ABSTRACT IMPACT: This study informs how substance use treatment programs responded to the COVID-19 pandemic, and highlights implication for future translational research and practice. OBJECTIVES/GOALS: The COVID-19 pandemic rapidly changed how substance use disorder (SUD) treatment services are organized and provided. This study examined what changes SUD treatment programs in Arkansas implemented (e.g., guidelines, technologies), and what factors influenced their ability to implement and sustain these changes. METHODS/STUDY POPULATION: Between May and August 2020, we conducted semi-structured phone interviews with 29 leaders (administrative and/or clinical leaders) at 21 residential and outpatient SUD treatment programs throughout Arkansas (i.e., in all five Arkansas public health regions). Interviews were based on the Consolidated Framework for Implementation Research and focused on what changes programs were implementing in response to the COVID-19 pandemic, barriers and facilitators to implementation, and recommendations for future. The interviews were on average about 30 minutes long, and we provided no participant compensation. Interviews were recorded and transcribed verbatim, then thematically analyzed. RESULTS/ANTICIPATED RESULTS: Programs implemented similar infection control practices: screening at entry, masks, hand hygiene, and social distancing. Residential programs stopped outside visitations and some capped admissions; outpatient programs stopped group sessions and switched most services to telehealth. Key facilitators included grants/loans (e.g., salaries), looser regulatory restrictions (e.g., telehealth), and good coordination with other organizations (e.g., state agencies). Key barriers included limited access to supplies (e.g., masks), no rapid testing (particularly for residential care), limited capacity for social distancing, and negative employee and client responses (e.g., anxiety). Key recommendations include better access to supplies and testing, telehealth continuation and better communication. DISCUSSION/SIGNIFICANCE OF FINDINGS: This study provides an insight into how SUD programs responded to the COVID-19 pandemic and what the ‘new normal’ is. This can inform D&I studies conducted in SUD settings, including studies examining what implementation strategies can help sustain these changes, or studies of other practices implemented during or after the pandemic.

OBJECTIVES/SPECIFIC AIMS: To further elucidate the role of estrogen receptor β (ER-β) in the early endometriotic lesion attachment. METHODS/STUDY POPULATION: EECs were immortalized using a telomerase vector. Immortalized cells and parental cells were characterized by genotyping, and expression of ER-β as well as other epithelial cell markers. ER-β was knocked-down in immortalized EECs using lentivirus-mediated shRNA transduction. ER-β knockdown was confirmed by RT-qPCR and Western analysis. EEC cells with or without ER-β knockdown were used to assess their attachment to PMCs in an established in vitro assay (Lucidi, 2005). Results were analyzed with Student t-test. RESULTS/ANTICIPATED RESULTS: Genotyping using karyotype assay confirmed a normal chromosomal profile. Also positive staining for cytokeratin and lack of any staining with vimentin confirms the epithelial origin of these cells. ER-β knockdown has a significant decrease in attachment compared to control (p=0.02). DISCUSSION/SIGNIFICANCE OF IMPACT: Primary and immortalized cells were 46XX, cytokeratin positive, and vimentin negative confirming their epithelial origin. ER-β knockdown has a significant decrease in attachment compared with control.

OBJECTIVES/GOALS: (1) Determine nurse (age, education level, years of experience, ID education/training, contact with people with ID, communication apprehension, beliefs about patient quality of life), and nursing unit (teamwork, staffing and resources, person-centered care) characteristics that are associated with and predictive of nurses’ attitudes, positive emotions, and negative emotions toward caring for adults with ID. (2) Explore nurses’ perspectives of perceived barriers and facilitators to providing nursing care to hospitalized persons with ID and medical comorbidity, and how nursing care differs when caring for a person with ID. METHODS/STUDY POPULATION: This mixed methods nested analysis will employ an internet survey of medical-surgical registered nurses to collect nurses’ attitudes and emotions toward caring for hospitalized persons with ID and medical comorbidity, nurse characteristics, and nursing unit characteristics. We intend to recruit 150 medical surgical nurses currently practicing in the United States via email invitation to the membership of the Academy of Medical Surgical Nurses. Purposeful maximum variation sampling will be used to invite a subset of respondents for qualitative, semi-structured telephone interviews to elicit barriers and facilitators to nursing care of persons with ID and how nursing care differs when caring for persons with ID. RESULTS/ANTICIPATED RESULTS: We hypothesize that lower nurse education level, fewer years of experience, less ID education/training, lower amount of contact with people with ID, increased communication apprehension, and lower beliefs about the quality of life of persons with ID will be associated with negative nurse attitudes and emotions toward caring for people with ID. Further, we hypothesize that lower levels of nursing unit teamwork, staffing and resources, and person-centered care practices will be associated with negative nurse attitudes and emotions toward caring for people with ID. DISCUSSION/SIGNIFICANCE OF IMPACT: The proposed research is an important first step in determining potential nurse and nursing unit factors influencing nurses’ attitudes toward caring for people with ID. It will lead to targeted interventions to enhance nursing care quality and reduce hospital-associated healthcare disparities among people hospitalized with intellectual disabilities and medical comorbidities.

OBJECTIVES/GOALS: This study examines health provider andcaregiver influences on adolescent dual prevention strategies, or the use of condoms and another form of contraception, to informa clinically focused triadic intervention, involving caregivers, adolescents aged 15-17, and health providers. METHODS/STUDY POPULATION: Data for the 2021 Teen and Parent Surveywere two online, cross-sectional surveys, a national sample of adolescents aged 15-19, and a survey of caregivers of 15–17-year-old adolescents. Data were matched to create a dyadic dataset (n=273). Drawing from the Actor-Partner-Dependance Model we will conduct a secondary retrospective analysis, specifically cross-sectional univariate, bivariate, and multivariate logistic regression analyses on sets of influences around contraception and sexual health: communication with parents and health providers, information delivery of sexual health, condom attitudes and self-efficacy around preventative behaviors. RESULTS/ANTICIPATED RESULTS: In preliminary unadjusted analyses, 91% of the sample were cis-gender females (n=249), of which 32% (n=87) had sexual contact with someone who could get them pregnant. In the past, 35% (n=86) discussed birth control pills and 9% (n=24) discussed long-acting contraception with a health provider. In the last health visit, 29% (n=72) discussed STI prevention. Caregivers discussed sexual decision-making (49%, n=144), how to prevent pregnancy (62%, n=169), and how to prevent STIs (55%, 151) at least once in the past year. At last sex (n=49) most used condoms (47%, n=23), followed by birth control pills (33%, n=16), and withdrawal (14%, n=7). Additional predictors and adjusted analyses will be further examined. DISCUSSION/SIGNIFICANCE: Dual prevention strategies can be influenced by caregivers and health providers, but they are contingent on communication. Triadic interventions may consider involving both caregiver and health provider communication around sexual health prevention.

OBJECTIVES/GOALS: The objective of my study is to test my overall hypothesis that CDK4/6 inhibitor-induced cellular senescence has long-lasting consequences on the tumor microenvironment that affect tumor growth and disease progression. METHODS/STUDY POPULATION: There is a lack of mechanistic understanding of the crosstalk of drug effects on different cellular pathways. One less-studied consequence of CDK4/6 inhibitors (CDKI) is their ability to induce cellular senescence in the non-malignant host cells (“stroma”), which causes secretion of a plethora of proteins that have lasting effects on the tumor microenvironment. Stromal cells are known to be able to enter senescence and promote a state of chronic inflammation that contributes to disease progression. I propose to study the stromal contribution to the tumor microenvironment and how this affects tumor growth and disease progression by using genetically engineered mouse models of breast cancer. RESULTS/ANTICIPATED RESULTS: We have found that palbociclib, a CDKI, inhibited growth and induced senescence of breast cancer cell lines xenografted into mice, and that while most on-target effects of palbociclib were reversed after treatment cessation, there was long-lasting down-regulation of interferon-γ and inflammatory response signaling pathways in the mouse host stroma that persisted after cessation of palbociclib treatment. In syngeneic models, we have found that palbociclib treatment influenced migration of T cells into CDKI-resistant tumors. DISCUSSION/SIGNIFICANCE: These studies will shed light on how senescence-inducing anticancer therapies, such as CDKI, affect tumor growth and disease progression. My studies will help elucidate new therapeutic avenues in combination with CDKI to combat therapeutic resistance in advanced breast cancer.

Objectives/Goals: In Fall 2024, we designed a collaborative scholar retreat model to create dialogue among our training programs. The purpose of the retreat was to foster collaboration and provide unique networking opportunity for our KL2, T32, and TL1 scholars to share their research across the translational spectrum and learn more about Clinical and Translational Science Institute (CTSI) resources and tools. Methods/Study Population: The CTSI Fall Scholar Retreat brought together a diverse group of 25 scholars who attended in-person a full-day program. The program included presentations on CTSI resources and Team Science on How to Become a Better Team Member in cross-disciplinary and cross-functional groups. The KL2 Scholars presented motivational talks on their career and professional development journeys. Mentoring roundtable included discussions on subthemes like characteristics of a good mentor/mentee, organizing your mentoring team, different mentor roles, and fears of approaching new mentor/mentee. TL1 and T32 scholars also presented posters describing their ongoing research project from the planning stages to initial observations to completed studies. Results/Anticipated Results: To measure the effectiveness and impact of the CTSI Fall Scholar Retreat, we conducted an evaluation using REDCap survey and received an 88% response rate. On the Likert scale of 1–5 (1 = not at all valuable, 2 = not very valuable, 3 = neutral, 4 = very valuable, and 5 = extremely valuable), 92% of the scholars found the sessions to be valuable. Net Promoter Score of 9.6 (scale of 1–10) was measured to collect the scholar feedback and most of them are likely to recommend the Scholar Retreat to other scholars. Discussion/Significance of Impact: The in-person retreat proved to be a unique platform to interact, collaborate, learn, and grow for all scholars at different levels of their career and research. Inclusion of HRSA-funded T32 post-doctoral program provided cross-level collaboration and helped promote a culture of continuous learning in clinical and translational science.

OBJECTIVES/SPECIFIC AIMS: Science and clinical practice are widely regarded as being complementary and synergistic. In an effort to enhance the team science, translational research capacity of the TL1 scholars at Icahn School of Medicine at Mount Sinai (ISMMS), the InCHOIR learning lab aims to provide an accessible, workforce-wide lecture series on the fundamental methods and concepts of randomized clinical trials. METHODS/STUDY POPULATION: The InCHOIR learning lab is a monthly 1 hour lecture series delivered by a range of expert clinical and translational researchers, followed by a 1 hour “Meet the Expert” session. The InCHOIR lecture series has covered a wide range of topics including, but not limited to: Decision Models; Race and Causal Inference; Innovative Strategies for Assessing Environmental Health across the Life Course; Statistics for Geneticists and Genetics for Statisticians; and From the Lab to Translation to Policy—The Neuroscience of Addiction. The “Meet the Expert” session offers TL1 predoctoral and postdoctoral scholars and KL2 scholars the opportunity to have intimate, informal discussions with experts about their career trajectories. RESULTS/ANTICIPATED RESULTS: Feedback from participants has been overwhelmingly positive. Participants have gained important insights into key topics relevant to early stage researchers. The “Meet the Expert” sessions have yielded honest and important conversations about crucial topics ranging from finding effective mentors to essential strategies for establishing a work-life balance, to overcoming adversity as underrepresented minorities and women in translational research. DISCUSSION/SIGNIFICANCE OF IMPACT: Attendance at the InCHOIR learning lab is increasing month on month, indicating the perceived need for this learning not just from early stage researchers, but also from students, senior faculty, and research staff more generally. The InChoir series provides added value through the creation of a video library, fostering new collaborations and contributing to the Icahn School of Medicine at Mount Sinai and Graduate Medical Education landscape. Priorities for the program are to increase internal visibility, in order to continue to grow attendance by MSHS students, research staff, nurses, postdoctoral fellows and residents. The program is also exploring how to engage external participation from regional CTSAs and from community advocates actively involved in community-academic research partnerships.

OBJECTIVES/GOALS: The purpose of this mixed methods project was to gain a comprehensive understanding and generate data on factors, including stress and inflammatory biomarkers, that may negatively impact glycemic levels in children aged 8-12 years with type 1 diabetes (T1D) from underrepresented backgrounds. METHODS/STUDY POPULATION: This study employed a two-phase sequential QUAN -> qual mixed methods design. Children and their parents were recruited from a pediatric endocrinology clinic in the southeastern United States. In phase 1 (n=34), we used quantitative methods to measure perceived stress, diabetes distress, cortisol, inflammation (IL-1b, IL-2; IL-6; IL-8; TNF-a; CRP), and glycemic level (HbA1c). Both children and their parent/guardian completed surveys, and children provided salivary and blood samples to measure cortisol and inflammatory markers. Phase 2 qualitative interviews in a subset (n=20) of children and parent/guardians from phase 1 are ongoing; preliminary findings will be included in the presentation. RESULTS/ANTICIPATED RESULTS: Mean age of children was 10.47 (sd=1.44), 67.6% were male, and 41.2% were black. HbA1c ranged from 6.8%-15% and only 2 (5.8%) children met ADA recommendations for HbA1c of 7% or less. HbA1c was associated with child reports of perceived stress (r = .403, p < .05), but not parent reports of child perceived stress (r = -.011, p > .05). Parent reports of perceived stress and diabetes distress in children were not significantly associated with child self-report of perceived stress (r = .11, p > .05) or diabetes distress (r = .018, p > .05). Exploratory models with PROCESS suggest that cortisol slope and IL-8 moderate the relationship between child’s perceived stress and glycemic control. DISCUSSION/SIGNIFICANCE: Stressors are emerging that are unique to this population and may help highlight disparities in care. While the study is ongoing, findings may help health professionals identify and mitigate stressors in children with T1D to help maintain optimal glycemic levels.

OBJECTIVES/SPECIFIC AIMS: Macrolides, linezolid, imipenem-cilastatin, fluoroquinolones, penicillin combinations, and ceftriaxone are known to be associated with Torsade de pointes/QT prolongation (TdP/QTP). Other antibiotics may also lead to TdP/QTP, but no study has systemically compared TdP/QTP risks of different antibiotics using recent data. Therefore, the objective of this study was to evaluate the association between TdP/QTP and antibiotics in recent years using the FDA Adverse Event Report System (FAERS). METHODS/STUDY POPULATION: FAERS reports from January 1, 2015 to December 31, 2017 were analyzed. The Medical Dictionary for Regulatory Activities (MedDRA) was used to identify TdP/QTP cases. We calculated the Reporting Odds Ratios (RORs) and corresponding 95% confidence intervals (95%CI) for the association between antibiotics and TdP/QTP. An association was considered to be statistically significant when the lower limit of the 95%CI was greater than 1. RESULTS/ANTICIPATED RESULTS: A total of 2,042,801 reports (including 5,221 TdP/QTP reports) were considered, after inclusion criteria were applied. Macrolides had the greatest proportion of TdP/QTP reports, representing 2.9% of all macrolide reports. TdP/QTP RORs (95%CI) for the antibiotics were (in descending order): macrolides 11.73 (9.74-14.12), linezolid 9.39 (6.45-13.68), amikacin 8.94 (4.22-18.92), imipenem-cilastatin 5.01 (2.38-10.56), fluoroquinolones 4.67 (3.96-5.52), penicillin combinations 3.52 (2.56-4.86), cephalosporins 1.90 (1.14-3.16), metronidazole 1.49 (0.74-2.99), vancomycin 1.26 (0.70-2.28), clindamycin 0.83 (0.27-2.58), trimethoprim-sulfamethoxazole 0.82 (0.31-2.18), and amoxicillin 0.57 (0.18-1.78). DISCUSSION/SIGNIFICANCE OF IMPACT: This study confirms prior evidence for TdP-QTP risks with macrolides, linezolid, imipenem-cilastatin, fluoroquinolones, penicillin combinations, and cephalosporins. This study provides new evidence for TdP-QTP risks with amikacin. Macrolides had the highest TdP/QTP ROR among the antibiotics evaluated in this study.

OBJECTIVES/GOALS: The University of Rochester CTSI Research Education Hub is designed to: 1) connect the local research community with essential internal and external educational resources; 2) create a community of inquiry and collaboration across the translational science workforce pipeline within the university. METHODS/STUDY POPULATION: The Research Education Hub (RE-Hub) utilizes the university’s widely used Learning Management System (LMS), Blackboard, and accessible to anyone at the university with a BlackBoard account. The RE-Hub greets users with an overview, an introduction of key local faculty experts in relevant research methodologies, and links to institutional research programs and helpdesks. Users are provided with curated educational resources organized by topic areas including, but not limited to, research methodology, statistical analysis, and grantsmanship. Discussion boards were created for users to ask general research questions and to connect with others in the translational research community. RESULTS/ANTICIPATED RESULTS: The RE-Hub was designed in Fall 2019 with the purpose of increasing utilization of university resources, including workshops, seminars, methods forums and consultation resources to improve translational science at the university. The RE-Hub was designed to be flexible and responsive to the changing needs of the local research community. User feedback will be used to identify improvements in the organization and content of the RE-Hub. Future improvements will include additional topic areas that span translational competencies, additional materials added to existing topic areas, and facilitation of better collaboration and integration of career development programs and grantsmanship resources. DISCUSSION/SIGNIFICANCE OF IMPACT: The Research Education Hub provides the University of Rochester translational science research community with a space to explore educational resources, to interact with colleagues and ask research related questions, and to help develop and/or improve other educational programs at the university.

OBJECTIVES/SPECIFIC AIMS: A growing concern about the declining physician-scientist workforce prompted the 2014 National Institutes of Health (NIH) Physician Scientist Workforce to recommended that “tools for assessing the strength of the biomedical workforce” be developed. To aid strategic planning, the Oregon Clinical and Translational Research Institute convened key stakeholders at its home university, Oregon Health and Science University (OHSU), to survey the local landscape of physician scientists. Surprisingly, few consensus methods were available to measure and benchmark OHSU with respect to national comparators. To address this deficit, we sought to develop clear and objective metrics describing physician-scientist success at our institution. By focusing on local funding, we were able to generate more complete and robust data than others have reported. These data also permit us to compare ourselves to the national workforce, using well-curated and accessible national databases. The goal of the analyses is to contribute to strategic decision-making by portraying the local physician-scientist workforce, comparing it to the national landscape, and making recommendations about mechanisms to address potential opportunities. This has led us to develop a simple quantitative dashboard, which now permits OHSU to craft strategic targets and address successes and opportunities. These approaches are likely to be valuable elsewhere. METHODS/STUDY POPULATION: OHSU is a medium-sized academic health center in Portland, Oregon with over 1200 principal investigators and over $230M in NIH funding. The primary focus of our investigation was physician-scientists who receive extramural funding. To align with other analyses, we distinguish physician-scientists with an M.D. only, or with an M.D. and a master’s degree, from physician-scientists who hold an M.D./Ph.D. For this distinction, we use the indicator “M.D.-only” to indicate the former. The study design consisted of (a) selection of available and relevant national level data on the physician-scientist workforce, (b) curating of local level data to align it with the national indicators, (c) comparing the 2 sets of data to look for differences in trends over time, and (d) supplementing the analyses with additional local data not available at the national level. Key comparisons were tested for statistical significance and plotted on a dashboard, which was then reviewed by an OHSU internal working group focused on physician-scientists. Data elements included degrees, age, gender, and grants awarded. National data come directly from the NIH Data Book, updated for fiscal year 2016. The NIH makes all funded project data available in the publicly downloadable ExPORTER Data Catalog. These project data were used to supplement the summarized data available from the NIH Data Book, allowing us to extract OHSU investigators and to complete the K to R comparative analysis. For analyses of OHSU investigators holding funding other than RPGs, we relied on institutional data from the OHSU grants and contracts office. Demographic data on OHSU investigators were obtained from departmental and human resource records. The time period for these analyses was 1998–2016. RESULTS/ANTICIPATED RESULTS: At OHSU, as nationally, there has been an increase in RPG-holding Ph.D.s but not in RPG-holding physician-scientists. At OHSU, nearly three-fourth of physician-scientist RPGs hold an M.D.-only degree, compared with nationally, where nearly half of physician-scientists are M.D./Ph.D.s. The percent of younger, early-career, RPG-holding physician-scientists has declined precipitously at OHSU and nationally. At OHSU, the percentage of RPGs held by women physician-scientists is below the national figure. Funding sources for physician-scientists at OHSU were more diverse than for Ph.D. scientists, and physician-scientists comprise the majority of Principal Investigators on clinical trials. These non-RPG sources of funding remain a critical source of support, although local analyses of time spent on research indicate that physician-scientists with NIH funding spend a greater percentage of their time on research than those without. OHSU PI’s have had success in transitioning from K08 and K23 grants to R-level grants, with similar percentages receiving RPGs within 5 years. A dashboard comparing these trends was developed. DISCUSSION/SIGNIFICANCE OF IMPACT: There were 3 key impacts from our analyses. First, we developed and disseminated a dashboard with both local data and national comparators. Second, in consultation with institutional leadership, we selected target values to define success for each metric. Third, we recommended actions that will help OHSU meet the selected targets. A major accomplishment of this structured approach has been the identification of opportunities for change that were not recognized previously. For example, leadership was not aware of the substantial and growing deficit in female physician-scientists at OHSU, compared with the impressive increases nationally. Thus, to reduce gender disparity at OHSU, we have recommended purposeful recruitment; one approach is to target female graduates of Medical Scientist Training Programs for faculty positions, as this group has better success at achieving R-level funding than do M.D.-only applicants. Another outcome is to help set ambitious but reasonable targets for improving the local landscape. Thus, we aim to reduce the average age of RGP-holding physician-scientists at OHSU by one year during the next 5 years. Although reversing current trends will not be easy, our analyses suggest that the average age of RPG level physician-scientists at OHSU would decrease were OHSU were to match the national-level proportions of women and M.D./Ph.D. physician-scientists. In addition to targeting gender disparities, we have recently implemented a program that supplements funding for recruiting young physician scientists, and then supporting their pursuit of RPG funding. Locally, a bright spot is the K to RPG transition rate for K23 awardees, which compare favorably with national data, an outcome that we plan to maintain. In analyzing this area of success, one reason is our strong mentorship program, called OCTRI Scholars, which is provided through our CTSA-sponsored institute. This has fostered an atmosphere of success among young physician-scientists and is one of the reasons that we endorse recommendation #9 from the PSWR, suggesting that Clinical and Translational Science Award (CTSA) Institutes play pivotal roles in monitoring and enhancing the success of the physician-scientist workforce. Thus, several perceived deficiencies might be addressed with adjustment of 1 or 2 specific institutional policies. While the specific opportunities and strengths may be different at other institutions, our proposed dashboard, which couples publicly curated, freely accessible databases, with readily available institutional resources, should help institutions to set and achieve their own goals.

OBJECTIVES/GOALS: Medications to treat opioid use disorder (mOUD) are available and can save lives, but are underutilized. We hypothesize that the rate of prescribing varies by treatment facility and these differences will shed light on barriers and facilitators to mOUD utilization. METHODS/STUDY POPULATION: We performed an exploratory analysis in MD Clone, a platform which generates non-identifiable synthesized data based on real patient data in the electronic health record (EHR) of St. Louis based hospitals. Our query included adults aged 18-70 with an OUD diagnosis using ICD-9 of -10 codes (opioid abuse, opioid dependence, opioid poisoning, opioid withdrawal) occurring between 2013 and 2022 along with prescriptions for buprenorphine, methadone, or naloxone within 7 days of the condition being entered in the record. We compared the rate of medication prescription within 7 days across settings and facilities where the patients were seen. We propose to replicate this analysis in actual patient records from the EHR following IRB approval. RESULTS/ANTICIPATED RESULTS: Our synthetic data comprised 24600 patient diagnoses. After filtering for patients seen in the ER or inpatient 16235 patients remained in the data set. Of these, 4376 fell into one of the categories that clearly warrant treatment with medication. Out of 4376 patients with a qualifying OUD related condition, only 815 (18.6%) received a prescription for any of the medications. Rates of prescribing within facilities varied between 67.2% of eligible patients receiving a prescription at a rural location to 0% at some urban centers. We anticipate similar findings from analysis of patient records obtained from the EHR. We will extend our analysis to explore factors which may be driving the wide difference in prescribing to better understand barriers and facilitators to mOUD utilization. DISCUSSION/SIGNIFICANCE: We identify under-utilization with differences across facilities in prescribing mOUD based on preliminary work in synthetic data. If true, this represents a gap in care and opportunity for intervention. By replicating the MD Clone results in patient data from the EHR we will confirm this finding and increase acceptability to clinicians.

OBJECTIVES/SPECIFIC AIMS: Aim 1: To compare microbiome diversity among patients who develop BSI post hematopoietic stem cell transplantation (HSCT) and patients without BSI. Aim 2: To compare microbiome diversity among patients who develop moderate to severe acute GVHD post HSCT and patients without GVHD. Aim 3: To describe alterations in specific bacterial orders (Enterobacteriaceae, Clostridia, and Lactobacillales) in pediatric patients undergoing HSCT. METHODS/STUDY POPULATION: Next-generation sequencing of the hypervariable V3 region of the 16s rRNA gene isolated from stool specimens collected at baseline (start of preparative regimen to transplant day), early (day 7–14 post HSCT), and late (day 21–28 post HSCT) from 46 children was performed. Microbiome diversity was assessed by the Shannon index as well as UniFrac analysis, and compared among patients with and without GVHD/BSI. Baseline bacterial diversity was compared among patients by primary diagnosis, race, timing of antibiotic introduction and method of supplemental nutrition. RESULTS/ANTICIPATED RESULTS: Median age was 9 years (range 0.5–19.2 years). There were 36 patients with hematologic malignancies. Patients with nonmalignant disease had a characteristic pattern of microbiome diversity (and microbiota order distribution) at baseline that persisted throughout the first month of transplant (p=0.004). Over all patients, there was an early and persistent drop in microbiome diversity throughout the transplant course. Early introduction of broad spectrum antibiotics (prior to transplant day) negatively impacted microbiome diversity (p=0.02). There was no difference in microbiome diversity among patients who developed BSI, when compared with patients without BSI. Similarly, we did not find an association between microbiome diversity and the development of moderate to severe acute GVHD. Ongoing analysis is examining the individual variations in microbiome at the species level, and their relation to transplant characteristics and clinical outcomes. DISCUSSION/SIGNIFICANCE OF IMPACT: In our analysis, microbiome diversity decreased during HSCT, but in contrast to published data, mainly in adult HSCT populations, we found no association between gut microbiome diversity and GVHD or BSI. There are ongoing clinical trials in children and adults using probiotics in HSCT with the aim of decreasing GVHD. Further analysis of our data at the species level may further inform the relationship between gut microbiome alterations and HSCT complications in children and guide clinical interventions.

OBJECTIVES/GOALS: Rare mutations in CHCHD10 gene are found in 1% of patients with familial Amyotrophic lateral sclerosis (ALS). The overall goal of this study is to utilize induced pluripotent stem cells (iPSCs) as an in vitro model organism for rare ALS variants to evaluate the mechanism of transcription adaptation of CHCHD10/2 as a potential therapeutic. METHODS/STUDY POPULATION: Point mutations on normal iPSCs was performed via Donorguide CRISPR/Cas9. The single stranded RNA/DNA donors contain genetic alterations of CHCHD10: Pro12Ser, Arg15Leu, Pro23Leu, Pro34Ser, Ser59Leu, Gly66Val, Pro80Leu, Tyr92Cys and Gln102His. Ribonucleoprotein electroporation was used to transfect iPSCs and DNA sequencing was used to validate gene editing. To validate transcriptional adaption, changes in levels of protein and gene expression were measured via immunoblot and quantification of CHCHD10 and CHCHCD2 was performed from whole cells lysates of the edited iPSCs. RESULTS/ANTICIPATED RESULTS: We anticipate that CHCHD2 transcriptional adaptation can functionally compensate for the locus loss of function of CHCHD10. This mechanism of transcriptional adaptation may contribute to an explanation for variation in clinical manifestations of patient phenotypes. DISCUSSION/SIGNIFICANCE: This study supplies further evidence for genetic modification as a treatment option for diseases with point mutation causal or enabling mechanisms, including some variants of ALS. Future work will explore the gene-correction from an ALS patient with a known CHCHD10-R15L variant.

Objectives/Goals: The University of Minnesota (UMN) CTSI and Medical School sought to increase the diversity of translational research-intensive faculty by recruiting highly promising new-to-UMN tenure track faculty in the Medical School. Increased resources and career development will increase recruitment and address barriers to their promotion and success. Methods/Study Population: In 2019, the Medical School Dean committed to fund 15 Early Career Research Awards (ECRA) Scholars to recruit outstanding new-to-UMN, tenure track faculty. Supplementing usual departmental recruitment packages, ECRA Scholars receive: 75% salary and fringe benefit support for 3 years; an additional $500,000 of research funds; and augmented mentoring and coaching with required participation in the relevant CTSI career development program. Department Chairs propose meritorious candidates for Review Committee consideration based on the Chair nomination letter, scientific plan, mentoring plan, CV, and additional letters of recommendation. To foster community building, there is an annual mini-retreat for the ECRA Scholars and other underrepresented CTSI Scholars with an external visiting professor. Results/Anticipated Results: Fifteen tenure-track faculty have been recruited as ECRA Scholars since 2019 into 9 different departments. One additional Scholar has been accepted and three have completed the program. Three ECRA Scholars were K awardees at the time of recruitment. The CTSI career development programs utilized were the K Accelerator (10), KL2 Scholar (2), and K-R01 (5) Programs, with 3 involved in two programs. The Scholar degrees include 10 PhDs, 3 MD/PhDs, and 2 MDs, with additional MPH/MS (5), MSW (1), and DPT (1) degrees. ECRA Scholars have been awarded multiple NIH R21, Foundation, and internal grants currently under review include Ks and R01s with 5 additional K, 2 new R01, and 1 revised R01 submissions planned for the 2024–2025 academic year. Discussion/Significance of Impact: The ECRA program has successfully augmented recruitment of outstanding underrepresented research-oriented early-stage faculty to the University of Minnesota School of Medicine, contributing to many Departments. The CTSI has provided career development, networking, and a broader community of Scholars, with increased diversity in CTSI programs.

ABSTRACT IMPACT: This research will improve human health by increasing screening for hepatitis C virus, thereby decreasing morbidity and mortality from hepatitis C-related disease. OBJECTIVES/GOALS: The worldwide incidence of liver cancer increased 75% from 1990 to 2015 due, in part, to chronic hepatitis C virus (HCV) infection. Individuals born 1945-1965 (baby boomers) have five times the prevalence of HCV infection compared to other birth cohorts, but fewer than 15% of this cohort have ever been screened. METHODS/STUDY POPULATION: Effective interventions to increase HCV screening among baby boomers are urgently needed. In partnership with a provider advisory board and a community advisory board, we will develop a multilevel intervention designed to increase HCV screening that will be delivered to both providers and patients in primary care. We will assess whether the intervention is feasible, acceptable, and usable from the perspectives of the target audiences (providers and patients) by conducting Concurrent Think Aloud (CTA) interviews with eight patients and eight providers. RESULTS/ANTICIPATED RESULTS: While the specific content of both intervention components will not be finalized until the completion of the study, we envision that the provider-level intervention will likely include a one-time educational session and monthly performance feedback provided via e-mail reporting each provider’s HCV screening rates. The patient-level intervention may include mailed reminder letters prior to a scheduled clinic visit informing them that HCV screening is recommended and a tablet-based in-clinic computer program to educate, engage, and activate patients to be screened. DISCUSSION/SIGNIFICANCE OF FINDINGS: The goals of this project are to: 1) develop an acceptable, feasible, and usable multilevel intervention aimed at increasing HCV screening in primary care; and 2) understand the relationship between the intervention components and HCV screening; and 3) reduce HCV-related morbidity and mortality.

OBJECTIVES/GOALS: #NAME? METHODS/STUDY POPULATION: Cell culture & protein identification: human T cells were purified from healthy blood, then activated & cultured for 5d. CAR-T cells were collected from infusion bags of cancer patients undergoing CAR-T. Silver staining of naive & activated healthy T-cell lysates was compared; B-II spectrin was upregulated and confirmed by Western blot. Migration assays: naive & activated T-cells were imaged during migration on ICAM-1 and ICAM-1 + CXCL12 coated plates. T-cells were transfected with BII-spectrin cDNA & the chemokine dependence of migration was compared with controls. In-vivo studies: in a melanoma mouse model, BII-spectrin transfected or control T-cells were injected; tumors were followed with serial imaging. Human patient records were examined to correlate endogenous BII-spectrin levels and CAR-T response. RESULTS/ANTICIPATED RESULTS: Activated T-cells downregulate the cytoskeletal protein B-II spectrin compared to naive cells, leading to chemokine-independent migration in in vitro assays and off-target trafficking when CAR-T cells are given in vivo. Restoration of B-II spectrin levels via transfection restores chemokine-dependence of activated T-cells. In a mouse melanoma model, control mice injected with standard activated T-cells showed fewer cells in the tumor site and more cells in the off-target organs (spleen, lungs) when compared to mice injected with B-II spectrin transfected cells. Furthermore, among 3 human patients undergoing CAR-T therapy, those with higher endogenous B-II spectrin levels experienced fewer side-effects, measured by the neurotoxicity and cytokine release syndrome grades. DISCUSSION/SIGNIFICANCE: A major hurdle to widespread CAR-T therapy for cancer is significant, often fatal side-effects. Our work shows that the protein B-II spectrin is downregulated during CAR-T production, and that restoring B-II spectrin levels decreases side-effects while increasing tumor clearance--hopefully translating to better CAR-T regimens for the future.

OBJECTIVES/SPECIFIC AIMS: The objective of this research was to assess the clinical impact of simulation-based team leadership training on team leadership effectiveness and patient care during actual trauma resuscitations. This translational work addresses an important gap in simulation research and medical education research. METHODS/STUDY POPULATION: Eligible trauma team leaders were randomized to the intervention (4-hour simulation-based leadership training) or control (standard training) condition. Subject-led actual trauma patient resuscitations were video recorded and coded for leadership behaviors (primary outcome) and patient care (secondary outcome) using novel leadership and trauma patient care metrics. Patient outcomes for trauma resuscitations were obtained through the Harborview Medical Center Trauma Registry and analyzed descriptively. A one-way ANCOVA analysis was conducted to test the effectiveness of our training intervention versus a control group for each outcome (leadership effectiveness and patient care) while accounting for pre-training performance, injury severity score, postgraduate training year, and days since training occurred. Association between leadership effectiveness and patient care was evaluated using random coefficient modeling. RESULTS/ANTICIPATED RESULTS: Sixty team leaders, 30 in each condition, completed the study. There was a significant difference in post-training leadership effectiveness [F(1,54)=30.19, p<.001, η2=.36] between the experimental and control conditions. There was no direct impact of training on patient care [F(1,54)=1.0, p=0.33, η2=.02]; however, leadership effectiveness mediated an indirect effect of training on patient care. Across all trauma resuscitations team leader effectiveness correlated with patient care (p<0.05) as predicted by team leadership conceptual models. DISCUSSION/SIGNIFICANCE OF IMPACT: This work represents a critical step in advancing translational simulation-based research (TSR). While there are several examples of high quality translational research programs, they primarily focus on procedural tasks and do not evaluate highly complex skills such as leadership. Complex skills present significant measurement challenges because individuals and processes are interrelated, with multiple components and emergent nature of tasks and related behaviors. We provide evidence that simulation-based training of a complex skill (team leadership behavior) transfers to a complex clinical setting (emergency department) with highly variable clinical tasks (trauma resuscitations). Our novel team leadership training significantly improved overall leadership performance and partially mediated the positive effect between leadership and patient care. This represents the first rigorous, randomized, controlled trial of a leadership or teamwork-focused training that systematically evaluates the impact on process (leadership) and performance (patient care).

ABSTRACT IMPACT: This work will help to identify ways to adapt family-based obesity treatment based on families’ food purchasing behaviors and beliefs. OBJECTIVES/GOALS: Families in obesity treatment are encouraged to make dietary changes. Dietary changes are impacted by food choices, which can be influenced by food cost. The objective of this research is to explore families’ food purchase behaviors and beliefs from the perspective of their health coach, and to assess how health coaches adapt treatment to address these. METHODS/STUDY POPULATION: Semi- structured telephone interviews were conducted with 10 health coaches in the Effectiveness of Family-Based Weight Loss Treatment Implementation in Primary Care (PLAN) study across four geographic locations in MO, NY, and OH. Topics covered were professional background, perspectives on working with families, and discussions with families regarding cost perception and food choice. Conventional content analysis was used through ‘open-coding’ of transcribed text by reading the transcripts and assigning labels. Codes were then organized into themes. In addition to the interviews, coaches were asked to complete a FRAME checklist to identify adaptations or modifications that were made to the treatment. RESULTS/ANTICIPATED RESULTS: The coaches reported that cost is a barrier to making healthier food choices for some but not all of their FBT families. Themes for cost as a barrier include: fast food is cheaper; justification to choose old food choices; sales on foods high in calories and sugar; bulk buying; and fewer sales on healthier options. Themes for what families consider when purchasing healthier items include: perishable foods, increased waste, picky kids, lack of knowledge about healthy eating on a budget, afraid of including new foods, and no money for new foods. The final stage of content analysis for the FRAME schematic checklist is ongoing. DISCUSSION/SIGNIFICANCE OF FINDINGS: The results exemplify that families’ have different food purchasing behaviors and beliefs and consider a variety of factors when making food choices. The data gathered from the FRAME checklists will help in characterizing the adaptations or modifications made by coaches and allow for better understanding of the impact on the families.

Objectives/Goals: Academic research centers struggle to recruit and retain a diverse, competent clinical and translational science (CTS) workforce. The clinical research professional career pathway is particularly underrecognized among undergraduates, despite offering multiple career opportunities. Methods/Study Population: To address these challenges, two undergraduate outreach programs were developed. First, an undergraduate certificate program in CTS (UC-CTS) was designed to equip students with the skills and knowledge needed to enter the workforce immediately after graduation. Second, a “CTS Roadshow” was launched to build awareness of CTS careers within a variety of undergraduate programs and majors. In this recruitment initiative, principal investigators (PIs) and CRPs visit classrooms to share information about CTS career pathways and offer insights into the roles, responsibilities, and professional opportunities available in the field. Results/Anticipated Results: The UC-CTS program launched in Fall 2024 as a 12-credit certificate that includes two paid internships: one in patient care and one in research. Currently, the program has 5 students enrolled with an anticipated increase in enrollment to 20 students by Spring 2025. Similarly, the CTS Roadshow has reached an increasing number of students each year. Since its inception in Spring 2023, the CTS Roadshow has introduced over 750 undergraduates across 21 courses to CTS careers. The CTS Roadshow has engaged students from a variety of majors, including biology, psychology, medical sciences, legal, finance, accounting, and pre-health programs, increasing awareness of and interest in CTS careers. Discussion/Significance of Impact: Both programs aim to expose students to CTS careers early in their education, better preparing them for full-time CTS roles after graduation. A rise in qualified applicants pursuing CTS careers locally and regionally is expected, improving job satisfaction and retention through enhanced preparation for the career field.