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.

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/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/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/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.

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.

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/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/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: 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.

OBJECTIVES/GOALS: The extent that Clinical and Translational Science Award (CTSA) programs offer resources accessible online for training in community-engaged research (CEnR) core competencies is unknown. This study cataloged CEnR resources accessible online from CTSAs and mapped resources to CEnR core competencies. METHODS/STUDY POPULATION: Eight domains of CEnR core competencies were identified: knowledge/perceptions of CEnR; personal traits necessary for CEnR; knowledge of/relationships with communities; training for performing CEnR; CEnR methods; program evaluation; resource sharing and communication; and dissemination and advocacy. A systematic review of CEnR resources accessible online from CTSAs was conducted between July 2018 and May 2019. Resource content was independently reviewed by two reviewers and scored for inclusion of each domain of CEnR core competencies. Domain scores across all resources and inter-rater reliability in scoring domains were assessed using descriptive statistics and Cohen’s kappa coefficients. RESULTS/ANTICIPATED RESULTS: Overall, 214 resources available from 24 CTSAs were eligible for full review. Scoring discrepancies for at least one domain within a resource initially occurred in 51% of resources. “CEnR methods” (50.5%; 108 of 214) and “Knowledge of/relationships with the community” (40.2%; 86 of 214) were most frequently addressed and “Program evaluation” (12.1%; 26 of 214) and “Dissemination and advocacy” (11.2%; 24 of 214) were least frequently addressed domains. Additionally, challenges were noted in navigating CTSA websites to access CEnR resources, and CEnR competency nomenclature was not standardized. DISCUSSION/SIGNIFICANCE OF IMPACT: Our findings guide CEnR stakeholders to identify CEnR resources accessible online and gaps to address in CEnR resource development. Standardized nomenclature for CEnR competencies is needed for effective CEnR resource classification. Uniform organization of CTSA websites may maximize navigability. CONFLICT OF INTEREST DESCRIPTION: In addition to the funding information listed previously (see above), within the last three years, R.J. Piasecki has been employed as: Project Coordinator, CEnR Online Learning Project, Johns Hopkins University School of Nursing (Current) Temporary Employee (Doctoral Student Intern), Michigan State University Institute for Health Policy (Current) Clinical RN, Intrastaff at the Johns Hopkins Health System (Past) Research Data Analysis Assistant, Maryland Institute for Emergency Medical Services (Past - contracted)

OBJECTIVES/GOALS: Inflammation-promoting exposures, including hyperglycemia and inflammatory cytokines, are common in the development and progression of multiple cancers. Here, we determine if high glucose drives the dysregulation of XRCC1, changing BER/SSBR capacity, and increasing resistance to DNA damaging agents. METHODS/STUDY POPULATION: Here, we acutely exposed cell lines models with 30 mM glucose to mimic hyperglycemic changes and monitored the gene and protein expression of STAT3 and XRCC1. We selected the osteosarcoma cell line U2OS, with high STAT3 activation before glucose challenge, and the non-tumorigenic human embryonic kidney cell line HEK293T, with low STAT3 activation before glucose challenge, to dissect the role STAT3 plays in dysregulating DNA repair. We also examined changes in STAT3 occupancy at the XRCC1 promoter following glucose challenge using chromatin immunoprecipitation (ChIP). Finally, we measured changes in the sensitivity to the alkylating agent methyl methanesulfonate (MMS) induced by the glucose challenge using cell survival and DNA strand break analysis. RESULTS/ANTICIPATED RESULTS: High glucose challenge increases the phosphorylation and activation of STAT3 and subsequently increases XRCC1 gene and protein content in the cell. Acute high glucose activated STAT3, driving the subsequent expression of XRCC1 in U2OS and HEK293T cells through increased STAT3 occupancy at the XRCC1 promoter. High glucose also reduced sensitivity to MMS, increasing cell survival. The most significant increase in resistance to MMS occurred in the HEK293T, which also showed the largest increase in XRCC1 protein expression following the glucose challenge. Increased survival correlated with the faster resolution of DNA strand breaks in glucose-challenged cell lines. DISCUSSION/SIGNIFICANCE: This work has identified a novel regulatory mechanism by which high glucose drives the expression of XRCC1 through STAT3 activation, increasing DNA repair and resistance to the DNA damaging agent MMS. These data suggest dietary choices induce sustained XRCC1 expression and may contribute to chemoresistance and poor survival outcomes in cancers.

OBJECTIVES/SPECIFIC AIMS: Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) skin and soft tissue infections (SSTIs) recurrence ranges from 16% to 43% and presents significant challenges to clinicians, patients, and families. The number of emergency department visits for SSTIs increased from 1993 to 2005 from 0.48 to 1.16 ED visits per 100 US residents (95% CI 0.94 to 1.39; p<0.001); high safety-net status EDs saw a 4-fold increase in visits. The CA-MRSA Project (CAMP2) comparative effectiveness research (CER) study aims to evaluate a home-based intervention implemented by Community Health Workers (CHWs) or “promotoras” to prevent recurrence and transmission of CA-MRSA in primarily low-income, minority patients presenting to primary care with SSTIs. The intervention disseminates and implements methods found effective in the REDUCE MRSA trial. The present analysis was conducted using publically available data set to characterize the national patterns of healthcare utilization for treatment of SSTIs. METHODS/STUDY POPULATION: An analysis was conducted using data downloaded from the CDC National Ambulatory Medical Care Survey (NAMCS) and the CDC National Hospital Ambulatory Medical Care Survey (NHAMCS) from 2012 (most recent data available) to evaluate the addition of Emergency Departments (EDs) as compared to Ambulatory Care as recruitment sources for a clinical trial to reduce CA-MRSA SSTI recurrence and household transmission. “Low-income” population was defined using “Expected Source of Payment” categories “Medicaid” and “Uninsured,” and ICD-9-CM dermatologic diagnosis codes for SSTIs and ICD-9-CM Procedure Codes for Incision and Drainage (I&D) were used to define a visit for SSTI treatment. RESULTS/ANTICIPATED RESULTS: In all patients, I&D was performed at a higher rate in EDs as compared with the ambulatory care setting (49.57 vs. 1.44 per 10,000 US residents in Medicaid and Uninsured; 44.48 vs. 5.24 per 10,000 US residents in all other insurance types). Nationally, low-income patients are 4 times more likely to have I&D procedure performed (OR 4.05, 95% CI 0.614–26.759, p<0.0001) and 5 times more likely to be diagnosed with an SSTI (OR 5.10, 95% CI 2.987–8.707, p<0.001) in the ED setting. DISCUSSION/SIGNIFICANCE OF IMPACT: These results confirm that low income patients seek primary care for SSTIs in both EDs and ambulatory care, such as Federally Qualified Health Centers (FQHCs). This also confirms the trend we have experienced in FQHCs in NYC, many of whom refer patients to the ED for the I&D procedure, and those patients return to the FQHC for follow-up. Thus, the most comprehensive test of using CHWs to disseminate and implement the findings from the REDUCE MRSA trial would engage both EDs and Ambulatory Care/FQHCs for patient identification and recruitment.