OBJECTIVES/SPECIFIC AIMS: Identify objective neurological substrates of cognitive fatigue in Parkinson’s disease and in aging. METHODS/STUDY POPULATION: Structural and diffusion MRI. Behavioral assessments for aged adults and Parkinson’s disease. RESULTS/ANTICIPATED RESULTS: Gray and white matter deficits that correlate with deficits in the basal ganglia for fatigued Parkinson’s disease patients Versus anterior cingulate cortex in healthy aged adults with fatigue. DISCUSSION/SIGNIFICANCE OF IMPACT: Over 50% of patients with Parkison’s disease and 38% of healthy older adults suffer from cognitive fatigue. However, diagnostics are limited to subjective surveys and there are no treatments for either population. Therefore, objective measures are greatly needed for better diagnosis and development of treatment targets.

OBJECTIVES/GOALS: The use of assistive technology (AT) devices is known to improve older adults’ independence in daily activities. However, little is known about the impact of using an AT web app in older Latinos’ life. This study aims to evaluate the value and usefulness of the My Assistive Technology Guide web app among older Latinos with physical function disabilities. METHODS/STUDY POPULATION: We employed a convergent parallel mixed-method design with 12 community-living older Latinos from Puerto Rico. Researchers provided training in the use of My Assistive Technology Guide, a Spanish evidence-based web app with detailed information on 97 AT devices and videos of older people using them. Participants were encouraged to use it for 30 days. Afterward, we collected quantitative data using the subjective quality domain of the User Mobile Application Rating Scale (uMARS), followed by qualitative data through individual interviews. Quantitative data were analyzed with descriptive statistics and qualitative data with thematic content analysis. RESULTS/ANTICIPATED RESULTS: My Assistive Technology Guide web app received high ratings in the uMARS subjective quality domain (mean 4.5 [SD 0.5] out of 5), indicating that participants highly valued the usefulness of the web app. Qualitative data fell into four main categories: functional health, meaningful participation, autonomy, and personal growth. DISCUSSION/SIGNIFICANCE: The findings suggest that the AT knowledge provided by the My Assistive Technology Guide web app has the potential to enhance the quality of life of older Latinos in the face of the challenges posed by physical function disabilities as people age.

ABSTRACT IMPACT: The successful conversion of an in-person biomedical research commercialization education course to a fully virtual and flipped experience (self-paced) allows greater participation from faculty investigators at CTSA institutions and serves as a model for similar educational programs intended to accelerate the translation of biomedical innovations to products of impact. OBJECTIVES/GOALS: Due to COVID-19, University of Michigan’s Fast Forward Medical Innovation developed new educational resources and leveraged virtual learning tools to convert a successful in-person research commercialization course to a fully virtual, flipped format and evaluated the effectiveness of the converted course compared to the in-person equivalent. METHODS/STUDY POPULATION: Two novel interactive modules (intellectual property and FDA regulation) and five instructional videos (customer discovery, value proposition, opportunity sizing, target product profile, and patent searches) were developed while Constant Contact and Zoom were used for a weekly progression of content delivery and to flip the course: (1) forming/testing value propositions, (2) intellectual property, (3) regulatory, (4) medical reimbursement, (5) business case development. A total of 32 faculty and graduate students completed the virtual, flipped course and submitted a post-course evaluation. Results of the converted course were compared to evaluation results from the in-person course. RESULTS/ANTICIPATED RESULTS: Open rates for the weekly email content were: (1)61%, (2)67%, (3)65%, (4)67%, and (5)59 %. Total views for the modules and videos were: IP-28, regulation-19, customer discovery-62, value proposition-21, opportunity sizing-66, target product profile-11, and patent searches-29. Evaluation results from the virtual course (n=22) were compared to mean results from the 5 previous in-person courses (n=42); 86% of virtual course respondents stated the course met the objectives compared to 85% of in-person respondents; 87% of virtual respondents stated the course met their expectations compared to 100% of in-person; 87% of virtual respondents said they would participate in a follow-up program compared to 94% in-person; 91% of virtual respondents would recommend the course to others compared to 97% of in-person. DISCUSSION/SIGNIFICANCE OF FINDINGS: Email open rates and content views suggest positive flipped participation. Overall, the converted course was comparable to the in-person course at meeting objectives, suggesting the virtual format is effective at delivering the course content and holds the potential for engaging a broader audience.

OBJECTIVES/GOALS:

• 1. Assess the institutional and individual training needs and gaps in the conduct of human research for PIs at the University of Minnesota.

• 2. Define the training program’s learning objectives.

• 3. Develop and implement an in-person training session that addresses the gaps.

METHODS/STUDY POPULATION:

• Establish a planning committee

• Identify required and optional training that is already available for PIs, then determine gaps

• Understand research training needs based on conversations with departmental and human research protection program leaders.

• Develop learning objectives and curriculum based on Federal and Local regulations, guidelines, and policies.

• Establish a feedback loop regarding research compliance with the HRPP, to assess trends and ensure continuous improvement.

• Evaluate the training program’s participants using confidence and satisfaction measures.

RESULTS/ANTICIPATED RESULTS: Developed and piloted a 90-minute in-person training program entitled “PI Primer” with the goals of:

• Increasing awareness and knowledge of the role and responsibilities of the Principal Investigator (PIs) according to the International Harmonization for Good Clinical Practice (ICH-GCP), Federal Regulations (FDA, DHHS, ect.), and University of Minnesota Policies.

• Identifying root causes for receiving an FDA 483 (inspection findings).

• Addressing and preventing common inspection findings (CAPA).

• Describe individual and institutional conflict of interest (COI), and identify the key steps necessary to manage COIs.

DISCUSSION/SIGNIFICANCE OF IMPACT: OHRP’s guidance on the “Responsibilities of Investigators” states that it is the Institution’s responsibility to provide human research training on a wide variety of topics to ensure the ethical conduct of research and protection of participants. PI Primer provides an in-person forum for investigators to build upon required responsible conduct of research and good clinical practice training to be able to apply the role and responsibilities of a PI to their own research. PI Primer also establishes a network of PIs in order to enhance connectivity and shared learning.

OBJECTIVES/GOALS: Side effects are why up to 50% of women with hormone-positive breast cancer prematurely discontinue aromatase inhibitor (AI) therapy. Pain from altered nociception without clear tissue/nerve damage (nociplastic) is a hypothesized contributing factor to this. Our objective was to evaluate the relationship between nociplastic pain and AI duration. METHODS/STUDY POPULATION: Patients with breast cancer diagnosed between 2012-19 were identified from the University of Michigan Genomics Initiative (MGI). Patients who were female, >65 years old at time of breast cancer diagnosis, and had hormone receptor-positive disease met inclusion criteria. Prior to undergoing surgery, patients completed validated surveys about overall worst pain (Brief Pain Inventory [BPI]), nociplastic pain (2011 Fibromyalgia Survey [FS]), and life satisfaction, with higher scores representing more of the factor. Breast cancer history, treatment, and patient demographics were abstracted from the medical record. Univariate analysis was conducted to evaluate the relationship between age, body-mass index (BMI), chemotherapy, BPI, FS, life satisfaction, and time to discontinuation of initial AI. RESULTS/ANTICIPATED RESULTS: 207 patients were eligible, 133 of whom initiated AI therapy. Of the 133 analyzed patients, mean age was 70.7 years and mean BMI was 30.3. 28 (21%) underwent adjuvant chemotherapy and 79 (59%) received adjuvant radiation prior to initiation of AI therapy. Average nociplastic pain score was 4.0/31 (standard deviation [SD] 4.6), worst pain was 1.5/10 (SD 1.9), and life satisfaction score was 7.3/10 (SD 2.8). The initial AI for 94% of patients (125 patients) was anastrozole. On univariate analysis, only higher nociplastic pain score was statistically associated with premature discontinuation of AI with a HR 1.07 (95%CI 1.00-1.13, p = 0.036). On multivariable analysis, no factors remained statistically significant, although there was a trend for nociplastic pain (HR 1.06, 95%CI 1.00-1.13, p = 0.068). DISCUSSION/SIGNIFICANCE: It is important to identify variables predicting tolerance to therapy so patients can be optimally counseled. Our study suggests that patients with pre-existing baseline pain disorders may be more likely to be nonpersistent with AI therapy. Future study should be conducted to determine if treatments for nocipastic pain improve AI persistence.

OBJECTIVES/SPECIFIC AIMS: Respiratory viruses cause enormous medical burden, yet many of the specific virus and host genetic factors that impact pathogenesis are still largely unknown or poorly understood. To better understand the drivers of both acute clinical pathogenesis and long-term impacts, such as the development of asthma, we investigated the host response to respiratory syncytial virus (RSV) infections in pediatric patients. METHODS/STUDY POPULATION: We collected nasopharyngeal swabs from 32 pediatric patients with acute RSV infection. The swabs represented a mixed cell population including epithelial and immune cells at the active site of infection. Unbiased RNA sequencing with ribosomal RNA depletion allowed the simultaneous detection of host gene expression and RSV infection. We sequenced samples 2×75 bp on an Illumina NextSeq 500. Sequences were mapped to the human genome using the TopHat 2 aligner and FPKM estimation of reference genes and transcripts and assembly of novel transcripts were conducted with Cufflinks 2. RESULTS/ANTICIPATED RESULTS: During acute RSV infection we identified 7343 genes that were significantly expressed. Pathway analysis using KEGG revealed significant upregulation of pathways involved in innate immune response infection, ribosome function, oxidative phosphorylation, spliceosome and autoimmune disorders. We found high levels of innate immune response genes including CXCL8, IFITM1, IFITM2, IFITM3, IL1RN, and ISG15. In comparing RSV subtype A to RSV B we found significant differential expression of multiple noncoding RNAs. DISCUSSION/SIGNIFICANCE OF IMPACT: Examination of the host gene response during acute RSV infections, yielded important insight into the mechanisms that cause clinical pathogenesis and may provide understanding of the mechanisms that lead to known long-term impacts, such as the development of asthma. Together, this data may be used to guide clinical treatment and management decisions for children with severe RSV infections.

Objectives/Goals: Clinical trial success requires recruiting and retaining diverse participants. The ER&R Certificate Program trains clinical research professionals (CRPs) in equity, diversity, and inclusion (EDI), addressing biases, and integrating regulatory knowledge with practical skills to foster inclusive research practices. Methods/Study Population: An interdisciplinary Steering Committee, supported by Duke CTSI and DOCR, developed and implemented an engagement, recruitment, and retention certificate program (ER&R) for CRPs. With expert-led instruction, including e-learning, group sessions, and hands-on activities, ER&R integrates EDI into participant engagement practices. Participants complete 7 core courses and at least 3 elective courses, reflecting their unique responsibilities. Program evaluation uses the Kirkpatrick model to assess participant learning, competency, and EDI integration into clinical research. Since launch, the program has expanded to include clinical research trainees from Durham Technical Community College. All elements of the program were designed to allow for sharing across academic medical institutions. Results/Anticipated Results: A total of 202 CRPs and trainees have participated since launch (2020), including 17 trainee participants from Durham Technical Community College (2022–2024). Post-program evaluations showed significant growth in recruitment and retention self-efficacy. An early evaluation of the first 2 cohorts (n = 59) included a self-assessment across defined competencies showing marked increases in comfort across all learning objectives, with notable gains in: Community and Stakeholder Engagement, Recruitment on a Shoestring Budget, Community-Engaged Research Initiatives, and Social Marketing. Participants valued the program’s focus on EDI and sought more practical strategies and peer collaboration. 50 additional institutions have engaged with our implementation consultations and program repository. Discussion/Significance of Impact: Barriers to equitable ER&R exist at the individual, study, and system levels. Addressing these requires more intentional engagement practices. The ER&R certificate program is an innovative model for integrating equity principles with practical and required knowledge and skills training for participant-facing research professionals.

OBJECTIVES/GOALS: “Cure Quest” is an adventure quest game about the process of new drug discovery and development. The player explores a magical island in search of a cure for a mysterious illness, traveling through different lands based on the stages of the drug discovery pipeline. Along the way, they must solve puzzles, decipher clues, and enlist the help of a ‘team science’ group of collaborators. The game uses a fantastical setting and engaging story to communicate the topic through metaphorical representations, instilling a sense of wonderment in the learning process. Real-world science is embedded into fictionalized lands such as the Labyrinth of Target Identification, the Forest of Small Molecule Discovery, the Tree of Biostatistics, the Mountains of FDA Approval and the Desert of Funding. The project represents a novel application of game-based learning to a complex topic not typically addressed through games. The process of designing and developing the game itself uncovers strong parallels between the interdisciplinary game design process and the interdisciplinary team science process. The objective of the game is to communicate high-level concepts of the drug discovery and development process, starting with the principles of ethical research and the motivations behind medical discovery, through the development of a new drug and finally to FDA approval. The goal is to improve understanding of clinical translational science among the different disciplines involved, and to raise overall awareness of the drug discovery process. METHODS/STUDY POPULATION: The game is being developed through a collaboration between faculty and students at ISMMS and the Games and Simulation Arts and Science Program at Rensselaer Polytechnic Institute. The first target audience is 2nd-3rd year medical students, with the future goal of adapting the game to a broader population. The game design is informed by specific learning outcomes, input from players in the target population and an ongoing iterative design process. The game is designed for mobile devices (iOS and Android), with an emphasis on narrative, exploration, and puzzle solving. Future evaluation will be performed through a quasi-experimental design comparing standard lectures with the game on a drug discovery. RESULTS/ANTICIPATED RESULTS: The game is currently in development, but the project has yielded insight into the design process for serious games in medicine. We found that for a game of this type it is essential not just to have both designers and subject matter experts, but to enable cross-pollination of modes of thinking. Through multiple design iterations and focus groups, we found that a game design approach rooted in narrative and allegorical abstraction would have a better ability to engage the target audience than one focused only on realistic simulation. When complete, we anticipate that the game will improve understanding of the core concepts in drug discovery. CureQuest is designed as an episodic game, following the sequence of stages in the drug discovery and development process. In this version of the game, we demonstrate five of the initial episodes: The City of Discovery of Unmet Medical Need; The Labyrinth of Target Identification; the Aquarium of Transgenic Phenotype Expression; the Rival Researcher Gang Quiz Battle; and the Desert of Funding. DISCUSSION/SIGNIFICANCE OF IMPACT: If successful, the game-based learning approach can help fill key gaps in current formal medical and scientific training, as well as gaps in understanding among the general public. The design process serves as an informative model of evolving collaborative team science.

OBJECTIVES/GOALS: Partner with the entertainment industry to build trust in science and research, especially among high-disparity and underserved communities, through inclusion of research themes on popular television shows. METHODS/STUDY POPULATION: To date, our partnerships with TV writers have led to inclusion of clinical research storylines on 10 popular TV shows (e.g., Grey’s Anatomy with an audience of 7M). We are now conducting research on show popularity among diverse audiences, and interviewing medical and entertainment experts to understand health priorities and potential entry-points to deliver targeted outreach. We are also analyzing keywords in scripts to assess frequency and sentiment of medical topics in entertainment. Our team also consults with the TV community regarding storylines and public service announcements on health and innovations in medicine. RESULTS/ANTICIPATED RESULTS: We anticipate reporting insights into current and shifting narratives around future-of-medicine topics. Building on work that reached over 64M viewers, more frequent and accurate depictions will likely be related to positive changes in attitudes, behaviors, and trust regarding health and science. The overall goal is to foster attitudes among high-disparity and underserved populations that will increase service utilization and early screenings, foster trust in research and evolving medical technologies, and combat misinformation. DISCUSSION/SIGNIFICANCE: By working with television writers of shows proven to be popular among key audiences, this initiative has the potential to reach millions of viewers in their homes with important and timely information modeling healthy behavior, providing accurate facts, depicting cutting edge research, and emphasizing diversity in medical research.

Objectives/Goals: Recognizing a critical need for sustained education and community beyond formalized training periods at Columbia University’s NCATS-CTSA, we created the TRANSFORM (TRaining And Nurturing Scholars FOr Research that is Multidisciplinary) Evolution program to preserve the networks cultivated during the KL2 program. Methods/Study Population: We will provide an overview of the genesis, expansion, key components, and programming for the TRANSFORM Evolution program. The program is designed for current and alumni of the KL2 program and late junior faculty that receive our CTSA’s Irving Scholar Award. TRANSFORM Evolution is a faculty and alumni network offering a platform to support the next generation of clinical and translational researchers while fostering a lasting community of collaboration and educational activities throughout a scholar’s career lifespan. Results/Anticipated Results: Salient components include the opportunities for social interaction, such as social/happy hours and member led education/career development sessions pertaining to topics that support thriving in an academic career. The program operates with financial resources and the support of a program manager. Evolution adopts a holistic, long-term approach, focusing on the entire professional lifespan by encouraging the development of enduring opportunities for our alumni. The program is intentionally structured to meet the evolving needs of its participants, through the beginning to more established phases in their professional careers. This continuity underscores the program’s capacity to adapt and remain relevant, informing and supporting sustained career progression and scholarly productivity. Discussion/Significance of Impact: The program has been an instrumental adjuvant in facilitating the transition to each career stage. By cultivating a community rooted in a common foundation – the KL2 and Irving Scholars programs, the program has created a robust support system that is crucial for the career development of clinician-scientists.

OBJECTIVES/SPECIFIC AIMS: Among college students with binge-type eating disorders who are overweight (BMI >25), does use of an online, guided self-help program for EDs combined with healthy weight-loss (WL) methods lead to reductions in ED symptoms and weight loss compared to controls referred to standard in-person treatment (Student Health Services)? Aim 1: Develop online, guided self-help program for intervention of ED psychopathology and weight reduction. Aim 2: Implement online, guided self-help program for intervention of ED psychopathology and weight reduction. Aim 3: Follow-up to track remission of ED psychopathology and symptoms and WL maintenance. METHODS/STUDY POPULATION: Up to N=60 college students who meet the criteria (clinical or sub-clinical binge-type ED and have a BMI > 25) and elect to participate will complete a baseline survey to enroll in the study, then will be randomized into a condition. Students in the intervention group (n=30) will be offered 8 weeks of online, guided self-help intervention for ED and WL. Students in the control group (n=30) will receive an email message encouraging them to seek support from Student Health Services for their WL and eating behavior concerns, along with appropriate contact information. All participants will receive follow-up 9 weeks after completing initial baseline, and a final follow-up survey 6-months after completing their baseline. RESULTS/ANTICIPATED RESULTS: Analysis of intervention and control groups will compare average Eating Disorder Examination Questionnaire (EDEQ) scores and WL (change in BMI) at the end of the intervention (9 weeks) and at 6-month follow-up. Group comparisons will be assessed via two-way mixed model ANOVA. DISCUSSION/SIGNIFICANCE OF IMPACT: Online, guided self-help interventions have been used for WL, as well as for treatment of EDs separately, but no program exists to manage these conditions together. Thus, the use of online intervention for ED psychopathology and WL in individuals with clinical and sub-clinical EDs is the next step. The goal of this study is to implement a program to reduce weight and shape concerns, reduce disordered eating symptoms, such as bingeing, and compensatory behaviors associated with binge-type EDs, while also reducing weight for individuals with EDs and comorbid overweight/obesity. This project will pilot an online, guided self-help ED intervention that offers cognitive behavioral based tools to improve ED symptoms in college students, while also teaching the healthy methods of behavioral WL, for students with clinical/sub-clinical binge-type EDs with comorbid overweight/obesity in order to examine effectiveness of the program compared to referral to Student Health Services for ED and WL concerns. Furthermore, the use of an online, guided self-help intervention is more scalable and can circumvent many of the barriers to traditional in-person treatment.

ABSTRACT IMPACT: This study works to improve the quality of clinical and translational workforce development programs in order to enhance the training of researchers in the field. OBJECTIVES/GOALS: Evaluating the impact of Clinical and Translational Science Awards (CTSA) Programs is crucial. To this end, the value of competency-based metrics to assess the professional growth of CTSA awardees is unknown. A needs assessment was conducted to determine the present use and potential need for a competency-based self-assessment tool. METHODS/STUDY POPULATION: A mixed methods study was conducted using synchronous live interviews and asynchronous online surveys. Study authors contacted 102 CTSA administrators nationwide for live interviews according to I-Corps ******„¢Customer Discovery Guidelines. Interviews were recorded and transcribed through Innovation Within, an I-Corps „¢online platform and independently analyzed by two members of the study team. An online REDCap survey was also distributed to 63 CTSA hubs via an internal listserv. In an attempt to elicit responses similar to the I-Corps „¢Customer Discovery Guidelines, the survey asked questions related to the use of competency assessments and requested explanatory responses but did not explicitly ask respondents if they needed a competency-based self-assessment tool. RESULTS/ANTICIPATED RESULTS: Overall, 30 unique CTSA hubs participated. Interview requests and surveys had a response rate of 22% (22 out of 102) and 33% (21 out of 63), respectively. Of the interviewees, 32% (7 out of 22) reported existing use of a competency-based assessment tool, and 59% (13 out of 22), inclusive of those already using a tool, indicated a clear need for one. Of the survey respondents, 62% (13 out of 21) already use a CBST. Interviewees highlighted preferred features for a CBST: customization, soft skills assessment, and integration with local academic institutions. Communication and teamwork were highly valued soft skills, a finding reinforced by survey results in which 80% of respondents marked oral and written communication and teamwork as important skills for their professional workforce. DISCUSSION/SIGNIFICANCE OF FINDINGS: Among CTSA administrators involved with workforce development, there is notable interest in a competency-based self-assessment tool, particularly one that is customizable, soft skill-focused, and integrated with local educational systems.

OBJECTIVES/SPECIFIC AIMS: As multidisciplinary, interdisciplinary, and transdisciplinary research has become imperative to solving the complex problems of contemporary healthcare, teaching researchers how to create and maintain high-functioning and innovative teams has also become paramount. In Fall 2016, the Center for Improvement Science (CIS) core, in collaboration with the Translational Workforce Development (TWD) core, at the Cincinnati Center for Clinical & Translational Science & Training (CCTST) began offering training in Team Science in an effort to better prepare researchers for collaborative work. Since then, the CIS has expanded Team Science education into a multifaceted and adaptable curriculum that includes workshops, team consultations, Grand Rounds, grant writing assistance, grant review, train-the-trainer, and a graduate-level course. METHODS/STUDY POPULATION: Over almost 2 years, we have offered 9 unique workshops attended by individuals from the University of Cincinnati, UCHealth, and Cincinnati Children’s Hospital Medical Center. Recruitment was primarily accomplished via email invitations. Topics ranged from introductory team science issues such as Creating Teams, Team Effectiveness, and Team Leadership to more advanced team science areas such as Team Dysfunctions and Conflict Management. In addition, we have consulted with researchers on Team Science components of grant applications and served as grant reviewers for Team Science elements in a competitive, internal research funding program. We have developed tools and teaching strategies for faculty members tasked with teaching students about collaboration (train-the-trainer). And finally, we offered a graduate level course on Collaboration and Team Science. RESULTS/ANTICIPATED RESULTS: Over 250 participants attended our workshops and Grand Rounds, many at the faculty level, but we also had research staff and graduate students register. Content was very well-received, with workshop evaluations typically scoring in the high 4.5 and above range (on a 5-point scale, with 5 being the highest rating). The CIS team received (and accepted) at least 2 follow-up invitations from workshop participants to provide training to an additional team or group. We are tracking data on long-term effects of team science training and consultation, both in research productivity and team satisfaction/longevity. DISCUSSION/SIGNIFICANCE OF IMPACT: The goals of Team Science training at the Cincinnati CCTST are 2-fold: to provide practical knowledge, skills, and tools to enhance transdisciplinary collaboration and to promote systemic changes at UC, CCHMC, and UCHealth that support team science. After almost 2 years of training, team science is gaining traction among key leaders at our local institutions and a broader audience of researchers who see how collaborative practice can enhance their professions.

Objectives/Goals: Cultivating authentic partnerships between community members and scholars requires significant time and effort. Scholars often encounter situations with insufficient time to build a mutually beneficial partnership. Our matchmaking events provide a space for researchers to connect with community members and begin their partnership journey. Methods/Study Population: UW-Madison Institute for Clinical and Translational Research (ICTR) partnered with UW-Madison Wisconsin Network for Research Support (WINRS) to invite scholars in ICTR Workforce Development Programs to attend a community advisory board meeting, share about their research, and invite feedback from community members. Each event was scheduled for 90 minutes in the evening at an accessible location in the community. Scholars met with WINRS in advance to share their intent for the meeting and receive guidance on how to best prepare. Each event allowed for a maximum of 3 scholars to attend. During these events, scholars shared either an overview of their area of research or a specific research project and invited feedback and guidance from community members. Results/Anticipated Results: Feedback from community members is a critical component of community-engaged research. Scholars across career stages have participated in matchmaking events, including PhD students, postdoctoral trainees, and faculty members. During the event, community members acknowledge the importance of the scholar’s research and suggest areas of improvement. Some community members offer to connect a scholar with a community organization that would be invested in their work, providing an opportunity to start building an authentic relationship. Scholars have subsequently participated in Community Advisory Board meetings, bringing their team members with them to advance their knowledge and skillsets related to community engagement. Discussion/Significance of Impact: After completing trainings on community-engaged research, scholars are unsure how to start connecting with community, demonstrating the utility of Matchmaking events. These events provide an opportunity to connect with community members and begin developing relationships with community members and organizations as part of their career.

OBJECTIVES/SPECIFIC AIMS: The use of digital practices and approaches can potentially increase the quality and efficiency of all phases of the traditional clinical translational research (CTR) process. The purpose of this qualitative study was to describe key stakeholders’ perspectives on the need to: (A) formalize training in digital practices and approaches among CTR trainees; and (B) develop an aligned educational framework that defines core competencies, educational methods, and evaluation metrics. METHODS/STUDY POPULATION: Participants (n=66) were recruited via email from June to November 2017 using purposive and snowball sampling methods across 4 groups: (1) English speaking national and international experts from academic and private sector institutions with working experience in using digital practices and approaches in research (n=36), (2) CTR educators (n=8), (3) CTR trainees (n=13), and (4) Members of the Southern California Clinical and Translational Science Institute at the University of Southern California (n=9). Online focus groups were conducted using a semi-structured, open-ended interview guide through Google Hangouts and a conference call interface. Sessions were recorded and transcribed verbatim, and 2 research team members performed independent content analyses to identify before and emergent themes using an inductive analytic approach. Kappa was calculated for inter-rater agreement and repeated until agreement was at least 0.70. RESULTS/ANTICIPATED RESULTS: Participants’ average age (41.2 yrs, SD 9.26), gender (59% females), non-Hispanic (97%), race (72% White), and doctoral degree (67%). In total, 85% reported experience in teaching digital practices and approaches in research, although 70% were currently not teaching in this field. Participants reported that complementary teaching in digital practices and approaches across the 15 Clinical and Translational Science Award (CTSA) CTR competency areas was relevant, especially in literature review, research implementation, statistical approaches, biomedical informatics, regulatory support, responsible conduct of research, scientific communication, translational teamwork, cross-disciplinary training, leadership, and community engagement; and less so in literature critique, study design, sources of error, and cultural diversity. Additional competencies were identified, for example, online study recruitment, crowdfunding, team and project management, scholarly impact metrics (Altmetrics), ethical and regulatory guidance for conducting research using digital approaches. Five main educational practices were identified including online training sessions, flexible on-demand modules, in-person consultations and training, and project-oriented hands-on workshops. Among the identified challenges were the need for clear metrics in order to evaluate such a training program. DISCUSSION/SIGNIFICANCE OF IMPACT: There was consistent support for a structured program to help CTR trainees to develop competency in digital research practices and approaches. Our results indicate that an education program focused on digital practices and approaches should include a step-wise approach to meet different research and training goals, allowing attendees to increase their awareness and specialized hands-on practical experience.

OBJECTIVES/SPECIFIC AIMS: To identify areas of variation in primary care clinician responses to secure messaging and to assess the quality of secure messages by clinicians. METHODS/STUDY POPULATION: This mixed-methods study included twenty one primary care clinicians from a Midwestern safety net hospital and Veterans Affairs medical center. Participants were presented with five short clinical vignettes and corresponding secure messages from hypothetical patients and asked to compose responses. Participants were interviewed about their cognitive approach to the responses as well as perspectives on quality of care as related to electronic communications. RESULTS/ANTICIPATED RESULTS: Every participant recalled having patients who misused secure messaging for urgent issues, suggesting the need for more patient education and the possible adverse consequences of overlooked messages. The study also uncovered key differences in several areas, include clinician timeliness, message management, the circumstances in which they would use messaging, and the content of the messages (including patient-centeredness). While participants agreed that messages about clinical issues should not be resolved via secure messaging, there was a lack of consensus regarding emotionally charged messages and messages dealing with medication adjustments. Some participants spoke of the need for more guidance in knowing when best to use secure messaging. “Sometimes,” one physician said, “it feels like we’re just making up [rules for secure messaging].” Although clinician responses were uniformly respectful, the patient-centeredness varied in the use of jargon and social talk, as well as clarity for patients. DISCUSSION/SIGNIFICANCE OF IMPACT: This study revealed variations in provider approaches to secure messaging, and the content of responses. These variations reflect lack of consensus about how care is delivered via secure messaging, and reveal the need for clinician guidance. They also suggest possible negative patient consequences if secure messaging is used ineffectively. The extent to which variations are undesirable remains unknown. Future work will explore the consequences of such variations.

OBJECTIVES/GOALS: Despite advances in precision medicine and understanding of the molecular pathways, melanoma remains the deadliest skin cancer, warranting identification of novel biomarkers. In this study, we performed bioinformatic analysis of melanoma patient tumors to identify novel dysregulated gene and micro-RNA (miRNA) targets responsible for survival. METHODS/STUDY POPULATION: Genetic sequencing data for 594 patient samples of melanoma and normal skin tissue from 10 databases were accessed using the NCBI Gene Expression Omnibus. Genes and miRNA that were significantly dysregulated (adjusted p-value < 0.05, log fold change > ± 2) in melanoma compared to normal skin were identified using the GEO2R program. Dataset expression profiles were cross-referenced to identify genetic elements dysregulated in at least 50% of datasets and filtered for association with poor survival using R2 Genomics Analysis and Visualization Platform. DAVID 6.8 provided pathway analysis of dysregulated genes. miRTarBase linked genes associated with poor survival and dysregulated miRNA from our database analysis. RESULTS/ANTICIPATED RESULTS: Bioinformatic analysis revealed consistent differential regulation of 205 genes (down=177 and up=28) and 38 miRNA across datasets with fold change >2 (bonf. p<0.05). Pathway analysis indicated that PPAR, phosphatidylinositol signaling, Rap1 signaling, and p53 signaling pathways were enriched by downregulated genes while the NF-kB pathway was enriched up regulated genes. Survival analysis of the differentially regulated genes identified 11 downregulated (ACSL1, CEBPA, CES4A, CRIP1, GATA3, HLADQB2, PTGS1, PYCARD, PPARG, PKP3, RSSF6) and 3 upregulated (DUXAP10, SLC2A3 and PRAME) hub genes to be associated with poor overall survival. Out of the 13 miRNA associated with hub genes, five miRNA (hsa-miR-125b-5p, hsa-miR-130b-3p, hsa-miR-26n-5p, hsa-miR-30b, hsa-miR-30c) were linked to multiple hub genes. DISCUSSION/SIGNIFICANCE: Our analysis identified 14 hub genes (regulators of PPARA, adipocyte differentiation, and transcriptional pathways) as well as miRNAs hsa-miR-30c (regulator of PTGS1 and SLC2A3) and hsa-let-7i-5p (regulator of ASCL1) as potential therapeutic targets. Further studies for validation of the targets are needed for clinical translation in melanoma.

OBJECTIVES/GOALS: The CDC-funded Program to Alleviate National Disparities in Ethnic and Minority Immunizations in the Community intersects two national networks that transform building trust in communities: Cooperative Extension Systems and Clinical and Translational Science Awardees, with the goal of reducing vaccine hesitancy and increasing vaccine uptake. METHODS/STUDY POPULATION: PANDEMIC included North Central Florida; Greater Sacramento, California; Bronx, New York; St. Louis and the Ozarks, Missouri; rural Kentucky; and Minnesota. Our 10 Promising Practices (PPs) focus on the equitable distribution of COVID-19 vaccines and health information, with two detailing collaborative efforts to better achieve health equity: PP3) Bringing Services and Vaccines to People Where They Are & PP5) Creating Coalitions with Trusted Neighborhood Partners. CHWs and Extension Educators, trusted community members, work together to deliver culturally/linguistically diverse health messages in plain language in areas of high vaccine hesitancy and bring vaccines to people where they are. All outreach activities are tracked and categorized by PP affiliation. RESULTS/ANTICIPATED RESULTS: From November 2021 – August 2023, PANDEMIC has administered nearly 11,000 COVID-19 vaccines at over 2,500 outreach events. At events, Community Health Workers (CHWs) listen to community members to assess vaccine perceptions and health needs/concerns. We adapt messaging and outreach initiatives to promote vaccination through data analyses that help us understand perceptions. Responses are calculated for the populations of focus (PoF)–Latino/Hispanic, African American/Black, American Indian/Alaskan Native, Asian, Native Hawaiian/Other Pacific Islander) compared to others (Non-Latino/Hispanic White or unspecified race). Over 16,000 surveys were collected from November 2021 – August 2023 with 60% coming from the PoF. Key differences in perceptions will be shown along with other cross-site metrics. DISCUSSION/SIGNIFICANCE: PANDEMIC offers an innovative model for collaboration among CTSAs and Cooperative Extension Systems to better understand community perceptions and support vaccination efforts and overall health promotion in communities of greatest need, with a focus on racial and ethnic minority communities and underinsured/uninsured populations.

Objectives/Goals: The scientific workforce has seen a trending decrease in future clinicians pursuing research over the last several decades. This study assessed effectiveness of a mentored research program to increase research skills and future research interest among medical students. Methods/Study Population: The Medical Student Research Program (MSRP) at UCIis designed to provide research training to medical students beginning their first year of medical school until graduation. All students applying to enroll in the MSRP complete a baseline survey prior to program enrollment and an annual survey yearly afterward. Baseline surveys collected students’ self-rated confidence in research skills, along with their future intent to use research as a clinician and to pursue a future research career after medical school. Annual surveys tracked change over time in students’ research competencies and their future intent to use research. Results/Anticipated Results: Annual surveys (N=128) assessed the change from baseline to one year in research competencies and students’ intent to use research in clinical practice (mixed design ANOVA) and in their intent to conduct research in their career. Evaluations indicated improved medical student research skills, with a significant increase in student research competencies across time (F(1, 173) = 25.4, p<0.001) found for both non-enrolled (M=3.76) and enrolled (M=4.07) MSRP students, with MSRP students reporting higher mean research competencies at one year. Yet similar to national trends, there was a decrease in students’ intentions to use research in their clinical career at one year (F(1, 173) = 25.4, p<0.001). This trend was more pronounced in students no longer enrolled in MSRP (F(1, 173) = 4.7, p = 0.006). Discussion/Significance of Impact: Preliminary findings demonstrate enhanced student research competencies during the first year of the program. However, the decline in students’ intentions to use research in the future highlights a need for continued investigation into the factors driving this decline and solutions to prevent decline in the research workforce.

OBJECTIVES/SPECIFIC AIMS: Rheumatoid arthritis (RA) is one of the most prevalent systemic autoimmune diseases. It is caused by a combination of genetic and environmental factors. In humans, the intestinal microbe Prevotella copri strongly correlates with RA in previously untreated new-onset rheumatoid arthritis (NORA) patients. Metagenomic assembly of P. copri from NORA patients and healthy controls suggests genetic differences between P. copri from each group. In order to test the hypothesis that genetic differences in P. copri from arthritis patients promote arthritis, I am performing genomic comparison of primary P. copri isolates from NORA patients and healthy controls, and analysis of the immune response to P. copri in mice. Mice colonized with P. copri have increased susceptibility to DSS-induced weight loss and death compared with uncolonized controls. Future experiments will assess the local and systemic immune response in P. copri-colonized, DSS-treated mice. If this work is successful, then it may be possible to exploit genetic variation in P. copri. This could lead to new biomarkers for human disease or even insight into drug metabolism. METHODS/STUDY POPULATION: To validate a strategy to screen for the presence of P. copri in feces, qPCR primers were designed to amplify 8 regions across the 3.5 Mb P. copri reference genome using NCBI PrimerBlast. Primers were validated with DNA from feces for which P. copri abundance was previously determined by 16S rDNA sequencing. P. copri genome-specific primers were used to screen bacterial isolates from NORA patients and healthy controls. The 16S V3-V4 region was sequenced and compared with the P. copri reference 16S sequence to confirm >97% similarity. Genomes of 2 NORA patient isolates were sequenced on Illumina MiSeq, and sequences were compared with the reference genome. A strategy was developed to colonize mice with P. copri: 3-week-old C57BL/6 mice were treated with antibiotics in drinking water for 2 weeks, then switched to water for 2 days before oral gavage with P. copri; 6–7 days after inoculation, P. copri colonization was assessed by plating feces from inoculated mice, and by qPCR of fecal DNA with P. copri-specific primers. A systemic immune response to P. copri was assessed by microbe-specific ELISA for IgG and IgA in the sera of colonized mice. RESULTS/ANTICIPATED RESULTS: P. copri was detected in the stool of 20% of healthy individuals and 50% of NORA patients. P. copri was isolated form 4 healthy individuals and 6 NORA patients. Whole genomes of 96 primary isolates from NORA patients and healthy controls will be sequenced on the Illumina HiSeq platform, and their genomes will be assembled and compared using Spades software. For 2 P. copri isolates for a NORA patient, 89% of 250 bp reads aligned >95% to the P. copri reference genome. Mice can be colonized with P. copri gavaged at >106 CFU. P. copri-specific IgG and IgA were detected in the sera of colonized mice. DISCUSSION/SIGNIFICANCE OF IMPACT: Several primary isolates of P. copri have been collected from healthy controls and NORA patients, which will enable whole genome comparison of these isolates. For the 2 P. copri isolates sequenced, 89% of 250 bp reads aligned >95% to the P. copri reference genome, indicating variability between NORA patient P. copri strains and the P. copri reference genome. The establishment of colonization of mice with P. copri will allow further characterization of the immune response to P. copri at steady state and under pro-inflammatory conditions. Further, the systemic immune response to P. copri indicates that this microbe may have potential to play a role in systemic disease.