OBJECTIVES/GOALS: Incomplete mucosal healingand dysbiosis prevent long-term remission after colitis. IL4 may restore colon homeostasis through its action on immune cells and the microbiome. We will demonstrate this mechanism using genetically modified mice and molecular tools. This may result in target therapies that prolong remission in patients with IBD. METHODS/STUDY POPULATION: Mice were treated with 3% dextran sulfate sodium (DSS) in drinking water for 5 days to induce colitis. Mice were monitored daily for changes in body weight, and to monitor colitis severity. At each endpoint, mice were sacrificed and colon length was measured. For disease severity assessment, mouse colons were prepared in paraffin sections by the 'swiss-rolling' method. For flow cytometry, lamina propria mononuclear cell isolation was performed and cellular populations were stained with fluorophore-conjugated antibodies. IL4-eGFP-expressing (4get) mice were used to analyze the cellular expression of IL4 after colitis. Cell-specific IL4 deletion mice were generated using the cre-lox system. RESULTS/ANTICIPATED RESULTS: IL4-deficient mice had worse colitis compared with wild-type controls. Flow cytometry of lamina propria cells from 4get mice showed that most IL4-producing cells after colitis are eosinophils (CD11b+SiglecF+). Flow cytometry of C57bl6 mice showed an influx of IL4Ra+ monocytes (CD11b+Ly6C+) and macrophages (CD11b+F480+). IL4-stimulated bone marrow-derived macrophages demonstrated an increase in HB-EGF mRNA transcription. Myeloid-specific IL4R deleted mice had no difference in colitis severity compared with controls. Neutrophil-specific IL4R-deleted mice had increased colitis severity and mortality. Co-housing of littermate mice rescued recovery after DSS in IL4 deficient mice. DISCUSSION/SIGNIFICANCE: IL4 appears to play a role in restoring homeostasis after colitis. The mechanism depends on eosinophil-derived IL4, and action through neutrophils. However, the reparative function of IL4 can be shared with deficient mice through the microbiome. I will study the cellular and microbial mechanism by which IL4 restores homeostasis after colitis.

Objectives/Goals: Acute myeloid leukemia (AML) is an aggressive blood cancer that hides from the immune system, which led to ~140,000 deaths worldwide in 2024. AML often recurs or resists therapy; therefore, our goal is to develop and test TriKE-PACCs, which combine dual tumor antigen targeting with NK cell activation, to overcome antigen escape and heterogeneity in AML. Methods/Study Population: TriKE-PACC molecules were engineered by combining a TriKE [anti-CD16 single-domain antibody (sdAb), an IL-15 moiety, and an antitumor antibody domain single-chain variable fragment (scFv) or an sdAb] with a PACC arm containing a second antigen-binding scFv/sdAb linked to IL-15Rα. TriKE-PACC constructs were produced in Expi293 cells. To identify clinically relevant AML tumor targets, we analyzed the expression of tumor antigens in AML bone marrow samples obtained from 20 patients using flow cytometry. We modeled antigen escape and heterogeneity using CRISPR/Cas9-generated knockout AML lines. TriKE-PACC-mediated NK cell activity was measured via degranulation, cytokine production, and Incucyte-based cytotoxicity assays against AML cell lines and CRISPR knockout models. Results/Anticipated Results: Our examination of AML patient bone marrow samples revealed diverse antigen profiles, highlighting the need for modular TriKE-PACC designs. The dual-targeting TriKE-PACCs enhanced NK cell activation via CD107a expression and the production of IFNγ and TNFα in co-culture assays with AML cell lines. Notably, TriKE-PACCs retained activity against AML models lacking a targeted antigen, demonstrating the ability of the second tumor targeting arm to overcome antigen escape. Furthermore, NK cell-mediated killing was improved against antigen-deficient AML cells when treated with the TriKE-PACCs compared to standard TriKEs. Discussion/Significance of Impact: TriKE-PACCs offer a modular and customizable NK-engaging immunotherapy to address AML heterogeneity and resistance. Our data, collected utilizing primary patient samples, support the use of this platform for the future development of personalized, dual-targeted therapies to enhance the efficacy of AML treatments.

OBJECTIVES/GOALS: Team science competencies are not well-defined for nonfaculty staff of Clinical Research Professionals (CRPs) who conduct research. Using an existing framework, our work has determined skills associated with team science competencies as related to CRPs. Our team also outlined examples of those skills on a fundamental, skilled, and advanced level. METHODS/STUDY POPULATION: The team consists of both CRPs and those working in the Team Science space. This team used a modified Delphi approach to determine the skills and leveling examples of each team science competency. The team broke into four groups and was assigned 3-4 competencies each. Each group determined skills needed to support (exhibit, promote) each competency and then described an example of this skill at the fundamental, skilled, and advanced levels. Once each group was finished with their assigned competencies, they were re-assigned to a different group for review and changes. Finally, team science and CRP experts reviewed the skills and levels. RESULTS/ANTICIPATED RESULTS: Our results are a rubric that defines 3-5 practical skills per described competency. These skills are needed to support and promote each competency as a CRP. An additional outcome from this work includes examples of each skill at the fundamental, skilled, and advanced levels in a CRP’s career. Each leveled example is described in a concise, actionable way using Bloom’s taxonomy. This rubric is meant to be easily understood, very useable and able to be used in conjunction with existing CRP competency frameworks. By using Bloom’s taxonomy, we set the stage for future educational programming in Team Science skill-building for clinical research professionals. DISCUSSION/SIGNIFICANCE: Team science concepts and competencies have been increasingly integrated into translational science teams. However, team science competencies related to CRPs have remained largely undefined. Our work helps to define these competencies for CRPs in a practical way. Our rubric fills gaps in, and builds on, existing CRP competency frameworks.

OBJECTIVES/GOALS: The UCLA Clinical and Translational Science Institute’s Population Health Program is creating versatile scientists who can solve population health problems. This means building learning capability in health care and public health agencies, and fostering a cross-sector, outcomes-based, regional ecosystem for implementation and improvement. METHODS/STUDY POPULATION: A synthesis of achievements and lessons learned reveals the Program’s trajectory. It maps progress in science leading to sustainable interventions for target populations. PHP goals are predicated on networked team science, rather than disorganized assortment of individual studies and interventions, and emphasize design, modeling and iteration. Evolving metrics include network analysis to document collaborative impact; extent of integrating real-world application into systems science and learning system curriculum; legislative and institutional policies developed and adopted; evidence of system orientation, cross-sector focus, and implementation research in scientists’ portfolios; and demonstration of population health impact. Barriers offer the opportunity for iteration and improvement. RESULTS/ANTICIPATED RESULTS: The PHP has progressed in its envisioned shared university-public health stewardship of translation and transformation. Milestones included galvanizing activities such as annual regional dissemination, implementation, and improvement (DII) symposia and Public Health Science Summits; pre- and post-doctoral experiential learning of system science and learning system methods based in Los Angeles County Health Agency initiatives; development of a regional CTSA network for implementation science training; strengthened public health policy practice (e.g., establishing a new Office of Youth Diversion and Development); learning healthcare system capability; and prototypes of population learning systems focused on hypertension, food insecurity, tobacco/vaping, and complex care management. DISCUSSION/SIGNIFICANCE OF IMPACT: PHP is committed to advancing science for population health. Prototypes were an essential initial phase. New areas include use of methodological advances (e.g., artificial intelligence, rapid assessments) in health and public health systems; an academic home for full-time, population-focused clinicians; and social policy innovations.

Objectives/Goals: Our objective in this study was to develop a nanoparticle-based RNA delivery system that reprograms Müller glia toward neuronal fates in human relevant models, enabling localized and transient regeneration without viral vectors. Methods/Study Population: - Results/Anticipated Results: Fabricated nanoparticles encapsulating RNA cargoes were ~110–150 nm in size with polydispersity indices of ~0.2–0.3 and encapsulation efficiencies >95%. Nanoparticles successfully delivered GFP mRNA in both organoid and retinal explant models, showing significant expression of fluorescent reporters in both live cell imaging and in slides prepared using immunohistochemistry. We anticipate that our delivery system will lead to transcription factor expression after delivery of corresponding RNAs with evidence of proliferation and neuronal marker upregulation. We also hypothesize that this approach will enhance neurogenesis in retinal organoids and explants, potentially establishing a platform for non-viral retinal regeneration. Discussion/Significance of Impact: This work demonstrates a clinically translatable, virus-free strategy for retinal repair through targeted RNA delivery. By enabling transient expression of neurogenic factors, nanoparticle-mediated reprogramming presents a scalable and adaptable approach for restoring vision in degenerative retinal diseases.

OBJECTIVES/SPECIFIC AIMS: The objective for the present study is to evaluate qualitatively the Team Leadership Assessment Center (LAC) at UTMB-Galveston. There has been much discussion about the need for leader development within team science (Börner, et al, 2010; Falk-Krzensinski, etal., 2011). The LAC was designed to examine the study participants’ beliefs and perceptions of and competencies in team leadership by means of a multi-trait multi-method approach. Our team competency model involves seven dimensions and twenty-five specific competencies. There were two complementary components to the evaluation: a quantitative survey and a series of qualitative interviews, to be discussed here. METHODS/STUDY POPULATION: The study population for the qualitative component consisted of seventeen volunteers from the pool of fifty-one LAC participants, including trainees (KL2 scholars, TL1 scholars) as well as assistant professors, and early career associate professors. Each volunteer respondent was engaged in a twenty to thirty-minute, recorded, conversational, telephone interview. They were asked to describe and evaluate their LAC experience in their own words, perceptions, and values. The study was reviewed by the Committee for the Protection of Human Subjects at UTMB. RESULTS/ANTICIPATED RESULTS: Major findings from respondents’ overall assessment of their Center experience include:. All respondents stated that the LAC was a worthwhile experience. All respondents stated they would be willing to participate in any follow-up LAC activity. Before the LAC experience, most respondents indicated that they perceived leadership as a condition or feature of a job, appointment, or profession and not an individualistic feature of personality or experience. Ideational or conceptual definitions of leadership were superseded by administrative or managerial tropes. Major categorical indexes were related to occupational status. The generally belief is one is not trained to be a leader, but to perform leadership tasks. Significant differences among respondents tended to cluster around occupational positions and statuses at UTMB, for example:. Surgeons feel they are team oriented and their work is organized according to necessary tasks. Assistant professors and post-docs generally perceive the design of leadership as defined by the demands of their specialized field, not determined institutionally or professionally. A general take-away was the sense that, although some participants did not consider themselves to be “leaders” before the training, most felt that the “pressure” to be or become a leader was relieved a bit by the LAC. One was only expected to develop leadership skills and strategies, not change one’s Self-Identity. DISCUSSION/SIGNIFICANCE OF IMPACT:. The more complex the job status, the less critical is the need to achieve the Self-Identity of “leader.” Complaints about the LAC were very few and non-modal in occurrence. A general recommendation would be for the facilitators of programs like LAC to take cultural differences more into consideration. The most highly rated feature of the LAC is the personal attention given to participants during the one-on-one evaluation profile.

OBJECTIVES/GOALS: This study seeks to elucidate the relationships between early life adversity (ELA), social learning, and empathic responding. Specifically, it aims to understand the impact of ELA on the expression of empathy and ability to adjust behavior after social observation. METHODS/STUDY POPULATION: 60 healthy participants ages 18-65 will be recruited from the greater Baltimore area. They will undergo a placebo manipulation paradigm with simultaneous EEG recording to capture neural oscillations in frontal and insular cortices and event-related potentials. Participants will observe a demonstrator who indicates pain relief in response to the application of an inert cream. Then, while undergoing heat pain stimulations, the participant will receive the same inert cream and rate their physiological and psychological pain experience using a visual analog scale. The heat stimulations will be lowered without their knowledge to measure placebo response. Participants will also answer a battery of questionnaires which assess personality, psychological factors, life history, empathy, and current social life. RESULTS/ANTICIPATED RESULTS: It is expected that ELA will result in decreased placebo response, interpreted as deficits in social learning. Further, we expect that this effect is moderated by state empathy, empathy in a specific context or moment. We predict that individuals with lower state empathy and exposure to adversity will have greater deficits in social learning. We also expect to see more robust event-related potentials preceding painful stimulations at electrodes corresponding to the medial and ventral prefrontal cortex and insula in ELA-exposed participants. Because these brain regions are connected to anticipatory and predictive circuits, this would indicate that the individual has not adjusted their expectations according to the social information gained via observation. DISCUSSION/SIGNIFICANCE: Results of this study will expand our understanding of how ELA impacts behavior throughout life. Individuals with a history of ELA often face social difficulties and a higher risk of psychiatric disorders. This study will illuminate possible neural correlates of these differences in social behavior and, more generally, the expression of empathy.

ABSTRACT IMPACT: This study evaluates the long term effects of pharmacologic weaning therapy for opiate exposed infants. OBJECTIVES/GOALS: Infants born to chronic opioid users often suffer from neonatal abstinence syndrome (NAS), a condition characterized by tremors, diarrhea, hyperirritability and an inconsolable high-pitched cry. Symptoms are treated with pharmacologic weaning therapy, but long-term effects of this treatment have not been established. METHODS/STUDY POPULATION: A sample of infants born between 2011-2017 was obtained from a large metropolitan hospital system. All infants who were exposed to opioids and received a Finnegan score were included in the sample (N=1,807). The analysis utilizes three dependent variables to measure developmental delay: motor delay, language delay or any delay, which includes general/non-specific delay in addition to motor and language delay. The treatment is defined as receipt of pharmacologic therapy with methadone or morphine. Maximum Finnegan score was also included as a continuous measure of the extent of the infant’s withdrawal symptoms. Linear models were utilized to determine a relationship between pharmacologic therapy and developmental delay with Maximum Finnegan score as an interaction term. RESULTS/ANTICIPATED RESULTS: In the linear models examining the main effects of weaning therapy on developmental delay, there was no relationship between pharmacologic therapy and motor delay (p=.260), language delay (p=.542) or any developmental delay (p=.176). When maximum Finnegan score was entered into the model as an interaction term the relationships were not significant. DISCUSSION/SIGNIFICANCE OF FINDINGS: These results suggest that while pharmacologic weaning is an appropriate treatment for withdrawal symptoms in infants, it is not a deterrent against developmental delays associated with NAS. This provides support suggest an increased focus on non-pharmacologic interventions such as breastfeeding as the first line of treatment for NAS infants.

ABSTRACT IMPACT: Through this research, I will transform the standard of care for infants with single ventricle physiology by incorporating the Capute Scales and General Movement Assessment into day-to-day clinical care for these infants, leading to early detection of neurodevelopmental disabilities and access to proven therapies. OBJECTIVES/GOALS: Our objective was to establish a new protocol to detect and quantify developmental delays in multiple domains in infants with single ventricle physiology, a type of congenital heart disease. This population is at high risk for neurodevelopmental disabilities. METHODS/STUDY POPULATION: We implemented a novel protocol using the Capute Scales and General Movement Assessment to evaluate early language, cognitive, and motor development in infants with single ventricle physiology. The infants were evaluated between 1-5 months of age in the cardiac neurodevelopmental program. We defined our primary outcomes as (1) language and (2) cognitive developmental quotients as per the Capute Scales and (3) results of the General Movement Assessment. We hypothesized that infants with single ventricle physiology would have typical language and cognitive development and normal General Movement Assessment results at their initial evaluation. RESULTS/ANTICIPATED RESULTS: We recruited ten infants with single ventricle physiology. All ten infants had typical language development, and nine of the ten had typical cognitive development, as measured by the Capute Scales. All of the infants had gross motor delay. Due to medical instability, we only evaluated four infants with the General Movement Assessment. All four of the infants had a normal result, suggesting that their central nervous system motor pathways were maturing appropriately. In future studies, we will track the neurodevelopmental outcomes of each participant as they mature. We expect to see a decrease in expressive language development and preserved receptive language and cognitive development. DISCUSSION/SIGNIFICANCE OF FINDINGS: The combination of General Movement Assessment and Capute Scales in the evaluation of infants with single ventricle physiology will provide early identification and intervention for these high-risk children, allowing access to proven treatments and therapies.

Objectives/Goals: * Examination of the acute glucose-lowering response to physical activity within a comprehensive behavioral weight loss intervention in adults without T2DM. * Explore whether the acute response to yogadiffers from the acute response to brisk walking and to examine whether these responses vary across the intervention period. Methods/Study Population: Participants in the behavioral weight loss and aerobic exercise group will start with 100 minutes per week of moderate-intensity aerobic activity, increasing every four weeks to 250–300 minutes, spread over five days. Activities will be self-selected, such as walking. Participants in the combined aerobic exercise and yoga group will do aerobic exercise three days a week and yoga two days a week, also progressing from 100 to 250–300 minutes weekly. All participants will follow an energy-restricted diet (1200–1800 kcal/day) and participate in weekly education sessions to learn lifestyle modification skills for successful weight loss. The study will explore differences in acute responses to yoga versus walking and how these vary during the intervention, controlling for initial and changing weight status. Results/Anticipated Results: Primary and secondary outcomes from the parent study will include body weight, BMI, body composition (via DXA), cardiorespiratory fitness, energy intake, and physical activity. Glucose and insulin levels will be measured pre- and post-exercise, with HOMA-IR computed. Continuous glucose monitoring (CGM) will be used to track glucose responses during each session, with the area under the curve (AUC) as the primary metric. The study will also explore advanced CGM analytics in collaboration with the KUMC Diabetes Institute that will include in-depth analyzation of peak and trough change velocity as well as novel correlations betwen glucose dynamics and physical activity patterns with an aim to uncover insights that transcend conventional CGM analyses. Discussion/Significance of Impact: This study uses advanced CGM analytics to examine glucose control during physical activity, collaborating with experts to create comprehensive models for glucose fluctuations. It compares acute responses to walking and yoga, addressing a key gap in research, with potential clinical insights for managing glucose in obesity.

Objectives/Goals: Diamond Blackfan anemia (DBA) is caused by loss of ribosomal proteins leading to death of red blood cell progenitors. We identified a novel heterozygous variant (c.167+769C>T) in RPL30 in a patient with DBA. We hypothesized that this variant, in a gene not previously studied in DBA, would demonstrate DBA phenotype and reveal early drivers of disease. Methods/Study Population: To study the role of our novel variant, we developed an induced pluripotent stem cell (iPSC) model, including wild type (WT) and CRISPR-edited RPL30 mutant clones. We differentiated the iPSC into hematopoietic stem cells, identified cell populations with flow cytometry, and applied single-cell RNA sequencing. We identified erythroid clusters for differential gene expression analysis, using R Studio DESeq followed by Gene Ontology (GO) enrichment analysis. We are differentiating cells into red blood cells for further comparison with flow cytometry, bulk RNA sequencing, protein analysis, and hemoglobin staining. Our approach has relied on multidisciplinary expertise in clinical hematology and genetics, basic science study of ribosomes, computational biology, stem cell, and hematopoietic biology. Results/Anticipated Results: Compared to WT hematopoietic stem cells, RPL30mutant cells had significantly decreased expression of RPL30. Analysis of top differentially expressed genes revealed downregulation of HSPA1A which encodes heat shock protein 70 (HSP70), chaperone of a critical red blood cell transcription factor. Loss of HSP70 protein has been implicated in RPL-mutated red blood cells previously as a potential modulator of severe DBA phenotype. Upon GO enrichment analysis of downregulated genes, biologic process terms GO:0042254 ribosome biogenesis, GO:1903708 positive regulation of hemopoiesis, and GO:0045646 regulation of erythrocyte differentiation were all highlighted as driver terms. We expect further differentiation to reveal early death of RPL30mutant cells with associated downregulated HSP70. Discussion/Significance of Impact: Our results support our hypothesis that the RPL30 variant downregulates erythropoiesis, with a potential early role of HSP70 protein. Upon completion of our study, we will demonstrate the role of RPL30in DBA pathogenesis as well as provide understanding of its drivers, which is critical for improved management of this disease.

OBJECTIVES/GOALS: To compare the effects of dietary fiber supplementation based on fermentability and viscosity on phosphorus fractional absorption and the gut microbiome in a rat model of chronic kidney disease-mineral and bone disorder (CKD-MBD). METHODS/STUDY POPULATION: 25-week-old Cy/+ male rats (CKD hereafter) will be randomly assigned to receive one of four fiber treatments (10% w/w each) based on fermentability and viscosity: 1) Cellulose (-fermentability, -viscosity), 2) inulin (+fermentability, -viscosity), 3) psyllium husk (-fermentability, +viscosity), or 4) pectin (+ fermentability, +viscosity). Diets will be formulated with a semipurified diet containing 0.7% phosphorus. Treatments will last for 10 weeks, and rats will be euthanized at 35 weeks of age, where animals have reached kidney failure. Intravenous and oral 33P will be used for intestinal phosphorus fractional absorption and cecal/fecal samples will be obtained at euthanasia for microbiome assessment using shotgun metagenomics. RESULTS/ANTICIPATED RESULTS: Our preliminary data show that fermentable dietary fiber (inulin) impacted phosphorus homeostasis by increasing the circulating levels of fibroblast growth factor-23 (a bone-derived hormone that increases phosphorus excretion in urine) and lowering circulating levels of phosphorus in the Cy/+ male rat model of progressive chronic kidney disease. We hypothesize that dietary fiber impacts phosphorus absorption in gut microbiome-dependent and independent mechanisms. For example, fermentable fiber enhances the production of short-chain fatty acids, lowering the intraluminal pH, and enhancing mineral solubility and absorption. Meanwhile, viscous fibers may encapsulate minerals limiting their absorption if these fibers are non-fermentable. DISCUSSION/SIGNIFICANCE: Hyperphosphatemia, or high circulating phosphorus, is a major factor in the pathogenesis of CKD-MBD. Treatment of hyperphosphatemia is focused on reducing intestinal absorption. However, available therapies vary in their efficacy and focus on phosphorus absorption in the small intestine, ignoring the possible impact of the large intestine.

OBJECTIVES/GOALS: To explore the patterns, sequence, quantity, frequency and duration of poly substance use among adults for back translation of information to rodent models. METHODS/STUDY POPULATION: From May –December 2019, we conducted 13 focus group discussions with adults 19 to 63 years of age who reported concurrent use of cocaine with alcohol and/or marijuana in the past 30 days. All participants were recruited from the community through community outreach activities. Written informed consent was obtained and all focus group discussions were audio recorded, transcribed and analyzed using the qualitative data analysis software Atlas Ti™. RESULTS/ANTICIPATED RESULTS: A total of 34 cocaine users, (68% male, and 59% minority) participated. The majority reported cocaine as the drug of preference, while marijuana and alcohol were used to extend or control the ‘highs’, or ‘to take the edge off’ after cocaine use. All participants reported when they used alcohol with cocaine, they could keep drinking a large amount of alcohol without feeling its effect. Participants also reported using marijuana throughout the day while driving, at work, or in class. Frequent patterns noted for the study included using two drugs at the same time or right before or after each other with alcohol used throughout the day. Participants also gave feedback on our Poly Substance Use (PSU) assessment that captures exact patterns so that the most common can be translated for the rodent models. DISCUSSION/SIGNIFICANCE OF IMPACT: Our focus group discussions provided detailed information on patterns, sequence, quantity, and types of poly substance use that could be useful for developing a poly substance use assessment in the collection of data for rodent models to understand effects of poly substance use.

OBJECTIVES/GOALS: In this study, we implemented deformable medial modeling as a morphometric approach in first trimester placentas to characterize morphometric differences between fully automated and manual segmentations. METHODS/STUDY POPULATION: Twenty placentas from singleton pregnancies between 11-14 weeks’ gestation were manually and automatically segmented from 3D ultrasound volumes. Automated segmentations were produced by a trained convolutional neural network pipeline. Dice overlap scores and volumes were computed between manual and automated segmentations. Deformable medial modeling was applied to both manual and automated segmentations to produce the following metrics: maternal and chorionic surface areas (SA), thickness, circumference, and diameter along the generated medial surface. Placental non-planarity was also determined as the greatest medial surface height difference. A paired t-test and simple linear regression was performed between manual and automated segmentations for each shape metric. RESULTS/ANTICIPATED RESULTS: Mean placental volume measurements between manual and automated segmentations were similar, with a percent difference of 3.28% and a mean Dice overlap score of 0.85 ± 0.07. There were strong, statistically significant (p <0.01) linear correlations with chorionic and maternal SA, SA difference, thickness, circumference, medial surface diameter, and medial surface height difference. No significant differences were noted with chorionic SA, thickness, circumference, maximum medial surface diameter, or medial surface height difference. However, statistically significant differences (p <0.01-0.03) were noted in maternal SA, SA difference, and mean medial surface diameter. Despite these differences, mean percent difference for all morphometric parameters was less than or equal to 10%. DISCUSSION/SIGNIFICANCE: A deformable medial model evaluate unique global and regional shape placental features with highly correlated values between manual versus automated placental segmentations. However, clinical studies are needed to determine if minor differences would impact the clinical utility of these features as potential indicators of placental function.

OBJECTIVES/SPECIFIC AIMS: To longitudinally track emerging research collaborations and assess their development and productivity. METHODS/STUDY POPULATION: In four administrations (2011, 2013, 2015, 2017), all full- and part-time University of Rochester Medical Center faculty received an email invitation to complete a research collaborators survey. Respondents indicated whether they were involved in research, and if involved in research, identified collaborators from a drop-down list of investigators in the institution. Space was provided for write-ins. Full- and part-time status, faculty rank, and departmental affiliation was associated with each investigator. Grant data were obtained from a grant management database maintained by the institution’s Office of Research and Project Administration. Grant data included all submissions (funded and not funded), award number, award effective data, award final expiration date, funding amounts, principal investigator and co-investigators. Using Mathematica SNA software, for each year we identified collaborator dyads (including their characteristics such as inter/intradepartmental; investigator characteristics) and networks (e.g. size, density). RESULTS/ANTICIPATED RESULTS: On average, 1800 (range 1730-2034) full- and part-time faculty received email invitations to complete the survey. An average of 403 respondents (range 385-441) completed the survey each administration. While the response rate seems low, the survey was distributed to every faculty member regardless of their primary appointment. Thus it included a large number of individuals whose role is exclusively clinical. Grant data included 4429 awards received between 2011 and 2018, involving 1395 investigators as principal or co-investigators. Survey respondents naming collaborators ranged from 233 to 280 (average 257) with 1594 to 2265 (average 1988) collaborations named each year. Overall density increased from.0204 in 2011 to.0342 in 2017. Density within the group of female investigators increased from.0219 in 2011 to.0412 in 2017. Within the group of male investigators, density increase from.0226 to.0333 in the same time span. Analysis by rank, changes over time and those with grant funding is underway. DISCUSSION/SIGNIFICANCE OF IMPACT: This methodology captured a consistent number of collaborations over an 8 year period. Analyses reveal network growth over time and of increasing heterogeneity (by gender). Analyzing research networks overtime provides an important metric to assess how research networks evolve and devolve and the characteristics of those that grow or stagnate. Further these analyses can demonstrate the impact of support provided to networks or teams by the CTSI, department or other institutional mechanism.

Objectives/Goals: Explore and compare the functional mechanisms of song-based exercises compared to speech-language pathology exercises for dysphagia. The long-term goal is to increase patient outcomes through song-based programs that are accessible, enjoyable, and personalizable. Methods/Study Population: We will pilot the use of combined electroencephalography (EEG) and electromyography (EMG) technologies to analyze both central and peripheral contributors to laryngeal control in a cohort of healthy individuals. This approach provides detailed insight into the coordination between neural and muscular activity, which will serve as a baseline for future studies in clinical populations. Song-based vocal exercises will be compared with standard dysphagia exercises prescribed by speech-language pathologists to assess their mechanistic differences. Results/Anticipated Results: We anticipate identifying specific song-based tasks, such as variations in pitch, rhythm, and intensity, which differentially impact laryngeal musculature. Additionally, we will localize neural activation hotspots using EEG during these tasks, providing a more comprehensive understanding of how song-based therapy influences both peripheral and central mechanisms. Discussion/Significance of Impact: This project will lay the groundwork for developing evidence-based song-based therapies for dysphagia, providing an alternative to traditional SLP exercises. By creating an engaging therapeutic program, we aim to reduce dysphagia’s healthcare burden, including aspiration events, healthcare costs, and related mortality.

ABSTRACT IMPACT: Learning Health System (LHS) Science that trains postdoctoral scholars from diverse professional backgrounds in methodological and professional skills to implement rigorous research in health care systems and populations, and to disseminate the findings of such research to improve healthcare delivery OBJECTIVES/GOALS: The WFUHS CTSA developed an innovative TL1 in Learning Health System (LHS) Science that trains postdoctoral scholars from diverse professional backgrounds in methodological and professional skills to implement rigorous research in health care systems and populations, and to disseminate the findings of such research to improve healthcare delivery METHODS/STUDY POPULATION: Training is centered around formal LHS science coursework and mentored research projects that address a pressing health system issue. Projects are closely guided by a primary mentor and a multidisciplinary mentoring team. Program mission and competencies were carefully evaluated in a competency-course matrix to design new courses for the LHS Certificate and MS program in Translational and Health System Science (THSS). Course domains include biomedical informatics; improvement and implementation science; system science and organizational change management; stakeholder engagement, leadership, and research management; ethics of health systems research; and health systems research methods. Scholars set up Individual Development Plans (IDP) and self-assess 7 domains of LHS core competencies. RESULTS/ANTICIPATED RESULTS: The first professionally diverse group of scholars (MD, PhD, DrPH, PharmD) began the program in Summer 2020; onboarding was conducted virtually. Scholars currently conduct most of their research and training in a virtual, synchronous format. Each developed a detailed IDP and LHS research project, which was reviewed by their LHS mentoring teams (includes a primary mentor, co-mentor, TL1 core faculty mentor, peer mentor, and health system mentor). Coursework, leading to a 1-year certificate or 2-year MS degree, was selected based on individual background and career goals and was begun in August 2020. In addition to the courses noted above, Scholars are embedded in a healthcare improvement team. We use the process of a LHS and hold weekly TL1 leadership meetings to swiftly address challenges and implement improvements DISCUSSION/SIGNIFICANCE OF FINDINGS: We envision that TL1 Scholars will build independent LHS research programs or lead health system innovation. Program evaluation includes assessments of Scholar fluency in LHS competencies and attainment of key milestones during and after training. Annual TL1 faculty retreats will address program fidelity and implementation of program refinements

Objectives/Goals: To assess the safety, tolerability, and adverse effects of adding acetazolamide to temozolomide in newly diagnosed MGMT-methylated malignant glioma, and to explore efficacy, survival outcomes, and Bcl-3 as a potential predictive biomarker. Methods/Study Population: Adults (>18 y) with newly diagnosed, MGMT-methylated, IDH-wildtype glioblastoma, and Karnofsky performance status > 60 receiving standard temozolomide (TMZ) + radiation (RT) were enrolled. Sixty patients (24 initial, 36 subsequent) received acetazolamide (ACZ) twice daily starting on the day of adjuvant TMZ initiation. ACZ began at 250 mg BID for 1 week, then escalated to 500 mg BID, given on days 1–21 of each 28-day cycle (TMZ days 1–5), for up to 6 cycles if not limited by tumor progression/toxicity. Clinical and MRI follow-up occurred every 2 months. Results/Anticipated Results: Preliminary data (initial 24 patients) have shown that no patient had a dose-limiting toxicity. Adverse events were consistent with known sequelae of acetazolamide and TMZ. In the 23 WHO Grade 4 patients, the median overall survival (OS) was 30.1 months, and the median progression-free survival was 16.0 months. The 2-year OS was 60.9%. In total, 37% of the study population had high BCL-3 staining and trended toward shorter OS (17.2 months vs N.R., P=.06) (Riley et al., 2024) All of these factors will be evaluated in a prospective study including 60 patients Discussion/Significance of Impact: Initial data in a smaller cohort showed that adding acetazolamide is safe and tolerable in GBM patients on standard temozolomide. Survival compares favorably to historical data in MGMT-methylated GBM. BCL-3 may be a prognostic biomarker. These findings will be assessed and discussed in a 60-patient prospective study.

OBJECTIVES/GOALS: NSF often requires cross-disciplinary team composition to be competitive for funding. To what extent do research teams have multidisciplinary authorships after they win an award, given that awards are not contracts? We examined the quantity and quality of multidisciplinary collaboration of NSF-funded teams before and after receiving their award. METHODS/STUDY POPULATION: Our sample was 150 PIs and Co-PIs (67% male) from 58 NSF-funded EAGER (EArly-concept Grants for Exploratory Research) grants between 2013 and 2019. Using publicly available information, we collected the number of conference papers, publications, and grants PIs/co-PIs produced with each other (all PIs and co-PIs in a team or a partial subset). Based on Ph.D. fields, we also cataloged whether the combination of PIs/co-PI authors on outputs represented unidisciplinary or multidisciplinary collaboration after their NSF award. Multidisciplinary collaboration consisted of multidivisional (Ph.D. disciplines across NSF divisions, e.g., political science and cognitive psychology) or multidirectorate (Ph.D. disciplines across NSF directorates, e.g., psychology and engineering) authorship. RESULTS/ANTICIPATED RESULTS: Of the 74% of PI and co-PI teams who collaborated after their EAGER award, almost 9 out of 10 chose to work with a collaborator from a different discipline, and almost 8 out of 10 chose to work with a researcher from an extremely diverse discipline from their own (e.g., computer science and psychology). Research on interdisciplinary teams largely emphasizes the challenges and problems they face but the current research demonstrated that 90% of the sample chose to continue working together across disciplines after EAGER awards. Therefore, future research should dedicate more attention to the nontangible benefits members receive in interdisciplinary teams. Moreover, quality measures revealed higher H-indices for multidisciplinary than unidisciplinary journals and conferences. DISCUSSION/SIGNIFICANCE: Our archival results revealed that NSF EAGER grants are having their intended effect of being a catalyst for 1) continued multidisciplinary (and especially multidirectorate) collaboration) and 2) high-quality multidisciplinary publication and conference output. These results have contributed to NSF policy changes to reinstate the EAGER grant.