OBJECTIVES/GOALS: Nurses are leaving the profession at an alarming rate due to increased workload and burnout.#_msocom_1 Computational models that are reliable and reproducible are needed to quantitatively examine nursing workload and estimate potential effect of interventions. This project developed a logical data model to represent nursing EHR interactions. METHODS/STUDY POPULATION: With nursing EHR interactions as a starting point, we expand upon literature that examined the EHR workload of physicians. We conducted an exploratory analysis of nursing EHR audit log data at a large academic medical center, and explored components of nursing workload that can be extracted from other health system data. Using concepts derived from the studying temporal biomedical data patterns, we formulated a data structure that describes nurse EHR interactions, nurse intrinsic and situational characteristics, and nurse outcomes of interest in a scalable and extensible manner. RESULTS/ANTICIPATED RESULTS: Temporal machine learning models are grounded in the concept of vectors. We developed a logical data model that describes tasks performed by nurses (NTask), nurse types (NType), and nursing outcomes (NOutcome). For each nurse (k), we define a function <NTask (k, i)>, i=1 to N as a vector of dimension N, where N is the number of time periods in the study. The i component corresponds to the activity that the nurse is doing. The model will allow the quantitative classification of activity patterns for any finite number of nurses for an arbitrary set of tasks and for time at any specified resolution. The expected outcome is a set of vectors that can then be utilized to quantitatively model nurse activity trajectories and other patterns of nurse EHR interactions. DISCUSSION/SIGNIFICANCE: By instantiating the logical data model, we will demonstrate how nurse EHR interactions can be studied using temporal unsupervised learning and state-of-the-art artificial intelligence methods. We plan to simulate the potential impact of workload interventions and predict risk for nurse burnout.

OBJECTIVES/GOALS: Open surgery prevails in low- and middle-income countries (LMICs) due to scarcity of laparoscopic equipment and poor access to training. LaparosopiX is a box trainer system designed for teaching hospitals in LMICs; it includes an open-source laser print design and an app to allow surgical trainees to receive feedback from laparoscopic experts. METHODS/STUDY POPULATION: This study aims to assess the usability of Laparoscopix for surgical trainees and mentors at five large teaching hospitals in Kenya. Surgical trainees and mentors who participate in this study will be observed while setting up and using the app to identify natural pain-points. A post-session survey will be conducted to assess immediate perceptions of the platform including ease of navigation and intuitive design. Over three months, aggregate data regarding platform usage at these hospital sites will be collected and analyzed to assess user retention rates, usage and traffic patterns, and skill progression over time. Surveys will be sent out to assess attitudes towards the platform and to elucidate any aspects of the system we can improve. RESULTS/ANTICIPATED RESULTS: We hope to find overall positive impressions towards the LaparoscopiX system during this study. We expect there to be some pain-points that arise during navigation of the app, but we expect no large changes to the application architecture required. We anticipate an immediate increase and eventual plateau of users recruited. We hope to see that surgical trainees are advancing through the app while gaining practice and confidence. We will gather insightful data on which aspects of the app were helpful for trainees, and which can be improved. We also hope to learn what factors may play into trainee and mentor retention in the system. DISCUSSION/SIGNIFICANCE: Through this study, we hope to elucidate ways in which we can improve the LaparoscopiX platform, identify which features to prioritize, and determine the direction of future app development. We believe and hope that LaparoscopiX can expand access to laparoscopic surgical mentorship to improve surgical outcomes and health equity worldwide.

Objectives/Goals: Conception to early childhood is reported to be one of the most critical developmental periods in human development. This study examines the role of adversity experienced by both mom and child during the pre-and post-natal periods on children’s cardiometabolic disease risk (CMDR) outcomes. Methods/Study Population: Data include responses from 852 biological mother-child dyads from the Family Life Project. Adversity during pregnancy was measured using the Life Experiences Survey. The number of life experiences that mothers reported as “bad” was included in the analyses. Children’s experiences with adversity were assessed using cumulative risk, a composite measure of adversity captured at four time points: 6, 15, 24, and 35 months. These variables were used to predict children’s obesity and mean arterial pressure, markers of cardiometabolic disease risk. Children’s obesity status was measured using standardized body mass index (BMIZ) values, assessed in children when they were 24, 35, 48, 58, 90, and 154 months. Mean arterial pressure was captured at 154 months. Results/Anticipated Results: Less than half of mothers (42.4%) and children (44.6%) identified as Black. Roughly half of the children (49.1%) were female. Most (78.2%) mothers were categorized as being of low economic status. Preliminary analyses revealed that number of negative life experiences reported by mothers were not significantly correlated with MAP. Children’s cumulative risk (CR) at 6 (r=0.11, p<0.01), 15 (r=0.11, p<0.01), 24 (r=0.11, p<0.01), and 35 (r=0.10, p<0.01) months were significantly correlated mean arterial pressure (MAP) at age 14. Associations between CR and MAP remained significant among girls at all time points and among boys only at months 6,15, and 24 months. There were no significant correlations between adversity experienced in utero on children’s BMIZ values at any timepoint. Discussion/Significance of Impact: The American Heart Association states that MAP is often used as an indicator of CMDR. Preliminary results from this study suggest a potential pathway from adversity experienced in infancy and adolescent MAP. Future studies should further explore these associations to better understand the pathways from early life adversity to high CMDR.

OBJECTIVES/SPECIFIC AIMS: Discrimination within the healthcare system and physician distrust have been associated with adverse clinical outcomes for people living with HIV; however, many studies do not link these variables to biological data. We hypothesize that perceived healthcare discrimination and physician distrust associates with higher longitudinal viremia among HIV-positive women. METHODS/STUDY POPULATION: A 2006 cross-sectional survey assessed healthcare-based discrimination and physician trust in 92 HIV-positive and 46 high-risk HIV-negative women from the Washington DC Women’s Interagency HIV Study (DC-WIHS). In addition, we identified HIV viral load trajectories and demographics from the HIV-positive women who contributed≥4 semi-annual visits from 1994 to 2015. Viral suppression was defined by assay detection limits (<80 to <20 copies/mL). Group-based probability trajectory analyses grouped women based on longitudinal viral load patterns, and identified 3 groups: sustained viremia (n=32) with low-viral suppression over time, intermittent viremia (n=27) with varying suppression over time, and non-viremia (n=33) with high-longitudinal viral suppression. Ordinal logistic regression models assessed trajectory group and discrimination variables, controlling for demographics, using stepwise selection with significance level of α=0.05. RESULTS/ANTICIPATED RESULTS: Most women were African American (60%), insured at the time of visit (89%) and nonsmokers (56%). While physician trust did not differ by HIV viral trajectory group, trust was lower among HIV-negative women compared with HIV-positive women (p=0.03). Over 1 in 5 HIV-positive women reported discrimination in the healthcare system based on HIV status (21.3%). Report of discrimination based on drug/alcohol use was higher among HIV-negative participants (19.2% vs. 6.5%, p=0.01). Among women with longitudinal sustained viremia, report of discrimination based on race ethnicity (29%, p=0.004) and sexual orientation (15.6%, p=0.008) were higher than within the nonviremic and intermittent trajectory groups. DISCUSSION/SIGNIFICANCE OF IMPACT: Physician trust did not associate with increased longitudinal viral suppression among HIV-positive women in Washington, DC. Lack of physician trust among high-risk HIV-negative women could have implications for uptake of prevention methods. Reports of discrimination vary between HIV-positive and HIV-negative women in the Washington, DC area. The findings of healthcare system distrust among HIV-negative women has implications outside the realm of HIV, as this lack of trust may impact risk for other disease states among similar populations of women.

ABSTRACT IMPACT: The proposed research study will provide critical pilot data on the effect of using the prebiotic (HAMS-AB) on the gut microbiome profile, Beta-cell function and immune markers in humans with T1D. OBJECTIVES/GOALS: The overall objective of this study is to assess how the prebiotic high amylose maize starch that has been acetylated and butyrylated (HAMS-AB) impacts the gut microbiome profile, short chain fatty acid (SCFA) production, glycemia, Beta-cell function/health and immune responses in newly diagnosed youth with type 1 diabetes (T1D). METHODS/STUDY POPULATION: We are performing a pilot randomized cross-over trial. We plan to recruit 12 newly-diagnosed T1D youth with residual Beta-cell function between 12-16 years of age. We will profile the gut microbiome using metagenomics, measure stool SCFA levels using mass spectrometry, assess glycemia using continuous glucose monitoring, assess insulin production using mixed meal tolerance testing, assess Beta-cell stress using proinsulin/C-peptide levels, and test immune responses by examining cytokine levels and frequency, phenotype and function of T cell markers in peripheral blood. RESULTS/ANTICIPATED RESULTS: Thus far, we have enrolled 3 participants, 1 has completed the study. Baseline assessments indicate that we have technical feasibility of performing the above studies and measurements. Recruitment and enrollment are ongoing. We hypothesize that the use of HAMS-AB in newly diagnosed youth with T1D will (i) improve the gut microbiome profile, (ii) increase SCFA production, (iii) improve overall glycemia and Beta-cell function and (iv) modulate the immune system and mitigate autoimmunity. DISCUSSION/SIGNIFICANCE OF FINDINGS: Given the failure to develop a cure for T1D despite multiple completed intervention studies and the unknown long-term effects of immune-modulatory therapy on those at risk for or those diagnosed with T1D, prebiotics such as HAMS-AB may offer a simple, safe, yet inexpensive and tolerated dietary alternative approach to mitigating disease.

OBJECTIVES/GOALS: To evaluate the usability of a HIE interface design among community pharmacists and technicians to identify opportunities for design improvements METHODS/STUDY POPULATION: Pharmacists and pharmacy technicians employed at Indiana community pharmacies participated in formative usability testing, via a Rapid Usability Evaluation (RUE), with an interactive, PDF prototype of the HIE interface. Participants were video-recorded to capture first impressions on the usability of the HIE prototype via the think aloud technique. Each participant had up to 1 hour to complete 4 clinical scenarios. Afterwards, participants completed the System Usability Scale (SUS; scale 0–100, with 100 being the best) to rate their satisfaction with the HIE prototype. RESULTS/ANTICIPATED RESULTS: Across 3 community pharmacies, 16 individuals participated in usability testing: 8 pharmacists and 8 technicians. The average SUS score for the HIE interface across participants from all sites was 70. Pharmacists on average scored the interface higher than technicians, 74 vs. 65, respectively. Initial findings from one pharmacy revealed that both pharmacists and technicians expressed a desire for improved efficiency (i.e. fewer clicks ) to access HIE data, alternative placement of HIE links within existing systems, and improved navigation to exit HIE links. DISCUSSION/SIGNIFICANCE: Initial results reveal opportunities to improve the HIE interface usability. Findings will inform design improvements to the interface and the creation of a toolkit to support the sustainable and scalable participation in HIE by community pharmacies.

OBJECTIVES/SPECIFIC AIMS: Nonalcoholic steatohepatitis (NASH) is a common cause of chronic liver disease in the United States characterized by fat accumulation, inflammation, and fibrosis. Higher amounts of fat-free mass (FFM) and lower amounts of fat mass (FM) have been associated with better outcomes in several chronic diseases, recently also in NASH. Body composition is highly influenced by diet. However, the role of diet on body composition in patients with NASH is largely unknown. We hypothesized that consumption of polyunsaturated fatty acids (PUFA), healthy fatty acids mainly found in fish, nuts, and some vegetable oils, is associated with improved body composition, specifically greater FFM and lower FM, in NASH patients. METHODS/STUDY POPULATION: In total, 13 patients with histologically confirmed NASH underwent body composition testing via bioelectrical impedance analysis to estimate FFM% (% of body weight), FM% (% of body weight), and FFM/FM ratio. PUFA and saturated fat consumption was determined by standardized 5-pass 24-hour dietary recall. Correlations were computed using the Spearman rank test. RESULTS/ANTICIPATED RESULTS: Median body mass index (BMI) was 35.7 kg/m2 (32.8–42.7), median age of the sample was 50 years (46.3–57.3), and 73% were female. Median percent of calories from polyunsaturated fat was 6.8% (5.4–9.6). Percent of calories from PUFA was positively and significantly associated with greater FFM% (R=0.56, p=0.049), lower FM% (R=−0.59, p=0.035), and greater FFM/FM ratio (R=0.58, p=0.037). Additionally, a higher PUFA to saturated fatty acids ratio was also significantly correlated with greater FFM% (R=0.58, p=0.039), lower FM% (R=−0.64, p=0.020), and greater FFM/FM ratio (R=0.57, p=0.043). DISCUSSION/SIGNIFICANCE OF IMPACT: In patients with NASH, the consumption of PUFA is associated with higher FFM and lower FM, which suggests a protective role of these nutrients on body composition. A larger study on patients with NASH is warranted to confirm our findings on PUFA consumption and body composition, as well as to determine whether these effects will improve clinical outcomes.

OBJECTIVES/GOALS: Clinical trials demonstrate that axillary lymph node dissection (ALND) is unnecessary for most breast cancer patients with 1-3 involved nodes, but whether this is true for those with ILC is unknown. We evaluate the impact of ALND on recurrence-free survival (RFS) in ILC and 1-3 positive nodes. METHODS/STUDY POPULATION: We performed a retrospective cross-sectional analysis of patients with ILC treated between 1992-2019 at our institution. All patients received either sentinel lymph node biopsy (SLNB) or ALND and underwent either breast conservation surgery (BCS) or mastectomy. The primary outcome was RFS, defined as the absence of locoregional or distant recurrence. RESULTS/ANTICIPATED RESULTS: Of 496 cases, 250 (50.4%) underwent BCS, and 246 (49.6%) underwent mastectomy. A total of 93% of patients were hormone receptor positive, and 89% had low or intermediate grade disease. Among patients with 1-3 positive nodes, there was no significant difference in 5- and 10-year RFS based on receipt of ALND for both BCS and mastectomy cohorts. Using a multivariate model, we found no association between ALND and RFS overall (HR = 0.98, 95% CI 0.36-2.7, p>0.20) and among those with 1-3 positive nodes (HR = 0.60, 95% CI 0.12-3.4, p>0.20). DISCUSSION/SIGNIFICANCE OF IMPACT: These findings support the safety of omitting ALND in patients with ILC and 1-3 positive nodes, regardless of whether they receive BCS or mastectomy. Further studies of axillary management in ILC, including imaging tools to predict nodal involvement and response to therapy, are warranted.

ABSTRACT IMPACT: If successful, this program can provide a scalable, patient-centered intervention to help patients taper off opioid medications in primary care settings. OBJECTIVES/GOALS: Tapering of chronic opioid therapy is often desirable but challenging in primary care and specialty clinics that lack behavioral health expertise. The objective of this pilot study is to determine the feasibility of testing a peer-delivered pain self-management program to assist primary care patients through an opioid taper. METHODS/STUDY POPULATION: To provide critical support to patients and providers during opioid medication tapering, we propose to conduct a 40 patient randomized controlled pilot of a 12-week telecare collaborative care program administered by a psychiatrist and peer recovery specialist team. The intervention will incorporate a validated positive psychology intervention for treating chronic pain. Additionally, participants will be invited to participate in semi-structured individual interviews to discuss their experience in the trial, what worked well, what could be improved, and potential strategies to bolster recruitment of additional patients in future studies. RESULTS/ANTICIPATED RESULTS: Our primary aim is to determine the effectiveness of our intervention in facilitating opioid medication weaning, with reduction in opioid dose as the primary outcome. Our secondary aims will be to assess pain outcomes, adherence to tapering, patient satisfaction, and barriers to adherence as described by patients. DISCUSSION/SIGNIFICANCE OF FINDINGS: This trial proposes a novel collaborative care approach for opioid weaning using proven, easy-to-deliver positive psychology tools for pain management that, if successful, could be implemented broadly in many clinics struggling to safely reduce opioid prescribing.

Objectives/Goals: Early identification and profiling of planned studies is a critical administrative challenge in providing timely support for clinical trials. Here we describe the collaborative design and development of a clinical trial tracking dashboard to enhance support and quality improvement for investigator-initiated clinical trials at our institution. Methods/Study Population: Trial-CARE organized a workgroup with key stakeholders from WashU business units that manage grants, information technology, bioinformatics, data repository stewardship, and clinical trial support. The workgroup strategized next steps in a “proof-of-concept” effort to determine whether NIH investigator-initiated clinical trial metrics would be accessible via the WashU Data Warehouse. The WashU Data Warehouse is a data repository that pulls in pre-award and post-award data from sources such as the WashU Research-Grant Management System (RMS) and the NIH Reporter Tool. The proof-of-concept findings lead to implementing a plan for Phase 1 of the design, development, and piloting of a visual dashboard to track and offer targeted and timely support to NIH investigator-initiated clinical trials at WashU. Results/Anticipated Results: WashU currently has 217 grants submitted and 114 grants awarded for NIH clinical trials. In the proof of concept, we confirmed and successfully matched over 100 awarded NIH investigator-initiated clinical trials at WashU across RMS and the NIH Reporter Tool. We determined Phase I of the dashboard would track clinical trial data from these two sources via the WashU Data Warehouse. The pilot of Phase I of the dashboard will begin in February 2025. We also identified mission critical data elements not accessible via the WashU Data Warehouse (e.g., enrollment diversity, IND, and IDE). The plan to procure this data will require continued stakeholder support in Phase II of the dashboard to (1) expand data capture in RMS and (2) ingest additional data into the WashU Data Warehouse from RMS or new systems (e.g., ClinicalTrials.gov). Discussion/Significance of Impact: Early access to robust data about NIH investigator-initiated clinical trials via our newly created Phase I dashboard will better position our centralized service cores to support trial success, compliance, and quality improvement across the lifecycle of these clinical trials. In Phase II, we plan to expand the data available in the dashboard.

Objectives/Goals: Hepatocellular carcinoma (HCC) is the third leading cause of cancer deaths worldwide. The epidemiology of HCC has been changing over the past several decades. The aim of this study is to examine changes in etiology, incidence, and survival of HCC in a population-based cohort in the Upper Midwest. Methods/Study Population: The Rochester Epidemiology Project (REP) is a medical records linkage system between healthcare systems that centralizes patient records to a database for investigators to access for approved research projects. The REP now includes 27 counties in southeastern Minnesota and western Wisconsin, with access to 2.9 million medical records linked to 1.4 million persons who resided in this region at some point between 2010-2024. In this study, we used ICD-9 and ICD-10 codes to identify any patient in the REP with one or more instances of the relevant HCC codes. Charts were manually reviewed to confirm diagnosis, residency, and clinical information. All patient data were analyzed as an overall cohort and stratified by era of diagnosis or demographic characteristics. Results/Anticipated Results: Metabolic disorders were the most prevalent HCC risk factor in this cohort, with hypertension, nonalcoholic steatohepatitis, and hyperlipidemia rates significantly increasing over the study period. Age- and sex-adjusted HCC incidence also increased over the study period from 5.39 (95% CI: 3.63, 7.98) per 100,000 person-years in 2010-2013 to 8.17 (95% CI: 6.10, 11.07) per 100,000 person-years in 2018-2021 (p=1.1844x10-4). Age, sex, and race stratification shows that this increase was driven by men, those age 65+ years, and non-Hispanic White individuals. The median survival in this cohort was 23.41 (95% CI: 19.81, 26.97) months, with surveillance status, BCLC stage at diagnosis, hypertension, and hypertriglyceridemia being associated with a significantly decreased hazard ratio of death. Discussion/Significance of Impact: This study highlights the changing landscape of HCC etiology and increasing incidence using a population-based Midwestern cohort. Overall survival remains low, highlighting the need for more robust prevention and screening in at-risk groups.

OBJECTIVES/GOALS: The overarching goal of the Mayo Clinic in Florida Clinical Research New Hire Training Programis to create a standardized work force development model that ensures all new research coordinators receive the same high-quality training and can perform their role. METHODS/STUDY POPULATION: Mayo Clinic implemented a comprehensive six-week in-class training program to teach research coordinators how to conduct clinical research studies and trials. A multi-disciplinary team with expertise in education, operations, study coordination, and human resources assisted in development. The program approaches education through the lens of application. Staff start on designated hire dates and have an assigned trainer, allowing them to complete the program in cohorts and build connections with one another. During the program, they complete assignments, checkpoints, and shadow within their units. At the conclusion, they take a one-on-one assessment with a trainer to confirm they can work independently. If a learner cannot pass, the trainer and supervisor implement a learning plan targeting their needs. RESULTS/ANTICIPATED RESULTS: The program has had 110 graduates since its April 2022 inception, with a steady improvement in learner satisfaction scores. Based on the question “My site’s new hire education program was good,” with 5 being strongly agree and 1 being strongly disagree, learners rate the current iteration as 4.38. The program has a positive correlation with retention and favorable quality reviews. 23.8% of new coordinators hired from April of 2021 to March of 2022 left within the first year. From April 2022 to September 2023, the first-year turnover rate fell to 14.55%. Additionally, 43% of quality reviews completed for graduates required no follow-up, compared to 35% of staff hired before implementation of the program. Only 5% of reviews for graduates required urgent follow-up, compared to 15% of those completed for existing staff. DISCUSSION/SIGNIFICANCE: Research Coordinators who complete the training program report a higher confidence level and demonstrate they can perform their role. The effects of our program have been so pronounced that the curriculum is being translated within Clinical Research across all of Mayo Clinic and our Florida site is researching ways to market it outside of Mayo Clinic.

OBJECTIVES/GOALS: Military personnel are at significantly greater risk for developing tinnitus, due to increased exposure to acoustic trauma. Many psychiatric disorders are common among individuals with chronic tinnitus, including posttraumatic stress disorder (PTSD). Although tinnitus and PTSD are clearly different, research supports the notion of shared mechanisms between both disorders. First, there are overlapping symptoms between tinnitus-related distress and PTSD, including irritability, distorted cognitions, persistent negative emotional states, diminished interests in activities, exaggerated startle response, sleep disturbance, concentration problems, and hypervigilance. Second, tinnitus and PTSD are highly comorbid with one another, whereas 34% of veterans with tinnitus also carry a PTSD diagnosis. Third, those with both disorders are significantly more emotionally impaired compared to those with tinnitus and any other psychiatric disorder. Lastly, neuroimaging research has shown similar regions within the auditory vigilance network are implicated among those with tinnitus, and separately, among combat PTSD patients, suggesting shared neurobiological mechanisms between both disorders. Though we are aware that tinnitus and comorbid PTSD presents as a significantly greater clinical concern, the relationship between tinnitus-related distress and PTSD symptomotology it is still unknown. Canonical correlation analyses will be conducted to examine the relationship between tinnitus-related distress and PTSD among veterans as a part of a larger clinical trial for posttraumatic headache. Results of the study will shed light on the relationship between tinnitus-related distress and PTSD, and may suggest a different phenotype for those with both disorders. Researchers and clinicians will further understand and conceptualize the relationships among the cognitive, emotional, and behavioral symptoms associated with tinnitus and PTSD, both individually and conjointly. METHODS/STUDY POPULATION: Baseline data (N = 112) from a larger clinical trial examining the effectiveness of two different psychotherapies for the alleviation of posttraumatic headache was examined. The primary aim of this project was to evaluate the relationship between tinnitus-related distress and PTSD based on the eight subscale scores of the Tinnitus Functional Index (TFI) and the four scales of the Clinician Administered PTSD Scale for the DSM-5 (CAPS-5), respectively. To address this aim, canonical correlation analysis was used where the tinnitus-related symptom subscales made up one variable set and PTSD symptom subscales made up the second variable set. First, we evaluated the overall model fit based on Wilks Lambda to determine if the two variable sets were related at the p < .05 level. Next, we evaluated the canonical correlations (comparable to an eigenvalue) for each canonical dimension to determine the required number of significant canonical dimensions (or latent constructs) that were necessary to understand the association between the two variable sets. Finally, the standardized canonical coefficients, which are analogous to regression coefficients, evaluate the magnitude of variate relationships and determine which subscales best describe significant canonical dimensions. RESULTS/ANTICIPATED RESULTS: Prior to the canonical correlation analysis, total score descriptive statistics and subscale score zero-order correlations were carried out. The CAPS-5 total score was 33.24 (SD = 9.39) and the TFI total score was 50.81 (SD = 21.88) in this sample. Interpretation of the zero-order correlations indicated that TFI Relaxation subscale was the only tinnitus-related subscale moderately associated with a PTSD subscale (i.e., Reexperiencing, r = .35). Canonical correlation omnibus model fit analysis via the Wilks Lambda overall multivariate test indicated that the tinnitus variable set was significantly associated with the PTSD variable set, F = 1.55, p = .04. Evaluation of the canonical correlations indicated that one dimension was significant in explaining the relationship between the two variable sets and accounted for 25% of the overall variance, F = 1.55, p < .04, R2 = .249. Standardized canonical coefficients indicated that the PTSD subscales Reexperiencing (b = 0.64) and Negative Alterations in Cognition and Mood (b = 0.55) were the most representative of the identified canonical dimension. In terms of the TFI, the Relaxation (b = 1.28) and Sleep (b = 0.72) subscales appeared to be most related to the canonical dimension. The TFI subscales Auditory Difficulty (b = −0.30) and Quality of Life (b = 0.30) also appeared to be related the canonical dimension to a lesser degree. DISCUSSION/SIGNIFICANCE OF IMPACT: Findings support prior research suggesting particularly deleterious functional outcomes among individuals with comorbid tinnitus and PTSD. Results of this study suggest a latent variable that can explain the unique experience of individuals with both disorders. This latent variable consists of two PTSD constructs: Reexperiencing traumatic events (i.e., flashbacks, nightmares, intrusive memories), and Negative Alterations in Cognition and Mood (i.e., self- and other-blame, strong negative feelings, loss of interest, feeling distant). This latent variable also consists of two tinnitus-related constructs: Sleep (i.e., trouble falling and staying asleep, peaceful sleep) and Relaxation (i.e., ability to relax, enjoyment of peace and quiet). Auditory Difficulty (i.e., hear clearly, understand people) and Quality of Life (i.e., social activities, relationships, difficulty performing tasks) also contributed to the latent variable, but to a lesser degree. It is suggested that the constellation of symptoms related to the latent variable is a Dysphoric Factor, unique to individuals with PTSD, tinnitus, and posttraumatic headache. It may be necessary to incorporate different techniques into existing evidence-based treatments for both tinnitus and PTSD, for optimal symptom improvement.

OBJECTIVES/SPECIFIC AIMS: The goal of this abstract/presentation is to share lessons learned from participation in the NIH SBIR I-Corps Train-The-Trainer Program, discuss our experiences offering programs at our local institutions, and communicate our plans to develop an I-Corps@NCATS program that can be disseminated across the CTSA network. We believe that an I-Corps@NCATS program will enhance the process of scientific translation by taking best practices from NSF I-Corps and adapting the program to meet the needs of biomedical scientists in academic medical centers. By integrating I-Corps@NCATS training, we hypothesize that the clinical and translational investigator base will be better prepared to identify new innovations and to accelerate translation through commercialization. METHODS/STUDY POPULATION: The diverse, interdisciplinary team of investigators involved in this project span 9 CTSA Hubs, including UAB, Rockefeller, UC Denver, HMC-Penn State, UMass, UC Davis, Emory/Georgia Tech, Miami and Michigan. This team was funded by NCATS in 2015–2016 to participate in the CTSA I-Corps Train-The-Trainer Program in conjunction with the NIH-SBIR/STTR I-Corps national program. The goals were to observe the curriculum, interact with and learn from the NSF National Teaching Team and begin implementation of similar programs at our home institutions. Our I-Corps@NCATS team has been holding monthly, and more recently weekly, conference calls to discuss our experiences implementing local programs and to develop a strategy for expanding CTSA offerings that include innovation and entrepreneurship. Our experience revealed several challenges with the existing NSF/NIH I-Corps program offerings: (1) there is no standard curriculum tailored to academic clinical and translational research and biomedical innovations in the life sciences, and (2) the training process to certify instructors in the I-Corps methodology is a much more rigorous and structured process than just observing an I-Corps program (eg, requires mentored training with a national NSF I-Corps trainer). Our team is proposing to address these gaps by taking best practices from NSF I-Corps and adapting the program to create the I-Corps@NCATS Program, tailored to meet the needs of researchers and clinicians in academic medical centers. RESULTS/ANTICIPATED RESULTS: There are 3 primary anticipated results of our project. First, develop a uniform curriculum for the I-Corps@NCATS Program using the National Teaching Team of experts from the NIH’s SBIR I-Corps program. Second, build the I-Corps@NCATS network capacity through a regional Train-The-Trainer Program. Third, develop a set of common metrics to evaluate the effectiveness and impact of the I-Corps@NCATS Program across the community of CTSA Hubs and their respective collaborative networks. DISCUSSION/SIGNIFICANCE OF IMPACT: Over the past 10 years, CTSA Hubs have accelerated science by creating/supporting programs that provide research infrastructure, informatics, pilot funding, education/training, and research navigator services to investigators. These investments help to ensure that we are “doing science right” using the best practices in clinical research. Even so, it is equally important to make investments to ensure that we are “doing the right science.” Are our investigators tackling research problems that our stakeholders, patients, and communities want and need, to make sure that our investments in science have real-world impact? In order to accelerate discoveries toward better health, scientists need to have a better way to understand the needs, wants and desires of the people for whom their research will serve, and how to overcome key obstacles along the path of innovation and commercialization. To fill this gap, we propose that the CTSA Hubs should include in their portfolio of activities a hands-on, lean startup program tailored after the highly successful NSF Innovation Corps (I-Corps) program. We hypothesize that by adapting the NSF I-Corps program to create an I-Corps@NCATS program tailored to medical research, we will better prepare our scientists and engineers to extend their focus beyond the laboratory and broaden the impact of their research. Investigators trained through I-Corps@NCATS are expected to be able to produce more innovative ideas, take a more informed perspective about how to evaluate the clinical and commercial impact of an idea, and quickly prototype and test new solutions in clinical settings.

OBJECTIVES/GOALS: To compare rates and types of neurological symptoms in children hospitalized with seizures and respiratory infections, including SARS-CoV-2, influenza, and endemic coronaviruses. METHODS/STUDY POPULATION: Retrospective cohort study of children between 0-21 years of age admitted to a single pediatric free-standing quaternary referral center from January 1, 2014 to June 1, 2021 for seizures who had positive respiratory infection PCR for SARS-CoV-2, other coronaviruses (Coronavirus NL63 and Coronavirus OC34), influenza (A and B), adenovirus, Mycoplasma pneumoniae, and parainfluenza 3 or 4 infections. Patient characteristics including age, race, sex, ethnicity, hospital length of stay, intensive care unit admission, intubation, chest x-ray, and MRI results were included. The primary outcomes were rates of neurological diagnoses and mortality. RESULTS/ANTICIPATED RESULTS: A total of 883 children were included: 68 SARS-CoV-2, 232 influenza, and 187 with other coronaviruses (OC), 214 adenovirus, 20 M. pneumoniae, 121 parainfluenza 3, and 41 parainfluenza 4. Mortality rates were 0% M pneumoniae to 4.9% in parainfluenza 4, with 2.9% in SARS-CoV-2. Encephalopathy was noted in 5-15.6% and strokes were seen in all infections except for coronavirus OC43 and M. pneumoniae, with 4.9% in parainfluenza 4 and 5.9% in SARS-CoV-2. The most common brain MRI abnormality was diffusion restriction. Differences between SARS-CoV-2 and OC were observed in stroke (5.9% vs. 0.5%, p-value=0.019), ICU admission (50% vs. 69%, p-value=0.008), and intubation (19.1% vs. 34.8%, p-value=0.021, respectively). However, the rates of neurological symptoms were similar between SARS-CoV-2 and influenza. DISCUSSION/SIGNIFICANCE: We found higher rates of stroke, but lower rates of ICU admission and intubation in SARS-CoV-2 versus OC. Strokes were observed in many infections. Rates of neurological symptoms were similar in SARS-CoV-2 versus influenza patients. Vigilance should be undertaken in treatment of children presenting with all respiratory illnesses.

OBJECTIVES/SPECIFIC AIMS: The main aim of this study was to investigate the interaction between glomerular filtration rate (GFR) and body mass index (as well as serum leptin) as determinants of peripheral and central insulin sensitivity (IS). METHODS/STUDY POPULATION: This was a cross-sectional investigation of 140 nondiabetic participants – 56 with CKD (GFR = 15-59 ml/min/1.73m2) and 94 with normal GFR (≥ 60 ml/min/1.73m2) – recruited as part of the relationship of insulin sensitivity in kidney disease and vascular health (RISKD) study. Peripheral (skeletal muscle) and central (hepatic) IS were assessed with the hyperinsulinemic euglycemic glucose clamp (HEGC) and homeostasis assessment of insulin resistance (HOMA-IR) respectively. Creatinine-based estimated GFR (eGFR) was obtained using the CKD-EPI equation and body mass index (BMI) was computed from baseline weight and height measurements. Linear regression models with robust standard errors (to relax homoscedasticity assumptions) and interaction terms were used to investigate GFR and BMI as predictors of HEGC-derived insulin sensitivity index (ISI) and HOMA-IR. RESULTS/ANTICIPATED RESULTS: The mean (SD) age was 53.9 (14.5) years; 50.7% were female and 36.7% were African-American. Compared to controls, CKD patients had significantly lower mean (SD) ISI [5.4 (3.2) vs. 3.1 (1.6), p < 0.0001]. Log ISI was positively correlated (r = 0.39, p < 0.0001) with eGFR and inversely correlated (−0.30, p < 0.0001) with BMI and log leptin (−0.42, p < 0.0001). In multivariable models adjusted for age, sex and race, a 10 ml/min/1.73m2 lower eGFR was associated with a greater decrease in ISI among non-obese (0.48; 95% CI: −0.25, −0.70) compared to obese participants (−0.18; 95% CI: −0.02, −0.35) (p-interaction = 0.04). Patients with low eGFR (in particular, the lower margin of the CKD stage 3 range, 30ml/min) had lower ISI even with BMI within normal range (Figure 1a). At higher eGFR, BMI had a greater impact on ISI. P-interaction = 0.046, for differential BMI effects at lower vs. higher eGFR. Log HOMA-IR was inversely correlated with eGFR (r = - 0.49, p < 0.0001) and positively correlated with BMI (r = 0.52, p < 0.0001) and log leptin (0.46, p < 0.0001). HOMA-IR was lower for persons with higher GFR compared to lower GFR, at any BMI value. For example, at a BMI of 30 and a GFR of 120, HOMA-IR was 1.2 compared to 4.8 at a GFR of 30 (Figure 1b). Also, persons with high GFR had low HOMA-IR even with BMI in the obese range. BMI had a greater effect on HOMA-IR at lower eGFR. P-interaction = 0.005, for differential BMI effects at lower vs. higher eGFR. Similar findings were obtained when using log leptin in lieu of BMI in models for ISI and HOMA-IR. DISCUSSION/SIGNIFICANCE OF IMPACT: Measures of adiposity (BMI and leptin) and GFR were independently predictive of insulin sensitivity (IS) but the magnitude of the effect of BMI (or leptin) on IS varied significantly across GFR levels and type of IS (peripheral versus central). The effect of BMI on central IS (HOMA-IR) was more pronounced at lower GFR with small changes in BMI translating into greater variations in IS. Conversely, at low GFR, peripheral IS (ISI) is less affected by BMI. Persons with GFR at the lower margin of the CKD stage 3 range were significantly insulin resistant (low ISI) regardless of their BMI. More studies are required to further elucidate these interaction patterns for central and peripheral IS.

OBJECTIVES/SPECIFIC AIMS: To describe adverse behavioral symptoms attributed to droxidopa therapy for neurogenic orthostatic hypotension (nOH). METHODS/STUDY POPULATION: BACKGROUND: Droxidopa, a norepinephrine (NE) precursor, improves symptoms of nOH by replenishing NE levels. Central NE effects are poorly described but may offer potential benefits given the pathophysiologic progression of α-synuclein-related disorders. Here we report a series of cognitive and behavioral side effects linked to droxidopa therapy. METHODS: We identified 5 patients treated at Vanderbilt University who developed behavioral symptoms including mania, irritability, and disorientation shortly after the initiation of droxidopa for nOH. Comprehensive chart reviews were performed for all patients, including analysis of droxidopa titration schedule and dosing, medical comorbidities, clinical course, and outcome. All patients had symptoms of synucleinopathy, manifesting with autonomic failure, REM behavior disorder, and parkinsonism. Four met criteria for idiopathic PD, and one was diagnosed with pure autonomic failure but had concomitant symptoms of parkinsonism and REM sleep behavior disorder. RESULTS/ANTICIPATED RESULTS: Our patients had no significant cognitive or behavioral symptoms before the initiation of droxidopa. The average decrease in blood pressure upon standing was 27 mmHg systolic and 17 mmHg diastolic. Behavioral disturbances were observed early in the titration period and at relatively low doses of droxidopa (total daily doses ranging from 300 to 800 mg/day; droxidopa therapeutic dose range 900–1800 mg/d). The most common symptoms reported were mania, irritability, and confusion. Symptoms resolved with dose reduction in 4 patients, and droxidopa was discontinued in 1 patient due to persistent irritability. No other medical comorbidities or alternative etiologies were identified to explain these effects. DISCUSSION/SIGNIFICANCE OF IMPACT: Droxidopa is a prodrug designed to act peripherally, but may also have important, yet poorly described, central effects. We hypothesize that these behavioral manifestations result from an “overdose” of key NE networks linking orbitofrontal and mesolimbic regions. Further studies are warranted to better characterize central NE effects in patients treated with droxidopa.

Deep learning has pushed the scope of digital pathology beyond simple digitization and telemedicine. The incorporation of these algorithms in routine workflow is on the horizon and maybe a disruptive technology, reducing processing time, and increasing detection of anomalies. While the newest computational methods enjoy much of the press, incorporating deep learning into standard laboratory workflow requires many more steps than simply training and testing a model. Image analysis using deep learning methods often requires substantial pre- and post-processing order to improve interpretation and prediction. Similar to any data processing pipeline, images must be prepared for modeling and the resultant predictions need further processing for interpretation. Examples include artifact detection, color normalization, image subsampling or tiling, removal of errant predictions, etc. Once processed, predictions are complicated by image file size – typically several gigabytes when unpacked. This forces images to be tiled, meaning that a series of subsamples from the whole-slide image (WSI) are used in modeling. Herein, we review many of these methods as they pertain to the analysis of biopsy slides and discuss the multitude of unique issues that are part of the analysis of very large images.

Translating scientific discoveries in tissue engineering and regenerative medicine (TE/RM) into clinically adopted therapies is hindered by fragmented development pipelines, regulatory and manufacturing challenges, and limited funding. Despite substantial investment by the U.S. National Institutes of Health (NIH), few NIH-funded TE/RM projects achieve commercialization or regulatory approval by the US Food and Drug Administration. The gap between academic innovation and clinical implementation is particularly evident in the dental, oral, and craniofacial (DOC) domain, where market and reimbursement constraints further restrict translation. To address these barriers, the National Institute of Dental and Craniofacial Research established the Dental, Oral and Craniofacial Tissue Regeneration Consortium (DOCTRC), comprising two nationwide Resource Centers tasked with guiding promising technologies from universities and small businesses through preclinical validation toward clinical adoption. This translational science case study outlines DOCTRC’s translational model, highlighting lessons learned from five cohorts of interdisciplinary translational project teams, strategies for navigating manufacturing and regulatory pathways, and approaches for aligning academic innovation with clinical and market needs. The unique impact of the DOCTRC framework demonstrates how disciplined product development activities, non-dilutive funding mechanisms, and a comprehensive support ecosystem can accelerate technology translation, offering a scalable model for other biomedical fields.