findings. Anticipated findings include outlined communication dynamics between researchers and their affected population. The approach of engaging with the population early in the research process to help determine research questions was thought of favorably; however, feasibility concerns, mostly around finding funding, were brought up often in the interviews. More anticipated findings include what career levels would be most beneficial for an “Aim 0” approach. Discussion/Significance of Impact: Engaging with the affected population earlier in the process will help streamline efforts of investigators to solve issues their populations are dealing with. This adds another step to the research process, and it helps to understand researcher’s perspectives of this added effort.

Objectives/Goals: UW-Madison ICTR Collaborative Network (ICON) is a team of research navigators who provide wrap-around services for investigators (e.g. study and recruitment planning). In 2025, an ICON objectives was to consult with newly awarded investigators to expedite their study activities. Methods/Study Population: The ICON team assisted postdoctoral (n=3) and faculty (n=8) investigators awarded 12- or 18-month Institute for Clinical and Translational Research (ICTR) pilot awards beginning in May or July 2025. ICON addressed concerns related to regulatory documentation creation, recruitment and retention, study personnel training, document editing, etc. Ten of 11 investigators consulted with ICON shortly after award onset, with plans for check-ins at the 6- and 12-month mark of their grant. Following the initial consultation, ICON devised an individualized assistance plan for each investigator. Investigators completed multiple surveys regarding their opinion on the usefulness of the service. Results/Anticipated Results: The results of the first survey indicated that three investigators found the ICON service to be highly valuable (highest ranking), overall, the mean value was 4.1 on a 5-point Likert scale. The written feedback from the investigators indicated that the service would have been more useful earlier in the pilot award process, such as prior to submission. The ICON team continues to execute the individualized assistance plan for each investigator and will provide tailored assistance at the 6- and 12-month check-ins to meet the investigator’s needs. We will survey the investigators quarterly for feedback on the usefulness of the service. Discussion/Significance of Impact: Survey feedback indicates the value of the ICON service but suggests that for some the consultation was delayed. The ICON team will continue to check-in with this cohort to determine if further assistance is needed. In the future, ICON will meet with awardees earlier in the application process.

Objectives/Goals: To determine the optimal adenine nephropathy induction protocol in C57BL6/J and Sv129 mice. Optimization is defined by the combination of the highest mean serum creatinine and best survival rate at20 weeks, accounting for the influence of sex. Methods/Study Population: We will use 8-week-old male and female wild-type C57BL6/J (Ahr^b) and Sv129 (Ahr^d) mice (n=120). Mice will be randomized into groups (n =10pergroupwith equal numbers of males and females) comparing two adenine diet protocols (0.25% for 2 weeks vs. 0.25% every other week for 6 weeks) against normal chow controls, which will allow us to investigate the impact of genetic background on disease severity. Renal function will be monitored via weekly weights and blood/urine collection at 16 and 20 weeks. Cardiac function will be assessed by echocardiography at 16 and 20 weeks to characterize chronic kidney disease-associated heart disease. Tissue (kidney, heart, brain) will be collected at human endpoint or20 weeks for downstream analysis. Statistical comparisons will primarily focus on diet effect within same sex and strain groups. Results/Anticipated Results: We anticipate identifying a superior adenine feeding protocol for each sex and strain combination based on the primary endpoints (creatinine and survival). Sex differences are expected, with males likely developing more severe nephropathy across both strains. The optimized protocol for each group will provide a standardized model for future research into uremic toxin. Discussion/Significance of Impact: Establishing a strain-specific adenine nephropathy protocol is vital for advancing CKD research. This work provides a foundation for accurately investigating the role of uremic toxins in both renal failure and CKD-associated cardiovascular disease, which is a major cause of death in CKD patients.

Objectives/Goals: To identify population-specific and ancestry-informed genetic loci for blood pressure traits, characterize X chromosome associations, and evaluate evidence for evolutionary pressures influencing blood pressure risk across ancestries, which may be used downstream clinically for personalized medicine and drug target identification. Methods/Study Population: We conducted multi-ancestry and ancestry-stratified genome-wide association studies (GWAS) of systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse pressure (PP) across >2.5M individuals (40% non-European) from 16 cohorts and biobanks. Analyses were adjusted for age, age², sex, body mass index, and the first 10 principal components. Fixed-effects meta-analyses were followed by SuSiEx cross-population fine-mapping to identify ancestry-specific loci. We evaluated genetic differentiation using the fixation index (FST) and allele frequency directionality using the sign test to infer potential evolutionary pressures. Results/Anticipated Results: Multi-ancestry meta-analyses identified 2,406 significant independent loci for SBP (1,594 novel), 2,358 DBP (1,509 novel), and 2,312 PP (1,432 novel). Chromosome X analyses revealed 8 SBP, 80 DBP, and 8 PP loci. SuSiEx fine-mapping identified ancestry-specific signals, including a pulse pressure SNP near CTSL (Asian-specific) and a DBP SNP in CACNA1D (African-specific). Sign tests indicated enrichment of DBP risk alleles when comparing African and Asian populations and when comparing Admixed American and Asian populations (p < 0.01), supported by elevated FST values for variants with larger effect sizes. These findings suggest that ancestry-specific selection may influence blood pressure regulation. Discussion/Significance of Impact: This is the largest and most ancestrally diverse blood pressure genetics study to date and one of few to include X chromosome analyses, which enabled discovery of thousands of novel and population-specific loci and revealed evolutionary and biological insights that may advance precision medicine for hypertension.

Objectives/Goals: To demonstrate how small grant funding (up to $5,000) for the dissemination of community-academic partnered research findings can accelerate translation by delivering relevant, actionable information to communities, supporting ongoing partnerships, and catalyzing future research and funding opportunities. Methods/Study Population: Promoting Academic and Community Engagement (PACE) dissemination grants were awarded through a competitive funding mechanism. Over four funding cycles, the program received 25 submissions and funded 15 projects, awarding a total of $75,000 to projects across Michigan. The grants supported established community-academic partnerships to share their community-engaged research (CEnR) findings with communities of interest. Dissemination was defined as returning research results to nonacademic audiences to accelerate translation. Traditional scholarly dissemination (e.g., publications or conferences) was not eligible. All awardees submitted final reports detailing their dissemination strategies, impacts, and outcomes. Results/Anticipated Results: The PACE grants were designed to accelerate the translation of research into communities through focused, community-facing dissemination. Across four funding cycles, 15 funded projects reported employing broad dissemination strategies, including community forums, multimedia campaigns, artistic expression, and local events. Final reports described increased community awareness, enhanced trust and engagement, and momentum for follow-up collaborations and funding proposals. The poster will present key findings and selected examples to illustrate how modest, targeted investments can lead to measurable impacts in research translation at the community level. Discussion/Significance of Impact: This poster will highlight how CTSAs can implement scalable, low-cost funding mechanisms to support community dissemination of research. Programs like PACE foster academic-community engagement, accelerate translation of findings, and offer a replicable model for supporting community-centered translational science.