Objectives/Goals: In alignment with the Clinical and Translational Science Awards (CTSA) UM1, continuous quality improvement (CQI) needs to be integrated into the elements and hub evaluation. As a first step to operationalizing this process, the University of Cincinnati hub (CCTST) evaluation team developed a systematic approach to prioritizing and sequencing tasks for aligning evaluation methods with CQI. Methods/Study Population: A scoring sheet was developed to provide a framework for prioritizing and developing the sequence and timeline for supporting elements in aligning their evaluation methods with CQI. The scoring sheet assessed: 1) impact – defined as the results from completing the task and implementing enhancements; 2) effort – defined as the amount of resources (time, personnel, and materials) needed to complete the tasks; 3) reach – defined as number of individuals (e.g., CTSA employees, members, researchers, trainees, and community members) impacted by the tasks or products of the tasks; 4) urgency – defined as a task that is time-sensitive due to a deadline and has a clear consequence if not completed on time. Each component was assessed using a 3-point scale (e.g., minimal, moderate, and high). Results/Anticipated Results: In Fall 2024, the CCTST evaluation team met with respective elements to collect data on their: 1) need from the evaluation team to support aligning their evaluation methods with CQI, 2) challenges and barriers to improving evaluation and aligning with CQI methods, 3) number of hours per month available to support improving evaluation methods, and 4) current resources to dedicated to conducting an evaluation. Next, the evaluation team will transcribe the data from the meetings and code the data into the scoring sheet for each element. The scoring sheet is anticipated to produce a score that will be used to develop the sequence, timeline, and initial tasks for supporting elements in improving evaluation methods and aligning with CQI over the first year of the UM1. Discussion/Significance of Impact: CTSA hubs’ evaluation teams operating at full capacity may encounter barriers to implementing CQI efforts. This systematic approach – assessing the impact, effort, reach, and urgency to sequence evaluation and CQI alignment – can support evaluation teams by ensuring a balanced workload and optimizing operations for quality improvement.

Objectives/Goals: We aim to explore the associations of race/ethnicity and socioeconomic status (SES): 1) with grip strength, walking speed, and comorbidity index cross-sectionally and 2) with the change in comorbidity index and mortality risk over four years of follow-up in cancer survivors. Both aims will examine the potential mediating role of cytomegalovirus (CMV) infection. Methods/Study Population: This study includes 1,602 cancer survivors (mean age = 72 years, 10% Black, 54% female) from the Health and Retirement Study (HRS), a nationally representative U.S. sample followed for health outcomes until 2020. HRS measured CMV immunoglobulin G (IgG) antibody levels (from blood samples), grip strength, and walking speed in 2016. We will apply linear regression to examine the associations of race/ethnicity and SES with grip strength, walking speed, and comorbidity index cross-sectionally and with the change in comorbidity index over four years of follow-up. We will apply Cox proportional hazard regression to examine the associations of race/ethnicity and SES with mortality over four years of follow-up. In all models, we will investigate the potential mediating role of CMV infection in these associations. Results/Anticipated Results: We expect that CMV infection mediates the associations of race/ethnicity and SES with age-related health outcomes, including muscle weakness (measured by grip strength), decreased functional performance (measured by walking speed), comorbidity index, and mortality in elderly cancer survivors. Discussion/Significance of Impact: If our hypothesis is confirmed, the findings may inform physicians to closely monitor CMV infection among cancer survivors from socially disadvantaged groups and apply treatment if needed. Several oral medications for CMV exist, and CMV vaccines are currently undergoing testing in clinical trials. This will make the treatment for CMV more accessible.

Objectives/Goals: Trainees in clinical and translational science (CTS) must learn to effectively communicate their research ideas and findings to a range of audiences. As part of our science communication curriculum, we developed ORAL and WRITTEN science communication rubrics for our trainees to use across their courses and research activities. Methods/Study Population: The Tufts CTS Graduate Program is the training core of the Tufts CTSI and its associated pre- and post-doctoral T32 awards. Approximately 10 trainees with a range of backgrounds (e.g., physicians, medical students, master’s-level researchers, and basic science PhDs) matriculate each year. Faculty members and staff with expertise in science communication and pedagogy formed a committee to develop the rubrics. Because oral and written communication require different skills, we developed separate rubrics for each. We reviewed our current science communication curriculum, reviewed existing communication rubrics, and identified common mistakes students make. Following pilot testing by students and faculty pilot for one semester, we modified the rubrics based on informal feedback. Results/Anticipated Results: Both rubrics include a section to identify the target audience and specific items organized by theme. Oral rubric themes include presentation content, slides, verbal communication, nonverbal communication, and following instructions. Written rubric themes include overall, manuscript/proposal sections, and following instructions. The rubrics serve as feedback tools for faculty and students to evaluate work others produce and as self-evaluation tools. Feedback elements include a 4-point rating for each rubric item, open text feedback for each theme, and an open text holistic assessment. We now use the rubrics in our study design course, which features student presentations of planned research, and in our writing course. We anticipate collecting formal student feedback to further evaluate the rubrics. Discussion/Significance of Impact: Our rubrics can supplement existing science communication training and can be integrated into all CTS coursework and research activities. For future clinical and translational scientists to have the greatest impact, they must learn to effectively communicate findings to multiple audiences, ranging from experts in their field to the general public.

Objectives/Goals: Micro-credentialing programs provide a rapid solution to the growing shortage of clinical research professionals (CRPs) by expanding the applicant pool and improving training efficiency. This study evaluates the impact of a micro-credential course on CRP education and its potential to reduce staffing shortages. Methods/Study Population: To address the CRP staffing shortage, new and existing clinical research staff at the Rutgers Cancer Institute of New Jersey (CINJ) participated in a micro-credential badging course developed by NJ ACTS and Rutgers’ Master’s in Clinical Research Management Program. The course focused on key clinical research topics designed to equip participants with foundational knowledge. Post-completion, surveys were administered to both participants and CINJ management to assess the program’s effectiveness. The survey measured perceived knowledge gains, interest in further opportunities, and the program’s potential to alleviate staffing shortages. Survey results were analyzed to determine the program’s overall impact on CRP education and staffing challenges. Results/Anticipated Results: Survey results demonstrated significant knowledge gains among participants, with 85% reporting increased confidence in clinical research topics after completing the micro-credential course. Additionally, 70% of participants expressed interest in pursuing further opportunities in the field. CINJ management reported smoother onboarding processes and noted an improvement in job readiness among new hires. The CRC Badge has since been integrated into CINJ’s formal onboarding process. Overall, the micro-credential program contributed to expanding the CRP applicant pool, improving training efficiency, and offering a short-term solution to alleviate staffing shortages. Discussion/Significance of Impact: This research demonstrates the effectiveness of micro-credentialing in addressing the critical shortage of CRPs. By rapidly equipping staff with essential knowledge, the program broadens the applicant pool, enhances onboarding, and offers an immediate solution to workforce gaps.

Objectives/Goals: This research aims to identify genetic alterations influencing congenital anomalies of the kidney and urinary tract (CAKUT) and bridge a fundamental gap in understanding the cellular mechanisms underlying kidney development, with the long-term goal of enhancing treatments for congenital renal anomalies. Methods/Study Population: We will use a loss-of-function approach in combination with immunofluorescent microscopy techniques to determine the influence of Dnmbp perturbation on Daam1 localization, actin assembly, and junctional turnover. Additionally, to establish a foundation for delineating the molecular mechanism of DNMBP during kidney development, we will utilize clinical whole exome sequencing data to identify human DNMBP mutations associated with urogenital anomalies. Furthermore, we will determine whether human DNMBP mutations linked to CAKUT lead to disruptions in nephron development through loss-of-function rescue experiments in Xenopus. Results/Anticipated Results: Here, we evaluate the dynamics of Dnmbp-mediated transport of Daam1 within the developing kidney and show preliminary data suggesting that Dnmbp and Daam1 directly interact to promote adhesive contact formation between nephron progenitor cells. Furthermore, we propose a model in which Dnmbp functions as a critical regulator of epithelial tissue morphogenesis and provides a functional link between the dynamic processes of actin cytoskeleton regulation, intracellular adhesion, and vesicular transport. Future studies will determine whether Dnmbp interaction with Daam1 facilitates junctional actin assembly by directing Daam1 to cell–cell contact sites via Dnmbp-associated vesicle targeting, enhancing our understanding of the cellular mechanisms influencing tubule morphogenesis. Discussion/Significance of Impact: This research will establish a previously unknown role for DNMBP in kidney development and provide a comprehensive understanding of the impacts of simultaneously regulating vesicular transport and actin dynamics in nephrogenesis.

Objectives/Goals: To strengthen postdocs’ skills in developing and reviewing competitive proposals, advancing translational research by leveraging core facilities at Indiana University, Purdue University, and the University of Notre Dame, fostering collaboration, and preparing participants of the program for future funding success. Methods/Study Population: The Postdoc Challenge is a state-wide program for postdoctoral scholars across Indiana to gain hands-on experience in developing and reviewing competitive grant proposals. Participants compete for a $5,000 award to use any of the Indiana Clinical and Translational Science Institute (CTSI)-approved core facilities. Through workshops and following NIH guidelines for the review process, participants refine their proposal-writing skills and serve as reviewers for peers’ proposals. The program is designed to support translational research, utilizing the core facilities at Indiana University, Purdue University, and the University of Notre Dame. Participants are trained in grant proposal writing, reviewing using NIH criteria, and engaging in peer discussions, developing critical skills necessary for future funding success. Results/Anticipated Results: Since its launch in 2014, the Indiana CTSI Postdoc Challenge has funded 54 postdoctoral researchers, with 276 applications reviewed. The program has strengthened participants’ grant proposal writing skills and peer review capabilities. Career outcomes include several postdocs securing assistant professor positions and other prestigious roles, such as an Associate Principal Investigator at the National Biodefense Analysis and Countermeasures Center, and a Toxicologist at the CDC. Participants also report enhanced collaboration, greater access to core facilities, and significant career advancement, including support for international postdocs seeking permanent residency. Discussion/Significance of Impact: The Postdoc Challenge has significantly improved postdoctoral researchers’ grant proposal writing and peer review skills, helping them secure faculty and research positions. By fostering collaboration across Indiana’s top universities and utilizing core facilities, the program accelerates translational research and career success.

Objectives/Goals: To assess the effect on the immune response to COVID-19 in children exposed to pesticides. The hypothesis is that increased pesticide exposure results in different immunological response to COVID-19. The goal of the proposal is to improve scientific knowledge on factors affecting COVID-19 and identify a modifiable factor to reduce these disparities. Methods/Study Population: A cross-sectional analysis of children (aged 5–17 years) with asthma to assess pesticide exposure and immune markers of SARS-CoV-2. SARS-CoV-2 infection or vaccination was determined with blood exposome RNA analyses assessed from blood samples taken at baseline. Immunological response was measured using neutralizing, phagocytizing, and NK-activating antibody responses biomarkers using plasma antibody isotyping, effector functions, T-cell activation-induced marker (AIM), and recall cytokine secretion assays on lysed, whole blood. Pesticide exposure was assessed as concentration of four urinary metabolites in a spot urine sample adjusted for creatinine. Unadjusted regression models were created to assess the effect of 3-phenoxy benzoic acid, a common pyrethroid pesticide, on immune markers. Results/Anticipated Results: Children’s (N = 30) average age was 10 years (interquartile range: 8–11) A majority of children were male (63%) and Non-Hispanic Black (73%). The majority of children had markers of SARS-CoV-2 infection (77%). Of the 4 pesticide metabolites assessed, only 3-PBA was commonly found (77% of samples > LOQ). Higher urinary concentrations of 3-PBA are associated with a significant (p Discussion/Significance of Impact: Significant associations in cytokine and inflammatory marker may indicate a Th2-skewed response, and dysregulated cytokine responses can lead to severe disease. A suggested increase in T-cell activation markers (e.g., CD4, CD8) may indicate potential exhaustion if excessively activated.

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: The goal of this study is to resolve the complexity of the adipose precursor cells and identify potential therapeutic targets/mechanism to treat obesity, diabetes, cancer cachexia, and related metabolic conditions in both white and brown adipose tissues. Methods/Study Population: White and brown adipose precursor cells were isolated from neonatal P0 mice and expanded in culture for single-cell RNA sequencing analysis. Unsupervised machine learning was used to unbiasedly cluster and categorize sequenced cells. Differentially expressed genes were used to identify populations via pathway analysis. Populations were then validated with published datasets via integration, reference mapping, and module scoring to ensure our dataset is reflective of known literature. Then, white and brown datasets were combined and unbiasedly clustered. Finally, signaling inferences using CellChat was used to identify significant signals being sent to and received from each cluster based on ligand–receptor pairs. Results/Anticipated Results: ScRNAseq revealed 7 subclusters in both white and brown adipose tissues. Differential expression and trajectory inferences revealed that white and brown precursors develop into two distinct fates: committed adipogenic precursors (CAPs), where these cells will be mature lipid-laden adipocytes; or fibro-adipogenic precursors-like (FAPLs), where these cells preferably stay in a fibroblast-like, antiadipogenic phenotype. Integrating white and brown cells with subsequent reclustering reveals that white and brown FAPLs are highly similar to one another by being clustered together. Cell signaling inferences and pathway analysis reveal that white and brown FAPLs may participate in the regulation of adipogenesis and angiogenesis of the adipose tissue. Discussion/Significance of Impact: Our results demonstrated that brown and white precursor cells share a common regulatory subpopulation with similar gene expression profiles, highlighting a more interconnected regulatory landscape in adipose tissue than previously understood. These findings reveal novel mechanisms of systemic metabolism and provide new therapeutic targets.

Objectives/Goals: Engage the research professional (RP) workforce in assessing job satisfaction, motivators, barriers, and levels of support throughout the research enterprise. The goal of this collaboration is to foster a positive culture, inform manager training, ensure RP retention, and enhance career mobility pathways. Methods/Study Population: Methods include a HR data compilation/analysis and focus groups for new RP’s (Results/Anticipated Results: This initiative will articulate the current culture and climate of the research enterprise and identify key strategic areas for growth. The UMN Clinical and Translational Science Institute (CTSI) will build off the design of an internal survey at Vanderbilt (2018) to encompass organization-specific challenges, the post-pandemic research landscape, and the UMass Diversity Engagement Survey. This process will also generate specific insights including RP sentiment statements, trends in how RP’s describe their day-to-day work, assessment of barriers, analysis of retention benchmarks, and defining employee hopes/motivators. The CTSI will also identify salient RP growth opportunities, leadership competencies, and areas of non-monetary compensation to improve satisfaction and career mobility. Discussion/Significance of Impact: Targeted interventions will be developed to address RP satisfaction barriers and leverage opportunities for KPI improvement. Results will be disseminated to managers, administrators, and the CTSI network. Resource development will include RP personas, job description/hiring templates, and strategic guides for key operational challenges.

Objectives/Goals: Some children with asthma benefit from care from asthma specialists: allergist/immunologists or pulmonologists. However, a limited supply of specialists poses access problems for some children. Our objective was to describe the state of specialist care for pediatric asthma in Maine. Methods/Study Population: Using Maine all-payer claims data for April 2018–April 2021, we identified children with asthma meeting criteria for subspecialist referral based on NIH Expert Panel Report criteria. We determined which of these children had encounters with an allergist-immunologist or pediatric pulmonologist during the study period and performed logistic regressions to determine what demographic traits were associated with receipt of care. Results/Anticipated Results: Among children meeting criteria for specialists referral, 33% had an encounter with an asthma specialist. Specialist encounters were associated with younger age (p<0.001) and male sex (p = 0.003). Encounters were negatively associated with Medicaid insurance (versus commercial, p<0.001) and living in more rural areas (RUCA codes 4–10, p<0.001), lower childhood opportunity index (high or less, <0.001), and longer travel time to pediatric asthma specialists in Maine (<0.001). Discussion/Significance of Impact: Specialist care for children with complex or severe asthma is an evidence-based practice that is not equally accessible to all children in Maine. This may restrict their access to specific asthma therapies such as allergic desensitization and monoclonal antibodies.

Objectives/Goals: Pancreatic ductal adenocarcinoma (PDAC) is a deadly disease with a mean survival of only 11 months even with the most advanced treatment to date. The desmoplastic microenvironment of PDA is thought to play a critical role in therapy resistance. One pathway that might be responsible for resistance to immunotherapy is the CXCR4-CXCL12 axis. Methods/Study Population: In this study, we propose to evaluate the effect of CXCR4-CXCL12 inhibition on dual checkpoint inhibition in KPC mouse model of PDAC and patient-derived explants. PDAC mouse models are made with pancreatic cancer cells driven by loss of TP53 and activation of KRAS. These models are treated with PD1 inhibitor Balstilimab and an FC-modified CTLA4 Botensilimab with or without CXCR4 inhibitor BL8040. In addition, we make explants of patient tumors along with their tumors and autologous peripheral blood mononuclear cells and this model is similarly challenged with BOT/BAL and BL8040. Using immunofluorescence and flow cytometry, we quantify and evaluate the spatial relationships between different cell populations. Most notably, we evaluate the relative abundance of CD8+ T cells in control and treated conditions. Results/Anticipated Results: We expect the inhibition of CXCR4-CXCL12 axis, along with two new potent checkpoint blockers, will lead to infiltration of CD8+ T cells in both the mouse and human PDAC models. We also expect this to translate into more tumor cell killing as demonstrated by Caspase activities and tumor shrinkage. Discussion/Significance of Impact: If our hypothesis is proven in both mouse and human PDAC models, this study will serve as a basis for a phase I/II clinical trial testing this combination of drug.

Objectives/Goals: To determine the heterogeneity in CD4:CD8 ratio in a well-characterized cohort of PWH and to investigate the predictors of intestinal CD4:CD8 ratio reconstitution (CD4:CD8>1) and its impact on systemic inflammation. Methods/Study Population: We enrolled 52 PWH on ART and with peripheral HIV-RNA Results/Anticipated Results: PWH had a lower CD4:CD8 ratio both in the peripheral blood [p1. This subset of PWH was more likely female (62% vs. 38%, p = 0.0158), diagnosed with HIV for a longer time [p = 0.0347] have longer duration of most recent viral suppression [p = 0.0365] higher CD4+ T cells at enrollment [p =  0.0262] and higher CD4+ T cell nadir. Multiple logistic regression showed that duration of HIV infection [OR 1.13 (95% C.I. 1.02–1.3)] and CD4 =  T cell nadir[OR 1.01 (95% C.I. 1.001–1.016)] were associated with colonic CD4:CD8 >1. Colonic CD4:CD8 ratio partially correlated with the peripheral blood CD4:CD8 ratio (r = 0.274, p = 0.068) and with the pro-inflammatory cytokines IL-20 (r =  -0.413, p = 0.036) and SLAMF-1 (r =  -0.329, p = 0.074). Discussion/Significance of Impact: In PWH, CD4:CD8 ratio

Objectives/Goals: The goal of the RC2 Systems Marketing Analysis for Research Translation (SMART) special innovation program is to develop and test a structured approach for working with research teams and communities to accelerate the translation of clinical and community innovations to address health inequities by integrating social marketing with community-based system dynamics. Methods/Study Population: The SMART program is a consultancy service for CTS teams focused on selecting and tailoring implementation strategies for advancing equity. We use social marketing for understanding the alignment of practice innovation feature sets with community priorities for advancing health equity; and community-based system dynamics to understand and refine the dynamics of scaling up and sustaining the implementation of innovations with sufficient reach to address regional health inequities. The program is implemented as community-engaged group model-building workshops with research teams, with follow-up marketing analyses and computer simulation of implementation strategies of innovations and development of implementation roadmaps. We use developmental program evaluation to revise the SMART program. Results/Anticipated Results: Anticipated results from piloting the SMART innovation program with four research teams include (1) design matrices pre and post-workshop for each innovation; (2) system dynamics simulation models and analyses of implementation and scale-up of innovations; (3) analysis of the SMART program for highest impact, with priors for estimating subsequent SMART program performance; and (4) a revised SMART program based on results from the developmental program evaluation. Discussion/Significance of Impact: This work highlights the feasibility and benefits of combining methods that have been cited in implementation science for understanding the complexity of implementation to accelerate the translation of innovations into clinical and community settings for advancing health equity.

Objectives/Goals: This study aims to evaluate common features of mobile health (mHealth) apps and their role in helping caregivers make health decisions for children. Methods/Study Population: A scoping review of literature on caregivers’ use of mHealth apps (published since 2008) was conducted across 5 databases (i.e., Embase, PubMed, CINAHL, Clinicaltrials.gov, and IEEE Xplore). Selected papers were categorized based on app purposes, target users, and mHealth agile development phases. Common features were also identified and analyzed along with users’ pros and cons. Further, primary feature requests were summarized to inform future development. Results/Anticipated Results: This review included 62 studies. Most apps were about maternity and infant care and specific diseases. Major users were caregivers and pregnant women. Around 20% of papers covered multiple phases in the mHealth agile development lifecycle. The effectiveness/clinical trial (phase III) was the most common. E-learning, personalization and customization, and health tracking features were the three most common features of mHealth apps included in this review. More positive feedback was found regarding features than concerns. Caregivers perceived apps as helpful and empowered them to make informed decisions. Concerns were mainly over 1) technical issues, 2) inappropriate design, and 3) ambiguous terms. Requested new features included content comprehensiveness, user engagement, and usage flexibility. Discussion/Significance of Impact: To our knowledge, this is the first review to investigate the usability of mHealth app features in this area. The results offer feasible strategies for developers to improve the effectiveness of apps for caregiver decision-making.

Objectives/Goals: The overall goal of this project is to determine bacterial transcriptional signatures from clinical sputum and assess their potential to monitor treatment response and predict the outcome of drug therapy in patients with tuberculosis (TB). Methods/Study Population: We are developing a novel transcript capture sequencing (TC-Seq) approach to sequence the mRNA of Mycobacterium tuberculosis (Mtb) and analyze transcriptomes from clinical samples containing minimal amounts of bacterial RNA. This protocol generates single-stranded biotinylated probes from Mtb DNA. Probes are hybridized to and allow enrichment of Mtb-specific mRNA within next-generation RNA sequencing libraries. We will apply TC-Seq to sputum samples collected throughout an 18-month Phase II clinical trial investigating response to TB treatment to compare the transcriptome of Mtb between patients whose treatment results in cure or relapse. Results/Anticipated Results: We have refined a technique to generate biotinylated probes starting from DNA of lab grown Mtb. This protocol achieves robust and unbiased sampling of the Mtb transcriptome from mixed samples containing both human and Mtb RNA. Preliminary sequencing of clinical sputum collected pretreatment has generated 1–4 million Mtb-specific reads, a sequencing depth that allows examination of the entire bacterial transcriptome. We will measure differential gene expression before and during treatment as well as between cure and relapse cases. These results will allow us to characterize bacterial response to treatment and identify bacterial markers that correlate with relapse. Discussion/Significance of Impact: Understanding Mtb activity during treatment will offer new ways to assess the efficacy of different treatment regimens. Crucially, identifying clear bacterial markers that demarcate a cure or relapse outcome will have a significant impact on determining patient eligibility for shorter drug therapy.

Objectives/Goals: We investigate how the gut microbiome protects against arsenic toxicity, showing antibiotic perturbation increases toxicity and causes interindividual susceptibility to a sepsis-like disease state in mice. Here, we aim to understand how baseline microbiomes from various mouse vendors impact these outcomes and characterize the observed disease. Methods/Study Population: We developed a novel mouse model where mice are exposed to an antibiotic (cefoperazone) for 2 days, followed by co-exposure to the antibiotic and 100 ppm arsenate. So far, we have evaluated C57BL/6N mice from MSU’s in-house colony, Taconic Biosciences (TAC), and Jackson Labs (JAX), along with C57BL/6J mice from JAX. To determine if the baseline microbiome drives inter-vivarium differences, we established in-house breeding colonies of TAC- and JAX-origin mice at MSU. This allowed us to assess whether, when housed under identical conditions, these mice still show differences in mortality based on their original microbiomes. To characterize the arsenic-induced sepsis-like disease, we performed blood biochemistry assays to quantify the white blood cell populations, and sepsis biomarkers used in clinical settings. Results/Anticipated Results: We observed differences in survival rates between genetically identical mice from MSU (45%), TAC (30%), and JAX (2.5%) in our model. From this, we characterized the baseline composition of the gut microbiomes of these mice and found they were significantly different from each other. We are still awaiting results from our in-house TAC and JAX experiments but expect them to have similar gut microbiome compositions to those directly purchased from TAC and JAX and respond similarly. In our blood biochemistry analysis, we found sick mice presented with low WBC counts and notable biomarkers indicative of liver, heart, and kidney distress. We also anticipate that 16S sequencing results of cecal contents will further support findings by providing evidence of a bacterial infection in the ceca of sick mice. Discussion/Significance of Impact: Collectively, our work demonstrates that antibiotic perturbation of the gut microbiome induces an inter-individual and inter-vivarium susceptibility to an arsenic-induced sepsis-like disease state. This work highlights the importance of considering antibiotic use in the risk assessment of arsenic to better protect the health of those exposed.

Objectives/Goals: Both diabetes and obesity are major health issues in the USA. Though much focus is given on the impact of lifestyle modifications to control diabetes and obesity, more information needs to be established about the association of social determinants of health and them. This study explores these associations, focusing on the DMV area. Methods/Study Population: The data for this study were collected for 158 counties which cover two states Maryland and Virginia, and Washington DC from PolicyMap. PolicyMap is a geography information system (GIS) that aggregates different types of data from different sources for research purposes. County-level data on public health related to different SDoH like median age, and percentages proportions of different ethnicity (Hispanic or Latino), percentages of different race, and nativity (foreign born), gender (ratio of male to female), access to primary healthcare, social vulnerability index (SVI), and median household income was used in this study. Statistical methods like multiple regression, one way ANOVA, and Pearson’s correlation coefficients were used to determine which factors are associated with these two conditions. Results/Anticipated Results: For both diabetes prevalence and obesity, multiple linear regression model with backward elimination was used to select variables which associated with them. The backward elimination process selected the set of factors for which the adjusted R square was the highest. In both cases, median household income, median age of population, social vulnerability level, percentage of white population, and percentage of foreign-born population were found to be significant at 5% level of significant. Pearson’s correlation coefficients showed significant positive relationship between factors like obesity and diabetes, median age and access to health care, and negative relationship between obesity and foreign born. Income, healthcare access, and white population were found to be significantly different SVIs from ANOVA. Discussion/Significance of Impact: This research study found that some SDoH affect diabetes and obesity in the same direction. The association is positive for median age and negative for income, SVI, percentage of white population, and foreign born. The associations were found between actionable and non-actionable factors like percentage of white population with access to health care.

Objectives/Goals: Our study team won a Public Health Answers to Speed Tractable Results (PHASTR) contract to conduct a target trial emulation to answer “Does metformin show a reduction of severe outcomes of COVID-19 or of Long COVID in the N3C Data Enclave?” We quickly delivered an answer due to productive technical and collaboration support in the N3C. Methods/Study Population: Our analytic plan was updated based on helpful feedback from the PHASTR program. We performed a trial emulation analysis using the N3C data, comparing adult new users of metformin to controls prescribed fluvoxamine, fluticasone, ivermectin, or montelukast. The composite outcome was Long COVID or Death (LC/D) within 180 days of COVID infection. We used entropy balancing to estimate the average treatment effect with a weighted log-linear model. Productivity was enhanced by reusing code workbooks and validated codesets from related N3C projects. The team of 4 (physician, informaticist, data programmer, and statistician) and key unpaid advisors spent 10 weeks developing and analyzing the data. Results/Anticipated Results: Totally, 9,660 patients were identified for analysis. After weighting, there were 248 in the metformin and control groups. In the metformin group, 4.0% developed LC/D vs. 8.5% in the control group, with an adjusted risk ratio (aRR) of 0.47 (95% CI 0.25 to 0.89). Results were consistent across subgroups and sensitivity analyses. The PHASTR contract structure helped produce high-quality results quickly by not only providing funding but also requiring a compressed timeline for a small team to focus on the study. The most time was spent on contract execution, enclave provisioning, and too many last-minute download requests. A project final report was submitted in March and a full manuscript was submitted in September. Discussion/Significance of Impact: The analysis was productive because the environment made reuse easy and supported rich collaborations among clinicians, informaticists, epidemiologists, statisticians, and data developers. Advice from PHASTR advisors (Axel) and N3C diabetes domain team members was also key to a faster completion.

Objectives/Goals: To assess the impact of the MATCH Program on mentees and mentors over the years, we have surveyed both groups on the effectiveness of the mentorship process, how the MATCH program influenced mentees’ future career plans, and their ongoing interest in clinical research. Methods/Study Population: To evaluate impact on mentees and mentors in the most recent cycle, we fielded two program evaluation surveys, for mentors and mentees. The surveys were distributed and collected using Qualtrics in May 2024. The mentee survey collected data on relationship with mentors, quality of mentorship, future career/education plans, and self-assessment of the program impact. The mentor survey collected data on relationship with mentees, mentees’ engagement, and a self-assessment of the program impact. Qualitative analysis was conducted to determine key themes expressed by participants. The responses were compared to assess the effectiveness of the mentoring relationship from both parties. Results/Anticipated Results: Respondents included 15/20 (75%) mentees and 15/20 (75%) mentors. All mentees (100%) and mentors (100%) stated they would like to continue their relationship outside of the program. The majority of mentees 13/15 (87%) and mentors 13/25 (87%) also viewed their mentee/mentor relationship to be excellent or good. Most mentors 10/15 (67%) stated it was their first time serving as a mentor for the program. Mentees also found their experience in the program very beneficial with 6/15 (40%) stating that MATCH changed their career plans. In addition, most mentees 14/15 (93%) indicated that they are community college or four-year college/university bound. Most mentees 11/15 (73%) indicated an interest in pursuing a health or medical career. Also, 10/15 (67%) mentees stated an interest in pursuing a career in research. Discussion/Significance of Impact: Both mentees and mentors have benefited from the program’s daisy chain mentoring and the program has helped facilitate a potential lifelong mentorship between mentees and mentors. The program also demonstrates promise of developing a pre-health pathway for historically underrepresented students in STEM.