Objectives/Goals: Colorectal cancer (CRC) is classified into right-sided, left-sided, and rectal cancer. Clinicopathological and molecular features vary along the colorectum, even within subsites, leading to inconsistencies in identifying relevant biomarkers. We created a CRC metabolome map to explore diagnostic and survival heterogeneity across subsites. Methods/Study Population: A total of 372 patient-matched tumor and normal tissue samples were collected from seven colorectal subsites: cecum (n = 63), ascending colon (n = 44), transverse colon (n = 32), descending colon (n = 28), sigmoid colon (n = 75), rectosigmoid colon (n = 38), and rectum (n = 92). Liquid chromatography–mass spectrometry was used to compare metabolite abundances. Cox proportional hazards regression assessed metabolite impact on survival, adjusted for clinical covariates. Parametric and nonparametric tests were applied to compare the metabolite abundances. An interactive, publicly accessible online platform was developed to allow researchers to explore and generate hypotheses from this data. Results/Anticipated Results: Our study identified 39 and 70 significantly altered metabolites, including bile acids and lysophosphatidylcholines, across tumors and normal mucosa, showing metabolic heterogeneity between CRC subsites. We observed significant linear trends in metabolite gradients from the cecum to the rectum, and it was depended on the disease status. Comparison of tumors to patient-matched normal mucosa revealed metabolite changes exclusive to each subsite. Metabolite differences correlated with survival were unique to each subsite. Additionally, we developed an interactive, publicly accessible CRC metabolome database to share this valuable resource: https://colorectal-cancer-metabolome.com/yale-university. Discussion/Significance of Impact: This study provides the first CRC metabolome map, revealing metabolic differences across colorectal subsites. It challenges the right vs. left CRC classification, highlighting subsite-specific biomarker identification. Findings offer insights for personalized treatments tailored to the tumor type to improve patient outcomes.

The emergence of the COVID-19 pandemic required an immediate global clinical research response. The ACTIV (Accelerating COVID-19 Therapeutic Interventions and Vaccines)-3 trials and the ACTIV-associated Outpatient Treatment with Anti-Coronavirus Immunoglobulin trial used Good Participatory Practices (GPP) to develop materials for study implementation from a global network perspective. GPP guidelines offer a framework for engaging stakeholders throughout the research process. This paper provides an overview of the materials developed and their applicability in various settings, reports results from a survey of study site personnel on the materials’ usefulness, summarizes important lessons learned, and serves as a reference for networks eager to apply GPP. Survey results showed that flipbooks and overview videos were highly ranked. Stakeholder input was valuable in developing easily understandable participant-facing materials with culturally appropriate images. Materials should be available to submit with the initial protocol submissions to ethics committees, and in formats that accommodate a wide range of institutional resources, policies, and infection-control practices. This article emphasizes the importance of GPP, including stakeholder consultation, in developing materials that support clinical research and address language, cultural, and sociopolitical barriers during a pandemic. The findings will be used to optimize efforts and resource allocation for new and ongoing studies.

Recent years have seen increasing focus, including by the National Institutes for Health (NIH), on developing the field of translational science (TS). TS focuses on improving the process of translational research (TR), including generating knowledge that can facilitate TR across specific diseases or translational stages. With TS as an emerging field, research organizations have an increasing need to understand how to develop capacity for and support the advancement of TS. To support such institutional and infrastructural change, this paper outlines a Translational Science Promotion and Research Capacity (T-SPARC) Framework. The T-SPARC Framework provides a foundation to 1) inform the development of TS-creating and science-supporting interventions and programs, and 2) examine the effectiveness of said interventions and programs. The framework outlines organizational levels that T-SPARC programs can target; mechanisms, or intervention activities, that can foster change; and outcomes, including specific attitudinal or behavioral changes, institutional changes, and domains on which TS changes can focus. T-SPARC’s capacity-building focus builds upon earlier efforts focused on conceptualizing and defining TS. T-SPARC supports movement towards TS goals of reducing longstanding challenges in the TR process, thus accelerating the health impact of TR, and ultimately improving health outcomes.

In this paper, we introduce the Team Effectiveness Model for Science (TEMS) and describe a multiphase set of interventions for forming a new team or developing an existing team. TEMS uses a shared mutual learning mindset as the model’s central and guiding element. It shows how team mindset leads to behavior and to results and how this affects the characteristics of effective team functioning. TEMS addresses two related questions: What are the variables that contribute to effective teams? and How do the variables need to be designed to make their relevant contributions? Team models often answer the first question without fully answering the second. By addressing three gaps, TEMS contributes to enhancing science team effectiveness. Gap 1 is the absence of explicit core values, assumptions, and norms that serve as the foundation for developing and maintaining science team effectiveness. Gap 2 is the absence of a process for integrating the science and relationship aspects of a science team. Gap 3 is the absence of team processes and structures that are derived from the team’s values, assumptions, and norms. Using TEMS to design new or intervene with existing teams focuses on shifting mindset, developing behavioral skills, and designing processes and structures congruent with the new mindset.

OBJECTIVES/SPECIFIC AIMS: Type 2 diabetes (T2D) is costly and burdensome, but strong evidence exists that lifestyle change and weight loss can improve glycemic control and lower co-morbidities for patients with T2D. We used national data to examine whether the frequency of diet and/or physical activity counseling for patients with T2D in ambulatory settings has been responsive to accumulation of evidence supporting lifestyle change. METHODS/STUDY POPULATION: We used National Ambulatory Medical Care Survey (NAMCS) data over the period 2005-2015 from 31,475 patients with provider-reported T2D. We built multivariate logistic regression models, adjusting for patient, provider, and practice level characteristics (i.e. patient demographics, physician specialty, site of care, and region), to assess changes over time in the provision of diet or exercise counseling during ambulatory care visits, as reported through provider/staff chart review. We also examined whether changes in counseling over time varied by key patient and provider characteristics. We used non-overlapping confidence intervals (CI) to assess for statistical significance. RESULTS/ANTICIPATED RESULTS: Proportions of patients with T2D who received diet or exercise counseling were no different over time: 30% in 2005 [95% CI: 25%-35%] and 25% in 2015 [95% CI: 18%-31%]. Adjusted models show Hispanic patients had higher likelihood of receiving diet or exercise counseling, compared to whites (OR: 1.38 [CI: 1.03-1.85] for diet; OR: 1.37 [CI: 1.01-1.85] for exercise), and younger age was associated with higher likelihood of diet or exercise counselling, compared to those over 75 (age 30-49, OR: 1.47 [CI:1.18-1.82] for diet OR: 1.63 [CI: 1.30-2.03] for exercise). Among provider and practice-level characteristics, metro area and type of provider were associated with higher odds of receiving any diet and/or exercise counseling with visits in a metro area (OR: 1.23 [CI: 1.03-1.48]) and with an advanced practice provider (OR: 1.77 [CI: 0.97-3.22] having higher likelihood of receiving any diet or exercise counseling. DISCUSSION/SIGNIFICANCE OF IMPACT: Up to 30% of Americans with diabetes received any diet or exercise counseling in ambulatory visits, and this remained low over a decade. There were significant differences in counseling across patient, provider, and practice characteristics. Future studies are needed to better understand what interventions might improve counseling in ambulatory settings.

OBJECTIVES/GOALS: The CTSA consortium’s Informatics Enterprise Committee has developed a maturity assessment model for Clinical Trial Management Ecosystems (CTME). This poster will show the improvements achieved using this model at the University of Iowa as well as guidance on how to apply it at other CTSA hubs. METHODS/STUDY POPULATION: The CTME maturity model consists of 11 categories including, study management; regulatory; financial; and reporting. Each category has 3 subcategories: standardization; complexity; and monitoring, while each subcategory is comprised of 1 to 5 maturity statements: initial; developing; aspiring; capable; and efficient. The maturity assessment team at Iowa—comprised of key personnel from clinical research and compliance, accounting, and administration—have used the CTME maturity model to assess Iowa’s research performance across the 11 categories. The initial maturity ratings for each category revealed any gaps in research operations, which led to developing strategies to address the gaps. RESULTS/ANTICIPATED RESULTS: The assessment team initiated a CTME maturity planning project—holding regular meetings to review Iowa’s CTME research maturity and plan changes to improve our CTME maturity ratings. This analysis is done at the statement level to minimize the scope of actions needed and keep resource loads for improvements low. Proposed improvements are assigned to a team member who serves as an “accountability leader.” Such leaders develop action plans aimed at increasing maturity at least one level. The leaders are responsible for acquiring the resources to carry out the plan. Each action plan identifies qualifiers reviewed by the team to confirm that the maturity level has been met. DISCUSSION/SIGNIFICANCE: The CTME maturity model has been shown to be effective in identifying gaps in organizational operations at the University of Iowa, where it has led to incremental steps to improve clinical research operations. The utilization of the model at other CTSA hubs will be discussed at this session.

OBJECTIVES/GOALS: A new mandate for Clinical & Translational Science Award (CTSA) Programs is for pilot grant funding to support clinical and translational science (CTS) projects that study challenges in the translational research pipeline. This pivot requires new structures and supports to help investigators design and implement high-quality CTS projects. METHODS/STUDY POPULATION: The Michigan Institute for Clinical & Health Research (MICHR) at the University of Michigan (U-M) has launched two rounds of pilot funding since March 2023. Faculty and staff across U-M’s three campuses, community members, and those at collaborating institutions and hospitals were eligible to apply. New pre-award supports included a CTS project framework; a recorded webinar that educated about CTS and the funding opportunity; office hours to provide tailored project feedback; a letter of intent to screen for alignment with CTS; and reviewer training for academic and community reviewers. Funded projects operate like 'mini cooperative agreements”, with MICHR experts partnering with awardees to refine evaluation plans, prepare work products, advise on dissemination, and navigate emergent challenges. RESULTS/ANTICIPATED RESULTS: The first round of funding was launched in the absence of pre-award supports; ten applications we received from faculty proposing translational research rather than CTS. We quickly re-released the FOA, expanding eligibility to staff. We received nine applications, ultimately funding four staff and one faculty studying operational challenges in translation and helping them create robust evaluation plans. We piloted the pre-award supports in our second round, with 40 individuals viewing our webinar and 11 attending office hours. Those who watched the webinar before attending office hours better understood how to embed CTS questions within their programs of research. We recently received 19 letters of intent, addressing both operational and scientific challenges, with 16 eligible to submit applications. DISCUSSION/SIGNIFICANCE: Education and personalized feedback seem to elicit a higher yield of CTS projects. Staff are already adept at solving operational challenges, so the pre-award supports were most critical for faculty accustomed to writing traditional translational research proposals. Staff have most benefited from guidance in evaluation and dissemination.

Objectives/Goals: Outline researchers’ perspectives on an “Aim 0” approach of engaging with people connected to the research topic to leverage their perspective when developing research questions. Worked with researchers at varying levels of career stage to understand their thoughts and concerns of this work. Methods/Study Population: Used human-centered design (HCD) methods to conduct nine semi-structured interviews with researchers at varying levels of career stage (early to senior level researchers). Interviews lasted 30–60 minutes while participants answered questions using collage cards, journey maps, and card sorting HCD methods. Questions related to communication dynamics between investigators and their population, how communication could be more population-centered, a research project journey including decisions on who and when to engage populations, and barriers and facilitators of engaging populations earlier in the research process to incorporate their voice in the development of research questions. Results/Anticipated Results: An HCD analysis approach will be conducted to outline findings. Anticipated findings include outlined communication dynamics between researchers and their affected population. The approach of engaging with the population early in the research process to help determine research questions was thought of favorably; however, feasibility concerns, mostly around finding funding, were brought up often in the interviews. More anticipated findings include what career levels would be most beneficial for an “Aim 0” approach. Discussion/Significance of Impact: Engaging with the affected population earlier in the process will help streamline efforts of investigators to solve issues their populations are dealing with. This adds another step to the research process, and it helps to understand researcher’s perspectives of this added effort.

Objectives/Goals: The objective of this study is to assemble a community advisory board (CAB) of interdisciplinary stakeholders to contextualize study results and co-create translational materials that can be used by local governments, community leaders, and community-based organizations to prevent electric bicycle (ebike) injuries. Methods/Study Population: This study merges community-engaged research and data science approaches. We are assembling an interdisciplinary CAB who are key stakeholders in informing ebike safety outside of the scientific research community. The CAB will advise on a retrospective observational data science study currently in progress that uses a California wide dataset to examine how features of neighborhoods and intersections impact ebike injuries. The CAB will provide context for study results based on their professional experiences and co-design translational materials (e.g., policy brief) that convey research findings for effective translation into policies and practices to prevent ebike injuries. We will track data on CAB activities, perceptions of participation from members, dissemination and reach of translational materials. Results/Anticipated Results: We assembled a CAB of five individuals who are policymakers, local government officials, first responders, school board members, and non-profit workers. We will report data on the frequency of meetings, themes emerging from each meeting based on discussions with CAB members, and perceptions of the experience by CAB members. We will also report on the type and content of the translational products created, the process dissemination of these translational materials, and the reach of the translational materials. Discussion/Significance of Impact: The translational aspect of this project is significant for disseminating findings to communities outside of the research realm who can implement changes that improve ebike safety. Our goal is to shorten the time for research to be translated into policies and interventions by leveraging community-engaged research and data science approaches.

Objectives/Goals: Identify risks in the regulatory reliance ecosystem, specifically for generic reliance pathways, using system theoretic process analysis (STPA), a proactive hazard analysis method, and create sustainable solutions to ensure global accessibility to the highest attainable standard of health. Methods/Study Population: A systematic literature review will assess the regulatory reliance ecosystem and interactions among National Regulatory Agencies (NRAs). This will involve using a hierarchical control structure (HCS) to identify operational loop failures, decision-making, and information flow. The HCS will inform an STPA to prevent adverse outcomes like patient harm or regulatory non-compliance. With IRB approval, 10 regulatory experts will also be interviewed to gather insights on risk scenarios. Their input will be used to integrate regulatory pathways into the HCS for adaptability, and a second round of interviews will be conducted to validate the scenarios and assess the effectiveness of recommendations. Results/Anticipated Results: A preliminary literature review on regulatory reliance pathways from PubMed, WHO guidelines, and the DIA global forum, revealed potential risks in NRA interactions, such as overly redacted reports obscuring critical details and discrepancies in product versions or incomplete reviews affecting evaluations. Diverging guidelines and failure to adapt to country-specific needs are potential risks that also impact patient access to essential medicines. The STPA framework, along with expert feedback, will uncover unknown risks like “secondary-reliance” and soft risks, leading to sustainable recommendations to improve and optimize the safety of regulatory reliance. Discussion/Significance of Impact: Safe regulatory reliance is crucial for global health equity and patient access to essential and innovative medicines. STPA will identify and address different layers of risk in the system, improving safety, efficiency, and innovation for timely patient access to therapeutics.

Objectives/Goals: Lung transplant is a life-saving surgery for patients with advanced lung diseases yet long-term survival remains poor. The clinical features and lung injury patterns of lung transplant recipients who die early versus those who survive longer term remain undefined. Here, we use cell-free DNA and rejection parameters to help elucidate this further. Methods/Study Population: Lung transplant candidacy prioritizes patients who have a high mortality risk within 2 years and will likely survive beyond 5 years. We stratified patients who died within 2 years of transplant as early death (n = 50) and those who survived past 5 years as long-term survivors (n = 53). Lung transplant recipients had serial blood collected as part of two prospective cohort studies. Cell-free DNA (cfDNA) was quantified using relative (% donor-derived cfDNA {%ddcfDNA}) and absolute (nuclear-derived {n-cfDNA}, mitochondrial-derived {mt-cfDNA}) measurements. As part of routine posttransplant clinical care, all patients underwent pulmonary function testing (PFT), surveillance bronchoscopy with bronchoalveolar lavage (BAL), transbronchial biopsy (TBBx), and donor-specific antibody testing (DSA). Results/Anticipated Results: Over the first 2 years after transplant, the number of episodes of antibody-mediated rejection (p) Discussion/Significance of Impact: Clinically, early-death patients perform worse on routine surveillance PFTs and experience a worse degree of CLAD. These patients also have higher levels of cfDNA as quantified by n-cfDNA and mt-cfDNA. These results provide preliminary evidence that early-death patients have worse allograft rejection, dysfunction, and molecular injury.

OBJECTIVES/GOALS: Our primary objective is to determine the demographic and linguistic characteristics of student research assistants (SRAs) in a large student-run free clinic associated with a mid-western university. Our secondary objective was to determine if the SRAs perceived any impact of those characteristics on their duties and ability to conduct research. METHODS/STUDY POPULATION: We plan to conduct a 15-question electronic survey of Student Research Assistants at the student run free clinic. There are a variety of projects that require varying levels of commitment from researchers, which will be aggregated. This survey has been modified from a previously validated survey that focused on the demographic and linguistic characteristics of pediatric research coordinators. This survey will be emailed out to student research assistants and will be done over a period of 3 months. The study population will be predominantly undergraduate students who are all interested in a career in healthcare, ages expected to range from 18-25. RESULTS/ANTICIPATED RESULTS: We anticipate that the majority of student research assistants will be older students and will be students who identify as non-white/caucasian, as the majority of students volunteering at this free clinic do not identify as white. Additionally, we anticipate that students will feel that their racial/ethnic identity will positively impact their recruitment efforts. We also anticipate that the ability of a student research assistant to speak another language is expected to positively affect their perceived recruitment efforts. We also anticipate that gender will influence the student researchers’ perceptions of their recruitment efforts. DISCUSSION/SIGNIFICANCE: An individual’s background can directly impact how they perceive their contributions towards research. Considering the paucity in research for underinsured and uninsured and the rise in undergraduate student research assistants, optimizing research efforts and SRA confidence is essential to increase the accuracy and efficiency of research.

Objectives/Goals: This research aims to modify an existing regulatory benchmarking framework, initially designed for medical products, to assess cosmetic product regulations in different countries. This tool will provide qualitative and quantitative comparisons of global regulatory approaches to cosmetics. Methods/Study Population: The World Health Organization’s global benchmarking tool (GBT) was selected as a suitable template for the adapted methodology. The GBT contains a comprehensive set of functions, indicators, and sub-indicators defining the high regulatory maturity standard. Although the 269 sub-indicators are tailored to the regulation of medical products, they can be intentionally adapted for other products. Relevant indicators specific to cosmetic regulation will be identified to construct a customized benchmarking tool. This tool will then be used to assess the regulatory maturity of selected countries and regulatory authorities, including the United States, the European Union, Japan, India, Brazil, China, Ethiopia, and Nigeria. Results/Anticipated Results: Preliminary analysis indicates a lack of harmonized standards for regulatory maturity across the global cosmetic market. The recent passage of the Modernization of Cosmetics Regulation Act of 2022 (MoCRA) has strengthened the United States’ regulatory framework, incorporating 11 of 13 adapted maturity indicators. The United States joins the European Union (10/13 indicators) and Japan (8/13 indicators) as leaders in cosmetic safety and manufacturing transparency. Common basic policies included good manufacturing practice regulations, while more advanced regulations cover adverse event reporting and premarket requirements. Discussion/Significance of Impact: Cosmetics, supplements, and homeopathic products lack transparency regarding safety and quality requirements. This project establishes a benchmark for cosmetic product regulation, addressing a historic gap in oversight. The benchmark supports regions with less developed regulatory policies to enhance cosmetic safety and quality standards.

OBJECTIVES/SPECIFIC AIMS: To further explore the role of vWF in the pathogenesis of scleroderma by identifying its location within the tissue of sample biopsies obtained as part of routine diagnosis with the use of immuno-histochemical staining. METHODS/STUDY POPULATION: We examined 8 skin biopsies from 2 patients with systemic sclerosis (SSc), 2 with localized scleroderma (LS) and 4 with JDM. Double immunofluorescence staining was performed in each tissue with antibodies against vWF and collagens type I and III. DAPI (4′, 6-diamidino-2-phenylindole) was also used for counterstaining of inflammatory cells. Tissue staining patterns were compared between groups. RESULTS/ANTICIPATED RESULTS: Biopsies were obtained from the upper extremity of 7 females and the lower extremity of 1 male. Median age, symptom duration, and serum levels of vWF antigen around the time of biopsy was 8 years (IQR 4.5-11), 5.5 months (IQR 2.5-7), and 245% (IQR 203-302 for 7 patients), respectively. All but 1 biopsy was performed prior to initiation of immunosuppressive therapy. Immunofluorescence staining showed a superficial and deep perivascular inflammatory cell infiltrate that co-localized with vWF in all tissues. There was expression of vWF in the extravascular tissue of patients with JScl co-localizing with collagen III in the reticular dermis (Figures 1 and 2). In comparison, vWF expression was restricted to the endothelium and did not co-localize with collagen in the dermis of patients with JDM (Figure 3). Patients with SSc had higher expression of vWF as compared to patients with LS. DISCUSSION/SIGNIFICANCE OF IMPACT: vWF may participate in the pathogenesis of cutaneous inflammatory conditions. We have demonstrated that vWF co-localizes with cellular inflammatory infiltrates in the perivascular areas and in the dermis of patients with JScl and JDM. We additionally speculate that vWF may participate in the pathogenesis of fibrosing skin diseases based on evidence of increased extravascular expression in the tissue of patients with JScl (vs. JDM), and its co-localization with collagen. vWF expression intensity in the dermis of JScl patients may relate to disease extension (SSc vs. LS).

Objectives/Goals: Problems with cognition are common and distressing for people with systemic sclerosis (SSc). We are developing a patient-centered cognitive rehabilitation intervention using the multiphase optimization strategy (MOST) framework. Our study aim is to identify patient needs, preferences, and priorities to help address their cognitive challenges. Methods/Study Population: We conducted semi-structured interviews with 15 individuals with SSc to capture in-depth perspectives on desired intervention features, potential barriers and facilitators to implementation, and overall relevance of the intervention to daily life. Transcripts were analyzed using the Rigorous and Accelerated Data Reduction technique in combination with thematic content analysis. Codes with similar content were merged and organized into subthemes and themes to understand the data. Insights from these interviews are used to inform and refine a conceptual model to guide intervention development in the MOST preparation phase, ensuring that resulting components are acceptable, feasible, and closely aligned with patients’ specific needs, preferences, and priorities. Results/Anticipated Results: Participants were 55 years old on average (100% female, 80% White). Forty percent had diffuse cutaneous SSc, and 53% were within 7 years of diagnosis. Participants reported cognitive challenges affecting short-term memory, attention, and processing speed. They highlighted the need for flexible online sessions (having multiple time options to choose from), extra time for discussion, and peer support (a space for connection and group discussion). Barriers to participation included symptom fluctuation, fatigue, and limited time. Facilitators included peer support and user-friendly resources. These insights will refine a conceptual model to guide development of an intervention that is acceptable, feasible, and tailored to the cognitive and lifestyle needs of people with SSc. Discussion/Significance of Impact: We will incorporate feedback from this study to create a patient-centered cognitive rehabilitation intervention that is tailored to people with SSc. Involving people with SSc in intervention development provides the foundation to build a robust, relevant intervention for people with cognitive challenges.