Objectives/Goals: The objective of this project was to develop electronic health record-based algorithms, or computational phenotypes, for carbapenem-resistant Enterobacterales (CRE) and extended-spectrum beta-lactamase-producing Enterobacterales (ESBL) infections based on public health surveillance case definitions. Methods/Study Population: We analyzed electronic health records (EHR) from a retrospective cohort of patients within the University of Colorado Health System. We detected CRE and ESBL infections using a set of string-matching algorithms for bacterial organism, specimen source, and antibiotic susceptibility test results. Infections were limited to the first case of each organism per patient in a 30-day period. We conducted manual chart review on a subset of cases and non-cases for validation purposes. We then performed a descriptive analysis to examine demographic characteristics of patients with CRE and ESBL infections including sex, age, infection type, and organism. All analyses were conducted using R statistical software. Results/Anticipated Results: There were 634 CRE infections from 2013 to 2023, with the majority from urine (n = 448, 70.7%) or blood specimens (n = 56, 8.8%). Over half of CRE case-patients were female (n =  362, 57.1%). The mean age was 65.0 years. Most isolates were identified as Enterobacter cloacae complex species (n = 353, 55.6%). There was a total of 4,363 ESBL infections from 2019 to 2023, and most were urine (n = 3,550, 81.4%) or blood specimens (n = 457, 10.5%). Most ESBL case-patients were female (n = 3,030, 69.4%) with a mean age of 61.2 years. The majority of isolates were identified as Escherichia coli (n = 2,932, 67.2%), followed by Klebsiella pneumoniae (n = 368, 8.4%). Validation results are pending, including sensitivity and specificity of the algorithms. Discussion/Significance of Impact: Demographic characteristics of CRE and ESBL case-patients were similar to findings from traditional public health surveillance. The algorithms will supplement traditional surveillance methods, inform future epidemiological research using EHR data, as well as contribute to the development of standardized EHR-based definitions for CRE and ESBL.

Access to an academic clinical research center (CRC) in health professional shortage areas (HPSA) can help address healthcare disparities and increase research accessibility and enrollment. Here we describe the development of a community-centered CRC in the underserved area of Sunset Park, Brooklyn, New York, centered within a larger academic health network and the evaluation of its outcomes within the first two years. In addition to resources and space, establishment of the CRC required a culturally competent and multilingual team of healthcare professionals and researchers and buy-in from the community. Between 1/2022 and 12/2023, the CRC opened 21 new trials (10 interventional and 11 noninterventional) with greater than 500 participant visits that reflect the racial and ethnic diversity of the community. These participants represent 110 distinct zip codes; 76% of these zip codes are underserved and designated HPSA. 60% self-identified as non-White and 20% identified as Hispanic, with 12 other distinct ethnicities represented. 28% of participants speak 11 languages other than English. Community-based CRCs can be created with sustainable growth to align with the mission of the National Institutes of Health and U.S. Food and Drug Administration to meet the ever-growing clinical, social, and research needs of the communities they serve.

The success of clinical research studies depends on effective recruitment and retention of study participants, yet only a small fraction of patients engage in research studies, even in academic health systems. Increasing awareness of research opportunities and facilitating connections with clinical research study teams would help to improve the success of research programs. In this Special Communications, we describe the creation and evolution of and tools used for the My Research Partners Concierge Service (MRPcs) of an academic health system. The MRPcs provides a centralized point of contact or hub for patients and community members, as well as clinical research organizations and academic partners, who have research-related questions or interests. The MRPcs helps to connect the users of the service with relevant research study teams, personnel, or resources to facilitate their engagement in a clinical research program. Our experience with the MRPcs informs our recommendation that peer institutions organize similar research service hubs for their clinical research programs to help increase awareness of and participation in clinical research by the public and to help increase the success of research programs at fulfilling their ultimate goal of improving the health of their population.

Objectives/Goals: We aimed to discover treatment candidates for uterine fibroids, a common benign tumor with adverse impacts on quality of life. Repurposing already approved medications for fibroids can expedite treatment option expansion. Using genetic proxies, we identified novel fibroid drug candidates and estimated their effect on risk of fibroid diagnosis. Methods/Study Population: We performed a genetically predicted gene expression (GPGE) analysis using S-PrediXcan and GTEx tissue models with multi-ancestry genome-wide association study (GWAS) summary statistics of fibroids (cases  =  74,294, controls  =  465). There were 81 genes significantly associated with fibroid risk. Querying drug–gene interaction databases identified 56 approved medications that target these genes, including two antihypertensives, hydralazine, and spironolactone. Using independent multi-ancestry GWAS summary statistics (N  =  635,969) for systolic (SBP) and diastolic blood pressure (DBP), we conducted GPGE analyses. Blood pressure (exposure) and fibroids (outcome) GPGE summary statistics in the same tissues were used for two-sample Mendelian randomization (MR) analyses to proxy medication effects. Results/Anticipated Results: GPGE analyses identified hydralazine/tumor protein P53 (TP53) activity and spironolactone/thyroid hormone receptor beta (THRB) activity as drug-gene candidate pairs. Both drugs increase gene activity of their paired gene. Increased TP53 expression was associated with SBP in four tissues (exposure). The MR results indicated hydralazine use, proxied by increased TP53 expression, may reduce fibroid risk by 42% per standard deviation of gene expression (odds ratio [OR]  =  0.58, p  =  1.43E-12). Increased THRB expression was associated with DBP in eight tissues and were included in the MR (exposure). The MR results suggest spironolactone use, proxied by increased THRB expression, may reduce fibroid risk by 23% per standard deviation of gene expression (OR  =  0.77, p  = 5.94E-6). Discussion/Significance of Impact: We provide biologically plausible evidence for repurposing hydralazine and spironolactone for reducing risk of fibroid diagnosis. Repurposing these hypertension medications could provide novel preventative treatments for fibroids, particularly for individuals disproportionately affected by both conditions.

Objectives/Goals: This systematic review aims to identify and synthesize evidence on the barriers and facilitators impacting the implementation of transcranial magnetic stimulation (TMS) in clinical practice, enhancing understanding for improved adoption and efficacy. Methods/Study Population: This systematic review follows PRISMA guidelines to identify relevant literature on barriers and facilitators to TMS in North America. We conducted a comprehensive search of databases including PubMed, Scopus, and PsycINFO, targeting studies published from 2000 onward. Eligible studies include qualitative and quantitative research focusing on adults aged 18 years and older in the USA and Canada. Two independent reviewers screened titles, abstracts, and full texts, extracting data on barriers and facilitators related to TMS implementation. Results/Anticipated Results: We anticipate identifying a diverse range of barriers and facilitators related to TMS implementation in North America. Expected barriers may include limited clinician knowledge, patient resistance, and logistical challenges in clinical settings. Facilitators could encompass supportive institutional policies, clinician training, and positive patient outcomes. The synthesis of findings will highlight key themes, guiding future research and practice. We aim to produce actionable recommendations for stakeholders, ultimately enhancing the effective integration of TMS in clinical care for adult populations. Discussion/Significance of Impact: This review will provide crucial insights into the barriers and facilitators of TMS implementation, informing clinicians, policymakers, and researchers. By highlighting actionable strategies, it aims to enhance TMS accessibility and efficacy, ultimately improving patient outcomes and advancing neurotherapeutic practices in North America.

Objectives/Goals: Port-site metastasis (PSM), defined as the spread of malignancies to the abdominal wall at the site of surgical ports, poses a significant challenge in cancer management. The objective of this summary overview is to describe the prevalence of and risk factors associated with PSM in various gynecological cancers after laparoscopic surgery. Methods/Study Population: Study design: Systematic Review and Meta analysis Search strategy: All international databases, without language limitations, from January 1990 to December 2023. Inclusion/exclusion criteria: Cohort, case–control, or cross-sectional observational studies reporting the frequency of, or risk factors for PSM in young and middle-aged women will be included (using the PRISMA checklist). Data extraction: two reviewers independently extracting pertinent data (using the STROBE checklist). Quality assessment and risk of bias: The quality of each study will be assessed according to the Quality Assessment Tool for Observational Studies. Results/Anticipated Results: This meta-analysis of 36 studies evaluated the proportion of successes across various populations, with a pooled proportion of 0.02 (95% CI: 0.01–0.02) based on a random-effects model. Significant heterogeneity was identified (I²  =  88.12%), reflecting notable variability between studies. Despite this, the overall effect was statistically significant (p  =  0.00). A subgroup analysis will be conducted to explore potential sources of heterogeneity, considering factors such as cancer stage, diagnostic methods, surgical approach (conventional or robotic), and study type (retrospective/prospective). Discussion/Significance of Impact: By identifying the prevalence of, and the risk factors for, PSM, this study will better inform personalized treatment approaches, surveillance strategies, and surgical decision-making to improve patient-related outcomes and long-term survival in women with gynecological malignancies.

Racially and ethnically minoritized individuals, first-generation college students, and women are significantly underrepresented in science, technology, engineering, and mathematics (STEM) careers. This lack of equal representation limits creativity and progress in these fields and perpetuates systemic barriers that discourage students from pursuing STEM pathways. This special communication introduces the three-tiered mentorship model employed in the Teen Science Ambassador Program (TSAP), which incorporates senior mentors, near-peer mentors, and high school ambassadors (i.e., mentees) to promote education, hands-on research, and career development in STEM for underrepresented students. We discuss the benefits and challenges of the three-tiered model and offer recommendations for optimizing its effectiveness to enhance mentorship experiences for all participants. Findings from the TSAP program suggest that the three-tiered approach benefited all participants: high school ambassadors gained STEM skills and confidence, near-peer mentors developed leadership and communication abilities, and senior mentors improved mentorship skills. However, the effectiveness of near-peer mentorship is highly dependent on clearly defined roles and structured involvement. Thus, feedback collected from each mentorship tier was used to inform subsequent iterations of the program. The layered mentorship structure fostered a sense of community and belonging, which is crucial for retaining individuals from underrepresented groups in STEM.

Objectives/Goals: Patients with multiple chronic conditions (MCCs) face care coordination challenges and poorer health outcomes. Outpatient telehealth may be an effective way to enhance MCC patient care given the need for multiple visits and specialists. This study seeks to describe telehealth utilization between 2013 and 2023 in Arkansas. Methods/Study Population: We utilized the Arkansas All-Payer Claims Database (APCD) to identify patients diagnosed with high-prevalence MCCs comprising diabetes with comorbid hypertension, hyperlipidemia, or asthma. We then measured telehealth utilization defined as any claim associated with a telehealth modifier code, a place of service code defining the service as occurring in the patient’s home, or remote patient monitoring. Finally, we created payer-specific (e.g., commercial or Medicaid) yearly measures of the number of any telehealth claims among MCC patients divided by the number of MCC patients for that year. Linear regression was used to measure the difference in utilization during the COVID-19 pandemic (i.e., 2020–2023) versus prior to the pandemic (i.e., 2013–2019). Results/Anticipated Results: Overall, the COVID-19 pandemic era was associated with an increase of telehealth utilization among commercial patients by 1.01 telehealth claims per MCC patient (95% CI: 0.39 to 1.62, p Discussion/Significance of Impact: Variations in telehealth uptake among MCC patients suggest heterogeneity in its suitability and necessity. We will later evaluate whether telehealth use is associated with different levels of inpatient and emergency department utilization. We expect the findings to provide clarity on the suitability of telehealth use by MCC disease status.

Objectives/Goals: Investigating the B-cell acute lymphoblastic leukemia (B-ALL)-associated germline SNP rs7090445, located in intron 3 of ARID5B, which is more frequently observed in individuals of Hispanic/Latino descent. Investigating the mechanisms behind this inherited single nucleotide polymorphisms (SNP) that may contribute to the higher incidence of B-ALL in this population. Methods/Study Population: Specific Aim 1: We hypothesize ARID5B SNP rs7090445 disrupts intrinsic enhancer function. Identification of critical DNA looping events impacted by ARID5B variants using Capture C. Affinity purification-mass spectrometry to identify potential ARID5B transcription mediators. Specific Aim 2: We hypothesize the B-ALL-associated SNP leads to a partial human B-cell differentiation block. Utilize Cas9-mediated homology-directed repair to create ARID5B SNP in primary human hematopoietic stem cells. Gene-edited HSCs will be differentiated into B cells using an ex vivo system. Fluorescence-activated cell sorting to sort our pool of cells into stages of B-cell development spectrum. Amplicon sequencing and variant allele frequency of rs7090445 SNP to evaluate its impact on B-cell development. Results/Anticipated Results: This proposal is conceptually innovative as it seeks to understand the mechanism by which the B-ALL-associated SNP rs7090445 in intron 3 of ARID5B disrupts enhancer function and investigates its impact on human B-cell development. Future research will investigate a tumor-suppressive role of ARID5B and whether it constitutes a “first-hit” of leukemogenesis. Discussion/Significance of Impact: Successful completion of this research will elucidate the critical role of the B-ALL-associated ARID5B SNP rs7090445 in human B-cell development and leukemogenesis. As this SNP is more prevalent in Hispanic/Latino populations, it will also provide crucial insights into the genetic factors behind the elevated incidence of B-ALL.

Objectives/Goals: This project investigates how early childhood neighborhood factors influence attention-deficit/hyperactivity disorder (ADHD) outcomes in adolescence. Poor neighborhood conditions have been linked to higher ADHD rates; however, the effects of these factors on academic achievement, social relationships, and risk-taking behaviors remain understudied. Methods/Study Population: A large, diverse, harmonized, cleaned dataset from a national multisite research program (Environmental Influences on Child Health Outcomes (ECHO)) will be used. Neighborhood factors will be measured using geocoded, census-level indices of neighborhood quality: the Child Opportunity Index 3.0. Adolescent outcomes include self and caregiver-reported measures of comorbid psychopathology, risk-taking behavior, and academic and social functioning. A series of regression analyses will be conducted to examine the relationship between these variables. An estimated 6000 children are expected to be included in the analyses. Results/Anticipated Results: We expect that poorer neighborhood conditions, particularly low social and economic resources, will be associated with lower overall functioning in adolescence, and that this relationship will be stronger among adolescents with ADHD relative to those without ADHD. Discussion/Significance of Impact: By identifying risk and protective factors, this project will help identify potential prevention and treatment targets for a substantial number of youth and may inform policy efforts to improve resource equity and reduce existing disparities.

Objectives/Goals: (1) Conduct a pilot study documenting prevalence of tinnitus in a sample of Puerto Rican adults at the Audiology Clinic of the Medical Sciences Campus-University of Puerto Rico, (2) categorize patterns of tinnitus, (3) document intervention received for tinnitus, and (4) study sociodemographic characteristics of Puerto Rican adult participants with tinnitus. Methods/Study Population: A descriptive retrospective study was performed reviewing 121 clinical records of patients seen at the Audiology Intramural Clinic of the Medical Sciences Campus of the Universidad de Puerto Rico between 2022 and 2023. They were analyzed to determine the prevalence of tinnitus among this cohort. The study was submitted to the Office of Human Participants for revision and approval under the exempt category. The data were used to categorize the type of tinnitus, episodic versus constant, tonal versus non-tonal and the sociodemographic description of the sample. Results/Anticipated Results: From these 121 records, 70.2% (n = 85) were females and 29% (n = 29.8) were males. Subject ages ranged between 21 and 65 years. About 30% reported being single 30.6% (n = 37), followed by 21.5% (n = 26) reporting being married. From the 62 revised clinical records of subjects that reported tinnitus, 24% (n = 29) classified their tinnitus, in terms of how long they experience its presence, as constant, while 14% (n = 17) classified their tinnitus as intermittent. From the 62 revised clinical records, 44 participants (36.4%) described their tinnitus as tonal and 64.6 % as a complex sound of those patients 38 (31.4%) reported the tinnitus as a high-frequency pitch sound. Of the 62 patient records, the majority (98.4%) informed that they never received the treatment for tinnitus. Discussion/Significance of Impact: The results indicate that more than half of adults evaluated in the UPR Audiology Intramural Clinic (51%) had tinnitus. Age range was broad developing at any age but most prevalent in middle-aged females. Manifested permanent as a tonal or a complex sound. About 98.4% informed that they never received treatment, therefore, there is a need to ensure intervention.

The potential for physicians, clinicians, and health professionals to contribute to the advancement of medical therapies through clinical research is significant. Yet, a lack of exposure to, or practical training in, the conduct of clinical research can inhibit health profession trainees from considering research careers, thus perpetuating the already limited influx of new talent. To enhance the sustainability of career pathways into research for all trainees, including those from traditionally underrepresented communities, trainees must experience early exposure to research concepts through robust training and hands-on opportunities. In 2015, the Duke Office of Clinical Research created a Research Immersion elective for Duke’s Master in Biomedical Sciences program, which prepares students for additional health professional training. The course trained students through didactic and practical experiences, with a unique interprofessional mentorship team including both principal investigator and clinical research professional mentors. Following eight cohorts of iterative course optimization, students’ confidence increased in all 24 research competencies assessed. A cross-sectional analysis of post-course outcomes in May 2024 revealed 40.4% of students had continued in research after the program and 60.6% had continued their health professions education. We attributed this success to applied learning and clear expectations and guidelines to support the mentor-student relationship.

Objectives/Goals: We will conduct a 12-week pilot randomized controlled trial (RCT) to test the feasibility, acceptability, and preliminary efficacy of a staged-intensity whole foods intervention on hemoglobin A1c (HbA1c) change in adults, diet quality change (via the 2020 healthy eating index [HEI-2020]) in adults and offspring, and diet adherence and social determinants of health (SDOH) considerations via focus groups. Methods/Study Population: In this two-arm, parallel RCT, 30 adults with prediabetes (25–59 years) and their offspring (6–18 years) will be randomized to receive the 1) 12-week whole foods intervention which includes a 2-week feeding period (all foods/recipies provided), a 6-week customizable feeding period (3 dinners/recipies weekly), and a 4-week maintenance period (no food/recipies). The control group will receive standard of care (i.e., single RD-led diet counseling session). Primary outcomes include feasibility (≥80% retention and completion of study outcome measures) and acceptability (≥75% adult self-reported diet satisfaction). Intervention effects include 1) HbA1c change at 12-weeks in adults and 2) adult/offspring HEI-2020 scores assessed via diet records. Focus groups will assess influences of SDOH on diet adherence. Results/Anticipated Results: We have received Institutional Review Board approval, and recruitment is planned for January 2025. We will enroll 30 families from the greater Nashville, TN area. An intent-to-treat analysis will be conducted to test the preliminary effects of the whole foods diet intervention on the 12-week change in HbA1c (adults only) and 2020-HEI diet quality scores during the intervention period (adults and offspring). Focus groups will be conducted to understand how individual and family needs/preferences and SDOH may be perceived barriers or facilitators of diet adherence. Data generated from this study will be used to guide a fully powered RCT of our whole foods intervention to assess long-term effects on additional diabetes and metabolic outcomes and assessment of SDOH influences to support long-term adherence. Discussion/Significance of Impact: A healthy diet pattern is an effective nonpharmacological solution to prevent T2D, but only if it can be maintained. A family-centered whole foods diet pattern that uses “food as medicine” and considers how individual and family needs/preferences, and SDOHs could be an effective and sustainable multigenerational solution to prevent T2D in families.

The attitudes toward genomics and precision medicine (AGPM) measure examines attitudes toward activities such as genetic testing, gene editing, and biobanking. This is a useful tool for research on the ethical, legal, and social implications of genomics, a major program within the National Institutes of Health. We updated the AGPM to explore controversies over mRNA vaccines. This brief report examines the factor structure of the updated AGPM using a sample of 4939 adults in the USA. The updated AGPM’s seven factors include health benefits, knowledge benefits, and concerns about the sacredness of life, privacy, gene editing, mRNA vaccines, and social justice.

Objectives/Goals: In mice, it has been shown that loss of Cib2 (calcium and integrin-binding protein 2) results in progressive retinal disease that recapitulates many characteristics of age-related macular degeneration (AMD). This study aims to characterize transcriptional changes in the retinal pigment epithelium (RPE) that underlie this disease process. Methods/Study Population: RPE tissue samples, pooled from 2–3 mice for each biological group, were collected from Cib2-KO and wildtype (WT) mice at two (young) and eight (aged) months of age. Bulk mRNA sequencing was performed using the Illumina HiSeq 4000. Reads were aligned to the UCSC mouse reference genome and quantified using HTSeq. Significant differentially expressed genes (DEGs) between mouse genotype and age groups were assessed using DESeq. CLICK unsupervised clustering followed by gene ontology analysis was performed to identify cellular processes and molecular pathways affected by loss of Cib2 as well as age. Results/Anticipated Results: CLICK analysis revealed several functional pathways that are differentially expressed between sample groups. For example, in both young and aged mice, pathways upregulated in Cib2-KO samples included calcium signaling, RhoA signaling, and integrin signaling. Uniquely downregulated DEGs in young Cib2-KO animals were related to complement and coagulation cascades, LXR/RXR activation (related to lipid synthesis and transport), and phagosomes. Aged Cib2-KO mice displayed the most significant downregulation of genes in the phototransduction pathway, indicating temporal changes in functional pathways that correlate with disease progression. Next steps in analysis include investigating patterns in RPE- and AMD-signature gene sets that may identify molecular pathways more specific to human disease. Discussion/Significance of Impact: Many current studies investigate the role of complement activation, vesicle trafficking, and ion transport as top contributors to AMD development. We identified DEGs paralleling many of these molecular pathways in Cib2-KO mice, highlighting their potential as a model to study age-related RPE pathologies and evaluate therapeutic interventions.