bluuebunny/crossref_metadata_2025 huggingface dataset:
215 Relationships between geospatial factors and adverse outcomes in Medicaid-enrolled children with asthma
Authors: Jefferson Akilah , Brown Clare C. , Eyimina Arina , Goudie Anthony , Rezaeiahari Mandana , Perry Tamara T. , Tilford J. Mick
Published: April 2023

OBJECTIVES/GOALS: To determine the relationship between race/ethnicity, geospatial (place-based) social determinants of health (SDOH; rurality and child opportunity index (COI)), and asthma-related adverse events (AAE: hospitalizations, emergency department (ED) visits) among children with asthma in Arkansas. METHODS/STUDY POPULATION: Using the Arkansas All-Payer Claims Database, we conducted a retrospective analysis of children (5-18 years). Medicaid-enrolled children with, 1 asthma diagnosis (ICD-10 J45.xx) for any type of medical event in 2019 were included. Race/ethnicity were self-reported (non-Hispanic White, non-Hispanic Black, Hispanic/Latino). Due to small sample size, all other racial/ethnic groups were classified as Other. Rural-Urban Commuting Area (RUCA) codes were used to determine rural-urban designation using 4-category classification by zip code. COI level was determined by zip code (scale: very low- to very-high opportunity). AAEs were identified using 2019 medical claims. RESULTS/ANTICIPATED RESULTS: The cohort (n=25,198) included 38.7% White, 32.9% Black, 6.0% Hispanic, 5.1% Other, and 17.3% Missing race/ethnicity children. Overall, 61.2% live in rural and 38.8% live in urban areas. Among rural children, 33.1% were in very-low, 34.4% low, 20.8% moderate, 11.6% high, and 0.1% very-high opportunity areas. Among urban children, 32.6% were in very-low, 12.4% low, 17.5% moderate, 19.5% high, and 18.0% very-high opportunity areas. Overall, Black children more frequently lived in very-low or low opportunity areas (75.4%). Among rural children, 9.3% had an AAE. White children had highest rates of AAE. Overall, AAE rates were variable by rurality/urbanity and COI level. DISCUSSION/SIGNIFICANCE: Differences in asthma outcomes by race/ethnicity, rurality, and COI level were unexpected, with similar rates of poor outcomes across the cohort. These finding underscore the complexity of the relationships between race/ethnicity, geospatial SDOH, and asthma outcomes.
218 Researcher and Stakeholder Partner Perspectives on Engaged Research During the COVID-19 Pandemic
Authors: Grewe Mary E. , Frank Simone , Torres Laura Villa , Jean-Baptiste Milenka , Bilheimer Alicia , Lightfoot Alexandra F.
Published: April 2023

OBJECTIVES/GOALS: We sought to explore how the COVID-19 pandemic impacted community and stakeholder engagement in research from both researcher and stakeholder partner perspectives and to identify challenges, strategies, and other facilitators affecting their experience, including those related to virtual engagement. METHODS/STUDY POPULATION: We conducted semi-structured interviews with ten researchers and eight stakeholder partners who conducted or collaborated on stakeholder-engaged health research during the COVID-19 pandemic (March 2020 onwards). Potential participants were identified purposively and through snowball sampling. Interviews were conducted via Zoom, recorded, and transcribed for analysis. The transcribed data were qualitatively analyzed through an iterative process involving memoing and consensus coding using inductive and deductive codes. We reviewed memos and code reports to identify and describe key categories and themes. RESULTS/ANTICIPATED RESULTS: The challenges and facilitators identified varied based on factors such as geographic scope of the partnership (local vs national) and previous engagement type (virtual vs in-person). Many challenges were related to virtual engagement, such as dealing with distractions, limited access to Internet, or difficulty forming relationships online, or to wellbeing and personal circumstances, such as feeling burnt out, managing increased caregiving responsibilities, or concern about risk of illness if conducting in-person activities. Facilitators identified included having strong existing partnerships, utilizing strategies to enhance virtual engagement, adapting activities to manage risk of in-person interactions, and showing support to stakeholder partners. DISCUSSION/SIGNIFICANCE: By better understanding challenges and facilitators affecting experiences of both researchers and stakeholder partners engaging in research during the COVID-19 pandemic, we can develop strategies and resources to better support research partnerships during future health emergencies.
223 Surgical Management of Degenerative Cervical Myelopathy: Comparing Outcomes Between Patients Admitted Through Clinic Versus Emergency Department
Authors: Pina Dagoberto , Watson Jared , Villegas Alex , Booz Zachary , Holland Joseph , White Micaela , Santamaria Gabriel , Wick Joseph , Vander Voort Wyatt , Ortega Brandon , Conry Keegan , Javidan Yashar , Roberto Rolando , Klineberg Eric , Lipa Shaina , Le Hai
Published: April 2023

OBJECTIVES/GOALS: Degenerative cervical myelopathy (DCM) can lead to pain, disability, and permanent spinal cord impairment. Timely diagnosis and surgical intervention is essential to optimize functional outcomes for patients with CSM. Here, we compared patients who were admitted through clinic versus the emergency department (ED) for surgical management of DCM. METHODS/STUDY POPULATION: Patients aged ≥18 years admitted for surgery for DCM through clinic (elective cohort) were compared to a surgical cohort who were evaluated through the ED (call cohort). Basic demographics included age, gender, race, ethnicity, and insurance payor. Sociodemographic characteristics were estimated using the Social Deprivation Index (SDI) and the Area Deprivation Index (ADI) for the state of California, which were obtained through aggregated Zip Code Tabulation Area (ZCTA). Cervical MRI was reviewed to assess severity of spinal cord compression. Other outcomes included number of motion segments operated on, functional outcome using the Nurick classification, length of stay (LOS), disposition, and 30-day reoperation and readmission rates. RESULTS/ANTICIPATED RESULTS: From 2015 to 2021, 327 DCM patients received surgery (227 Elective Cohort, 100 Call Cohort). Elective cohort was mainly female (48.0 vs 30.0%, p=0.002) and white (72.7 vs 51.0%, p=0.0001). Call cohort was mainly uninsured/covered by Medicare/Medicaid (78.0 vs 67.0%, p=0.04), had higher SDI (68.0 vs 56.2, p=0.0003), ADI (7.9 vs 7.2, p=0.009), and cervical cord compression on MRI (78.0 vs 42.3% Grade III, p DISCUSSION/SIGNIFICANCE: Compared to DCM patients undergoing elective surgery, those admitted through the ED were more likely to be male, non-White, and socioeconomically disadvantaged, as measured by SDI and ADI. Postoperative outcomes were less favorable for these patients, including longer hospital stay, discharge disposition, and less Nurick grading improvement.
232 Trauma-informed, culturally responsive clinical and translational research with African American communities
Authors: Wolf De’Sha
Published: April 2023

OBJECTIVES/GOALS: To present a community engaged pilot study of minority participation in clinical research that translates principles of trauma informed care and culturally responsive education into research practices for Investigators that elevate African American patients’ trauma survivorship, and prioritize their values for meaningful research engagement. METHODS/STUDY POPULATION: Data will generated from Phase 1 pilot project research activities including: a) a scoping review of trauma-informed care and culturally responsive education principles, and published recommendations for translating these principles to clinical research practices, b) semi-structured Key Informant interviews (~10) capturing the perceived impact of trauma on Portland-area African Americans’ health, well-being, and clinical research participation, and c) a 2-day stakeholder council meeting with clinicians, patients, community health workers, Investigators, and IRB staff that will prioritize the clinical research principles and practices that matter most to African American patients, from pre-design to dissemination. Data will be collected Fall 2022/Winter 2023, and analyzed in Winter 2023. RESULTS/ANTICIPATED RESULTS: The results will empirically validate published recommendations on how to apply trauma-informed, culturally responsive (TICR) principles to clinical research practices, specifically for African American patients. They will illuminate the sociocultural and historical contexts under which clinical research is conducted with minoritized patients--drawing on the experiences of personnel who intersect at various levels of the clinical research ecosystem, and African American patients with varying experiences with clinical research. Results will illuminate challenges, needs, assets, cultural funds of knowledge, and values for meaningful research engagement, and provide practical, tangible strategies for Investigators to align with equity- and justice-based clinical research practices. DISCUSSION/SIGNIFICANCE: The TICR research approach disrupts the cycle of trauma, health disparities, and low minority research participation through a paradigm shift that equips Investigators to exercise universal precautions to minimize harm, protect African American research participants from retraumatization, prioritize their cultural values, and promote safety.
234 Understanding the utility of an evaluation instrument and a feedback mechanism in community-based participatory research (CBPR) partnerships
Authors: Chandanabhumma P. Paul , Berry Jane , Wilson-Powers Eliza , Rowe Zachary , Reyes Angela G. , Lachance Laurie , Brush Barbara L. , Israel Barbara A.
Published: April 2023

OBJECTIVES/GOALS: To examine i) how longstanding (≥6 years) community-based participatory research (CBPR) partnerships nationwide implemented a validated questionnaire to measure success and its contributing factors and ii) how the CBPR partnerships utilized and applied a feedback mechanism, or reports of findings from the questionnaire and a facilitation guide METHODS/STUDY POPULATION: This mixed methods study builds upon a larger NIH-funded project entitled ’Measurement Approaches to Partnership Success (MAPS). MAPS developed and validated the 109-item MAPS questionnaire to measure success in longstanding (≥6 years) CBPR partnerships. In 2020, 55 CBPR partnerships nationwide completed the MAPS Questionnaire and, a year later, received the MAPS Feedback Mechanism, consisting of questionnaire findings and a facilitation guide on how to present the findings. In this follow-up study, we administered multi-method surveys to each partnership contact person in 2022 to examine their experience with and utility of the MAPS Questionnaire and the MAPS Feedback mechanism. We performed descriptive analysis of quantitative responses using SAS and thematic analysis of qualitative responses. RESULTS/ANTICIPATED RESULTS: Survey responses have been presently collected from 14 partnerships. Preliminary findings suggest that the most frequently reported benefits of completing the MAPS Questionnaire included stimulating partnership reflections and ease of completion. Many partnerships shared results of the MAPS Questionnaire by e-mail or during partnership meetings. Nearly half of the partnerships rated components of the MAPS feedback mechanism as useful. Over one-third of the partnerships reported that the COVID pandemic limited their capacity to engage with the MAPS Feedback Mechanism. Key qualitative suggestions included making the MAPS Questionnaire shorter, providing it in a different format, and offering additional facilitation to support the implementation of the MAPS Feedback Mechanism. DISCUSSION/SIGNIFICANCE: This study examines how CBPR partnerships utilize an evaluation instrument and apply results on success. Current findings suggest potential utility of the MAPS Questionnaire and Feedback Mechanism for ongoing evaluation. Reducing the questionnaire length and providing facilitation resources may enhance implementation across diverse settings.
242 Listening to and Learning from the Community: A Model for Community Engagement and Building Trust
Authors: Wolfe Nicole , Rubio-Diaz Mayra , Garcia Alma , Calderon Sara , Kipke Michele D.
Published: April 2023

OBJECTIVES/GOALS: We have developed a community engagement model that embraces several core values: bi-directional, co-equal, co-created, inclusive, culturally centered, and trust. Our promotoras de salud and community health workers (CHWs) facilitate listening sessions to understand the most pressing health needs and concerns as perceived by the community. METHODS/STUDY POPULATION: Our Southern California CTSI Community Engagement team includes promotoras de salud and community health workers who are trusted individuals within our targeted communities–Latino and Black populations in South and the Eastside of Los Angeles. Listening sessions identify the community’s perceived health needs and concerns, and our team in turn delivers a workshop series that addresses those concerns. Workshops are co-developed by community members, offered in English and Spanish, and delivered both virtually and in-person in community venues. Workshop topics have included mental health, depression, anxiety in children; child development and autism; COVID-19 testing, variants, and vaccines; monkeypox; and a primer on understanding clinical research. RESULTS/ANTICIPATED RESULTS: In 2022, we held 49 workshops that delivered evidence-based information including how to access needed resources. We had a total of 1212 participants, 60% of whom were returning, meaning they had attended at least one prior workshop. An evaluation of the workshop program demonstrated that our promotoras de salud and community health workers are trusted by the community and that workshops are meeting community needs. 677 surveys were completed by participants, 87.5% of whom were female. 85% of respondents stated that they will use the information they learned in their daily life, and 90% said they would attend another workshop. Feedback from the evaluation will inform future workshop format and topics. DISCUSSION/SIGNIFICANCE: Academic-community partnerships are key to advancing health equity, especially in diverse and under-resourced communities. This is one model of community engagement, which includes promotoras de salud and CHWs that was designed to build trust, empower individuals through education, and to address the health needs as defined by the community.
247 Private equity acquisition of nursing homes and the impact on long stay residents and racial disparities in care outcomes
Authors: Akosionu-deSouza Odichinma , Huckfeldt Peter , Shippee Tetyana
Published: April 2023

OBJECTIVES/GOALS: To investigate nursing homes (NHs) acquired by private equity (PE) firms and estimate the effect of PE NH acquisitions on NH care quality for NH residents and whether PE NH acquisitions exacerbate racial inequities in quality of care. METHODS/STUDY POPULATION: My research estimates the causal effect of NH PE acquisitions on NH access and quality of care for NH residents and whether acquisitions exacerbate racial disparities in NH care for about 115 PE-owned NHs in the US, measuring the quality of care at the facility survey year level, and using an array of NH-level data sources. I identified 115 PE-owned NHs (treatment group) and 665 non-PE-owned NHs between 2003 and 2010, using the Online Survey Certification and Reporting database to obtain facility characteristics. I compare facility characteristics (e.g., payer mix, staffing levels, and quality measures such as pressure ulcers, unexpected weight loss, acuity, and health deficiencies). I will then test whether effects differ by race, with hypotheses informed by Public Health Critical Race Praxis approach. RESULTS/ANTICIPATED RESULTS: Preliminary results show that staffing levels differ between PE and non-PE-owned NHs in a way that aligns with a shift in focus toward the Medicare population i.e. short stays. We also find that deficiencies increased in PE-owned NHs compared to non-PE-owned NHs. We expect that PE acquisitions may lead to slightly widening racial disparities in NH care quality. Results may show that PE-owned NHs have a higher share of low-rated, high-BIPOC facilities. In weak markets, PE-owned NHs may have a higher share of BIPOC residents compared to highly competitive markets. This is because PE managers may prioritize cost over quality by cutting services. However, since quality measures are self-reported, except for measures related to deficiencies, this predicted lower quality of care may not be evident in observed data. DISCUSSION/SIGNIFICANCE: Understanding how PE ownership impacts nursing home care quality for long-stay residents, especially those funded by Medicaid, can help develop intervention strategies to effectively mitigate racial inequities in NH care, as Medicaid funded NH residents are more likely to be Black, Indigenous, and people of color.
248 Self-Reported Race, Street Race, and Sleep Quality & Hours During the COVID-19 Pandemic Outbreak
Authors: Keller Nathan , Dush Claire M. Kamp , VanBergen Alexandra , Berrigan Miranda N. , Manning Wendy D.
Published: April 2023

OBJECTIVES/GOALS: Our objective is to assess whether street race is a stronger predictor of sleep quality and sleep hours than self-reported race. We also seek to understand whether the association between race and sleep quality/hours can be explained by experiences of microaggressions. METHODS/STUDY POPULATION: This study uses data from the National Couples’ Health and Time Study (NCHAT), a population-representative sample of 20–60 year-olds (N=3,642) who were married or cohabiting during 2020-2021 when the COVID-19 pandemic disproportionately negatively impacted racial and ethnic minorities in the U.S. (Boserup et al., Yip et al.). During this time, incidents of racial trauma increased (Tessler et al.). Using NCHAT data we examine whether street race is a stronger predictor of sleep quality and sleep hours than self-reported race. We also seek to understand whether the association between race and sleep quality/hours can be explained by experiences of microaggressions. RESULTS/ANTICIPATED RESULTS: Results show that microaggressions mediate the link between identifying as Black and being perceived as Black or Asian and sleep quality/hours. Identifying as Black and being perceived as Black or Asian, compared with non-Latinx White respondents, is associated with more frequent microaggressions. More microaggressions are associated with poorer sleep quality and fewer sleep hours. Asian street race is a marginally better predictor of microaggressions than self-reported race. In all models, microaggressions are associated with poorer sleep quality and less sleep hours. DISCUSSION/SIGNIFICANCE: With a growing non-white population, the wellbeing of our future generations is in everyone’s best interest. Poor sleep increases the risk of cardiovascular disease, diabetes, obesity, and cancer. The United States spends $93 billion in excess medical care costs due to health disparities.
249 Addressing Structural Racism Using Community Based System Dynamics
Authors: Gullett Heidi , Brown Gregory , Collins Delores , Mathews Michael , Stange Kurt , Hovmand Peter
Published: April 2023

OBJECTIVES/GOALS: 1. Describe method of Community Based System Dynamics. 2. Describe CBSD as used in addressing structural racism in a previously redlined community. 3. Review example causal loop diagrams and simulation models developed using CBSD focused on structural racism as a social determinant of health. METHODS/STUDY POPULATION: Community Based System Dynamics (group model building and computer simulation development). Cuyahoga County, Ohio, a previously redlined community of more than 1.2 million people. RESULTS/ANTICIPATED RESULTS: Actionable Community identified leverage points for action to mitigate structural racism. Computer simulation models built on causal loop diagrams built by Community members with loved experience. DISCUSSION/SIGNIFICANCE: Structural and social determinants of health, such as racism, have profound impacts on the health of individuals and populations, however they remain challenging to address in pragmatic ways. CBSD is a novel method to engage community members not proximal to the impact of structural racism in generating maps of the complex, dynamic system they live in.

Precision Medicine/Health
254 A systems genomics approach to identify novel drug targets of Ewing sarcoma through ancestry-informed human iPSC modeling
Authors: Moss Rachel M , Becklin Kelsie , Mills Lauren J , Moriarity Branden S , Webber Beau R , Spector Logan G
Published: April 2023

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.
258 Analysis of the Hepatic Microenvironment Before and After Direct-Acting Antiviral (DAA) Therapy for Viral Hepatitis C
Authors: Millian Daniel , Saldarriaga Omar A. , Arroyave Esteban , Wanninger Timothy , Krishnan Santhoshi , Rao Arvind , Moghe Akshata , Stevenson Heather L.
Published: April 2023

OBJECTIVES/GOALS: The effect of the Direct-Acting Antiviral (DAA) on hepatic histopathological features from patients treated for HCV has not been thoroughly evaluated. The goals of this retrospective study were to determines differences between the liver biopsies collected before and after DAA treatment and correlated the histopathology with clinical outcome. METHODS/STUDY POPULATION: Spectral imaging was used to evaluate differences in intrahepatic macrophage (CD68, CD14, CD16, MAC 387, and CD163) and T cell (CD3, CD4, CD8, CD45, and FoxP3) phenotypes in paired liver biopsies collected from the same patient before (n=10) and after (n=10) achieving SVR (Figure 1). Imaging analysis and machine learning algorithms were used to evaluate changes in these key immune cells. We also compared differential gene expression of over 700 genes using RNA isolated from liver biopsies with NanoString. RESULTS/ANTICIPATED RESULTS: Multispectral imaging analysis showed a significant increase of proinflammatory/M1-like (e.g., CD14+) and anti-inflammatory/M2-like macrophage (e.g., CD163+) phenotypes in pre-treatment versus post-treatment biopsies, respectively. Gene expression analysis revealed enrichment of inflammatory (HLA-B, STAT1, CXCL10) and interferon induced-antiviral (ISG15, OAS3, MX1 and IFIT1) genes in the pre-treatment vs the post-treatment group. Cell deconvolution analysis also showed a significant increase of M1-like macrophages in the pre-treatment group when compared to the post-treatment group or controls. Upregulation of genes associated with cell proliferation and differentiation (c-KIT and Fos) was observed in the post-treatment biopsies of patients with persistent inflammatory infiltrates. DISCUSSION/SIGNIFICANCE: Protein and gene expression profiles observed in patients before DAA therapy showed a strong macrophage-mediated inflammatory response against HCV infection in the liver that shifted significantly to a tissue remodeling microenvironment after treatment.
265 Connecting Electronic Medical Record Sub-phenotypes of Obstructive Sleep Apnea to Adverse Outcome Risks
Authors: Borza Victor , Upender Raghu , Wei Wei-Qi , Malin Bradley
Published: April 2023

OBJECTIVES/GOALS: Prior work has established subtypes of OSA and linked them to risks of future adverse events but rarely with the longitudinality and richness of data available in the EMR. Our goal is to leverage EMR data identify clinically meaningful sub-phenotypes of OSA and better study how they affect risks of adverse outcomes. METHODS/STUDY POPULATION: Vanderbilt’s EMR database has over 61,000 adult patients with a literature-validated EMR definition of OSA with a median EMR follow-up period of 4 years after OSA diagnosis. Of these patients, 12,516 have fully recorded sleep study data in addition to EMR variables such as age at study and most recent BMI. We applied several clustering methods including to identify natural sub-phenotypes of OSA and assessed cluster quality. We also applied techniques which allow a single patient to belong to multiple clusters in various degrees. After selecting final clusters, we plan to analyze the associations between OSA sub-phenotypes and risks using statistical tools like logistic regression and Cox proportional hazards regression, with and without adjusting for factors such as age, gender, and certain medications. RESULTS/ANTICIPATED RESULTS: Preliminary clustering with primarily sleep study data has shown overlap with literature-described patient clusters, including a severe, high non-REM stage 1 sleep, high BMI cluster and a high nocturnal limb movement cluster. As we incorporate more EMR variables, we will select a final set of OSA sub-types. We anticipate patients in different clusters to have different risks of various adverse OSA-associated outcomes that are tracked in our EMR data. Notable outcomes with sufficient incidence rates (>3%) after OSA diagnosis include essential hypertension (43.4%), hyperlipidemia (28.8%), type 2 diabetes (21.9%), anxiety disorder (19.2%), coronary atherosclerosis (14.9%), cerebrovascular disease (7.7%), and pulmonary heart disease (5.9%). DISCUSSION/SIGNIFICANCE: If our results match anticipations, we will show how EMR data can be used to define OSA sub-phenotypes and predict patient risks of various OSA-associated outcomes. This analysis enables work in personalized risk and treatment predictions for OSA patients. By better understanding these risks, providers can better tailor treatments to patients.
266 Decoding the role of polyamine metabolism on anti-tumor immunity in head and neck cancer
Authors: Harbison Richard Alexander , Andrews William , Mikula Michael , Ogurtsova Aleksandra , Engle Liz , Nwankwoala Ogechi , Willis Reagan , Sadhukhan Pritam , Burns Mark , Pardoll Drew , Seiwert Tanguy , Fakhry Carole , Casero Robert A. , Fertig Elana , Pearce Erika
Published: April 2023

OBJECTIVES/GOALS: The effect of immunosuppressive metabolites on anti-tumor immunity in human papillomavirus (HPV)-associated vs carcinogen-driven head and neck cancer is unknown. The objective of this study is to define the extent to which metabolites impair this response and identify novel metabolic targets for enhancing anti-tumor immunity. METHODS/STUDY POPULATION: HPV-associated and carcinogen-driven head and neck squamous cell carcinoma specimens were frozen following surgical excision, and tumor sections were cut onto glass slides. Slides were coated in alpha-cyano-4-hydroxy-cinnamic acid (CHCA) matrix and subjected to mass spectrometry imaging using matrix-assisted laser desorption ionization (MALDI) on a Bruker SolariX XR 12T Hybrid QqFT-ICR mass spectrometer run in positive mode. Slides were then stained for immunohistochemistry (IHC) using markers of CD8 T cells, macrophages (CD163), B cells (CD20), and tumor cells (panCK). Mass spectrometry imaging and IHC spatially resolved data will be co-registered and metabolite intensity in regions of interest (cell types) quantified. RESULTS/ANTICIPATED RESULTS: A total of seven HPV-associated (three metastatic lymph nodes and four primary tumors) and six carcinogen-driven (primary tumors) HNSC specimens were subjected to MALDI and IHC. Metabolites significantly enriched in HPV-associated HNSC relative to carcinogen-driven HNSC include 2,3-diphosphoglyceric acid, xanthine, 2,3,5-Trichloromaleylacetate, and indole-3-carboxyaldehyde. Metabolites significantly enriched in carcinogen-driven HNSC relative to HPV-associated HNSC include hesperetin 3'-O-sulfate, hypoxanthine, phosphorylcholine, and L-homocysteine sulfonic acid. In ongoing analyses, we anticipate identifying a relationship between CD8+ T cell enriched vs depleted regions and immunosuppressive metabolites (e.g., kynurenine, adenosine monophosphate). DISCUSSION/SIGNIFICANCE: Defining the extent to which CD8+ T cells interact with the metabolic milieu of the microenvironment will provide a foundation for metabolic Precision Medicine. Strategically targeting metabolic pathways to enhance the anti-tumor immune response will be leveraged for the design and implementation of immune modulatory metabolic therapy.
270 Development of a Predictive Nomogram for Circumferential Resection Margin in Rectal Cancer Surgery
Authors: Shroder Megan , Ford Molly M , Ye Fei , Zhao Zhiguo , Khan Aimal , McChesney Shannon , Hopkins M. Benjamin , Hawkins Alexander T.
Published: April 2023

OBJECTIVES/GOALS: A negative circumferential resection margin (CRM) after surgical resection of rectal cancer decreases local recurrence and increases overall survival. While MRI is used to predict this risk, there is no predictive model that incorporates clinical factors to predict the risk of CRM positivity. METHODS/STUDY POPULATION: Utilizing the National Cancer Database from 2010-2014, we performed a retrospective study evaluating factors predictive for positive CRM after surgical resection of rectal cancer. The primary outcome was positive CRM (tumorâ‰¤1 mm from the surgical margin). Our population included patients with clinical stage I-III rectal cancer who underwent total mesorectal excision. For the primary outcome, multivariable logistic models were used to estimate the probability of a positive CRM. Model performance was evaluated by using the area under the receiver operating characteristic curve (AUC). Model calibration was assessed by examining the calibration plot. Bootstrapping method (300-iteration) was used to internally validate and estimate optimism-adjusted measures of discrimination and overall model fit. RESULTS/ANTICIPATED RESULTS: There were 28,790 patients included. 2,245 (7.8%) had positive CRM. Older age, race, larger tumor size, higher tumor grade, mucinous and signet tumor histology, APR, open operative approach, facility location, higher T stage, lymphovascular invasion, lack of neoadjuvant chemotherapy/radiation, and perineural invasion were all significantly associated with positive CRM (p DISCUSSION/SIGNIFICANCE: An objective model that predicts positive CRM and associated poor clinical outcomes is possible to be used in conjunction with MRI. Positive CRM is associated with specific patient demographics, tumor characteristics, and operative approach. These factors can be used to predict CRM positivity in the preoperative period and plan accordingly.
278 Eight Pharmacokinetic-related Genetic Variants Were Not Associated with Bleeding from Direct Oral Anticoagulants in Non-valvular Atrial Fibrillation Patients
Authors: Campos-Staffico Alessandra M. , Dorsch Michael P. , Barnes Geoffrey D. , Zhu Haojie , Limdi Nita A. , Luzum Jasmine A.
Published: April 2023

OBJECTIVES/GOALS: Assess the association of PK-related single nucleotide variants (SNVs) with the risk of bleeding from DOACs in non-valvular AF patients. METHODS/STUDY POPULATION: A retrospective cohort study was carried out with 2,364 Caucasians with non-valvular AF and treated with rivaroxaban or apixaban. Patients were genotyped as part of the genomic biobank at the University of Michigan Health System. The primary endpoint was a composite of major and clinically relevant non-major (CRNM) bleeding. Cox proportional hazards regression with time-varying analysis assessed the association of 8 SNVs in 5 PK genes (ABCB1, ABCG2, CYP3A4, CYP3A5, CYP2J2) with the risk of bleeding from DOACs in unadjusted and covariate-adjusted models. Six tests were performed as 3 of the SNVs are in the same haplotype. P-values below the Bonferroni-corrected level of 8.33e-3 were considered statistically significant. RESULTS/ANTICIPATED RESULTS: A total of 412 (17.4%) major and CRNM bleeding events occurred over 2.27 ± 2.03 years of follow-up. None of the PK SNVs were significantly associated with bleeding risk on DOACs in both unadjusted and covariate-adjusted Cox regression models. DISCUSSION/SIGNIFICANCE: The effects of these eight genetic variants on exposure to DOACs may not be strong enough to translate into differences in clinical outcomes. Especially if the genetic inheritance underlying the risk of bleeding from DOACs is polygenic, reinforcing the need for further genomic studies on this subject.
286 Genetic, laboratory and clinical factors associated with low-dose aspirin failure in the prevention of preeclampsia
Authors: Rottenstreich Amihai , Vaughan Roger , Coller Barry S
Published: April 2023

OBJECTIVES/GOALS: Low-dose aspirin is an established treatment to prevent preeclampsia, a leading cause of maternal and perinatal complications. Nevertheless, aspirin failure is not uncommon. We are investigating whether a gain-of-function genetic polymorphism in a platelet thrombin receptor is associated with aspirin failure in the prevention of preeclampsia. METHODS/STUDY POPULATION: Women who had preeclampsia in an initial pregnancy who then received low-dose aspirin in a subsequent pregnancy will be evaluated. We will compare between women who developed preeclampsia despite aspirin (aspirin non-responders) to women who did not develop preeclampsia with aspirin treatment (aspirin responders). Specifically, we will evaluate the allelic frequency of a single nucleotide variant (rs773902) in PAR4 thrombin receptor on platelets. This variant is associated with increased platelet function and potentially aspirin resistance. In addition, we will analyze the platelet response to PAR4 activation before and 1 hour after administering a single 81 mg enteric-coated aspirin tablet. RESULTS/ANTICIPATED RESULTS: We hypothesize that the prevalence of the PAR4 variant will be significantly higher among women who had recurrence of preeclampsia despite aspirin therapy. We also postulate that women who developed preeclampsia despite aspirin prophylaxis and have the polymorphism will have increased platelet aggregation in response to activation of PAR4, either by thrombin or peptides that activate the receptor, both at baseline and 1 hour after aspirin administration. DISCUSSION/SIGNIFICANCE: If our hypothesis that aspirin failure in preeclampsia prevention is associated with the gain-of-function polymorphism in the platelet PAR4 thrombin receptor, there may be justification for additional experimental studies to assess whether better pregnancy outcomes can be obtained by targeting thrombin itself using low molecular weight heparin.
287 Genomic and Immunologic Characterization of Lung Adenocarcinoma in Never Smokers vs. Smokers
Authors: Li P. Jonathan , Tsui Jessica , Ding Vivianne W. , Combes Alexis J. , Krummel Matthew F. , Jablons David M. , Kratz Johannes R.
Published: April 2023

OBJECTIVES/GOALS: Smoking is a well-established risk factor for lung cancer, but never smokers account for up to 25% of lung cancer cases. There is mounting evidence that lung cancer in never smokers is biologically distinct. We aim to characterize the genomic and immunologic features of lung adenocarcinoma in never smokers versus smokers. METHODS/STUDY POPULATION: We examined clinical, genomic, and bulk-RNA sequencing data from 499 patients in the TCGA lung adenocarcinoma cohort. Tumor mutation burden was analyzed using maftools (R package). Tumor immune characterization was completed using CIBERSORTx, a digital cytometry tool that uses single cell reference profiles to determine immune cell type frequencies from bulk-RNA sequencing data. Single cell reference profiles for 19 different immune cell types were constructed from sequencing of freshly resected lung tumor tissue from UCSF patients. Partitioning Around Medoids (PAM; R package) was used to identify distinct immune phenotypes based on immune cell composition. Fisher’s exact test was used to evaluate for associations between immune phenotypes and smoking status. RESULTS/ANTICIPATED RESULTS: Of the 499 TCGA lung adenocarcinoma patients, 75 were never smokers, 269 were female, and 246 were over the age of 65. Never smokers had lower tumor mutation burden and lower predicted neoantigen burden compared to smokers (p < 0.001). There was no difference in total tumor immune cell infiltration between never smokers and smokers. PAM yielded 2 distinct clusters/immune phenotypes. The first was enriched in M1 Macrophages, cytotoxic T Cells, helper T Cells, regulatory T Cells, and Plasma Cells. The second was enriched in plasmacytoid Dendritic Cells, M2 Macrophages, and exhausted cytotoxic T Cells. Never smoking status was associated with an increased odds of having the first immune phenotype (OR 1.95, 95% CI: 1.15 - 3.35) and this association was statistically significant (p = 0.0086). DISCUSSION/SIGNIFICANCE: Our findings suggest that never smokers have an immune phenotype that is distinct from that observed in smokers. The distinct immune characteristics we observed could explain clinical trial data suggesting immune checkpoint inhibitors are less effective in never smokers and hold implications for tailoring therapy.
290 Hepatomegaly and fatty liver infiltration among unhealthy weight pediatric population in Puerto Rico
Authors: Candelaria Bá¡rbara L Riestra , Rodriguez-Mojica Wilma , Valez Camille , Ramírez Claudia , Alvarado Ariana , Camareno Gabriel , González-Rodríguez Loida A.
Published: April 2023

OBJECTIVES/GOALS: A quarter of Puerto Rican pediatric population are overweight or obese. Pediatric obesity is established as a global public health concern that will develop liver complication as a Non-alcoholic fatty liver disease (NAFLD). This study aims to determine the association between body weight, liver size and texture in Puerto Rican pediatric population. METHODS/STUDY POPULATION: Twenty-nine (n=29) pediatric participants (20 unhealthy weight and 9 healthy weight) between 7 to 19 years underwent panoramic ultrasound imaging of the RLL. Craniocaudal RLL measurement and liver texture were evaluated. Body mass index and waist circumference were also compared. Shapiro-Wilk test and students t-tests were attained with significance at p < 0.05. RESULTS/ANTICIPATED RESULTS: Statistical differences were detected between healthy weight and unhealthy weight pediatric patients: (1) RLL craniocaudal diameter (p=0.006); (2) waist circumference (p < 0.001); (3) BMI (p < 0.001). Unhealthy weight (overweight and obese) pediatric patients presented a greater number of livers with fat infiltration (13) and hepatomegaly (15). DISCUSSION/SIGNIFICANCE: This preliminary results showed that liver size was larger and fatty infiltration are relatively frequent among overweight and obese pediatric patients. Prevention of unhealthy weight and the diagnosis of changes in liver texture and size among pediatric patients is important to prevent progressing of liver disease and avoid irreversible damage.
306 Long-Term Appearance and Outcomes after Strip Craniectomy Compared with Open Cranial Vault Reconstruction for Sagittal Craniosynostosis
Authors: Danial Elizabeth , Danial Elizabeth , Sun Peter , Pomerantz Jason
Published: April 2023

OBJECTIVES/GOALS: Strip craniectomy with orthotic helmet therapy (SCOT) and open cranial vault reconstruction (OCVR) are mainstay surgical treatments for sagittal craniosynostosis. The purpose of this study is to compare long-term morphologic outcomes of the skull, subjective appearance, and perioperative outcomes between patients who underwent SCOT and OCVR. METHODS/STUDY POPULATION: Patients who underwent SCOT or OCVR for isolated, non-syndromic sagittal craniosynostosis with preoperative computerized tomography (CT) imaging were identified at UCSF between 2000 and 2020. Perioperative outcomes were extracted from the medical chart. Anthropometric measurements will be used to assess baseline severity using preoperative CT imaging and postoperative skull morphology using 3D camera imaging. Patient satisfaction surveys will be administered to parents at the time of postoperative 3D imaging. Subjective appearance will be rated among adolescents and craniofacial surgeons using patients’ postoperative 3D imaging. Descriptive statistics will be calculated using Student’s t test and Mann-Whitney U. Chi-square tests and Fisher exact tests will be used to compare categorical outcomes. RESULTS/ANTICIPATED RESULTS: 47 patients were included in the study (18 SCOT and 29 OCVR) with similar follow-up between groups (SCOT 2.3 +/- 1.5, OCVR 2.6 +/- 2.0). There were no significant differences in sex or race. OCVR had longer operative times (p-value 0.0003), higher estimated blood loss (p DISCUSSION/SIGNIFICANCE: SCOT was associated with superior perioperative outcomes compared with OCVR due to its minimally invasive technique. Our results for long-term healing outcomes and subjective appearance may further guide craniofacial surgeons in selecting the most optimal operative technique.
307 Machine learning identification of diabetic foot ulcer severity to reduce amputation risk
Authors: Flores Mario , Paniagua Karla , Jin Rivera Yufang
Published: April 2023

OBJECTIVES/GOALS: Target: Computationally identify the markers of ulcer severity and risk of amputation from datasets that include demographics data, clinical, laboratory data, and medical history over 6000 patients. METHODS/STUDY POPULATION: In this study we will use tables of demographics such as age, gender, and ethnicity/race. Inspired by previous research we’ll include wound age (duration in days), wound size, number of concurrent wounds of any etiology, evidence of bioburden/infection, Wagner grade, being non ambulatory, renal dialysis, renal transplant, peripheral vascular disease, and patient hospitalization. Another table will include laboratory vital signs to include physiological variables such as height, weight, body mass index, pulse rate, blood pressure, respiratory rate, and temperature. We’ll include also social data like smoking status, socio-economic status, housing condition. RESULTS/ANTICIPATED RESULTS: Our project aligns with previous efforts to identify high risk Diabetic Foot Ulcer individuals but also takes a different perspective by collecting and marking clinical data from a subset of patients (e.g., severity, Hispanic versus non-Hispanic) and computationally process these data to provide a tool that can identify DFU severity and high-risk patients. We will obtain samples from Hispanics and non-Hispanics because these two groups are likely to have significant differences in the progression of ulcer severity. The rationale is that by comparing these two groups, we will assess and study the factors that are differentially present. It is our expectation that the proposed project will provide an easy-to-use tool for DFU progression and risk of amputation and contribute to identify high-risk individuals. DISCUSSION/SIGNIFICANCE: Diabetes prevalence estimates in Bexar County, TX exceeds national estimates (15.5% vs. 11.3%) and diagnosed cases are higher among Hispanic adults (13.4%) compared to their non-Hispanic white counterparts (9.5%). Late identification of severe foot ulcers minimizes the likelihood of reducing amputation risk.
308 Machine learning to predict genetic variation and cardiovascular risk in Hispanic patients with Systemic lupus erythematosus
Authors: González-Meléndez Ariana , Roche-Lima Abiel , Amaya Ardila Claudia P. , Vilá Luis M. , Brown Elizabeth
Published: April 2023

OBJECTIVES/GOALS: Cardiovascular disease (CVD) is the most common cause of death in systemic lupus erythematosus (SLE). Genome-wide association studies have identified single nucleotide polymorphisms linked with CVD risk, but the association with SLE is not well established. We aimed to determine associations using machine learning in a multi-ethnic lupus cohort. METHODS/STUDY POPULATION: We will use data from the established SLE cohort study named Genetic Profile Predicting the Phenotype (PROFILE). PROFILE was constituted in 1998 by combining existing cohorts at multiple sites which are also of defined ethnicity (Hispanics of Mexican ancestry and Puerto Rico, African American, and Caucasian). The cohort consists of 3,118 individuals and the database contains socioeconomic–demographic, clinical, laboratory, and genetic variables. Genetic data consist of 196,524 single nucleotide polymorphisms. To detect risk genes and predict an individual’s SLE risk will design a random forest classifier using SNP genotype data. Logistic regression models will be performed with CVD as the outcome, adjusted for age, sex, ethnicity, disease duration, and traditional and nontraditional risk factors for CVD. RESULTS/ANTICIPATED RESULTS: We expect to find several established and new susceptibility genes associated with CVD. DISCUSSION/SIGNIFICANCE: This approach offers an opportunity to characterize distinct genetic risk factors and the relationship of CVD with SLE. These data may be important in the identification of patients at high risk for such events and may allow the design of preventive strategies which may beneficially have an impact on the morbidity and mortality of SLE patients.