OBJECTIVES/SPECIFIC AIMS: The goal of this study is to use patient-centered qualitative techniques to determine what strategies caregivers use to cope with the stress of a child having recently (ie, within the past month) undergone surgical removal of a brain tumor. Results will eventually be evaluated and compared with results of quantitative measures of psychosocial risk and distress as well as demographic and medical characteristics. METHODS/STUDY POPULATION: All caregivers of patients with a newly diagnosed brain tumor requiring neurosurgery admitted to Children’s of Alabama (with English or Spanish-speaking parents) are eligible for enrollment. Participants are enrolled during their child’s initial hospitalization for surgical removal of a brain tumor. Approximately 1 month after hospital discharge, during a routine follow-up clinic visit, caregivers participate in a semistructured interview with a research assistant. Interview questions are used to obtain information about parent and family coping by asking first broadly about stress management over the previous month and then specifically about individual coping strategies. Semistructured interviews are audio recorded, transcribed, and coded for common themes. Interviews are coded by using specific words or phrases to describe various domains of the experience from the caregiver’s perspective. Each participant is given a study ID and study IDs are logged with each code word or phrase endorsed during the interview. RESULTS/ANTICIPATED RESULTS: To date, 22 caregivers have been enrolled and 15 have completed interviews. The most common coping mechanisms fall into the domains of active, avoidance, emotion-focused, and spiritual coping. Active coping consists of information seeking (eg, taking notes, internet research, asking questions), openly communicating emotions, celebrating small victories (eg, focusing on a good scan or test result, thinking that the diagnosis or treatment could have been worse), planning (eg, focusing on 1 d at a time), and maintaining normalcy (eg, maintaining extracurricular activities, returning to school if possible, continuing to see family and friends). Avoidance coping consists of evading discussions about emotions, withdrawal from family members, denial (eg, keeping a cancer diagnosis from the child), and avoiding seeing people or participating in activities. Emotion-focused coping consists of crying, laughing, and staying strong in front of the patient. In general, those who self-identify as coping poorly tend to be those who utilized more avoidance-focused coping strategies. Further, caregivers tended to identify active coping strategies (eg, taking notes, focusing on 1 appointment or treatment at a time) as the most helpful. DISCUSSION/SIGNIFICANCE OF IMPACT: It will be helpful for providers to more deeply understand the experience of caregivers whose children have recently undergone brain tumor resection and the strategies used to cope with the stress of the first month postsurgery. This information can be used to create standardized interventions for use during posthospitalization clinic visits. For example, if families continue to endorse that active coping mechanisms are the most helpful, providers can assist caregivers in developing these strategies (eg, uniformly provide notebooks and encourage caregivers to keep track of questions and appointment information, pair caregivers who are struggling with others who use more active coping strategies). Those utilizing more avoidance coping strategies may need more coaching and recommendations. A brief assessment could potentially be developed for caregivers dealing with this diagnosis, in order to quickly assess coping strategies and provide appropriate recommendations. Future analyses will determine whether initial coping strategies and adjustment are predicted by child age or medical information.

OBJECTIVES/SPECIFIC AIMS: A retrospective analysis was done at the Cardiovascular Center to evaluate reperfusion strategies, including stemi infarcts and non-stemi classified as stemi in a period of 2 years. METHODS/STUDY POPULATION: Review the records of stemi infarcts in a period of 2 years. RESULTS/ANTICIPATED RESULTS: In total, 101 cases were classified as stemi, but after strict analysis (time wise) 24 cases were non-stemi; 47% had inferior myocardial infarction and 38% an anterior myocardial infarction with a mean age of 65 years. All cases were immediately catheterized. Although the non-stemi, classified originally as stemi did not meet the time limit (<2 h) for cath. The stemi group (77 P.) 58 P. had angioplasty with stent implantation. 19 P. had an EF of 45% and remained that way during follow up. The rest of the P. the EF went up to 50% or more. The non-stemi group (24 P.) had angioplasty with stent implantation. The EF remained around 40% during follow up, which was the EF on admission. Fibrinolysis was given erratically. No changes were seen in the EF on follow up in the fibrinolytic group. DISCUSSION/SIGNIFICANCE OF IMPACT: This shows the importance of classifying the P. well between stemi and non-stemi. The time frame to catheterization should be kept as strict as possible, due to transmural infarcts, and catheterized in <2 hours to avoid deterioration of the left ventricular function and its consequences. This strict classification will save money to the institution when emergency catheterization is avoided in the non-stemi group.

OBJECTIVES/GOALS: Studies show a decrease in injury-related emergency department (ED) visitsduring COVID.There is a gap in the literature regarding the effect of the pandemic on breast injury-related ED visits. We aim to compare these visits pre- and post-COVID, and whether this subset reflects the same trends seen in overall injury-related ED visits. METHODS/STUDY POPULATION: A retrospective study of breast injuries was conducted between 2018 and 2022, using the National Electronic Injury Surveillance System. Patients were categorized into pre-COVID and post-COVID groups, for visits occurring before and after January 20, 2020. A total of 1077 breast injuries were stratified into pre-COVID (n = 444) and post-COVID (n = 633) groups. Clinical data on patient demographics, diagnosis, disposition, location, and alcohol use were collected. RESULTS/ANTICIPATED RESULTS: Mean age was significantly different: pre-COVID mean age was 37.29; post-COVID’s was 40.40 (p = 0.0338). >90% of patients were female (p = 0.4066). White patients accounted for 36.0% of pre-COVID visits and 47.2% of post-COVID; BIPOC patients were 32.88% and 31.75% respectively. There was significant difference between race and COVID groups (p = 0.0013). No significant differences were found when considering all diagnoses (p = 0.3841) or the top three diagnoses (other, contusions/abrasions, and burns/scald) (p = 0.6176). Incident location showed a weak evidence of association (α = 0.1), when including unrecorded data (p = 0.1365) and removing those entries (p = 0.0832). Alcohol use did not reveal a significant association (p = 0.2110). DISCUSSION/SIGNIFICANCE: There are more breast injuries reported post-COVID. No significant difference was identified in the types of injuries diagnosed, the location these injuries took place, and how these injuries were treated. However, the demographics (age, race) of patients seeking care were significantly different.

OBJECTIVES/SPECIFIC AIMS: To better understand African American (AA) parents and their adolescents perceptions towards the immunization neighborhood to improve HPV vaccination rates. METHODS/STUDY POPULATION: We conducted qualitative interviews among a purposive sample of 30 AA parent-child dyads. We engaged the community (community advisory boards, community organizations) in the design and implementation of this study. Before each interview, we provided participants a brief survey to assess acceptability of various vaccination settings (i.e., pharmacies, health departments, and schools). An inductive, qualitative content analysis approach was used to analyze the data, and a constant comparison method was used to compare codes for theme development. Descriptives (i.e., frequencies) were used to analyze survey data with the SPSS version 23 software. RESULTS/ANTICIPATED RESULTS: Findings demonstrate that many parents were willing to get their adolescents vaccinated at the health department (n=19) followed by the pharmacy (n=17). However, majority of parents were less willing to get their adolescent vaccinated at school (n=21). Mixed results were found for children with many having positive attitudes towards alternative settings (health department=21; pharmacy=14; school=16). Parents viewed the health department as being stigmatized and unclean for adolescent immunizations in general, while children were unsure of the difference between the health department and the medical home for the vaccine. Both parents and adolescents viewed the pharmacy as “too open” but would use it if a nurse administered the shot and had a good tracking system. Both also expressed strong feelings against school vaccinations, especially HPV vaccine shots. However, would consider for convenience or if administration was done by a nurse. DISCUSSION/SIGNIFICANCE OF IMPACT: Findings from this study provide intervention targets to improve access to HPV vaccination in alternative settings. It further demonstrates the importance of community engagement for the success of translational research, in which we will use it to disseminate this study’s findings. Ultimately, this study could play a role in shifting the traditional model of the HPV vaccine being provided solely in the medical home to improve HPV vaccination rates.

OBJECTIVES/SPECIFIC AIMS: Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) skin and soft tissue infections (SSTIs) are commonly seen in primary care, with recurrence rates that range from 16% to 43%, and present significant challenges to clinicians, patients, and families. This comparative effectiveness research study aims to develop and evaluate a home-based intervention implemented by Community Health Workers (CHWs) or “promotoras” to prevent recurrence of CA-MRSA in patients presenting to primary care with SSTIs and transmission within their households. This presentation will examine associations between wound microbiology, clinical presentation, and housing characteristics, including housing density and household surfaces contamination. METHODS/STUDY POPULATION: In partnership with 3 Community Health Centers and 3 community hospitals in NYC, this study will recruit patients (n=278) with confirmed MRSA SSTIs and their household members. Participants will be randomized to receive either a CHW/Promotora-delivered decolonization-decontamination intervention (based on the REDUCE MRSA trial) or usual care. The highly engaged stakeholder team finalized the intervention protocol, developed and implemented CHW and clinician training, and developed an online health portal application for data management and exchange. RESULTS/ANTICIPATED RESULTS: We have collected 923 isolates from 237 individuals, including 240 wound culture isolates and 683 surveillance culture isolates (nares, axilla, groin). MRSA and MSSA were found in 19% and 21.1% of wound cultures, respectively; 59.5% with MRSA+ wound culture had 1 or more MRSA+ surveillance culture; 67.8% with MSSA+ wound culture had 1 or more MSSA+ surveillance culture. Of those with MRSA or MSSA infections, 70% of subjects were male, with an average age of 37.9 (SD=15.9 y). The most frequent sites of infection were the leg (20%), axilla (18%), buttock (17%), and abdomen/torso (12%). There was no association between the location and type of infection (MRSA/MSSA) (p-value=0.09). The kitchen floor (14.05%) and bedroom floor (14%) were the most common surfaces contaminated with MRSA. These were also the most common surfaces contaminated with MSSA, which was recovered from 10.2% and 9.1% of kitchen floors and bedroom floors, respectively. For individuals with an MRSA or MSSA wound infection, there was an average number of 3.2 (SD=1.6) co-residents per household, and 36.5% of household members were colonized with either MRSA or MSSA. There is no association between household density (number of co-residents) and type of infection (MRSA/MSSA) (Fisher’s p-values=0.171 and 0.371, respectively). In households of participants with MSSA wound infections, the number of colonized sites is positively associated with the level of household MSSA contamination (p=0.027). Further analyses will examine the associations between molecular subtypes, wound location, household surface contamination and household member colonization and infection. DISCUSSION/SIGNIFICANCE OF IMPACT: This study aims to understand the patient-level and environmental-level factors associated with SSTI recurrence, surface contamination and household transmission, and to examine the interactions between bacterial genotypic and clinical/phenotypic factors on decontamination, decolonization, SSTI recurrence and household transmission. This study will evaluate the barriers and facilitators to implementation of home visits by CHWs in underserved populations, and aims to strengthen the evidence base for implementation of strategies to identify and reduce household reservoirs and then control SSTI recurrence and household transmission.

OBJECTIVES/SPECIFIC AIMS: This project will present the analysis assessing which of the admission criteria is a useful tool to predict completion of all program requirements METHODS/STUDY POPULATION: All admission criteria from graduates (2003-2016) will be analyzed. Outcomes will be measured according to the scholar’s performance during the two-year of studies and its success in completing on time all program requirements. Descriptive and inferential statistical analyses will be used to determine potential association in each criteria and in the total score. RESULTS/ANTICIPATED RESULTS: We expect that the PPC and total score will be correlated with a higher rate of successful outcomes. DISCUSSION/SIGNIFICANCE OF IMPACT: A systematic admission process should lead to timely program completion.

OBJECTIVES/GOALS: Supervision is a promising strategy for supporting high-fidelity implementation of evidence-based practices (EBPs) in substance use disorder (SUD) settings. In this study, we explore current supervision practices in community SUD programs and identify organizational and environmental factors that shape them. METHODS/STUDY POPULATION: We interviewed 25 leaders and counselors at 8 community SUD programs in Arkansas, and 16 leaders at external stakeholder organizations (e.g., regulators, payers, licensing boards). Interview guides were based on the i-PARIHS framework. Interviews were conducted on Zoom or phone, lasted ~1 hour, and were recorded and transcribed. Below we outline findings based on preliminary analyses; full thematic analyses will be completed before presentation. RESULTS/ANTICIPATED RESULTS: Participants generally recognized the importance of utilizing EBPs and supporting their use through supervision. Counselors professional backgrounds and training vary substantially, necessitating continuing education and supervision. However, different professional, licensing and regulatory standards create a complex web of requirements and practices. Supervisors typically require clinical experience, but are rarely trained in supervision. They are internal or external to the organization, and provide individual or group supervision. Supervisors most often rely on case summaries and chart reviews, sometimes on direct observations and role-playing, and rarely (one program) on session recordings. Supervision goals are broad, and while EBP use is encouraged, it is rarely the focus of supervision. DISCUSSION/SIGNIFICANCE: To enhance supervision in community SUD settings and improve implementation of EBPs, new supervision strategies need to fit the various norms, expectations, and standards (e.g., professional, regulatory) that characterize community SUD programs, their workforce, and their environments.

ABSTRACT IMPACT: This study will showcase the importance if incorporating patient stakeholders in the development of an interview guide for a women of color with uterine fibroids, an understudied population. OBJECTIVES/GOALS: Black women and Hispanic/Latinas report having greater symptom burden from uterine fibroids (UF), non-cancerous neoplasms, compared to White women. These disparities may be linked to cultural factors resulting in treatment delays. The objective of this study is to provide insights to barriers and facilitators to timely treatment. METHODS/STUDY POPULATION: In partnership with the Fibroid Foundation, a UF advocacy organization, we plan to conduct a virtual community engagement (CE) studio to serve as a first step for a pilot study with a national cohort of Black women and Hispanic/Latinas who receive treatment in the United States for UF. The studios will include a presentation about UF treatment options and a facilitated discussion. The CE team will use past research and constructs from Model of Improvement and Health Belief Model to develop materials for the studio. A qualitative researcher will guide the discussion, a note-taker will take notes, and they will thematically code the notes. The results will be used to create and implement a cross-sectional in-depth qualitative study with a national sample. RESULTS/ANTICIPATED RESULTS: We hypothesize that timely treatment will be impacted by cultural factors, such as health literacy in uterine fibroids and menstruation. We expect that detailed feedback from this national cohort will contribute to greater insight to the experiences of women of color with UF and address barriers and facilitators to treatment. We anticipate the anecdotes will provide information about the influence of culture in seeking treatment for UF. We will utilize this experience to understand the impact of a virtual CE studio in elucidating open discussion among women of color on a challenging and personal topic. DISCUSSION/SIGNIFICANCE OF FINDINGS: Using CE process with advocates and research partners attains a deeper understanding in the development of an interview guide to examine the cultural impact on the treatment of UF for women of color. Understanding cultural barriers and facilitators can help overcome treatments delays in UF along with other gynecological diseases.

OBJECTIVES/GOALS: Studies using Medicare data indicate that physical therapists (PTs) and physical therapist assistants (PTAs) are not providing falls prevention to at-risk older adults in rehabilitation. We aimed to identify PTs and PTAs knowledge and use of the Centers for Disease Control and Prevention’s STEADI fall prevention toolkit. METHODS/STUDY POPULATION: We conducted a cross-sectional survey distributed to a convenience sample of PTs and PTAs in the United States through email blasts and social media. Descriptive statistics were used to summarize the demographic characteristics of the respondents. Some categorical variables were combined to provide more meaningful classifications or due to small frequencies. We used independent samples t-tests for continuous data, and chi-square and Fisher’s Exact tests for categorical data to compare characteristics between respondents that do and do not conduct falls risk screenings.Frequency counts and percentages were used to summarize survey responses related to falls risk screening and knowledge/use of STEADI. SAS® version 9.4 was used for all statistical analyses. RESULTS/ANTICIPATED RESULTS: PTs and PTAs (N = 425) who responded to the survey and worked in clinical settings with older adults were included. Eighty-nine percent of respondents reported conducting clinical falls risk screening, yet only 51% were 'familiar’ to 'very familiar’ with STEADI. Twenty-two percent of respondents were not familiar at all with STEADI. Of the respondents who were 'very familiar with the STEADI (n = 132, 31.1%), 84.1% (n = 111) reported using STEADI in clinical practice. Seventy-six percent of respondents who use the STEADI implemented it by choice even though the majority (52.1%, n = 63) did not have it embedded in their workflow or documentation. DISCUSSION/SIGNIFICANCE: PTs and PTAs in the United States have some familiarity with and use STEADI in clinical falls prevention, and those who are very familiar with it use it by choice. Further research is needed to address the knowledge gap of STEADI and support PTs and PTAs providing falls prevention to older adults attending rehabilitation.

OBJECTIVES/GOALS: There is increased recognition that patients and community members are critical to creating impactful research. To this end the UCLA CTSI Community Engagement & Research Program modified an established multidisciplinary team science communication module to train academic-community research teams. METHODS/STUDY POPULATION: Community partners who have had previous experience in participatory research provided input such as limiting the emphases of individual academic introductions to group icebreakers (to level the playing field), reduced academic jargon to lay language, reducing the amount of text to key principles, and changed academic team scenarios for the team activity to represent community-academic teams. Academic partners articulated institutional barriers to integrating community into institutional systems. Iterative testing and modifications occurred through pilots with eleven teams (49 individuals). RESULTS/ANTICIPATED RESULTS: Embedding community partners in team science training involved creating a level playing field with less emphasis on academic credentials, using lay language in the didactic sessions and ensuring accessibility in all aspects of the training. An example of modifications: communication scenarios were read out loud by participants, which community partners felt were not inclusive of potential varying literacy levels and all partners may not feel comfortable reading aloud in a group setting. The vignettes were replaced with short videos of the scenarios with audio recordings. Several modifications were made the training’s team activity of the training module. DISCUSSION/SIGNIFICANCE OF IMPACT: Traditional academic team science training required significant modifications for an academic/community-partnered team to allow for optimal collaboration, inclusion, and strategically reduce the power dynamics that can naturally occur. Long-term followup to assess their effectiveness is needed.

OBJECTIVES/GOALS: The Community Research Liaison Model (CRLM) is a novel model to facilitate community engaged research (CEnR) and community–academic research partnerships focused on health priorities identified by the community. We describe the CRLM development process and how it is operationalized today. METHODS/STUDY POPULATION: The CRLM, informed by the Principles of Community Engagement, builds trust among rural communities and expands capacity for community and investigator-initiated research. We followed a multi-phase process to design and implement a community engagement model that could be replicated. The resulting CRLM moves community–academic research collaborations from objectives to outputs using a conceptual framework that specifies our guiding principles, objectives, and actions to facilitate the objectives (i.e., capacity, motivations, and partners), and outputs. RESULTS/ANTICIPATED RESULTS: The CRLM has been fully implemented across Oregon. Six Community Research Liaisons collectively support 18 predominantly rural Oregon counties. Since 2017, the liaison team has engaged with communities on nearly 300 community projects. The CRLM has been successful in facilitating CEnR and community–academic research partnerships. The model has always existed on a dynamic foundation and continues to be responsive to the lessons learned by the community and researchers. The model is expanding across Oregon as an equitable approach to addressing health disparities across the state. DISCUSSION/SIGNIFICANCE: Our CRLM is based on the idea that community partnerships build research capacity at the community level and are the backbone for pursuing equitable solutions and better health for communities we serve. Our model is unique in its use of CRLs to facilitate community–academic partnerships; this model has brought successes and challenges over the years.

OBJECTIVES/SPECIFIC AIMS: Early career researchers at Mount Sinai have access to a wide range of resources and support. It can, however, be challenging for new investigators to know where to find information and who to ask for help. To address this issue, an Emerging Investigators website was conceived to bring together resources, provide educational support and foster a community of early career investigators at Mount Sinai. In order to ensure this resource effectively meets the needs of this cohort of researchers, and to determine the scope and content of the proposed website, a series of focus group interviews were undertaken with early career researchers at various stages of their careers. The aims of these focus groups were to 1) explore the self-perceived challenges faced by early career researchers that could be addressed through education and / or support, 2) explore the self-perceived learning needs of early career researchers that are not currently being addressed at Mount Sinai, 3) determine the website content that early career researchers would find valuable to support them in their development. METHODS/STUDY POPULATION: A convenience sample of early career researchers at Mount Sinai were contacted for participation (N = 20). A total of 13 participants responded and three focus groups were conducted, one with the KL2 scholars (N=4), one with TL1 postdocs (N=4) and one with PORTAL students (N=5) during Spring 2018. Participants were initially asked to consider the challenges that early career researchers face. They were subsequently asked to consider which of these challenges they thought could be addressed through education or support. Participants were then asked to consider what they wished they knew more about in relation to research knowledge, skills or behaviors. Participants were finally asked to discuss the resources or support they thought would help them to manage the challenges or meet the learning needs they identified. The interview questions were semi-structured to allow the conversation to flow, and to allow the participants to discuss issues of importance to them. At the end of the discussion, participants were asked to rank their top priorities for inclusion in an Emerging Investigators website, up to a maximum of 3 per person. Focus group sessions lasted between 1 and 1.5 hours. All key points were captured by the participants on flip-chart paper and sticky notes. RESULTS/ANTICIPATED RESULTS: Interview data was transcribed and thematic analysis was used to identifying patterns or themes within the data. A theoretical thematic analysis was conducted, driven by the specific research questions. Each segment of data that was relevant to the research questions or captured something interesting was coded. These codes were examined and further grouped into six key themes that were consistent across all three focus groups. These themes were categorized as: Mapping the research pathway, Research skills, Personal development, Mentorship, Community of Practice and Opportunities at Mount Sinai. Within each of these themes, more specific codes align directly with learning needs for early career investigators at Mount Sinai. When asked to prioritize topics for inclusion in the website, the pre-doc PORTAL students selected research skills that included statistics, navigating the IRB and writing and publication, as well as mapping the research landscape at Mount Sinai. Both the post-doc TL1s and the KL2s also selected some research skills such as scientific writing and conference presentation, but also prioritized personal development and “soft skills” such as leadership, management, collaborating with others and finding a work-life balance. DISCUSSION/SIGNIFICANCE OF IMPACT: The themes articulated by the focus group participants have formed the basis for developing the Emerging Investigators website. Each of the key themes will be reflected in the learning and resources provided on the website. The prioritization of topics differed between groups, reflecting the different stages and levels of experience of these researchers. As a result, the website provides key learning and “top tips” suitable for all levels of early career researchers, but with links to further reading and resources for those at a more advanced level who are interested in learning more. In addition, the reported need for communication, collaboration and social interaction with peers and other researchers across Mount Sinai resulted in the addition of further web-based resources such as a discussion forum, a blog to feature research and provide a sounding board for research efforts, and a calendar of events targeted specifically at early career researchers. The focus groups provided much valued insight to underpin this project and ensure that a valuable resource is created that will meet the needs of early career researchers. The website is currently under development with a view to launch a pilot site in early 2019.

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: Overall response rates for metastatic uveal melanoma (UM), regardless of treatment modality, are less than 20%, highlighting an urgent need for novel therapies. Herein, we present a UM patient-derived organoid (PDO) biobank as a novel platform for translational research. METHODS/STUDY POPULATION: Patients with primary choroidal or ciliochoroidal UM undergoing enucleation from 7/1/2019-9/30/2022 were invited to enroll. Tumor tissue was harvested within 30 minutes of globe removal. Cells were isolated using the human tumor isolation kit and gentleMACS dissociation protocol (Miltenyi Biotech). PDOs were placed on Cultrex-coated multiwell plates and cultured in supplemented RPMI media. DNA and RNA were isolated using kits from Zymo Research. Exon-enriched libraries and RNA were sequenced using an Illumina HiSeq 4000. Immunohistochemistry (IHC) assessed the following histone post-translational modifications: H3K4me1/3, H3K27Ac, and H3K27me. RESULTS/ANTICIPATED RESULTS: PDOs were established in 19 of 20 (95%) attempted cases. BAP1 protein expression was retained (n=7) or lost (n=12) in the primary tumors, with matching phenotype confirmed in PDOs. In 9 sequenced cases, a driving mutation was present in GNAQ (n=4), GNA11 (n=4), or CYSLTR2 (n=1). Morphology ranged from spindle-like to epithelioid clusters, mimicking primary tumor histopathology. Pigmentation increased with time in culture. Growth in culture was slow, and 1-2 months were allotted prior to passaging in most cases. Whole exome and RNA-sequencing confirmed distinct molecular profiles, with differential staining of active chromatin marks by IHC. DISCUSSION/SIGNIFICANCE: A biobank of primary UM PDOs with unique morphological and molecular characteristics has been established. These will serve as a model of human disease to facilitate translational research and investigate personalized treatments for patients with UM.

ABSTRACT IMPACT: By identifying clear gaps in our knowledge of racial and ethnic disparities in antibiotic-resistant infections, this research is informing the design of (a) community-based interventions and (b) patient-centered research studies that we are currently leading to address these disparities and improve human health. OBJECTIVES/GOALS: Antibiotic resistance (AR) is widely considered to be the next global pandemic. As with COVID-19, the potential for AR to disproportionately impact racial/ethnic minorities is a major concern. Our goal was to identify gaps in knowledge of AR disparities in order to inform the types of interventions that might be most appropriate to address this. METHODS/STUDY POPULATION: We reviewed the literature to examine evidence of racial/ethnic disparities in (a) infections with the most concerning drug-resistant bacteria in the United States, and (b) underlying social-economic or behavioral factors that could contribute to such infections. We searched PubMed and Google Scholar to identify studies published in English between August 1973 - August 2020. We used keywords that included: antibiotic resistance, antibiotic-resistant infections, antibiotic-seeking behavior, prescription/non-prescription antibiotic use, antibiotic education, or health literacy AND race, ethnicity, or socioeconomic status. We screened all abstracts to identify US-based studies that assessed (a) or (b) above. RESULTS/ANTICIPATED RESULTS: We identified 11 studies investigating racial/ethnic disparities for 5 of the 17 drug-resistant bacteria flagged in the CDC’s 2019 Antibiotic Resistance Threats Report. Black, Hispanic, and lower-income individuals were found to be at higher risk of some community-acquired antibiotic-resistant infections. We identified multiple factors that may contribute to disparities in AR-related morbidity and mortality, including reported differences in antibiotic use, higher likelihood of living in crowded/multigenerational homes, more frequent employment in potentially high exposure settings (e.g. slaughterhouses), lower health literacy, and more frequent underlying comorbidities, which increases risks for hospitalization and subsequent acquisition of drug-resistant infections. DISCUSSION/SIGNIFICANCE OF FINDINGS: Given the small number of studies on this topic, educational interventions that aim to raise awareness of this issue must target not only the public but also researchers. Community-based interventions that seek to address disparities in ‘antibiotic resistance literacy’ among minority and underserved groups could be particularly impactful.

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.