Expanded access (EA) is a United States regulatory approach for the use of investigational drugs/devices that do not yet have conventional approval, in clinical care contexts. We conducted a retrospective study to analyze the neighborhood characteristics of patients who have received EA treatments at our academic medical center between 2018 and 2023. EA patient neighborhoods showed lower median family income, lower proportion of bachelor’s degree graduates, and a higher proportion of people identifying as non-Hispanic White ethnicity compared to the surrounding (Washtenaw) county. These differences may underly differential interest in EA treatments or may point to disparities in access to evidence-based care.

The learning sciences have yielded a wealth of insights about the mechanisms and conditions that promote learning, yet the findings from this body of research often do not make their way into educational practice. This fundamentally translational problem is one we believe that educators from translational fields, with their evidence-based orientation and familiarity with the challenges and importance of translation, are well-positioned to address. Here, we provide a primer on the learning sciences to guide educators in the Clinical and Translational Science Institutes and other organizations that train translational researchers. We (a) describe the unique teaching and learning environment in which this training occurs, and why it necessitates attention to learning research and its appropriate application, (b) explain what the learning sciences are, (c) distill the complex science of learning into core principles, (d) situate recent developments in the field within these principles, and (e) explain, in practical terms, how these principles can inform our teaching.

Objectives/Goals: Radiation nephropathy results in morbidity and mortality in patients receiving cancer treatment. In addition, low birth weight and low nephron number are associated with increased risk for chronic kidney disease. This study examined the development and severity of radiation-induced renal hemodynamic dysfunction in a low renal mass mouse model. Methods/Study Population: Male mice (C57Bl/6, 8–12-weeks) were used to determine a suitable radiation dose regimen. Mice were subjected to fractionated bilateral kidney irradiation with 5–6 fractions of an X-ray dose of 0, 6, 8, and 10 Gy at 24-hr intervals using a CT-image-guided irradiator. Body weight and mortality were monitored for 5 weeks in mice. In a separate set of experiments, the low renal mouse model, ROP Os/+, and their normal counterpart, ROP +/+ mice were subjected to 5 fractionated bilateral kidney irradiations at 24-hr intervals with an X-ray dose of 6 Gy. Renal blood flow was assessed from renal artery resistive index (RRI) over 5 weeks post-irradiation using an ultrasound system. Transcutaneous measurement of FITC-sinistrin clearance was used to determine glomerular filtration rate (GFR). Results/Anticipated Results: The C57Bl/6 mice that received 5–6 fractions of 8 and 10 Gy had more than 50% mortality, while 100% of the mice exposed to 5 fractions of 6 Gy survived for 5 weeks. Body weight was also significantly decreased in mice exposed to 5 or 6 fractions of 8 or 10 but not 6 Gy radiation. Nonirradiated C57Bl/6, ROP +/+, and ROP Os/+ mice had similar baseline GFR and RRI. Irradiation of 5 fractions at 6 Gy decreased GFR and increased RRI in C57Bl/6 and ROP +/+ mice. Interestingly, following 5 fractions at 6 Gy irradiation ROP Os/+ mice had 25% lower GFR than wild-type ROP +/+ mice (946.3 ± 50.3 vs. 1232.9 ± 69.3 µL/min/100g BW, p Discussion/Significance of Impact: Our study determined a suitable fractionated bilateral kidney irradiation dose regimen to evaluate radiation nephropathy. Data demonstrated that fractionated bilateral kidney irradiation leads to decreased renal hemodynamics in mice. We also demonstrated that irradiation caused greater renal hemodynamic dysfunction in low renal mass mice.

Objectives/Goals: Given the challenges that early career research scientists face, especially preparing for promotion and tenure, the decision on whether to join a research team can be fraught. We developed a novel training to support informed decision-making regarding new scientific teaming opportunities. Methods/Study Population: A team science workshop entitled “Should I join this research team” was designed for early career investigators from varied disciplinary backgrounds. Learning objectives for attendees included 1) describing the role of team science in translational research, 2) determining if teaming opportunities are a good fit, and 3) crafting thoughtful responses to requests. The training was initially delivered to 38 attendees (11 K scholars) during a virtual national meeting. We adapted this training for in-person delivery to K and T scholars at our CTSA regional partners. Instructional methods shared across virtual and in-person modalities included self-reflection, think and share activities, and scenario application. In-person delivery also included short video clips and small group discussions. Results/Anticipated Results: Multiple Likert-scale items were completed by workshop participants before and after completing the workshop to evaluate attendees’ confidence in their perceived abilities to explain strengths and limitations of team science, identify characteristics of effective science teams, evaluate a team invitation, assess costs and benefits, negotiate collaborative team invitations, etc. Preliminary data from the virtual workshop suggests that 54.6% of scholars were either not at all or only slightly confident in evaluating a teaming invitation. After the workshop, 45.5% reported being very confident, and 9.1% reported extreme confidence in evaluating a team invitation. Evaluation of the in-person training, along with a comparison of virtual and in-person learning outcomes will also be presented. Discussion/Significance of Impact: Our multimodal training is designed to equip early career investigators with the tools needed to evaluate and respond effectively to research team invitations. We believe this novel training will result in informed teaming decisions for early career research scientists.

This report highlights the design, implementation, and key lessons from the William Schnaper Visiting Scientist (WSVS) Program, developed to foster scientific exchange among predoctoral and postdoctoral Translational Science (TS) Trainees across Clinical and Translational Science Award (CTSA) hubs. Trainees were part of TL1 and T32 CTSA programs funded by the NIH National Center for Advancing Translational Sciences. The WSVS program includes three complementary training opportunities: Mini-Symposium, Debate Forum, and Grand Rounds (GR) which is the subject of this report. The GR program provides advanced trainees with opportunities to present their research at another CTSA institution through a virtual forum, offering national-level exposure and constructive feedback from experts. In addition to formal presentations, participants engage in personalized, one-on-one meetings with faculty members at the host institution, gaining insights into other academic cultures and expanding their professional networks. We surveyed trainees and host institutions who participated in the program using single-and multiple-response items, Likert scales, and short open-text response questions. Survey respondents were overwhelmingly positive; all trainees recommended the program to peers and affirmed the value of the program. This demonstrates a scalable approach to enhancing TS education, advancing professional development, and promoting a more interconnected biomedical research community.

Underrepresented minorities have higher attrition from the professoriate and have experienced greater negative impacts of the COVID-19 pandemic. The purpose of this study was to compare the impact of COVID-19 on the lives of 196 early-career physician-scientists versus PhD researchers who are underrepresented in biomedical research. Participants in the Building Up study answered questions on the impact of the COVID-19 pandemic on their personal and professional lives, and a mixed-methods approach was used to conduct the analysis. While most participants experienced increases in overall stress (72% of PhD researchers vs 76% of physician-scientists), physician-scientists reported that increased clinical demands, research delays, and the potential to expose family members to SARS-CoV-2 caused psychological distress, specifically. PhD researchers, more than physician-scientists, reported increased productivity (27% vs 9%), schedule flexibilities (49% vs 25%), and more quality time with friends and family (40% vs 24%). Future studies should consider assessing the effectiveness of programs addressing COVID-19-related challenges experienced by PhD researchers and physician-scientists, particularly those from underrepresented backgrounds.

Disability is a common and universal human experience. Yet, people with disabilities (PWDs) are in poorer health and have less access to quality healthcare than their non-disabled peers. In fact, the National Institutes of Health’s (NIH) designated PWDs as a health disparities population in 2023. This paper illustrates the application of translational science (TS) principles to overcoming roadblocks to reducing PWDs’ health disparities. Part I provides an overview of health disparities among PWDs and the recent designation – situating both within a TS framework. Part II summarizes literature on specific factors that contribute to PWDs’ exclusion from research, how these factors are reflected in background reports that impelled the designation of PWDs as a disparity population, and how the suggested steps to implement the designation reflect TS principles and its research agenda. Part III describes “Reducing Researcher Roadblocks to Including People with Disabilities in Research (D2/R3),” a TS solution to overcoming PWDs exclusion from research. D2/R3 is our institution’s Clinical and Translational Science Award research project – a mixed-methods study that targets research teams’ knowledge, attitudes, biases, and perceptions that contribution to under representation of persons with developmental disabilities in research.

Objectives/Goals: Team science (TS) competency is important for translational science team collaboration. However, there are few educators available to assist teams. Asynchronous learning is an effective strategy for delivering TS content. The goal of this project is to expand TS education by providing online access to our learners using online modules. Methods/Study Population: The Collaboration and Team Science (CaTS) team at the University of Cincinnati provides a robust TS education and training program. As the need for team science gains recognition, CaTS has received increased requests for services, leading to a need to broaden TS offerings. To address this demand, the CaTS team created “Team Science 101,” an online, asynchronous, series of 15 modules covering basic team science concepts. Each module consists of an educational recording lasting an average of 20 minutes, optional topic resources, pre- and post-module surveys assessing learners’ confidence and satisfaction, post-module knowledge checks, and evaluation questions. Upon completing all modules, participants receive a completion certificate. Results/Anticipated Results: TS 101 will be piloted with a group of participants who expressed interest in asynchronous TS content and will be adjusted based on the feedback received. The associated pre- and post-module survey, post-module knowledge check, and evaluation questions will be monitored to determine learning levels and improve TS 101 overall. Canvas is the educational platform that houses these modules, allowing for participant follow-up and scalable dissemination. The CaTS team plans to disseminate TS 101 nationally and internationally for anyone interested in this resource. Discussion/Significance of Impact: There is a national effort to collect and curate TS education, training, and toolkits. TS 101 will be a useful educational tool that will expand the reach of team science educators, provide the foundation for educators to explore topics more deeply by building on the module topics, and provide education to broader audiences who lack access to TS experts.

Objectives/Goals: Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system that affects 2 million people worldwide causing severe disability. This study uses the Gamt-GFP transgenic mouse line as a novel approach to track oligodendrocyte lineage cell regeneration in inflammatory demyelination for identifying potential therapies. Methods/Study Population: We previously showed that Gamt, an enzyme required for creatine synthesis, is essential for oligodendrocyte (OL) maturation and survival using the Gamt-Green Fluorescent Protein (Gamt-GFP) reporter line. In this study, we capitalize on this finding and track OL lineage cells in an experimental autoimmune encephalomyelitis (EAE) mouse model by inducing immune-mediated demyelination in the Gamt-GFP reporter line. At 7 days postimmunization (dpi), both control and EAE mice receive 4 mg/kg tamoxifen for 4 consecutive days to induce GFP expression. GFP+ cells and those also expressing OL lineage markers [Olig2 (pan-OL lineage cell marker), NG2 (OL precursor cells; OPCs), and CC1 (mature OL)] are quantitated by immunofluorescent staining of spinal cord sections collected at 28 dpi. Results/Anticipated Results: Preliminary data using immunofluorescent staining demonstrated GFP was expressed in Olig2+ cells in the inflammatory ventral white matter lesions of mice with EAE, whereas no GFP labeling was present in the control mice. Moreover, GFP+ cells also expressed NG2+. In contrast, few CC1+ cells were detected in the inflammatory lesions. The low number of dual labeled GFP+CC1+ cells in these lesions suggests OPCs under the EAE environment are unable to efficiently differentiate into mature OL. Therefore, the Gamt-GFP reporter mouse can be used to identify and track activated OL lineage cell populations (i.e., GFP+CC1) in inflammatory lesions in the EAE mouse model. Discussion/Significance of Impact: The Gamt-GFP reporter line identifies activated OL lineage cells responding to inflammatory demyelination, making it a valuable tool for testing potential therapeutics aimed at enhancing remyelination. This model helps bridge the gap between preclinical and clinical research to guide MS therapy development.

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

Objectives/Goals: Understanding cognitive habits and values of individuals or groups, and providing tools to apply them to collaborative, interdisciplinary endeavors to better communicate between different industries, functions, and cultures. Methods/Study Population: Using literary research to establish groupings of common core values in interpersonal communications, applying established 5 patterns of “thought languages” to scale to group communications. Accepted psychological personality inventories for individuals will overlay into cognitive values, primarily using the current big five OCEAN model. Demonstrating these values to find common goals among interdisciplinary collaborations can identify prospective members, cultural differences in industry, patient communication, and public messaging in STEM. Integrating these tools into research groups to establish more efficacious communication between teams, governing bodies, and patient communication can be sampled via pre and post research surveys of feeling understood. Results/Anticipated Results: The results of feeling understood by various parties in collaborative research would be a measure of not just effective expressed communication, but received communication. Feeling understood is a current metric of communication that is correlated with satisfaction, trust, and interdependence. All of these results are integral to the successful operations of collaborative projects. Demonstrating a positive correlation between applying the 5 thought languages and better-surveyed outcomes of understanding will guide the effectiveness of this as a future collaborative tool for translational sciences. Discussion/Significance of Impact: The significance of effective communication based on positive reception will foster future collaborations. Encouraging familiarity between differing individuals, groups, and industries, even between subjects and researchers, patients and healthcare. More satisfaction, more trust, and more interdependence will propagate between these groups.