Objectives/Goals: To develop, pilot, and evaluate an accessible, Bilingual Community Health Worker (CHW) Certification Training Program that equips CHWs with core competencies, strengthens professional pathways, and supports integration into California’s evolving health and social care systems. Methods/Study Population: The 8-week, 40-hour hybrid program aligned with the CHW Core Consensus (C3) Project and California’s CalAIM standards. The pilot cohort (n=22) included Spanish-speaking Promotoras with 1–10 years of experience. The training combined online asynchronous modules, live weekly Zoom sessions, and in-person sessions at orientation and graduation. Participants completed weekly assignments and a final community-based project. Evaluation through weekly surveys and a retrospective pre–post evaluation assessing knowledge and confidence gains in addition to qualitative feedback were collected. A Steering Committee and a Community Advisory Board (CAB) provided guidance on curriculum design, accessibility, and cultural responsiveness. Results/Anticipated Results: The pilot achieved high satisfaction (mean 3.8/4.0). Participants reported an average +32.9% increase in perceived knowledge and +36.1% increase in confidence/self-efficacy across CHW competencies. The largest gains were in advocacy, resource navigation, and community assessment. Over 95% indicated they were likely to apply learned skills with only 5% who had yet to apply what they learned 3-months post-training. Qualitative feedback emphasized empowerment, peer learning, skill-building relevance, and remaining challenges related to advancement as CHWs. Participants valued the real-world application through a capstone community project. Discussion/Significance of Impact: This pilot demonstrates a scalable, culturally responsive CHW training model that builds professional confidence and readiness. Ongoing evaluation and expansion aim to strengthen the CHW workforce, open professional pathways, and create a sustainable model that advances public health by improving community capacity and health equity.

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: Endometriotic lesions visualized during diagnostic laparoscopy are heterogenous in their appearance. Our research aims to 1) assess the interobserver variability of surgeons in their description of endometriotic lesions and 2) assess their accuracy for prediction of invasion into underlying tissues. Methods/Study Population: We will recruit at least 3 gynecologic surgeons to review a dataset of a planned minimum of 120 coded abdominopelvic endometriotic lesions that were biopsied during diagnostic laparoscopy and that are linked to pathology results. Surgeons will independently classify each lesion by visual appearance according to standard and established criteria and predict the presence of deep tissue invasion for each lesion using a binary yes/no classification system with pathology as the reference standard. We will analyze interobserver variability using Cohen’s k statistic. For the accuracy of the prediction of lesion invasion, we will use sensitivity, specificity, and +/- predictive values and +/- likelihood ratios. Results/Anticipated Results: We expect that our results for aim 1 will be consistent with prior studies that demonstrate variability in the description of the visual appearance of endometriotic lesions by gynecologic surgeons. We also expect that for aim 2, there will be a discrepancy between surgeon predicted lesion depth invasion and findings on pathologic analysis, highlighting the limitations of visual inspection and interpretation of endometriotic lesion behavior. Discussion/Significance of Impact: Improving our understanding as to the visual perception of endometriotic lesions will allow for a better understanding of the variability of lesion types and will inform ongoing studies for the development of a machine learning system for the detection and classification of endometriosis.

Goals: Asthma is a common condition affecting over 25 million Americans. Despite high prevalence, asthma is often undertreated, resulting in significant preventable morbidity and mortality. Our goal was to identify and characterize individuals with undertreated asthma to inform tailored interventions designed to improve care access and outcomes. Methods/Study Population: We used electronic health records (EHR) to identify patients with suspected undertreated asthma receiving care in a large, multi-site state-wide healthcare system serving >2 million people. Undertreated asthma was defined by 1) history of emergency department visit or hospitalization for asthma exacerbation or asthma-related symptoms and 2) no prior history of treatment with inhaled corticosteroids, the standard of care preventative treatment for patients with asthma. Asthma symptoms were defined as wheezing, cough, and dyspnea. Patients were required to have been treated with systemic corticosteroids and inhaled beta agonists (standard treatment for asthma exacerbation) and have history of eosinophilia to increase the specificity of asthma diagnosis. Results/Anticipated Results: We identified 3,318 people with suspected undertreated asthma evaluated between 2019 and 2024. These patients had high rates of healthcare utilization with a mean of 7.3 any-cause emergency department visits and 1.4 hospitalizations over the 5-year study period. Black and Hispanic patients were less likely to have a documented primary care physician or prior pulmonologist referral order when compared to white and non-Hispanic patients, respectively. Insurance coverage rates did not differ significantly between these racial/ethnic groups. Discussion/Significance of Impact: Individuals identified as having suspected undertreated asthma were found to have high healthcare utilization. Significant racial and ethnic disparities were observed, with associated gaps in primary and specialty care not explained by insurance status, highlighting potential opportunities for improving care and addressing disparities.

Objectives/Goals: Treatments for adults with anorexia nervosa (AN) are inadequate, with no FDA-approved medications and only 30% achieving remission in psychotherapy trials. This ongoing KL2-funded pilot study evaluates Exposure Therapy for AN (Exp-AN), which targets anxiety about weight gain – a key mechanism maintaining AN. Methods/Study Population: Preliminary results (target N=16) include six adults (100% female, 83% White, 17% Black, ages 18–24, mean=20.5 years) with AN or atypical AN who have completed Exp-AN, a standardized 20-session outpatient therapy delivered in both in-person and virtual formats over 20 weeks. Exp-AN combines in vivo (e.g., stepping on a scale) and imaginal (e.g., listening to scripts about catastrophic weight gain) exposures to challenge anxious beliefs and enhance tolerance related to weight gain. Measures assessing treatment acceptability, AN symptomatology, and anxiety about weight gain were administered at baseline and end-of-treatment. Mean scores and effect sizes were calculated and compared to predetermined benchmarks to evaluate preliminary signals of acceptability, efficacy, and target engagement. Results/Anticipated Results: On two acceptability items (scale: 1=“not at all” to 7=“extremely”), participants rated Exp-AN as 5.8/7 on helpfulness and 6.3/7 on logic, meeting our 5/7 benchmark. All within-subjects effect sizes (Cohen’s d from paired samples t-tests) met our benchmark for large effects (d≥0.8), indicating improvements from baseline to end-of-treatment in: AN symptomatology (d=1.37), anxiety ratings about weight gain (d=1.22), anxious beliefs about weight gain (d =1.06), and tolerance of weight gain (d=1.40). Pearson’s correlations exploring whether changes in weight gain anxiety were associated with AN symptom improvement met our benchmark (r≥0.5) for anxiety ratings (r=0.55) and anxious beliefs (r=0.65), but not tolerance of weight gain (r=0.18). Discussion/Significance of Impact: Results support Exp-AN’s acceptability and preliminary efficacy. Reductions in weight gain anxiety correlated with symptom improvement, suggesting target engagement. By targeting specific mechanisms, this work advances precision medicine and treatment optimization. Findings warrant a fully powered randomized controlled trial.

Objectives/Goals: The objective of this pilot interventional study is to assess feasibility and preliminary efficacy of implementing a supervised, outpatient aerobic, and strength exercise regimen in newly diagnosed children and young adults with ALL. We hypothesize that early implementation of exercise is feasible and may prevent cardiometabolic late effects. Methods/Study Population: We aim to enroll 10–20 children with newly diagnosed ALL between 11 and 21 years old to participate in a 12-month supervised, structured outpatient exercise regimen (STRONGER ALL). This regimen consists of low- to moderate-intensity aerobic and strength exercises (either in person or coached virtually per patient preference) 3 times a week. This study includes 2 physical fitness assessments: 1) baseline and 2) end of study. Assessments include resting energy expenditure, peak oxygen uptake, bone density, upper and lower extremity strength, flexibility, and questionnaires (feasibility and quality of life). Additionally, blood and urine specimens will undergo metabolomic analysis to identify biomarkers predictive of future cardiometabolic outcomes. In the first year, 7/8 eligible patients have enrolled. Results/Anticipated Results: We expect that early implementation of STRONGER ALL in children undergoing chemotherapy will be feasible and preliminarily effective at mitigating risk factors for long-term cardiometabolic outcomes in survivors. Feasibility will be defined by recruitment capability (at least 50% of eligible patients agree to enroll), acceptance/compliance (at least 50% of participants complete the program with participation in at least 50% of sessions), data acquisition (collection and outcomes measures are appropriate), and practicability (program shows promise of being successful with pediatric ALL patients as measured by validated surveys administered to patients and caregivers). We anticipate that ALL patients participating in STRONGER ALL will have improved fitness and quality of life. Discussion/Significance of Impact: We aim to show that exercise during intensive chemotherapy for children with ALL is safe, feasible, and beneficial. Participants train 3x/week for 12 months (in-person or virtual), complete fitness tests, and answer health and quality-of-life surveys to inform future care. This work addresses barriers to implementing exercise in this population.

Objectives/Goals: Our objective is to develop and validate a human iPSC-derived 3D osteosarcoma (3D-iOSA) model that replicates chromosomal instability (CIN), metastasis, and chemoresistance. The model will serve as a platform to evaluate chemotherapy and immune cell therapeutics, offering improved predictive fidelity compared to 2D and spheroid systems. Methods/Study Population: Human iPSCs were engineered by CRISPR/Cas9-mediated knock out of TP53 and RB1, differentiated to mesenchymal stem cells with overexpression of cMYC ± hRAS. Cells were embedded in hyaluronan and osteogenically differentiated to generate 3D organoids (3D-iOSA), with osteoblastic commitment confirmed by RUNX2 and BGLAP immunohistochemistry (IHC). Tumorigenic and metastatic potential was assessed via subcutaneous implantation into immunodeficient mice, followed by histopathology, IHC, RNA sequencing, and 5X whole genome sequencing (WGS). MAP (methotrexate, doxorubicin, and cisplatin) chemotherapy response and chimeric antigen receptor (CAR)-immune cell cytotoxicity were compared across 2D and 3D systems to evaluate chemoresistance, immune evasion, and translational fidelity of the 3D-iOSA model. Results/Anticipated Results: 3D-iOSA exhibited osteogenic lineage commitment with RUNX2 and BGLAP expression and disorganized, anaplastic morphology correlated with mutational burden. Tumors displayed greater histologic complexity than 2D-derived tumors, with pulmonary metastases in 50% of primary and 70% of secondary recipients. WGS revealed recurrent copy number alterations and subclonal variation, indicating ongoing CIN. MAP half-maximal inhibitory concentration values were 106-260× higher in 3D-iOSA organoids than 2D cultures, increasing with genetic complexity. B7H3 CAR-iPSC NK-cell and B7H3/HER2 dual-CAR γδ T-cell screening showed system-dependent efficacy, with reduced cytotoxicity in 3D-iOSA organoids versus 2D and spheroid cultures, highlighting 3D-iOSA superior predictive power for immunotherapy evaluation. Discussion/Significance of Impact: 3D-iOSA is the first human OSA model to replicate CIN-driven evolution, chemoresistance, and metastasis. It distinguishes differential immune therapy responses with greater predictive power than 2D or spheroid models, providing a scalable, physiologically relevant platform to accelerate targeted therapy development.

Objectives/Goals: The primary objective of this research is to examine current implementations of Artificial Intelligence (AI) models in clinical trials, focusing on advantages, limitations, and ethical considerations associated with their application in pediatric populations. Methods/Study Population: A comprehensive literature search was conducted using PubMed and Google Scholar databases. The initial search used the key terms “artificial intelligence” and “pediatric.” The results were refined to include publications from 2023 to 2025. The keyword “imaging” was added, focusing on studies exploring AI-based diagnostic tools. Articles were included if they had at least one of the following: (1) the need for pediatric-specific databases, (2) diagnostic accuracy within pediatric populations, or (3) ethical considerations in AI-driven pediatric research. Data were retrieved from ClinicalTrials.gov, where “artificial intelligence” was specified. Eligibility criteria were limited to pediatric participants and restricted to studies conducted in the USA to ensure regulatory consistency. Results/Anticipated Results: An analysis of trials from ClinicalTrials.gov further highlighted the underrepresentation of pediatric subjects in AI-related clinical research, emphasizing a critical gap in age-appropriate AI model development and validation. AI models demonstrate great potential for improving diagnostic accuracy, but effectiveness remains limited by lack of pediatric-specific training data. In pediatric chest imaging, AI algorithms achieved diagnostic performance comparable to adult populations in detecting bacterial pneumonia (Morcos et al., 2023). Conversely, a large-scale review of public medical imaging datasets revealed an increase in false-positive rates among younger patients, reflecting model performance disparities (Zamora et al., 2024). Discussion/Significance of Impact: Implementing AI-driven models can accelerate data analysis and streamline trial design. The application of AI models in pediatric clinical trials can accelerate the timeline for treatment and reduce misdiagnosis. Addressing data gaps and ethical considerations about consent and algorithmic bias are crucial to improve pediatric health outcomes.

Objectives/Goals: At academic institutions, numerous programs aim to foster academic–community connections. We describe a collaborative infrastructure that streamlines and enhances community-engaged research, demonstrating how coordinated systems and shared expertise can reduce duplication, strengthen partnerships, and expand reach and impact. Methods/Study Population: At an academic medical center, community-facing programs of three major institutes – a Clinical and Translational Research Institute (CTSA), Cancer Institute, and Practice-based Research Network – unite to establish a collaborative infrastructure designed to leverage resources, minimize competition, enhance collaboration, and present a unified effort. Employing one platform to collect, track, and respond to technical assistance (TA) requests from academic and community partners, representatives from each institute meet weekly, using a group-developed standard operating procedure, to efficiently and collaboratively advance community-engaged research efforts. This unified approach is coordinated by the CSTA and supported by joint leadership across all three institutes. Results/Anticipated Results: Since 2021, we have reviewed and responded to numerous TA requests supporting academic and community partners. Academic partners sought support related to incorporating community perspectives into study design and implementation, participant recruitment, and grant development. Community partners requested assistance with data analysis and interpretation, program evaluation, and grant support. TA projects came from diverse regions, including rural and frontier counties outside of the metropolitan academic medical center. We collaborated with a variety of community organizations, and many projects involved cross-institute teams. Final analysis, including detailed breakdowns by partner type, service category, and geographic distribution, will be presented. Discussion/Significance of Impact: Backbone coordination, shared leadership, and centralized data systems sustain complex collaborations. In the future, we plan to assess partner satisfaction and expand to include additional academic institutes. This collaborative infrastructure coordination is a scalable model for enhancing community-engaged translational science.

Objectives/Goals: To quantify between-study heterogeneity in TP53 expression across DLBCL studies using frequentist and Bayesian meta-analytic frameworks; estimate the association between TP53 status and cell-of-origin (GCB vs. non-GCB); and identify methodological and biological sources of variation, using study-level data. Methods/Study Population: Four retrospective study-level datasets (n=457) from France, Canada, Brazil, and the USA were included. TP53 status was primarily assessed by immunohistochemistry (IHC) with study-specific thresholds (20–50% positive cells). Cell-of-origin classification followed the Hans or Choi algorithms as reported by each study. We fit frequentist random effects models with REML (R metafor) and Bayesian hierarchical models (R rstan) Results/Anticipated Results: Frequentist random effects meta-analysis indicated moderate-to-high heterogeneity (I² = 66.7%, p = 0.038) and a pooled odds ratio for GCB among TP53-positive vs. TP53-negative cases of 0.953 (95% CI: 0.682–1.330). The Bayesian hierarchical model estimated P(GCB | TP53+) with a posterior mean of 0.71 (95% CrI: 0.38–0.93); study-level posterior means ranged from 0.37 to 0.53. Both approaches confirm substantial between-study variation attributable to methodological factors (IHC thresholds, COO algorithms) and biological differences Discussion/Significance of Impact: This analysis clarifies the heterogeneity of TP53 expression in lymphoma and shows how methodological and biological variability influence results. Bayesian modeling enhances reliability in small, heterogeneous biomarker syntheses, supporting standardization of TP53 assessment and improving reproducibility in DLBCL.

Objectives/Goals: The WF DICQI team uses targeted messaging across many platforms to inform investigators across the Advocate Health (AH) enterprise of available programs and services, turning research into action. Translational science is valued at Wake Forest University School of Medicine, the academic core of AH. Methods/Study Population: The DICQI team partners with all Wake Forest CTSI teams to create tailored communication and dissemination plans for their resources and initiatives, designed to help investigators translate research into practice. Participants include program leaders, staff, and high users of CTSI services. Efforts focus on interviewing previous program participants and producing related articles, alongside developing targeted plain language messaging for internal newsletters, social media, and providing customized flyers and email content. This initiative enhances awareness among investigators along with driving engagement and collaboration. Results/Anticipated Results: These dissemination strategies motive investigators to use CTSI resources and engage in continuous learning. An increase in CTSI service usage is expected after implementing the dissemination plans. Plain language messaging and visually appealing graphics make scientific findings more accessible to a broader audience, so increased engagement on social media is also anticipated. These efforts make it easier for readers to understand research findings, apply them, and encourage collaboration. We will work with more AH centers and programs to create tailored plans and amplify the impact of WF CTSI. We plan to share our approach with other institutions, fostering collaboration nationwide. Discussion/Significance of Impact: The WF CTSI DICQI’s dissemination efforts are designed to increase awareness and utilization of available resources, which will drive more robust research from investigators, and more engagement from a broader audience, bridging practice–research collaboration across the AH enterprise.

Objectives/Goals: Sporadic Alzheimer’s disease (sAD) lacks effective preventive therapies, underscoring the need to target upstream pathogenic drivers. We identified an evolutionarily expanded role for postsynaptic mGluR3 receptors in DLPFC and ERC regions, where they regulate cAMP–calcium-K+ channel signaling to sustain neuronal firing and working memory. Methods/Study Population: Here, we employed liquid chromatography–tandem mass spectrometry (LC-MS/MS) to define the proteomic consequences of chronic 2-MPPA treatment in vulnerable (ERC and DLPFC) versus resilient (primary visual cortex) regions. Aberrant calcium signaling, closely linked to neuroinflammation, is an early event in sAD. Aged rhesus macaques, naturally APOE-ε4 homozygotes, show cognitive decline, calcium dysregulation, amyloid deposition, and tau pathology, providing a translational model. mGluR3 signaling is driven by N-acetylaspartylglutamate (NAAG) and constrained by glutamate carboxypeptidase II (GCPII), whose expression rises with age/inflammation and is inhibited by 2-MPPA, providing an opportunity to interrogate unique therapeutic strategies in vulnerable primate cortices. Results/Anticipated Results: We identified >2,400 proteins across experimental conditions, and label-free quantification revealed region-specific differential expression patterns paralleling known vulnerability gradients in sAD. Gene ontology enrichment implicated pathways governing protein deneddylation, amyloid and tau-associated processes, synaptic plasticity, mitochondrial homeostasis, electron transport chain, and oxidative stress, revealing putative targets for therapeutic intervention in sAD. Chronic inhibition of GCPII with oral bioavailable inhibitor 2-MPPA improved task-related neuronal firing critical for higher-order cognition, working memory behavioral performance, and reduced pT217Tau pathology, the most robust biomarker that heralds future neurodegeneration in aged macaques and sAD. Discussion/Significance of Impact: GCPII inhibition activates region-specific molecular programs in the aging primate cortex, protecting circuits vulnerable to sAD. The proteomic signatures reveal candidate biomarkers and targets for preventing calcium-driven degeneration, warranting deeper study of these therapeutic pathways in dementia and neurodegenerative disorders.

Objectives/Goals: Intratumoral B-cells are associated with better survival, but their antigenic targets are unclear. Here, I will delineate B-cell responses in human papillomavirus (HPV)-positive head and neck cancer (HNC) patients against all major HPV E proteins to identify immunodominant responses. Methods/Study Population: To profile tumor-infiltrating antibody-secreting cells (ASCs), I will analyze freshly prepared single-cell suspensions of lymphocytes from HPV+ HNC tumors using ELISpot assays. To profile circulating memory B-cells in circulation, peripheral blood mononuclear cells obtained at time of surgery will be differentiated into ASCs, followed by ELISpot analysis. To assess systemic antibody titers, ELISAs will be performed on matched plasma samples. Due to the reliance on fresh tumor samples, our study population consists mostly of stage I HPV+ HNC patients, for which surgical resection is often the primary treatment option. Notably, HPV+ HNC is known to disproportionally affect males. Results/Anticipated Results: I will identify the immunodominant targets of the HPV-specific B-cell response in HPV+ HNC. Based on my preliminary data, I expect that the HPV-specific responses will primarily target E1, E2, and E4, as opposed to the classical oncoproteins E6 and E7. I expect the magnitude of the intratumoral HPV-specific ASC response to be reflected in the systemic antibody level, with systemic antibodies, thus serving as viable surrogates for intratumoral HPV-specific responses. Additionally, I expect minimal presence of intratumoral B-cell response against antigens unrelated to the tumor, such as influenza or Epstein–Barr virus, in contrast to abundant systemic antibody titers and memory B-cells. Discussion/Significance of Impact: The majority of current immunotherapeutic treatment options for this malignancy focus solely on targeting E6 and E7. However, if other HPV E proteins are shown to be more immunogenic, targeting these antigens could enable more efficient immunotherapies.

Objectives/Goals: Clinical trial recruitment needs innovative strategies to increase efficiency. Participant-driven recruitment (PDR) strategies are an advancement of snowball sampling that have been tested in observational studies (e.g., as respondent-driven sampling) but are infrequently used in clinical trials. Methods/Study Population: In preparation for testing participant-driven recruitment as a clinical trial innovation, we conducted interviews with experts (principal investigators, project managers, and methodologists (e.g., biostatisticians)) involved in ongoing trials. The expert’s trials included behavioral, screening, and pharmaceutical therapies. We described the PDR concept to our experts and asked what sorts of trials might be amenable to the approach. We asked experts to discuss when in the course of trial workflow would be ideal for engaging current participants to identify and refer others who might be interested and eligible; and what methods concerns might result from using PDR. Results/Anticipated Results: Experts (n = 10) noted studying disease prevention or screening, or focused on a common condition (e.g., diabetes, hypertension) was most amenable to PDR, whereas rare disease trials would be challenging. Opinions differed regarding when in the enrollment process might be best to engage participants to refer others (time of consent versus after completion of active intervention). From a methods standpoint, common concerns were contamination (if socially connected individuals were randomized to different arms) and that participant-referred individuals would not be independent, thus requiring special statistical considerations. Most experts (8 of 10) expressed interest in learning best practices for PDR (e.g., incentivizing referrals, setting referral quotas and timelines) and implementing the process. Discussion/Significance of Impact: PDR has the potential reduce the time to complete enrollment, and early reports suggest, as referral chains spread through social networks, the heterogeneity and representativeness of the sample increases. Integrating PDR into trials requires a tailored approach.

Objectives/Goals: New educational approaches are needed for healthcare in the 21st century. Here, we describe the entrepreneurship, biomedical innovation, and design pathway curriculum at UMass Chan and provide preliminary assessment data. The lessons learned are informing further adjustments to the content and learning objectives of this pathway. Methods/Study Population: This new pathway curriculum introduces students to the principles of innovation, entrepreneurship, basic engineering principles, and technology commercialization. It is modeled after the I-Corps curriculum with added material regarding engineering principles. I-Corps was initially developed by the National Science Foundation (NSF) to help scientists understand the commercial potential of their inventions. Major elements include the Business Model Canvas and Customer Discovery. Eleven first-year (Class of 2027) and twenty-one second-year (Class of 2026) pathway students were invited to participate in online surveys evaluating course material, student self-efficacy, and knowledge of course content. Results/Anticipated Results: This pathway gives students a hands-on customer discovery learning experience that teaches students how to successfully transfer knowledge into products and processes that benefit society. At the end of each semester, students were invited to complete a pathway evaluation survey. Initial results show that the program was well received. 15/20 (75%) first-year students in the Fall 2023 and 13/21 (62%) in the Spring 2024 rated the experience as good or excellent. There was a noticeable increase in the students’ levels of comfort and self-assessed understandings of engineering material, and students’ knowledge of engineering material significantly improved after the three lectures. Discussion/Significance of Impact: Despite small sample sizes impacting generalizability, the results show improvements in student comfort with the material, students’ knowledge of the material, and their enjoyment and applicability of the curriculum. As additional cohorts move through the curriculum, we will continue to measure student satisfaction and learning outcomes.

Objectives/Goals: A clinical decision support tool (CDS) with an individualized prescribing approach was piloted to determine impact on opioid overprescribing rates for surgical patients at discharge. As a follow-up, clinicians were interviewed to determine current challenges to opioid prescribing and required components of an effective CDS for discharge opioids. Methods/Study Population: In the EHR-based randomized control trial, patients admitted to a qualifying surgical service for 24+ hours postoperatively were randomized to the individualized CDS tool with a taper based on inpatient opioid use or the standard discharge order set. Performance of the CDS tool was assessed by rate of opioid mismatch, that is, the difference between median inpatient and daily discharge dose in morphine milligram equivalents (MMEs). Pilot results were further investigated using a sequential explanatory design. Semi-structured interviews were held with discharging clinicians. A purposive sampling strategy with snowball sampling was used to identify providers. Data saturation was used to determine sample sufficiency. Interview transcripts were coded and thematically analyzed, with 40% group coded. Results/Anticipated Results: Among 61 randomized patients, median discharge MME (30 [IQR 22.5, 45] remained four times the median inpatient MME (7.5 [IQR 0, 30]) after the pilot period. Nine nurse practitioners and six general surgery residents were interviewed (n=15). Perceived challenges to opioid prescribing centered on three themes: limited protocolization for standard cases; lack of workflow efficiency; and systemic barriers (patient insurance and pharmacy). Clinicians identified at least one useful component of the tool for their current practice. Crucial CDS tool components identified by prescribing clinicians included seamless integration with the electronic health record, adequate clinician training, effective communication of treatment plan with the patient, and clinician buy-in to overcome current prescribing culture. Discussion/Significance of Impact: Multiple patient- and system-related factors impede standardization of opioid prescribing for postoperative patients. CDS tools in this area are a well-received idea, and the tool is now being redesigned to promote effective integration into clinician workflow with multiple stages of intervention, prior to resuming the randomized control trial.

Objectives/Goals: Mass incarceration, i.e., extremely high rates of incarceration concentrated in impoverished racially segregated communities, is associated with poor neighborhood health, but it is unclear if this is due solely to formerly incarcerated individuals. We examine these population health effects through neighborhood premature mortality rates. Methods/Study Population: We calculated census tract-level overall, gender-, and race-specific age-adjusted premature mortality rates using mortality data (2010-2014) from the New York City Department of Health. We excluded tracts with subgroup population <800. Exposure was the NY State imprisonment rate (2010), modeled as quintiles. As covariates, we included % non-Hispanic Black; poverty, education, and violent crime rates; and population density. We used GLM regression models with the census tract as the unit of analysis. To test if spatial clustering of incarceration (i.e., high-incarceration census tracts surrounded by high-incarceration census tracts) was associated with premature mortality rate independent of covariates and tract incarceration rate, we used LISA cluster values and proximity to high-high clusters. Results/Anticipated Results: Across 1985 tracts, incarceration rate ranged from a median of 19 (quintile 1) to 698 (quintile 5) per 100,000 people. In unadjusted models, neighborhoods in Q5 of incarceration rate had 2.4x higher rate ratios of premature mortality versus Q1. In fully adjusted models, Q5 tracts had 62% higher rate ratios (aOR 1.62, 95% CI 1.50-1.75; P<0.001), sex-specific findings were similar for males and females, Black and Hispanic (aOR 1.36; 95% CI 1.04-1.78 and aOR 1.49, 95% CI 1.24-1.79, specifically) rate ratios were both P<0.001 but Asian and White were NS. Being in a high-high cluster was significantly associated with premature mortality independent of covariates and tract incarceration rate (aOR 1.13, 95% CI 1.06-1.20), whereas low-low clusters were protective (aOR 0.90, 95% CI 0.85-0.94), both P<0.001. Discussion/Significance of Impact: Premature mortality rates are substantially higher in high-incarceration neighborhoods even accounting for confounders. Sex-specific findings suggest spillover to never-incarcerated people, and race-specific findings suggest concentration in social networks of the incarcerated. Spatial analyses suggest true neighborhood-level effects.

Objectives/Goals: Identify how graduates and talent acquisition specialists perceive the value and limitations of MS Clinical Research degrees in today’s clinical research workforce. Apply insights from this study to reimagine curriculum, mentorship, and industry partnerships that strengthen the value and recognition of MSCR programs. Methods/Study Population: This descriptive qualitative study investigated the perceived value of the Master of Science in Clinical Research (MSCR) degree amidst pharmaceutical industry shifts. Data were collected from 23 participants: 17 degree completers (DCs) and 6 talent acquisition specialists (TASs). Using purposive and snowball sampling, participants engaged in semi-structured focus groups, dyadic conversations, and individual interviews. Data were coded through directed qualitative content analysis, guided by Sheth et al.’s consumption values framework, with inductive coding to capture emergent themes. Results/Anticipated Results: Findings revealed that DCs emphasized professional identity formation, recognition barriers, curriculum impact, and beyond-the-classroom value; TASs stressed practical value, industry disruption, and bridging academia-workforce gaps. Both cohorts acknowledged MSCR’s symbolic and strategic value but highlighted persistent “experience paradoxes” where degrees alone could not overcome entry barriers. Discussion/Significance of Impact: Study shows MSCR builds core knowledge yet remains misaligned with industry needs due to skill gaps and credential ambiguity. Findings call for systemic professionalization, coordinated interventions across stakeholders, and research on identity, credential pathways, and employer perceptions.

Objectives/Goals: Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive neuromodulation therapy FDA-cleared for adjunct treatment of major depressive disorder (MDD) in adolescents. Here, we describe a double-blind, randomized study that explores the use of anhedonia severity as a predictor of treatment response. Methods/Study Population: This study included 41 participants (25 females) aged 12–18 years who had a Children’s Depressed Rating Scale-Revised (CDRS-R) score greater or equal to 40. Participants underwent daily rTMS at either 1 Hz or 10 Hz (randomly assigned) 5 days/week, for 6 weeks. Anhedonia was measured via a composite score using certain items from the CDRS-R and Beck Depression Inventory (BDI)-II. Treatment response was assessed via the Clinical Global Impressions – Improvement (CGI-I) scale. A logistic regression approach was used to estimate the likelihood of clinical improvement from baseline. A linear mixed model of repeated measures was used to assess changes in anhedonia scores over the study duration, across both frequency groups. Results/Anticipated Results: A significant improvement in anhedonia scores was observed across both 1 Hz (p< 0.0001, d=0.8536) and 10 Hz (p<0.0001, d=0.9032) groups. However, no significant group differences (p=0.2559) were observed for 1 Hz (m=5.121, SE=0.450) versus 10 Hz (m=5.894, SE=0.486). Notably, our analysis revealed a significant inverse relationship between changes in anhedonia symptom severity and CGI-I response for both 1Hz (d= -1.1017, SE=0.5003, p=0.0277) and 10 Hz (d= -0.8581, SE=0.3371, p=0.0109) groups. No significant interaction between TMS treatment group and changes in anhedonia or CGI-I scores were observed (p=0.3204). TMS stimulation frequency (1 Hz vs 10 Hz) did not have specific effects on the change in anhedonia scores or CGI-I response. Discussion/Significance of Impact: This study shows that TMS (1 Hz or 10 Hz) can help with specific symptomology in depression via significant decreases in anhedonia and how anhedonia may moderate overall TMS response. Future research should further elucidate predictors or moderators of TMS treatment response to inform clinical decision-making and care for adolescents with MDD.