OBJECTIVES/GOALS: Our objective is to explore the evolving role of evaluators within Learning Health Systems (LHSs) and the implications for evaluation approaches in these dynamic healthcare environments. We aim to disseminate lessons learned to help inform best practices for other CTSA hubs operating under a LHS model. METHODS/STUDY POPULATION: Our investigation builds upon our prior qualitative analysis of the LHS literature and contextualization of unique challenges, and potential remedies, of a LHS in Academic Health Centers. As evaluators, we are particularly interested in understanding how evaluation work is conducted in LHSs and exploring ways to optimize the role of evaluators and their skillset in this context. For this investigation, we examined the competencies necessary for evaluators working in LHS and the specialized evaluation approaches needed to fulfill these requirements. Our approach drew from multi-faceted data and experience. We leveraged insights from our literature review, direct experience within WFUSOM CTSI, and discussions with other evaluators. This combination of data sources provided the foundation for our analysis. RESULTS/ANTICIPATED RESULTS: We expect that as more health systems move toward the LHS model, they will have an increased need for various forms of evaluation, requiring resources well beyond what they are currently dedicating to evaluation. Expectations for evaluators will be enhanced in the following distinct, yet complementary, categories: generating new knowledge and translating research knowledge into practice. Anticipated results include identifying essential competencies for evaluators in LHS, such as data proficiency, clinical understanding, and adaptive skills. We also expect to uncover various evaluation approaches specific to LHS, including quality improvement studies, pragmatic trials, and stakeholder-engaged research. DISCUSSION/SIGNIFICANCE: Understanding the evolving role of evaluators and specialized evaluation approaches in LHS is crucial. It enhances the ability to generate localized evidence, customize interventions, and improve patient care. This knowledge empowers healthcare systems to adapt, innovate and deliver high-quality care for a higher impact on patient outcomes.

OBJECTIVES/GOALS: RNA-seq of urine and kidney allograft biopsies (bx) found that urinary cell immune landscape reflects intragraft molecular events and we discovered a shared set of 127 mRNAs in urine matched to T cell mediated and antibody mediated rejection bx. We prioritized ITM2A, SLAMF6 and IKZF3 mRNAs and herein investigate if these accurately predict rejection. METHODS/STUDY POPULATION: We collected urine samples from adult kidney allograft (KA) recipients at the time of KA bx. KA bx were classified by pathologists by Banff criteria. Total RNA was isolated from KA bx-matched urine samples. Absolute copy numbers of ITM2A, SLAMF6, and IKZF3 mRNAs and 18S rRNA were measured using our customized RT-qPCR assays. Logistic regression used to derive an equation for a combined signature score of 18S-normalized urinary cell mRNA levels of ITM2A, IKZF3, and SLAMF6 that best predicts Acute Rejection (AR= both T cell mediated rejection and antibody mediated rejection). Area under the ROC curve (AUC) was calculated to discriminate between AR and No Rejection (NR) biopsies for 18S-normalized urinary cell levels of ITM2A, IKZF3 and SLAMF6 and the composite signature score. AUCs were compared by DeLong Method. RESULTS/ANTICIPATED RESULTS: Urinary cell 18S-normalized levels of ITM2A, IKZF3, and SLAMF6 mRNAs in urine discriminated KA recipients with AR biopsies (n=95) from those with NR biopsies (n=160) (All P values <0.05, Mann-Whitney test) and the AUC was 0.69 (95%CI, 0.62 to 0.76) for ITM2A, 0.61 (95%CI, 0.53 to 0.68) for IKZF3, and 0.60 (95%CI, 0.53 to 0.68) for SLAMF6. The derived combination signature score of urinary cell 18S-normalized levels of ITM2A, IKZF3, and SLAMF6 mRNA discriminated KA recipients with AR from those with NR (P<0.0001, Mann Whitney test) and the combined signature score AUC was 0.72 (95%CI, 0.65 to 0.79). The combination signature score discriminated AR vs NR better than IKZF3 and SLAMF6 alone, but was not significantly different than ITM2A alone (DeLong method). (Additional results/figures to be included in poster) DISCUSSION/SIGNIFICANCE: Our RNA-seq offered a unique opportunity to diagnose AR by measuring the mRNAs in urine. We now found that urinary cell mRNA levels of ITM2A, IKZF3, SLAMF6 and the combined signature are diagnostic of AR, a major and serious post-transplant complication. This allows for much-needed KA molecular surveillance and personalization of immunosuppression.

OBJECTIVES/GOALS: In the U.S., over 4 million people including children experience transient periods of undernutrition annually. Cardio-metabolic and renal diseases are more prevalent in this population. We are investigating therapeutic strategies to reverse the long-term risk of these diseases in a rat model of transient undernutrition followed by refeeding. METHODS/STUDY POPULATION: Thirty six female Fischer rats (3-months of age) were initially divided into 2 groups. Half were fed regular chow (CT) while the other half were severely food restricted (sFR) by 60% from 0-2 weeks (wks) followed by refeeding from 2-14 wks (sFR-Refed). These 2 groups were then subdivided and treated ± metformin (Met) from wk 7 to wk 12 (n=9/group). High precision ultrasound was conducted on live rats to assess heart and kidney function immediately after the sFR period ended (wk 2) and at the end of the study (wk 14). At the conclusion of the experiment, the rats were sacrificed and the histology of the kidney and heart tissues were analyzed in hematoxylin and eosin-stained sections. The protein to DNA ratio was also calculated in homogenates from these tissues. RESULTS/ANTICIPATED RESULTS: In sFR-Refed rats, cardiac output (CO), heart rate (HR) and renal artery blood flow (RBF) were decreased by 11 ± 1.5%#, 7.0 ± 6.0% and 22 ± 0.6%#, respectively, compared to control (CT) rats; #p<0.05. Mean glomerular diameter was reduced in the kidneys of sFR-refed rats compared to CT and this effect was attenuated by metformin treatment [(µm): CT, 406 ± 31; sFR-Refed, 383 ± 11, p<0.06; CT+Met, 393 ± 18; sFR-Refed+Met, 407 ± 18*]. Furthermore, the mean cardiomyocyte thickness was reduced in sFR-Refed rats compared to controls while metformin treatment prevented this effect [(µm): CT, 16.4 ± 3.6; sFR-Refed, 11.5 ± 2.3#; CT+Met, 16.4 ± 3.6; sFR-Refed+Met, 15.9 ± 3.2*]. #p<0.05 vs. CT, same treatment; *p<0.05 vs. Met, same diet; two-way ANOVA. DISCUSSION/SIGNIFICANCE: These findings have promising implications for metformin use to mitigate long-term impairments in heart and kidney structure and function in individuals who have experienced bouts of undernutrition earlier in life for either voluntarily (e.g., very low calorie dieting) or involuntary (e.g., very low food security) reasons.

OBJECTIVES/GOALS: Estimating kidney function for drug dosing poses safety and efficacy concerns with critical medications. This study aims to develop a pragmatic method for measuring kidney function, ensuring that critical clinical decision points based on kidney function are universally applicable to all patients, leading to improved health outcomes. METHODS/STUDY POPULATION: This is a single-dose pharmacokinetic (PK) study to evaluate the concordance between iopamidol- and iohexol-measured glomerular filtration rate (mGFR), as determined by their respective serum clearances, in a cohort of 24 adults with varying kidney function. Participants with estimated glomerular filtration rates (CKD-EPI eGFRcr) ranging from >30 to 120 mL/min will be recruited from the Michigan Medicine health system. Enrolled participants will be stratified into 3 kidney function groups based on conventual kidney dosing considerations. IV micro doses of iohexol and iopamidol will be administered, followed by blood sampling. PK analysis will be used to compare the clearance of these substances. The agreement between iohexol and iopamidol in measuring GFR will be assessed via bioequivalence analysis. RESULTS/ANTICIPATED RESULTS: We expect no statistically significant difference between iopamidol and iohexol CL due to the high similarity of iopamidol and iohexol molecular and PK properties. We also expect that the ordinary least square regression analysis of iopamidol mGFRand iohexol mGFR will show limited variability across GFR measurements. These expected results will support the use of iopamidol as a marker of mGFR and its interchangeability with the gold standard iohexol. DISCUSSION/SIGNIFICANCE: Addressing eGFR errors is crucial for accurately dosing critical medications. This study aims to develop a novel mGFR methodology that accommodates various kidney function levels. This will enable precision dosing and streamline clinical trials. It also eliminates biological variability, enhancing generalizability and health outcomes.

OBJECTIVES/GOALS: Our goal is to determine whether microplastic fibers (MPFs) provide signals for dendritic cell-induced Th2 polarization via epithelial-cell-derived thymic stromal lymphopoietin (TSLP). We seek to highlight a potential mechanism for MPF-induced airway toxicity associated with asthma exacerbation. METHODS/STUDY POPULATION: Primary human bronchial epithelial cells (NHBEs) were grown and differentiated at an air-liquid interface. Dyed and undyed polyester MPFs (14x45 µm) generated using a cryomicrotome were delivered to NHBEs through a custom designed mesh-hopper system. After the exposure period (6, 12, 24 hrs), cell viability was assessed using alamarBlue, and RT-qPCR was performed to determine mRNA expression of asthma associated genes (i.e., TSLP, IL-13, IL-33, etc.,) in NHBEs. Bulk mRNA-sequencing followed by bioinformatics will be performed to observe other plausible pathways tweaked by lung cell exposure to MPFs. RESULTS/ANTICIPATED RESULTS: Through gravimetric analysis, it was determined that the mesh-hopper system can achieve delivery efficiencies of at least 85% for as low as 500 fibers. Following exposure, results show polyester MPFs (500 - 1,000 fibers) exposed to NHBEs at multiple time points (6, 12, 24 hrs) did not result in a statistically significant decrease in cell viability. Treatment with 500 undyed MPFs resulted in a slight increase in TSLP expression at 6 hrs that decreased over time, whereas all other treatment groups resulted in TSLP downregulation. Similarly, 500 undyed MPFs resulted in an increase in IL-13 expression at both 6 and 12 hrs with all other treatment groups leading to IL-13 downregulation. We anticipate the RNA-seq results will show pro-inflammatory pathways are highly targeted following NHBE exposure to MPFs. DISCUSSION/SIGNIFICANCE: This study is one of the first to mechanistically assess the impact of MPFs on lung cells while simultaneously addressing the need for a reliable system that delivers MPFs to ALI cultures to better mimic inhalation and avoid inadequate resuspension of particles in liquid medium.

OBJECTIVES/GOALS: Quantitative Staff are an essential workforce for biomedical research. While faculty can engage with peers locally and through national organizations, similar opportunities are limited for staff and often do not meet their unique needs and interests. Creating a professional community is valuable for supporting and developing this workforce. METHODS/STUDY POPULATION: We established the Quantitative Scientific Staff National Network (QS2N2) with the mission to provide professional development and networking opportunities, and to serve as an information resource and advocate through the fostering of community among staff quantitative analysts at any career stage. The initial membership outreach was to all Biostatistics, Epidemiology, and Research Design (BERD) programs through members of ACTS BERD Special Interest Group (SIG). We created a Leadership Team and an Advisory Board consisting of staff and faculty biostatisticians with experience working as or managing staff to govern the network. A Core Planning Committee consisting of 15 members guides planning, implementation, and execution of network activities as operationalized through subcommittees. RESULTS/ANTICIPATED RESULTS: The network currently has 131 members from over 30 health science institutions. Subcommittees focused on Education and Training, Membership, Communication and Web Development, and Mentoring were created and are developing events, programs and infrastructure to further the network’s mission. Network events such as webinars will be offered quarterly; with our first event planned for Nov 3rd. Expansion and maturation of QS2N2 will be done through regular remote meetings where members can connect with peers at other institutions, engage in career development activities, and attend technical seminars. Additional membership outreach will seek to connect with staff in government and private sectors. DISCUSSION/SIGNIFICANCE: Knowledgeable, highly skilled collaborative analysts (e.g., biostatisticians, data scientists) are an essential workforce in clinical and translational science and health research centers.The QS2N2 will support professional development, engagement and growth of this critical workforce which is necessary to advance quality research.

OBJECTIVES/GOALS: Preeclampsia increases cardiovascular (CV) risk, likely via persistent endothelial dysfunction and angiotensin II type 1 receptor autoantibodies (AT1R-Ab). We aim to assess coronary endothelial function (CEF) and AT1R-Ab levels in postpartum preeclampsia with a hypothesis this mediates CV risk. METHODS/STUDY POPULATION: We prospectively enrolled age and CV risk factor matched postpartum women. Coronary MRI was performed at rest and with isometric handgrip stress, an endothelial dependent stressor. CEF was quantified as % stress-induced change in coronary cross-sectional area (%CSA) and in coronary blood flow (%CBF). AT1R-Ab was measured using a novel antigen capture enzyme-linked immunosorbent assay. RESULTS/ANTICIPATED RESULTS: Women with and without preeclampsia were similar in age (mean 32.7+5.0 years), BMI (mean 28.0+6.3 kg/m2) and race/ethnicity (58% White, 35% Black and 4% Hispanic). %CSA was lower with (-2.1+13.6) vs without preeclampsia (8.8+17.1), p=0.023. %CBF was also lower with (11.3 [-11.8, 25.2]) vs without preeclampsia (25.7 [-0.7, 62.9]), p=0.039. AT1R-Ab was higher among women with preeclampsia (p=0.029) and was inversely associated with %CBF (beta coefficient -4.6 [-8.9, -0.3], p=0.037) but not with %CSA. DISCUSSION/SIGNIFICANCE: Women with preeclampsia have elevated AT1R-Ab and impaired CEF demonstrated by insufficient coronary reserve with exercise. Coronary endothelial dysfunction and dysregulation of the renin-angiotensin pathway likely contribute to long-term CV risk and should be considered for targeted risk reduction.

OBJECTIVES/GOALS: Although the approval of immune checkpoint inhibitors (ICIs) revolutionized the treatment of metastatic breast cancer (BC), yet about 30% remain unresponsive. Since the potency of ICIs depends on the efficient presentation of tumor-specific antigens by cancer cells, compounds which increase such presentation could increase efficacy of ICIs. METHODS/STUDY POPULATION: A library of the ester and urethane derivatives of polyether ionophore antibiotic, monensin (MON) has been synthesized. MTT cell viability assays were performed on the panel of human and mouse BC cell lines, and non-cancerous breast epithelial cells to determine IC50 values of MON and its derivatives. Selectivity Indexes were calculated to identify the most selective compounds towards cancer versus non-cancer cells. Major Histocompatibility Complex (MHC) class I and II presentation and Programmed death-ligand 1 (PD-L1) expression have been determined using flow cytometry. Proteins involved in apoptosis, autophagy and immunogenic cell death were identified through immunoblotting. At least three biological replicates have been performed for each experiment. RESULTS/ANTICIPATED RESULTS: MON and several of its derivatives shown activity in nanomolar range against MDA-MB-231 human BC cell line. MON and its most potent derivatives significantly increased MHC class I and II presentation and downregulated the expression of PD-L1 in BC cell lines. DISCUSSION/SIGNIFICANCE: Present findings will lead to the development of new therapeutic approaches that can serve as single agents or be used in combination with existing ICIs for the treatment of metastatic BC. By pushing the boundaries of our understanding and developing new therapies, this research can make an impact in improving outcomes for patients with metastatic BC.

OBJECTIVES/GOALS: Numerous diseases, including AL amyloidosis, are due to expression of aberrant antibodies. Significant effort has gone into plasma cell toxic therapies with varying degrees of success, but no therapies preventing antibody synthesis have been developed. The goal of this study is to assess BiP targeting to prevent antibody secretion in plasma cells. METHODS/STUDY POPULATION: Using 4 multiple myeloma cell lines (KMS11, RPMI8226, ANBL-6, U266), we knocked down BiP expression with RnaseH dependent siRNA or subA toxin, a bacterial toxin that specifically cleaves BiP, and measured changes in unfolded protein and intracellular light chains by flow cytometry during drug induced ER stress created by the intracellular calcium depleting agent thapsigargin. BiP is the master regulator of the unfolded protein response (UPR), an ER stress pathway important for protein folding. BiP is also an ER resident protein folding chaperone important for proper antibody folding. We hypothesized that BiP downregulation will lead to decreased folded antibody in the cell, increased unfolded antibody and constitutive activation of the UPR. RESULTS/ANTICIPATED RESULTS: 1 to 4 hours after treatment with thapsigargin plus siRNA against BiP, levels of BiP are significantly decreased. The levels of intracellular light chains decrease, and the level of unfolded protein within the cells increases dramatically. Interestingly, in alignment with the UPR literature, 24 hours post treatment, these levels have normalized again in surviving cells. SubA treatment increased BiP expression by 4 hours, contrary to our hypothesis, and minimally increased unfolded proteins and minimally decreased intracellular light chains. We expect that further functional testing of antibody secretion by ELIspot assays will show decreased secretion of antibody with BiP siRNA treatment. Combination therapies with other UPR stressing agents may act synergistically to affect antibody production. DISCUSSION/SIGNIFICANCE: BiP knockdown reduces antibodies and boosts unfolded proteins. SubA toxin ineffectiveness likely stems from increased BiP due to feedback loops. Combining anti-BiP treatments with UPR stressing drugs like bortezomib may halt antibody synthesis and induce cell death. These findings support BiP as a viable drug target for antibody-related diseases.

OBJECTIVES/GOALS: LSD1 is a histone demethylase important in GBM regulation. Our goal is to design a therapeutic strategy for LSD1 inhibitors to meet clinical needs in GBM. Despite the abundance of LSD1 inhibitors, resistance emerges in GBM mouse models. We aim to understand the relevance of proliferative signaling pathways, such as MAPK, in LSD1 inhibitor resistance. METHODS/STUDY POPULATION: Following LSD1 knockdown in GBM cells, we determined differentially expressed genes using RNA-seq and gene set enrichment analysis (GSEA). Kinase signaling processes enriched for LSD1 expression were identified. Utilizing western blot, we assessed LSD1’s impact on MAPK signaling in patient-derived GBM stem cells (GSCs) and pediatric high-grade glioma cell models. Pharmacological evaluation of LSD1 involved five inhibitor candidates. Additionally, we explored LSD1 inhibition in combination with brain penetrant kinase inhibitors, osimertinib and ulixertinib, directed against the epidermal growth factor receptor (EGFR) and MAPK, respectively. The treatment combinations were assessed at multiple concentrations and analyzed using SynergyFinder. RESULTS/ANTICIPATED RESULTS: Pharmacological LSD1 inhibition after 24 hours induced increased phosphorylated ERK1/2 across multiple glioma cell lines. Concurrent LSD1 and EGFR/MAPK inhibition demonstrated improvedin vitro efficacy compared to individual agents. Notably, the combination of Iadademstat (ORY-1001) and osimertinib demonstrated the highest synergy score of 37.2 using the bliss synergy model in the GSC17s. Furthermore, 11 out of the 12 combination treatments tested had a synergistic relationship, with bliss synergy scores greater than 10. DISCUSSION/SIGNIFICANCE: Our study addresses the pressing need for novel therapeutic strategies in GBM. We leveraged pharmacological tools of LSD1 inhibition to determine how they could be used most effectively, revealing kinase inhibition as a promising strategy with demonstrated in vitro efficacy. Future efforts will focus on validating these findingsin vivo.

OBJECTIVES/GOALS: Minority faculty have inequitable access to information, professional development, and research resources. A structured research-mentoring program could help strengthen the research acumen of underrepresented (UR) faculty, provide a community, and support to ensure their success in becoming independent investigators. METHODS/STUDY POPULATION: The Translational Research Institute (TRI) STARs program aims to build a peer support community of UR in biomedical, clinical, behavioral and social sciences to support career development and research success. The program provides a structured peer support group with a 3-month grant training and development program and addresses issues of isolation often felt by UR faculty in academic settings. It encourages the development of innovative research ideas in a safe environment. This peer support group can also help improve confidence and self-efficacy in clinical and translational research development and execution by UR faculty. At the didactic program’s conclusion and seed grant application submission, STARs provides $10,000 as a TRI DEI Equity, Diversity, and Grantsmanship Expertise project. RESULTS/ANTICIPATED RESULTS: Since its launch in 2021, 11 scholars have enrolled in the program;three have fully completed the program, and all three have received subsequent grant funding. Four scholars have completed the didactic program and are in the process of using seed funding to collect initial data and working on initial publications. The remaining scholars are currently in the didactic program. Initial scholar satisfaction with the program is high: 100% reported satisfaction with their participation (Very Satisfied/Satisfied), and 100% agree the program provides adequate support to their research project (Strongly Agree/Agree). Overall, scholars reported an average increase in confidence of 7.9% in grantsmanship skills (Scale 0-10). The return on investment is 3106%, with over $1.9 million in subsequent funding. DISCUSSION/SIGNIFICANCE: Research shows diverse teams working together, capitalizing on innovative ideas, and distinct perspectives outperform homogenous teams. Our preliminary experience demonstrates success for the model. Additional, long-term support will be furthered developed to address additional challenges experienced by UR faculty across their careers.

OBJECTIVES/GOALS: The goal of this study is to develop a multi-centered Translational Studio model that can help in the development of quality translational studies using resources from four different institutional partners (University of Texas Medical Branch, Texas Southern University, University of Houston Clear Lake and Houston Methodist). METHODS/STUDY POPULATION: We conducted two rounds of four Futures Workshops for a total participation of 28 stakeholders from four different partners. Future Workshops were used to critique, envision, and articulate novel “futures” that can be achieved at least partly through design practices (Muller, 2002). In the first round of workshops, we asked participants about their institutions’ strengths, weaknesses, resources and investigator needs regarding the Studio. In the second round we asked about different studio models, pros and cons of each model and guiding principles for a studio. Alongside a pragmatic content analysis, multi-stage deductive and inductive qualitative analyses were used to understand people’s views on the future of a multi-institutional Clinical Trials Studio. RESULTS/ANTICIPATED RESULTS: The first-round workshops’ analysis described peoples’ goals for what the studio should be. The future desired studio was described as guide, matchmaker, initiator and advocate. The second-round workshops’ analysis discussed the pros and cons of a variety of possible models including, centralized, decentralized, and topic-specific (and allowed other suggestions) while also describing principles for the guidance of a studio. Here the analysis showed people wanted certain characteristics for the studio (i.e. effective, efficient, locally-responsive, consistent, etc.). They also prescribed four principles that a studio should be guided by: non-hierarchical partnership, user-centeredness, respect/collegiality, and sharing. DISCUSSION/SIGNIFICANCE: The future workshops were useful in developing a shared multi-institutional Clinical Trials Studio model that is planned to be deployed in 2025. Participants valued a studio that was both directly supportive to participants and played a role in creating or advocating for institutional resources and policy for research.

OBJECTIVES/GOALS: Empowering the Participant Voice (EPV) is a 6-CTSA Rockefeller-led collaboration to developcustom REDCap infrastructure to collect participant feedback using the validated Research Participant Perception Survey (RPPS), demonstrate its value in use cases, and disseminate it for broad adoption. METHODS/STUDY POPULATION: The EPV team developed data and survey implementation standards, and specifications for the dashboard and multi-lingual RPPS/REDCap project XML file. The VUMC built a custom At-a-Glance Dashboard external module that displays Top Box scores (percent best answer), with conditional formatting to aid analysis, and response/completion rates. Results populate site dashboards, and aggregate to a multi-site dashboard for benchmarking. Results can be filtered by participant/study characteristics. Sites developed individual use cases, leveraging local infrastructure, initiatives and stakeholder input. Infrastructure and guides were designed for dissemination through public websites. RESULTS/ANTICIPATED RESULTS: Five sites sent 23,797surveys via email, patient portal or SMS. 4,133 (19%) participants diverse in age, race, and ethnicity, returned responses. Sites analyzed their data and acted on selected findings, improving recruitment, communication and feeling valued. Aggregate scores for feeling listened to and respected were hight (>90%%); scores for feeling prepared by the consent process were lower (57-77%) and require action. Some groups experiences were better than others. Sites differed significantly in some scores. Dissemination of EPV is underway. Infrastructure and guides are downloadable free of charge, with advice from the EPV team. In 2023, a sixth site began piloting a lower literacy survey version and syncing data to the consortium dashboard. DISCUSSION/SIGNIFICANCE: The EPV RPPS/REDCap infrastructure enabled sites to collect participant feedback, identify actionable findings and benchmark with peers. Stakeholders and collaborators designed and tested local initiatives to increase responses and diversity, address disparities, and discover better practices.

OBJECTIVES/GOALS: The objective for this study was to evaluate the associations between weight stigma and symptoms of depression, anxiety, and binge eating following bariatric surgery. METHODS/STUDY POPULATION: Bariatric surgery is the leading evidence-based treatment for severe obesity; however, mental health challenges can compromise long-term improvements in quality of life. Weight stigma is a major contributor to mental health challenges for individuals with obesity generally; however, the role of weight stigma post-operatively after significant weight loss is poorly understood.148 patients underwent pre-bariatric surgery psychological evaluation and completed a follow-up study approximately 2 years after. Measures included the Stigmatizing Situations Inventory-Brief, Patient Health Questionnaire, Generalized Anxiety Questionnaire, and Binge Eating Scale. RESULTS/ANTICIPATED RESULTS: In regression models controlling for demographic covariates (sex, age, education, race), body mass index, and baseline measure of each outcome (e.g., depressive symptoms pre-surgery in models predicting depression post-surgery), weight stigma was independently associated with depression (p=.023), anxiety (p <.001), and binge eating (p=.008) symptoms post-surgery.Above and beyond weight, demographics, and pre-surgery measurements of mental health, weight stigma continues to influence mental health outcomes in the years following bariatric surgery. Despite weight loss after bariatric surgery, this data suggests the cumulative experiences of stigma and discrimination continue to negatively impact mental health. DISCUSSION/SIGNIFICANCE: Interventions for bariatric surgery patients must consider the effects of weight stigma, at both the societal and individual levels. Interventions countering stigma could optimize long-term quality of life and associated outcomes.

OBJECTIVES/GOALS: Historically, Latino farmworkers have lacked access to healthcare. 1 Telehealth promises to bridge this gap in hardly-reached populations. 2 We evaluated the impacts of ACTIVATE, a community-engaged project co-developed withcommunityp artnersAmplaHealth, and a local grower. METHODS/STUDY POPULATION: Mixed-methods outcome evaluation included attitudes survey, knowledge tests, attendance records, exit interviews, and participant observations. Attitudes survey, based on the Unified Theory of Acceptance and Use of Technology (UTAUT) model 3, measured Latino farmworkers’ telehealth acceptability. Pre/Post knowledge tests measured participant knowledge gained on telehealth and mental health services. Semi-structured exit interviewsidentifiedthe impacts of incentives, Promotora training, and health education curricula on participants and community partners. Structured participant observation as certained the level of participant engagement and Promotora facilitation skills. RESULTS/ANTICIPATED RESULTS: Results [https://drive.google.com/file/d/1jQpQdDM3dIR_PzMc1xXPh45Jvz8uBka6/view] On what aspects of the project worked well: “This project really helped us… to make it a priority, to do [health education] workshops. When I was hired, we went out to a few farms and shared information about our services, but it wasn’t anything hugely structured like what you proposed. We hadn’t done a whole lot of Promotora health education prior to this project.” -Ampla Health Administrator The most significant change observed: “Their attitudes… I feel that the very first session, I saw how they were more laid back, not really answering questions, just listening to us. And then the second one… they were more talkative and the very last one they were more comfortable sharing.” -Promotora DISCUSSION/SIGNIFICANCE: Attendence and participant engagement increased over time. Results from the evaluation point to greater telehealth acceptability among participants, increased health education capacity among Ampla Health, and farm worker cohesiveness at the workplace.

OBJECTIVES/GOALS: At UNC-Chapel Hill’s CTSA hub – the NC Translational and Clinical Sciences Institute (NC TraCS) – we conducted a participatory evaluation of a new community and patient advisory board (CPAB) to assess member experiences, and the outcomes and early impacts of their work on institutional programming related to equity and inclusivity in research. METHODS/STUDY POPULATION: NC TraCS staff conducted informal interviews with CPAB members to discuss how they envision success in their work, ideas for measuring progress towards their goals, and how they have seen similar work measured by others. These conversations guided the development of outcomes, indicators, and data collection methods for the CPAB evaluation plan. CPAB member satisfaction, experiences, and perceptions of accomplishments were assessed via an online survey. Concurrently, an Outcome Harvesting approach was used, through which NC TraCS staff retrospectively identified key outcomes of the CPAB’s work through team discussion of programmatic changes and review of internal documents and data. RESULTS/ANTICIPATED RESULTS: CPAB members (n=10) were highly satisfied with meetings, group dynamics, activities and accomplishments, and 90% of members felt that NC TraCS was very responsive to their feedback. Key outcomes included: 1) co-creating a shared vision, goals, and operational policies for the CPAB; 2) co-developing a training series for research teams about patient and community engagement; 3) disseminating best practices for co-developing advisory boards; 4) providing guidance to improve NC TraCS consultations, services, and resources related to enhancing equitable participation in research (e.g., developing an Equity in Research Framework); and 5) contributing to institutional initiatives related to diversity, equity, and inclusion (e.g., improving compensation processes for research participants and partners). DISCUSSION/SIGNIFICANCE: Evaluations of CPABs often focus on process measures, while assessments of outcomes and impacts are lacking. Our evaluation data highlight the early outcomes and value of a newly formed CPAB. Furthermore, our approach can inform the creation and evaluation of equity-focused advisory boards within other research institutions.

OBJECTIVES/GOALS: Annually, 1.5 million global patients receive maxillofacial reconstruction. The gold standard, involving bone particulate, lacks reproducibility. To improve this, we have developed a custom 3D-printable, porous cover-core design. This study optimizes the hydrogel core properties and growth factor (GF) release for enhanced bone regeneration. METHODS/STUDY POPULATION: Different ratios of Methacrylated Gelatin (GelMa), Methacrylated Alginate (AlgMa) and tricalcium phosphate (α²-TCP) were combined to optimize cell viability, GF sequestration and mechanical stability. Material characterization was performed using a rheometer to determine the viscoelastic properties of the blends. Release from disks loaded with FGF-containing PLGA microparticles was quantified with an ELISA kit. Furthermore, scanning electron microscopy (SEM) was conducted to quantify hydrogel porosity. In vitro studies were performed using NIH 3T3 murine fibroblasts in Corning Transwells while immunofluorescent, metabolic and osteogenic studies were performed in 96 well plates to investigate cell infiltration, cell adhesion, viability and differentiation, respectively. RESULTS/ANTICIPATED RESULTS: By adjusting the AlgGelMa ratio, we manipulated matrix properties. GelMa possesses excellent durability and cell adhesion due to intrinsic RGD-binding motifs. AlgMa enhanced swelling by 30%, growth factor sequestration by 50% in 24hrs, and matrix storage modulus without increasing the loss modulus which could cause cell migration away from the hydrogel. Varying the AlgGelMa ratio lowered pH, promoted cell infiltration, and reduced fibronectin accumulation. The addition of β-TCP is anticipated to improve cell differentiation towards an osteogenic lineage due to improved elastic modulus, calcium and phosphate ion concentration improving mineral deposition. DISCUSSION/SIGNIFICANCE: These findings suggest through the use of this composite, early cell infiltration can be increased and promoted due to FGF release, leading to increased osteointegration. Our porous cover-core design ensures efficient clot integration and early cell infiltration, enhancing osteointegration through FGF release.

OBJECTIVES/GOALS: Clinical and Translational Science Award (CTSA) hubs are launching D&I Science cores to provide resources and services to promote the translation of clinical evidence into practice. We developed a D&I Science Core strategic plan reflecting our research community’s needs by assessing Implementation Science (IS) competencies. METHODS/STUDY POPULATION: The Tufts CTSI D&I Science Core was launched in early 2023. To design services that meet research community needs, we conducted a survey and key informant interviews based on Padek etal.’s list of Implementation Science (IS) competencies. The competencies are organized into four domains (Definition, Background, and Rationale; Theory and Approaches; Design & Analysis; and Practice-Based Considerations) and categorized by expertise level (beginner, intermediate, advanced). Participants who had attended or expressed interest in a D&I interest group were asked via an email survey to rate their level of confidence in completing selected IS-related research activities, about their experience with IS research or practice, and the types of resources, services and training they desired. RESULTS/ANTICIPATED RESULTS: Twenty researchers (20/65, 31%) submitted survey responses and six researchers participated in in-depth interviews. Survey respondents felt most confident in engaging stakeholders in IS research and least confident selecting a model or framework for a study. Results suggest that researcher capacity building is needed to: • Understand IS models and frameworks and their approaches, strengths, and limitations • Select and use models and frameworks in studies • Assemble IS teams and prepare grant proposals Suggestions for resources, services, and training, include: • Customized education to address diverse needs, knowledge levels, and learning styles • Promotion of D&I Core consultations and grant support services • Sharing of successful proposals to help researchers learn how to apply IS methods DISCUSSION/SIGNIFICANCE: A strategic workplan for the D&I Science Core was developed and implemented to address the findings. Initial emphasis is on developing easily accessible resources and timely consultations for investigators new to IS needing to apply these methods in current grant proposals, while also providing training resources for deeper skill building.

OBJECTIVES/GOALS: The Translational Science Benefits Model offers an approach for evaluating the downstream health and social impact of research. Using the new Translating for Impact Toolkit of nine web-based tools, researchers can create free, secure accounts to plan, track, and demonstrate the impact of their work. METHODS/STUDY POPULATION: Development of the online toolkit includes 6 phases: 1) Review of existing tools, 2) Development of fillable PDF tool prototypes, 3) Pilot testing, 4) Development of web-based tools, 5) Usability testing, and 6) Refinement of web-based tools. First, we reviewed existing tools for measuring research impact. We then created prototypes of nine tools, published on the TSBM website, and pilot tested with researchers. Based on feedback and testing, we developed and launched web-based versions of the tools. We are currently conducting usability testing with researchers, which we will use to evaluate the ease-of-use and quality of the tools, identify areas for improvement, and refine the tools. RESULTS/ANTICIPATED RESULTS: Researchers can sign up for user accounts, create projects, invite collaborators and program administrators, and save progress as the complete the nine tools in the Translating for Impact Toolkit. The tools are divided into three steps: Plan (Roadmap to Impact, Benefits 2x2, Partner Mapper, and Team Manager), Track (Impact Tracker), and Demonstrate (Product Navigator, Case Study Builder, Impact Profile, and Dissemination Planner). The toolkit also includes a dashboard that provides a quick snapshot of translational impact for each project. The toolkit will help both individual translational scientists demonstrate the impact of their work and CTSA hubs evaluate impact of their projects. DISCUSSION/SIGNIFICANCE: The TSBM online toolkit is a free, secure, easy-to-use platform researchers can use to plan for, track, and demonstrate the impacts of their work. The toolkit provides a structured process that will help the next generation of scientists prioritize and promote translational impact in their work.

OBJECTIVES/GOALS: Caregivers often identify signs of autism in infancy but face multiple barriers when seeking specialized evaluations and subsequent services. This study sought to understand the experiences of families with early developmental concerns to identify acceptable and feasible strategies to support them during this period of uncertainty. METHODS/STUDY POPULATION: We interviewed 15 families participating in a larger longitudinal project developing telehealth assessments for infants with early developmental concerns. Interviews were conducted virtually following the final toddler-age assessment, and focused on caregivers’ experiences navigating early concerns, appropriateness of existing supports, and suggestions for future directions. Interviews were transcribed and coded across multiple passes, focusing on both phenomenological experience and frequency of specific supports mentioned. RESULTS/ANTICIPATED RESULTS: Core themes expressed across multiple included: (1) Uncertainty; (2) Navigating Supports; (3) Community and Connection; and (4) Information is Power. Caregivers also provided specific suggestions for addressing these areas. These included suggestions for parent coaching topics, modalities for sharing information with parents (e.g., group meetings, online modules), and research practices. DISCUSSION/SIGNIFICANCE: There have been recent efforts to develop pre-diagnostic interventions for infants, but few studies have investigated the needs and priorities of families during this period. Our approach can help bridge the gap between research and practice by identifying family priorities to target when developing interventions.