We used Cerner Real-World Data™, representing hospital admission records from 2020, to examine patients with co-occurring sickle cell disease and COVID-19 by discharge disposition grouped as death/hospice versus transfers to other facilities, returned home, or left against medical advice. Among the death/hospice group, we found older age and higher rates of congestive heart failure and diabetes. There were also significant differences in tachypnea, mechanical ventilation, minimum O2 saturation, and length of stay with higher rates in the death/hospice group. Awareness of such factors and associated mortality risks for this population may aid in patient care.

The United States Government (USG) public-private partnership “Accelerating COVID-19 Treatment Interventions and Vaccines” (ACTIV) was launched to identify safe, effective therapeutics to treat patients with Coronavirus Disease 2019 (COVID-19) and prevent hospitalization, progression of disease, and death. Eleven original master protocols were developed by ACTIV, and thirty-seven therapeutic agents entered evaluation for treatment benefit. Challenges encountered during trial implementation led to innovations enabling initiation and enrollment of over 26,000 participants in the trials. While only two ACTIV trials continue to enroll, the recommendations here reflect information from all the trials as of May 2023. We review clinical trial implementation challenges and corresponding lessons learned to inform future therapeutic clinical trials implemented in response to a public health emergency and the conduct of complex clinical trials during “peacetime,” as well.

Women remain underrepresented in National Institutes of Health (NIH) study sections, panels of scientists who review grant applications to inform national research priorities and funding allocations. This longitudinal, retrospective study examined the representation of women on study sections before and during the COVID-19 pandemic. Overall, 16,902 reviewers served on 1,045 study sections across 2019, 2020, and 2021, of which 40.1% (n = 6,786) were women. The likelihood of reviewers being women significantly increased from 2019 to 2021, except among chairpersons. Understanding the representation of scientists influencing NIH grant decisions is important to ensuring scientific discovery that meets the nation’s pluralistic needs.

OBJECTIVES/SPECIFIC AIMS: Immune cells within the tumor microenvironment (TME) play an important role in the development and progression of non-small cell lung cancer (NSCLC). However, data evaluating the impact of individual immune cell types on NSCLC outcomes is limited and often conflicting. We performed a meta-analysis of existing data and used The Cancer Genome Atlas (TCGA) to evaluate the effect of several immune cells on surgical outcomes of stage I-IIIA NSCLC. METHODS/STUDY POPULATION: PubMed was searched to identify eligible studies evaluating survival of surgically resected stage I-IIIA NSCLC patients according to immune cell infiltration. Meta-analysis was performed using a linear mixed-effects model to determine overall, disease specific and progression free survival. We then used a similar patient subset found in the TCGA to validate the meta-analysis findings. For the TCGA analysis, sample-specific scores for different immune cells were computed via xCell using level three RNAseq data. After stratifying the cohort by histologic subtype, the association between each cell type and survival was assessed via Cox Regression, while adjusting for stage, gender and smoking status. RESULTS/ANTICIPATED RESULTS: From the meta-analysis (37 articles eligible; N = 8,162 patients), high levels of CD20+ B cells (hazard ratio [HR]: 0.36, 95% confidence interval [CI]: 0.15-0.85), natural killer (NK) cells (HR: 0.64, 95% CI: 0.41-1.0), and dendritic cells (0.34, 95% CI: 0.13-0.84) were significantly associated with better overall survival (OS); T regulatory cells (HR: 1.85, 95% CI: 1.35-2.54) were associated with worst OS. High CD8+ T cell infiltrates were associated with improved disease-free survival (DFS; HR: 0.85, 95% CI 0.73-0.99), while CD68+ macrophages (HR> 2.83, 95% CI: 1.28-6.24) were associated with worst DFS. In the TCGA cohort, lung adenocarcinomas rich in CD4 T cells, CD8 T cells, B cells, and NK cells were associated with improved OS in unadjusted analysis. In adjusted analysis, only NK cells were associated with improved OS (HR: 0.82, 95% CI: 0.69-0.98). There was no significant association of any immune cell type for DFS in lung adenocarcinomas and with both OS and DFS in Squamous Cell Lung Cancers (p>0.05 for all comparisons). DISCUSSION/SIGNIFICANCE OF IMPACT: The presence of tumor infiltration by specific immune cell subsets may potentially predict survival outcomes in resected stage I-III NSCLC patients. However, the impact of immune cells may not be similar in all histologic types and after adjusting for important clinical confounders.

Objectives/Goals: As life expectancy increases in people with HIV, neurocognitive impairment is becoming more common, and women with HIV (WWH) are disproportionately impacted. This work investigated mitochondrial function and oxidative stress in WWH in order to understand the relationship between mitochondrial function and cognition in future studies. Methods/Study Population: Peripheral blood mononuclear cells were isolated from virally suppressed WWH (n = 64) and underwent the Seahorse Cell Mito Stress test to assess different realms of mitochondrial function. Cells were then lysed for direct DNA extraction, and quantitative PCR was performed to understand mitochondrial DNA expression (mtDNA) levels as a measure of oxidative stress. A series of simple linear regressions was then conducted to understand the relationships between mitochondrial function and mtDNA content. Future work will expand this analysis to investigate associations between demographic dynamics, such as trauma history, and mitochondrial function, as well as to understand the relationships between mitochondrial function and cognitive outcomes in WWH. Results/Anticipated Results: In our cross-sectional analysis of mitochondrial dynamics in WWH, we found a significant association between maximum mitochondrial respiration ability and mtDNA content, with greater mtDNA expression associated with increased levels of maximum respiration following stimulation. There was no association between basal respiration and levels of oxidative stress. There was also a significant variation in mitochondrial function in our participants, indicating that future analyses to investigate the source of that variation are warranted. The work presented here sheds light on mitochondrial dynamics in WWH and will be the basis for future studies that will investigate how demographic dynamics may be associated with mitochondrial function, as well as how mitochondrial dynamics may predict cognitive outcomes. Discussion/Significance of Impact: There is significant variation in mitochondrial function in WWH. More analysis is needed to understand what may be associated with these variations, including an investigation of both clinical factors as well as cognitive outcomes. This analysis will inform directions for future mechanistic work aimed at mitigating adverse cognitive outcomes in WWH.

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

Objectives/Goals: Collaborative agreements are vital for building strong partnerships, particularly during the formation of new research teams. To support team scientists during critical stages of team formation, we developed a flexible, on-demand eLearning module on collaborative agreements with examples and guidelines for developing tailored agreements. Methods/Study Population: The on-demand Collaborative Agreement module empowers learners to complete a full overview of collaborative agreement concepts or to directly access topics of interest within the module. Designed for real-time applications, it includes conversation prompts, downloadable templates, and example scenarios to guide team building and maintenance. To date, the module has been used by clinical and translational science trainees, early-career investigators, faculty participating in mentor training programs, and PIs of a multi-site research project. Early feedback has prompted the development of a consultative service to support teams in developing their own collaborative agreements after team members complete the module. Results/Anticipated Results: We are collecting data through pre- and post-training assessments embedded within the module. Post-assessment also invites respondents to share contact information for follow-up evaluation of their adoption. As of October 2025, we have collected 21 pre-assessment responses and 14 post-assessment responses. We anticipate gathering more data prior to Translational Science 2026. We will summarize assessment data focused on the tool’s effectiveness, learner’s intention to adopt collaborative agreements, and their confidence in building their own agreements. Additionally, we will provide feedback on the value of support services post-training for team implementation of collaborative agreements. Discussion/Significance of Impact: The just-in-time online tool facilitates the use of collaborative agreements for individual learners, teams, and between mentors and mentees. It supports effective collaboration by clarifying shared expectations. Feedback for the module will inform enhancements as well as future translational science workforce development eLearning projects.

OBJECTIVES/GOALS: To establish and develop a high-level, dynamic, and self-sustainable Translational Science – research center in Colombia that promotes and articulates collaborative participation among different disciplines at Universidad de La Sabana to generate impactful solutions in health to transfer the knowledge to the local community. METHODS/STUDY POPULATION: With the support of core units of the University, internal funding was given for the establishment of the Research Center. An internal call was performed for recruiting researchers for multiple disciplines interested in joining the UCTS. After the researchers were selected, training of the research community in translational science and funding acquisition was performed towards the objective of interdisciplinary projects with impact in the local community. Project management strategies have been used for the follow-up of the advancements of the implementation of the UCTS. Operational structure and business plan for future self-sustainability are being designed. UCTS is proposed as an articulating party among different actors in clinics, research, and industry, for science and funding management. RESULTS/ANTICIPATED RESULTS: As an starting point, 8 research groups of different disciplines of the University have been integrated with the UCTS, increasing the research capacity in translational science. Internal administrative processes have been articulated within the institution and unified processes for international grants applications have been established in order to optimize the funding acquisition and management. Training programs for the research community, and community engagement activities have been offered as well. Networking relationships have been strengthened among the researchers enhancing international collaborations. Novel research projects are being designed towards real solutions in health for the local community, promoting the transference of knowledge from the benchside to the community. DISCUSSION/SIGNIFICANCE: The implementation of the UCTS led to the integration of disciplines within the University, towards new research projects with common interests for the local community. It has been an enriched experience using the project management approach, fulfilling a huge milestone for the University, aligned with the internal strategic priorities

OBJECTIVES/SPECIFIC AIMS: Aim 1: To evaluate whether psoas muscle size on CT imaging can be used as univariate predictor for increased risk of morbidity and mortality in trauma patients 65 years or older with rib fractures. Primary outcomes will be 30 day mortality. Secondary outcomes will include length of stay, 30 day readmission rate, need for operative/procedural intervention, ICU days, ventilator days, discharge to rehabilitation. Aim 2: An eventual goal of the project will be to use the results of the single variable psoas size study to inform the development of a predictive model for readmission rate in this population based on clinical variables present at admission. METHODS/STUDY POPULATION: This retrospective cohort study will utilize the Maine Trauma Registry to conduct a database review for all persons 65 years of age and older admitted to Maine Medical Center between January 1, 2015 and December 31, 2017 with rib fracture as diagnosed by CT imaging. Psoas caliber will be measured on admission CT. Patient outcomes will be assessed via EMR review. RESULTS/ANTICIPATED RESULTS: Anticipate finding a relationship between decreased psoas caliber and increase in 30 day mortality and post trauma complications. DISCUSSION/SIGNIFICANCE OF IMPACT: If a relationship is demonstrated between decreased psoas caliber and poor outcomes in elderly patients with rib fractures, this early indicator could be used to identify those patients at most risk, for whom targeted interventions may make the greatest difference. Knowing a measure of frailty could also help guide goals of care discussions, because it would allow clinicians to have a more detailed understanding of a patient’s baseline. Those patients identified as frail could be admitted to an ICU level of care and more closely monitored and treated. Alternatively, some frail patients and their families may choose to focus more on comfort and quality of life after achieving a better understanding of a patient’s frailty and risk, changing the direction of care provided. Being able to identify the higher risk patients with an objective measure would allow clinicians to provide more personalized medicine.

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.

OBJECTIVES/GOALS: High turnover rates of clinical trials staff pose obstacles to the quality and efficiency of conducting clinical trials. We have explored alternative staffing models to address these translational barriers and to improve the financial viability and return on investment of a centralized clinical trials office. METHODS/STUDY POPULATION: Implementation of an alternative clinical trials staffing model that leveraged burnout rates in clinical service areas by hiring APPs, RNs, EMTs, OTs and PTs in tandem with traditional CRAs/CRCs. Financial modelling of employing higher salaried clinical professionals was analyzed with regards to greater staff retention, trials efficiency, and operational cost savings. RESULTS/ANTICIPATED RESULTS: Since 2014, 30 of 51 (59%) staff left the clinical trials office with 49% of these leaving prior to 2 years employment. Using average local CRCII compensation values, the costs associated with these transient staff amounted to $2.51 million (i.e., recruitment, replacement, and training). Models of staffing that replace 2 CRAs, 2 CRCIs and 2 CRCIIs with an RN, APP, CRCI and 3 CRAs increases compensation by 24.1%. This increase, however, is offset by greater workload capacity, retention, and more efficient trials operations. In addition, revenue generating PI clinical activity is sustained by employing credentialed APPs for study visits. DISCUSSION/SIGNIFICANCE: Long-term financial savings and greater clinical trial operational efficiency may be accomplished by seeking clinical professionals looking for alternative opportunities with greater work-life balance while leveraging their advanced clinical skills and licensing.

OBJECTIVES/SPECIFIC AIMS: Projected to soon become the most prevalent cause of End-Stage Liver Disease, the frequency of Non-Alcoholic Fatty Liver Disease (NAFLD) has been rising in the US community. However, studies on NAFLD among inpatients are lacking. Aims: To report the 1) prevalence and trends, 2) outcomes of NAFLD associated hospitalizations in the US. METHODS/STUDY POPULATION: NAFLD cases were identified in the National Inpatient Sample (2007-2014) with ICD-9-CM codes, and the prevalence and trends over the 8-year period were calculated among different demographic groups. After excluding secondary causes of hepatic fat accumulation from the NAFLD cohorts (n = 210,660), the impact of sex, race, and region on outcomes (mortality, discharge disposition, length of stay [LOS] and cost) of NAFLD was computed with generalized estimating equations (SAS 9.4). RESULTS/ANTICIPATED RESULTS: Admissions with NAFLD tripled from 2007-2014 at an average rate of 79/100,000 hospitalizations/year (p-value < 0.0001), with a larger rate of increase among males vs. females (83/100,000 vs. 75/100,000), Hispanics vs. Whites vs. Blacks (107/100,000 vs. 80/100,000 vs. 48/100,000), and governmental-/un-insured patients vs. privately-insured (94/100,000 vs. 74/100,000). Males had higher mortality, LOS and cost than females. Blacks had longer LOS and poorer discharge destination than Whites; while Hispanics and Asians incurred higher cost than Whites. Uninsured patients had higher mortality, longer LOS and poorer discharge disposition than the privately-insured. DISCUSSION/SIGNIFICANCE OF IMPACT: Hospitalizations with NAFLD is rapidly increasing in the US, with a disproportionately higher burden among certain demographic groups. Measures are required to arrest this ominous trend and to eliminate the disparities in outcome among patients hospitalized with NAFLD.

OBJECTIVES/GOALS: In a 2022 NASEM Report, “… successful inclusion of underrepresented populations in research is investing in diverse research teams to enhance congruence and to optimize recruitment and retention success.” Thus, academic research institutions must provide safe, respectful and inclusive work environments to support diverse research teams. METHODS/STUDY POPULATION: Resources, policies and protocols related to disruptive research participants have not been well articulated at our institution. Given this dearth of information, we launched a new initiative across our CTSA, IRB, Office of General Counsel and Department of Population Health. The multipronged approach includes: 1) Conduct a scoping review of published and gray literature to identify best practices, trainings and resources to mitigate discrimination, harassment of research team members; 2) Co-develop new institutional policies and procedures to ensure safety and respect for both research staff and participants; 3) Develop an online training on research team field and workplace safety; and 4) Widely disseminate policies and resources to address the overall gap in academic research. RESULTS/ANTICIPATED RESULTS: Our ongoing scoping review has shown that here is an overall lack of information on bias, discrimination and harassment perpetrated by research participants towards research teams. Based on our activities, new Human Research Protection policies were launched. These include defining what disruptive participant behavior in research is, the introduction of a Statement on the Conduct of Participants in Research Studies, and steps study teams may implement to manage disruptive behavior initiated by a research participate. Next steps include the development of training resources for study teams on the new policies and to introduce de-escalation and situational awareness strategies and trainings. DISCUSSION/SIGNIFICANCE: As research teams become increasingly diverse, there is a need to better support them and ensure that the research field and work settings are safe, inclusive environments with articulated policies that mitigate/prevent discrimination, bias and harassment perpetrated by study participants.

Objectives/Goals: This pilot study uses an ethnographic analysis to examine provider knowledge, experiences, perception, and attitudes in delivering care in rural, primary care health professional shortage areas. Methods/Study Population: Ethnographic study relying on qualitative methods (semi-structured and open-ended interviews). Study population includes rural healthcare professionals (HCP), including physicians, physician assistants, nurses, dentists, therapists, and pharmacists. Results/Anticipated Results: Anticipated Results: Understandings of why rural HCP choose to deliver healthcare in resource-limited communities, and how this figures into their knowledge, experience, attitudes, and perceptions. A focus on barriers as well as strengths of HCP practicing in rural, HPSA. HCP in rural settings often face distinct working conditions precipitated by resource limitations, which may lead to higher levels of negative emotional or mental health conditions in comparison to their urban counterparts. This study will also attune to the extent to which their work, specifically as HCP in rural settings – as a SDOH – affects their mental health status. Discussion/Significance of Impact: This research contributes to the literature on global health by examining HCP in relation to rurality and in resource-limited settings in the Global North. This will expand the current global health discourse beyond the Global South and bring much needed attention to the health and well-being of communities in the Global North.