OBJECTIVES/GOALS: Few preclinical models exist to study how tumors transition from prolonged stable disease ('equilibrium') to progressive disease ('escape'). We characterized a new murine tumor model the exhibits such behavior, and sought to identify and validate the role of unique tumor-infiltrating immune cell subsets in this process. METHODS/STUDY POPULATION: We evaluated growth of NPK-C1 (originally LM7304; received from Dr. Cory Abate-Shen at Columbia University), a cell line developed from spontaneous prostate cancer lung metastases in NPK mice (Nkx3.1CreERT2/+Ptenflox/floxKrasLSL-G12D/+R26R-LSL-YFP/+), in immune competent (C57BL/6) and immune deficient mice (J/Nu). We determined the role of CD4 and CD8 T cells in regulating the 'equilibrium to escape’ growth dynamics of NPK-C1 via in vivo cell depletions at key inflection points of tumor growth. To deeply profile the immune contexture of NPK-C1 at these inflection points, we developed a 28-color immunophenotyping panel for use on a Cytek Aurora spectral flow cytometer. We performed dimensionality reduction and clustering analyses on these data using tSNE and FlowSOM algorithms within FlowJo (v10.6). RESULTS/ANTICIPATED RESULTS: We found that activated CD4 effector T cells are enriched in regressing NPK-C1 tumors, highlighting a role for CD4 T cells in antitumor immunity. CD8 T cells are also important for NPK-C1 control; specifically central memory-like cytotoxic CD8 T cells. Depletion of either CD4 or CD8 T cells during the equilibrium phase of NPK-C1 growth confirmed the role of these cells in antagonizing NPK-C1 escape. Tregs as a whole were counterintuitively enriched in regressing tumors, however high dimensional analysis reveals their significant phenotypic diversity, with a number of Treg subpopulations enriched in progressing tumors. In the myeloid compartment, we found that iNOS+ DC-like cells are enriched in regressing tumors, while CD103+ DCs are associated with late stage tumor progression. DISCUSSION/SIGNIFICANCE: In total, these analyses of the NPK-C1 model provide novel insights into the roles of lymphoid and myeloid populations throughout key phases of tumor/immune co-evolution, and highlight a role for multi-dimensional flow cytometry-based analyses to more deeply understand immune cell dynamics in the tumor microenvironment.

ABSTRACT IMPACT: NJ ACTS provides mentored coaching in NIH grant writing for early stage investigators. OBJECTIVES/GOALS: Launching an independent academic careers requires the ability to effectively communicate the purpose and impact of biomedical research in order to obtain extramural funding. We sought to develop and evaluate an interactive grant writing group of junior faculty and senior postdoctoral fellows mentored by trained coaches. METHODS/STUDY POPULATION: Participants meet monthly for 1 hour to peer review Specific Aims pages for grant applications to NIH and private foundations. Sessions are moderated by two senior faculty trained as coaches by the National Research Mentoring Network. Participant grant submission and review of the program are collected annually. RESULTS/ANTICIPATED RESULTS: From 2019-2020, 15 faculty and 2 postdoctoral fellows participated in the grant writing group with an average of 5.7 participants each month. Over the year, participants submitted 53 grant applications (68% submitted to NIH with the majority being R21 or R01 grant mechanisms). Half of grants submitted were discussed during peer review sessions. Of the grants reviewed, 42% were funded or near/below the funding payline. Using a 5-point Likert scale, participants highly rated the quality of coaching (mean/SD: 4.9 ±0.2), time discussing their research (mean/SD: 4.5 ±0.8), and the input from other participants (mean/SD: 4.5 ±0.5). DISCUSSION/SIGNIFICANCE OF FINDINGS: In conclusion, a monthly meeting of junior investigators hosted by two grant writing coaches is an effective means to receive peer review of grant application aims and support submissions for extramural funding.

OBJECTIVES/SPECIFIC AIMS: Women with pulmonary arterial hypertension (PAH) exhibit superior right ventricular (RV) function and survival compared with men, a phenomenon attributed to poorly understood cardioprotective effects of 17β-estradiol (E2). We hypothesize that E2, through ERα, attenuates PH-induced RV dysfunction by upregulating the pro-contractile and pro-angiogenic peptide apelin. This ERα-mediated increase in apelin is mediated by the myocardial remodeling effector bone morphogenetic protein receptor 2 (BMPR2). METHODS/STUDY POPULATION: ERα, BMPR2, and apelin were measured (western blot) in RVs from patients with PAH-induced RV failure and in RV homogenates from male or female Sprague-Dawley rats with sugen/hypoxia (SuHx) or monocrotaline (MCT)-induced PH. H9c2 rat cardiomyoblasts and cardiac endothelial cells were stressed with TNF-α (10 ng/mL) or staurosporine (50 nM)±E2 (100 nM; 24 h). ERα-, BMPR2-, and apelin-dependence were evaluated by siRNA (5 pM). Downstream apelin target and pro-survival factor ERK1/2 expression was measured (western blot). p<0.05 by ANOVA was considered significant. RESULTS/ANTICIPATED RESULTS: ERα correlated positively with BMPR2 and apelin expression in SuHx-RVs and human RVs. Treatment of SuHx-PH rats with E2 or ERα agonist increased RV BMPR2 and apelin, whereas RV apelin was decreased in E2-treated hypoxic ERα knockout mice (p<0.05), but not in ERβ knockout mice. In H9c2 cells, E2 or ERα agonist attenuated TNF-α- or staurosporine-induced decreases in BMPR2, apelin, and phospho-ERK1/2 (p<0.05 for all endpoints). E2 protection was lost in presence of siRNA directed against ERα, BMPR2, or apelin (p<0.05). ERα was necessary for E2-mediated increases in BMPR2, apelin, and ERK1/2, and BMPR2 was required for the E2-mediated increase in apelin (p<0.05 for siRNA vs. scramble). ERα, BMPR2, and apelin protein was increased in decompensated human RVs but downstream phospho-ERK signaling was disrupted. DISCUSSION/SIGNIFICANCE OF IMPACT: E2, via ERα, increases BMPR2 and apelin in the failing RV and in stressed rat cardiomyoblasts. The E2-mediated increase in apelin is BMPR2-dependent and likely occurs through direct binding of ERα to the BMPR2 promoter. Harnessing this E2-ERα-BMPR2-apelin axis during RV compensation may lead to novel, RV-targeted therapies for PAH patients of either sex.

OBJECTIVES/GOALS: This study aims to assess associations over time between several area-based indices of concentration at the extremes and COVID-19 hospitalization and death in Los Angeles County, from January 2020 to June 2023. These measures reflect concentrations of racial/ethnic and economic segregation at the census tract level. METHODS/STUDY POPULATION: Indices of concentration at the extremes (ICEs) for economic segregation, racial/ethnic segregation, and a combination of the two were constructed for each Los Angeles County (LAC) census tract, using 2015-2019 ACS data. The index ranges from -1 to 1 and is the number of advantaged households (HH) minus the number of disadvantaged HH over the total number of HH measured. Economic segregation is HH income over $100,000 vs. below $25,000 per year and racial/ethnic segregation defined as White and Non-Hispanic vs. non-White or Hispanic HH. The distribution of index scores was divided into quintiles (Q1-Q5) for all LAC census tracts. Age-adjusted hospitalization and death rates were derived at the census tract level by quarter (QTR) based on Los Angeles County Department of Public Health surveillance data. RESULTS/ANTICIPATED RESULTS: Age-adjusted hospitalization and death rates were consistently higher across all quarters in Q1 (most deprived) vs. Q5 (most privileged) for all ICE measures. For ICE of economic segregation, the age-adjusted hospitalization and death rate ratios between Q1 and Q5 were 2.12 (range: 1.32 - 4.15; peak 2020 QTR2) and 2.02 (range: 1.46 - 3.21; peak 2021 QTR1), respectively. For ICE of racial segregation, the age-adjusted hospitalization and death rate ratio between Q1 and Q5 was 2.03 (range: 1.08 - 3.95; peak 2020 QTR3) and 1.77 (range: 1.03 - 2.80; peak 2021 QTR1). The ICE of economic/racial segregation combined was the highest, with averages of the age-adjusted hospitalization and death rate ratios between Q1 and Q5 being 2.26 (1.16 - 4.43; peak 2020 QTR2) and 1.99 (range: 1.22 - 3.32; peak 2021 QTR1). DISCUSSION/SIGNIFICANCE: This study assesses the impact of geographic segregation based on indices that quantify the concentration of both deprivation, privilege, and racial/ethnic group, demonstrating that segregation and economic deprivation are consistently associated with higher rates of age-adjusted hospitalization and death from COVID-19 in LAC.

OBJECTIVES/SPECIFIC AIMS: To create prevention strategies targeting ARA and CDA, it is critical to educate and mold adolescent recognition, behavioral intentions, and attitudes regarding healthy dating relationships. Thus, the purpose of this study was to examine if high school students’ recognition of ARA, the students’ behavioral intentional to intervene during ARA episode of someone they know, and the students’ attitudes about the importance of healthy relationship serve as a protective factors against experiencing ARA. Aim 1: Do baseline (T1) recognition, behavioral intentions, and attitudes serve as protective factors against experiencing ARA in high school students at 3-month follow-up (T2)? Aim 2: Do baseline (T1) recognition, behavioral intentions, and attitudes serve as protective factors against CDA in high school students at 3-month follow- up (T2)? METHODS/STUDY POPULATION: To examine the relationships between recognition, behavioral intentions, and attitudes of ARA and CDA, a secondary analysis using a descriptive correlational design was used to analyze electronic survey data from a large randomized controlled parent study. The parent study consisted of 1,011 high school students ages 14 to 19 years who sought health service through one of eight school-based health clinics in California. This secondary analysis consisted of 819 students, with 640 (78.1%) female, 178 (21.7%) males, and 1 (0.2%) transgender participant. There were 42 (5.1%) Caucasians, 141 (17.2%) Asians, 218 (26.7%) African Americans, 313 (38.2%) Hispanics, 42 (5.1%) American Indians/Alaskan Natives, and 63 (7.7%) students who responded multi-racial. To measure recognition of ARA, a 10-item, 5-point Likert scale was used with responses ranging from 1=“not abusive” to 5=“extremely abusive” (Cronbach’s a = 0.85). To assess behavioral intentions to intervene, a 5-item, 5-point Likert scale was used to ask participants how likely they would be to stop the ARA behavior if they witness a peer perpetrating ARA with responses ranging from 1=“very unlikely” to 5=“very likely” (Cronbach’s a = 0.89). A 6-item, 3-point Likert healthy relationship tool measured participants’ attitudes regarding healthy relationship with responses ranging from 1=“not important” to 3=“very important”. Both ARA and CDA were assessed using a “yes/no” response choice for the lastthree months. To account for the hierarchical nature of the data analysis, a binary logistic regression was used in SPSS 24. To take into account the clustering coefficients of the eight different school clinics and as well as the parent study’s intervention and control groups, these clusters were examined as co-variates. Sex, race, and age were included as covariates, also. RESULTS/ANTICIPATED RESULTS: The relationship status of high school students consisted of 262 (32.0%) who were single, 97 (11.8%) who were going out, dating, or hooking up with more than one person, 423 (51.7%) who were seriously dating one person, and 37 (4.5%) who were not sure. At 3-month follow-up assessment, 111 (13.6%) of high school students experienced ARA, and 476 (58.1%) experienced CDA. The mean recognition of ARA score was 3.90 + 0.67, mean behavioral intentions score was 4.00 + 0.83, and mean attitudes score was 2.54 + 0.37. When examining the full ARA model including all three predicators controlling for the demographics and group assignment, none of the predictor variables were significant (p>0.05) in predicting ARA in high school students. Also, all three predictors were not significant in predicting ARA in the main effects model. When examining the full CDA model, with no interaction, all three predictors were significant. Recognition had 0.784 decrease odds (95% CI = 0633-0.971, p = 0.026) of predicting CDA. However the odds of CDA increase non-linearly up to the mean (2.537709) for the attitudes variable after which the odds then decreases non-linearly. The odds of CDA is increasing non-linearly up to 3.073913 for the behavioral intention variable after which the odds then decrease non-linearly. DISCUSSION/SIGNIFICANCE OF IMPACT: Adolescence is typically a time of exploration, transition, and social development. Researchers should investigate the efficacy of ARA and CDA prevention programs that focus on recognition, behavioral intentions, and attitudes to educate adolescents on healthy relationships. Results showed that behavioral intention to intervene and attitudes about healthy relationship can serve as protective factors against CDA. From our data, more students experienced CDA compared to ARA. Thus, it may by useful to recognize the use of technology as a social force within the adolescent culture in defining adolescents’ experiences of healthy relationships and potential experience of CDA.

OBJECTIVES/GOALS: The goal of this project was to develop and evaluate a pilot mentor training program for clinical research professionals. This project presents an evidence- and theory-based mentoring program that has been developed, implemented, and evaluated for this group of translational research professions. METHODS/STUDY POPULATION: The curriculum for the program was designed for aspiring mentors and aligned with the topics of existing Entering Mentoring curriculum for translational workforce (Pfund, Branchaw & Handelsman, 2015). Eleven experienced CRPs participated in the pilot training program. The training was delivered in two-hour meetings over eight weeks. Qualitative e-mail interviews and a validated mentoring competency assessment (Fleming et al., 2013) and mentor role assessment (Dilmore, 2010) tool were used for process and outcome evaluation. Cases studies specific to the CRPs work environment were developed and used to facilitate discussions throughout the training. RESULTS/ANTICIPATED RESULTS: Pre- and post-training scores for mentoring competency assessment were compared across six sub-indexes. Paired t-tests showed a significant difference for the maintaining effective communication competency, p = 0.0202. Comparisons of individual items also showed positive changes in the promoting professional development competency, p = 0.0161). Qualitative assessment revealed that most mentor trainees recognized a distinction between a mentor and a supervisor or on-the-job-trainer. Furthermore, most have been informal mentors without a formal role assignment, the need for ongoing mentoring, and potential of mentoring networks. DISCUSSION/SIGNIFICANCE OF IMPACT: CRPs is a diverse group of research support professionals who may hold the roles of research study coordinators, research nurses, regulatory and compliance specialists. Tailored mentoring can provide essential infrastructure for ongoing professional development and support talent retention.

OBJECTIVES/SPECIFIC AIMS: Trichuris trichiura, is a leading cause of chronic colitis worldwide, resulting in growth stunting, anemia, and cognitive deficits, predominately in children. Our long-term goal is to develop a vaccine against T. trichiura. Both T. trichiura and the closely related Trichuris muris release excretory/secretory (ES) macromolecules from the stichosome organ, which facilitates intracellular invasion into the cecum. We exploited the high degree of genetic sequence homology between T. trichiura and T. muris to evaluate T. muris stichosome proteins as vaccine candidates. METHODS/STUDY POPULATION: Through immunological screening of the T. muris stichosome cDNA library and T. muris ES macromolecules generated in culture, we identified, cloned, and expressed several vaccine candidates. In ranking these antigens, we selected the most promising recombinant proteins, WAP and CAP-1, and vaccinated AKR mice to evaluate the immunogenicity and efficacy of our candidate. In addition, we collected 240 serum samples in the T. trichiura endemic region of Honduras to measure the recognition of WAP and CAP-1 in naturally infected human. RESULTS/ANTICIPATED RESULTS: We measured a statistically significant reduction in larval worm burden in WAP and ES vaccinated mice, but not CAP-1, by microscopy and real-time PCR of T. muris DNA. We found a significant relationship between antigen-specific IgG1:IgG2a ratio in the mouse serum and degree of protection. Mouse splenocytes, vaccine-sensitized draining lymph nodes, and mesenteric lymph nodes were antigen-stimulated and their secreted Th1, Th2, and Th17 cytokines were measured by Luminex®. Stimulated mouse lymphoid cells were further analysed for T helper, T cytotoxic, and central/effector memory T cells by Flow Cytometry. Human IgG1, IgG2, and IgE antibody titers against WAP and CAP-1 were measured by ELISA. DISCUSSION/SIGNIFICANCE OF IMPACT: In our study, we describe the T cell dependent mechanism of humoral immunity of 2 promising ES-derived vaccines recombinant proteins, WAP and CAP-1. We evaluated the immune response, indicating a driving a Th2-induced humoral response necessary for protection. We further predict protection and allergenicity of WAP in humans using serum from a cohort in an T. trichiura endemic region.

OBJECTIVES/SPECIFIC AIMS: According to the US census, there are 3.3 million Americans who have to use wheelchairs in order to maintain their mobility. About 50% of these patients develop a pressure ulcer at some point during their life time. Three major factors contribute to pressure ulceration; pressure, tissue temperature, and maceration due to sweating. The objective of this study is to develop a temperature regulating wheelchair cushion in order to address elevated tissue temperatures and related sweating. METHODS/STUDY POPULATION: We instrumented a wheelchair with cooling elements, a water filled cushion and a pump. The pump moves the water through the cooling elements where water temperature drops down to 15°C. The water then moves to the cushion where it cools the tissue and then back to the cooling elements. RESULTS/ANTICIPATED RESULTS: We recruited 1 healthy subject to sit on the instrumented wheelchair and then obtained thermographs of the cushion surface using an infrared thermal camera. After 1 minute of sitting on the cushion the minimum temperature was recorded as 27°C. After 10 minutes the temperature dropped to 23.3°C. DISCUSSION/SIGNIFICANCE OF IMPACT: In this ongoing proof-of-concept study we are investigating if circulating chilled water inside a wheelchair cushion is a feasible method to regulate tissue temperatures at the 25–28°C range. This range has been shown to delay ulceration under loading conditions that simulate sitting on a wheelchair. Initial results indicate that this may be an effective ulcer prevention method.

OBJECTIVES/GOALS: This study aims to determine 1) which urine biomarkers of kidney health measured in the ambulatory setting predict incident hospitalization; 2) to determine whether time-updated measures of ambulatory urine biomarkers and their changes/trajectories have added value over baseline alone. METHODS/STUDY POPULATION: Participants in the Predictors of Acute Renal Injury Study (PARIS), a prospective cohort of 478 HIV+ patients followed at the Johns Hopkins HIV Clinic, had sociodemographic, clinical data, and biosamples taken until hospitalization or up to 3 years annually. Among those hospitalized, clinical data and biosamples were collected serially during hospitalization and at 3 and 12 months post-discharge. For each of the 10 biomarkers measured, we will evaluate the association of the biomarker and risk of incident hospitalization using Cox hazards regression, adjusting for sociodemographics, comorbidities, HIV history, and medications. Biomarkers will be evaluated at baseline and as time-updated and change over time. RESULTS/ANTICIPATED RESULTS: We anticipate that higher baseline levels and increasing levels of urine albumin, α1M, β2M, NGAL, IL-18, KIM-1, MCP-1, YKL-40 will be independently associated with increased risk of incident hospitalization whereas higher and increasing levels of uromodulin and EGF will be associated with lower risk of incident hospitalization. These biomarkers collectively capture the following dimensions of kidney health: endothelial injury, tubular injury and function, inflammation, and fibrosis. We anticipate increased risk of incident hospitalization in HIV+ persons in the highest tertile of baseline, time-updated, and change over time biomarkers, relative to those within the lowest tertile. DISCUSSION/SIGNIFICANCE: This study will improve our understanding of the evolution of biomarkers of kidney health from the ambulatory to the hospitalized setting and will quantify the clinical implications of subclinical kidney damage among people living with HIV, a high-risk patient population with unique kidney pathophysiology.

OBJECTIVES/GOALS: To summarize baseline characteristics and risk factors for major adverse cardiovascular events (MACEs) and develop a prediction model by testing the association between genetic variants and MACEs in Caribbean Hispanic patients on clopidogrel using machine-learning (ML) techniques. METHODS/STUDY POPULATION: This is a secondary analysis of available clinical and genomic data from an existing database of 600 Caribbean Hispanic cardiovascular (CV) patients on clopidogrel. MACEs is defined as the composite of all-cause death, myocardial infarction, stroke and stent thrombosis over 6 months. Dataset is divided into training (60%) and testing (40%) sets, respectively. Two different supervised ML approaches (i.e. multiclass classification and regression algorithms) are applied to the study dataset using Python v3.5 and WEKA, and tested by receiver operating curve (ROC) analysis. A case-control association analysis between MACEs at 6 months and genotypes is performed by using chi-squared test. RESULTS/ANTICIPATED RESULTS: Average age of participants was 68 years-old, 55% males, with high prevalence of risk factors (i.e., overweight: 28.4 kg/m2; hypertension: 83.8%; hypercholesterolemia: 71.9% and diabetes: 54.8%). MACEs rate is 13.8%, with 33.5% resistant to clopidogrel. Logistic regression, KNN and gradient boosting showed the best performance, as suggested by ROC analysis and AUC CV scores of 0.6-0.7. A significant association between MACE occurrence and ≥3 risk alleles was found (OR=8.17; p=0.041). We anticipate that these genetic variants (CYP2C19*2, rs12777823, PON1-rs662, ABCB1-rs2032582, PEAR1-rs12041331) will uniquely contribute to clopidogrel resistance and MACEs in Caribbean Hispanics. DISCUSSION/SIGNIFICANCE: Our findings help address in part the long-standing problem of excluding minorities from research, which entails a gap of knowledge about clopidogrel pharmacogenomics in Puerto Ricans. This study provides a possible ML model that integrates clinical and pharmacogenomics for MACE risk estimation.

OBJECTIVES/GOALS: Investigators are looking to integrate DE&I into trials, increasing study population diversity. In response, the Community and Recruitment programs of the Oregon Clinical and Translational Research Institute (OCTRI), built a collaborative, community-focused system for investigators interested in community engagement and recruitment. METHODS/STUDY POPULATION: Historically, the OCTRI Community and Recruitment programs operated independently. To build a community-focused support system for investigators, we began with the programs learning about each other’s goals, values, and operations over a six-month period. Over the next two years, we then began integrating into each other’s team meetings and processes. Each team has their own process for providing services to investigators, consisting of intake and consultations. To these, we added tags for the other’s program topics. This allowed efficient identification of opportunities for referrals and joint consultations. Program leads meet regularly to discuss referrals and partnerships allowing for more effective and consistent collaboration. RESULTS/ANTICIPATED RESULTS: Over the last two years, OCTRI Community and Recruitment built a collaborative process that allows investigators to work with both programs, receiving comprehensive, supportive assistance and education on how to design their study, engage with community, and recruit participants in a community-based setting. During this time, the programs have: provided consultations that discussed the other’s program (N=21); made direct referrals to the other program (N=4); and, provided joint consultations (N=2). Studies that are investigator-initiated, in planning phase, and population focused were found to benefit most from the collaborative efforts. Additionally, we have improved the collaborative process during this time, resulting in more streamlined, efficient support services for investigators. DISCUSSION/SIGNIFICANCE: Diverse study populations and DE&I are essential to research. This collaborative, community-engaged recruitment approach by our programs allows investigators to leverage both programs’ resources and expertise. We continue to identify best practices and study types that benefit from this collaborative approach to improve our services.

OBJECTIVES/SPECIFIC AIMS: The need to diversify the biomedical research workforce is well documented. The Career Education and Enhancement for Health Care Research Diversity (CEED) program at the University of Pittsburgh Institute for Clinical Research Education (ICRE) promotes success and helps seal the “leaky pipeline” for under-represented background (URB) biomedical researchers with a purposefully designed program consisting of a monthly seminar series, multilevel mentoring, targeted coursework, and networking. METHODS/STUDY POPULATION: Over 10 program years, we collected survey data on characteristics of CEED Scholars, such as race, ethnicity, and current position. We created a matched set of URB trainees not enrolled in CEED during that time using propensity score matching in a 1:1 ratio. RESULTS/ANTICIPATED RESULTS: Since 2007, CEED has graduated 45 Scholars. Seventy-six percent have been women, 78% have been non-White, and 33% have been Hispanic/Latino. Scholars include 20 M.D.s and 25 Ph.D.s. Twenty-eight CEED Scholars were matched to non-CEED URB students. Compared with matched URB students, CEED graduates had a higher mean number of peer-reviewed publications (9.25 vs. 5.89; p<0.0001) were more likely to hold an assistant professor position (54% vs. 14%; p=0.004) and be in the tenure stream (32% vs. 7%; p=0.04), respectively. There were no differences in Career Development Awards (p=0.42) or Research Project Grants (p=0.24). DISCUSSION/SIGNIFICANCE OF IMPACT: Programs that support URB researchers can help expand and diversify the biomedical research workforce. CEED has been successful despite the challenges of a small demographic pool. Further efforts are needed to assist URB researchers to obtain grant awards.

OBJECTIVES/GOALS: We focus on the following mission aligned activities centered upon optimizing the culture around inclusion, equity and diversity in the clinical and translational research faculty at UAB:

• To identify, support and promote Diversity, Equity and Inclusion (DEI) faculty award recognition and leadership program participation locally, regionally and nationally

• To identify, support and promote senior faculty representation on DEI-focused regional, national, and international scientific advisory committees of foundation, professional society and federal programs

• To identify opportunities and support the development of competitive DEI-focused foundation, professional society and federal grant applications

• To support the academic advancement, promotion and tenure among DRIVEN community

• To sponsor and convene professional development and social activities for the DRIVEN community

METHODS/STUDY POPULATION: A partnership of the Center for Clinical and Translational Science Training Academy and the Scientific Community of Outcomes Researchers (SCOR), DRIVEN is a multi-faceted solution to enhance workforce diversity by promoting individual and collective professional development, recognition, and advancement to foster an inclusive, equitable, and diverse research workforce. DRIVEN provides a platform, a community, and a common place where individuals can access resources to more easily identify opportunities aligned with their specific research goals, as well as peer and network support at every step along their professional journey. DRIVEN is uniquely aligned to assist investigators with applying for funding through NIH diversity supplements, foundation opportunities, and other national awards. RESULTS/ANTICIPATED RESULTS: DRIVEN provides networking opportunities, information, and writing support for funding opportunities. Since its inception, less than a year ago, we have seen an increase in writing groups, matched investigators with funding opportunities, and provided networking opportunities for mentors and mentees to meet and for peer mentoring to occur. The interest and momentum surrounding DRIVEN both from internal advisory groups and external advisory groups is significant and will only continue with the endorsement of UAB leadership. DRIVEN is expected to be used as a tool for the recruitment and retention of diverse faculty not only within the UAB community but across the CCTS Partner Network thus changing healthcare in the region. DISCUSSION/SIGNIFICANCE OF IMPACT: According to the NIH, research shows that diverse teams who capitalize on innovative ideas and distinct perspectives outperform less diverse teams. Not only is achieving diversity in the biomedical research workforce critical, but providing diverse researchers with access to support and community is competitive necessity.

OBJECTIVES/SPECIFIC AIMS: This retrospective study aims to create and train machine learning models using a radiomic-based feature extraction method for two classification tasks: benign vs. pathologic PI and operation of benefit vs. operation not needed. The long-term goal of our study is to build a computerized model that incorporates both radiomic features and critical non-imaging clinical factors to improve current surgical decision-making when managing PI patients. METHODS/STUDY POPULATION: Searched radiology reports from 2010-2012 via the UPMC MARS Database for reports containing the term “pneumatosis” (subsequently accounting for negations and age restrictions). Our inclusion criteria included: patient age 18 or older, clinical data available at time of CT diagnosis, and PI visualized on manual review of imaging. Cases with intra-abdominal free air were excluded. Collected CT imaging data and an additional 149 clinical data elements per patient for a total of 75 PI cases. Data collection of an additional 225 patients is ongoing. We trained models for two clinically-relevant prediction tasks. The first (referred to as prediction task 1) classifies between benign and pathologic PI. Benign PI is defined as either lack of intraoperative visualization of transmural intestinal necrosis or successful non-operative management until discharge. Pathologic PI is defined as either intraoperative visualization of transmural PI or withdrawal of care and subsequent death during hospitalization. The distribution of data samples for prediction task 1 is 47 benign cases and 38 pathologic cases. The second (referred to as prediction task 2) classifies between whether the patient benefitted from an operation or not. “Operation of benefit” is defined as patients with PI, be it transmural or simply mucosal, who benefited from an operation. “Operation not needed” is defined as patients who were safely discharged without an operation or patients who had an operation, but nothing was found. The distribution of data samples for prediction task 2 is 37 operation not needed cases and 38 operation of benefit cases. An experienced surgical resident from UPMC manually segmented 3D PI ROIs from the CT scans (5 mm Axial cut) for each case. The most concerning ~10-15 cm segment of bowel for necrosis with a 1 cm margin was selected. A total of 7 slices per patient were segmented for consistency. For both prediction task 1 and prediction task 2, we independently completed the following procedure for testing and training: 1.) Extracted radiomic features from the 3D PI ROIs that resulted in 99 total features. 2.) Used LASSO feature selection to determine the subset of the original 99 features that are most significant for performance of the prediction task. 3.) Used leave-one-out cross-validation for testing and training to account for the small dataset size in our preliminary analysis. Implemented and trained several machine learning models (AdaBoost, SVM, and Naive Bayes). 4.) Evaluated the trained models in terms of AUC and Accuracy and determined the ideal model structure based on these performance metrics. RESULTS/ANTICIPATED RESULTS: Prediction Task 1: The top-performing model for this task was an SVM model trained using 19 features. This model had an AUC of 0.79 and an accuracy of 75%. Prediction Task 2: The top-performing model for this task was an SVM model trained using 28 features. This model had an AUC of 0.74 and an accuracy of 64%. DISCUSSION/SIGNIFICANCE OF IMPACT: To the best of our knowledge, this is the first study to use radiomic-based machine learning models for the prediction of tissue ischemia, specifically intestinal ischemia in the setting of PI. In this preliminary study, which serves as a proof of concept, the performance of our models has demonstrated the potential of machine learning based only on radiomic imaging features to have discriminative power for surgical decision-making problems. While many non-imaging-related clinical factors play a role in the gestalt of clinical decision making when PI presents, we have presented radiomic-based models that may augment this decision-making process, especially for more difficult cases when clinical features indicating acute abdomen are absent. It should be noted that prediction task 2, whether or not a patient presenting with PI would benefit from an operation, has lower performance than prediction task 1 and is also a more challenging task for physicians in real clinical environments. While our results are promising and demonstrate potential, we are currently working to increase our dataset to 300 patients to further train and assess our models. References DuBose, Joseph J., et al. “Pneumatosis Intestinalis Predictive Evaluation Study (PIPES): a multicenter epidemiologic study of the Eastern Association for the Surgery of Trauma.” Journal of Trauma and Acute Care Surgery 75.1 (2013): 15-23. Knechtle, Stuart J., Andrew M. Davidoff, and Reed P. Rice. “Pneumatosis intestinalis. Surgical management and clinical outcome.” Annals of Surgery 212.2 (1990): 160.

ABSTRACT IMPACT: We present new programs aimed at training, retaining and preparing a diverse cadre of scientists to lead the field in transforming population health and advancing health equity OBJECTIVES/GOALS: To mitigate biases inherent to the R01 grant funding process, trainees from backgrounds underrepresented in medicine (URM) may benefit from enhanced mentorship and a longer ‘runway’ to funding. As such, we have deployed two synergistic programs that aim to support URM retention and advancement. METHODS/STUDY POPULATION: The URM Program for Advising in Research and Development (UPwARD) pairs URM trainees with 2 mentors: 1) an institutional leader from outside their discipline to serve as an internal advocate and 2) an external eminent scholar who will facilitate the scholar’s development and prominence within their discipline. Additionally, the KL2 Program to Launch URM Success (KL2 PLUS) offers URM trainees a third year of funding to focus on scholarship, grant writing and leadership development. Four specific training components of KL2 PLUS include: 1) PLUS II Seminar Series, 2) Faculty Success Program, 3) attendance at the AAMC Minority Faculty Leadership Conference, and 4) CTSI Committee Service. RESULTS/ANTICIPATED RESULTS: Along with measures of productivity (papers, grants, K to R transition), we will utilize social network analyses and measures of collaboration, retention, and future CTSI engagement to evaluate the programs “success’‘ as both are designed to enhance trainee scholarly development and expand their professional and social networks. UPwARD does so by supporting engagement with external mentors at professional meetings and travel to present work across institutions. PLUS writing accountability groups will enhance publication rates and grant submissions, while also building connections with other URM faculty. Trainees also serve on IN CTSI committees to groom talent for future IN CTSI leadership. DISCUSSION/SIGNIFICANCE OF FINDINGS: Systemic inequities underlie the ‘leaky pipeline’ challenge we face in cultivating a diverse cadre of senior scientists and independent investigators. With intentional programming and targeted investments, IN CTSI aims to advance more equitable funding outcomes and diverse leadership.

OBJECTIVES/SPECIFIC AIMS: Epidemiologic studies have found that the incidence of pancreatic cancer is greatest in countries that consume diets high in fat. The gastrointestinal peptide cholecystokinin (CCK) is released from the duodenum in response to dietary fat. CCK has also been shown to stimulate growth of pancreatic cancer through the CCK receptor that is over-expressed on pancreatic cancer cells. The aim of this investigation was to determine if dietary fat promotes growth of pancreatic cancer through the actions of CCK at its receptor. METHODS/STUDY POPULATION: The effects of dietary fat on growth of murine Panc02 pancreatic cancer xenografts were studied in 3 different systems with immune competent mice: (1) pharmacologic blockade with a CCK receptor antagonist, (2) genetic knockout of the CCK receptor by CRISPR, and (3) in genetically engineered mice lacking the CCK peptide (CCK-KO). After injection of 2×106 Panc02 cells subcutaneously, mice were fed either a high-fat diet or a control diet for 37–42 days. Tumor volumes and weights were measured and histology performed. RESULTS/ANTICIPATED RESULTS: Dietary fat significantly increased the size of pancreatic cancer xenografts and this effect was reversed by CCK receptor blockade. Receptor antagonist therapy also significantly reduced tumor-associated fibrosis and increased the influx of CD8+ lymphocytes in the micro-environment. Panc02 cancer cells lacking CCK receptors failed to respond exogenous administration of CCK in vitro and to dietary fat in vivo. Dietary fat did not stimulate Panc02 tumor growth in CCK-KO mice. DISCUSSION/SIGNIFICANCE OF IMPACT: The mechanism by which dietary fat stimulates growth of pancreatic cancer is by CCK and this effect is independent of obesity. This is a significant finding because of the potential beneficial effects of medications which can block the effects of CCK in populations at risk for pancreatic cancer consuming a high-fat diet.

The first human case of monkeypox virus (Mpox) was reported in 1970. In the years after 1970, human infection with Mpox and human-to-human transmission was not widely observed, and more cases were seen in endemic areas. In that year, Mpox spread was confirmed through the export of infected animals to other parts of the world. Every few years, sporadic infections were reported in different parts of the world from human contamination and human-to-human transmission. In recent years, with the slow decline of the COVID-19 pandemic, the outbreak of Mpox was observed in many countries of the world. To deal with the spread of this viral infection, we need to know the ways to diagnose the infection, treat the infection, care for the patients, and implement a wide program of vaccination. Currently, there are no specific drugs available for this virus, but according to previous studies related to smallpox, drugs such as tecovirimat, cidofovir, and brincidofovir, which were used for smallpox and other orthopoxviruses in the past, can be considered to deal with Mpox. Also, some vaccines such as JYNNEOS, IMVAMUNE, and MoVIHvax that have been used against smallpox can be useful to some extent in preventing Mpox.

Evidence is limited on how to synthesize and incorporate the views of stakeholders into a multisite pragmatic trial and how much academic teams change study design and protocol in response to stakeholder input. This qualitative study describes how stakeholders contributed to the design, conduct, and dissemination of findings of a multisite pragmatic clinical trial, the COMprehensive Post-Acute Stroke Services (COMPASS) Study. We engaged stakeholders as integral research partners by embedding them in study committees and community resource networks that supported local sites. Data stemmed from formal focus groups and continuous participation in working groups. Guided by Grounded Theory, we extracted themes from focus group and meeting notes. These were discussed as a team and with other stakeholder groups for feasibility. A consensus approach was used. Stakeholder input changed many aspects of the study including: the care model that treated stroke as a chronic condition after hospital discharge, training for hospital-based providers who often lacked awareness of the barriers to recovery that patients face, support for caregivers who were essential for stroke patients’ recovery, and for community-based health and social service providers whose services can support recovery yet often go underutilized. Stakeholders brought value to both pragmatic research and health service delivery. Future studies should test the impact of elements of study implementation informed by stakeholders vs those that are not.