Objectives/Goals: Arsenic (As) in drinking water and rice is a major public health issue. In areas where rice is a staple food, it is unclear whether As in water, raw rice, or cooked rice best represents total exposure. Here, we disentangle the relative contributions of dietary rice and drinking water to total As exposure to help prioritize As measurement and intervention. Methods/Study Population: We used samples from the Health Effects of Arsenic Longitudinal Study (HEALS) cohort based in Araihazar, Bangladesh, an area where there is substantial As contamination in well water and where the diet is rice-rich. We measured total As in matched water, raw rice, cooked rice, and urine samples collected in 2016 from 396 households in HEALS. We also measured As species (organic vs. inorganic As) from a 194-household subsample. We compared the levels of total, organic, and inorganic As in rice before and after cooking across levels of As in cooking water. Using urinary As as a biomarker of internal As dose, we calculated which matrix (raw rice, cooked rice, or cooking water) or combination of matrices explained the most variance in true As exposure using linear models adjusted for age and sex. Results/Anticipated Results: Inorganic As (iAs) is the most toxic As form. We found a nonlinear relationship between water and rice iAs wherein rice iAs decreased if cooked with low-As water but increased with high-As water. Accordingly, cooked rice was overall a better indicator of urinary iAs than raw rice, since it captured variation in both rice and water. However, when As levels in rice and water were below safety limits, neither matrix explained meaningful variance in urinary As. This suggests that in populations where rice and water As are low (e.g., the USA), other exposure sources predominate. Organic As in rice moderately decreased after cooking, but starting abundance of organic As in rice varied greatly and correlated with organic As in urine. Therefore, rice may be a previously under-appreciated exposure source of organic As. Discussion/Significance of Impact: Cooked rice As was the most informative single exposure measurement, but neither rice nor water As predict internal As dose when at low levels. These results highlight that As exposure measurements should be tailored to the study population to maximize research resources and that multiple As exposure routes should be considered simultaneously.

Objectives/Goals: This project, at the intersection of psychological and neuroimaging science, aims to develop and validate an open, transparent, and reproducible workflow for measuring functional brain activity using functional near-infrared spectroscopy (fNIRS), advancing methodological rigor and translational potential in human neuroscience. Methods/Study Population: A Python-based workflow using MNE was designed to improve reproducibility in fNIRS data acquisition. The workflow includes the following: (1) electromagnetic digitizer accuracy testing and distortion correction; (2) integration of head shape and source-detector location data; (3) visualization tools for verifying optode placement accuracy before data collection; and (4) implementation entirely in an open-source software to promote accessibility and transparency. Results/Anticipated Results: Difference in data quality, spatial accuracy, and reproducibility between standard fNIRS practice and this open workflow will be systematically evaluated. Discussion/Significance of Impact: This project advances translation in neuroimaging by embedding rigor and transparency into all stages of the workflow. By openly sharing software tools and validation methods, the workflow enables independent replication, fosters methodological transparency, and reduces reliance on proprietary systems.

Objectives/Goals: We aim to develop and optimize extracellular vesicle (EV)-mediated delivery of Cas9/single-guide RNA (sgRNA) ribonucleoprotein (RNP) complex to target ACSL4, a key driver of dysregulated fatty acid metabolism in androgen receptor (AR)-independent prostate cancer, and to evaluate its therapeutic potential in vitro and in vivo. Methods/Study Population: We examined ACSL4 gene editing using lentiviral delivery and EV-mediated delivery of Cas9/sgRNA constructs. In HEK-293T cells, we optimized EV treatment frequency and concentration. In PC3 cells, we analyzed gene editing efficiency in detached cell population in comparison to attached cell population. Editing was determined by next generation sequencing. To examine EV-mediated gene editing in vivo, we employed a xenograft mouse model produced by subcutaneous injection of PC3 cells. EVs were administered by intratumoral injection three times a week for three weeks, and tumor growth, histology, and gene editing were assessed. Future studies will include patient-derived xenograft models to evaluate translational relevance. Results/Anticipated Results: Lentiviral delivery achieved up to 36% ACSL4 gene editing. EV-mediated delivery showed dose-dependent gene editing in HEK-293T cells, which contained up to 13% editing. Gene editing was enriched in detached PC3 cells, reaching a maximum editing efficiency of 47%, potentially contributing to cell death. Attached PC3 cells showed 1-2% editing and reduced proliferation after EV treatment. In the ongoing xenograft mouse model experiments, EV treatment is expected to decrease tumor growth, reduce proliferation, and induce apoptosis, confirmed by histology and sequencing. Further optimization of EV dosing and delivery aims to further enhance editing efficiency and therapeutic impact. Discussion/Significance of Impact: EV-mediated delivery of Cas9/sgRNA RNP to target ACSL4, a key metabolic driver of aggressive disease, represents a novel therapeutic strategy for treatment-resistant prostate cancer. Continued work on this nonviral platform will enable targeted, tumor-specific editing while minimizing safety concerns associated with viral delivery.

Objectives/Goals: We aimed to evaluate the representativeness of the patient population that is accessible through PCORnet®, both at the network level and within individual studies that enroll patients using the network, and to develop concrete recommendations regarding the design and evaluation of future studies. Methods/Study Population: We evaluated potential study participants that could be recruited through PCORnet, defined as patients with a healthcare encounter and any diagnosis recorded at a participating network site in 2023, relative to US population data from the American Community Survey (ACS) with respect to demographic, geographic, and socioeconomic summary data. Individual studies, conducted using the network, rarely involve all PCORnet patients, but rather those who meet clinical eligibility criteria and pass through a series of operational filters, such as site selection. We evaluated all patients at sites that have participated in at least 10 studies, as well as individual studies published in the COVID-19 clinical domain, compared to corresponding, eligible patients across the entire network. Results/Anticipated Results: PCORnet included data from over 47 million people across the USA with everyday healthcare encounters in 2023. This population of potential study participants was generally representative of the US population, though less likely to be from rural communities (11.7% vs. 18.4%) and low socioeconomic status (SES) (18.9% vs 25%). Patients from sites that frequently participate in PCORnet studies (10+) were representative of PCORnet overall, with an opportunity to improve inclusion of Hispanic populations. Among individual studies in the COVID-19 clinical domain, retrospective studies were largely representative, but prospective studies demonstrated large gaps in representation. Discussion/Significance of Impact: PCORnet provides access to a representative population of patients receiving healthcare. Differences in SES and rurality may be explained by differences in healthcare access. Population-level data, available through PCORnet, can be used to improve study design and evaluation, particularly for prospective studies.

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: The aim of this study is to create a profile of Puerto Rican adults that either developed auditory or balance problems after contracting or being vaccinated against COVID-19 or whose symptoms got worse after the infection or vaccination against the coronavirus. Methods/Study Population: This research has two arms: a descriptive explorative survey designed arm and experimental profiling. Four cohorts of Puerto Rican adults between 21 and 64 years old were profiled; subjects that developed auditory or balance disorders after contracting COVID-19, subjects who’s auditory and balance conditions got worse after contracting COVID-19, subjects who developed auditory or balance disorders after being vaccinated against COVID-19 and subjects who’s auditory and balance conditions got worse after being vaccinated against COVID-19. Subjects were recruited, assessed, and interviewed at the University of Puerto Rico-Medical School Intramural Clinic after the research protocol was approved by the Office of Protection of Research Participants of the University of PR-Medical Sciences Campus. Results/Anticipated Results: Results reflected that fifty-seven percent of the subjects experienced hearing difficulty which worsen after contracting or being vaccinated against COVID-19. Seven percent of the subject’s that were vaccinated developed constant Tinnitus which was bilateral in the majority of the subjects (55%). Fourteen percent of the subjects that already had Tinnitus reported that the level of their Tinnitus increased after either contracting or being vaccinated against COVID-19. Discussion/Significance of Impact: This pilot research study adds to the evidence of the impact of COVID-19 infection and vaccination against the coronavirus on the inner ear of Hispanics of Puerto Rican ethnicity. Its significance lies in documenting the different auditory pathologies that can emerge or that can become worse by the contraction of the coronavirus.

Objectives/Goals: To present practical considerations especially important for early career investigators using large cloud-based data portals, with lessons learned from a descriptive project characterizing chronic pain among young Black adults. Our translational science goal is to improve investigators’ engagement with these types of data sources. Methods/Study Population: Lessons learned from our analytic experience conducting secondary data analyses using data from the NIH All of Us Research Program (AoU). The analytic activities are in support of Aim 1 of an NIH K01 Mentored Research Scientist award focusing on young Black adults with chronic pain. Engagement with data was a collaboration across junior and senior investigators with expertise in quantitative and qualitative methods. We assessed AoU data for usability, data completeness, accessibility, and program support. Variables of interest in the K01 project include physical and mental health, commodities, health care utilization, SDoH, and demographics. We present qualitative descriptions of our user experiences, paired with descriptive and summary statistics for the pain-related data. Results/Anticipated Results: “Controlled-tiered” data were easily accessible. Data completeness differed by variable type: variable categories (e.g., chronic pain) had fewer missing data than survey items used to calculate composite variables (e.g., GAD-7). The cohort comprised 146 Black adults aged 18–24 and 3,315 aged 25–44. We compared pain intensity, self-rated health, SDoH, and healthcare utilization by age. Limited EHR-recorded pain severity, and responses to disability and comorbidity survey items prevented comparisons by age. Program support for accessing the data met expectations. A quantitative PhD graduate student was needed to engage. Advanced coding skills required to use the cloud-based data portal challenges broad usability of the data and claims for inclusive use of this data resource. Discussion/Significance of Impact: AoU can be leveraged to examine key health indicators for large cohorts of underrepresented adults. However, the skill level and time required to fully engage with these data is beyond that of most early career investigators. We encourage CTSAs to coordinate capacity-building efforts to use these large population data and support a team science approach.

Objectives/Goals: Given previously demonstrated relationships between decline in proteinuria to thresholds below 0.3-1.5 g/g and kidney failure, we sought to assess if this relationship was maintained when proteinuria change was measured on a continuous scale and to compare the difference in association between changes measured at 12- and 24-months post-index. Methods/Study Population: PARASOL is a consortium of academic scientists, patient advocacy organizations, and industry partners who came together to identify candidate surrogate endpoints for clinical trials in focal segmental glomerulosclerosis (FSGS). Data were harmonized among international cohorts and registries of adults and children with clinically adjudicated FSGS without other causes. Index was identified as the first observed urine protein-creatinine ratio (UPCR)≥1.5 g/g with associated eGFR≥30 ml/min/1.73m2. Change in UPCR from index to 12 and 24 months was evaluated using the difference in log(UPCR) from baseline and follow-up and transformed to percent change. Time-updated landmark Cox regression models were fitted, and the interaction between UPCR change and the 24-month timepoint indicator was assessed. Results/Anticipated Results: 1366 participants with at least 12 months of follow-up post-index and UPCR measurements 6-12 and/or 18-24 post-index were included. Mean age was 27 years (SD=21); 46% were pediatric at index. Median (IQR) eGFR and UPCR at index were 83 (57, 110) ml/min/1.73m2 and 3.7 (2.3, 7.0) g/g, respectively. A 50% decrease in UPCR from index was associated with a 28% and 32% reduction in the probability of kidney failure at 12 and 24 months, respectively, with no difference detected based on timing of UPCR (HR [95% CI] = 0.72 [0.65-0.80] at 12m, 0.68 [0.63-0.74] at 24m, interaction p-value = 0.46). In subgroups based on age, UPCR, and eGFR at index, results were consistent (HR range 0.66-0.72 at 12m and 0.58-0.78 at 24m), with only the eGFR≥60 ml/min/a.73m2 subgroup showing patterns of larger effects at 24m (HR = 0.62 vs. 0.72, p=0.08). Discussion/Significance of Impact: Continuous measures of proteinuria demonstrated consistent associations with kidney failure at 12- and 24-months post-index and across patient subgroups. If validated, these relationships support potential variation in timing of endpoint evaluation in clinical trials where there is mechanistic justification for earlier assessment.

Objectives/Goals: Researchers have an ethical responsibility to disseminate their discoveries beyond the walls of academia, tailoring communications about their research to various audiences. Learning to articulate and convey the impact of their work is a critical skill for translational scientists to develop. Methods/Study Population: Trainings were developed to prepare investigators to describe the impact of their biomedical research to stakeholders. A one-credit class was designed for doctoral students and consisted of knowledge-based training and skill development. It included instruction in developing an impact statement and conveying research impact to various audiences. Then, students practiced engaging different stakeholders by developing and presenting tailored research presentations. Also, a seminar series on research impact, with a didactic curriculum similar to the class, was created for our wider research community, and the series will be offered in the spring. Results/Anticipated Results: Six graduate students participated in the class during its initial offering and completed a post-course survey that included quantitative and qualitative measures. All students strongly agreed or agreed that the course increased their interest in research dissemination, helped them become more competent in dissemination, and provided training that they plan to apply to their work. In response to open-ended questions, students stated that expert feedback about their presentations helped them better refine their impact messages for distinct audiences. Similar survey data will be collected from seminar participants when the series is offered in the spring. Discussion/Significance of Impact: Investigators must discuss research impact with non-academic audiences to bridge the scientific discovery to real-world application gap. Intentional training in articulating and disseminating impact helps investigators be competent and confident in discussing research implications with stakeholders.

Objectives/Goals: Lung cancer remains one of the leading causes of cancer-related mortality, primarily due to late-stage diagnosis. This project explores both universal technical limitations and region-specific socioeconomic barriers of screening strategies and the importance of novel biomarkers within the Puerto Rican healthcare context. Methods/Study Population: We conducted a comprehensive review of peer-reviewed literature of lung cancer detection strategies, ranging from the current clinical standard – LDCT – to emerging non-invasive technologies, including serum protein biomarkers (CYFRA 21-1, CEA, SCC, NSE, ProGRP, HE4), exhaled breath analysis (nitric oxide/nitrites and volatile organic compounds), and liquid biopsies (ctDNA). Each approach was examined for its technical constraints and the implementation challenges it poses in Puerto Rico, such as limited access, high cost, and logistical barriers. Results/Anticipated Results: While LDCT remains the global gold standard and has demonstrated mortality reduction, its application in Puerto Rico is hindered by false positives and limited accessibility. Novel non-invasive biomarkers CYFRA 21-1, CEA, SCC, NSE, ProGRP, HE4, nitric oxide/nitrites, volatile organic compounds, and ctDNA) show significant potential but currently suffer from inconsistent sensitivity and specificity. We are conducting an ongoing study recruiting newly diagnosed lung cancer patients to quantify these biomarkers and compare them with healthy controls. Discussion/Significance of Impact: Developing an integrated, multi-marker, non-invasive diagnostic panel represents a promising strategy to overcome healthcare disparities, enhance early detection, and ultimately reduce lung cancer mortality in Puerto Rico.

Objectives/Goals: Most studies house mice at temperatures known to trigger moderate cold-induced hypermetabolism in addition to failing to consider sex as a biological variable, thereby limiting translatability. The major goal of this study was to evaluate metabolic responses to burn injury in male and female mice housed at standard and thermoneutral temperatures. Methods/Study Population: Following randomization, young male and female C57BL/6J mice (n=64; 16 per group, 50% male) were housed at room temperature (24°C; RT) or thermoneutrality (30°C; TN) for 14 days post sham or burn injury. Burn injuries involved 6.5cm2 in female mice and 8.6cm2 in male mice, translating to roughly 12.5% of the total body surface area. Energy expenditure was assessed through metabolic phenotyping, and DEXA scans (prior to injury and euthanasia) were performed to assess body composition. Semi-quantitative untargeted metabolomics were carried out on brown adipose tissue, heart, kidney, liver, plasma, spleen, and white adipose tissue. Results/Anticipated Results: Compared to TN, housing mice at RT resulted in 83% and 94% greater basal energy expenditure in male and female mice, respectively (p<0.0001 for both). Burns resulted in moderate hypermetabolism in mice housed at TN only, evidenced by ~20% increase in BEE (p = 0.037). Cachexia was greater in TN-housed mice, where males subjected to burn injury demonstrated greater BAT and WAT wasting when compared to RT housed mice (p < 0.01). At the proteomic level, RT housing masked the burn-stress response. Ingenuity pathway analysis and mitochondria-specific analyses revealed changes in the mitochondrial proteome were more pronounced in mice housed at TN compared to RT housed mice. Further, sexual dimorphisms in the global proteomic stress response to burn injury were more evident in mice housed at TN. Discussion/Significance of Impact: Housing mice below TN masks key physiological and tissue-specific proteomic responses to burn injury, thereby limiting the translational value of these models. Humanizing rodent physiology by housing mice at TN temperatures represents a tool to enhance the utility of mouse models to recapitulate stress response to burn trauma.

Objectives/Goals: To evaluate longitudinal trends in HPV vaccination initiation and series completion among adolescents aged 9–17 years in Puerto Rico from 2017 to 2024 and to determine the extent to which sustained coverage patterns following the 2018 school-entry mandate align with Healthy People 2030 targets. Methods/Study Population: A retrospective cross-sectional analysis was conducted using longitudinal registry data from PREIRS, Puerto Rico’s modernized immunization system integrating legacy PRIR records with electronic reporting. Records included adolescents with at least one vaccination event between 2017 and 2024 (N = 3,584,516). Vaccination status was categorized as initiated (≥ 1 HPV dose) or series completed (2–3 doses per ACIP recommendations) for each calendar year. Descriptive crosstabs and chi-square tests assessed annual differences (p < .001). Multiyear comparisons were performed independently for each cohort year to evaluate temporal changes, and stratified analyses were used to assess trends across sex and age groups. Data were analyzed using IBM SPSS Statistics (IBM Corp., Armonk, NY). Results/Anticipated Results: HPV vaccine initiation increased from 25.8% (2017) to 35.7% (2024), and series completion rose from 16.4% to 28.1% (χ²=18,498.85; df=7; p<.001). The steepest rise occurred between 2019–2021, coinciding with the school-entry mandate, followed by stabilization post-2021. Female coverage remained higher but differences narrowed annually. Publicly insured adolescents comprised over 80% of vaccine recipients, indicating socioeconomic influence. Coverage was highest among 11- to 13-year-olds, reflecting effective policy reach. Despite gains, both initiation and completion remain below the ≥80% Healthy People 2030 target, signaling the need for renewed HPV vaccination promotion and policy reinforcement among adolescents. Discussion/Significance of Impact: HPV vaccination gains in Puerto Rico demonstrate the sustained impact of the 2018 school-entry mandate and PREIRS infrastructure. Narrowing sex-based gaps indicate improved program consistency, while post-2021 plateau and public-insurance dominance highlight persistent socioeconomic barriers to long-term sustainability.

Objectives/Goals: To implement and evaluate the Quality by Design (QbD) framework integrating team science and project management to increase quality and efficiency in clinical and translational studies. Goals include achieving 80% on-time completion and sharing tools to expand QbD use across other CTSA hubs. Methods/Study Population: The SC CTSI launched the QbD program in 2022 to support pilot grants, KL2 Scholar projects, and other CTSI-funded studies. Program elements include 1) Design Studios, facilitated by a QbD Specialist and attended by interdisciplinary advisors, to anticipate risks to timely study completion; 2) ongoing project management with regular check-ins; and 3) team science support for multidisciplinary research teams. Study teams establish milestones and track risks across the timeline. Ongoing evaluation follows studies across a wide variety of disease areas, using mixed methods to assess feasibility, perceived value, and impact on scientific productivity and institutional culture. Results/Anticipated Results: The QbD program has been delivered consistently, demonstrating it is feasible and well-received, with 93% of PIs reporting QbD as valuable for identifying risks and refining protocols. Early evidence suggests QbD support may reduce delays, with shorter extensions, while common barriers stemmed from institutional and administrative hurdles. PI interviews highlight QbD as a constructive framework for strengthening early planning and risk mitigation, with feedback prompting ongoing refinement such as adjusting the timing of Design studios. Anticipated results include continuous evaluation outcomes, ongoing program improvements, and broader dissemination with other CTSA hubs. Discussion/Significance of Impact: Evaluation will clarify how QbD implementation influences study planning and risk mitigation to prevent delays. Broader outcomes will include toolkit development and fostering a culture to advance proactive, quality-focused research services across institutions.

Objectives/Goals: Navigating uncertainty with emerging technologies used in human research is an ongoing concern for HRPPs and IRBs. This poster aims to describe how collaboration between IRB Offices within a geographic region yields support to address questions and explore possible solutions in a local context. Methods/Study Population: The Southeastern Wisconsin, Clinical and Translational Science Institute (CTSI) includes joint faculty appointments, shared research resources, and various partnerships between researchers and the IRBs of the institutions. In response to increases in projects using AI, one of the partnering institutions inquired with partnering IRB administrators for information on their processes reviewing AI-related research and the connection resulted in monthly meetings between the IRBs. The meetings began with an AI-specific focus but have since developed into a mechanism to support researchers with group members conferring on example submissions and discussing overlapping initiatives. Results/Anticipated Results: This effort has assisted in furthering the mission of the CTSI by lowering barriers to conducting collaborative research. The workgroup partnered to develop a guidance document for researchers seeking to utilize AI in research and for IRB members reviewing the projects. Also, several institutions adapted similar content for protocol submissions, and three implemented consistent questions within the submission forms for research involving AI. In addition, the workgroup has driven individual action at each institution and increased comfort with reaching out to one another for general guidance and advice. Discussion/Significance of Impact: The group was successful in building resources and infrastructure around the review of research utilizing artificial intelligence. A local IRB work group has the potential to address ongoing IRB-related issues and topics within the local context of the geographical region.

Objectives/Goals: To generate actionable insights into the commercialization process in academic translational science by using comparative case studies to identify strategies, success factors, and challenges across CTSA hubs, informing best practices for innovators and institutions. Methods/Study Population: We will employ a comparative case study approach, engaging 11 CTSA hubs to document two or more product-specific commercialization case studies, including at least one successful and one unsuccessful example. To ensure the comprehensiveness and consistency of data collection and analysis across cases, a standardized framework developed by the TCSC WG is followed by all participating hubs for both quantitative data (e.g., milestones, funding) and qualitative insights (stakeholder interviews). Coding and downstream cross-case analysis is leveraged to identify unifying themes and discriminating factors in commercialization strategies and associations with success and failure. Results/Anticipated Results: We aim to identify patterns, barriers, and catalysts in academic commercialization, defining key resources along with effective practices and strategies. Findings will clarify the role of CTSA hubs and their collaboration with institutional partners such as Technology Transfer. Results will highlight best practices in IP management, funding, team dynamics, partnerships, and regulatory navigation. A comparative analysis across CTSA hubs will yield a case study repository, cross-case report, educational materials, and a peer-reviewed publication. Collectively, we expect findings to provide practical guidance to NCATS and academic institutions for accelerating biomedical innovation. Discussion/Significance of Impact: This study fills a critical gap by providing real-world, comparative insights into the commercialization process within academic medicine. Outcomes will support CTSA hubs, healthcare systems, innovators, and policymakers in improving translational efficiency and maximizing innovation impact.

Objectives/Goals: This initiative accelerates translational science by integrating infrastructure, engagement, and workforce development to overcome barriers and improve efficiency in building a new academic health center. The primary objective is to overcome translational roadblocks while fostering a culture of innovation and collaboration. Methods/Study Population: The Florida State University (FSU) Health Research Connections ticketing and navigation system serves as a centralized system for research support, data capture, and service coordination. Pilot projects include utilizing group model building, a systems science approach, to map barriers and facilitators in community clinics; and testing community-engaged, trustworthy recruitment strategies into FSU Health Research Link, a community facing research portal. The initiative engages academic researchers, community members, healthcare providers, and trainees across Florida, adapts existing UF/FSU hub resources, and develops new resources that capitalize on FSU’s strengths and needs. Evaluation applies the Translational Science Benefits Model to assess impact across domains. Results/Anticipated Results: Preliminary outcomes from CTSA-supported initiatives at FSU demonstrate measurable progress in breaking translational barriers and boosting efficiency. The HRC ticketing system has streamlined research support. Metrics to be presented include the number of individuals enrolled in the FSU Health Research Community Portal, use of HRC tools and services, engagement in training workshops, external funding and scholarly outputs, utilization of big data, and adoption of findings into clinical practice. Findings from community-engaged recruitment pilots and trust metrics will also be presented. Discussion/Significance of Impact: FSU Health offers a replicable model for new academic health centers, particularly relevant for newer CTSA hub partners. Embedding evaluation and engagement sets a new standard for community-partnered, efficient, and impactful translational science infrastructure and accelerates discovery into practice.

Objectives/Goals: The objective is to study the association of subjective tinnitus, hearing status, clinical symptoms and the psychosocial effects on Puerto Rican adults with the condition. A specific aim is to describe auditory status, tinnitus characteristics and subject’s performance on the Tinnitus Handicap Inventory (THI). Methods/Study Population: This is a Transversal Descriptive pilot study, where 30 clinical records of adult Puerto Rican subjects diagnosed with Tinnitus on the Intramural Audiology Clinic of the Medical Sciences Campus, located at the University of Puerto Rico, during 2022 to 2024 were analyzed to establish a profile. Subjects between 21 and 64 years old from both genders were studied. This research was conducted after the Office of Research Participant’s Protection-IRB of the Medical Sciences Campus of the University of Puerto Rico gave the approval. Results/Anticipated Results: The study found that Tinnitus can have a significant impact in the individual’s life. The effects were registered mainly in the following areas: •Emotional Area: Subjects reported anxiety associated to experiencing Tinnitus. •Mental Health: Subjects reported being stressed due to their Tinnitus •Cognitive Functioning: Subjects reported difficulties to concentrate, think with clarity o recall information. Also subjects indicated that Tinnitus interferes with their sleep patterns affecting rest and having negative synergic effects resulting in confusion and fatigue. The condition impacts daily living productivity as well as occupational tasks. Eighty-three percent of research participants reported that their Tinnitus interfere with household tasks. Discussion/Significance of Impact: This pilot study adds to the body of evidence that validates the need to address Tinnitus in an integral manner treating its effects in all the physical and mental health dimensions affected by the condition. Also, the results of this study can be used to promote health plans coverage in Puerto Rico for Tinnitus assessment and rehabilitation.

Objectives/Goals: Stroke and Alzheimer’s disease (AD) often co-occur. The ADAPT-MRI study faced major enrollment challenges while assessing stroke’s impact on AD. This analysis examined recruitment and retention barriers in enrolling adults with early cognitive impairment and recent stroke for a longitudinal imaging study. Methods/Study Population: The ADAPT-MRI study is a prospective, observational study targeting 50 participants aged ≥50 with mild AD or mild cognitive impairment and recent acute ischemic stroke/transient ischemic attack (AIS/TIA). Participants underwent serial cognitive testing, advanced MRI, and blood sample collection over 12 months. Screening logs from 1,981 individuals obtained over a period of 2 years (2022–2024)were analyzed to assess eligibility, exclusions, and reasons for non-participation. Data included demographics, stroke type, and cognitive status. Descriptive statistics were used to quantify recruitment outcomes and retention rates, highlighting logistical, psychosocial, and protocol-related barriers. Results/Anticipated Results: Of 1,981 individuals screened, only 11 participants (22% of target) were enrolled. The most frequent exclusions were stroke outside the protocol time window (20%), unrelated diagnoses (19%), and hemorrhagic stroke (18%). Of the 46 individuals who met eligibility criteria, 16 consented, 5 were later classified as screen failures, and 11 were successfully enrolled. Declining participation was most often due to disinterest (57%), caregiver or patient overwhelm (18%), and travel or scheduling difficulties (14%). Retention declined over time, with 63.6% completing Visit 1 and only 45.5% completing all scheduled follow-up visits. Discussion/Significance of Impact: Recruitment was hindered by protocol rigidity, limited imaging access, and participant barriers. Future stroke-AD studies should use flexible criteria, decentralized imaging, and caregiver support, emphasizing pragmatic, participant-centered approaches.

Objectives/Goals: For older adults with subjective cognitive decline (SCD, N=38), we aim to qualitatively understand and describe the 1) unique participant perspectives, 2) unexpected quantitative findings, 3) complex symptom experience and resultant impact on quality of life (QoL) to further inform clinical and public health with non-pharmacological interventions. Methods/Study Population: From an RCT (12 weeks, 150 min/week), pre-post-aerobic cycling intervention (n=30) vs. control (n=8), symptoms and QoL were assessed with 4 questionnaires/individual interviews. The data were analyzed with Pearson’s r correlation coefficient/Spearman’s Rho and ANCOVA/Quade test. With mixed methods, we aim to 1) analyze the baseline interviews of cognitive and affective symptoms (anxiety and depressive) and QoL for themes to better understand the variations between SCD+ (preclinical Alzheimer’s disease more likely [n=24]) vs. non+ (n=14), 2) compare the cross-sectional data for emergent themes and patterns to explore the reasons for the unexpected correlations, and 3) describe symptomology changes and impact on QoL. Qualitative results will show varied convergent or divergent themes. Results/Anticipated Results: Significant correlations (N=38, p<.05) were shown between anxiety and depressive symptoms (r=0.44); anxiety symptoms and overall (r=-0.38) and psychological (r=-0.57) QoL; and depressive symptoms with overall (r=-0.49) and psychological (r=-0.53) QoL. Some remained correlated in SCD+; cognitive and depressive symptoms were correlated (r=.41, p<.05). The cycling group worsened in all aspects while the control group had non-significant improvements. Significant predictive relationships between worsening depressive symptoms following cycling were found for overall QoL (p=0.01) and physiological QoL (p<0.01). We will show similar/varied explanatory themes for SCD+ versus non+. Merged data, pre- and post-cycling, will explain the preliminary results from the participants’ perspectives. Discussion/Significance of Impact: The COVID-19 pandemic (during the study) and loneliness likely impacted results. We seek to understand these findings through a thematic analysis, build a body of evidence, inform the assessment and treatment of cognitive and affective symptoms in SCD, improve QoL, and positively impact brain/overall health at the clinical and public health levels.

Objectives/Goals: The number of FDA-approved cellular and gene therapy products has doubled from 23 in 2022 to 46 in 2025. For allogeneic cell therapies, cell banks are essential both during preclinical development and manufacturing clinical products. The objective of this study is to establish a cell bank system for preclinical research of a cartilage repair biologic. Methods/Study Population: To conduct large animal preclinical studies required by the FDA for load-bearing cartilage repair products, the FDA has described in its guidance documents for Investigational New Drug (IND) applications the use of an animal-based “analogous cellular product” (ACP). Here, costal chondrocytes from 6 minipigs (3 male, 3 female) were isolated and expanded to create master cell banks (MCBs) at passage 2. ACPs (i.e., tissue-engineered neocartilage) were generated from each MCB, and the critical quality attributes, properties such as morphology and mechanics, were assessed. By comparing functional properties of the ACPs to those of the native cartilage tissue they intend to replace, donors were selected for inclusion in working cell banks (WCBs) to support both academic research and ongoing IND-enabling research. Results/Anticipated Results: All six donors produced tissue-engineered cartilage that passed morphologic release criteria (i.e., round, flat). However, ACPs showed distinct donor-based variability in terms of mechanical release criteria (e.g., tensile Young’s modulus and compressive aggregate modulus). Based on release criteria data, two types of WCBs were created at passage 5: 1) a pooled donor WCB for academic studies that require multiple donors and 2) multiple single-donor WCBs for manufacturing ACPs tested in ongoing IND-enabling dose-response and pivotal long-term studies. It is estimated that between 160k-400k, ACP constructs can be produced from each of the six MCBs, analogous to clinical-scale manufacturing. Discussion/Significance of Impact: Overall, this study illustrates a cell bank system that can be used to support IND-enabling research. This cell bank produced preclinical neocartilage analogous to the intended clinical product, and it is currently being used in dose-response and pivotal long-term large animal studies for temporomandibular joint disc repair.