OBJECTIVES/GOALS: We have evaluated the primary factors behind successful expansion of the predoctoral TL1 training grant at OHSU to all research-intensive universities in the state, evaluating the precepts that were key to integration. We also evaluate inclusion of social and behavioral sciences in clinical and translational science training, METHODS/STUDY POPULATION: OHSU contains three professional schools (medicine, nursing, and dentistry) as well as graduate studies in science. There are also three research-intensive universities in Oregon: Portland State University (PSU); Oregon State University (OSU) in Corvallis; and the University of Oregon (UO). We report evaluation of our 7-year experience with a predoctoral TL1 program and the precepts behind successful implementation of statewide outreach. We have tracked applicants from each university and program, trainee feedback, and success of the applicants as measured by persistence in research, inclusion of translational methods, additional training acquired, and subsequent research funding. We also evaluate participation by behavioral and social scientists. RESULTS/ANTICIPATED RESULTS: The predoctoral TL1 has included 40 scholars over 7 years, with 65% PhD graduate students and 35% MD students who pursue an additional research degree (PhD, MCR). Of PhD graduate students, the distribution is similar among universities: OHSU 31%, PSU 19%, OSU 27%, UO 23%. 38% of all graduate student trainees are in behavioral or social science. Key precepts behind success include: concentration on specific graduate programs at each university; implementing a common curriculum based on the MCR curriculum; interinstitutional mentor teams; leadership team that spans universities; required core TL1 activities; and a competitive application process with an interinstitutional review committee. Applicants are required to identify how translational science education enhances their research career. DISCUSSION/SIGNIFICANCE: Creating a statewide resource for TL1 translational science training has increased opportunities to expand translational research throughout Oregon through providing new opportunities to enhance excellence through disseminating resources and training across the universities.

OBJECTIVES/GOALS: Composition of demographics or image types in publicly available datasets may detract from deep learning (DL) diagnosis performance of underrepresented melanoma subtypes. We evaluate a DL model’s performance on melanoma subtypes (acral; head and neck) that have known association with poor prognosis. METHODS/STUDY POPULATION: We trained a CNN using a single InceptionV3 model for 30 epochs on dermoscopic images of pigmented lesions from the International Skin Imaging Collaboration (ISIC). The ISIC 2018 challenge training set had 10008 total images, with 1113 total nevi, 6705 total melanomas, 97 acral nevi, 10 acral melanomas, 256 head and neck (H&N) nevi, and 164 H&N melanomas. The non-acral test set had 117 melanomas and 200 nevi. The acral test set had 201 melanomas and 161 nevi. The H&N test set had 199 melanomas and 128 nevi. Area under the receiver operating curve (AUC) was calculated. The model was retrained with acral lesion oversampling (10x) and performance on the acral test set was re-evaluated. RESULTS/ANTICIPATED RESULTS: The model performed on the non-acral test with an AUC of 80.5%, on the acral test with an AUC of 76.3%, and on the head and neck test with an AUC of 83.8% After oversampling acral lesions within the training set, the model showed nearly the same performance as without oversampling on acral lesions: AUC of 75.6%. DISCUSSION/SIGNIFICANCE OF IMPACT: Diagnosis of high-risk melanoma subsets (acral; H&N) remains reliable despite underrepresentation during training, increasing validity for broad implementation of DL technology. Datasets for individual subtypes may not be warranted as findings suggest features may be learned from other skin lesions.

Objectives/Goals: This scoping review examines how socioeconomic status (SES) and sociodemographic status (SDS) disparities are considered in transition interventions for congenital heart disease (CHD) patients. By identifying gaps, it aims to guide future research and interventions to address inequities in transitional care. Methods/Study Population: A systematic search of the literature was performed using PubMed, Scopus, and Web of Science. Literature was searched from January 1990 to October 2024 and revealed 823 articles. Upon initial screening, 71 duplicates, 76 non-SES focused articles, and an additional 128 irrelevant articles were excluded. A total of 548 full-text articles were reviewed. Articles that did not focus on transition interventions for CHD patients were excluded. Studies were analyzed for factors affecting care transitions with special attention to SDS and SES factors. SDS factors were defined as age, gender, race/ethnicity, and geographic location, while SES factors were defined as income level, education, employment status, and access to care. Results/Anticipated Results: Out of 548 articles reviewed, only 18 addressed SES factors, and 10 examined SDS factors in the transition from pediatric to adult care. The most common interventions were patient education (33%), care coordination (29%), and family support (21%), but they lacked tailoring to SES/SDS factors. Patients from low-income households were 50% more likely to experience care discontinuities and 40% less likely to participate in transition programs. Health literacy interventions were generic, overlooking socioeconomic differences. Tailored transition programs are needed to address low health literacy and financial barriers, potentially improving outcomes for disadvantaged patients in rural and underserved areas. Discussion/Significance of Impact: This review exposes the limited focus on SES and SDS disparities in CHD transition interventions. Disadvantaged patients face barriers like limited access to care and low health literacy. Developing tailored programs to address these gaps is crucial for enhancing transitions and improving long-term outcomes for vulnerable CHD patients.

OBJECTIVES/GOALS: The goals of this study are to 1) adapt a mindfulness-based intervention that supports the development of trust-promoting behaviors of OBGYN providers with patients who identify as Black women based on the input of providers and patients, and 2) assess the feasibility of implementation for OBGYN healthcare providers. METHODS/STUDY POPULATION: Goal 1: Focus groups will be conducted with members of the populations of providers and Black women patients in Alachua County, Florida to identify essential intervention content to complement the central component of mindfulness and spiritually based practices. This complementary content will serve to address the institutional and cultural context of the intervention setting. Goal 2: Providers will be recruited to participate in interviews about their perceptions of intervention feasibility. These aspects include recruitment potential, acceptability of the intervention content and delivery, implementation practicality, identification of appropriate outcomes, and identifying strategies to recruit Black women patients to participate in program evaluation. RESULTS/ANTICIPATED RESULTS: Goal 1: We will elicit the perspectives of providers and Black women patients regarding the respective roles and relationship of mindfulness and spirituality to increase trust-promoting behaviors with patients who are Black women. We also anticipate identifying additional content to complement the core intervention components that participants perceive as necessary to develop the knowledge, skills, and behaviors which convey the trustworthiness of providers to patients. Goal 2: We expect to gain key insights into intervention design, implementation, and evaluation feasibility from the perspective of providers. Interview data will be aggregated and qualitatively analyzed for themes pertaining to feasibility. DISCUSSION/SIGNIFICANCE: An intervention that builds on mindfulness and spiritual practice is an innovative approach to improving interpersonal outcomes in provider-patient relationships. By investigating the feasibility of such an intervention, we will gain insight into how to design and deliver a program to increase the trust-promoting behaviors of OBGYN providers.

OBJECTIVES/SPECIFIC AIMS: Test the hypothesis that neprilysin inhibition with sacubitril/valsartan will increase endogenous intact GLP-1 after a mixed meal compared with valsartan. METHODS/STUDY POPULATION: Adults 18–80 years with pre-diabetes or type 2 diabetes and elevated blood pressure. RESULTS/ANTICIPATED RESULTS: We anticipate higher intact GLP-1 area under the cure after the meal when subjects receive sacubitril/valsartan compared with valsartan. DISCUSSION/SIGNIFICANCE OF IMPACT: Neprilysin inhibition may be a target for anti-diabetes therapy by decreasing degradation of GLP-1.

OBJECTIVES/GOALS: To improve the implementation of FDRs in translation research. Current statistical packages are hard to use and fail to adequately convey strong assumptions. We developed a software package that allows the user to decide on assumptions and choose the hey desire. We encourage wider reporting of FDRs for observed findings. METHODS/STUDY POPULATION: We developed a user-friendly R function for computing FDRs from observed p-values. A variety of methods for FDR estimation and for FDR control are included so the user can select the approach most appropriate for their setting. Options include Efron’s Empirical Bayes FDR, Benjamini-Hochberg FDR control for multiple testing, Lindsey’s method for smoothing empirical distributions, estimation of the mixing proportion, and central matching. We illustrate the important difference between estimating the FDR for a particular finding and adjusting a hypothesis test to control the false discovery propensity. RESULTS/ANTICIPATED RESULTS: We performed a comparison of the capabilities of our new p.fdr function to the popular p.adjust function from the base stats-package. Specifically, we examined multiple examples of data coming from different unknown mixture distributions to highlight the null estimation methods p.fdr includes. The base package does not provide the optimal FDR usage nor sufficient estimation options. We also compared the step-up/step-down procedure used in adjusted p-value hypothesis test and discuss when this is inappropriate. The p.adjust function is not able to report raw-adjusted values and this will be shown in the graphical results. DISCUSSION/SIGNIFICANCE OF IMPACT: FDRs reveal the propensity for an observed result to be incorrect. FDRs should accompany observed results to help contextualize the relevance and potential impact of research findings. Our results show that previous methods are not sufficient rich or precise in their calculations. Our new package allows the user to be in control of the null estimation and step-up implementation when reporting FDRs.

OBJECTIVES/GOALS: Engagement with art may reduce the social disconnection that accompanies chronic pain. Disaggregating specific from non-specific effects of arts-based programs is challenging. This study creates an experimental virtual museum to identify the separate and joint effects of art and social connection. METHODS/STUDY POPULATION: Two x two factorial experiment with repeated measures: (1) Artwork present condition is a virtual exhibition featuring paintings from the Google Arts & Culture collection; (2) Artwork absent condition is the same exhibition space but with the paintings removed; (3) Social connection condition asks participants to write about a situation in which they felt more socially connected to others; (4) Social disconnection conditions asks participants to write about a situation in which they felt more socially disconnected from others. Participants: (1) English language proficiency; (2) ≥18 years; (3) Chronic moderate to severe pain; (4) Lonely; (5) Has electronic device with internet connection. RESULTS/ANTICIPATED RESULTS: Participants will be recruited through a 3-month social media campaign conducted by StudyPages, a clinical trial recruitment and management platform. This study will evaluate the effects of virtual art exposure and social connectivity priming on pain and social disconnection reduction among lonely IWCP. Pre-intervention scores for pain intensity, pain unpleasantness, and perceived social disconnection will be compared to post-intervention scores. Secondary outcome measures include (a) Museum visit data (e.g., user movement, click, object interaction, open comments) and (b) perceptions about artwork. DISCUSSION/SIGNIFICANCE: Psychosocial support for IWCP may improve pain-related outcomes. This studys data will help to optimize virtual museum interventions and provides the first data we are aware of to evaluate the specific effects of art in virtual museum engagement to reduce pain and social disconnection among IWCP.

OBJECTIVES/GOALS: Misprescription of opioids has led to an epidemic of opioid use disorder (OUD). Females, among other differences, have increased susceptibility to the addictive properties of opioids. Yet, the exclusion of female subjects from many foundational studies on reward processing had hindered our ability to fully understand these disparities. METHODS/STUDY POPULATION: Estradiol (E2), a neuronal sex steroid, may play a role in sex differences in OUD. In this study, we used fadrozole, an aromatase inhibitor, to characterize the role of centrally produced E2 in heroin cue extinction memory retention (EMR, “remembering to forget”). Male and female rats self-administered heroin in a long-access paradigm (6hr/day) for 8 days, where a light/tone cue was co-presented with each infusion of heroin. This was followed by 1 day of cued extinction (6hr; light/tone but no heroin). Just prior to this session, fadrozole was infused into the basolateral amygdala (BLA) through implanted cannulas. The next day, subjects were given a cued EMR test (1hr; light/tone but no heroin) following another infusion of fadrozole. RESULTS/ANTICIPATED RESULTS: Females took more heroin than males (mg/kg) despite having similar active nose poke responding during acquisition. Regardless of aromatase inhibition, females had higher active nose pokes during the first hour of cued extinction relative to males. Both males and females treated with fadrozole in the BLA prior to cued extinction had impaired EMR on test, evidenced by increased active nose pokes and lower extinction indices relative to vehicle controls. Upon examination of the brains, we expect that aromatase inhibition will have impaired neuronal plasticity, as evidenced by decreases in numerous measures of plasticity. Furthermore, we expect to find sex differential expression of estrogen receptor (ER) subtypes throughout the BLA, suggesting a convergent sex effect of E2 on heroin EMR. DISCUSSION/SIGNIFICANCE: This study is the first to examine a behavioral role for central E2 in the BLA. Future studies will examine specific roles for ER subtypes on this behavior and synaptic plasticity. A better understanding of sex specific E2 signaling will promote further research on sex differences and allowing us to better address disparities in disorders like OUD.

ABSTRACT IMPACT: Current, complete, unbiased, and accurate information, which includes patient social and environmental context, is necessary to understand health outcomes. OBJECTIVES/GOALS: Literacy in technology empowers patients in improving their health. We hypothesize that by integrating this information into clinical information, obfuscated relationships may become apparent. To test this, we have combined technological literacy elements with clinical data and test results from patients at risk for severe COVID-19 reactions. METHODS/STUDY POPULATION: Zip level data was appended to approximately 55,000 clinical records of COVID-19 positive and negative patients with comorbidities linked to high illness severity (e.g., diabetes, heart disease). The patient zip code was matched to zip code level health and technology interest indicators. Health interest indicates the level of interest in health such as research, exercising, better dieting, preventive care, etc., and is ranked from 0 to 9. The technology interest indicator is a binary flag indicating technology adopters. These lifestyle factor data points were obtained from survey data and purchasing patterns using transactional and response information from self-reported sources. For each zip code, the index values were represented by a percentage of that population. RESULTS/ANTICIPATED RESULTS: There is a pronounced difference between urban and rural areas with respect to interest in health and technology. In neighborhoods where most residents are interested in both health and technology, the percentage of COVID-19 cases was smaller. A Wilcoxon signed-rank test indicated that the distributions were statistically different (p-value = 4.606e-06) when evaluating the low interest values for health and technology, and (p-value = 1.069e-09) when there was high interest in health and technology against COVID-19 results. In addition, the health and technology indicator variables are not correlated with income at the zip code level. At the low index values, interest in health and technology, the correlation was -0.0856, and at the high end, the correlation was -0.0436. DISCUSSION/SIGNIFICANCE OF FINDINGS: This result is significant for COVID-19 research because it describes a methodology for identifying patients who may be at higher risk for contracting the disease. This relationship was reflected in electronic health record data only after zip-level information was added. Moreover, this was true at across income levels.

OBJECTIVES/SPECIFIC AIMS: This report describes the evolution of scientific culture since the NIH/translational science (TS) mandate. The transition of the conduct of science to an increasingly translational model involves 2 dimensions of change. The first dimension consists of change in the structure and process of scientific work, in terms of factors such as funding, administration, application of new knowledge, and so forth. The second dimension consists of change in culture of scientific work. The culture of science is the set of values, assumptions, meanings, and traditions that inform the conduct of science. As part of the comprehensive evaluation of TS at the University of Texas Medical Branch-Galveston, we have monitored the status of the culture of science there through a sociological framework. We focused on the ways the changing culture of science facilitates and/or inhibits creative and effective medical research. We argue that the long-term success of TS is dependent upon the evolution of assumptions, everyday practices, and taken-for-granted ways of conducting research. Culture also provides meanings for who its people are and helps us define who we are to ourselves (ie, self-concept). In terms of the scientific enterprise, self-identity provides the motivation to participate in group activities or to be content with being a “lone ranger” researcher; the orientation to be either a leader or a follower; the security to take creative chances with one’s work or to simply conduct “normal science”; and the sense of esteem for being the best or simply doing one’s job. TS requires a constant “reengineering” of its total enterprise. Consequently, we raised the following research questions: (1) What is the traditional culture of science at UTMB? (2) How has the culture of science at UTMB changed since the introduction of the Clinical and Translational Science Award project? (3) What has been the relationship between the culture of science and the conduct of science at UTMB since CTSA? (4) How have cultural influences on self-concept changed? METHODS/STUDY POPULATION: Data have been collected by means of ongoing 1-on-1 interviews with CTSA participants at all levels; observations of lab and classroom interaction; participation in organizational and planning committees; and other everyday organizational activities. RESULTS/ANTICIPATED RESULTS: Following the grounded theory method of qualitative analysis and discovery, we found 3 stages of cultural change. Stage 1 is Cultural Invasion of the existing culture at UTMB by the implementation of the CTSA project. Stage 2 is Cultural Accommodation by which internal responses to change follow the normal scientific paradigm. Stage 3 is Cultural Expansion by which the organizational and cultural platform for conducting science has expanded regionally, nationally and cross-disciplinarily. DISCUSSION/SIGNIFICANCE OF IMPACT: Whether a distinct fourth stage emerges depends on such factors as funding and programmatic directives from NIH; the tension between research and clinical demands for resources; and the emergence of junior investigators schooled on the principles of TS.

OBJECTIVES/GOALS: To evaluate whether the default mode network experiences age-related changes in functional connectivity and to identify these patterns of progression across seven decades of life. The overall goal is to evaluate whether quantifying these functional changes can serve as potential neurobiomarkers of aging for further quantitative genetic analyses. METHODS/STUDY POPULATION: Scans were performed at the RII on a 3T Siemens Trio scanner with an 8-channel head coil. Whole-brain, rsfMR imaging was performed using a gradient-echo EPI sequence sensitive to the BOLD effect (TE/TR = 30/3000 ms; flip angle = 90°; isotropic 1.72 mm2). Subjects were instructed to lie in dimmed light with their eyes open and try not to fall asleep. Image analysis was performed with FMRIB’s Software Library tools (www.fmrib.ox.ac.uk/fsl). Preprocessing of resting state data includes motion correction, brain extraction, spatial smoothing, and high-pass temporal filtering. Time series data was extracted from 9 DMN ROIs using FSL’s Featquery tool with 6mm radius spherical ROI masks created in Mango. After extraction, DMN connectivity was assess using structural equation modeling implemented in Amos 22.0 (IBM, Inc.). RESULTS/ANTICIPATED RESULTS: The exploratory SEM (eSEM) default mode network (DMN) model used consists of 9 regions of interest and 13 functional connectivity paths. The eSEM DMN model exhibited exceptional model fit to a primary resting state data set of 1169 subjects from the Genetics of Brain Structure project (1R01MH078111-01, David Glahn PI) with an RMSEA of 0.037. This model also had excellent model fit in 7 cohorts that were grouped by decade age (10s – RMSEA: 0.058, 20s – 0.051, 30s – 0.045, 40s – 0.048, 50s – 0.043, 60s – 0.035, 70s – 0.037). Analysis of the decade group-wise path coefficients identified 7 of the 13 paths (pC -> LMTG, pC -> PCC, PCC -> MPFG, PCC -> vACC, MPFG -> vACC, LIPL -> RIPL, LMTG -> RMTG) significantly negatively correlated with age-related changes. As early as the 1st decade of life, the functional connectivity within the DMN decreases. DISCUSSION/SIGNIFICANCE OF IMPACT: The DMN experiences progressive age-related decreases in connectivity, beginning in the first decade of life. Our results suggest that DMN path coefficients can serve as biomarkers of cognitive aging, which can then be used as quantitative traits for genetic analyses to identify genes associated with normal aging and age-related cognitive diseases.

OBJECTIVES/SPECIFIC AIMS: Describe the process used to develop job descriptions and how this translates into consistent hiring practices. Describe how competencies are used to provide transparency into professional development opportunities. Discuss planned incorporation of competencies into efforts to train the clinical research workforce. METHODS/STUDY POPULATION: These processes were developed at Duke, an academic medical center with over 2000 active clinical research protocols and 300 new clinical trials per year. Over 1000 employees were evaluated for mapping into clinical research positions, with 685 mapping into new research positions (makeup of workforce to be depicted). RESULTS/ANTICIPATED RESULTS: Prior to this initiative, the clinical research workforce was not well-defined. Through the mapping process, employees were mapped from over 80 different positions into 10 (figure), resulting in a workforce that allows for visible career ladders and greater opportunity for development. As the initiative evolves and grows to include competency-driven performance evaluations, training modules, and assessments, we anticipate the ability to see the relationship between the competencies and high-quality clinical research support. DISCUSSION/SIGNIFICANCE OF IMPACT: The use of competencies in the context of workforce development is not new, yet in clinical research, they provide a much-needed framework for an ever-evolving profession. This comprehensive use of competencies throughout a workforce development initiative is key to ensuring strong support of high-quality clinical research.

OBJECTIVES/GOALS: To teach the historical development of CTR, make a compelling scientific presentation, and use bibliographic databases and library resources. In addition, students learn how to write the research question, design the career development plan, know the protection of human subjects in research, and understand the mentor-mentee relationship. METHODS/STUDY POPULATION: The course includes a variety of educational strategies and activities that allow the student to increase their knowledge and initiate their interest in the field of CTR. Both academic semesters (August to December and January to May) are offered remotely in two-hour synchronous sessions on Fridays from 3:00 p.m. to 5:00 p.m. through videoconferences, in addition to asynchronous activities. Invited expert lecturers and faculty reinforce the course content in each of the topics they address. In addition, course coodinators assign guided tasks where the students perform the work. Then, they present or send their work to the course coordinators for evaluation. RESULTS/ANTICIPATED RESULTS: The course began in January 2020 and has six offerings, including one in the current academic semester (August to December 2023). Its first offering was in the semester from January to May, and due to the interest generated in students in August 2022, it is now avalilable in both semesters. From its beginning to the present, the course has included students from the University of Puerto Rico (UPR) Bayamón, Cayey, Humacao, Mayagüez, and Rio Piedras campuses, impacting all geographic areas of Puerto Rico. The course has also represented an opportunity for graduate faculty to teach CTR to undergraduate students. Until 2023, 56 students have enrolled. DISCUSSION/SIGNIFICANCE: Upon completing six-course offerings, the evaluation carried out by the students demonstrates satisfaction with the learning obtained. The knowledge and skills achieved have led them to participate in CTR with the mentoring of collaborating course professors and starting a new professional development opportunity for undergraduate students.

OBJECTIVES/SPECIFIC AIMS: To study the role of OSA as an independent predictor of perioperative outcomes. METHODS/STUDY POPULATION: For this single-institution cohort study, we included data from patients who were enrolled into 1 of 3 prospective parent studies. All participants underwent in-patient surgeries, excluding neurosurgeries, which required general anesthesia and a postoperative stay of at least 1 day. Patients included in this study were assessed daily for postoperative delirium and pain severity as part of the parent studies. In the current study, determination of delirium diagnosis was based on the 3-minute Diagnostic Confusion Assessment Method (3D-CAM), and the Visual Analogue Pain Scale (VAS) was used for pain severity. Data on OSA diagnosis (determined by sleep study); OSA risk (determined by the STOP-Bang tool; snoring, tiredness, observed apnea, high blood pressure, body mass index>35 kg/m2, age>50, neck circumference, male gender); and compliance with treatment were obtained from the preoperative assessment record. Participants were grouped into 1 of 3 categories: high risk of OSA (HR-OSA; including patients with a previous positive sleep study or STOP-Bang score ≥5); intermediate risk of OSA (IR-OSA; including patients with a STOP-Bang score of 3 or 4); and low risk of OSA (LR-OSA; including patients with a previous negative sleep study or STOP-Bang score <3). Candidate risk factors for delirium and pain were also extracted from this record. RESULTS/ANTICIPATED RESULTS: Logistic regression will be used to test whether OSA independently predicts postoperative delirium and linear regression to assess OSAs relationship to acute pain severity. We hypothesize that patients in the HR-OSA category will experience a higher incidence of postoperative delirium and greater postoperative pain severity. We also predict a step-wise increase in risk of these adverse outcomes when analyzing patients stratified by OSA risk (HR-OSA vs. IR-OSA vs. LR-OSA). For our secondary analyses, we anticipate these outcomes are modified by compliance with CPAP treatment. We believe patients with OSA who do not use prescribed CPAP will experience a higher incidence of postoperative delirium as well as increased pain severity. DISCUSSION/SIGNIFICANCE OF IMPACT: OSA is a common and frequently undiagnosed perioperative problem associated with altered pain processing and a high incidence of postoperative delirium. While likely providing stronger evidence of OSA’s reported impact on postoperative delirium and pain, our findings might also help discern points of intervention for treatment and prevention. Since OSA’s presumed impact poses challenges to clinicians and patients, prospective, randomized trials testing preventative or mitigating interventions are necessary. We hope to use these results to design such trials and clinical plans, with the goal of reducing postoperative delirium and acute postsurgical pain severity for the large number of patients at risk due to OSA.

ABSTRACT IMPACT: This work will be used to improve the design of engineered dermal replacements that can be used to treat difficult-to-heal wounds such as burns or ulcers. OBJECTIVES/GOALS: Wounds of the skin are among the most common and costly medical problems experienced. Engineered dermal replacements have been developed to improve outcomes, but the optimal design features are unknown. Here we describe a hypothesis-driven study of scaffold parameters using a computational model of wound healing to simulate a variety of treatments. METHODS/STUDY POPULATION: The computational model, which was informed by animal data, was used to simulate cell, cytokine, and collagen density fields. There are reciprocal mechanobiological interactions between the cells and collagen that guide the wound healing process. We analyzed initial wound properties such as scaffold stiffness, microstructure, degradation, and wound geometry by running a one-at-a-time order-of-magnitude parameter change. We then conducted a derivative-based local sensitivity analysis for simulated experimental conditions and constructed a surrogate model of wound contraction using Gaussian process regression. RESULTS/ANTICIPATED RESULTS: We conducted finite element model simulations of scaffolds that varied in physical properties. A sensitivity analysis demonstrated that wound contraction was highly sensitive to collagen fiber stiffness and density. Wound contraction rate was also dependent on initial wound size and surface area. Collagen fiber orientation in the scaffolds affected contraction directionality and the orientation of the final wound area. A Gaussian process regression model was fit to the simulation results for use in rapid prototyping of scaffolds for design optimization. The Gaussian process model was able to reproduce the wound contracture for training and test cases. DISCUSSION/SIGNIFICANCE OF FINDINGS: This work further analyzes a computational model of wounds treated with collagen scaffold dermal replacements. The hypothesis driven analysis of the model suggested several key design features of scaffolds. The model surrogate will further be used for the purposes of prediction and optimization of tissue regeneration outcomes.

Objectives/Goals: Evaluate the effectiveness of ChatGPT as a complementary tool for addressing the mental health needs of Hispanic LGBTTQI+ young adult patients. We will also explore the experience of clinical healthcare providers with the integration of ChatGPT as a complementary tool in psychotherapy with Hispanic LGBTTQI+ young adults. Methods/Study Population: In this mixed-method study, we will create hypothetical clinical cases that reflect common mental health challenges experienced by LGBTTQI+ Hispanic population. These cases will be presented to three groups: 1) ChatGPT app, 2) clinical mental health care providers, and 3) clinical mental health care providers collaborating with ChatGPT. Each group will provide a diagnosis and a treatment plan based on the case information. A panel of experts will evaluate each plan using a standardized rubric to provide a score on clinical accuracy and on the ability to address specific needs of Hispanic LGBTTQI+ patients. Statistical analysis will be used to evaluate the differences in the scores of each domain and qualitative content analysis to evaluate the experience of clinical mental health care providers using ChatGPT. Results/Anticipated Results: The results will provide evidence of the effectiveness of ChatGPT as a supportive tool in mental health care. We anticipated that the combination of a clinical mental health care provider and ChatGPT to develop a diagnosis and treatment plan would produce better outcomes than either ChatGPT or the clinical mental health care provider working independently. We will also expect to find a positive attitude toward the integration of ChatGPT applications, viewing them as useful tools that complement traditional psychological interventions for Hispanic LGBTTQI+ young adults. The study will provide evidence of the effectiveness of ChatGPT to complementing clinical practice involving Hispanic LGBTTQI+ young adults. Those results in a preclinical phase are preconditions to a more applied intervention. Discussion/Significance of Impact: We aim to improve the quality of life for LGBTTQI+ Hispanics by developing innovative psychological treatments enhanced by AI apps. By developing innovative treatments, we are addressing and mitigating health disparities within the LGBTTQI+ Hispanic community in Puerto Rico and contributing to a broader effort of inclusivity and health equity.

OBJECTIVES/SPECIFIC AIMS: Pembrolizumab is an anti-PD-1 immune checkpoint antibody that has demonstrated promising anti-tumor activity in patients with solid tumor malignancies, including patients with brain metastases from malignant melanoma and non-small cell lung cancer. Leptomeningeal disease (LMD) is a rare form of malignant spread to the central nervous system (CNS), that occurs in 2%–10% of patients with solid tumors, most commonly in breast cancer and non-small cell lung cancer. We propose an open-label phase II study of pembrolizumab in patients with LMD from advanced solid tumors (NCT03091478). This study aims to determine if pembrolizumab therapy can lead to a radiologic, cytologic or clinical response in the CNS, in patients with LMD. METHODS/STUDY POPULATION: Patients with pathologically confirmed advanced solid tumors, and either radiologic or cytologic evidence of LMD, will be identified at a single institution. Radiologic LMD will be defined as a >4 mm area of measurable LMD on gadolinium-enhanced MRI brain/total-spine; and cytologic LMD will be defined as the presence of malignant cells on CSF cytology. Patients will be excluded if they have: active autoimmune conditions that require immunosuppression, received radiation therapy to the only area of measurable LMD within 3 months of study enrollment, have an ECOG performance status <1. Once enrolled, patients will receive pembrolizumab 200 mg intravenously every 3-weeks, until disease progression or unacceptable toxicity. Patients will have CSF sample sampling, blood draws, radiologic imaging of the body (CT), brain/total-spine (gadolinium-enhanced MRI) pre-treatment, after 2 and after 4 cycles of therapy, for response assessment and correlative studies. The primary endpoint of the study is CNS response assessed at 12 weeks/after 4 cycles of pembrolizumab, defined either as radiologic response (reduction in size of LMD on gadolinium-enhanced MRI) and/or cytologic response (conversion of positive to negative CSF cytology on 2 consecutive samples) and/or clinical response. Secondary endpoints will include progression-free survival, overall survival, and safety. To explore the mechanisms by which pembrolizumab may affect LMD, we will assess dynamic changes in genomic and immunologic markers in the CSF and serum pre and post pembrolizumab using next-generation sequencing and multi-color flow cytometry, respectively. RESULTS/ANTICIPATED RESULTS: We will aim to accrue a total of 20 patients, allowing for a 10% drop-out rate, the final sample size will include 18 patients who have received at least 1 dose of pembrolizumab. CNS-response at 12 weeks will be assessed radiologically +/− cytologically, and the proportion of patients with CNS response and associated 95% confidence interval with be reported. CNS-progression-free survival and overall survival will be assessed using the Kaplan-Meier method. Cause of death will be recorded. Safety will be assessed as detailed above, and monitored as per an institutional Data Safety and Monitoring Plan. Exploratory endpoints will include genomic testing of tumor cells and cell-free DNA in CSF and serum, and immunologic studies of immune cells in CSF and serum at pre-defined timepoints. These data will be presented descriptively. We conservatively estimate that we will accrue 1 patient per month at our institution. Study duration will be approximately 24 months, allowing 18 months for accrual and 6 months for follow-up and data analysis. DISCUSSION/SIGNIFICANCE OF IMPACT: There are no currently FDA-approved therapies for patients with LMD from solid tumors. Anti-PD-1 immunotherapy is a promising class of agents, with known efficacy in patients with CNS metastatic disease, across tumor types. This study seeks to identify whether pembrolizumab may lead to CNS responses in patients with LMD. Additionally, genomic and immunologic analyses in CSF and blood pre and post-pembrolizumab may identify mechanisms by which immunotherapy affects the CNS in patients with LMD.

OBJECTIVES/GOALS: Predictive models for health outcomes often have poor calibration potentially due to interactions that are ignored by standard methods. Using AHRQ models for Inpatient Quality Indicator (IQI) 11 Abdominal Aortic Aneurysm Repair and IQI 09 Pancreatic Resection mortality, we hypothesize that identifying interactions may improve model calibration. METHODS/STUDY POPULATION: We used adult discharge data from 16 states obtained from AHRQ Healthcare Cost and Utilization Project (State Inpatient Database), California Department of Health Care Access and Information, and New York State Department of Health. We used AHRQ’s v2021-1 Clinical Classifications Software Refined (CCSR) with present on admission flags to create features for risk-adjustment. We compared the performance of Least absolute shrinkage and selection operator (LASSO) model and first-order interaction models estimated using Hierarchical Group Lasso Regression (HGLR), after splitting the data into training and test sets. C-statistics, area under the precision-recall curve and Hosmer-Lemeshow calibration plots are reported. Finally, logistic regression models with selected CCSRs were evaluated on the test set. RESULTS/ANTICIPATED RESULTS: IQI 11 has four strata: open and endovascular repair of ruptured aneurysms (39% and 21% mortality, respectively); open and endovascular repair of unruptured aneurysms (6% and 0.8% mortality, respectively). IQI 09 has two strata: with and without pancreatic cancer (2% and 2.5% mortality, respectively). Comparing the HGLR model (with interaction effects) with Lasso models (without interactions), we noticed meaningful improvements in discrimination and calibration. However, for IQI 09, the extremely low mortality rate did not result in good HGLR or LASSO models. Interactions involving CCSRs could be identified using the novel HGLR method, which improved model performance given a heterogeneous population in IQI 11 with a mix of high and low event rates, unlike the more homogeneous patient population in IQI 09. DISCUSSION/SIGNIFICANCE: Standard implementations of regression models fail to address critical issues that arise in healthcare data – (a) quadratic explosion of potential interactions that cannot be manually identified, and (b) categorical variables with multiple levels or values (e.g., age categories). We propose innovative use of HGLR to robustly address these issues.

ABSTRACT IMPACT: A one-stage Bayesian multilevel model for meta-analysis integrating different survival data is introduced to complete the information synthesis without assuming proportional hazard. OBJECTIVES/GOALS: To develop a general modeling approach to perform efficient and robust meta-analyses using aggregated data (AD) for survival type endpoint and apply to a meta-analysis to examine the association between measurable residual disease (MRD) and disease-free survival (DFS) and overall survival (OS) in patients with acute myeloid leukemia (AML). METHODS/STUDY POPULATION: A Bayesian semi-parametric hierarchical model with a time-varying HR effect was presented. Three common types of survival information, including reconstructed survival data, the hazard ratio (HR) estimates with corresponding CIs and survival rates at specific time points, are synthesized such that all literature from the systematic review can contribute properly to the estimation and uncertainty quantification of the model parameters. The time-varying effects was modeled by assuming piecewise hazard risk and piecewise constant hazard ratio. The heterogeneity across studies was expressed by an additive random study effect and a random treatment-by-study interaction. The method was applied to a systematic review of 81 publications reporting on 11,151 AML patients. RESULTS/ANTICIPATED RESULTS: In simulation studies that the proportional hazard assumption is either valid or violated, the proposed method was efficient to achieve comparable performance to IPD meta-analysis, a gold standard approach, in estimating the survival rates, the restricted mean survival time at specific time points and median survival time with the point estimates close to the true values. When HR is not proportional over time, the proposed method was robust in estimating HR and significantly outperformed the classical random-effects meta-analysis. In the application to AML study, the average HR for achieving MRD negativity was 0.36 (95% CrI, 0.33-0.39) for OS and 0.37 (95% CrI, 0.34-0.40) for DFS. The association of MRD negativity with OS and DFS was significant and consistent across all subgroups. DISCUSSION/SIGNIFICANCE OF FINDINGS: The proposed novel method provided a flexible framework for meta-analysis of survival data, to accommodate various types of survival data in one model without assuming proportional hazards assumption. The findings of AML meta-analysis suggest that achievement of MRD negativity is associated with superior DFS and OS in patients with AML.

OBJECTIVES/SPECIFIC AIMS: We aim to leverage our analysis of the scientific collaboration network at a research university to design an innovative pilot program and foster scientific productivity. We test the impact of creating a new collaboration in a research community, which decreases the average network distance and accelerates the diffusion of information and expertise among the community’s investigators. METHODS/STUDY POPULATION: We mapped the whole network of co-authorship on publications and co-participation on extramurally awarded grants at the University of Florida (UF) between 2013 and 2015. We used network science methods to identify research communities of investigators who have consistently worked together and/or have other collaborators in common with at least one researcher based in the UF Health Science Center. We selected pairs of communities with (i) similar productivity levels, research interests, and network structures and (ii) no research projects in common. Communities in each pair were randomly assigned to a treatment or control group. In each treatment community, we selected 1 pair of investigators who had not collaborated in the past 3 years and whose connection would maximally reduce average network distance in the community. The pair was provided with an economic incentive to collaborate for the submission of a CTSA pilot proposal. RESULTS/ANTICIPATED RESULTS: We successfully identified 15 pairs of treatment/control communities. In each of 8 treatment communities, a pair of potential collaborators agreed to participate in the intervention. DISCUSSION/SIGNIFICANCE OF IMPACT: Network-informed Clinical Translational Science Awards (CTSA) pilot programs can identify research communities and create innovative collaborations. Statistical experiments can establish the programs’ causal effects on scientific productivity.