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: Ovarian cancer is the most lethal gynecologic cancer with emergence of recurrent and resistant disease being frequent. We sought to identify novel ways to effectively kill chemotherapy-resistant forms of ovarian cancer and to prevent recurrence following curative intent with surgical and adjuvant regimens. Methods/Study Population: Our group identified CTPS1 as a novel dependency in triple negative breast cancer (TNBC) and ovarian cancer. We found CTPS1 was highly expressed in breast and ovarian tumor tissues and therapy-resistant models. We demonstrated siRNA knockdown of CTPS1 reduced proliferation in sensitive and resistant cell lines. In collaboration with Step Pharma, who developed the first CTPS1 inhibitor (STP938), we performed genome-wide CRISPR KO screens on STP938-sensitive and -resistant cells. Top synthetic lethal hits identified included TSC1, TSC2, and PPP2R2A. Synergy assays were conducted with STP938 in combination with mTOR inhibitors (Everolimus, Sirolimus, and Temsirolimus) and the PPP2R2A inhibitor LB-100 to evaluate the therapeutic benefit of combination therapies. Results/Anticipated Results: We identified CTPS1 as a novel vulnerability in many ovarian cancer cell line models, including models of chemotherapy and/or PARP inhibitor resistance. The first-in-class CTPS1 inhibitor (STP938) was shown to be a highly effective anticancer agent in sensitive and resistant forms of ovarian cancer, both in vitro and in vivo. Genome-wide CRISPR KO screens identified central components of the mTOR pathway (TSC1 and TSC2), as well as PPP2R2A, as synthetic lethal targets in the setting of STP938 exposure. We anticipate that combinatorial treatment of mTOR inhibitors and PP2R2A inhibitors with STP938 will further enhance efficacy and reduce the risk of recurrence when used in the adjuvant treatment of ovarian cancer patients. Discussion/Significance of Impact: This study will validate synthetic lethal interactions from our CRISPR screen, reveal genes that could be mutated in ovarian cancer patients that may be driving resistance to STP938, and uncover combination therapies that can be used to increase efficacy in ovarian cancer patients treated with STP938.

Objectives/Goals: Build systematic evaluation capacity within a CTSA hub’s Community Engagement program to assess community-engaged research partnerships, programs, and capacity-building activities using mixed methods while advancing translational science through continuous quality improvement. Methods/Study Population: The University of Minnesota CTSI’s Community Engagement program (CEARCH) developed a comprehensive evaluation approach combining participatory approaches with systematic data collection. The CEARCH Management Council, composed of faculty and community partners, guides evaluation strategy. Methods and data sources include surveys, focus groups, program evaluations, grant progress reports, partnership assessments, and environmental scans. Tools include evaluation logic models, running evaluation inventories, REDCap and Zoho data management platforms, and an accessible dashboard tracking grant impacts, community partnerships, training and consultation outcomes. Results/Anticipated Results: CEARCH established systematic tracking of multiple evaluation domains: grant programs (demographics, topics, satisfaction), partnership metrics (meeting frequency, satisfaction, project numbers), training data (attendance, satisfaction), and impact. Visual dashboards and infographics display pilot grant outcomes including dissemination activities, significant outcomes, and stakeholder engagement. Community Health Collaborative Pilot Grants demonstrated diverse community-engaged research across health topics, populations served, and Minnesota regions. Evaluations identified needs for improving partnership processes, defining capacity readiness, and documenting community-identified assets, needs, and priorities. Discussion/Significance of Impact: This case demonstrates how translational science organizations can build sustainable evaluation approaches for community engagement programs. Systematic evaluation infrastructure enables continuous quality improvement, documents translational impact, and strengthens authentic academic-community partnerships.

Objectives/Goals: This study assesses mercury exposure in dogs and cats from Heredia, Costa Rica, near artisanal gold mining areas. As companion animals share environments with humans, they may serve as sentinel species for mercury contamination in mining-affected regions. Methods/Study Population: Noninvasive hair samples are being obtained by trained veterinary professionals from each animal through opportunistic collection or with owner’s consent, ensuring minimal stress. One hundred and fourteen samples were collected from Costa Rica, and matched samples are being collected from the Colorado sites. Mercury concentrations will be measured using inductively coupled plasma mass spectrometry (ICP-MS). Results/Anticipated Results: Results will be reported in parts per billion and assessed for statistical significance between groups. The results of this feasibility study will help determine whether companion animals living near ASGM sites exhibit higher mercury accumulation compared to those in less contaminated or historically impacted regions. Discussion/Significance of Impact: Findings may inform future public health surveillance, environmental monitoring, and policy decisions related to mining practices and community exposure risk.

Objectives/Goals: Identify genetic variants associated with the development of diabetic retinopathy (DR) and its advanced complication, diabetic macular edema (DME). Despite DME being a leading cause of vision loss among people with diabetes, genetic findings have been limited by small sample size, underrepresentation of diverse populations, and poor study design. Methods/Study Population: Genome-wide association studies (GWAS) were conducted to identify genetic variants linked to DME. GWAS were conducted separately by ancestry (African, European, and Admixed American) in the Million Veteran Program and All of Us cohorts, adjusted for age, sex, BMI, diabetes duration, mean HbA1c, and 10 principal components. We then combined population groups to perform a multi-ancestry meta-analysis (Multi) using a software called METAL. Analyses included autosomes and chromosome X for DME versus DR controls (14,211 cases and 47,005 controls). Gene expression analyses were performed using S-PrediXcan across 49 tissues to identify genes whose predicted expression is associated with DME risk. APOL1 variant and haplotype analyses were conducted to assess ancestry-specific associations with DME and type 2 diabetes. Results/Anticipated Results: Genome-wide significant loci included G6PD (Multi and African), previously reported to influence diabetes diagnosis, and APOL1 (Multi and European), previously linked to kidney disease in African ancestry. Gene expression analyses revealed 32 significant gene–tissue pairs (Multi 18 and African 18), corresponding to 9 unique genes. In APOL1, E150K was strongly associated with DME in Europeans (OR=1.22, P=2.9×10−8) and modestly in Africans (OR=1.18, P=5.3×10−4). N264K also showed significant effects in Europeans (OR=1.42, P=9.8×10−4) and weaker but consistent effects in Africans (OR=1.04, P=0.025). The high-risk G1/G2 haplotype demonstrated a modest association in African ancestry (OR=1.15, P=0.048). Discussion/Significance of Impact: This is the largest genetic study of DME, uncovering genetic risk factors that could potentially be driving risk, such as APOL1, a gene historically tied to kidney disease among individuals of African ancestry. Our results indicate its involvement may extend to diabetic complications more generally.

Posthodiplostomum minimum (MacCallum, 1921) Dubois, 1936 (Digenea, Diplostomidae) was described from adult worms from a great blue heron (Ardea herodias; Ardeidae) in New York. Metacercariae have been widely reported from diverse freshwater fishes, despite early experimental work and recent molecular data indicating exclusive infection of minnows (Leuciscidae) in North America. We compared the type specimens of P. minimum to adults taken from domestic chicks (Gallus gallus domesticus) fed metacercariae from fathead minnow (Pimephales promelas; Leuciscidae), as well as adults in naturally infected ardeid hosts. Sequences of cytochrome c oxidase I (CO1) showed these specimens were conspecific with worms from leuciscids and ardeids sampled across North America. However, adult morphology of the species with metacercariae in North American leuciscids differed markedly from the type specimens of P. minimum. Consequently, we resurrect and transfer to Posthodiplostomum Dubois, 1936, the earliest name for the lineage infecting leuciscids in North America: Posthodiplostomum vancleavei (Agersborg, 1926) n. comb. In North America, the four most likely junior synonyms of P. minimum are Posthodiplostomum aztlanensis González-García, López-Jiménez, Ortega-Olivares, Sereno-Uribe, Pérez-Ponce de León et García-Varela, 2024, Posthodiplostomum dawnsherryae Achatz, Von Holten, Pritchard et Keel, 2025, Posthodiplostomum nanum Dubois, 1937, and Posthodiplostomum seminolense Achatz, Von Holten, Pritchard et Keel, 2025. Sequences of CO1 indicate P. vancleavei n. comb. has been introduced in Japan and we discuss the high likelihood of its establishment in Europe. The complete rDNA operon and near-complete mitochondrial genome sequence of P. vancleavei show expected phylogenetic affiliation with Posthodiplostomum centrarchi Hoffman, 1958.

Objectives/Goals: The ConQuER study is randomized controlled trial testing the impact of a personal training program in patients with CKD. We are conducting an implementation evaluation of that trial to measure RE-AIM (Reach, Effectiveness, Adoption, Implementation, Maintenance) outcomes and identify barriers to clinical research participation. Methods/Study Population: This is a convergent mixed-methods study. The qualitative component is a thematic analysis of semi-structured interviews with study participants and staff. Participant eligibility requires thrice-weekly chronic hemodialysis for at least 6 months with clinical stability and adequate dialysis (single-pool Kt/V > 1.2). We will use an interview guide that solicits general perceptions about the trial and questions aligned with the RE-AIM domains. Data collection and analysis will occur iteratively using a combined inductive and deductive approach; deductive codes will pertain to RE-AIM domains. The quantitative component is a cross-sectional analysis of trial administrative documents and patient demographics. We synthesized qualitative and quantitative data in a table organized by RE-AIM domains. Results/Anticipated Results: We anticipate completing 30 interviews to achieve thematic saturation. We assume qualitative findings will suggest several factors contributing to exercise adherence, including dialysis regimen and schedule, reliable transportation access, and community support. We anticipate that familiarity with and understanding of the goals of clinical research will be factors contributing to participation. Social risk factors may also play a role, as patients with greater social risk may be unable to routinely participate in clinical research. We anticipate qualitative and quantitative findings will converge and that qualitative data will explain unanticipated quantitative results. Discussion/Significance of Impact: This study will identify how social risk, health status, and patient perspectives contribute to exercise and clinical research participation. With this knowledge, clinicians can capitalize on the enablers and work to minimize barriers to both exercise adherence and clinical research participation, increasing study population diversity.

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: 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: To translate quantitative ultrasound (QUS) from imaging biophysics into clinical dermatology by evaluating its reproducibility, diagnostic differentiation, and potential as a noninvasive, point-of-care tool for nail disease assessment. Methods/Study Population: Diagnosing nail disease is difficult due to overlapping features and the invasiveness of biopsy. In a prospective study (recruitment ongoing), patients with onychomycosis, inflammatory nail disease (psoriasis or lichen planus), and controls underwent 15-MHz ultrasound of fingernails and toenails (n = 26 patients, 152 nails). Raw radio-frequency data were processed to derive three QUS parameters: Homodyned-K [α] (microstructural organization), effective scatterer diameter (ESD) (scatterer size reflecting tissue texture), and effective acoustic concentration (EAC) (scatterer density reflecting compactness). Metrics were analyzed with t-tests and mixed-effects models. Within-patient consistency and parameter reproducibility were evaluated to assess clinical translation feasibility. Results/Anticipated Results: Diseased fingernails (33 vs 54 controls) showed reduced α (−1.11, p < 0.001), reflecting loss of microstructural organization. Onychomycosis had the largest change (−1.25), while inflammatory nails were moderately reduced (−0.93). ESD showed opposite trends (+0.85, p = 0.02) indicating coarser scatterers in fungal disease, and EAC was uniquely elevated in lichen planus (+1.30, p < 0.01), consistent with fibrotic regions. In the toenail cohort (16 diseased vs 49 controls), onychomycosis showed parallel changes (α −0.9, p < 0.001; ESD +1.0, p = 0.02), supporting reproducibility across nail sites. Findings were confirmed by mixed-effects models. Together, these parameters quantify disease-specific microstructure and demonstrate technical and biological feasibility for clinical translation. Discussion/Significance of Impact: QUS provides interpretable biophysical markers that differentiate fungal, inflammatory, and fibrotic nail diseases. By bridging imaging physics with clinical diagnosis, QUS offers a scalable, noninvasive approach for point-of-care dermatologic imaging and advances the translation of QUS into practice.

Objectives/Goals: Cerebral palsy (CP) results in impaired selective motor control (SMC), or the ability to move joints independently. This study leverages computer vision algorithms to create a scalable, low-cost, and accessible tool that automatically quantifies SMC behavior in infants born preterm, allowing for earlier screening and intervention for CP. Methods/Study Population: In single-camera videos of 600 15-week-old infants, all of whom have standardized clinical SMC scores available, human pose estimation algorithms will be used to derive 3D joint trajectories and kinematic metrics. These features will be used to train and cross-validate a machine learning model aimed at automating clinical scoring of SMC from single-camera video recordings of infants. Then, this model will be used to automatically score the SMC in longitudinal single-camera videos of 47 preterm infants (collected every two weeks from birth until 16 weeks of age). The SMC score trajectories between infants who eventually received a CP diagnosis and those who did not will be compared to establish an inflection point at which SMC development begins to diverge, establishing an optimal timepoint for intervention. Results/Anticipated Results: Preliminary results show that 3D angles of 22 joints across the infant’s body can be estimated in each frame of a 1 to 3 minute single-camera video. We anticipate that the error between the 3D angle estimated from a custom fitted kinematic model and the 2D angle calculated using human pose estimation measures will be less than 5 degrees for all joints measured. With a dataset of over 1,500 videos from over 600 infants, we expect that the trained machine learning model will achieve a sensitivity and specificity of over 90% in predicting the clinical SMC score. Finally, we expect that the automated, longitudinal SMC score trajectories will begin to significantly deviate in infants with a later CP diagnosis, from those without, at around term age (40 weeks gestational age), based on recent clinical findings. Discussion/Significance of Impact: We provide the first automated, quantitative analysis of SMC from video recordings that can be used within real-world settings such as the NICU, at home, or at daycare. This work will result in a cost-effective, precise, smartphone-accessible tool that empowers earlier, more equitable diagnosis and treatment planning.

Objectives/Goals: Established in 2006, Clinical and Translational Science Awards (CTSA) support programs at research institutions that accelerate the “bench to bedside” timeline. This project explores how funded hubs describe their programs’ contributions to scientific rigor and transparency. Methods/Study Population: Grant information associated with CTSA hub awards were extracted from NIH Reporter through their application programming interface (API). The primary author utilized text mining to analyze the corpus with a predetermined list of terms indicating support of research transparency and reproducibility. As a point of comparison, a second set of terms were drawn from key attributes of “gold standard science” described in Executive Order 14303. Frequency distributions were used to quantify the usage of specific vocabulary across cooperative (U), career development (K), and training (T) grant types, and over time (2006 to 2024). Results/Anticipated Results: As a less-structured metadata field, project abstracts have posed challenges for data cleaning and analysis. The abstracts retrieved through the API occasionally contain irregular formatting and unexpected insertions. Preliminary findings show that CTSA hub awards most frequently and consistently described “interdisciplinary,” “multidisciplinary,” “collaboration,” or “collaborative” approaches. Over time, abstracts increasingly emphasized “reproducible” science or “reproducibility.” Among abstracts for cooperative agreements (UL1 and UM1), mentions of “data sharing” and “data commons” infrastructure peaked in parallel with the COVID-19 pandemic. Discussion/Significance of Impact: The strategy employed in this project demonstrates how existing commitments made through CTSA may align with the framework proposed for “gold standard science”.

Objectives/Goals: To validate 20 culturally tailored clinical vignettes for a translational study assessing ChatGPT’s diagnostic support in adolescent and young adult mental health. The validation ensures methodological, ethical, and cultural rigor to examine ChatGPT’s potential in collaborative clinical decision-making. Methods/Study Population: Twelve licensed clinical psychologists evaluated 50 culturally adapted vignettes using a nine-item instrument assessing diagnostic agreement (Fleiss κ), content validity (I-CVI, S-CVI/Ave), comorbidity sensitivity, difficulty, ethical sensitivity, and perceived risk. Qualitative feedback refined clarity and realism. Vignettes meeting κ ≥ 0.60, S-CVI ≥ 0.80, and ethics ≥ 3 were retained, ensuring one easy, two moderate, and one difficult case per condition. The resulting 20 validated cases will serve as standardized stimuli to assess ChatGPT’s diagnostic accuracy and its ability to collaborate effectively with clinical psychologists. Results/Anticipated Results: High inter-rater reliability (κ ≥ 0.60) and strong content validity (S-CVI ≥ 0.85) are expected. Balanced difficulty and accurate risk detection will confirm calibration. Qualitative feedback will enhance realism and cultural appropriateness. Validated vignettes will enable rigorous assessment of ChatGPT’s diagnostic accuracy and clinical decision-support potential within a translational research framework. Vignette cases will be presented to three groups: 1) ChatGPT app, 2) Clinical mental health care providers, and 3) Clinical mental health care providers collaborating with ChatGPT. Each group will provide a diagnosis and confidence level to compare accuracy, sensitivity, and collaborative value across human-AI and human-only conditions. Discussion/Significance of Impact: This validation provides a rigorous foundation for evaluating ChatGPT’s translational role in mental health diagnostics. Psychometrically and ethically sound vignettes strengthen evidence-based integration of AI tools into precision mental health care and promote responsible human-AI collaboration.

Objectives/Goals: CTSA hubs are developing career ladders for clinical research professionals (CRPs) to professionalize roles and provide consistency. While these ladders classify roles based on responsibilities, skill, and experience, requirements for demonstrating professional abilities and promotion vary widely among institutions.Methods/Study Population: At the ACTS meeting in April 2025, we conducted a panel session to encourage audience discussion regarding the role that career ladders and certification play in robust workforce development. Fifty-seven people attended, representing 34 universities and institutions. Audience members worked in small groups to identify the benefits and challenges of developing career ladders at their institutions. Each group included a facilitator to encourage discussion and take notes. Six open-ended questions were provided to guide discussion surrounding the topics of career progression, certification requirements, and standardized job descriptions. Attendees were also provided with a QR code to answer five additional online survey questions regarding the structure and hiring climate at their institution. Results/Anticipated Results: Content analysis was conducted by two reviewers, and survey summary statistics were generated. Discussion group analysis identified nine themes including working with human resources on career ladders, coordinating competencies with promotion, job progression for those not conducting clinical trials, decentralization of systems, certification requirements for promotion, employee turnover, choosing job titles, strategies to train CRPs, and transparency in career ladder expectations. Thirty-one people completed the online survey with 85% indicating their institution had a decentralized structure, 61% had a formal CRP career ladder, 54% considered certification but did not require it for promotion, and 63% did not provide financial assistance to CRPs to complete professional certification. Discussion/Significance of Impact: Analyses show that as institutions in the CTSA Consortium develop career ladder programs to professionalize the CRP role in the workforce, there continues to be wide variability in structure and requirements. These results can be used by hubs to help create roadmaps for career progression and to make decisions regarding their career ladder programs.

Objectives/Goals: In CTSA funding calls issued since 2021, the NCATS has differentiated the terms “translational research” and “translational science” which has resulted in confusion between the terms. We explore why this distinction has become challenging for CTSA hubs to implement as a requirement of pilot and UM1 awards and reflect on ways to reduce confusion. Methods/Study Population: We conducted a historically informed critical analysis of data collected from three sources. First, we looked at the scholarly literature on definitions of translational science and translational research since 2006. Second, we analyzed NCATS funding calls from 2006-2024 to identify if and how translational science and translational research were defined and utilized. Lastly, we used our professional experience over the last five years working at a CTSA hub and developing trainings to differentiate translational research and translational science for pilot awards. Results/Anticipated Results: Results suggest three reasons why challenges are commonplace. First, we demonstrate that NCATS has not consistently communicated this distinction, resulting in different interpretations of the concept of translational science. Second, we argue that the systems-level conceptualization of translational science is uncommon in biomedical science training, potentially contributing to gaps in understanding. Third, we show that the academic performance measures, funding, and infrastructures for biomedical research in the United States are not designed to support translational science projects, systems, and careers. Most notably, there are no NIH R01 mechanisms dedicated to translational science that provide standard NIH career pathways. Discussion/Significance of Impact: We propose education and peer-to-peer brainstorming sessions to improve the ability of CTSA investigators to understand the scope of translational science and translational research. However, to truly support long-term work in translational science, NCATS would need to develop a clear career path that includes R01s in translational science.

Objectives/Goals: Trial accrual via electronic health records (EHRs) are limited by workflow and communication issues. We used a root cause analysis to identify barriers and guide changes in a pragmatic trial of metformin vs lifestyle change for prostate cancer. The goal is to evaluate strategies to increase accrual. Methods/Study Population: We previously conducted a mixed-methods root cause analysis to examine barriers along the enrollment pathway. The study required two consents: 1) prostate cancer research consortium participation and 2) trial specific. We assessed the trial’s EHR-embedded consent workflow and Best Practice Alert (BPA) implementation and aggregated and harmonized data from multiple EHR sources to reconstruct the full enrollment pathway in a CONSORT diagram. We conducted semi-structured interviews with eligible patients (n = 10) and engaged clinicians (n = 4). Based on interview findings and enrollment pathway insights, the study team designed and evaluated impact of several accrual enhancement strategies. Results/Anticipated Results: We identified two types of feasible accrual enhancement strategies: 1) patient-focused, including a) tracking consent status in the enrollment pathway report; b) proactively messaging patients with upcoming visits about consent; and 2) clinician-focused, including a) tailored EHR-based messages before eligible patient visits; b) targeted education; and c) BPA optimization to improve reach to appropriate clinicians. In the 6 months prior to strategy implementation, enrollment averaged 0.33 patients/month. In the 6 months post-implementation, enrollment increased to an average of 3.17 patients/month. Discussion/Significance of Impact: Sustained enrollment in pragmatic trials demands greater-than-expected engagement. In partnership, the study and informatics teams oversaw intervention processes based on trial-specific issues, identified issues quickly, explored feasible solutions, and refined the process to support trial success.

Objectives/Goals: Resource navigator programs (RNPs) improve care coordination and access to social resources, but designs vary widely. We aim to evaluate patient and family experiences across three distinct pediatric RNPs, focusing on how program structure and context influence satisfaction and perceived impact. Methods/Study Population: Using purposive, criterion-based sampling, we will recruit families who completed one of three established Bay Area RNPs. Surveys will assess satisfaction and perceived support addressing social needs, while qualitative semi-structured interviews informed by the Consolidated Framework for Implementation Research and literature review will examine participants’ lived experiences with the RNPs, probing family attitudes on identifying social needs, their experiences in being connected with community-based organizations, and their perceived impact on their child’s health and well-being. Dedoose will be used for qualitative data management and coding organization. Survey and interview findings will be triangulated to identify converging themes. Results/Anticipated Results: Our interview guide has been developed and we are in the process of recruiting participants. Two of the sites are tertiary children’s hospitals and one is a safety-net hospital. The programs vary in structure and intensity, from a student volunteer model and a community health worker model with 6-month follow-up to an interventionist-led model with 1-year follow-up. We hypothesize that clinics serving medically complex patient populations will benefit most from longitudinal RNPs with dedicated interventional staff, given their extended contact with the healthcare system, whereas volunteer-based programs with shorter follow-up may be more effective in primary care settings, reaching larger populations with less intensive needs. Discussion/Significance of Impact: Insights from patient and family experiences can guide adaptation to local contexts and inform evidence-based decisions for hospitals implementing or refining RNPs. Findings will better inform the design and implementation of a new RNP for socially vulnerable pediatric surgical patients in the Bay Area.

Objectives/Goals: Develop a precision hydrogel-organoid model to determine how extracellular matrix (ECM) biomechanics drive the malignant transformation of oral epithelial dysplasia (OED) to oral squamous cell carcinoma (OSCC) and identify mechanoresponsive pathways. Methods/Study Population: Patient-derived oral epithelial dysplasia (OED) and oral squamous cell carcinoma (OSCC) organoids will be encapsulated in an interpenetrating network hydrogel engineered with tunable stiffness and viscosity to mimic healthy, dysplastic, and cancerous tissue. Organoid growth, morphology, and expression of mechanosensitive markers will be analyzed by imaging and immunostaining. Single-cell RNA sequencing will identify mechanoresponsive markers across genetically diverse patient lines. Targeted inhibitors of EGFR, YAP, and p53 pathways will text whether blocking these signals can prevent mechanics-driven malignant transformation. Results/Anticipated Results: We anticipate that OED organoids in stiffer matrices similar to OSCC tumor stroma will exhibit increased proliferation, altered morphology, and activation of tumorigenic markers similar to OSCC. scRNA-seq is expected to reveal conserved and patient-specific mechanosensitive pathways. Targeted inhibition of these pathways should mitigate mechanics-driven malignant transformation. These outcomes will define molecular mechanisms linking ECM biomechanics to tumor progression and reveal new therapeutic opportunities for early intervention. Discussion/Significance of Impact: This hydrogel-organoid model links patient-specific genetics and ECM biomechanics to tumor progression, enabling controlled studies of how mechanical cues drive malignancy and therapeutic response in a clinically relevant, precision medicine context.

Objectives/Goals: In 2019, we began a novel team-science based research program aimed at producing more clinically relevant and practical patient-focused solutions, more quickly and efficiently. Methods/Study Population: We created a novel funding opportunity requiring broad multidisciplinary team participation, including patients, community members, and health system representatives. Inclusion of these non-traditional team members was required to help transcend long-standing research silos. Teams collaborated using team science principles. Successful teams were awarded a $50K “line of credit,” limited to pre-approved expenditures for supplies, services, and staff – no salary support for research faculty. Teams were granted project manager support. Grant budgets were not required, and there were no project end dates. We tracked several research metrics to determine if this less restrictive funding mechanism led to more collaboration, efficiency, innovation, and productivity. Results/Anticipated Results: From 2019 to 2024, 68 teams submitted proposals, and 29 teams were approved to receive a line of credit. Collectively, these teams submitted 43 extramural and intramural grant applications; of these, 11 applications were awarded, totaling $15M. The average time to first grant submission for teams was 20.4 months, and the average time to first grant award start date was 33.8 months. The teams produced 69 total peer-reviewed publications, with an average time to first publication of 15.6 months. A comparison of publication rates found that team members, on average, experienced a 72% increase in monthly publication rates after teams were formed and funded. An analysis of output (return on investment) found that every dollar invested in these funded teams delivered $21 in new grant funding. Discussion/Significance of Impact: This novel funding mechanism, created at the Clinical and Translation Science Institute of Southeast Wisconsin, may facilitate increased productivity, conservation of research dollars, and broader multidisciplinary collaboration that leads to practical, effective, real-world patient solutions. Continued analysis of outcomes is planned.