OBJECTIVES/GOALS: Artificial intelligence (AI) depends on quality machine learning (ML) algorithms constructed with high-quality training data. This TL1 trainee project develops a disease-agnostic computable phenotype framework for ML algorithm construction, modeling male puberty as a case example. METHODS/STUDY POPULATION: A computable phenotype of male puberty was constructed to answer the question: “Does early pubertal timing increase the risk of developing type II diabetes (T2D) in males?” A computable phenotype of males < 18 years old was created in the TriNetX© Diamond Network utilizing Boolean operator data queries. TriNetX© contains patient electronic health record information (ICD-10 diagnoses, anthropometric measures). An exploratory analysis of patient counts reflecting various computable phenotypes allowed for outcome (T2D) comparison of males diagnosed with precocious puberty (E30.1, ICD code for early pubertal timing) to those without, controlling for body mass index (BMI). RESULTS/ANTICIPATED RESULTS: Subjects (n=12,996,132) displayed the following computable phenotype: Male, < 18 years old, without ever having a BMI documented >85th percentile. Males diagnosed with precocious puberty (E30.1) were 6.89 times more likely to develop T2D when aged 14-18 years old than those without (OR 6.89, 95% CI: 5.17-9.19, p<0.0001). Next steps involve training a ML model on each computable phenotype groupings’ health data, with anticipated results identifying underlying salient pathophysiologic variables. A generalized computable phenotype approach is further developed to: 1) explore clinical questions in large databases like TriNetX©, and 2) model disease development with AI/ML algorithm construction. DISCUSSION/SIGNIFICANCE: Computed phenotypes reveal males with precocious puberty may have increased T2D risk. Next steps utilize subject data to train an AI/ML algorithm, model development to identify salient pathophysiologic variables, and synthesize a generalized AI/ML developmental research framework for dissemination.

OBJECTIVES/GOALS: There are178 million bone fractures globally each year, and 46% of fractures that have accompanying vascular damage (ischemia) will not heal without surgical intervention. Using single cell RNAseq we identified Cdk8 as a gene upregulated under ischemic fracture. Our work seeks to inhibit Cdk8 to assess its potential as a therapeutic target. METHODS/STUDY POPULATION: Most bone injuries heal through a cartilage intermediate that requires mesenchymal progenitor cells (hMSCs) to become cartilage forming chondrocytes. hMSCs underwent pelleted 3D chondrogenic differentiation in the presence of Cdk8 inhibitor, Senexin B. Chondrogenic gene expression was assessed via gene analysis of Aggrecan, Collagen II, and Collagen X. Content of sulfated glycosaminoglycans (sGAGs) was quantified through DMMB analysis. With IACUC approval, C57Bl/6 WT mice underwent femoral artery isolation and resection to create an ischemic environment prior to a transverse tibia fracture. Mice underwent intraperitoneal injections of Senexin B from day -1 to 8 and were harvested at 10 days post fracture. Control mice received vehicle injection. Calluses were analyzed through µCT and histomorphometry. RESULTS/ANTICIPATED RESULTS: At 14 days, Senexin B increased chondrogenic gene expression and improved sGAG content in hMSCs. This persisted to day 21, suggesting that Cdk8 inhibition via Senexin B promotes chondrogenesis and matrix deposition. Histomorphometric analysis reveals thatin vivotreatment with Senexin B increases cartilage content and reduces mineralization of the fracture callus compared to the Control. µCT analysis corroborates this, with distinctly less peri-cortical mineral present in Senexin B-treated calluses, and a decrease in total bone volume. These results suggest an altered progression of cartilage formation and endochondral ossification with Cdk8 inhibition. DISCUSSION/SIGNIFICANCE: Our findings reveal that increased Cdk8 is associated with poor healing in ischemic fractures. Inhibition of Cdk8 appears to increase chondrogenesis of hMSCsin vitroand in the murine fracture callusin vivo. Targeting Cdk8 offers potential to improve callus formation in impaired healing scenarios.

OBJECTIVES/GOALS: High serum copper (Cu) levels have previously been described in bariatric patients. The kidneys are a target organ for Cu toxic insult but the role of Cu on kidney function (eGFR) is uncertain. This study examines the association between Cu and eGFR in a bariatric population in Southeast Louisiana. METHODS/STUDY POPULATION: Seven hundred fifty patients will be recruited from the Bariatric Center of the University Medical Center in New Orleans. Inclusion criteria include: age ≥ 18 years, clinic visit between June 1, 2018 – May 31st 2024, and having a serum Cu test result. Covariables such as inflammatory markers and hormonal contraception use will be assessed as potential confounders. Blood pressure will be assessed as a potential effect modifier. Data will be obtained from electronic medical records. Two cohorts will be assembled, a pre-surgery cross-sectional cohort and another followed post-surgery. Separate models will be developed stratified by race-ethnicity. RESULTS/ANTICIPATED RESULTS: In a pilot study of bariatric patients 26% had elevated (>155 mcg/dl) serum Cu and pronounced racial differences were noted. Characteristics consisted of a mean BMI of approximately 50 kg/m2; 91% were female and 69% were Black. Black patients had approximately double the prevalence (OR 1.98; 95% CI: 1.15, 3.4) compared to white patients. Due to the dual nature of the kidneys’ involvement in metabolism via excretion and being the target organ for toxic insult, racial differences in exposure, coupled with the disproportionate rates of chronic kidney disease in Black adults, may be an explanation for the association between elevated Cu levels and eGFR in Black adults in this study. DISCUSSION/SIGNIFICANCE: Results from this study will provide insight into the prevalence of Cu and its association with kidney function in a bariatric population. Chronic kidney disease or other forms of renal impairment may result in the need for more conservative guidelines for dietary copper in bariatric medicine.

OBJECTIVES/GOALS: Many providers share patients resulting in networks where clinical information is exchanged, and which can impact the quality and efficiency of care. Here we analyzed the network properties of a primary care service area (PCSA) in Harris County TX, motivating our ongoing analysis of how they are associated with disparities in cancer screening. METHODS/STUDY POPULATION: Data.All providers (n=731, Medicare 2018) from the PCSA with the most providers in Harris County TX, with gender, specialty, and the number of shared patients. Method. Modeled the data as a network consisting of provider nodes, connected in pairs by edges if they shared >11 patients (an empirically-determined threshold). Analyzed the network structure using (1) modularity maximization and its significance to identify densely-connected communities; (2) degree centralization to measure whether a few providers shared many patients, and betweenness centralization to measure whether a few providers connected densely-connected communities; and (3) chi-squared to measure if pairs of connected providers tended to be of the same gender compared to disconnected provider pairs. RESULTS/ANTICIPATED RESULTS: The results (Fig. 1, http://www.skbhavnani.com/DIVA/Images/Fig-1-SNA-Network.jpg [http://www.skbhavnani.com/DIVA/Images/Fig-1-SNA-Network.jpg]) revealed a fragmented network with 120 small components (connected subnetworks, not part of any larger connected subnetwork), and 1 large component. The large component (n=244) had strong and significant modularity (Q=0.73, z=53.13, P<.001) with communities of providers that shared more patients than expected by chance; low degree centralization (dc=0.11) suggesting that no provider dominated patient sharing, in addition to high and significant betweenness centralization (bc=0.5, P<.01) suggesting that a few providers were responsible for connecting the densely-connected communities; and a significant gender bias (X2=10.05, df=1, P< .01) among those that shared patients, versus those that did not. DISCUSSION/SIGNIFICANCE: The analysis revealed a specific type of vulnerability (betweenness) for network fragmentation, and a gender bias in how patients were shared. These results motivated our ongoing analysis on how the network properties are associated with disparity in cancer screening within PCSAs across Texas.

OBJECTIVES/GOALS: Improving physical activity of African American women experiencing disproportionate health risks from sedentarism, educational and socio-environmental barriers. BeFit: Building Empowerment through Fitness is based on “What I Learned At Home” project, run by Women Under Construction Network, for residents of the Birmingham Housing Authority. METHODS/STUDY POPULATION: A qualitative study design to understand unique cultural context and challenges faced by African American women residing in the Birmingham Housing Authority, regarding physical activity engagement, including sedentarism. A needs assessment approach will help determine barriers, support systems, and social networks. Semi-structured, pre, mid, and post program focus groups will identify challenges and opportunities for health, such as diet and exercise, and will be analyzed by hand with a thematic analysis. The project framework uses exercise and home repair tools with a life-building/life repair curriculum to influence health, self-efficacy, and program engagement. The Study enrollment will include 50 women over two cohorts in a 12-week project. RESULTS/ANTICIPATED RESULTS: This research addresses the urgent health needs of African American women in low-income communities. These women face heightened health risks due to sedentary lifestyles, educational gaps, and socio-environmental barriers. This project targets the pronounced prevalence of allostatic burden in this population by applying a culturally sensitive, bottom-up approach. Our goal of incorporating healthy lifestyles to improve health in at-risk women and their families requires multiple projects. This project is a necessary first step in engaging with a community to identify local environmental circumstances and barriers to increasing the relevance of physical activity within the home. These barriers can then be addressed by adapting an exercise promotion program to the needs of this community. DISCUSSION/SIGNIFICANCE: Black women in under-resourced communities are more likely to be sedentary and have poor health. Exercise programs can be a powerful tool to address disparities and help prioritize health. The circumstances of women in public housing in Birmingham, AL, need community partners to adapt exercise engagement programs to meet environmental challenges.

OBJECTIVES/GOALS: The Title V project team is offering an elective course to teach the historical development of CTR, make a compelling scientific presentation, and use bibliographic databases. In addition, students learn: to write the research question, design a career development plan, protect human subjects in research, and the mentor-mentee relationship. METHODS/STUDY POPULATION: The course includes a variety of educational strategies and activities that allow the student to increase their knowledge and initiate their interest in the field of CTR. Both academic semesters (August to December and January to May) are offered remotely in two-hour synchronous sessions on Fridays from 3:00 p.m. to 5:00 p.m. through videoconferences, in addition to asynchronous activities. Invited expert lecturers and faculty reinforce the course content in each topic they address. In addition, course coordinators assign guided tasks where the students perform the work. Then, they present or send their work to the course coordinators for evaluation. RESULTS/ANTICIPATED RESULTS: The course began in January 2020 and has had six offerings, including one in the current academic semester (August to December 2023). Its first offering was in the semester from January to May, and due to the interest generated in students in August 2022, it is now available in both semesters. From its beginning to the present, the course has included students from the University of Puerto Rico (UPR) Bayamon, Cayey, Humacao, Mayagüez, and Rio Piedras campuses, impacting all geographic areas of Puerto Rico. The course has also represented an opportunity for graduate faculty to teach CTR to undergraduate students. Until 2023, 56 students have enrolled. DISCUSSION/SIGNIFICANCE: Upon completing six-course offerings, the evaluation carried out by the students demonstrates satisfaction with the learning obtained. The knowledge and skills achieved have led them to participate in CTR with the mentoring of collaborating course professors and starting a new professional development opportunity for undergraduate students.

OBJECTIVES/GOALS: We report an automated manufacturing system, and a series of cylindrical multi-layer microfluidic artificial lungs manufactured with the system and tested for fluidic fidelity and function. METHODS/STUDY POPULATION: A Roll-to-Roll (R2R) system to engrave multiple-layer devices was assembled. A 100 um-thick silicone sheet passes through an embedded CO2 laser engraver, which creates patterns of any geometry on the surface. The sheet is plasma-activated to create an irreversible bond, and rerolled into a processed device. Unlike typical applications of R2R, this process is synchronized to achieve consistent radial positioning. This allows the fluidics in the device to be accessed without being unwrapped. The result is a cylindrical core surrounded by many layers of microfluidic channels that can be accessed through the side of the device or through fluidic vias. This core is cut to expose the microfluidic layers, and then installed into a housing which routes the fluids into their respective microfluidic flow paths. RESULTS/ANTICIPATED RESULTS: To demonstrate the capabilities of the R2R manufacturing system, this method was used to manufacture multi-layer microfluidic artificial lungs (µALs). Gas and blood flow channels are engraved in alternating layers and routed orthogonally. The close proximity of gas and blood separated by gas-permeable PDMS permits CO2 and O2 exchange. Three µALs were successfully manufactured. Their flow paths were visualized using dyed water and checked for leaks. Then they were evaluated using water for pressure drop and CO2 gas-exchange. The top performing device had 15 alternating blood and gas layers. Test with whole blood demonstrated oxygenation from venous (70%) saturation levels to arterial (95%) saturation levels at a flow rate of 3 ml/min. DISCUSSION/SIGNIFICANCE: The ability to cost-effectively produce high surface area microfluidic devices would bring many small-scale technologies from the realm of research to clinical and commercial applications. In particular, most microfluidic artificial lungs only have small rated flows due to a lack of manufacturing processes able to create high surface area devices.

OBJECTIVES/GOALS: To facilitate data exploration at an academic medical center, we piloted self-service data science tools to provide easy access to research data and provide analytical workspace. The objectives are: i) data delivery with data governance and cohort discovery under a managed self-service model and ii) data science and analytics tool for advanced users. METHODS/STUDY POPULATION: Using existing commercial frameworks, we implemented a few pilot self-service tools. The key characteristics of the tools were i) high degrees of functionality and flexibility for data access and data governance, ii) lower cost to build and maintain, and iii) long-term organizational strategic alignment with the academic medical center. We conducted a two-phase evaluation with the pilot self-service tool: functionality-based assessment, prioritizing tools for data science users, and usability-based assessment, evaluating selected tools through customized maturity models and surveys. The evaluation study targeted a focus group study with five diverse faculties and researchers in an academic medical center seeking improved access to research resources. RESULTS/ANTICIPATED RESULTS: In evaluation phase 1, we explored seven self-service tool frameworks suitable for our research data warehouse (RDW). In phase 2, we implemented the top two tools selected from phase 1, QlikView and Palantir Foundry. Although the tool built on Palantir has higher mean and individual scores for user feedback than Qlik's, there is no statistically significant difference. Both tools had steep initial learning curve. Palantir has better feedback from qualitative responses. Our study findings highlight prioritized functionalities (efficiency, flexibility, sustainability, security, and cost reduction) for data science tool users; however features and the tool itself requires long term organizational planning and investment. DISCUSSION/SIGNIFICANCE: Academic and research medical centers strongly focus on efficient pilot data access for researchers to aid hypothesis generation. Establishing a clinical research-focused self-service data tool addresses the well-established demand for research resources and offers a model for similar organizations.

OBJECTIVES/GOALS: Metastasis to regional areas decreases invasive breast cancer (IBC) survival rate by 13%. Despite the clinical importance of lymph node involvement, the role of extracellular matrix (ECM) remodeling in metastases is unknown. We hypothesize that the spatial dysregulation of the collagen proteome facilitates pro-tumorigenic immune infiltration. METHODS/STUDY POPULATION: Lymph node metastases were compared to patient-matched primary tumor and normal lymph nodes using tissue microarrays (TMA) from 31 generational South Carolina women with IBC (black women, BW n=10, white women, WW n=21) and lumpectomies from 5 triple-negative breast cancer (TNBC) patients (BW n=3; WW n=2) by ECM-targeted mass spectrometry imaging. RESULTS/ANTICIPATED RESULTS: Between metastatic and normal lymph nodes, 10% of peptides, primarily from fibrillar collagens, were significantly different by area under the receiver operating curve (AUROC>70%; p-value< 0.01) within the TMAs. In a subsequent preliminary study of the TNBC metastatic niche, a segmentation analysis of 152 putatively identified peptides and 117,909 pixels revealed 10 uniquely localized proteomic groups. 12 peptides were found to have significantly decreased relative peak intensities in lymph node metastases compared to the primary tumor and normal lymph nodes by a one-way ANOVA test (p< 0.05). 7 peptides could discriminate between metastatic and normal lymph nodes, while 22 peptides could discriminate between metastatic lymph nodes and the primary tumor (AUROC>0.70; p-value < 0.05). DISCUSSION/SIGNIFICANCE: Our preliminary interrogation highlights emerging differences between lymph node metastases, the primary tumor, and normal lymph nodes. Future work is needed to connect these discrete ECM proteomes to immune infiltration alterations, which could contribute to disparate patient outcomes.

OBJECTIVES/GOALS: To develop and validate a tool to systematically identify benefits accruing to research within the Translational Science Benefits Model (TSBM) framework. We used a Delphi panel to reach consensus among a group of experts on criteria required for a clinical, community, economic, or policy benefit to be verified as coming from research. METHODS/STUDY POPULATION: A coding tool with proposed criteria to verify each of the 30 benefits was created at UCI to confirm the TSBM benefits resulting from funded research. We convened 11 experts from 8 CTSA hubs, who consisted of evaluators (faculty and staff) with experience using the TSBM. A web-based survey was used for Round 1, followed by a panel discussion of remaining unvalidated criteria, and a Round 2 survey as the final decision for inclusion of items in the tool. Response options for each criterion were “yes, required” or “no, not required”. Criteria that reached consensus (>70% agreement) were considered validated for inclusion in the final version. Panelist suggested criteria in Round 1 were also incorporated in the Round 2 survey for consideration by the experts. RESULTS/ANTICIPATED RESULTS: In the web-based survey for Round 1, all 11 experts participated and 92% of criteria reached the determined consensus level (N = 157). The remaining 8% of the criteria (N = 13) were discussed during the panel meeting. The discussion, in which 8 experts participated, was moderated by UCI and took place virtually via Zoom. All experts were sent a recording of the discussion and given the opportunity to post comments online about the remaining criteria before, during, and for a day after the discussion. Round 2 will include 50 newly proposed criteria from panelists and the 13 criteria that did not reach consensus in Round 1. Based on the results of Round 2, the criteria that reach consensus will be included in the final version of the coding tool that can be used across all TSBM benefits. DISCUSSION/SIGNIFICANCE: Using the Delphi Methodology, we will have a standardized set of criteria that may be applied to determine whether a TSBM benefit has resulted from a specific research project or program. This standardization will allow for aggregation and comparison of data across CTSA hubs and further multi-level evaluation of impact.

OBJECTIVES/GOALS: UNC-Chapel Hill’s CTSA implemented a community feedback session (CFS) service to help researchers gather actionable, authentic, and constructive feedback on their projects from community experts. Simultaneously, we conducted an ongoing, participatory evaluation process to improve the experience for researchers and community members. METHODS/STUDY POPULATION: Informed by the Community Engagement Studio model (Yoosten, 2015), a CFS is a 2-hour consultative session that includes facilitated discussion with community experts around topics or questions posed by a research team. UNC-Chapel Hill’s CTSA staff conducted 7 CFSs during the pilot phase of the service and collected evaluation surveys from researchers and community experts. We held a data party – a participatory evaluation method – to analyze and interpret survey data. Resulting recommendations were used to improve CFS materials and processes. We conducted 11 CFSs after the pilot phase, then analyzed survey data again to gauge improvement and make further adjustments to the service. We also surveyed researchers three months after their last CFS to assess the impact of community experts’ feedback on their studies. RESULTS/ANTICIPATED RESULTS: Since January 2022, 108 community experts have participated in 18 CFSs spanning 9 research projects. Data party interpretations of pilot evaluation data yielded several changes in service delivery; since those changes were instituted, all researchers have highly rated the service, unanimously recommending it to colleagues. Researchers praised well-structured sessions and productive engagement, citing direct benefits to their work and significant impact on recruitment processes 3 months post CFS. Community experts also echoed satisfaction, with 100% finding CFSs worthwhile and 95% desiring to participate again, emphasizing the sessions' supportive atmosphere. A community expert reported that the sessions 'made me feel seen and allowed for a greater understanding of what I have been dealing with.' DISCUSSION/SIGNIFICANCE: The CFS model allows research teams to elicit rapid and meaningful community input, which is key to improving research relevance and impact. Ongoing participatory evaluation of the service ensures continuous improvement, yielding more meaningful interactions and studies that reflect the perspectives of people affected by the research.

OBJECTIVES/GOALS: In this study, we implemented deformable medial modeling as a morphometric approach in first trimester placentas to characterize morphometric differences between fully automated and manual segmentations. METHODS/STUDY POPULATION: Twenty placentas from singleton pregnancies between 11-14 weeks’ gestation were manually and automatically segmented from 3D ultrasound volumes. Automated segmentations were produced by a trained convolutional neural network pipeline. Dice overlap scores and volumes were computed between manual and automated segmentations. Deformable medial modeling was applied to both manual and automated segmentations to produce the following metrics: maternal and chorionic surface areas (SA), thickness, circumference, and diameter along the generated medial surface. Placental non-planarity was also determined as the greatest medial surface height difference. A paired t-test and simple linear regression was performed between manual and automated segmentations for each shape metric. RESULTS/ANTICIPATED RESULTS: Mean placental volume measurements between manual and automated segmentations were similar, with a percent difference of 3.28% and a mean Dice overlap score of 0.85 ± 0.07. There were strong, statistically significant (p <0.01) linear correlations with chorionic and maternal SA, SA difference, thickness, circumference, medial surface diameter, and medial surface height difference. No significant differences were noted with chorionic SA, thickness, circumference, maximum medial surface diameter, or medial surface height difference. However, statistically significant differences (p <0.01-0.03) were noted in maternal SA, SA difference, and mean medial surface diameter. Despite these differences, mean percent difference for all morphometric parameters was less than or equal to 10%. DISCUSSION/SIGNIFICANCE: A deformable medial model evaluate unique global and regional shape placental features with highly correlated values between manual versus automated placental segmentations. However, clinical studies are needed to determine if minor differences would impact the clinical utility of these features as potential indicators of placental function.

OBJECTIVES/GOALS: We aim to identify neurodevelopment delays among children who were born prematurely. We will also calculate the sensitivity and specificity of the assessment tools used to measure the neurodevelopmental profile in early childhood of children exposed to the Neonatal Intensive Care Unit (NICU). METHODS/STUDY POPULATION: This cross-sectional study will include 100 premature children who were born between 32 to 37 weeks of gestational age and admitted to NICU at the University Pediatric Hospital in Puerto Rico. Their neurodevelopment will be measured with the Bayley III. Statistical analysis will be performed using IBM SPSS Statistics 25.0. Descriptive statistics will be used, normality distributions among all continuous variables, frequency distribution for categorical variables and logistic regressions to test association of GA and neurodevelopment delay. We will use the raw item scores for each domain of the Bayley III assessments to measure internal consistency using Cronbach’s alpha and factor analysis. RESULTS/ANTICIPATED RESULTS: We anticipate identifying the ND among children born prematurely between 32 to 37 weeks of gestational age and who were admitted to NICU at the University Pediatric Hospital in Puerto Rico. We also expect to find if gestational age impacts adversely ND in children who were born between 32 to 37 weeks of gestation. We will be able to assess if lower gestational age will impact global ND in contrast to higher gestational age neurodevelopment delays in one specific area of development. We will also be able to assess the sensitivity and specificity of the Bayley- III. DISCUSSION/SIGNIFICANCE: Premature is a major global health problem with a 12.0% prevalence. We want to promote early identification of ND in a diverse Hispanic Puerto Rican population so we can guide public health decisions and lead research initiatives to improve outcomes in the future or facing prematurity.

OBJECTIVES/GOALS: Contingency management (CM), wherein patients earn prizes for behavior change, is the gold-standard for reducing stimulant misuseand has been shown to improve medication adherence.We aim to describe the feasibility, acceptability, and effectiveness of CM to reduce stimulant use and optimize ART adherence in Women’s HIV primary care. METHODS/STUDY POPULATION: Using the ADAPT-ITT model for adapting evidence-based HIV interventions, we implemented the CoMBostudy at the Ward 86 Women’s Clinic at San Francisco General Hospital. Inclusion criteria are (1) adult age women with HIV, (2) suboptimal ART adherence, (3) stimulant use disorder with goal of reduced-use. Participants receive weekly CM for 12 weeks with escalating incentives for point-of-care urine testing negative for stimulants and positive for tenofovir ART. We use mixed methods to evaluate feasibility and acceptability ofCoMBowith quantitative process measures, sequential explanatory in-depth interviews with participants and staff, and effectiveness by proportion of point-of-care urine tests without stimulants and with tenofovir. RESULTS/ANTICIPATED RESULTS: CoMBoStudy enrollment began in September 2023; n=10 participants have enrolled with an additional n=20 planned.We will report feasibility and acceptability using:1) the number of women with HIV, stimulant use disorder, and suboptimal ART adherence enrolled vs. recruited, 2) the number and proportion of CM sessions attended/missed, 3) cost per participant, and 4) participant-reported facilitators and barriers to CM engagement. We will report preliminary effectiveness based on: 1) proportion of POC tests negative for stimulants, positive for ART, and 2)trend in self-reported stimulant use assessed weekly during CM. DISCUSSION/SIGNIFICANCE: Women with comorbid HIV and stimulant use disorder have demonstrated poor outcomes including reduced ART adherence and faster progression to AIDS. This work aims to expand access to evidence-based treatment for stimulant use disorder for women with HIV and share key opportunities and challenges for doing so in the women’s health HIV primary setting.

OBJECTIVES/GOALS: We created an online, competency-based training program for Healthcare Delivery Science (HDS) that incorporates a wide range of disciplines and best educational practices. METHODS/STUDY POPULATION: In collaboration with a curriculum design expert and thirteen content experts from multiple schools and departments, we reviewed and adapted a published set of competencies for learning health system researchers. We followed educational best practices to collaboratively create learning objectives, aligned content with the objectives, and created quiz questions that addressed the objectives. After recording the coursework and building the program in a learning management system, we tested, evaluated, and revised the courses. RESULTS/ANTICIPATED RESULTS: The systematic approach resulted in a novel set of eight online courses: Introduction to Healthcare Delivery Science, Research Methods, Dissemination & Implementation Science, Behavioral Economics, Leadership & Management, Quality Improvement, Systems Engineering, and Multi-Stakeholder Engagement. The courses are applicable to learners from diverse fields, including medicine, public health, pharmacy, engineering, health system administration, and translational science. Students can earn digital badges for individual courses and a certificate of completion for the entire set of courses. DISCUSSION/SIGNIFICANCE: Compared to previously available offerings, the new training program offers a more comprehensive view of this important field. Next, we plan to develop additional courses and create a Masters program that includes synchronous learning and a complementary experiential component for hands-on application of HDS principles.

OBJECTIVES/GOALS: Faculty pursuing their first independent research grants often struggle to express their ideas in a concise, compelling way. Thus, we developed the “Research and Scholarship Storytelling Bootcamp” to equip these faculty with narrative development skills applicable across disciplines and mechanisms. METHODS/STUDY POPULATION: Early-career researchers who were preparing either their first NIH R-series application or an NSF CAREER award proposal were invited to participate. Enrollment was limited to 20 participants. Those accepted learned the “And-But-Therefore” narrative framework by reading a short book and attending 4 synchronous lectures. Between sessions, they applied the framework by drafting abstracts and Specific Aims/Project Summary documents and reviewing their fellow participants’ work. We assessed participants' comfort with storytelling, perceptions of preparedness, and confidence regarding funding chances, before and after the program using a visual analog scale (max 100 points) and calculated Cohen’s d to evaluate the effect size of any changes. RESULTS/ANTICIPATED RESULTS: Thirty people applied for 20 slots, indicating strong demand. Eleven NIH applicants and 9 NSF applicants enrolled. Before the program, participants rated their comfort with storytelling at 45 ± 25, their preparedness at 39 ± 24, and their funding confidence at 39 ± 26. Nine total participants completed all sessions, assignments, and surveys. Completion rates were comparable for NIH- and NSF-targeting participants. After the program, completing participants reported increases in their comfort with storytelling (68 ± 14 post vs 32 ± 20 pre, d = 1.46), perceived preparedness (64 ± 20 post vs 48 ± 26 pre, d=0.58), and confidence in funding chances (56 ± 19 post vs 40 ± 27 pre, d=0.75). DISCUSSION/SIGNIFICANCE: This program was the first of its kind for multidisciplinary early-career faculty at our institution. The program successfully achieved its objectives for those who completed all activities. Future analysis of survey comments and proposal success rates will reveal barriers to full program engagement and opportunities for further training.

OBJECTIVES/GOALS: Endovascular peripheral vascular interventions (PVIs) are increasingly utilized for the treatment of peripheral artery disease (PAD). We aimed to assess characteristics of patients receiving PVI at ambulatory surgical centers and office-based labs (ASC/OBL) versus the outpatient hospital (hospital) site of service. METHODS/STUDY POPULATION: We performed a retrospective analysis using 100% Medicare fee-for-service claims data between January 1, 2017 and December 31, 2022. We used Current Procedural Terminology (CPT) codes to identify patients undergoing angioplasty, stenting, or atherectomy. Patient demographics were collected from the Medicare Master Beneficiary Summary File and associated comorbidities and PVI indications were identified using International Classification of Disease (ICD)-10 codes. We used patient ZIP codes to determine patients’ residence densities and regions. We used site of service codes to determine whether PVI were performed in the ASC/OBL versus hospital. Results were analyzed with descriptive statistics. RESULTS/ANTICIPATED RESULTS: Of 817,241 patients undergoing PVI for PAD, 461,068 (56.4%) were treated in an ASC/OBL. Compared to patients treated in the hospital, patients receiving PVI at ASC/OBLs were more likely to be older, female, non-white race, with fewer comorbidities (end stage renal disease, diabetes, hypertension, and any history of tobacco use) (all, P<0.001). Patients treated in ASC/OBLs more frequently resided in urban (vs. rural) locations, and in the South and West (both, P<0.001). Indication for PVI was predominately chronic limb-threatening ischemia, and clinically similar between groups (77.1% vs. 76.2%). There was a significant change in site of service over time: a minority (47.6%) of PVIs were performed in the ASC/OBL in 2017, whereas the majority (64.7%) of PVIs were performed in the ASC/OBL in 2022 (P<0.001). DISCUSSION/SIGNIFICANCE: Patients treated in ASC/OBLs were less medically complex compared to those treated in the outpatient hospital setting. Further study is needed to examine whether differences in patient characteristics versus other factors (e.g. reimbursement) are driving the increase in PVIs performed in the ASC/OBL over time.

OBJECTIVES/GOALS: As mortality and morbidity from acute COVID-19 decline, the impact of COVID-19 on short- and long-term quality of life (QoL) becomes critical to address. We assessed the impact of re-purposed COVID-19 therapies on QoL as a secondary outcome measure in ACTIV-6, a decentralized platform trial. METHODS/STUDY POPULATION: Adults aged ≥30 with mild-to-moderate COVID-19 enroll in ACTIV-6 online or through a study site. Patients are randomized to a medication of interest or placebo. Medications are mailed and symptoms are tracked using electronic diaries. QoL is measured#_msocom_1 using the PROMIS-29 questionnaire. Adjusted Bayesian logistic regression models are used to measure effects of treatment on the seven PROMIS-29 QoL domains at days 7, 14, 28#_msocom_2 and 90. Covariates are treatment, age, gender, symptom duration and severity, vaccination status, geographic region, call center#_msocom_3#_msocom_4, and calendar time. Treatment effects are described using ORs, 95% credible intervals, and posterior probabilities of efficacy, P(eff). RESULTS/ANTICIPATED RESULTS: There are 5,362 patients included, representing four of the study arms in ACTIV-6. We report results where P(eff)<0.025 and P(eff)>0.975 in the table below. Table 1. Scale Day: OR* (95% credible interval, P(eff)) Therapy Physical Anxiety Depression Fatigue Sleep Social Pain Ivermectin 400 — Ivermectin 600 D7: 0.77 (0.61-0.96, 0.01) D14: 0.65 (0.49-0.85, <0.01) D28: 0.69 (0.52-0.92, 0.01) — D7: 0.79 (0.64-0.97, 0.01) — D14 0.78 (0.60-1.00, 0.02) D28: 0.66 (0.50-0.87, <0.01) Fluticasone - D14: 0.77 (0.60-0.99, 0.02) — D7: 0.76 (0.62-0.93, <0.01) D90: 0.79 (0.64-0.98, 0.01) — D7: 0.74 (0.59-0.93, 0.01) Fluvoxamine D7: 0.66 (0.51-0.84, 0.01) — D28: 1.38 (1.02, 1.85, 0.98) D7: 0.78 (0.63-0.97, 0.01) D7: 0.77 (0.62-0.95, 0.01) — *OR > 1 favors active intervention DISCUSSION/SIGNIFICANCE: Results suggest fluvoxamine may improve depression scores by day 28, while placebo is favored in several other scales across treatments. Differences between treatment and placebo are not seen at most other timepoints. This trial is ongoing and future work will include results from additional ACTIV-6 study arms.

OBJECTIVES/GOALS: As of 2021, the lung transplantation waiting list has a mortality rate of 7.6 deaths per 100 patient-years. Bioengineered human organs is an emerging field of tissue engineering with a goal of developing suitable organs for transplantation. The focus of the project is to evaluate the efficacy of bioengineered lungs using a human-to-swine model. METHODS/STUDY POPULATION: This project will involve designing and assessing the bioengineered lung by establishing a human-to-pig xenotransplantation survival model. The project aims to evaluate how well the bioengineered lung functions within a living model. The bioengineered lung is constructed using swine connective tissue scaffolding, which has been recellularized with human cells. Anatomically, the lung will resemble a swine lung but will possess the immunological and cellular markers of human tissue. The proposed model will initially assess the immunological response of swine to human lung tissue. Lung function will be assessed during surgery using pulmonary vein gas samples and tissue sampling. Following the end of the study, additional tissues samples will be taken to evaluate the immunological response to the tissue. RESULTS/ANTICIPATED RESULTS: Xenotransplantation and bioengineered organs are two new emerging fields of research that have just begun to enter the large animal testing phase. This model will provide a novel human-to-pig xenotransplant survival model that will be used to test the efficacy of bioengineered lungs function in a dynamic living organism. The design has taken the principles of immunology learned from the current clinical and xenotransplant research and has incorporated this knowledge into the known pig-to-pig transplant models. We anticipate that this model design will be easily reproducible and can be expanded to other bioengineered organs as an effective means to test functionality. DISCUSSION/SIGNIFICANCE: The COVID-19 pandemic’s aftermath may lead to an increased demand for lung transplants. Bioengineered lungs could provide an additional source of organs to supplement current availability. This novel approach has the potential to offer a means to test several different types of bioengineered organs in the future.

OBJECTIVES/GOALS: Specialty care for asthmatic children should prevent adverse asthma outcomes. This study of children receiving care in the Arkansas Medicaid program used a comparative effectiveness research design to test whether allergy specialty care was associated with reduced adverse asthma outcomes. METHODS/STUDY POPULATION: Using the Arkansas All Payer Claims Database we studied Medicaid-enrolled children with asthma using a propensity score greedy nearest neighbor one-to-one matching algorithm. We matched children with (treatment) and without (comparison) an allergy specialist visit in 2018. The propensity score model included 26 covariates (demographic, clinical, and social determinants of health). Multivariable adjusted logistic regression was used to estimate adverse asthma events (AAE: emergency department visit or inpatient hospitalization with a primary or secondary diagnosis of asthma in 2019). RESULTS/ANTICIPATED RESULTS: We identified 3,031 children with an allergy specialist visit in 2018, and successfully propensity-score matched 2,910 of the treatment group with a non-allergy specialist visit comparison group. The rate of AAEs in 2019 was 9.5% for individuals with an allergy specialist visit versus 10.1% among those without a specialist visit (p=0.450). The adjusted regression analysis showed 20.3% lower rates of AAEs (aOR: 0.797; 95% Confidence Interval: 0.650, 0.977; p=0.029) in 2019 for children with an allergy specialist visit in 2018 compared to those that did not. DISCUSSION/SIGNIFICANCE: Utilizing allergy specialist care was associated with better asthma outcomes in our statewide study of Arkansas Medicaid-enrolled children with asthma. Asthma quality metrics based on guideline-based recommendations for allergy specialist care should be considered in population health management programs.