Objectives/Goals: To implement and evaluate the Quality by Design (QbD) framework integrating team science and project management to increase quality and efficiency in clinical and translational studies. Goals include achieving 80% on-time completion and sharing tools to expand QbD use across other CTSA hubs. Methods/Study Population: The SC CTSI launched the QbD program in 2022 to support pilot grants, KL2 Scholar projects, and other CTSI-funded studies. Program elements include 1) Design Studios, facilitated by a QbD Specialist and attended by interdisciplinary advisors, to anticipate risks to timely study completion; 2) ongoing project management with regular check-ins; and 3) team science support for multidisciplinary research teams. Study teams establish milestones and track risks across the timeline. Ongoing evaluation follows studies across a wide variety of disease areas, using mixed methods to assess feasibility, perceived value, and impact on scientific productivity and institutional culture. Results/Anticipated Results: The QbD program has been delivered consistently, demonstrating it is feasible and well-received, with 93% of PIs reporting QbD as valuable for identifying risks and refining protocols. Early evidence suggests QbD support may reduce delays, with shorter extensions, while common barriers stemmed from institutional and administrative hurdles. PI interviews highlight QbD as a constructive framework for strengthening early planning and risk mitigation, with feedback prompting ongoing refinement such as adjusting the timing of Design studios. Anticipated results include continuous evaluation outcomes, ongoing program improvements, and broader dissemination with other CTSA hubs. Discussion/Significance of Impact: Evaluation will clarify how QbD implementation influences study planning and risk mitigation to prevent delays. Broader outcomes will include toolkit development and fostering a culture to advance proactive, quality-focused research services across institutions.

Objectives/Goals: Community Advisory Boards (CABs) offer researchers community perspectives and empower CAB members to learn about research. The Mayo Clinic Center for Clinical and Translational Science (CCaTS) engages communities through six CABs. We describe our efforts over the past 17 years to develop, implement, align, and evaluate the six Mayo Clinic CCaTS CABs. Methods/Study Population: CABs were established in Jacksonville, FL (2008), Rochester, MN (2011), Phoenix, AZ (2014), Pediatrics, MN (2019), Native Tribal Health, MN (2021), Rural, Midwest (2022), and each operated independently. To harmonize CAB structure and function, a framework was developed in 2024 through an assessment of current CAB practices, guidelines, and feedback from CAB members. Through this process, a shared vision, mission, and strategy were created. The goal of harmonization was to align the six CABs with community health needs identified through local Community Health Needs Assessments (CHNAs). This information was consolidated into a new Guiding Document that outlines our unified approach to engaging the community in research through CABs. This harmonization framework provides both structure and flexibility. Results/Anticipated Results: As part of CAB harmonization framework, annual evaluations assess CAB impact, satisfaction, and growth opportunities. One CAB was evaluated in 2023, two in 2024, four in 2025, and all in 2026. CABs have four roles: Members, Board Chairs, Coordinators, and Scientific Leads. Each CAB has 15–20 members serving 3-year terms. CABs meet quarterly, with one in-person meeting annually. Meeting topics fall into four categories: site-based programs, planning, or evaluation; community-engaged research partnerships; research addressing an identified community health need; or a member selected topic that enhances information, education, or capacity building. Members receive orientation, annual training, and compensation. This framework supports community voices in research and aligns with local needs. Discussion/Significance of Impact: By aligning the purpose, structure, and function through a harmonization framework, we unified and amplified community voices in research. Few institutions support such a broad CAB network. With no existing model to meet our unique needs, we developed this flexible framework that fosters alignment while addressing each community’s unique needs.

Objectives/Goals: This collaboration explores magnetic-responsive scaffolds toward modeling Salmonella infection via the small extracellular vesicle (sEV) route. We aim to elucidate the mechanism by which sEVs reflect host–pathogen interactions to inform new Salmonella therapeutics. Methods/Study Population: Human intestinal epithelial cells (INT-407) are being cultured on magnetic-responsive scaffolds under controlled mechanical stimulation and infected with Salmonella Typhimurium 12023 WT. Kinetic assays are assessed via confocal microscopy, flow cytometry, and qPCR. sEV isolation is being performed by NanoPoms immunomagnetic capture and characterized by nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM), and Western blotting for canonical markers (CD9, CD63, and CD81). Additionally, sEVs derived from human THP-1 cells are being used to treat naïve INT-407, in which cytokine responses and proteomic shifts are analyzed. Results/Anticipated Results: We anticipate that INT-407 in 3D magnetic scaffolds will shift the Salmonella infection kinetics compared to the unstimulated controls and traditional 2D culture. We expect the sEVs from infected cells to be enriched in antigenic proteins and canonical sEV markers. Furthermore, sEVs from infected THP-1 cells are anticipated to induce pro-inflammatory cytokine release and proteomic shifts toward intracellular signaling and inflammatory processing in naïve INT-407 following treatment. Taken together, these findings will elucidate the mechanism by which magnetic-responsive scaffolds better recapitulate the gut microenvironment for modeling host–pathogen interactions. Discussion/Significance of Impact: This project’s findings will indicate if 3D magentic scaffolds provide a sound model for Salmonella infection. Analysis of sEVs derived from INT-407 and THP-1 will provide insight into the functional characteristics sEVs have in the gastrointestinal environment upon pathogen insult.

Objectives/Goals: To develop and assess a multidimensional measure of arousability by integrating respiratory, autonomic, cortical, and movement-related events and to identify sex-specific arousal phenotypes using clustering analyses and LASSO-based machine learning for feature selection and model optimization. Methods/Study Population: We will conduct a retrospective cross-sectional analysis using sleep and clinical data from >10,000 adults in three different cohorts. Arousability will be defined by event-level metrics across respiratory, autonomic, cortical, and movement domains. Variable clustering will be used to construct a multidimensional composite index of arousability based on those domains. Generalized linear models will test sex differences in individual metrics composite indices. LASSO regression will be applied to select arousability features most predictive of sex, mortality, and cardiovascular disease (CVD). Results/Anticipated Results: We anticipate identifying distinct arousability dimensions and sex-specific arousal profiles. Women are expected to show greater non-respiratory arousals, while men will show higher respiratory-related arousals. The resulting multidimensional index will capture arousal burden more comprehensively than traditional metrics like the apnea–hypopnea index. This will aid in understanding sex-based difference of sleep fragmentation, as well as understanding the sleep mechanisms most associated with mortality and CVD. Discussion/Significance of Impact: This study will advance precision sleep medicine by developing a multidimensional, data-driven arousability index and identifying sex-specific phenotypes. These findings may improve diagnostic accuracy, influence tailored interventions, and inform risk stratification beyond traditional metrics.

Objectives/Goals: Define how CKD and iron therapy influence tubular epithelial cell (TEC) iron handling through parallel kidney and urine studies in mice and patients, uncovering cellular signatures that predict injury or recovery and may guide individualized iron therapy in CKD. Methods/Study Population: We used two mouse models of CKD and fresh urine samples from pediatric CKD patients and healthy controls to assess tubular iron handling. Kidney tubular epithelial cells (TECs; CD45−AQP1+) were analyzed by flow cytometry for labile iron pool (LIP) using FerroOrange and sorted into LIP^hi and LIP^low subsets for RNA-seq. Expression of injury markers such as KIM1 and NGAL was used to evaluate tubular stress, linking iron accumulation to epithelial injury and adaptive responses. By combining mouse CKD models with patient urine analysis, we traced how kidney tubular epithelial cells (TECs) manage iron across species. Results/Anticipated Results: In CKD mouse models, tubular epithelial cells (TECs) showed reduced labile iron pool (LIP) and increased ferroptosis, with a smaller population of iron-overloaded cells exhibiting elevated KIM-1 and EMT-related transcriptional changes. Iron chelation lowered LIP in tubular cells and iron therapy exasperated KIM-1 expression. Urinary TECs mirrored tissue findings, with LIP and KIM-1 levels reflecting systemic iron status and CKD severity. In human CKD, urinary LIPHI TECs expressed higher KIM-1 and injury-associated signatures, validating urinary TEC profiling as a noninvasive readout of tubular health. In both species, iron handling and toxicity proceeded differently depending on the nature of the damage (tubular or glomerular), identifying urinary TECs as a noninvasive window into kidney iron toxicity. Discussion/Significance of Impact: Chronic kidney disease affects 10–15% of the world population, and anemia is a common complication. Iron therapy is toxic to kidney cells, contributing to tubular injury. Our studies identify urinary cells as a noninvasive test of renal iron status and link iron handling to injury, enabling safer, personalized therapy to slow kidney damage in patients.

Objectives/Goals: Amyloid deposition in the ligamentum flavum (LF) is associated with LF hypertrophy and resulting lumbar stenosis (LS) in some patients. Whether amyloid causes inflammation and subsequent fibrosis in the LF is unclear. An association between amyloid and markers of inflammation may present an opportunity to treat early stenosis with medical therapy. Methods/Study Population: LF specimens from 66 patients with lumbar stenosis (LS) were analyzed, including 33 amyloid-positive and 33 amyloid-negative patients matched by age and diagnosis. We performed immunohistochemistry on 7 tissue sections per specimen for biomarkers of inflammation (IL-6, C9) and fibrosis (Collagen, Elastin, TGF-β1, α-SMA, ROCK1). All biomarkers were quantified using a validated random forest classifier in QuPath. In Aim 1, we compared the collagen-to-elastin ratio between groups as an indicator of fibrosis, with secondary comparison of the collagen and elastin percent (α=0.025 each, Bonferroni corrected). In Aim 2, we will compare expression of IL-6, C9, TGF-β1, α-SMA, and ROCK1 using a multivariate mixed-effects regression model to identify inflammatory and fibrotic patterns linked to amyloid deposition. Results/Anticipated Results: This study tests the hypothesis that amyloid deposition in the ligamentum flavum (LF) drives fibrosis, and the resulting LF hypertrophy and lumbar stenosis (LS), via an inflammatory pathway. Aim 1 analyses are complete, and amyloid-positive LF demonstrated a higher collagen-to-elastin ratio, with a mean difference of 0.31 (0.07–0.55, p = 0.014). This difference is driven by elastin, which covers 7.5% less tissue area in amyloid-positive LF (p = 0.008). This is the first histological evidence that amyloid is associated with altered extracellular matrix composition in the LF. We hypothesize that amyloid-positive LF will show elevated expression of IL-6 and C9, comparable TGF-β1 and α-SMA, and lower ROCK1, supporting an inflammatory pathway to LF hypertrophy distinct from pathways triggered by mechanical stress. Discussion/Significance of Impact: This work will provide evidence on a possible role of amyloid in the pathophysiology of LS in a subset of patients. Our results will guide more robust quantitative analyses, including proteomics and transcriptomics, and for the first time, may support trial of anti-amyloid medical therapies to slow the progression of this primarily surgical disorder.

Objectives/Goals: To investigate renin–angiotensin system (RAS) modulation as a therapeutic target for uterine fibroids using a xenograft model, translating insights from cardiometabolic–fibroid comorbidity into accessible treatment strategies for underserved populations. Methods/Study Population: We established a xenograft model by implanting matched human fibroid and myometrial tissue into NOG mice (n=6 per group) supplemented with estrogen pellets. This translational model mimics the clinical context of hypertensive patients with fibroids treated with RAS-modulating drugs. Mice were randomized to receive angiotensin II, losartan, enalapril, or vehicle control. Tumor volumes were measured weekly by caliper. At endpoint, xenografts are analyzed for proliferation (Ki67), fibrosis (α-SMA, collagen), and immune composition using flow cytometry and immunofluorescence. Results/Anticipated Results: Preliminary data from all 24 mice reveal variable fibroid xenograft growth across treatment groups, with no consistent dose–response pattern in gross tumor volumes. Ongoing molecular and cellular analyses may uncover treatment effects not reflected in volume measurements alone. Final analyses will integrate proliferative indices, fibrotic markers, and immune cell profiles to determine whether RAS modulation influences fibroid biology at the cellular level despite heterogeneous morphological responses. Discussion/Significance of Impact: Fibroids disproportionately affect Black women and are closely linked to cardiovascular disease. Repurposing FDA-approved antihypertensives offers an accessible, low-cost therapeutic avenue and exemplifies translational science by bridging mechanistic discovery with equitable treatment innovation.

Objectives/Goals: To evaluate the incremental value of post-approval adverse event reporting and population exposure in characterizing a drug’s safety profile, using PD-1 inhibitors as a model class to assess how continued clinical experience enhances safety knowledge. Methods/Study Population: Using PD-1 inhibitors as a model, we are exploring FDA Adverse Event Reporting System (FAERS) database to capture real-world post-marketing safety information on drugs in this class approved by FDA since 2014. Findings from FAERS will be compared with the safety profile in the initial package insert used for FDA approval for each of the drugs. The nature of novel adverse events will be characterized and compared with the extent of exposure as determined through the use of marketing databases (e.g., IQVIA, Cortellis). We seek to identify relationships between the observation of novel adverse events and levels of population exposure. We will explore whether the safety experience with older products in this drug class could be predictive of safety outcomes in newer class candidates. Results/Anticipated Results: The findings would aim to inform the development of a “Goldilocks” approach (the value of incremental exposures), to explore how post-marketing exposure impacts changes in the safety profile of drugs in this class. Results will be used to explore whether a particular level of post-approval exposure is predictive of the occurrence of novel adverse events, excluding idiosyncratic events, among PD-1 inhibitors. Discussion/Significance of Impact: The study will guide the understanding of the incremental value of additional population exposure to refining the safety profile within a class of well-defined drugs and may inform a systematic approach towards consistent class labeling.

Objectives/Goals: Research administration roles are integral to the orchestration of translational and clinical research, yet they are often unknown to job seekers and often lack established degree pathways. To address this, we developed a “High Demand Hidden Careers” curriculum that aims to equip unemployed individuals for employment in research administration. Methods/Study Population: To facilitate multidisciplinary, comprehensive training experiences, we identified three key research administration areas: Research Education, the Office of Clinical Research, and the Institutional Review Board. To develop the curriculum, we determined the skills required for the three administrative areas. The curriculum was implemented across the course of 12 weeks, in a hybrid format, which allowed for in-person shadowing, with self-paced online educational modules dispersed throughout. In addition to research administration experiences, interns were paired with a human resources recruiter who advised on resume development, job application process, and interview skills. At the conclusion of the program, interns were asked to complete a post-internship survey. Results/Anticipated Results: Our institution enrolled three individuals into the program. Two of the interns completed the entire 12-week curriculum; one intern concluded the program in one month due to successful employment. We tailored the curriculum to align with the interests of interns to ensure that they received the skills and practical experiences for their future careers. In addition to shadowing, interns completed certification in human subject protections and good clinical practice via the CITI Program web-based curriculum. Two interns were employed in positions in, or adjacent to, research administration, and the third is actively pursuing opportunities. All interns strongly agreed that the opportunity expanded their skills and prepared them for jobs in research administration and all would recommend the internship to a peer. Discussion/Significance of Impact: The internship curriculum addresses an educational and experiential gap that exists in the field of translational science administration. The developed curriculum can be expanded to other areas of research administration and thus easily replicated at other institutions, while creating a pathway for employment and workforce sustainability.

Objectives/Goals: Our goal is to improve health outcomes for sepsis survivors experiencing immune-paralysis. We propose a functional diagnostic tool to identify at-risk patients and a novel therapeutic called interleukin-7 to boost the patient’s T-cell-mediated immunity against infection. Methods/Study Population: This multi-center research study recruits healthy adult volunteers and adult septic patients in the intensive care unit to consent to giving blood draws. Blood draws containing immune cells are assessed for functionality through our diagnostic tool. Interleukin-7, a therapeutic candidate to improve immune cell activity, is assessed by flow cytometry, ELISA, and bulk RNA sequencing. Results/Anticipated Results: Using IL-7 during T-cell stimulation in the ELISpot assay increased the number of T-cells producing protective effector protein IFNgamma. Statistical analysis was performed using Brown-Forsythe ANOVA test with Dunnett’s T3 multiple comparisons test with a P-value<0.001. Flow cytometry confirms IL-7 treatment increased the frequency of T-cells to produce IFNgamma and preferentially impacts memory T-cells in sepsis patients. Bulk mRNA sequencing demonstrated increased differentially expressed mRNA transcripts FDR<.001 related to cell survival and T-cell-mediated effector molecules with IL-7-treated cells. IL-7 improved effector protein production was confirmed by a multiplex assay. Discussion/Significance of Impact: There are no diagnostic tools to identify immunocompromised patients or therapies to reverse the immune suppression. Our ELISpot diagnostic tool identifies at-risk immune-impaired patients. Furthermore, our results demonstrate interleukin-7 as a potential therapeutic to improve immune activity.

Objectives/Goals: There remains an urgent need for the development of safe and effective therapeutics for the long-term management of pain. We evaluated our novel analgesic in multiple pre-clinical models to assess its abuse liability, analgesic efficacy in models of chronic pain, and its mechanism of action in ex vivo spinal cord slices. Methods/Study Population: We evaluated SSA3’s abuse liability by utilizing an IV self-administration paradigm. In this experiment, rats are placed in a chamber and have the option to press a drug-infusion lever or a control lever. Abuse liability was determined based on extent of lever pressing on the drug-infusion lever. To evaluate chronic pain efficacy, mice underwent a spared nerve injury (SNI) which induces sustained hypersensitivity in their hind paw. Mice were then treated with SSA3, and their hypersensitivity was assessed. Finally, the mechanism of action was investigated through patch clamp electrophysiology recordings taken from excised spinal cord slices in mice. We recorded currents from neurons involved in the pain signaling pathway before and after application of our compound to observe drug efficacy at the cellular level. Results/Anticipated Results: Our results demonstrated that in a pre-clinical IV self-administration paradigm, SSA3 exhibited no abuse liability, indicated by a lack of drug intake or escalation of drug intake. Results from our SNI model of chronic pain reveal that when SSA3 is administered directly onto the spinal cord via intrathecal injection, it is efficacious in reversing the pain hypersensitivity established by the model, suggesting a spinally mediated mechanism of action. Finally, we observed that SSA3 effectively reduced the amplitude of NMDA receptor-mediated excitatory postsynaptic currents in a concentration-dependent manner. This reduction in amplitude suggests our compound’s analgesic efficacy comes from the inhibition of spinally mediated NMDA receptor signaling. Discussion/Significance of Impact: This investigation into the therapeutic potential of substituted agmatine for the management of chronic pain revealed several key insights. Our drug is efficacious in models of chronic pain and, importantly, lacks the abuse liability commonly seen with analgesic drugs. Our drug’s mechanism of action involves inhibition of spinal NMDA receptors.

Objectives/Goals: Differences in gait patterns related to post-traumatic (PTOA) and idiopathic (IDIO) knee osteoarthritis (OA) in aging adults is not well understood. Therefore, the purpose of this study was to assess the impact of knee OA phenotype (PTOA vs IDIO) on the knee total joint moment (TJM) during walking in aging adults with and without end-stage knee OA. Methods/Study Population: Six adults with PTOA and six adults with IDIO were tested prior to knee replacement. Data from 12 healthy, asymptomatic adults were used as control data. All subjects underwent 3D gait analysis at a self-selected speed. TJM was calculated as the square root of the sum of the squared planar internal sagittal, frontal, and transverse plane knee moments across the stance phase. The corresponding sagittal, frontal, and transverse plane moments at the peak TJM in the 1st (TJM1) and 2nd (TJM2) half of the stance phase were extracted. A repeated-measures ANOVA was used to assess group differences in biomechanical parameters of the dominant (control group) and surgical (OA groups) limb, while knee pain (VAS: 0 – 10) during the walking task for the PTOA and IDIO groups was compared using an independent t-test (alpha=0.05). Results/Anticipated Results: Both the PTOA and IDIO groups walked at slower speeds compared to the control group (p<0.01). There was a main effect of knee OA phenotype on frontal plane TJM (p=0.003). The PTOA group exhibited a significantly lower frontal plane moment at TJM2 compared to the control (p=0.047) and IDIO (p=0.019) groups. There were no differences in sagittal, frontal, or transverse plane knee loading at TJM1 nor any differences in sagittal and transverse plane knee loading at TJM2 (p > 0.05). In addition, there were no differences in self-reported knee pain during walking between the PTOA and IDIO groups (p=0.25). Discussion/Significance of Impact: People with PTOA exhibit more rapid knee joint degeneration than those with IDIO. Lower frontal plane loading during TJM2 in PTOA may be associated with a more rapid decline in knee muscle function. Further evaluation of knee muscle function in PTOA and IDIO will provide better insight into these differences in gait patterns between PTOA and IDIO.

Objectives/Goals: Within the machine learning “fairness” literature, models audits are point estimates, and only effect size is considered. The well-developed frameworks in biostatistics for diagnostic testing apply directly to classifiers more generally; these principles can be extended to have statistically valid fairness audits. Methods/Study Population: We made original linkages between machine learning methodology and biostatistics, particularly to diagnostic testing, to get analytic biostatistical methods for model evaluation that are applicable to fairness testing. Results/Anticipated Results: The use of odds ratios to compare ratios of binomial proportions is superior to taking ratios of binomial proportions directly, as is currently standard in machine learning. Odds ratios also have an analytic asymptotic approximation for standard errors, by which we can test if a point estimate (effect size) is greater than what we would expect from noise. In diagnostic testing, the odds ratios considered are generally across the cells of a confusion matrix, but we can form odds ratios for specific marginal quantities (positive predictive value, negative predictive value, true positive rate, true negative rate) for specific aspects of model performance or fairness. Discussion/Significance of Impact: Biostatistics can make direct contributions to instantly improve the state of machine learning practice, giving ready-made methods that can take account generations of hard-won lessons about the importance of uncertainty quantification and sample size in making claims and conclusions.

Objectives/Goals: For older adults with subjective cognitive decline (SCD, N=38), we aim to qualitatively understand and describe the 1) unique participant perspectives, 2) unexpected quantitative findings, 3) complex symptom experience and resultant impact on quality of life (QoL) to further inform clinical and public health with non-pharmacological interventions. Methods/Study Population: From an RCT (12 weeks, 150 min/week), pre-post-aerobic cycling intervention (n=30) vs. control (n=8), symptoms and QoL were assessed with 4 questionnaires/individual interviews. The data were analyzed with Pearson’s r correlation coefficient/Spearman’s Rho and ANCOVA/Quade test. With mixed methods, we aim to 1) analyze the baseline interviews of cognitive and affective symptoms (anxiety and depressive) and QoL for themes to better understand the variations between SCD+ (preclinical Alzheimer’s disease more likely [n=24]) vs. non+ (n=14), 2) compare the cross-sectional data for emergent themes and patterns to explore the reasons for the unexpected correlations, and 3) describe symptomology changes and impact on QoL. Qualitative results will show varied convergent or divergent themes. Results/Anticipated Results: Significant correlations (N=38, p<.05) were shown between anxiety and depressive symptoms (r=0.44); anxiety symptoms and overall (r=-0.38) and psychological (r=-0.57) QoL; and depressive symptoms with overall (r=-0.49) and psychological (r=-0.53) QoL. Some remained correlated in SCD+; cognitive and depressive symptoms were correlated (r=.41, p<.05). The cycling group worsened in all aspects while the control group had non-significant improvements. Significant predictive relationships between worsening depressive symptoms following cycling were found for overall QoL (p=0.01) and physiological QoL (p<0.01). We will show similar/varied explanatory themes for SCD+ versus non+. Merged data, pre- and post-cycling, will explain the preliminary results from the participants’ perspectives. Discussion/Significance of Impact: The COVID-19 pandemic (during the study) and loneliness likely impacted results. We seek to understand these findings through a thematic analysis, build a body of evidence, inform the assessment and treatment of cognitive and affective symptoms in SCD, improve QoL, and positively impact brain/overall health at the clinical and public health levels.

Objectives/Goals: Anemia occurs universally among preterm infants who are also at risk of severe retinopathy of prematurity (ROP), a vision-threatening morbidity. We aim to determine the effect of anemia and its treatment with iron on the anatomical and molecular development of retinopathy and subsequent retinal function. Methods/Study Population: Oxygen-induced retinopathy (OIR) was induced in rat pups per the well-validated 50/10 OIR model, through 14 days of cyclic hyperoxia (50% FiO2) and hypoxia (10% FiO2) followed by recovery in normoxia. Anemia was induced by phlebotomy from postnatal day (P) 3 to P20, to a target hematocrit of 18%. Half of the pups were housed with a dam receiving standard iron chow (40 mg/kg) and half with a dam receiving high iron chow (400 mg/kg). Rat pups were euthanized at P20 during the neovascular phase of OIR. Retinal vascular morphometry (percent avascular and neovascular areas) was compared between groups by two-way ANOVA. Future outcome measures include retinal single-cell sequencing, flow cytometry, and molecular measures. Results/Anticipated Results: Anticipated Results: We anticipate that iron deficiency anemia will reduce the severity of OIR and that high dose iron treatment will increase it. We anticipate that high-dose iron treatment will induce oxidative stress, induce inflammation, and reduce the hypoxia-like effect of iron deficiency and angiogenic markers. Discussion/Significance of Impact: Upon completion, the results of this study can inform clinicians regarding preclinical effects of isolated anemia and treatment with iron on the development of retinopathy. This research has the opportunity to improve visual outcomes in preterm infants by improving clinical care of this population in the neonatal intensive care unit.

Objectives/Goals: To achieve the greatest impact, protocols must be rigorous and feasible. The University of Minnesota’s Clinical Research Support Center developed a feasibility review (FR) to identify barriers, offer solutions, and strengthen translation through multidisciplinary expertise. Improvements are tracked using an Impact Scoring System. Methods/Study Population: Established in 2018, the FR was designed to address operational barriers that delay study start-up and help researchers strengthen protocols before regulatory submission and implementation. Drafts are reviewed by a multidisciplinary panel with expertise in logistics, recruitment, biostatistics, monitoring, and regulation. Each protocol undergoes a 1-week review process culminating in a 90-minute structured discussion between the panel and study team. A written report summarizes strengths, concerns, available resources, and next steps. To assess impact, we developed a novel scoring system that assigns each protocol a pre- and post-review score, objectively measuring how protocols improve in response to feedback. Results/Anticipated Results: Since its launch, 186 clinical studies from nine schools and colleges have completed FR. Study teams report high satisfaction (average rating 4.8/5), noting clearer recruitment plans, improved logistics, and valuable resource connections. The Impact Scoring System provides measurable evidence of change: on average, protocols increased their score by 28% from pre- to post-review, reflecting greater operational readiness and likelihood of success. Tracking also shows that FR participation is associated with fewer protocol-related IRB stipulations, offering an additional objective indicator of improved quality. Together, these results demonstrate both the perceived value and the measurable operational impact of the FR process. Discussion/Significance of Impact: The FR addresses operational barriers early, ensuring protocols are both rigorous and feasible before launch. Its Impact Scoring System provides objective evidence of improvement and a scalable model other institutions can adopt to advance rigor, efficiency, and trustworthy translation.

Objectives/Goals: This study aims to quantitatively examine successful US researchers who may engage in pragmatic ’negotiation’ over time with external funders, their university administration, and other scientific and scholarly parties about their research lines and content. Methods/Study Population: The purpose of this quantitative correlational research is to pilot a new quantitative survey tool to measure researcher autonomy in selecting and pursuing their research agendas. The current study is modeled after a landmark peer-reviewed publication on negotiated space in evaluating researchers’ agendas in Finland and the United Kingdom by Luukkonen and Thomas in 2016. Using a mixed methods design, the study surveys NIH Director’s Pioneer and Keck Foundation Awardees (2018–2021) to assess perceptions of autonomy, competition, and institutional support. This study examines how NIH-funded researchers adapt grant strategies to shifting NIH priorities while preserving autonomy. Results/Anticipated Results: Of 24 respondents, most were White and male, with varied project portfolios and funding levels. Many described their fields as resource-intensive, with typical projects lasting 3–5 years. Primary funding sources were generally flexible, though stability and administrative burdens were concerns. Most researchers reported shifts in research aims driven by field developments rather than institutional pressures, with limited involvement in commercialization. Collaborations with global and industry leaders were common and largely stable. Overall, findings suggest US researchers adapt strategically to funding realities while balancing autonomy, collaboration, and institutional support. Discussion/Significance of Impact: This study demonstrates how US researchers balance autonomy with demands from funders and institutions within a “negotiated space.” Funding is flexible but administratively burdensome. Findings highlight the tension between innovation and external directives shaping research agendas.

Objectives/Goals: The PSCTSI provides critical resources and services at PSU/PSCOM. Our objectives are to map PSCTSI resources among the PSU/PSCOM research infrastructure, increase researcher knowledge of resources, services, and processes, and ensure improved PSCTSI integration within the research infrastructure. Methods/Study Population: PSCTSI will utilize process and resource mapping techniques and systems analysis to align our services and resources within the PSU/PSCOM research infrastructure. Methods: Identify and map PSU/PSCOM research infrastructure processes, services, offices, and resources. Identify and map PSCTSI resources and services within the PSU/PSCOM infrastructure. Highlight areas where PSCTSI resources and services fill critical gaps in the PSU/PSCOM infrastructure Results/Anticipated Results: Navigating the research process is often confusing for researchers, especially where there are gaps within the infrastructure. Process and resource mapping techniques and systems analysis can provide a complete picture of PSCTSI’s vital role and impact on the PSU/PSCOM research infrastructure. Results of this analysis will benefit three audiences: PSU/PSCOM researchers – to better understand research processes, PSU/PSCOM research leadership – to illustrate the importance and synergy of PSCTSI within the research infrastructure, and PSCTSI and other CTSAs – to share their impact and ensure improved integration Discussion/Significance of Impact: CTSAs rely on external and potentially institutional support despite their essential roles within the research infrastructure. Resource and process mapping of PSCTSI within PSU/PSCOM’s infrastructure has two benefits: improving knowledge on resources and services and ensuring improved integration.

Objectives/Goals: Team Science is an essential element of Clinical and Translational Research (CTR), and a Translational Science Principle key for generating innovation. As CTSA hubs work to improve the practice of CTR through Translational Science, many seek evidence-based interventions from the field of the Science of Team Science to make teamwork more impactful. Methods/Study Population: Two evidence-informed Team Science interventions were offered to CTSA hubs for implementation and evaluation: Collaboration Planning & Research Jams. Thirteen CTSAs signed up to implement Collaboration Planning; 12 implemented at least one session by the end of the project. Four CTSAs signed up to implement Research Jams; all implemented at least one session. Implementers, CTSA-based Team Science leaders, received training in intervention delivery. We collected pre-/post-implementation survey data on feasibility and usability of the interventions, as well as post-training satisfaction. We also collected post-implementation data to capture implementers’ experience in delivering the interventions. Further, participants in each intervention were surveyed about their experience. Results/Anticipated Results: Implementers agreed that the interventions were feasible and usable, while sharing challenges they encountered. Key challenges included limited buy-in from leadership and teams and the need for better marketing about the benefits of participation to increase uptake. Scheduling busy researchers was also a challenge. Implementers noted that the interventions aligned with their CTSA’s Team Science goals and would help them provide additional support to teams. CP participants reported increases in understanding about their team processes and found the intervention to be both valuable and useful. Suggested improvements included longer, more personalized sessions. RJ participants agreed that RJs were helpful in surfacing shared ideas and requested additional resources to move the work forward post-session. Discussion/Significance of Impact: Team Science interventions can provide CTR teams with strategies that improve the conduct of CTR, while also serving the needs of CTSA-based Team Science leaders in facilitating more efficient and effective Team Science. Our data show the feasibility of implementing such interventions by providing training delivering team-based interventions.