Objectives/Goals: Community engagement has long been an underutilized strategy when conducting dementia research, especially for the recruitment of high-risk communities such as refugees. We created CHAMP: Championing Healthy Aging in Multicultural Populations Health and Resource Fair, aimed to promote early cognitive screening in aging Black refugees. Methods/Study Population: On August 9, 2025, the Health and Aging from Multicultural Perspectives Lab (HAMPLAB), in partnership with Global Lexington and the Lexington Senior Center, hosted the inaugural CHAMP Health and Resource Fair. Twenty-two vendors participated in the fair, including the Neurology department, pharmaceutical practice department, Bluegrass Lions Diabetes Project, local fire department, and the Alzheimer’s Association. Over 200 Black refugees in Lexington Kentucky and 18 volunteers attended the event. Complimentary services provided at the health and resource fair include health screening (e.g., A1C and blood pressure measurements), fresh food produce, fire safety, and back-to-school supplies. Results/Anticipated Results: Thirty-eight percent of the 55 attendees screened for A1C exhibited elevated levels. Many of these individuals were not previously diagnosed with prediabetes or diabetes and were offered counseling and follow-up. Also, over 100 people were screened for high blood pressure, and 62 eligible middle-older age adults signed up for various dementia research participation. These results indicate the importance of community-based events in which high-risk individuals can be identified and presented with practical next steps. Discussion/Significance of Impact: The CHAMP Health and Resource Fair illustrates the dual benefit of community engagement: advancing public health awareness through immediate health feedback and strengthening recruitment for ongoing research initiatives.

Objectives/Goals: Endometrial cancer (ECa) incidence is rising rapidly in women under 40 years of age, and response rates and progression-free survival remain poor in advanced ECa. New targeted therapies are urgently needed. The objective of this study is to develop and test a potent inhibitor that targets midkine (MDK) for treating ECa. Methods/Study Population: Using the three-dimensional structure of human MDK, we rationally designed a small organic molecule (HBS-101) that directly binds with MDK and that functions as a MDK inhibitor. Microscale thermophoresis assay (MST) and in silico docking studies were used to demonstrate direct binding of HBS-101 to MDK. In vitro activity was tested using MTT, clonogenicity, and apoptosis assays. Mechanistic studies were conducted using Western blot, RT-qPCR, STAT3 and NFkB reporter gene assays, RNseq, and TEM. Status of MDK in ECa was determined using TNMplot database. Pharmacokinetics, Maximum Tolerable Dose, and in vivo efficacy studies were conducted using mouse models. HBS-101 efficacy in chemotherapy-resistant ECa was demonstrated using therapy-resistant primary ECa (TR-ECa) cells generated in-house. Results/Anticipated Results: MDK is highly expressed in ECa tumors compared to normal tissues. MDK and its receptors are expressed in established and primary ECa cell lines. Knockdown of MDK reduced ECa cell proliferation and colony formation. HBS-101 directly binds to MDK with nanomolar affinity, and a potential interaction surface on MDK was identified. HBS-101 decreased ECa cell viability and colony formation with an IC₅₀ ranging from 0.5 to 5 µM. Mechanistic studies showed that HBS-101 suppressed STAT3 and NFκB activity and induced cell death, ER stress, and ferroptosis. TR-ECa cells exhibited sensitivity to HBS-101. HBS-101 possesses favorable drug-like properties, including oral bioavailability, in vivo stability and little in vivo toxicity up to 10 mg/kg. HBS-101 significantly inhibited tumor growth in ECa PDX models. Discussion/Significance of Impact: HBS-101 is a novel therapeutic agent that targets MDK via a unique mechanism, shows favorable pharmacokinetics, and induces apoptosis and ferroptosis in ECa cells by blocking MDK signaling. HBS-101 shows promise in treating high-grade and therapy-resistant ECa and may help overcome the current lack of good treatment options for these patients.

Objectives/Goals: Autoantibodies targeting beta-2-glycoprotein I (anti-β2GPI) are found in many patients with antiphospholipid syndrome (APS), where they trigger the release of pathogenic neutrophil extracellular traps (NETs). Here, we investigated the relevance of the cell signaling protein CD14 in this process to assess its potential as a therapeutic target. Methods/Study Population: Peripheral blood was collected from healthy donors or primary APS patients (all meeting the most recent ACR/EULAR Criteria). Isolated neutrophils were subjected to bulk RNAseq analysis. Neutrophil expression of CD14 and activation markers was validated by immunoblotting and flow cytometry. For mechanistic studies, affinity-purified anti-β2GPI IgG was added to isolated primary human neutrophils or whole blood in the presence or absence of the CD14 blocking antibody atibuclimab. CD14 and activation marker expression were assessed by flow cytometry, and NETs were visualized by immunofluorescence microscopy and quantified via SYTOX green assay. Ongoing work will involve CD14 blockade in mice subjected to the electrolytic inferior vena cava model of thrombosis, accompanied by APS or control IgG injection. Results/Anticipated Results: Neutrophils from APS patients overexpressed CD14 when compared to healthy controls, and patient neutrophil surface CD14 showed a strong positive association with the activation markers CD11b, CD18, and CD66b. Further, healthy neutrophils activated with patient-derived anti-β2GPI increased surface expression of CD14. Given the association between CD14 and APS-associated neutrophil activity, we asked whether CD14 blockade with atibuclimab could mitigate the effects of anti-β2GPI on neutrophils. Indeed, atibuclimab treatment attenuated anti-β2GPI-induced expression of CD11b, CD18, and CD66b, and NET formation. In vivo, we anticipate that CD14 blockade will reduce APS IgG-enhanced thrombi size and plasma levels of NET biomarkers and inflammatory cytokines. Discussion/Significance of Impact: Neutrophil CD14 appears to be required for neutrophil activation and NET formation triggered by anti-β2GPI in patients with APS. This work identified neutrophil surface CD14 and its associated downstream pathways as novel therapeutic targets with the potential to restrain not only thrombosis but also the upstream inflammation that underlies APS.

Objectives/Goals: The Dissemination, Implementation, and Continuous Quality Improvement (DICQI) team at the Wake Forest Clinical and Translational Science Institute (WF CTSI) has implemented the Translational Science Benefits Model (TSBM) to assess impact evaluation and drive excellence in translational science. Methods/Study Population: The DICQI team collaborated with the Work Force Development, Community & Stakeholder Research Engagement, and Pilot programs to implement TSBM questions into already established surveys and applications in an effort to reduce fatigue. Respondents select up to five benefits they anticipate their project impacting and provide a brief description of each. A follow-up survey is deployed at project completion to ask if the benefits were actually impacted, with space to add additional benefits if needed. The REDCap team assisted with the build, so the anticipated benefits automatically populate into the follow-up surveys, which are typically sent after one year but are project/program dependent. Results/Anticipated Results: We anticipate that by including TSBM questions into established surveys and applications, survey burden will be low and response rate will be high. These data will be used to create impact profiles and case studies. A section of our CTSI website will be dedicated to these deliverables, we will disseminate them internally, and we will submit the most compelling ones to the TSBM website. Once we have enough TSBM data gathered, we will create dashboards to display a broad evaluation of our CTSI impact. We will also use the dashboards to identify gaps in our impact and adjust pilot funding to support projects that address such gaps. Discussion/Significance of Impact: By keeping the TSBM questions brief, auto populating the follow-up survey with previous responses, and adding to existing surveys, we expect a high response rate leading to robust data for long-term evaluation, informed decision-making, and effective dissemination.

Objectives/Goals: Hypermobile Ehlers-Danlos syndrome (hEDS) and endometriosis are under-diagnosed conditions that are not well understood by many clinicians. This study aims to increase provider readiness to diagnose and treat women with these conditions by identifying clinicians’ perceived gaps in knowledge and preferred educational resources and modalities. Methods/Study Population: A national survey of clinicians (N = 121) was created in the Qualtrics survey-building platform, with recruitment taking place via the Prolific online research platform from 09/04/25 to 10/02/25. Clinicians responded to a series of established, closed-ended measures assessing their educational experiences regarding hEDS and endometriosis, comfort with diagnosing and managing the care of women with these two conditions, perceived barriers to diagnosis and care management, and preferred educational/training modalities for enhancing their understanding of these conditions. To be eligible for participation, respondents had to self-report that they were a) clinicians, b) at least 18 years of age, and c) working in the US healthcare sector. Descriptive statistics were performed on all variables of interest. Results/Anticipated Results: Clinicians first heard about hEDS from medical texts (60%) and patients (15%), and endometriosis from medical texts (50%) and personal relationships (including own diagnosis; 33%). A substantial proportion of clinicians reported being not at all comfortable understanding diagnostic criteria (hEDS 36%, endo 17%), diagnosing patients (hEDS 46%, endo 30%), or making plans of care (hEDS 42%, endo 17%). Top barriers included lack of knowledge, confidence, and mentoring. Respondents identified Online activities and Internet Point-of-Care as the most desirable CME resources, and Evidence-Based Medicine and Case-Based Learning as the most desirable learning modalities. Online learning offered flexible timing and self-paced modules, whereas in-person learning offered interaction with experts and peers. Discussion/Significance of Impact: This project recognizes the dearth of resources on hEDS and endometriosis available to clinicians and fills that gap by soliciting feedback directly from clinicians on their educational needs. Results will be translated into two prototypes of specialized educational interventions tailored to clinicians’ desired resources and methods of learning.

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.

Objectives/Goals: This pilot study uses an ethnographic analysis to examine provider knowledge, experiences, perception, and attitudes in delivering care in rural, primary care health professional shortage areas. Methods/Study Population: Ethnographic study relying on qualitative methods (semi-structured and open-ended interviews). Study population includes rural healthcare professionals (HCP), including physicians, physician assistants, nurses, dentists, therapists, and pharmacists. Results/Anticipated Results: Anticipated Results: Understandings of why rural HCP choose to deliver healthcare in resource-limited communities, and how this figures into their knowledge, experience, attitudes, and perceptions. A focus on barriers as well as strengths of HCP practicing in rural, HPSA. HCP in rural settings often face distinct working conditions precipitated by resource limitations, which may lead to higher levels of negative emotional or mental health conditions in comparison to their urban counterparts. This study will also attune to the extent to which their work, specifically as HCP in rural settings – as a SDOH – affects their mental health status. Discussion/Significance of Impact: This research contributes to the literature on global health by examining HCP in relation to rurality and in resource-limited settings in the Global North. This will expand the current global health discourse beyond the Global South and bring much needed attention to the health and well-being of communities in the Global North.

Objectives/Goals: Triple-negative breast cancer (TNBC) is an aggressive subtype lacking targeted therapies. This study explores whether the Niclosamide derivative HJC0152 can act as an immune modulator to reprogram the immunosuppressive tumor microenvironment and enhance immunotherapy efficacy. Methods/Study Population: Niclosamide-derived HJC0152 was developed as a novel cancer therapeutic and immunomodulating agent. Human and murine TNBC cell lines, as well as primary mouse MDSC cells, were treated with HJC0152. PD-L1 expression in TNBC cells and key immunosuppressive markers in MDSCs (Arg1, Arg2, and iNOS) were evaluated. The immunosuppressive function of MDSCs was further assessed using a T cell co-culture assay. In vivo studies are planned to assess the therapeutic efficacy of HJC0152 in combination with anti-PD-1 therapy using syngeneic TNBC mouse models. Results/Anticipated Results: HJC0152 exhibits improved solubility compared to Niclosamide and displays potent anticancer activity both in vitro and in vivo. RNA-Seq analysis of human TNBC cells treated with HJC0152 revealed significant downregulation of PD-L1 gene expression, which was further validated at the protein level by Western blot analysis. In addition, HJC0152 suppressed Arg1 expression in mouse MDSCs, a key mediator of immunosuppressive myeloid cell function. Together, PD-L1 and Arg1 pathways represent critical mechanisms of tumor immune evasion, and our findings highlight HJC0152 as a promising immune modulatory agent capable of enhancing the efficacy of immune checkpoint blockade in TNBC. Discussion/Significance of Impact: This study presents a novel immunotherapy strategy for TNBC using HJC0152, which downregulates tumor-derived PD-L1 and inhibits Arg1 signaling in MDSCs. As the first investigation of HJC0152 combined with anti-PD-1 in TNBC models, it may support future clinical trials and offer a new therapeutic option for TNBC patients.

Objectives/Goals: Efficacy-and-Effectiveness Too (EE2) randomized clinical trials pair a controlled efficacy cohort with a pragmatic effectiveness cohort. We will deliver a Bayesian EE2 framework with interim go/no-go rules and adaptive cross-cohort borrowing for time-to-event endpoints. Methods/Study Population: We formalize three approaches: 1) simultaneous: both cohorts start together, and interim looks apply predictive success probability (PSP) to enable early efficacy or futility stopping within each cohort; 2) staggered: the trial begins with the efficacy cohort and, at 50% information, initiates the effectiveness cohort only if the PSP under a retained-effect assumption (e.g., ≥70% of the efficacy log-HR retained) exceeds a prespecified threshold; 3) sequential: the efficacy trial is completed first, and the effectiveness trial is designed using the efficacy posteriors. Across approaches, the Bayesian method relies on piecewise-exponential modeling with Gamma-Poisson conjugacy, Negative-Binomial predictive counts, and power or commensurate priors with robust discounting. Results/Anticipated Results: Operating characteristics (type I error, power, bias/coverage, borrowing Effective Sample Size) will be evaluated through simulation studies across heterogeneity scenarios and prior-data conflict. We will re-analyze the RUBY and NRG-GY018 endometrial trials (endpoints: Progression-Free Survival and Overall Survival) as EE2 case studies (efficacy: mismatch repair-deficient tumors; effectiveness: mismatch repair-proficient tumors) using dynamic borrowing and the appropriate interim logic to demonstrate feasibility, robustness, and gains in precision. We anticipate improved precision for each cohort and for the combined effect and stable decisions under partial retention. Discussion/Significance of Impact: This work provides the first end-to-end Bayesian EE2 toolkit spanning simultaneous, staggered, and sequential implementations, with interim rules, principled borrowing, and software, to accelerate the generation of generalizable evidence while safeguarding against prior-data conflict, advancing efficient, patient-centered translation.

Objectives/Goals: The Bench Program offers academically talented high school students a unique opportunity to engage in cutting-edge research. Students are paired with a UTMB graduate student or postdoc and mentored by faculty, gaining hands-on experience in a rigorous, research-focused setting. Methods/Study Population: The Bench Tutorials course is open to all Ball High students and pairs each student with a UTMB graduate or postdoctoral mentor based on scientific interests. Students commit at least four hours weekly to supervised research and instruction, totaling about 40 hours per semester. This 5.0-credit course mirrors college-level rigor, with regular lab meetings and mentorship. Students present their research at two symposiums annually, including a Year-End event. Successful completion is considered an advanced academic achievement. Results/Anticipated Results: The Bench Program continues to serve as a model biomedical training program for qualified GISD high school students. Since its start, it has enrolled over 490 students, many of whom have pursued science-related college paths. For the upcoming year, we aim to maintain a high-quality, intensive experience by enrolling around 16 students, each paired with one of 8 dedicated mentors. This structure ensures personalized guidance and hands-on research training, helping to shape the next generation of scientific leaders. Discussion/Significance of Impact: The Bench Program gives high school students hands-on research experience with UTMB scientists. It mirrors graduate-level rigor, requiring time management and independent learning. The program is expanding to reach more students through GGCTSA partnerships.

Objectives/Goals: Although diet quality is known to influence psychological health, this is under-explored in studies designed to improve diet quality. This secondary analysis aims to investigate the effects of culinary-focused nutrition education relative to standard nutrition education on dimensions of psychological health and well-being. Methods/Study Population: This is an exploratory analysis of the SPICE UP MyPlate Pilot Study, a randomized clinical trial investigating the effects of a novel 12-week culinary-focused nutrition education intervention on diet quality relative to standard nutrition education in healthy adults aged 31–59 years. The intervention included eight modules focused on flavorful healthy eating. The control group received a printed MyPlate resource about healthy eating. Psychological health and well-being outcomes included depression and anxiety symptoms, perceived stress, loneliness, and psychological well-being. Linear mixed models will be used for analysis. Results/Anticipated Results: Data collection for the SPICE UP MyPlate Pilot Study is ongoing at the time of this writing and will be completed in December 2025. All baseline visits have been completed, and 55 participants have been randomized. At baseline, the sample is predominately female (76% female; 24% male) and White (91% White; 5% Asian; 4% African American) with a mean age of 46 ± 8 years and a mean BMI of 27.2 ± 6.39 kg/m2. Results of this analysis are anticipated to show the preliminary effectiveness of culinary-focused nutrition education compared to standard nutrition education on 1) depression and anxiety symptoms, 2) perceived stress, 3) loneliness, and 4) psychological well-being. Discussion/Significance of Impact: Poor diet quality and poor psychological health are independent risk factors for leading causes of death. Understanding the effectiveness of culinary-focused nutrition education for improving diet quality and psychological health is important for developing population-level interventions that meaningfully reduce disease risk.

Objectives/Goals: Widespread COVID-19 vaccine hesitancy was a critical barrier to managing the pandemic. Rural populations represent a key demographic in this challenge, yet the specific drivers of their hesitancy remain underexplored. To address this gap, we analyzed a survey of 454 participants in rural Mississippi to identify key predictors of vaccine hesitancy. Methods/Study Population: We employed six machine learning models and a logistic regression model, using feature importance and partial dependence analyses to understand the influence of demographic, behavioral, and belief-based factors. Results/Anticipated Results: Among participants, 98 (21.6%) reported vaccine hesitancy. The Bayesian Additive Regression Trees (BART) model identified vaccine safety as the most critical predictor, with hesitancy probabilities dropping from 0.4 to below 0.1 among those who agreed that vaccines are safe. Different from some other studies, factors such as vaccine accessibility and healthcare provider support had limited influence. Belief in vaccine safety and education level were the primary drivers of vaccine hesitancy in the rural population. Discussion/Significance of Impact: These findings suggest that public health interventions targeting rural communities must better communicate vaccine safety to effectively combat hesitancy.

Objectives/Goals: Accurate detection of peritoneal metastases during staging laparoscopy is critical for treatment planning, yet even skilled surgeons miss lesions. Thus, an optimized low-compute image-processing pipeline that maximizes recall while filtering non-lesion tissue can assist with this task. Methods/Study Population: The study population consists of 1414 images containing 5943 annotated lesions from 163 subjects undergoing staging laparoscopy for GI-origin cancer. All images were obtained during staging laparoscopy by the senior author (TS). From the original images, five binary masks were produced using red, green, blue, Canny, and Gabor filters. These were combined into a composite image, thresholded, and binarized after smoothing into a final prediction. Given the complex 16-dimensional space, a genetic fitness algorithm was used to optimize the final set of parameters to maximize recall while also penalizing coverage. Results/Anticipated Results: Preliminary data show that the algorithm has a mean recall of 0.90 ± 0.18 and a mean predicted positive rate of 0.48 ± 0.20. Thus, the algorithm is able to exclude 52% of the image area while capturing 90% of lesion pixels. We plan to further validate these results and maximize this pipeline to demonstrate that simple tools can yield useful results. Discussion/Significance of Impact: This project aims to develop a computationally simple image-processing pipeline that can achieve high recall while minimizing predicted positive coverage. This will be useful to highlight where lesions are most likely to exist and may be combined in the future with classification models.

Objectives/Goals: Mentoring is essential for the development of investigators, and while many mentorship programs exist, few focus exclusively on the challenges associated with community-engaged research (CER). This program focused on forging lasting mentoring relationships with CER experts and strengthening connections with community partners. Methods/Study Population: The 9-month program focused on: Exclusive focus on CER mentorship. The curriculum drew on best practices from CTSC partner institutions (Emory University, University of Wisconsin-Madison) and local expertise from the NIH-funded U54 Investigator Development Core. Prior work identified the lack of CER-specific mentorship as a barrier to success, prompting the creation of this dedicated program. Small cohorts with community mentors: Each bi-monthly cohort comprised four mentees and one community mentor, supported by CTSC staff. This structure created a safe space for sharing project challenges and offered grounded perspectives on community-partner needs and expectations. Mentor coaching mentors received targeted coaching, enhancing their capacity to guide mentees and boosting overall mentor satisfaction. Results/Anticipated Results: Evaluation surveys captured satisfaction, confidence, and likelihood of continued participation. Key findings include * High Satisfaction: Both mentors and mentees reported strong satisfaction with program elements. * Skill Development: Mentees cited support across project design, grant development, networking, and policy work. * Future Participation: 100 % of mentors and mentees indicated they would join again or recommend the program to colleagues. * Community Impact: Participants highlighted the program’s sense of community, passion, and peer support. Discussion/Significance of Impact: This CER mentoring program addresses a critical gap: traditional career mentors often focus on clinical or academic specialties, overlooking the unique challenges of building equitable community partnerships. By centering mentorship on CER and incorporating coach-driven mentor development, the program fosters bidirectional growth.

Objectives/Goals: To assess the feasibility and utility of using the community-informed Healthy North Carolina 2030 (HNC 2030) goals as a framework to evaluate CTSA-supported research; identify where NC CTSAs align with state health priorities; and enhance evaluation, planning, and communication of impact. Methods/Study Population: Three North Carolina CTSA hubs (UNC-Chapel Hill, Duke University, and Wake Forest University) collaboratively examined how the HNC 2030 indicators could be applied as an impact evaluation framework. Each hub independently identified projects with demonstrated or potential alignment to one or more HNC 2030 goals using institutional databases, project records, and stakeholder input. The feasibility and utility of this approach were assessed through structured reflections on practicality, appropriateness, and usefulness. Representative cases illustrate how alignment decisions were applied across clinical and public health domains. Results/Anticipated Results: Findings indicate that mapping CTSA activities to state health priorities is feasible, minimally burdensome, and adaptable across institutional contexts. The process identified both areas of strong engagement (e.g., maternal health, adolescent reproductive care) and opportunities for further investment (e.g., social determinants of health). Challenges included defining alignment boundaries, addressing cross-cutting indicators, and distinguishing between demonstrated and potential impact. This approach could strengthen communication of translational impact and inform strategic planning, helping CTSA hubs demonstrate the relevance of their work to statewide health goals. Discussion/Significance of Impact: Using community-driven state public health goals as an organizing framework enhances the relevance, transparency, and accountability of translational research. This exploratory mapping approach offers a scalable model for other CTSAs seeking to evaluate and communicate population-level impact.

Objectives/Goals: Asynchronous imaging workflows delay follow-up for abnormal screening mammograms. Real-time artificial intelligence (AI) flags high-risk scans for synchronous, immediate review. We present pre-implementation qualitative and quantitative assessments to inform AI-enabled workflow redesign and improve outcomes. Methods/Study Population: We conducted a workflow study in the largest of 14 breast imaging centers in our health system. A multidisciplinary team of experts in breast imaging, implementation science, and AI/informatics conducted four clinical shadowing visits held on different weekdays (August 2023) and a time-motion study (February 2024) to identify opportunities for optimization in the current breast cancer screening imaging workflows. To determine the optimal time for potential AI workflow integration, we used statistical process control (SPC) charts to visualize patient volumes based on 2022 to 2023 scheduling data. Results/Anticipated Results: The selected site had an average daily patient volume of 67, including 29 screening mammography patients, 3 of whom with abnormal findings prompting a diagnostic workup. During shadowing, observers recorded time stamps for each breast imaging exam step, from check-in to check-out, to calculate exam duration and estimate waiting room capacity for diagnostic and screening mammography or ultrasound. We analyzed workflow to identify unnecessary tasks and radiologists’ disruptions that, if changed, could create the space for real-time reading without more difficult changes to workflow, for example, the number of radiologists and their deployment. SPC charts indicated that selected clinic days would be most promising for testing the new real-time workflows without major disruption to the system. Discussion/Significance of Impact: A detailed understanding of the workflow ensures future implementations achieve intended outcomes. This analysis helped identify modest opportunities in radiologist and staff downtime to support the new workflow, potentially improving satisfaction, reducing anxiety, and shortening time to diagnosis.

Objectives/Goals: To evaluate the feasibility, acceptability, and usability of DAPHNE, an AI-powered chatbot for health-related social needs screening and referral in pediatric primary care, and to assess feasibility of study procedures to inform a future large-scale trial. Methods/Study Population: This pilot randomized controlled trial will enroll 60 caregivers of children ≤2 years from Nationwide Children’s Hospital pediatric primary care clinics. Participants will be randomized 1:1 to DAPHNE or standard care. The intervention provides private, natural language-based HRSN screening and personalized resource referrals via a secure, HIPAA-compliant mobile/web chatbot. Primary outcomes include feasibility (enrollment ≥70%, retention ≥70%), acceptability (WEQ ≥80%), usability (SUS ≥68), and technical performance (accuracy F1 ≥0.7, latency <3 seconds). Secondary outcomes include caregiver stress, self-efficacy, satisfaction, quality of life, provider workflow integration, study burden, and EHR-derived care utilization. Results/Anticipated Results: We anticipate that feasibility thresholds for enrollment, retention, and procedural adherence will be met. We expect caregivers to rate the chatbot above usability and acceptability thresholds, with high engagement and accurate resource navigation across devices. Provider surveys and interviews are anticipated to show positive perceptions of workflow integration. EHR data will capture referral patterns, visit adherence, and utilization trends. Findings will generate pilot data to refine the chatbot, optimize trial design, and inform comparator selection and clinical outcomes for a subsequent R01-level efficacy study. Discussion/Significance of Impact: This study will provide critical feasibility data on AI-driven HRSN screening in pediatrics. If effective, DAPHNE could reduce stigma, improve caregiver access to community resources, and inform scalable strategies for integrating conversational AI into pediatric primary care.

Objectives/Goals: Our study’s primary objective is to develop a multivariate random effects meta-analysis model that estimates risk ratio at a series of clinically relevant time points. Our goal in doing so is to address gaps in traditional hazard ratio (HR) meta-analyses due to observed time-varying treatment effects. Methods/Study Population: Our model estimates pooled risk ratios (RRs), the ratio of cumulative event probabilities, at predefined timepoints (e.g., 12, 24, 36 months). We derive the variance of the log-RR for each trial at each time point by applying the delta method to the Kaplan-Meier (KM) estimator function. Furthermore, we will derive the covariance to account for the correlation between RR estimates at different time points within the same trial. We would then like to incorporate these derivations of within-trial variance and covariance at each available time milestone into our multivariate model to increase the precision of our pooled RR estimated for both Overall Survival (OS) and Progression-Free Survival (PFS). Results/Anticipated Results: We identified 7 trials by consulting 5 systematic reviews published through 2021-2025 to ensure use of updated data. We reconstructed the pseudo-Individual Patient Data of these trials by applying PDFs of published KM curves to a validated survival curve reconstruction algorithm. For the outcome of overall survival, the max amount of follow-up time recorded is 108 months. On the other hand, there are 96 months of available follow-up for the outcome of progression-free survival. In a univariate random effects meta-analysis of HR for OS, the pooled HR was found to be 0.81 (CI: 0.74 – 0.89). Additionally, the pooled HR for PFS was found to be 0.68 (CI: 0.59 – 0.79). For both outcomes, we anticipate the multivariate random effects analysis of Risk Ratio to yield more precise confidence intervals than those of HR. Discussion/Significance of Impact: The proposed multivariate meta-analysis model will improve precision of treatment effect estimates which will add to the ongoing evaluation of immunotherapies as a current standard of care. This is significant to translational science as it provides time-specific treatment effect estimates that could be more interpretable in a clinical setting.