Objectives/Goals: Dissemination and implementation scientists often conflate or confuse pragmatic trials and effectiveness-implementation trial designs. This study evaluates the barriers and facilitators affecting these scientists’ collaborative work to design, plan for, and conduct these different kinds of trials. Methods/Study Population: This is a sequential mixed-methods study. For the quantitative evaluation secondary data collection and surveys of roughly 200 investigators constituting an Implementation Science Network were carried out to identify research needs and impacts associated with the Translational Science Benefits Model. Surveys were prepopulated with respondents’ grant awards and prompts to define the study designs being used. Interviews of respondents are being conducted to identify barriers and challenges they faced in conducting different implementation trials and to develop case studies of their resultant research agendas. A peer-reviewed interview protocol designed for Clinical and Translational Research Institutes to conduct case studies of translational research is being used for this qualitative evaluation. Results/Anticipated Results: The 182 ISN members submitted 1590 research proposals since 2020, 52% of which were funded. ISN members responding to surveys (N = 30) self-identified many of these studies as being Hybrid 3 (29%), Hybrid 1 (17%), or Pragmatic trials (7%), although the largest proportion included studies classified “other” (33%), and some could not be classified (12%). Surveys of ISN members also indicated that many want to conduct pragmatic trials (36%) or hybrid trials (8%) but need more opportunities to collaborate (19%). Twelve (40%) ISN members agreed to be interviewed and another 11 (37%) indicated that they would do so in fall 2024 if available. Initial findings suggest that regular interactions with colleagues helped investigators new to the field understand how varied study designs could advance their implementation science. Discussion/Significance of Impact: These findings will show how U-M implementation scientists collaborate to conduct implementation trials. If the kinds of barriers faced by investigators differs by trial type, research supports and initiatives can be tailored to better support all implementation scientists in the CTSA Consortium.

Objectives/Goals: The second highest fear of the aging population is cognitive decline. Diet is associated with brain aging; therefore, the objective is to determine the effects of a Western diet (WD) on cognitive decline and the efficacy of a Mediterranean diet (MeDi) fecal microbiota transplant (FMT) in WD-induced cognitive deficit progression in aged rats. Methods/Study Population: For Study 1, 12-month-old Fischer344 rats (NIA Aging Colony) will be randomly assigned to a WD, MeDi, or control (positive control) for 6 or 12 months. Microbiota composition, blood pressure, and body composition (DXA Scan) will be longitudinally assessed. Groups will undergo a battery of neurobehavioral assessments to measure cognitive performance. At the end of the study, mitochondria bioenergetic assays in isolated cerebral microvessels will be used to determine changes in cerebrovascular function. For Study 2, 18-month-old Fischer344 rats (NIA Aging Colony) will be randomly assigned to a WD, MeDi, or control for 6 months. At month 4, the WD+ MeDi-FMT group will receive once weekly MeDi-FMT for two months. Assessments will be performed as described in Study 1. Results/Anticipated Results: It is anticipated that the WD-related gut dysbiosis will increase blood pressure, fat-free mass, neurovascular dysfunction, and induce cognitive impairment relative to a MeDi. When using a MeDi-FMT as an intervention, it is anticipated that there will be measurable improvements in cognitive function relative to a WD through the regulation of gut dysbiosis, blood pressure, fat-free mass, and neurovascular dysfunction. Discussion/Significance of Impact: These results are expected to have an important positive impact because they will provide insights into the WD-induced gut dysbiosis-associated cognitive impairments, and evaluate the roles and mechanisms of MeDi-FMT in the therapeutic intervention of aged rats.

Objectives/Goals: 1. Build a network of stakeholders (WomenWise) empowered as a Community Advisory Board (CAB). 2. Expand knowledge about patient-centered outcomes research (PCOR) and comparative effectiveness research (CER), specifically related to alcohol use in women. 3. Report facilitators, barriers, and CAB members’ experience with developing WomenWise. Methods/Study Population: Female stakeholders from nonprofit organizations (NPOs), persons and family members with lived experience with alcohol misuse, and health professionals were organized into a CAB (n = 17). CAB members receive education on PCOR/CER and sex-related disparities in alcohol treatment and create resources for large-scale community dissemination. Members will also host partnered learning sessions in their community alongside NPOs to teach the public about alcohol misuse in women and engage in PCOR/CER. Surveys and descriptive statistics assess CAB members’ understanding of educational material, engagement, and project feasibility. A Governance Council of co-investigators, collaborators, patient representatives, and a CAB chairperson oversee project progress and completion. Results/Anticipated Results: Two CAB meetings were completed thus far, with five meetings continuing into the next year. The first two CAB meetings were attended by 14/17 (82%) of members. After receiving education on Research Fundamentals, among those completing the survey (11/14), the knowledge assessments scores were very high. The Governance Council began planning the first large-scale community dissemination symposium to be held in Summer 2025, and three additional CAB meetings will be held before the ACTS conference poster presentation. We will share data on the process to initiate this capacity-building project, PCOR/CER education, stakeholder engagement and feedback, challenges and responses, and overall evaluation of the project’s feasibility and sustainability. Discussion/Significance of Impact: Historically, women have been unrepresented in alcohol misuse research, and studies rarely analyze sex and gender differences. WomenWise, a network of women stakeholders knowledgeable about these disparities and PCOR/CER, will lead efforts to educate community members about alcohol treatment disparities and engage them in future research.

Objectives/Goals: The expanding emphasis on translational science necessitates a rethinking of traditional academic formats. To align with the central themes of CTS, we have redesigned our PhD journal club and WIP sessions, introducing novel and innovative approaches that enhance the relevance of these activities to real-world scientific and clinical challenges. Methods/Study Population: The newly adapted journal club format for CTS Predoctoral students at Mayo Clinic maintains the traditional focus on literature review but now incorporates a structured analysis of the clinical implications and potential applications of the research. This innovation aims to foster a deeper understanding of how basic research findings can be translated into improved patient outcomes and healthcare practices. Similarly, the WIP sessions have been restructured to offer an engaging and dynamic learning environment designed to empower clinical and translational science predoctoral students to effectively present their research while emphasizing the challenges they have overcome, demonstrating the translational potential of their findings, and enhancing their communication skills. Results/Anticipated Results: Feedback from participants demonstrates strong support for the new format. Students report a greater engagement with the material and a clearer understanding of how their research can contribute to improving patient outcomes. Discussion/Significance of Impact: These changes accommodate the diverse projects in CTS and embody a commitment to pushing the boundaries of knowledge in CTS. This dual transition marks a significant advancement in preparing PhD students for careers in translational science, ensuring that their research is not only rigorous but also impactful in the real world.

Objectives/Goals: Goals for this work include identifying areas for continuous curricular improvement as well as documenting best practices in multidimensional mentoring in innovation. Programmatic goals include pivoting early career scientists toward translational science solutions that are commercially viable. Methods/Study Population: Using Likert-scaled perception surveys of fellowship participants, preliminary pre- and post-fellowship responses are presented. Preliminary regression analyses are used to identify trends in participants’ ratings across innovation pathways and customer-focused design. Results/Anticipated Results: Focusing on the initial cohort of fellows’ perceptions of their competencies in the areas of technology propositions and industry networking, we observed a near twofold improvement reported competency, suggesting a key strength area for the Fellowship program. Discussion/Significance of Impact: First of its kind at Penn State College of Medicine, the Center for Medical Innovation’s partnership with Clinical and Translational Science Institutesignals enhanced commitment to developing early career fundamental scientists in the areas of intellectual property, customer-focused design, and commercialization. Significance of this work includes capturing best practices.

Objectives/Goals: Increased numbers of senescent cells have been detected in both traumatic brain injury and epilepsy, suggesting them as targets for therapeutic intervention for treating posttraumatic epilepsy (PTE) and underscoring the need for innovative methods to identify and target senescent cells as a means of alleviating pathology. Methods/Study Population: C57BL/6 mice will receive a single controlled cortical impact (CCI) before having their brains removed at 1 week, 2 weeks, 4 weeks, 1 month, 2 months, and 4 months post injury (n = 5 per time point). Brain sections will then be co-labelled for glial and senescent markers to observe which cells begin to express senescent markers at various time points. We will also perform single-cell RNA sequencing to observe genetic changes associated with both TBI and epileptogenesis. Mice will also be treated with navitoclax, a BCL2 inhibitor being investigated as a senolytic agent, to determine if treatment results in decreased senescence and epileptogenesis, as well as improved behavioral outcomes. Results/Anticipated Results: Preliminary data revealed that senescent microglia begin to arise in the mouse hippocampus as early as 1 week post injury and continue to increase in concentration over the course of the following month, with up to 25% of microglia expressing p16, a known marker of senescence. We anticipate that further staining will reveal senescent astrocytes and neurons in a similar time-dependent manner. Further, we hypothesize that the single-cell sequencing of microglia from injured mice will reveal alterations to the expression of genes associated with neuronal excitability, inflammation, and/or synaptic modeling, features known to be associated with epilepsy. Finally, we anticipate treatment with navitoclax will alleviate the senescent phenotype, resulting in decreased epileptogenesis and improved behavioral outcomes. Discussion/Significance of Impact: Considering the lack of any studies examining senescent cell prevalence in PTE, these data will be the first to identify these cells as etiological factors in PTE onset, as well as druggable targets for improving pathological outcomes in PTE patients.

Objectives/Goals: Unhealthy lifestyle habits may increase medical students’ risk for metabolic dysfunction-associated fatty liver disease (MAFLD) and non-alcoholic fatty pancreatic disease (NAFPD). This study aims to investigate how these lifestyle factors affect liver and pancreas health in preclinical medical students using diagnostic ultrasound imaging. Methods/Study Population: Using diagnostic ultrasound imaging, we propose a research study to evaluate the anatomical changes of the liver and pancreas associated with lifestyle among medical students in UCC. Forty-two (42) medical students from the Central University of the Caribbean who are in their preclinical years will be recruited to perform an abdominal ultrasound. To measure the diameter of the right liver lobe, we will employ the craniocaudal measurement method established by Riestra. et al. (2018). The parameter established by Rumack et al. (2011) will be utilized to assess liver texture and categories by Lee JS et al. (2009) to pancreas fat infiltration grades. Results/Anticipated Results: This study expects to reveal a significant correlation between the lifestyles of preclinical medical students and the health of their liver and pancreas, particularly in size and texture. We anticipate identifying specific lifestyle factors – such as dietary habits and physical activity levels – that contribute to the prevalence of hepatic and pancreatic steatosis. Additionally, we expect to highlight the need for targeted interventions to promote healthier lifestyles among medical students to mitigate risks associated with MAFLD and NAFPD. Discussion/Significance of Impact: This study is significant for monitoring changes in liver and pancreas health, preventing complications, and improving health quality while reducing future costs. It may guide the creation of tailored wellness programs for medical students, enhancing their well-being and contributing to better healthcare practices and educational strategies.

Objectives/Goals: Neurodegenerative diseases involve progressive neuronal loss or dysfunction, often due to accumulated damage and impaired repair mechanisms. Our research evaluates the role of innate immune recognition proteins to provide insights into age-related neurodegeneration and cognitive decline. Methods/Study Population: We will utilize transcriptomic data from the Long-Life Family Study (LLFS), a cohort rich in genetic and phenotypic data related to aging and longevity. Our approach includes assessing a set of innate immune recognition proteins, also known as pattern recognition receptors (PRRs) expression across various age groups, focusing on potential correlations with cognitive performance. By analyzing serum transcriptomic profiles, we aim to map changes in expression and DNA repair genes over time, evaluating their connection to cognitive health and neurodegeneration in aging populations. Results/Anticipated Results: We anticipate that the expression of some PRRs will increase with age and correlate with cognitive decline, suggesting a role in age-related neurodegeneration. We also expect a decrease in DNA repair pathway gene expression in older age groups, contrasting with an increase in genes involved in endogenous DNA detection. These results will reveal how PRRs may function as neuroprotective factors and how their expression changes may relate to the decline in DNA repair processes with age, providing a better understanding of innate immune recognition in cognitive health. Discussion/Significance of Impact: This study will reveal the role of PRRs in aging and neurodegeneration, potentially establishing them as a key player in neuronal protection. Findings may guide future research into therapeutic strategies targeting them for Alzheimer’s and other age-related neurodegenerative diseases.

Objectives/Goals: We reorganized the University of Illinois Chicago, Center for Clinical and Translational Science education programs in part to extend assessment beyond funding success. We evaluated the impact of early career grant coaching on applicants’ perceived preparedness for grant submission, confidence in securing grants, and self-reported benefits. Methods/Study Population: Modeled after the National Research Mentoring Network, groups of ~5 investigators who wanted to submit a career development grant proposal met weekly for ~12 weeks with a senior faculty coach to refine aims pages, biosketches, and career development plans using a real-time peer review process. To evaluate impact, we assessed perceived preparedness (“How prepared do you feel to submit your grant proposal?”) and funding confidence (“How confident do you feel in your proposal’s funding chances?”) on entrance and exit surveys using a visual analog scale (max 100 points). Exit surveys also included an open-ended question: “What did you learn or accomplish during the coaching group?” We used paired t-tests to evaluate pre-to-post participation changes and reviewed free responses for additional context. Results/Anticipated Results: From June 2023 to September 2024, 21 people (12 postdocs/1 research assistant professor/7 tenure-track assistant professors/1 other; 13 female) were enrolled in 4 sessions. Seven people did not finish the sessions and were lost to follow-up. For the 14 participants who completed both the entry and exit survey, perceived preparedness for grant submission increased from 30.1 ± 23.5 to 67.1 ± 24.6 (p  =  0.001). Funding confidence in securing funding also increased from 40.8 ± 19.1 to 64.0 ± 20.7 (p  =  0.003). Participants valued the structure and accountability of the groups and reported other benefits, such as improved writing skills. Opportunities for feedback were also appreciated, with one participant stating, “I learned to face my fear of constructive criticism.” Discussion/Significance of Impact: Coaching improved perceived preparedness for grant submission and confidence in securing funding for participants’ current submissions and provided potentially durable benefits such as receiving and positively responding to constructive feedback. The impact of such programs likely exceeds the short-term financial return on investment.

Objectives/Goals: This proposal outlines the successful deployment of a research training initiative to support the formation of a Learning Healthcare System. Mayo Clinic Health System (MCHS) rural providers were offered the opportunity to the fundamentals of clinical research via Clinical and Translational Science Awards core curriculum, mentorship, and an online seminar series. Methods/Study Population: MCHS funded 4 key introductory research courses: 1) Manuscript Writing, 2) Grant Writing, 3) Basic Biostatistics, and 4) Essentials of Clinical and Translations Science Program. In addition to course offerings, a Research Interest Group was formed to guide novice rural researchers on topic selection and study design. This cultivated interest to create a 16-month clinical research webinar series offering CME credits. Subsequently, an internal MCHS RFA was launched seeking early-stage investigator pilot proposals focused on rural health. Results/Anticipated Results: In 2023, over 140 MCHS providers enrolled in 324 CCaTS research courses. This training led to the submission of 53 proposals to the inaugural MCHS 2023 RFA, of which 15 were awarded. Additionally, 14 MCHS extramural grants were submitted in 2023. Training efforts expanded in 2024 to include an online research seminar series covering various study topics and providing CME credit, with an approximate attendance up to 196 attendees per session. The second annual MCHS RFA resulted in 4 internal awards, with an additional 22 extramural grant submissions. These collective efforts have increased the number of MCHS first and last author publications and the number of MCHS providers with academic rank. Discussion/Significance of Impact: Leadership’s commitment of resources to educate, mentor, and engage clinicians was crucial to our success and demonstrated a strong return on investment. To maximize impact in community-based practice, continued commitment is needed in the form of protected research time, funding, and research administration support of projects of interest

Objectives/Goals: The Clinical and Translational Research (CTR) pathway aims to increase the number of health science professionals participating in CTR in their careers throughout the WWAMI Region (Washington, Wyoming, Alaska, Montana, and Idaho). Methods/Study Population: The first cohort of thirty-one students started in January 2024 and were organized into three groups that met weekly. One in-person group of students in Anchorage, AK; one in-person group in Seattle, WA; and a group of students from across the WWAMI region convened virtually. Students completed a year-long series of elective courses addressing fundamental concepts of designing, conducting, and presenting the results of a research project. Over the summer between year 1 and year 2 of medical school, students dedicated 8 weeks to full-time research activities under the supervision of their research project mentor. In Fall 2024, students prepared and presented research posters at regional poster sessions and abstracts and oral presentations for submission to the Western Medical Research Conference in January 2025. Results/Anticipated Results: The ultimate goal of the CTR pathway is to increase the number of medical providers across the WWAMI region with significant awareness, interest, and experience in research. Many students hesitate to engage in research due to a perceived lack of necessary skills. The CTR pathway addresses this gap by equipping students with the research competencies needed to participate confidently in scientific inquiry. Feedback from the inaugural cohort has been overwhelmingly positive, with many students highlighting how the CTR pathway enhanced their confidence and knowledge, empowering them to execute their proposed research projects successfully. Our second cohort of students joined the CTR pathway in January 2025. Discussion/Significance of Impact: The CTR pathway positions early medical students to engage in research more deeply during their medical training and prepares them to seek additional training opportunities toward a career in research. The majority of students in the first cohort were located at regional sites and many have interest in practicing in rural or underserved areas.

Objectives/Goals: In recent years, there has been growing interest in the development of air pollution prediction models, particularly in low- and middle-income countries that are disproportionately impacted by the effects of air pollution. Recent methodological advancements, particularly in machine learning, provide novel opportunities for modeling efforts. Methods/Study Population: We estimate daily ground-level fine particulate matter (PM2.5) concentrations in the Mexico City Metropolitan Area at 1-km2 grids from 2005 to 2023 using a multistage approach. Spatial and temporal predictor variables include data from the moderate resolution imaging spectroradiometer (MODIS), Copernicus Atmosphere Monitoring Service (CAMS), and additional meteorological and land use variables. We employed machine-learning-based approaches (random forest and gradient boosting algorithms) to downscale satellite measurements and incorporate local sources, then utilized a generalized additive model (GAM) to geographically weight predictions from the initial models. Model performance was evaluated using 10-fold cross-validation. Results/Anticipated Results: On average, the random forest, gradient boosting, and GAM models explained 75, 82, and 83% of variations measured in PM2.5 concentrations. PM2.5 levels were generally higher in densely populated urban centers and lower in suburban and rural areas. Important predictors of ground-level PM2.5 included wind (both u and v components), 2-meter mean air temperature, elevation, and the normalized difference vegetation index (NDVI). Discussion/Significance of Impact: Using novel machine learning-based approaches, we developed robust models with fine-scale spatial (1-km2) and temporal (daily) variations of PM2.5 in Mexico City from 2005 to 2023. The predicted PM2.5 concentrations can further advance public health research on air pollution in Mexico City and beyond.

Objectives/Goals: Clinical research professionals (CRPs) are vital to the conduct of clinical research and require ongoing, high-quality training to be effective. This poster will explore participating CRPs’ assessments of the impact of the inter-institutional Research Professionals Network (RPN) Workshops on their work and ability to perform their roles. Methods/Study Population: The RPN Workshops are a consortium of four academic medical centers and their affiliates that collaborate to host peer-led workshops for CRP continuing education. CRP presenters and attendees include a wide variety of roles, responsibilities, and levels of experience. From September 2023 to December 2024, workshop attendees received bi-annual evaluations to assess the workshop impact, including skill application and understanding of topics. Responses from these bi-annual evaluations, along with monthly session evaluations, were analyzed to identify key outcomes on the workshops’ impact in regard to participating CRP application of learnings and confidence in their role. Results/Anticipated Results: Preliminary review of the bi-annual RPN Workshop Impact Survey data, alongside monthly workshop evaluation responses from workshop participants, revealed attendees indicated that they valued the topics presented. Key findings indicated that CRPs’ participation in the workshops: reinforced their existing practices,tncreased their confidence in knowledge and/or skills discussed, enhanced their collaboration with CRPs from other institutions, and more detailed results of the analysis will be presented. Discussion/Significance of Impact: Overall results demonstrated increased confidence in CRP roles. Participants valued the inter-institutional collaboration, which is facilitated by the sharing of best practices and diverse perspectives within the workshop format.

Objectives/Goals: Our objectives were to describe the characteristics of patients initially listed with inactive status on the liver transplant waitlist to identify if disparities exist and compare the prevalence of initial inactive status listings across transplant centers. Methods/Study Population: This was a retrospective cohort study of candidates waitlisted for liver transplant between March 1, 2023 and February 12, 2023, utilizing the Scientific Registry of Transplant Recipients, a national database including all solid organ transplant candidates. 224,736 candidates were included in analysis, and covariates included race, ethnicity, sex, age, body mass index, primary payer, MELD at listing, and etiology of liver disease. Results/Anticipated Results: Totally, 8,131 (3.62%) candidates were initially listed for liver transplant with inactive status. Although there were statistically significant differences between those listed initially with active status and those listed initially with inactive status in each covariate, these differences did not reach clinical significance. Of the 151 transplant centers, 128 listed any patients with an initial inactive status, with inactive status listings compromising 0–49.36% of total listings by transplant center. There is significant variation between listing centers in the practice of listing with initial inactive status by both liver disease etiology and across different eras of liver allocation policies. Discussion/Significance of Impact: Despite no significant clinical difference in the characteristics of patients listed with initial inactive status, there is significant variation across transplant centers of the prevalence of listing with initial inactive status. Subsequent investigations will focus on understanding these differences in listing practices between centers.

Objectives/Goals: Novel therapeutics to control Staphylococcus aureus (S. aureus) infections are needed for people with cystic fibrosis (CF, PwCF). In this study, our objective is to determine if the pharmacologic MEK1/2 inhibitor compound ATR-002 can restrict the growth of S. aureus clinical isolates and modulate infection in a murine model of S. aureus infection. Methods/Study Population: To evaluate the anti-inflammatory effects of ATR-002 on human macrophages, cells were stimulated with TLR2 agonists FSL1 or Pam3CSK4 with a dose range of ATR-002, and secretion of proinflammatory cytokines were measured by ELISA. To determine the direct antibacterial effect of ATR-002, minimum inhibitory concentration (MIC) assays were performed with the community-associated methicillin-resistant S. aureus strain USA300 and 40 S. aureus isolates from PwCF. To validate our results in vivo, mice were provided i.p. treatment with either vehicle, the MEK1/2 inhibitor compound PD0325901 (20 mg/kg), or ATR-002 (10 mg/kg) prior to intranasal infection with 1x10^7 CFU of USA300. Bacterial burdens at 4- and 24-hour post-infection (p.i.) and inflammatory cell recruitment at 24 hours p.i. were quantified. Results/Anticipated Results: Macrophages treated with ATR-002 exhibited a dose-dependent decrease in secretion of proinflammatory cytokines TNF and IL-8 following TLR stimulation. Our studies identified that ATR-002, but not PD0325901 or other MEK1/2 inhibitors, had direct antibacterial effects, and ATR-002 had an MIC range of 8 to above 64 ug/mL on CF S. aureus isolates. In the murine pulmonary infection model, delivery of ATR-002 and PD0325901 significantly prevented infection-induced loss of body mass and decreased neutrophil inflammation. However, when bacterial burdens were quantified 4-hours p.i., only ATR-002 treatment reduced lung bacterial burden compared to vehicle or PD0325901-treated groups. Discussion/Significance of Impact: These results are the first demonstration of the in vivo anti-inflammatory and antibacterial effects of ATR-002. Our results further demonstrate that ATR-002 exhibits direct antibacterial effects across a collection of clinical isolates of S. aureus. Future studies will continue to investigate the therapeutic potential of ATR-002.

Objectives/Goals: We developed an educational online module to equip researchers with knowledge, skills, and resources for conducting community-engaged research, aiming to foster meaningful collaboration between academia and communities. Methods/Study Population: A working group was formed, including three research faculty, four staff members, and four community partners who have partnered with researchers on community engaged projects. The working group first identified three objectives for the module and outlined what should be covered for each objective. The working group identified existing resources, texts, and videos that would address the objectives and worked in small groups to create additional content for the module. A smaller subgroup then took this content, organized it, and worked with the Office of Online Education to put the content into an interactive online format. Results/Anticipated Results: The three objectives identified for the online module are 1) Describe community engaged research, the purpose it serves, and why researchers do it; 2) Identify how to seek and collaboratively engage with a community partner; and 3) Identify and connect with resources for conducting community engaged research in Indiana. Each objective contains text, interactive figures and images, links to external resources or further reading, and videos of researchers and community partners talking about their own experiences and lessons learned. Each objective also includes activities and prompts for the learner to complete to apply the module content to the work they want to do. Discussion/Significance of Impact: Community engagement ensures research addresses real-world needs, builds trust, and includes diverse perspectives. Many researchers lack best practices to do this ethically. This module teaches skills needed to foster trust through transparency, respect, and by incorporating community voices.

Objectives/Goals: In January 2023, Mayo Clinic set a goal to have 10% of studies open for six months or more without accrual. At that time, Mayo Clinic Florida had 19% non-accruing studies and 18% non-accruing clinical trials. Research administration implemented strategies to improve accrual outcomes. Methods/Study Population: Two strategies were developed to address non-accruing trials: a clean-up approach and a proactive approach. The clean-up approach involves escalating studies that haven’t been enrolled in over 6 months, identifying barriers, and escalating communication with the principal investigator (PI) and research administration alongside a physician partner. The proactive approach targets studies at the 3-month mark to address issues before reaching 6 months without accrual. Both strategies aim to reduce the cost and effort of non-accruing studies by either creating an enrollment plan or closing the study. Results/Anticipated Results: Since implementation, Mayo Clinic Florida’s non-accruing study portfolio decreased by 10%, and its clinical trials non-accruing portfolio decreased by 7% as of October 2024. Research Administration tracks key metrics (reasons for no enrollment, justifications, and actions) to identify trends and mitigate future accrual risks. A REDCap electronic data capture tool hosted at Mayo Clinic (supported by CCaTS grant UL1TR002377)1 notifies principal investigators when their studies are non-accruing. Future plans include establishing an API with Mayo Clinic’s portfolio management system to streamline the process while maintaining awareness and collaboration. Discussion/Significance of Impact: Through increased monitoring, enhanced communication, and deeper collaboration, Mayo Clinic Florida effectively reduced non-accruing studies in its research portfolio. This approach minimizes effort and costs associated with under-enrolled studies while tracking key metrics to inform future study development.

Objectives/Goals: SARS-CoV-2 infection has been shown to impact multiple organ systems, including the brain, and is associated with increased cognitive decline in vulnerable populations. The gut microbiome may play a significant role in modulating these effects, as shifts in microbiota composition have been linked to inflammation and systemic disease processes. Methods/Study Population: To explore these interactions, we conducted an acute COVID-19 study using 12-week-old C57 mice intranasally inoculated with 1x10^4 PFU of the Mouse Adapted 10 (MA-10) strain of SARS-CoV-2. On day 5 postinfection, we performed 16S ribosomal RNA sequencing on fecal samples, analyzed using QIIME2 and DeSeq2, to assess microbiome alterations and identify changes in metabolic pathways associated with inflammatory responses. Results/Anticipated Results: Analysis revealed notable shifts in the gut microbiome during the acute phase of COVID-19 infection, with significant alterations in metabolic pathways related to inflammation and immune regulation. These changes suggest that early gut microbiome disruptions may contribute to the host response in acute COVID-19. Discussion/Significance of Impact: Our findings indicate that acute SARS-CoV-2 infection leads to rapid alterations in the gut microbiome, which could underlie inflammatory and immune pathways impacting disease progression. These insights highlight the potential for microbiome-targeted therapies to mitigate acute COVID-19 morbidity and warrant further investigation.

Objectives/Goals: The demands on MICHR’s Evaluation team are profuse and varied. Quarterly team meetings were used to keep track projects, identify new projects, and relay important new initiatives from MICHR leadership. The MICHR Translational Innovation team took on the task of assessing the Evaluation team’s processes to design better workflow and effectiveness. Methods/Study Population: The process included 5 stages, Empathize, Define, Ideate, Prototype and Test. Sixteen interviews were conducted with MICHR faculty and staff. Interviews were coded and summarized. Seventeen themes were mapped and distilled into 5 key insights. From the key insights, design principles were identified to guide a design session with Translational Innovation staff and Evaluation staff. New work processes were proposed, designed, and tested by both teams. The Evaluation team “test-drove” the prototype and iterative design sessions were conducted to determine which new elements were successful. The Evaluation team was positioned to begin utilizing the newly designed process at the beginning of MICHR’s new grant year. Results/Anticipated Results: The MICHR Evaluation team is instrumental to the development, conduct, and dissemination of Clinical & Translational Science (CTS), a primary objective of MICHR’s work. Three types of evaluation projects were identified through the design process: required reporting, CQI/program improvement, and CTS/impact evaluation. The service design process enabled the Evaluation team, and MICHR program leads to better identify and prioritize collaborations between the Evaluation and program teams that improved the quantity and quality of MICHR CTS outputs. Discussion/Significance of Impact: Generating CTS is critical to the missions of NCATS and MICHR. Thoughtfully designing processes that facilitate and increase CTS output that can be shared and duplicated across the consortium is invaluable.

Objectives/Goals: There has been a significant increase in the engagement of researchers with persons with lived and living experience, driven by a growing recognition of the invaluable insights and expertise these individuals bring to the research process. However, there remains a need for research teams to learn how to engage with patients and community partners. Methods/Study Population: The EMPOWER project is a collaborative of members with lived/living expertise of substance use during pregnancy. EMPOWER meets three times per month in support of their goals of patient-centered research, changing the narrative through conversations, and building the capacity of persons with lived experience to co-lead research. Through over 4 years of active collaboration and co-learning, EMPOWER has identified and created methods that support meaningful patient engagement and capacity building. Results/Anticipated Results: EMPOWER has identified the following methods that support meaningful engagement and capacity building: Mind-Mapping Exercises, Personal and Collective Journey Mapping, 8-month research training curriculum, Digital Storytelling, Learning Labs, and World Cafe Meetings. These methods have led to a collaborative of 20 individuals with lived experience of substance use to identify research gaps, prioritize research questions, design data collection tools, analyze research data, disseminate research results, and consult with healthcare teams in efforts to improve clinical care. To-date EMPOWER have given over 10 invited presentations and is currently writing manuscripts. Discussion/Significance of Impact: Meaningful patient and community engagement is critical to developing and implementing healthcare interventions. Unfortunately, engagement efforts are often lack in building capacity of patients and community, which impedes their ability to fully engage in all phases of research.