Objectives/Goals: The timing of neurosurgery is highly variable for post-hemorrhagic hydrocephalus (PHH) of prematurity. We sought to utilize microvascular imaging (MVI) in ultrasound (US) to identify biomarkers to discern the opportune time for intervention and to analyze the cerebrospinal fluid (CSF) characteristics as they pertain to neurosurgical outcome. Methods/Study Population: The inclusion criteria for the study are admission to the neonatal intensive care unit (NICU) with a diagnosis of Papile grade III or IV. Exclusion criteria are congenital hydrocephalus and hydrocephalus secondary to myelomeningocele/brain tumor/vascular malformation. We are a level IV tertiary referral center. Our current clinical care pathway utilizes brain US at admission and at weekly intervals. Patients who meet certain clinical and radiographic parameters undergo temporary or permanent CSF diversion. Results/Anticipated Results: NEL was implemented at our institution for PHH of prematurity in fall 2022. To date, we have had 20 patients who were diagnosed with grade III or IV IVH, of which 12 qualified for NEL. Our preliminary safety and feasibility results as well as the innovative bedside technique pioneered at our institution are currently in revision stages for publication. Preliminary results of the MVI data have yielded that hyperemia may confer venous congestion in the germinal matrix, which should then alert the neurosurgeon to delay any intervention to avoid progression of intraventricular blood. With regard to CSF characteristics, we anticipate that protein, cell count, hemoglobin, iron, and ferritin will decrease with NEL. Discussion/Significance of Impact: The timing of PHH of prematurity is highly variable. We expect that MVI will offer radiographic biomarkers to guide optimal timing of neurosurgical intervention. A better understanding of CSF characteristics could potentially educate the neurosurgeon with regard to optimal timing of permanent CSF diversion based on specific CSF parameters.

Objectives/Goals: The importance of interprofessional communication in healthcare is well documented. However, there has yet to be a theoretical framework for understanding this complex phenomenon. The purpose of this project was to develop a situation-specific theory about the culture of communication in the interprofessional healthcare setting. Methods/Study Population: We conducted individual virtual qualitative interviews with 16 healthcare professionals at different levels and from various disciplines. Participants were practicing clinicians at a tertiary care academic medical center. We transcribed audio-recordings of the interviews verbatim and aligned each transcript for accuracy, confidentiality, and representativeness. Data analysis was conducted using dimensional analysis, including open- and theoretical-coding utilizing an explanatory matrix for theory generation. Results/Anticipated Results: Our findings produced a situation-specific theory on the culture of interprofessional communication in the healthcare setting. Participants described the environments in which they practiced in terms of hierarchical system structures and through a conceptual perspective of resource investment. In other words, they viewed their time and their effort as valuable – and notably, scarce – resources, which they invest in patient care, interprofessional communication, and other tasks. There are two key pathways that characterize the culture of interprofessional communication: collaborative communication and transactional interactions, depending on whether an individual perceives the goals of another person, department, or level of the hierarchical institution as aligned with their own goals. Discussion/Significance of Impact: Positive cultures of interprofessional communication in the healthcare setting depend on perceived goal alignment among individuals, departments, and leadership. Future research can explore how perceptions of goal alignment are developed and empirically test this situation-specific theory in other healthcare system settings.

Objectives/Goals: Transmission-blocking vaccines hold promise for malaria elimination by reducing community transmission. But a major challenge that limits the development of efficacious vaccines is the vast parasite’s genetic diversity. This work aims to assess the genetic diversity of the Pfs25 vaccine candidate in complex infections across African countries. Methods/Study Population: We employed next-generation amplicon deep sequencing to identify nonsynonymous single nucleotide polymorphisms (SNPs) in 194 Plasmodium falciparum samples from four endemic African countries: Senegal, Tanzania, Ghana, and Burkina Faso. The individuals aged between 1 and 74 years, but most of them ranged from 1 to 19 years, and all presented symptomatic P. falciparum infection. The genome amplicon sequencing was analyzed using Geneious software and P. falciparum 3D7 as a reference. The SPNs were called with a minimum coverage of 500bp, and for this work, we used a very sensitive threshold of 1% variant frequency to determine the frequency of SNPs. The identified SNPs were threaded to the crystal structure of the Pfs25 protein, which allowed us to predict the impact of the novel SNP in the protein or antibody binding. Results/Anticipated Results: We identified 26 SNPs including 24 novel variants, and assessed their population prevalence and variant frequency in complex infections. Notably, five variants were detected in multiple samples (L63V, V143I, S39G, L63P, and E59G), while the remaining 21 were rare variants found in individual samples. Analysis of country-specific prevalence showed varying proportions of mutant alleles, with Ghana exhibiting the highest prevalence (44.6%), followed by Tanzania (12%), Senegal (11.8%), and Burkina Faso (2.7%). Moreover, we categorized SNPs based on their frequency, identifying dominant variants (>25%), and rare variants (Discussion/Significance of Impact: We identified additional SNPs in the Pfs25 gene beyond those previously reported. However, the majority of these newly discovered display low variant frequency and population prevalence. Further research exploring the functional implications of these variations will be important to elucidate their role in malaria transmission.

Objectives/Goals: Global surgical education is largely driven by high-income countries (HICs), with curricula not tailored to the needs of low- and middle-income countries (LMICs). This study assessed country-specific needs for global surgical curricula and used generative AI to develop tailored curricula. Methods/Study Population: A curriculum framework was developed using expert opinion. Using a focused needs assessment survey, we evaluated international medical students’ and trainees’ needs for structured global surgery curricula, covering research, education, data and develop tailored curriculum templates for each country, ensuring alignment with the distinct needs of respective LMIC and HIC respondents. The AI-generated curricula were then compared across countries to identify variations in content and focus areas. Results/Anticipated Results: A total of 145 respondents from 18 countries and 6 continents participated, with 94 from LMICs and 51 from HICs. Four countries [Uganda (n = 31), Nigeria (n = 34), the USA (n = 23), and the UK (n = 23)] had more than 10 respondents, with the creation of a country specific global surgery curriculum. Curricula developed by HIC trainees focused on access to resources and infrastructure, future directions of global surgical research, and the role of medical students and early career development with a decreased focus on the history of global surgery. LMIC country-based curriculum focused on introducing the concepts of global surgery, quantifying the burden and epidemiology of surgical disease and had a greater emphasis on case studies and use cases, with decreased focus on resources and collaboration. Discussion/Significance of Impact: The research introduces a “precision education” approach that could help close the surgical education access gap globally. Further pilot and qualitative studies are necessary to validate the feasibility of AI-generated needs-based curricula.

Objectives/Goals: Team science (TS) competency is important for translational science team collaboration. However, there are few educators available to assist teams. Asynchronous learning is an effective strategy for delivering TS content. The goal of this project is to expand TS education by providing online access to our learners using online modules. Methods/Study Population: The Collaboration and Team Science (CaTS) team at the University of Cincinnati provides a robust TS education and training program. As the need for team science gains recognition, CaTS has received increased requests for services, leading to a need to broaden TS offerings. To address this demand, the CaTS team created “Team Science 101,” an online, asynchronous, series of 15 modules covering basic team science concepts. Each module consists of an educational recording lasting an average of 20 minutes, optional topic resources, pre- and post-module surveys assessing learners’ confidence and satisfaction, post-module knowledge checks, and evaluation questions. Upon completing all modules, participants receive a completion certificate. Results/Anticipated Results: TS 101 will be piloted with a group of participants who expressed interest in asynchronous TS content and will be adjusted based on the feedback received. The associated pre- and post-module survey, post-module knowledge check, and evaluation questions will be monitored to determine learning levels and improve TS 101 overall. Canvas is the educational platform that houses these modules, allowing for participant follow-up and scalable dissemination. The CaTS team plans to disseminate TS 101 nationally and internationally for anyone interested in this resource. Discussion/Significance of Impact: There is a national effort to collect and curate TS education, training, and toolkits. TS 101 will be a useful educational tool that will expand the reach of team science educators, provide the foundation for educators to explore topics more deeply by building on the module topics, and provide education to broader audiences who lack access to TS experts.

Objectives/Goals: The growing burden of hypertension in the USA disproportionately impacts individuals with lower socioeconomic status and those in rural communities. This study aims to investigate specific social determinants of health associated with uncontrolled hypertension among rural, underserved patients residing in Alabama. Methods/Study Population: A retrospective review of electronic health records data from the UAB Selma Family Medicine clinic was conducted. The deidentified data were entered into the Population Health Assessment Engine (PHATE) to render social characteristics and community vital sign (CVS) scores, a social deprivation index, by census tracts. We provide descriptive statistics and compare the stated factors between patients with controlled and uncontrolled hypertension using logistic regression models. We are conducting phone surveys to gather individualized data on social determinants of health to assess the perceived social needs of patients with hypertension. The Protocol for Responding to & Assessing Patients’ Assets, Risks & Experience tool was used to develop the survey, and survey responses will be compared with the PHATE results. Results/Anticipated Results: Among 2129 patients, 375 (17.6%) had uncontrolled hypertension with a mean age of 58.7 ± 14.4 years. Women comprised 66.7% (250) and 65.1% (1142) of the uncontrolled and controlled hypertension populations, respectively. The prevalence of uncontrolled hypertension was 19.1% among Black patients and 8.2% in White patients. Patients with uncontrolled hypertension had a CVS of 82.37 ± 7.31 and 81.81 ± 8.40 patients with controlled hypertension. Patients with uncontrolled hypertension lived in areas where an average of 46 ± 11% were not employed, 36 ± 9% rented, and 28 ± 1% lived below the federal poverty line (FPL). Adjusting for age, race, and sex, a unit increase in the proportion of people below the FPL was associated with 43% higher odds of uncontrolled versus controlled hypertension (OR  =  1.43, 95% CI 0.44, 4.64). Discussion/Significance of Impact: Rural, underserved patients with hypertension experience multiple adverse social determinants, such as nonemployment rates, low income, and rental housing. Survey results will allow us to compare assessed and individualized social determinants that may be important to address when caring for this population.

Objectives/Goals: The goal of this study is to determine the function of the rete ovarii (RO), an uncharacterized secretory epithelial appendage to the ovary. I am testing the hypothesis that the RO is critical for the maintenance of the ovarian reserve and fertility, and progesterone signaling plays a role in the function of the RO. Methods/Study Population: For this project, I am utilizing a mouse model. To visualize the rete ovarii (RO) in vivo, I am using a Pax8rtTA; TRE-H2B-Gfp (PTG) reporter mouse, which expresses green fluorescent protein in the RO. To determine the role of the RO in fertility and maintenance of the ovarian reserve, I will surgically ablate the RO or perform a sham surgery on adult female PTG mice. Then, I will follow-up with quantification of the ovarian reserve and long-term fertility tracking studies. To determine how the RO responds to progesterone, the RO will be cultured ex vivo in the presence and absence of progesterone. I will perform a morphometric analysis of the RO, as well as collect secreted proteins from the media for proteomic analysis. Results/Anticipated Results: If the RO is important for ovarian homeostasis, I expect that in the absence of the RO, ovarian functions such as maintenance of the ovarian reserve and fertility will be impaired. Additionally, because the RO expresses progesterone receptors, I anticipate that the RO will be responsive to progesterone as shown in changes in the morphometric analysis and in changes in secreted proteins in the presence of progesterone. Discussion/Significance of Impact: A major gap in knowledge regarding female physiology and reproductive health is the role of the RO. We expect this work to reveal that progesterone signaling in the RO is important for regulating ovarian functions and to show that the RO is a critical modulator of female fertility and reproductive function.

Objectives/Goals: Germinal matrix hemorrhage (GMH) is a devastating disease of infancy that results in brain-related pathologies. Following rupture of vasculature in the brain, red blood cell (RBC) lysis, and hemoglobin breakdown results in heme/iron-related toxicities. We hypothesize that these cellular pathologies are mediated in part by the complement system. Methods/Study Population: Post-natal mice on day 4 (P4) were subjected to collagenase induced-GMH and treated with various complement inhibitors that function at different points in the complement pathway and differentially prevent the generation of specific complement activation products. The principle bioactive complement activation products are C3 opsonins (C3b, iC3b, and C3d), the proinflammatory anaphylatoxins (soluble C3a and C5a peptides), and the terminal cytolytic membrane attack complex (MAC). Experimental groups consisted of: Wild-type (WT) naïve mice, and WT GMH-mice treated with either PBS (vehicle), CR2-Crry (C3 inhibitor that blocks all activation products), anti-C5 mAb (blocks C5a and MAC), C5aRA (blocks C5a-C5a receptor interaction), or anti-C7 mAb (blocks MAC). Study endpoints were P7 or P14. Results/Anticipated Results: Following GMH, CR2-Crry treatment decreased MAC deposition on RBC and additionally decreased heme oxygenase-1 expression, heme deposition, and iron-induced inflammation measured at P7. In support of a specific role for the MAC, anti-C7 mAb treatment resulted in similar outcomes and was similarly protective. Anti-C7 mAb treatment also reduced hydrocephalus development at a later time point (P14). A similar result was obtained using C7 deficient mice and with anti-C5 mAb treatment. On the other hand, no protective effect was seen with C5aR blockade, and double knock out of C3aR/C5aR also did not provide protection, indicating no role for the anaphylatoxins C3a and C5a and their receptors expressed on leukocytes and endothelial cells in exacerbating deteriorating outcomes. Discussion/Significance of Impact: Our data indicate a key role for the MAC in RBC induced hemolysis after GMH which serves as a driver of inflammation and early GMH pathogenesis. We further show that we can effectively increase precision by targeting solely the MAC complex acutely. Future work will be undertaken to determine temporal roles of individual complement activation products.

Objectives/Goals: To identify clinical trial teams that are at risk of not meeting their recruitment goals as early in the recruitment period as possible, this project aims to provide timely accrual information and projected forecasts for accruals by the end of the recruitment period across all trials at USC. Methods/Study Population: This project aggregates recruitment accrual data periodically from OnCore to create per-study accrual pages that contain an up-to-date accrual chart, metrics like expected and actual accrual per month, and projected recruitment based on an X-month moving average (3 months by default). Trials at risk are identified as early as possible by using these projections to classify risk. In this initial phase, we’ve classified trials as medium risk (80%–99% accrual) or high risk (less than 80% accrual). The dashboard is currently available for all clinical trials at USC and users are automatically restricted to the studies that they administer or work on depending on their role. Results/Anticipated Results: The dashboard will provide visibility across the institution for the current accrual for all clinical trials in a standard, user-friendly format and use the same metrics and definitions of risk for trial accruals not meeting their targets. This will allow the institution to identify trials that need intervention to get back on track using a single set of criteria across all research teams. Users in different roles, whether department heads, principal investigators, or study coordinators can view the current accrual for all the trials that they administer or work on in one central location. The dashboard will also help to identify quality issues in OnCore by performing data quality checks nightly. Discussion/Significance of Impact: By providing a central location for role-based access to timely clinical trial accrual for the institution, the dashboard helps to identify trials at risk of not meeting their recruitment targets as early as possible to provide corrective advice/measures.

Objectives/Goals: The goal of this poster is to 1) describe the development of a graduate certificate program for community-engaged research for health (CEnRH) in a Clinical and Translational Science Awards-funded institution; 2) describe the initial impact of the program; and 3) discuss strengths, implications, and potential improvements for the future. Methods/Study Population: The CEnRH graduate certificate is a 12-credit, postbaccalaureate program offered at the University of Cincinnati co-created by faculty from the Community Engagement and Translational Workforce Cores of the CCTST with community partners. The goal is to support learning about community-engaged research (CEnR) and enhances capacity for academic-community partnered research. Student demographics are collected as part of university registration. Quantitative course evaluations are collected each semester. Program evaluations including qualitative data are collected from students enrolled in the program during and upon completion of the certificate. Results/Anticipated Results: The CEnRH curriculum includes 3 existing courses/electives in the College of Medicine and Psychology and three new courses in social justice and action research methodologies. Notably, the committee advocated for a scholarship to cover tuition for the certificate program to promote access for community partners. Since the fall of 2022, 17 students have enrolled in the CEnRH program, including 9 Faculty/Staff within CCTST institutions, 2 University of Cincinnati PhD Students, 5 Fellows, and 1 Community Member (who receives the scholarship). Notably, 24% of these students are from underrepresented minority backgrounds. Impact and evaluation data, as well as lessons learned, will be presented. Future directions for the CEnRH program will also be discussed. Discussion/Significance of Impact: The CEnRH is an impactful program for trainees, faculty, and staff who are planning to conduct CEnR, while also strengthening research capacity among community partners and advocates. This certificate program may be especially valuable to academic researchers as more funding agencies require community and stakeholder engagement in their proposals.

Objectives/Goals: As life expectancy increases in people with HIV, neurocognitive impairment is becoming more common, and women with HIV (WWH) are disproportionately impacted. This work investigated mitochondrial function and oxidative stress in WWH in order to understand the relationship between mitochondrial function and cognition in future studies. Methods/Study Population: Peripheral blood mononuclear cells were isolated from virally suppressed WWH (n = 64) and underwent the Seahorse Cell Mito Stress test to assess different realms of mitochondrial function. Cells were then lysed for direct DNA extraction, and quantitative PCR was performed to understand mitochondrial DNA expression (mtDNA) levels as a measure of oxidative stress. A series of simple linear regressions was then conducted to understand the relationships between mitochondrial function and mtDNA content. Future work will expand this analysis to investigate associations between demographic dynamics, such as trauma history, and mitochondrial function, as well as to understand the relationships between mitochondrial function and cognitive outcomes in WWH. Results/Anticipated Results: In our cross-sectional analysis of mitochondrial dynamics in WWH, we found a significant association between maximum mitochondrial respiration ability and mtDNA content, with greater mtDNA expression associated with increased levels of maximum respiration following stimulation. There was no association between basal respiration and levels of oxidative stress. There was also a significant variation in mitochondrial function in our participants, indicating that future analyses to investigate the source of that variation are warranted. The work presented here sheds light on mitochondrial dynamics in WWH and will be the basis for future studies that will investigate how demographic dynamics may be associated with mitochondrial function, as well as how mitochondrial dynamics may predict cognitive outcomes. Discussion/Significance of Impact: There is significant variation in mitochondrial function in WWH. More analysis is needed to understand what may be associated with these variations, including an investigation of both clinical factors as well as cognitive outcomes. This analysis will inform directions for future mechanistic work aimed at mitigating adverse cognitive outcomes in WWH.

Objectives/Goals: This project will enrich our understanding of basal breast carcinogenesis, highlighting the distinct biological differences in breast cancer risk between non-Hispanic Black (NHB) or non-Hispanic White (NHW) women, but also has the potential to provide real-world solutions thereby contributing to reducing health disparities in breast cancer outcomes Methods/Study Population: In the biological investigation, I am utilizing a unique cohort of normal breast tissues from Mayo Clinic patients who underwent breast reduction surgery that have self-identified as NHB or NHW premenopausal women. From these tissues, we are able to subculture human mammary epithelial cells, which we will use for our consequent experiments. For the qualitative study, I aim to recruit up to 40–50 eligible NHB women identified at increased risk for breast cancer and conduct semi-structured qualitative interviews informed by the National Institute on Minority Health and Health Disparities Research Framework. Results/Anticipated Results: Gene expression profiling on our cohort of 15 NHB and 40 NHW premenopausal women identified a gene expression signature in NHB women indicative of elevated Hedgehog signaling, a key factor in triple-negative breast cancer (TNBC) development and progression. I hypothesize that persistent activation of Hedgehog signaling within NHB women instigates the proliferation and transformation of basal stem cells within the breast, thus fueling TNBC development. Understanding the perceptions and experiences of NHB women that are identified as being at an increased risk for BC will aid in the identification of barriers and facilitators to their risk reduction care and in turn provide implementation strategies that could contribute to alleviating the racial disparity seen in TNBC morbidity, mortality, and preventative care. Discussion/Significance of Impact: The significance of this project lies in its dual approach, uncovering basal breast cancer mechanisms in a high-risk group using normal breast tissue and evaluating the perspectives from NHB women to enhance the practical relevance of our findings.

Objectives/Goals: We assessed the feasibility of using a large language model (LLM) to create lay language descriptions of study protocols for recruitment, which has the potential to improve accessibility and transparency of clinical studies and enable participants to make informed decisions. Methods/Study Population: All studies from a clinical research recruitment platform were included, which features human-written lay descriptions and titles for study recruitment. Corresponding protocol summaries in the IRB system were extracted and translated into lay language using a LLM (gpt-35-turbo-0613). A subset was used to develop prompt variations through an iterative process. Prompt strategies evaluated include chain-of-thought and few-shot prompting techniques. LLM-generated and human-written descriptions were compared for readability using Flesch–Kincaid and Simple Measure of Gobbledygook (SMOG) reading grade levels and information completeness using Word Movers’ Distance (WMD). Results/Anticipated Results: A total of 55 study descriptions were included – 10 were used to develop prompts and 45 were used for evaluation. The final LLM instructions included multistep prompts. The LLM was first instructed to produce a two- to three-sentence long description without using scientific jargon and included two pairs of examples. The LLM was then asked to shorten the description and finally to provide an engaging title. LLM-generated and human-written summaries were similar in length (median (IQR) 328 (278.5–360.5) vs. 342 (203–532.5) characters, respectively). LLM-generated summaries had lower Flesch-Kincaid grade level (5.15 vs. 8.28, p Discussion/Significance of Impact: An LLM can be used to generate lay language summaries that are readable at a lower grade level while maintaining semantic similarity. This approach can be used to improve the drafting of summaries for recruitment, thereby improving accessibility to potential participants. Future work includes human evaluation and implementation into practice.

Objectives/Goals: A summer research program for medical students was implemented using real-world evidence (RWE) – electronic health record (EHR) databases to develop and answer research questions. Medical students were trained in capabilities of traversing the large RWE-EHR so they may query, extract, and analyze data as well as refine their research questions. Methods/Study Population: Ten medical students and 9 non-data scientist mentors underwent training in how to use the IU School of Medicine-Evansville RWEdataLab (CRC/Sidus Insights) national real-world cardiology and psychiatry deidentified EHR databases. The program began with students attending introductory training teaching database, spreadsheet, and statistical program usage. During the remainder of the program, a weekly best practices meeting took place among mentors and a weekly cohort meeting of students and mentors discussed student presented findings. At the end of the program, students generated abstracts and poster or podium presentations to share their findings at local symposia. A survey was also distributed to students to assess the impact of the tools, trainings, and program. Results/Anticipated Results: All students were able to define a question of interest, query and extract data related to their research question, and analyze multiple aspects of their data. Projects were well received at local symposia, with 2 receiving special honors, and 2 projects have been presented at regional/national conferences. Students rated the program highly and were likely to recommend the program to other students. They self-rated improvements in asking scientific questions, using excel, data presentations, and problem-solving. Students valued weekly “check-in” meetings and interactions with mentors more than lectures or technical “help desk” support. Discussion/Significance of Impact: The program provides mechanisms for non-data scientists and medical trainees, to learn and access RWE-EHR databases to address research questions. The cohort interactions fostered discussion among mentors and students promoting research question refinement and clarity findings. The program also introduces a new tool for potential patient care.

Objectives/Goals: Large-scale tumor sequencing efforts have led to annotations of novel cancer hotspot mutations that may underlie driver or cooperative function. We have sought to define the molecular consequences of such hotspots associated with pediatric DICER1 syndrome cancers, with the ultimate goal of revealing novel targets that may inform new standards of care. Methods/Study Population: We have performed genomic analysis to identify tumor types (in TCGA and MSK-IMPACT patient data) for which mutations in the Dicer1 gene (encoding Dicer protein) emerge as the dominant signature of driver function. As Dicer is a critical RNA processing factor responsible for the generation of microRNAs, which are posttranscriptional gene regulatory molecules, we have modeled these mutations in human embryonic stem cells in order to study the direct effects on miRNAs and their target genes in an isogenic background. In addition to providing the required setting for unambiguous attribution of function to specific mutations, clonal human ES cells offer an opportunity for modeling of both developmental and cancer requirements associated with altered Dicer function. Results/Anticipated Results: Through generation of genomics and functional datasets from matched genotypes in Dicer mutated human ES cells, we have identified specific alterations in miRNAs and their effects on target genes. Unexpectedly, we found direct evidence for both loss of function and gain of function attributable to Dicer mutations. In addition, through integrated analysis of genomic data from tumor sequencing datasets and our human ES cell models, we have identified potential miRNA and target gene alterations that underlie tumorigenic potential, nominating gene candidates for targeted therapy in DICER1 syndrome. Direct mouse modeling of such candidate gene targets has revealed evidence for driver function of identified miRNA and their targets. Discussion/Significance of Impact: DICER1 syndrome cancers comprise a wide variety of rare pediatric tumor types. Presently, we still lack an effective standard of care. Furthermore, the previous lack of molecular profiling precluded targeted therapy opportunities. Our precise knock-in modeling of Dicer hotspots and deep profiling of relevant tumors now provide candidate targets.

Objectives/Goals: The purpose of this study was to document the publicly available literature, measurement tools, secondary data, and expert perspective on the intersectional care gaps and disparities of children with palliative needs in foster care. Methods/Study Population: Four data collection methods determined the frontier of available information on the palliative needs of children in foster care. A literature review assessed the quality and content of published evidence. A catalogue of relevant measures tools and validation results determined what psychometric tools exist for the population, how well they performed in validation studies, and if any incorporated community members in their development. The National Data Archive for Child Abuse and Neglect was consulted to assess whether existing secondary data was fit for purpose. Informal interviews will be conducted with subject matter experts (pediatrics, palliative care, foster care) to determine the legitimacy and urgency of the problem. Results/Anticipated Results: Health inequities among children in foster care and children with medical complexity (CMC) suggest a strong likelihood of unmet palliative care needs for CMC in foster care; however, no literature or data describe the scope and severity, and few insights support development of safe and supportive interventions to meet these needs. No national publicly available datasets include both foster-related case or placement information and diagnosis or service-specific data, including Medicaid data and the Adoption and Foster Care Analysis and Reporting System (AFCARS). No work has been published integrating foster parents or former foster youth input on palliative needs. Participatory action research methodologies with critically ill patients have led to improvements in patient experience and clinical care. Discussion/Significance of Impact: The lack of data, community engagement, and validated measures to identify palliative needs of children in foster care stymie efforts to identify and correct health inequities. Participatory action research is needed to meaningfully engage foster and health care partners to determine what palliative care needs should be prioritized and measured.

Objectives/Goals: The bromodomain PHD finger transcription factor (BPTF) is an oncogenic driver of neuroblastoma. Our objective is to pioneer the discovery of the first class of chemical compounds that engage the PHD finger of BPTF and inhibit its biological function in cellulo, thereby establishing first-in-class chemical probes for this epigenetic reader. Methods/Study Population: Our previous work has identified a collection of small molecules that engage BPTF PHD in vitro. Following structure–activity relationships analysis, candidates will be used in a neuroblastoma cell model to validate BPTF PHD interaction in cellulo and predict therapeutic potential. Nanoluciferase bioluminescence resonance energy transfer (NanoBRET) will be used to confirm BPTF PHD engagement by compounds. Selective toxicity in neuroblastoma cells upon inhibitor treatment will be gauged by comparing cell growth and viability in the IMR-32 cell line against the HEK293 cell line. Treated HEK293 cells will be subjected to the assay for transposase-accessible chromatin (ATAC) and RNA sequencing methods to monitor changes in chromatin structure and transcriptional signatures against untreated cells. Results/Anticipated Results: We hypothesize that compounds with low micromolar potency for BPTF PHD in vitro will engage the target in cellulo and displace NanoLuciferase tagged protein from its HaloTagged® peptide binding partner. Additionally, we anticipate that our inhibitors will show cytotoxicity for IMR-32 cells with limited effects on HEK293 cells. We envision that inhibitor treatment in HEK293 cells will correlate with reduced chromatin exposure, suggesting that blocking the BPTF–histone interaction via PHD finger inhibition hinders the remodeling of transcriptionally silent heterochromatin into a transcriptionally active state. Finally, we expect that inhibitor treatment will result in diminished gene expression of oncogenic transcription factors, including N-Myc, a biomarker of neuroblastoma. Discussion/Significance of Impact: These first-in-class chemical probes for BPTF PHD will enable further investigation of BPTF and high-risk neuroblastoma progression, as well as its role in other diseases. In addition, these compounds will serve as a platform for the development of new anticancer agents that may improve outcomes for children that suffer from high-risk neuroblastoma.

Objectives/Goals: The STEM-Coaching and Resources for Entrepreneurial Women (CREW) Program was developed to promote systemic change in entrepreneurship by engaging women faculty and post-doctoral fellows through educational opportunities, mentorship, and professional coaching to close the gender gap in entrepreneurial leadership. Methods/Study Population: We solicited applications from women at the junior faculty or post-doctoral fellowship stage. Applications were reviewed by the CREW leadership and mentors. Applicants accepted into the program participated in monthly large group coaching sessions, one-one-one coaching, and small group mentoring sessions. Applicants also completed an online entrepreneurship course and participated in a shark tank-like competition during annual innovation awareness month. Coaches were professionally credentialed and oriented to the biomedical context. Entrepreneurial experts served as mentors. Our program evaluation used the RE-AIM framework. The evaluation included assessments of the program’s ability to reach a diverse population, satisfaction with program offerings, and changes in entrepreneurship outcomes. Results/Anticipated Results: To date, three cohorts consisting of 35 women from 13 states participated in the program. Results from Cohort 1 show significant improvements in self-assessed confidence in entrepreneurial activities and high satisfaction with the program. All measures of confidence showed increases, with the largest gains in the areas of “estimating customer demand for new products or services”; “Clearly and concisely explaining my business idea in everyday terms”; and “Getting others to identify with and believe in my vision and plans for a new business”. The percentage of participants who have invention disclosures significantly increased from 33.3% to 83.3% after completing the program. The percentage who launched start-up companies also increased from 17% to 33%. Cohort 2 results will be available before the conference. Discussion/Significance of Impact: Participants in the CREW program showed improvement in all measures of evaluation. The program is unique in complementing mentoring with coaching. Because the coaching component takes a holistic approach by encouraging women to craft a vision for their work and life, it provides value that will last beyond entrepreneurship activities.

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: With qualitative interviews we aim to 1-Describe barriers and facilitators for post-transplant lymphoproliferative disease (PTLD) survivors’ access to late effects (LE) care. 2-Investigate clinicians’ perceptions of current and ideal PTLD LE care. Our long-term goal is to develop and pilot implementation strategies to standardize PTLD LE care. Methods/Study Population: Study population: We will recruit 20–25 PTLD survivors or their caregivers and 10–15 health care workers (HCW) from oncology, LE, and solid organ transplant (SOT) teams at St. Louis Children’s Hospital (SLCH). PTLD is a lymphoma-like cancer that occurs in solid organ transplant (SOT) recipients. PTLD survivors experience LE from cancer, yet many do not receive LE care. Research strategy: We will conduct qualitative semi-structured interviews based on the Consolidated Framework for Implementation Research (CFIR). A preliminary codebook will be based on CFIR and refined through transcript review. Team-based coding includes double coding and checking for intercoder reliability. We will generate coding reports to understand themes and identify barriers and facilitators of LE care. Results/Anticipated Results: We hypothesize survivors, caregivers, and HCWs will identify actionable factors to inform future studies to optimize LE care. We will examine the CFIR inner setting (resources, communication, and structural characteristics), outer setting (local attitudes and external pressures), innovation domain (adaptability, evidence base, and relative advantage), individuals domain (need, opportunity, and motivation), and implementation process domain. Our contribution will be novel. 1-This is the first assessment of barriers and facilitators for LE care in pediatric PTLD survivors. 2-We will consider input from HCWs across various disciplines delivering care to PTLD survivors. 3-We anticipate identifying unique contextual factors in PTLD survivors that will influence implementation of evidence-based LE care. Discussion/Significance of Impact: Pediatric cancer survivors experience LE. Coordinated care mitigates LE. PTLD survivors experience a high burden of LE, but less than 10% of PTLD survivors at SLCH follow in LE clinic. No studies have evaluated ideal delivery of LE care for PTLD survivors. Our findings will inform an implementation trial to improve delivery of LE care for PTLD survivors.