OBJECTIVES/GOALS: Learners will:

• Identify social structures that serve as root causes of health disparities

• Critically evaluate the ways in which racism, culture, and power perpetuate disparity

• Use critical reflection to shape their research and advocate for institutional change

METHODS/STUDY POPULATION: The Integrated Translational Health Research Institute of Virginia (iTHRIV) Health Equity curriculum provides a lens for participants to view health disparities, social structures that create and perpetuate disparities, and the path to a more equitable future. This longitudinal workforce curriculum incorporates the principles of critical race theory (CRT), including: race as a social construct, structural determinism, intersectionality, and the social construction of knowledge. Learners gain practical experience through facilitated group discussions and critical reflection of their own work including research question design, recruitment, dissemination, and enhancing the faculty pipeline. RESULTS/ANTICIPATED RESULTS: To measure the impact of the curriculum, we will evaluate learners’ participation in mentoring activities for persons from underrepresented backgrounds; participation in local and national diversity and inclusion efforts; engagement in community-based research; ability to account for implicit bias and power imbalances in their research design, including in recruitment and retention; and share research findings with community members and research participants. Evaluation strategies will include quantitative and qualitative methodologies. DISCUSSION/SIGNIFICANCE OF IMPACT: There is growing recognition of the impact of racism on the development and perpetuation of health disparities. Public health critical race praxis (an adaptation of CRT) is emerging as a theoretical framework to empower researchers to challenge the status quo in order to achieve health equity.

OBJECTIVES/GOALS: We leverage the disparate incidence of Ewing sarcoma (ES) between European (EUR) and African (AFR) ancestry to study ES tumorigenesis in iPSC-derived cells from donors with a range of AFR ancestry via functional / molecular profiling. Integrated multi-omics analysis furthers explore local regulatory networks in pursuit of novel drug targets of ES. METHODS/STUDY POPULATION: In our pilot, eight induced pluripotent stem cell lines were obtained, differentiated into neural crest cells, and then transduced with a lentivirus expressing GFP-2A-EWS/FLI1. We compared wild type (WT) to EWS-FLI1-induced cells and then compared cell survival, gene expression, and EWS-FLI1 binding differences at varying levels of EUR / AFR ancestry admixture. We will build on this pilot data by expanding the number of cell lines and measuring chromatin state. Subsequently we will refine our understanding of the relationships between local ancestry, epigenetic and gene expression changes, and phenotype in tumor progression via integration of multi-omics datasets. Our systems genomics approach will utilize directed local regulatory networks in a Bayesian structure learning framework. RESULTS/ANTICIPATED RESULTS: Induction by EWS-FLI1 resulted in gene expression changes enriched in known ES gene sets. Higher %EUR ancestry correlated with prolonged maintenance of EWS-FLI1. We identified thousands of ancestry-linked changes to gene expression and EWS-FLI1 binding. Eighty of these genes are both differentially expressed and differentially bound based on AFR ancestry admixture level and may be some of the early critical targets that initiate the cascade of molecular changes in ES. We will identify novel drug targets, with potential cross functional use of known drugs. Once we have developed directed local regulatory networks, we will use them to test in silico potential perturbations due to small molecules or novel drugs and predict expression changes. DISCUSSION/SIGNIFICANCE: With a limited number of cell lines, we identify 80 ancestry-linked candidate loci for functional validation through genome engineering. As EWS-FLI1 itself has proven elusive to direct targeting, studying its immediate downstream effects has the potential for establishing new druggable biologic pathways for treatment of ES.

Methods/Study Population: We partnered with a local urban public school district to access school records for K5-5th grade students (N = 16, 528) in the district during the 2023–2024 school year. Students were matched to teachers and their SELC instruction records. Number of SELC lessons received over the school year was evaluated a predictor of discipline referrals and suspensions. Mixed effects zero-inflated negative binomial regression controlled for classroom- and school-level variation and the left-shifted distribution of disciplinary outcomes. Moderators were student race/ethnicity and gender. Covariates included age, economic disadvantage, special education status, days absent, and school characteristics including number of discipline referrals and suspensions per student and percent SELC completion. Results/Anticipated Results: We found that the number of SELC lessons predicted significantly fewer referrals for chronic disruption (β = −0.21, p < 0.001). Referrals for disorderly conduct, fighting, and chronic disruption were most common. On average per student, there were 1.44 (SD 1.49) referrals, 0.28 (SD 0.53) suspensions, and students received 11 (SD 9) of 20 total SELC lessons over the school year. However, SELC was 90% less effective for African American students, 80% less effective for Hispanic students, and not at all effective for Asian students compared to non-Hispanic White students in reducing chronic disruption referrals. SELC was also more effective for female students compared to male students for reducing chronic disruption referrals and not effective for reducing fighting referrals or suspensions among male students. Discussion/Significance of Impact: SELC had an inequitable impact on reducing chronic disruption referrals by race, ethnicity, and gender. The groups impacted tended to have fewer chronic disruption referrals compared to non-Hispanic White students, which may have contributed to this finding. However, the degree of difference suggests a need to improve equitable impacts of SELC.

ABSTRACT IMPACT: Strengthening investigator and community engagement to improve human health OBJECTIVES/GOALS: Community Engagement is one of the 14 core competencies for CT research defined by the CTSA Education Core Competency Work Group. To meet this, the UMN CTSI created the Community Mentor for Scholars Program with goals to: 1) train Scholars to engage stakeholders; and 2) provide community with formal mentoring training and linkages to researchers at UMN. METHODS/STUDY POPULATION: The CM Program was implemented over 12 months and includes four components. One, Scholars were trained in stakeholder identification and working with a community mentor (CM) through two seminars presented by expert faculty and staff. Two, CMs were identified, recruited, and matched with Scholars through a collaborative effort of our CTSI Education and Community Engagement cores. Three, Scholars and CMs learned about the program from a 2-hour Kick-Off event. Four, CMs and Scholars each completed four online modules developed through an NCATS administrative supplement. Scholar-CM pairs met at least four times to plan and hold a bi-directional ‘Community Conversation’ with an audience of key stakeholders convened by the CM. The CM Program was evaluated through in-person interviews. RESULTS/ANTICIPATED RESULTS: In 2019-2020, CTSI initiated the pilot program with four KL2 Scholar - CM pairs. Two pairs did not complete the program due to time pressures, a parental leave, and the COVID-19 pandemic. Feedback from the two Scholar - CM pairs was positive, specifically:

CMs reported the training modules were useful, resulting in better understanding of CTSI research programs and increased capacity to mentor

Scholars felt the interactions with CMs positively impacted their future research

Mentors supported experiential learning, offered insight on community perspectives, and successfully facilitated community engagement principles. DISCUSSION/SIGNIFICANCE OF FINDINGS: The second cohort launched in late 2020 with inclusion of TL1 Scholars. They will be matched with CMs in spring 2021. After Cohort 2 completion, the program design and materials will be updated based on evaluation results from scholars and mentors and then will be piloted with select CTSAs before sharing across the CTSA consortium.

OBJECTIVES/SPECIFIC AIMS: Research on social determinants of health (SDHs) in type 2 diabetes have largely examined disease etiology rather than severity. To find factors associated with complications, we investigated socio-demographics, healthcare access, and healthcare utilization in individuals with type 2 diabetes with respect to related comorbidity. METHODS/STUDY POPULATION: Community health workers assessed 8494 participants for type 2 diabetes (n=939; 11%) through HealthStreet, a community-engagement model implemented in North Central Florida. Comorbidities were defined as neuropathy, retinopathy, high cholesterol, hypertension, and kidney failure. We conducted multivariate analyses to test the association of socio-demographic factors and comorbidity status. RESULTS/ANTICIPATED RESULTS: Of 939 members with type 2 diabetes, 164 (17%), 272 (29%), 370 (39%), and 133 (14%) reported having 0, 1, 2, and 3+ comorbidities, respectively. There is a smaller proportion of African-Americans reporting 3+ comorbidities compared with other comorbidity groups (p=0.003). Those with more comorbidity are less employed (p<0.0001) and are more likely to have Medicare/Medicaid (p=0.03) than those without comorbidity. Those with no comorbidity are more likely to be uninsured compared to those with comorbidity (p=0.0297). Adjusting for age, race, gender, and BMI, those that have at least 1 comorbidity are 1.4 times more likely to be food insecure (p=0.004) and are 1.9 times more likely to have seen a doctor in the past 12 months (p=0.002) compared to those without comorbidity. DISCUSSION/SIGNIFICANCE OF IMPACT: Although there is complexity among the relationships between SDHs and diabetic comorbidity, results suggest significant sociodemographic and healthcare-related disparities among individuals living with type 2 diabetes. Members with more comorbidity utilize healthcare, but are more likely to be food insecure among other factors. Those with no comorbidity are least likely to see a physician, which could imply a gap in the care continuum. This analysis gives insight into the importance of efficient diabetes management, focused on disparities in economic stability and healthcare access and utilization.

OBJECTIVES/SPECIFIC AIMS: To build a multisite de-identified database of female adolescents, aged 12–21 years (January 2011–December 2012), and their subsequent offspring through 24 months of age from electronic health records (EHRs) provided by participating Community Health. METHODS/STUDY POPULATION: We created a community-academic partnership that included New York City Community Health Centers (n=4) and Hospitals (n=4), The Rockefeller University, The Sackler Institute for Nutrition Science and Clinical Directors Network (CDN). We used the Community-Engaged Research Navigation model to establish a multisite de-identified database extracted from EHRs of female adolescents aged 12–21 years (January 2011–December 2012) and their offspring through 24 months of age. These patients received their primary care between 2011 and 2015. Clinical data were used to explore possible associations among specific measures. We focused on the preconception, prenatal, postnatal periods, including pediatric visits up to 24 months of age. RESULTS/ANTICIPATED RESULTS: The analysis included all female adolescents (n=122,556) and a subset of pregnant adolescents with offspring data available (n=2917). Patients were mostly from the Bronx; 43% of all adolescent females were overweight (22%) or obese (21%) and showed higher systolic and diastolic blood pressure, blood glucose levels, hemoglobin A1c, total cholesterol, and triglycerides levels compared with normal-weight adolescent females (p<0.05). This analysis was also performed looking at the nonpregnant females and the pregnant females separately. Overall, the pregnant females were older (mean age=18.3) compared with the nonpregnant females (mean age=16.5), there was a higher percentage of Hispanics among the pregnant females (58%) compared with the nonpregnant females (43.9%). There was a statistically significant association between the BMI status of mothers and infants’ birth weight, with underweight/normal-weight mothers having more low birth weight (LBW) babies and overweight/obese mothers having more large babies. The odds of having a LBW baby was 0.61 (95% CI: 0.41, 0.89) lower in obese compared with normal-weight adolescent mothers. The risk of having a preterm birth before 37 weeks was found to be neutral in obese compared with normal-weight adolescent mothers (OR=0.81, 95% CI: 0.53, 1.25). Preliminary associations are similar to those reported in the published literature. DISCUSSION/SIGNIFICANCE OF IMPACT: This EHR database uses available measures from routine clinical care as a “rapid assay” to explore potential associations, and may be more useful to detect the presence and direction of associations than the magnitude of effects. This partnership has engaged community clinicians, laboratory, and clinical investigators, and funders in study design and analysis, as demonstrated by the collaborative development and testing of hypotheses relevant to service delivery. Furthermore, this research and learning collaborative is examining strategies to enhance clinical workflow and data quality as well as underlying biological mechanisms. The feasibility of scaling-up these methods facilitates studying similar populations in different Health Systems, advancing point-of-care studies of natural history and comparative effectiveness research to identify service gaps, evaluate effective interventions, and enhance clinical and data quality improvement.

OBJECTIVES/GOALS: To describe how the Community Engagement (CE) Program at the Michigan Institute for Clinical & Health Research (MICHR), a Clinical & Translational Science Award (CTSA) site at the University of Michigan, is adopting human-centered design (HCD) to advance the science of community engagement in translational research and CE’s programmatic efforts. METHODS/STUDY POPULATION: The MICHR CE Program supports academic-community partnerships to transform translational research across the state of Michigan. As the team aims to better engage partners to help guide the direction of their work, CE is collaborating with MICHR’s Design and Innovation Core to incorporate human-centered design (HCD). HCD is an approach that prioritizes the needs, values, and perspectives of direct users during the creation of a new product or service. The MICHR team created interactive HCD activities for two statewide retreats to elicit feedback from community and academic members on ways to enhance community-engaged research (CEnR). Retreat participants worked on a variety of problems, such as barriers to partnering and defining impact for CEnR. These activities generated authentic, contextual, and multi-view data captured in various artifacts for systematic analysis. RESULTS/ANTICIPATED RESULTS: In the first retreat, a HCD activity had participants reflect on their own barriers to partnering in research and potential solutions. In the second retreat, an HCD activity facilitated participants interviewing each other on their views of the impact in CEnR. Results from the first activity identified a set of common barriers to CEnR, some related to partnership formation, communication, and partner equity, among others. These led the CE Program to specific programmatic efforts, such as designing a statewide partnership platform, hiring a communication program manager, and sponsoring community partners to join national conferences. The second retreat activity produced rich data to identify overlaps between different perspectives to inform how impact can be defined and measured in CEnR. DISCUSSION/SIGNIFICANCE OF IMPACT: HCD activities provide means to include community and academic members in the science of CEnR. They allow systematic ways to gather information directly from the diverse set of current or prospective partners of community engagement programs about their needs, experiences, and values, which can be translated to programmatic innovation.

OBJECTIVES/GOALS: The COVID-19 pandemic limited family caregivers’ in-person visits to their loved one’s healthcare appointments, and many switched to phone and video calls with their loved one’s healthcare providers. We sought to determine the relationship between virtual communication with their loved one’s healthcare providers and caregiver’s mental stress. METHODS/STUDY POPULATION: This research utilizes cross-sectional retrospective data from the National Study of Caregiving (NSOC) Round VI (June 2021 – January 2022), a nationally representative cohort of caregivers of Medicare enrollees ages 65+. Caregivers reported the frequency of contact with their loved one’s healthcare providers and the healthcare provider’s rated helpfulness. Univariate, bivariate, and multivariate analyses will be performed in Stata to characterize how communication frequency between caregivers and their loved one’s healthcare providers may be associated with outcome variables including symptoms of anxiety and depression, as measured by the Generalized Anxiety Disorder-2 (GAD-2) and Patient Health Questionnaire-2 (PHQ-2) scales. RESULTS/ANTICIPATED RESULTS: Analysis is ongoing. We anticipate that this research will help in determining significant symptoms of anxiety and depression as measured by the GAD-2 and PHQ-2 scales amongst caregivers according to their virtual communication use. In addition, we anticipate that results may vary based on sociodemographic characteristics including gender, age, race, ethnicity, socioeconomic status, and level of education. Other possible covariates that might be associated with varying levels of stress in using virtual communication include caregiver’s health status and comfort with technology. DISCUSSION/SIGNIFICANCE: This research is important as many caregivers cannot attend their loved one’s healthcare appointments in-person, like in situations of geographic distance or inflexible work hours. Further, study results may identify stress disparities among caregiver sociodemographic groups for future targeted intervention.

OBJECTIVES/SPECIFIC AIMS: 1.Assess changes in clinical research workforce landscape at Duke 2.Optimize and evaluate efficacy of a tier advancement process for clinical research career progression at Duke 3.Implement CRP engagement as a change management mechanism for workforce innovation METHODS/STUDY POPULATION: We evaluated 857 clinical research positions at Duke to understand changes in the workforce (demographics, numbers in each position and tier) since implementing the tier advancement process in 2016. To understand the efficacy of the tier assessment process, data from a subset of this population (n=84) who underwent the advancement process was examined for success rate. Individual employees and their managers were surveyed to understand their perception of the advancement process and identify areas for improvement. We also describe implementation of multiple mechanisms of community engagement to manage expectations around the tier advancement process and to provide opportunities for employees to self-manage their career planning, including portfolio planning and leadership opportunities. RESULTS/ANTICIPATED RESULTS: Whereas the clinical research workforce has grown by 5.5% since tiering began (2016, n=810; 2018 n=857). Nearly 13% of that growth has been in managerial or senior positions (2016, n=111; 2018 n=127). Distributions across job classifications changed only slightly, representing realignment of positions with study-level responsibilities over department-level responsibilities. Notably, clinical research nurses (CRNC & CRNC Sr.) was the only category including tiered and non-tiered positions to drop overall numbers between 2016 (n = 136) and 2018 (n=115), representing a shift in the workforce from research nurses to research coordinators. General demographics (gender, age) remained largely the same. A total of 359 positions have been hired during this time frame, nearly half of which were entry-level positions (175/359): 47 of these positions represent expansion of the workforce. Of 359 new hires since 2016, 271 currently still work in one of the research roles. Of the 84 employees who underwent the tier advancement process, 84% (43/51) succeeded in tier 2 advancement, 70% (14/20) succeeded in tier 3 advancement (CRC, CRNC, and regulatory coordinators), and 77% (10/13) of research program leaders (RPLs) succeeded in achieving tier two, which is the highest tier for this group. Fifty-five employees (65%) and 32 managers responded to a voluntary feedback survey. Overall confidence in the process improved in both groups from 2016 to 2018, most notably with managers. Both groups indicated a 10 hour reduction (employees = 35hr, 2016 and 25hr 2018; managers 25hr, 2016 and 15hr 2018) in time required to complete the tier advancement process. DISCUSSION/SIGNIFICANCE OF IMPACT: The use of objectively-assessed competencies is an important step in the development of a workforce. By 1) maintaining alignment with industry standards for competencies, 2) upholding high standards, and 3) offering a consistent approach to career growth, Duke is working to develop and maintain a workforce that supports high quality research. Since the implementation of standardized job classifications and competency-based tier advancement, the positions have undergone rigorous competency-based needs evaluation. This leads to better matched jobs to study needs as well as increased standardization across the clinical research workforce. We believe that the subtle workforce shifts represent alignment of our positions with the business needs of our clinical research enterprise. Additionally, approximately 15% of our clinical research workforce has taken advantage of the opportunity to advance their own careers. We have made significant improvements in the following tier advancement processes: standardization of assessments, scoring guides, and modes; changes from LMS to a REDCap delivery of the knowledge assessments; streamlined the utilization of electronic documentation; and additional guidance for employees and managers regarding portfolio inclusions. These improvements have increased satisfaction and acceptance with the advancement process and were made possible through strategic communication across the workforce. Regular town hall meetings and focus group feedback sessions have included the clinical research community in discussions of WE-R initiatives and provided a much-needed feedback loop for process improvement and change management. Moreover, inclusion of WE-R discussion in our Research Professional Network events has provided opportunities to discuss career advancement strategies as well as volunteer opportunities to grow and demonstrate leadership competencies.

Objectives/Goals: This project (1) assesses provider behavior at the Galveston Secure Against the Fentanyl Epidemic (G-SAFE) Clinic in providing evidence-based care for underserved patients in our community and (2) implements evidence-based anti-stigma intervention in local health care. Methods/Study Population: The efficacy and impact of G-SAFE on healthcare utilization, health outcomes, and patient satisfaction will be determined. Evaluations assessing provider behavior will be made across at least 25 clinic patient visits, taking note of medical students, clinicians, and health providers’ interactions with patients related to decision-making, care plan creation, and communication. Health provider discussion groups will provide essential data in understanding the successful management of SUDs, management of safety and risk, and how best to pilot and assess interventions that promote greater trust-building and a harm-reduction approach to clinical care for patient empowerment and positive outcomes. Results/Anticipated Results: Observations in the clinic will be turned into interventions to improve diagnostics and therapeutics for SUD medical care and behavioral change. We will recruit 40 medical students (with/without exposure to UTMB’s free clinics) as well as 20 clinicians in the G-SAFE Clinic, Emergency Medicine, and Primary Care. Baseline stigma will be measured with the Medical Condition Regard Scale and the Drug and Drug Problems Questionnaire alongside measures of care approaches. The data collected and the educational intervention for medical students and clinicians will make a positive impact on the lives of those affected by SUDs and serve as a model for future interventions on a larger scale. Discussion/Significance of Impact: Health provider’s SUDs stigma undermines both care quality, patient empowerment, and recovery success. Addressing provider stigma is crucial for necessitating a shift toward collaborative, responsive, and creative clinical decision-making to tackle the ethical challenges posed by the opioid crisis.

There is a known disparity in clinical trial enrollment of rural-dwelling residents in the United States, largely due to financial constraints and travel burden. A big data study of an Intermountain West rural-serving healthcare system reported strong retention rates of historically underrepresented populations with adapted approaches. This exploratory qualitative descriptive study describes the lived experience and perceptions of eleven rural residents who participated or were interested in clinical trials from this healthcare system. Thematic analysis of interviews identified co-existing dualities between culture and traditional trial models, which suggest adapted designs are necessary to achieve opportunity equity in rural regions.

Retrospective case studies of initiatives supported by the National Institutes of Health’s Clinical and Translational Science Award (CTSA) hubs can be used to identify facilitators and barriers of translational science. This case study investigates how a CTSA Expanded Access program adapted to changing FDA guidance issued in 2020 to support clinicians’ treatment of COVID-19 patients in Michigan. We studied how this program changed throughout the pandemic to support physicians’ requests for remdesivir, convalescent plasma, and other uses of unapproved drugs and novel medical devices. A protocol for retrospective translational science case studies of health interventions developed by CTSA evaluators was used for this case study. Data collection methods included seven interviews and a review of institutional data, peer-reviewed publications, news stories, and other public records. The barriers identified include evolving guidance, misalignment of organizational operations, and the complexity of the research infrastructure. The facilitators of translation include collaboration between research and care teams, increasing engagement with a broad network of supporters, and ongoing professional development for research staff. The findings of this case study can be used to inform future investigations of the principles underlying the translational process.

OBJECTIVES/SPECIFIC AIMS: (1) Develop a concept map of ideas from diverse stakeholders on how to best improve training programs. (2) Assess the degree of consensus amongst stakeholders regarding importance and feasibility. (3) Identify which ideas are both important and feasible to inform policy and curricular interventions. METHODS/STUDY POPULATION: Concept mapping is a 4 step approach to data gathering and analysis. (1) Stakeholders [pediatricians (peds), MH professionals (MHPs), trainees, parents] were recruited to brainstorm ideas in response to this prompt: “To prepare future pediatricians for their role in caring for children and adolescents with mental and behavioral health conditions, residency training needs to...”. (2) Content analysis was used to edit and synthesize ideas. (3) A subgroup of stakeholders sorted ideas into groups and rated for importance and feasibility. (4) A large group of anonymous participants rated ideas for importance and feasibility. Multidimensional scaling and hierarchical cluster analysis grouped ideas into clusters. Average importance and feasibility were calculated for each cluster and were compared statistically in each cluster and between subgroups. Bivariate plots were created to show the relative importance and feasibility of each idea. The “Go-Zone” is where statements are feasible and important and can drive action planning. RESULTS/ANTICIPATED RESULTS: Content analysis was applied to 497 ideas resulting in 99 that were sorted by 40 stakeholders and resulted in 7 clusters: Modalities, Prioritization of MH, Systems-Based, Self-Awareness/Relationship Building, Clinical Assessment, Treatment, and Diagnosis Specific Skills. In total, 216 participants rated statements for importance, 209 for feasibility: 17% MHPs, 82% peds, 55% trainees. There was little correlation between importance and feasibility for each cluster. Compared with peds, MHPs rated Modalities, and Prioritization of MH higher in importance and Prioritization of MH as more feasible, but Treatment less feasible. Trainees rated 5 of 7 clusters higher in importance and all clusters more feasible than established practitioners. DISCUSSION/SIGNIFICANCE OF IMPACT: Statements deemed feasible and important should drive policy changes and curricular development. Innovation is needed to make important ideas more feasible. Differences between importance and feasibility in each cluster and between stakeholders need to be addressed to help training programs evolve.

OBJECTIVES/GOALS: To identify the role of sialoglycans in the mechanisms underlying cancer-associated fibroblast-derived exosomes (CAFEX) immuno-regulatory properties. The central hypothesis is that CAFEX manipulates the immune response to allow immunoevasion and glycomic approaches can identify the signaling factors involved. METHODS/STUDY POPULATION: Cancer associated fibroblasts (CAFs) were isolated from primary head and neck tumors, expanded, characterized and cryopreserved prior to experimentation and isolation of CAFEX. Sialoglycan expression was determined using lectin-specific staining of cells and bead-captured CAFEX in combination with flow cytometry analysis. Siglec expression and expression of M2-macrophage markers were also determined by flow cytometry analysis and cytokine bead arrays. Inhibition studies involved either the enzymatic removal of cell-surface sialoglycans or alternatively, a specific small molecule analog inhibitor of sialoglycan transferases. RESULTS/ANTICIPATED RESULTS: Both CAFs and CAFEX expressed abundant levels of cell-surface sialoglycans. CAFEX induced an M2-macrophage phenotype in primary monocytes, based on surface marker expression and cytokine secretion profiles. The induction of the M2 phenotype in macrophages was attenuated upon the removal of sialoglycans from the surface of CAFEX either by enzymatic removal or via a small molecule inhibitor. CAFEX were also able to directly bind members of the Siglec family, which are sialoglycan specific lectin receptors expressed on immune cells, including macrophages. DISCUSSION/SIGNIFICANCE: Collectively, these studies suggest that surface presentation of sialoglycans by CAFEX may induce an immunosuppressive phenotype in monocytes/macrophages. Consequently, this may be a novel mechanism by which cells within the tumor bed facilitate immunoevasion during tumor progression.

Objectives/Goals: This study aimed to explore Puerto Rican adolescents’ mental health experiences, focusing on risk and protective factors, and cultural perspectives on mental health. Methods/Study Population: Three focus groups were conducted: two with 20 adolescents aged 12 to 18 years of both genders and one with five adults who work with adolescents. Data were analyzed using interpretative phenomenological analysis. Results/Anticipated Results: The majority of participants in both groups of adolescents identified five key themes: social pressures, barriers to discussing mental health, the impact of social media, coping strategies, and institutional interventions. The adult focus group highlighted adolescent mental health problems, support systems, family and social factors, the church’s role, and recommended interventions. Discussion/Significance of Impact: The findings emphasize that social and familial pressures, mental health stigma, and social media significantly impact adolescent mental health. Coping strategies, such as sports, art, and nature, were also identified. These themes underscore the need for safe, supportive spaces, and targeted approaches to address youth mental health.