Objectives/Goals: Adults from minority groups report more severe and pervasive pain than those in majority groups, resulting in a disproportionate burden of pain. Whether race disparities in pain outcomes exist in persons with multiple sclerosis (MS) is unknown. We examined the association of race with pain intensity, pain interference, and pain phenotypes in MS. Methods/Study Population: Ambulatory adults with medically documented MS completed a comprehensive survey battery including demographics and clinical data. Pain outcomes were assessed with four measures: Patient Reported Outcome Measurement Information System (PROMIS) pain intensity and pain interference short forms, the American College of Rheumatology Fibromyalgia Survey Criteria (a surrogate of degree of nociplastic pain), and the PainDETECT (a surrogate of neuropathic pain). Participants were categorized as either Black/African American or White based on their self-reported race. Four sets of unadjusted and adjusted (including sex, age, years since diagnosis, MS subtype and Patient Determined Disease Steps—PDDS score) linear regression models were built to examine the associations between race and pain outcomes. Results/Anticipated Results: A total of 258 participants (200 White and 58 Black), with a mean age of 51 ± 12 years, mostly female (77%), an average of 15 ± 10 years since diagnosis, a PDDS score ranging from 0 to 6, and mostly diagnosed with RRMS (79%), were included in the analyses. Unadjusted regression models indicated that pain intensity (β  =  5.20; 95% CI 2.73 – 7.66, p < 0.001), pain interference (β  =  5.17; 95% CI 2.29 – 8.06, p < 0.001), and nociplastic pain (β  =  2.41; 95% CI 0.40 – 4.42, p  =  0.019) were all higher for Black/African American participants compared to White participants. The differences remained statistically significant in adjusted models. No differences in neuropathic pain were observed between Black/African American and White participants in both unadjusted and adjusted models. Discussion/Significance of Impact: We highlight an increased burden of pain in Black/African American with MS compared with their White counterparts. The findings illuminate potential future targets of interventions to reduce disparities in the experience and impact of pain. A comprehensive examination of the role of social determinants in pain outcomes in MS is further warranted.

Objectives/Goals: The National Research Mentoring Network Coordination Center (NRMN CC) received funding from NIH to create an Online Community of Practice (OCoP) for Research Managers (RM). These RM contributed to advancing the research on the science of mentorship in STEMM. In a Proof of Concept, RM explored various aspects of their mentorship research support work. Methods/Study Population: An OCoP met 18 times across the 5-year grant to share experiences working to advance the science of mentorship in STEMM. Topics, frequency, and length of meetings were selected based upon several needs assessments surveys from the RM community. RM were invited to join the OCoP based on their roles as the point people for administrative activities in research projects (e.g., finances, budgets, training, and project management). RM often supervised staff, collected data, monitored IRB protocol compliance, and conducted research. RM played a pivotal role in the gathering and sharing of common measures across the 11 U01 studies to allow for greater confidence in research findings on mentorship (McConnell, 2021). Results/Anticipated Results: Our primary goal was to provide a supportive community for RM contributing to mentorship research and data sharing. The results from several needs assessments exemplified a request for this support from the community to engage in an OCoP focused on their professional development. Therefore, the OCoP served as a starting point to explore the duties, functions, roles and responsibilities of RM, and extended into providing professional development. Although the number of RM attending decreased as the grant entered the no-cost extension phase, a subgroup of RM expressed interest in continuing the OCoP to focus on dissemination of research findings, further supporting the need for this community. Discussion/Significance of Impact: RM supported 11 research projects and contributed to the data collection for over 6,000 participants. Few opportunities exist to create an OCoP for large scale data collection on experiences with mentorship in STEMM. RM were pivotal in their role with the NRMN to enhance the training and career development of individuals from diverse backgrounds.

Objectives/Goals: Trainees in clinical and translational science (CTS) take courses in biostatistics, epidemiology, and other quantitative areas. To be most successful, trainees require competency in algebra. We developed a quantitative assessment and study guide to assess trainee’s quantitative skills and provide review material to address weaknesses. 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) and varying math education experiences matriculate each year. We wanted to address the resulting range of quantitative skills to help students succeed in our program. In Spring 2023, we met with faculty teaching quantitative courses to identify core algebra concepts needed to succeed in their classes. A graduate student in computational mathematics with extensive tutoring experience then drafted assessment questions, a comprehensive study guide, and brief cheat sheet. The material was reviewed and revised with input from quantitative faculty. Results/Anticipated Results: We developed a 20-item quantitative assessment covering properties of operators; identity elements and inverses; simplification of arithmetic and algebraic expressions; solving algebraic equations; functions; equations of a line; and exponents/logarithms. A cheat sheet provided trainees with a brief refresher for these topics. A study guide provided more detailed instruction, example exercises and solutions, and referenced publicly available, online resources (e.g., Khan Academy). During the introductory summer course for the Tufts CTS Program, trainees were allowed to use the cheat sheet and were given 1 hour to complete the assessment. Trainees who got questions incorrect were directed to relevant sections in the study guide. We anticipate collecting formal feedback to evaluate the material. Discussion/Significance of Impact: Trainees must have adequate foundational algebra skills to succeed in CTS graduate programs and as future researchers. Developing a quantitative assessment allowed us to identify areas of weakness resulting from educational disparities or reflecting other aspects of their backgrounds and to provide material to reinforce their preparation.

Objectives/Goals: Community engagement is critical to promoting equity for those affected by clinical and translational research. Despite its importance, investigators rarely involve community stakeholders in ancillary projects such as secondary analyses. I use a study example to demonstrate how to meaningfully partner with communities in ancillary research. Methods/Study Population: Using data collected in a previous study, the aim of this secondary analysis was to examine whether pregnant women’s reports of social adversity during the third trimester were associated with their infant’s resting cortisol level at 1, 6, and 12 months of age. Community engagement at the study design phase included consultation with an institutional Community Advisory Board (CAB) whose expertise included lived experiences relevant to the context of the study (i.e., social adversity and pregnancy). Community engagement at the analysis and dissemination stage included deeper collaboration with three community research consultants (CRCs) from the CAB; all identified as women of color and mothers with relevant lived experiences. CRCs received compensation for time and effort and an invitation for co-authorship. Results/Anticipated Results: Consultations included written review as well as a live presentation and discussion with the CAB for feedback on the study proposal prior to submission for IRB approval. The focus of discussion was around the use of inclusive terminology and ensuring respectful and equitable representation of all participants in the original study, including those who reported experiences with social adversity during pregnancy. After receiving study approval, statistical analyses were finalized and CRCs actively engaged in discussions with the PI around the interpretation of results. CRCs significantly contributed to the development of solutions-oriented implications for practice, policy, and future research. All CRCs were co-authors on the study manuscript that was published in a top-tier international journal. Discussion/Significance of Impact: Community engagement in ancillary research is feasible and essential. True equitable collaboration requires partnership during all study activities, including critical phases (e.g., developing aims, data analysis). Researchers also should prioritize the use of datasets from studies that incorporated community partnership and engagement.

Objectives/Goals: • To determine the impact of liraglutide on inflammation and organ injury during sepsis. • To investigate the protective effects of liraglutide on microvascular dysfunction in a clinically relevant model of sepsis. • To provide evidence for the potential therapeutic use of GLP-1 receptor agonists in endothelial dysfunction in sepsis. Methods/Study Population: Sepsis was induced in mice (N = 34) by intraperitoneal injection of cecal contents (1.8 mg/g body weight) and 24-hour hyperoxia (FiO2 90–95%). Mice received saline or liraglutide (0.1 mg/kg) at 6 and 18 hours post-injection and fluids and antibiotics at 12 hours. At 24 hours, mice were euthanized for plasma, bronchoalveolar lavage (BAL), and tissue collection. Plasma inflammatory markers, organ injury markers, and BAL components were measured. In vitro, primary human lung microvascular endothelial cells (HLMVECs) were treated with saline or liraglutide for 24 hours before exposure to saline or LPS (100 ng/mL). HLMVEC barrier dysfunction was evaluated using express permeability testing (XPerT) and electric cell-substrate impedance sensing (ECIS) to measure transendothelial electrical resistance (TER). Results/Anticipated Results: In murine sepsis, illness severity scores and lung injury were improved in mice pretreated with liraglutide (N = 10). Plasma blood urea nitrogen (BUN; P = 0.0036), alanine transaminase (ALT; P = 0.0311) and vascular inflammatory markers MCP-1 (P = 0.0172), ICAM-1 (P = 0.0356), and Pecam-1 (P = 0.0493) in plasma were reduced in mice treated with liraglutide. In HLMVECs, liraglutide (1.5 nM) significantly reduced LPS-induced barrier dysfunction measured by XPerT assay (P = 0.0030) and ECIS (P = 0.0075). Discussion/Significance of Impact: Liraglutide reduces illness severity, vascular inflammation, and organ injury in a two-hit model of sepsis. Liraglutide has direct effects in the microvascular endothelium, limiting LPS-mediated barrier dysfunction. These findings support a protective role for GLP-1 receptor agonism in sepsis, mediated through the microvasculature.

Objectives/Goals: To identify gaps in policy that influence enrollment trends of patients with multimorbidity in Phase III clinical trials. We aim to propose policy recommendations for increasing use of real-world evidence (RWE) that increases safety and efficacy information for patients with multimorbidities. Methods/Study Population: Conduct a systematic policy analysis on the current regulatory landscape of RWE, referencing the 2020 FDA Guidance “Enhancing the Diversity of Clinical Trial Populations.” Evaluate guidelines using the Department of Health and Human Services’ (HHS) 2016 Regulatory Impact Assessment (RIA) Framework. Utilize the Center for Drug Evaluation and Research’s New Molecular Entity Database to identify novel hypertensive drugs approved after 2006, and assess clinical studies’ alignment with the 2020 Guidance. Review additional policies, FDA guidelines, and ICH documents to establish baseline compliance. Two case studies will evaluate past policy impacts on drug development. Assess costs and benefits of increasing multimorbid patient enrollment to inform a policy framework. Results/Anticipated Results: Anticipated results include all components of the HHS’s RIA and a policy framework informed by the assessment. To identify problems, an analysis of clinical trial exclusion criteria in novel hypertensive drugs will be conducted to show diversity and enrollment gaps in regulatory policy, referencing the FDA’s 2020 Guidance. The RIA’s cost–benefit analysis will highlight costs faced for utilizing RWE and expanding enrollment criteria in Phase III studies. The cost–benefit analysis, RIA, and case studies will inform a policy framework that explains dynamics between stakeholders and outline policies that increase clinical trial representation in ways that are less burdensome to sponsors and patients. Discussion/Significance of Impact: By understanding the barriers to enrolling participants with multimorbid conditions, we can outline incentives to increase diverse trial populations, helping healthcare providers choose more treatments for complex conditions. This research supports policy recommendations to make drugs more representative of conditions the population faces.

Objectives/Goals: This study aim to identify cervical cancer prevention barriers and facilitators, assess the associations between social determinants of health factors and cervical cancer prevention, and examine the association between levels of health literacy and willingness to undertake HPV vaccine and cervical cancer screening among Black and Hispanic women. Methods/Study Population: To achieve Aim 1, we will conduct a quantitative survey on barriers and facilitators to cancer prevention among non-Hispanic Black and Hispanic women. For Aim 2, we will assess the relationship between Social Determinants of Health and HPV vaccination/cervical cancer screening using the AHC Health-Related Social Needs Screening Tool. For Aim 3, health literacy will be measured using the SAHL–S&E test and its association with willingness to vaccinate or cervical cancer screening. We will analyze the results using chi-square and logistic regression models. Participants will be recruited through multiple methods. We will recruit 250 individuals who were assigned female at birth and identify as non-Hispanic Black or Hispanic, aged 18–26 years, from Caddo and Bossier Parishes. Results/Anticipated Results: We expect to identify several barriers and facilitators to cervical cancer prevention among non-Hispanic Black and Hispanic women, including factors like access to care, cultural beliefs, and knowledge gaps. Social determinants of health (SDOH), such as income, education, and healthcare access, will likely show a strong association with lower HPV vaccination, Pap smear, and HPV screening rates. Additionally, we anticipate that lower health literacy will correlate with reduced willingness to vaccinate or screen for HPV. These findings can bridge the gap between research and practical health applications by guiding the design of community-based behavioral interventions that enhance cervical cancer prevention among minority populations. Discussion/Significance of Impact: This research is the first to assess how SDOH factors impact cervical cancer prevention among Blacks and Hispanic women in North Louisianawhile also exploring the role of health literacy in HPV vaccination and screening. Findings will drive practical interventions to reduce disparities and improve outcomes.

Objectives/Goals: Mathematical models of airborne virus transmission lack supporting field and clinical data such as viral aerosol emission rates and airborne infectious doses. Here, we aim to measure inhalation exposure to influenza aerosols in a room shared with persons with community-acquired influenza and estimate the infectious dose via inhalation. Methods/Study Population: We recruited healthy volunteer recipients and influenza donors with polymerase chain reaction (PCR)-confirmed community-acquired infection. On admission to a hotel quarantine, recipients provided sera to determine baseline immunity to influenza virus, and donor infections were confirmed by quantitative real-time polymerase chain reaction. Donors and recipients were housed in separate rooms and interacted in an “event room” with controlled ventilation (0.2 – 0.5 air changes/hour) and relative humidity (20–40%). We collected ambient bioaerosol exposure samples using NIOSH BC-251 samplers. Donors provided exhaled breath samples collected by a Gesundheit-II (G-II). We analyzed aerosol samples using dPCR and fluorescent focus assays for influenza A and sera by hemagglutinin inhibition assay (HAI) against donor viruses and vaccine strains. Results/Anticipated Results: Among two cohorts (24b and 24c), we exposed 11 recipients (mean age: 36; 55% female) to 5 donors (mean age: 21; 80% female) infected with influenza A H1N1 or H3N2. Eight G-II and two NIOSH bioaerosol samples (1–4 µm and ≥4 µm) were PCR positive. We cultured virus from one G-II sample. Based on previous literature, we hypothesized that ~50% of immunologically naïve people (HAI Discussion/Significance of Impact: We demonstrated that it is feasible to recruit donors with community-acquired influenza and expose recipients to measurable virus quantities under controlled conditions. However, baseline immunity was high among volunteers. Our work sets the stage for designing studies with increased sample sizes comprising immunologically naïve volunteers.

Objectives/Goals: Alzheimer’s disease (AD) has limited treatments and an extremely high rate of clinical trial failure. Through a collaborative effort, Agomelatine (AGO) was identified as having repurposing potential for AD. This study sets out to evaluate the preclinical potential of AGO for the treatment of AD. Methods/Study Population: The TgF344-AD rat model (expresses human mutant “Swedish” amyloid-precursor protein and a Δ exon 9 presenilin 1) was used to test AGO’s potential to reduce cognitive deficits and neuropathology. The model was chosen due to its age-dependent progressive AD pathology and cognitive decline. Treatment with AGO at ~10 mg/kg body weight/day began at 5 months of age (pre-pathology) and continued until 11 months of age when cognitive testing (active place avoidance task) and tissue collection occurred. Immunohistochemistry was used to evaluate amyloid beta plaque burden and microglial response in the hippocampus. Results/Anticipated Results: AGO-treated female TgF344-AD rats showed reduced cognitive deficits with an increased latency to first entrance in aPAT testing compared to nontreated transgenic littermates. There were no differences between the cognitive performance of AGO treated and untreated male TgF344-AD rats. Interestingly, this reduced cognitive deficit did not correlate with decreased amyloid beta pathology in female AGO-treated rats yet male transgenic treated rats did have decreased amyloid burden in the dentate gyrus (DG) of the hippocampus. AGO modulated microglial activation in the DG of female transgenic rats. Discussion/Significance of Impact: AGO reduced cognitive deficits in females, but did not change their amyloid burden. This suggests that AGO could increase resilience to amyloid deposition in female rats. With the recent development of amyloid targeting drugs, novel non-amyloidogenic treatments have a large translational potential.

Objectives/Goals: High-performing translational teams (TTs) effectively draw knowledge from empirical data to develop health solutions. However, some TTs lack rigorous data approaches, resulting in inefficiency. The ICTR data science initiative integrates team-oriented data science for more innovative and reproducible translational research. Methods/Study Population: To help TTs better leverage data science, the Institute for Clinical and Translational Research (ICTR) at the University of Wisconsin-Madison orchestrated a strategic initiative involving four main actions. • Assess needs. Determine how TTs are using data science and identify essential tools for success. • Establish partnerships. Develop strategic relationships to centralize resources and engage data scientists. Provide team science training to ensure effective integration. • Develop educational pathways. Design and implement workshops to demystify novel data science tools and upskill translational scientists. • Facilitate culture change. Identify ways that all ICTR services can help identify needs, foster educational pathways, and encourage partnerships to help TTs better leverage data science. Results/Anticipated Results: Initial assessments indicated that fewer than 25% of TTs receiving pilot awards used data science tools, and only 10% had a data scientist on their team. Data from collaboration planning sessions indicated that few TTs used data science, but all were interested in learning more. To address this deficiency, ICTR partnered with the Data Science Institute and the Section of Applied Clinical Informatics. This expertise informed resource development (e.g., a data science primer, websites) and generated workshops. Educational opportunities include tailored workshops to help TTs better curate data and create more efficient workflows, graduate course modules to improve rigor and reproducibility, and seminars illustrating translational applications of AI, visualizations, and large data integration. Discussion/Significance of Impact: The ICTR Data Science Initiative was designed to empower TTs to more effectively integrate data to power translation. As data science approaches and expertise are embedded within teams, we anticipate continued increases in interest and usage of data science tools, collaborative publications, and data rich applications for extramural funding.