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: Our objective is to evaluate how access to oral health care and tobacco use in patients with serious mental illness (SMI) impact their oral health outcomes identifying barriers and service utilization disparities affecting the prevalence and severity of oral diseases. Methods/Study Population: A secondary retrospective data analysis study will use records from the electronic database (All of Us). The study population includes individuals over 21 years old, diagnosed with SMI. Data will be collected focusing on their oral health status, access to oral health care (frequency of visits, availability of services, etc.), tobacco use, and social determinants of health. The study will evaluate the impact of access to oral health care on the prevalence of oral health outcomes (e.g., periodontal diseases and oral cancer), analyzing socioeconomic factors, mental health status, and tobacco use as independent variables. A quantitative, descriptive-correlational analysis will be performed to explore the study variables. Results/Anticipated Results: We anticipate that limited access to oral health care, influenced by socioeconomic factors, the presence of SMI, and tobacco use, will correlate with worse oral health outcomes in Hispanics. Disparities in access, such as financial limitations, transportation issues, and stigma, are expected to significantly hinder service utilization and increase the prevalence of oral diseases in patients with SMI who smoke. Discussion/Significance of Impact: This research highlights the need to address disparities in oral health access for Hispanic marginalized populations, particularly those with severe mental illness and tobacco use. It will contribute to reducing health inequalities and improving oral health outcomes through culturally adapted interventions that address these barriers.

Objectives/Goals: Despite significant advancements, adolescent and young adult (AYA) patients with hematologic malignancies continue to have inferior improvement in survival over time compared to their younger and older peers. This project assesses which patient and neighborhood characteristics are associated with clinical trial enrollment in this population. Methods/Study Population: We will perform a retrospective study of individuals, aged 15–39, diagnosed and treated at Children’s Healthcare of Atlanta (CHOA) or Winship Cancer Institute for hematologic malignancies between 2011 and 2023. Our primary exposure variables will be race/ethnicity, the area deprivation index (ADI), and the index of concentration at the extremes (ICE). The primary study outcome will be enrollment in an open frontline therapeutic clinical trial (yes vs. no). Our analyses will estimate the crude and adjusted odds ratio of clinical trial enrollment according to race/ethnicity, ADI, and ICE; these analyses will be adjusted for co-variables of interest (e.g. patient primary language, and insurance provider). As a secondary analysis, we will further subdivide the patients by treatment location and by age tertiles. Results/Anticipated Results: Our study team completed preliminary work looking at institutional clinical trial enrollment in a pediatric-only (Discussion/Significance of Impact: We expect that this study conducted in a large, diverse AYA cohort will reveal key associations about likelihood of clinical trial enrollment. Once these associations are known, we can develop and test interventions –such as augmented social work involvement and assistance with transportation– to mitigate the effect of amenable risk factors.

Objectives/Goals: Retention in care is vital for people living with HIV. We used human-centered design (HCD) to engage a community-based research panel over a 5-year period, allowing us to incorporate their insights on research guidance and interpretation of findings to investigate correlates of HIV care outcomes. Methods/Study Population: We recruited a diverse panel of individuals who were living with HIV, HIV clinicians, and/or providing non-clinical HIV services in Marion County, Indiana. We conducted biannual sessions using a variety of HCD tools and activities to engage participants. Each session took about three hours, and panelists were compensated for their participation. Due to the COVID-19 pandemic, sessions were initially held virtually. Sessions were designed for project discussion and to facilitate exploration of concerns and challenges facing receipt of HIV services. Our HCD approach put participants in the center of discussion and empowered them to externalize ideas and collaborate meaningfully with our team. Results/Anticipated Results: Since project inception, 48 individuals have joined the panel. Thirty-five are actively engaged, participating in one or more of six sessions conducted to date. We have learned much from the panel. One example is that a residential move might be a risk or protective factor for retention in care and the amount of time one had lived with HIV is a crucial factor. Panel insights have helped guide and prioritize analyses, aided in identification of data missing from our ecosystem, helped interpret results, provided feedback on future interventions, led to a quality improvement project with the local health department, and led to a presentation at a local health equity conference. Discussion/Significance of Impact: Community engagement is essential to impactful and sustainable research. HCD was a successful approach to engage our panel to inform interventions more relevant to the community. We anticipate these methods will be important for others conducting community-engaged research.

Objectives/Goals: The goal of this study is to investigate the peri-metastatic rims of peritoneal lesions to determine features that predict malignancy using both imaging processing techniques and machine learning. This information will subsequently be added to our existing knowledge of peritoneal lesions to improve classification accuracy as benign or malignant. Methods/Study Population: The study population consists of 521 imaged lesions from 163 subjects with cancers of GI-origin with biopsy results as well as the clinical subject information and follow up. All images were obtained during staging laparoscopy by the senior author (TS). On the images, the central lesion as well as the surrounding peri-metastatic rim will be segmented as regions of interest (ROIs). Image processing will be used to calculate a variety of metrics for these two regions. A general estimating equation approach will be used to determine significance of these metrics compared to the dependent outcome of malignancy determined on the pathology report as the ground truth. These ROIs and significant metrics will then be used to improve the accuracy of a machine learning model to classify these lesions as benign or malignant. Results/Anticipated Results: Our previous research showed that experts performed this task at only a 52% accuracy rate (classifying lesions as malignant or benign based on imaging). A previous machine-learning model on a much smaller dataset was able to achieve by contrast an area under the curve of 0.78. We anticipate that by including a larger dataset in addition to including the peri-metastatic rim, we will be able to improve the accuracy of the the model in this task while uncovering significant biomarkers as well that can be used in future studies. Discussion/Significance of Impact: Classifying peritoneal lesions determines the correct treatment for cancer patients whether chemo-radiation, definitive surgery or palliative surgery. This project aims to develop an improved model that can perform this task using nonlabeled laparoscopic imaging with a particular focus on the diagnostic value of the peri-metastatic rim.

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: Our study’s objective is to evaluate RadOnc-GPT, a GPT-4o powered LLM, in generating responses to in-basket messages related to prostate cancer treatment in the Radiation Oncology department. By integrating it with electronic health record (EHR) systems, the goal is to assess its impact on clinician workload, response quality, and efficiency in healthcare communication. Methods/Study Population: RadOnc-GPT was integrated with patient EHRs from both hospital-wide and radiation-oncology-specific databases. The study examined 158 pre-recorded in-basket message interactions from 90 non-metastatic prostate cancer patients. Quantitative natural language processing analysis and two randomized single-blinded grading studies, involving four clinicians and four nurses, were conducted to evaluate RadOnc-GPT’s response quality in completeness, correctness, clarity, empathy, and estimated editing time. Response times were measured to estimate the time saved for clinicians and nurses. The study population included patient messages across all phases of care (pre-, during, and post-treatment) for those undergoing radiotherapy. Results/Anticipated Results: In the single-blinded grader study, clinician graders evaluated 316 responses (158 from human care teams and 158 from RadOnc-GPT). Results showed RadOnc-GPT outperformed human responses in empathy and clarity, while humans excelled in completeness and correctness. Sentiment analyses using TextBlob and VADER revealed RadOnc-GPT responses had a positive mean score of 0.25, whereas human responses clustered around neutral. VADER analysis indicated a high median score for RadOnc-GPT, nearing 1.0, reflecting predominantly positive sentiment, while human responses displayed a broader sentiment range, indicating sensitivity to context. Clinicians averaged 3.60 minutes (SD 1.44) to respond, compared to 6.39 minutes (SD 4.05) for nurses, highlighting RadOnc-GPT’s efficiency in generating timely responses. Discussion/Significance of Impact: RadOnc-GPT effectively generated responses to individualized patient in-basket messages, comparable to those from radiation oncologists and nurses. While human oversight is still necessary to avoid errors, RadOnc-GPT can speed up response times and reduce pressure on care teams, shifting their role from drafting to reviewing responses.

Objectives/Goals: Radiation nephropathy results in morbidity and mortality in patients receiving cancer treatment. In addition, low birth weight and low nephron number are associated with increased risk for chronic kidney disease. This study examined the development and severity of radiation-induced renal hemodynamic dysfunction in a low renal mass mouse model. Methods/Study Population: Male mice (C57Bl/6, 8–12-weeks) were used to determine a suitable radiation dose regimen. Mice were subjected to fractionated bilateral kidney irradiation with 5–6 fractions of an X-ray dose of 0, 6, 8, and 10 Gy at 24-hr intervals using a CT-image-guided irradiator. Body weight and mortality were monitored for 5 weeks in mice. In a separate set of experiments, the low renal mouse model, ROP Os/+, and their normal counterpart, ROP +/+ mice were subjected to 5 fractionated bilateral kidney irradiations at 24-hr intervals with an X-ray dose of 6 Gy. Renal blood flow was assessed from renal artery resistive index (RRI) over 5 weeks post-irradiation using an ultrasound system. Transcutaneous measurement of FITC-sinistrin clearance was used to determine glomerular filtration rate (GFR). Results/Anticipated Results: The C57Bl/6 mice that received 5–6 fractions of 8 and 10 Gy had more than 50% mortality, while 100% of the mice exposed to 5 fractions of 6 Gy survived for 5 weeks. Body weight was also significantly decreased in mice exposed to 5 or 6 fractions of 8 or 10 but not 6 Gy radiation. Nonirradiated C57Bl/6, ROP +/+, and ROP Os/+ mice had similar baseline GFR and RRI. Irradiation of 5 fractions at 6 Gy decreased GFR and increased RRI in C57Bl/6 and ROP +/+ mice. Interestingly, following 5 fractions at 6 Gy irradiation ROP Os/+ mice had 25% lower GFR than wild-type ROP +/+ mice (946.3 ± 50.3 vs. 1232.9 ± 69.3 µL/min/100g BW, p Discussion/Significance of Impact: Our study determined a suitable fractionated bilateral kidney irradiation dose regimen to evaluate radiation nephropathy. Data demonstrated that fractionated bilateral kidney irradiation leads to decreased renal hemodynamics in mice. We also demonstrated that irradiation caused greater renal hemodynamic dysfunction in low renal mass mice.

Objectives/Goals: To evaluate equity in utilization of free initial health evaluation (IHE) services among members of a limited health care program, the World Trade Center (WTC) Health Program (Program), to inform intervention development and provide insights for similar healthcare programs. Methods/Study Population: We included Program members who newly enrolled during 2012–2022, and who had an IHE or were alive for ≥ 1 year after enrollment. Program administrative and surveillance data collected from January 2012 to February 2024 were used. We evaluated two outcomes: timely IHE utilization (proportion of members completing an IHE within 6 months of enrollment) and any IHE utilization (proportion completing an IHE by February 2024). We described IHE utilization by enrollment year and various members’ characteristics and conducted multivariable logistic regression models to estimate adjusted odds ratios for IHE utilizations to identify factors related to potential inequities for the two member types: Responders, who performed support services, vs. Survivors, who did not respond but were present in the New York disaster area. Results/Anticipated Results: A total of 27,379 Responders and 30,679 Survivors were included. Responders were 89% male, 70% 45–64 years old at enrollment and 76% White. Survivors were 46% female, 54% 45–64 years old at enrollment, and 57% White. Timely IHE utilizations remained relatively stable (~65%) among Responders across time and increased from 16% among Survivors who enrolled in 2017 to 68% among Survivors who enrolled in 2021. Timely IHE utilization was lower for younger members (enrolled Discussion/Significance of Impact: This study highlights Program achievements and gaps in providing equitable IHE services. Strategies to improve members’ equitable IHE utilization can include: adopt/expand flexible scheduling; increase non-English language capacity and cultural competency; and facilitate transportation/assistance for members with accessibility barriers.

Objectives/Goals: We evaluated the implementation of a peer-facilitated research best practices training for Community Health Workers and Promotoras (CHW/Ps) at four new partner sites to increase the capacity and capability of a workforce increasingly involved in community-engaged research. Methods/Study Population: Staff were trained using a train-the-trainer model, and materials were disseminated to partners at three academic institutions and one community-based organization. Each site delivered the training virtually or in-person in English and/or Spanish. CHW/P learners at all sites completed online evaluation surveys about the impact of the training on their knowledge and skills for participating in research-related work, and two CHW/Ps from each site participated in follow-up interviews to gather feedback about their experiences. Staff completed fidelity monitoring, follow-up interviews, and three brief surveys regarding feasibility, acceptability, and appropriateness of implementing the training. Results/Anticipated Results: The four sites conducted six trainings with a total of 42 CHW/Ps. Two sites each conducted one in-person training in English while the other two sites each conducted two virtual trainings, one in English and one in Spanish. Staff noted facilitators to successful implementation, including providing a facilitator guide and course materials in both languages and tips sheets for navigating REDCap; using the train-the-trainer model; and compensating CHW/P learners for attendance. The primary barrier noted was not having a budget for in-person trainings (e.g., refreshments, printed materials). CHW/P learners reported positive experiences with few suggestions for improving the training. Discussion/Significance of Impact: Preliminary results suggest the research best practices training for CHW/Ps is feasible, acceptable, and appropriate for implementation by partners at academic institutions and community-based organizations, regardless of language (i.e., English or Spanish) or delivery (i.e., virtual or in-person).

Objectives/Goals: The never in mitosis kinase (NEK) family regulates vital processes, namely cell cycle progression, but their potential as therapeutic targets in TNBC has not been fully explored. Our studies aim to develop a toolkit to investigate the functional roles of NEKs in pathologies including carcinogenesis. Methods/Study Population: To assess differential NEK expression in normal and tumor tissues and correlation of gene expression with patient survival, we used Gene Expression Profiling Interactive Analysis (GEPIA) and Kaplan–Meier Plotter (KMPlot) pan-cancer analysis, respectively. Basal NEK protein levels were determined by immunoblot across a panel of cell lines, including breast cancer, osteosarcoma, hepatocellular carcinoma, and non-cancerous cells, to identify appropriate systems for evaluation of NEK function. Doxycycline-inducible cell lines were generated by transduction with lentiviral stocks of NEK shRNA and overexpression constructs and antibiotic selection. Expression was analyzed by qPCR and immunoblot. Results/Anticipated Results: Expression of NEK2, 4, 5, 6, 8, and 11 was higher in breast tumors compared to normal tissue by GEPIA analysis. Further examination using KMPlot showed a correlation between elevated NEK6 expression and decreased overall survival in patients with aggressive cancers. As an initial proof-of-concept study, we analyzed NEK6 protein expression in breast cancer cells. Levels of NEK6 were elevated in TNBC cells (MDA-MB-231) compared to hormone receptor positive (HR+) breast cancer cells (MCF7). Using complementary approaches to investigate the functional role of NEK6 in breast cancer, we depleted NEK6 expression using shRNAs in TNBC cells and expressed NEK6 in HR+ cells Discussion/Significance of Impact: Because kinase dysregulation promotes oncogenesis and metastasis, targeting kinases is a key strategy in therapeutic development. A NEK-specific molecular toolkit allows researchers to elucidate NEK functions and contributions to carcinogenesis, promoting advancement of novel therapies.

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: The University of Minnesota’s two-year TL1 program provides flexible and individualized education and training for a diverse cohort of scholars committed to pursuing impactful careers in clinical and translational science (CTS). The program aims to strengthen the nation’s biomedical workforce by developing scientists skilled in clinical and translational research. Methods/Study Population: The TL1 program recruits PhD candidates and postdoctoral fellows from a wide variety of graduate programs in colleges and departments across the University. To date, we have trained 26 predoctoral and 9 postdoctoral Scholars in 3 cohorts. Scholars represent dozens of disciplines and the full translational spectrum. These interdisciplinary cohorts are in a unique position to realize the fundamental characteristics of a translational scientist. Entrance/exit surveys and exit interviews provide program leadership with information for quality improvement and areas scholars believe contribute the most to their education and training in CTS. Results/Anticipated Results: Entrance/exit surveys indicated Scholar-perceived benefits of training in an interdisciplinary program, including growth in translational scientist characteristics (e.g., Boundary Crosser, Team Player). Exit interviews showed Scholars appreciated the cohort model bringing together trainees from many different research areas. They valued exposure to varied perspectives, talking through challenges and solutions with each other, and learning others shared similar issues. They valued the Scholar community they developed. Several felt siloed in their careers before the program and reported that TL1 participation connected them to others outside their own area of focus, expanded their knowledge about different research methods and revealed more pathways for translation. Discussion/Significance of Impact: Recruiting and training a diverse interdisciplinary cohort of pre- and postdoctoral TL1 Scholars promoted synergy in translational research, science skills and competencies, and transformed the perspectives of Scholars’ views on the importance of interdisciplinary collaboration to accelerate science.

Objectives/Goals: Our research goal is to translate medical guidelines for adolescent-centered contraceptive counseling into improved clinical practice. Here, we describe the process of co-designing a training program for adolescent-serving primary care clinicians with teen, caregiver, and clinician advisory boards. Methods/Study Population: We recruited teens, caregivers, and clinicians residing in North Carolina to participate in three virtual advisory boards separated by role. Eligible teen advisors were assigned female at birth and 15–19 years old; eligible clinicians provided care for teen patients; and all groups were purposively sampled to reflect diverse identities and experiences. At each advisor meeting, we used human-centered design techniques to elicit participant priorities, generate training content and engagement strategies, and obtain feedback on the final training program. We conducted a focus group at our final meetings and used rapid qualitative analysis to understand our advisors’ experiences participating in program co-development. Results/Anticipated Results: We partnered with 20 advisors with diverse identities across geographic location, race and ethnicity, sexuality, and experiences with disability. During 15 meetings from January to May 2024 (five with each advisor group), we developed a 3-hour virtual, synchronous training for adolescent-serving primary care providers to improve their contraceptive counseling skills. The curriculum includes five interactive modules and a resource toolkit. Advisors described motivations to participate (e.g., chance to share their perspective, desire to make change), positive experiences with the advisory boards (e.g., opportunities to learn, to connect with others), and opportunities for improvement (e.g., better technology orientation). Discussion/Significance of Impact: We describe developing a successful longitudinal partnership with three community advisory boards and co-creating a training program that incorporates community-led priorities and perspectives, including youth. This approach can be adapted for other clinician training programs seeking to center community voices.

Objectives/Goals: To investigate interventional clinical trial participation overall and by race, gender, and age. Methods/Study Population: We used Epic Cosmos, an aggregated, de-identified EHR platform including over 270 million patients, to examine overall clinical trial participation and the race, gender, and age composition of participants versus non-participants. Patients ≥5 years old with known race and gender and at least one healthcare encounter between 2021 and 2024 were included. Interventional trial enrollment was identified by a “research flag” indicating current or past participation in an interventional study within an Epic system contributing data to Cosmos. Race was categorized as American Indian, Asian, Black, Native Hawaiian, or White. Age-adjusted relative representation (RR) ratios were used to compare participation, with RR >1 indicating over-representation and RR Results/Anticipated Results: Of 130,455,189 patients meeting eligibility criteria, 0.52% (673,425) of patients were active or inactive in an interventional clinical trial. Results are shown in the figure below. The poorest representation was from Asian and NH/PI persons. Representation was most similar to the patient population for whites and AI/AN persons. Black males participated less and women, more than predicted by patient composition. Older patients participated more frequently than younger (age, mean (SD), y, 53 (22) vs. 46 (23); p Discussion/Significance of Impact: This is the first study we know of describing interventional trial participation in the USA across millions and millions of patients. Further research is needed to clarify whether these differences are due to the nature of the studies themselves (e.g., OB/GYN trials including only women, etc.) versus disparities in recruitment or otherwise.

Objectives/Goals: Predictive performance alone may not determine a model’s clinical utility. Neurobiological changes in obesity alter brain structures, but traditional voxel-based morphometry is limited to group-level analysis. We propose a probabilistic model with uncertainty heatmaps to improve interpretability and personalized prediction. Methods/Study Population: The data for this study are sourced from the Human Connectome Project (HCP), with approval from the Washington University in St. Louis Institutional Review Board. We preprocessed raw T1-weighted structural MRI scans from 525 patients using an automated pipeline. The dataset is divided into training (357 cases), calibration (63 cases), and testing (105 cases). Our probabilistic model is a convolutional neural network (CNN) with dropout regularization. It generates a prediction set containing high-probability correct predictions using conformal prediction techniques, which add an uncertainty layer to the CNN. Additionally, gradient-based localization mapping is employed to identify brain regions associated with low uncertainty cases. Results/Anticipated Results: The performance of the computational conformal model is evaluated using training and testing data with varying dropout rates from 0.1 to 0.5. The best results are achieved with a dropout rate of 0.5, yielding a fivefold cross-validated average precision of 72.19% and an F1-score of 70.66%. Additionally, the model provides probabilistic uncertainty quantification along with gradient-based localization maps that identify key brain regions, including the temporal lobe, putamen, caudate, and occipital lobe, relevant to obesity prediction. Comparisons with standard segmented brain atlases and existing literature highlight that our model’s uncertainty quantification mapping offers complementary evidence linking obesity to structural brain regions. Discussion/Significance of Impact: This research offers two significant advancements. First, it introduces a probabilistic model for predicting obesity from structural magnetic resonance imaging data, focusing on uncertainty quantification for reliable results. Second, it improves interpretability using localization maps to identify key brain regions linked to obesity.

Objectives/Goals: This study aims to harmonize quality indicators (QIs) across University of Toronto-affiliated microbiology labs to establish universal benchmarks that enhance performance, patient safety, and health outcomes. Harmonized QIs will enable effective comparisons and enhance the consistency of care. Methods/Study Population: The study employed the Delphi method, a structured and iterative process to build consensus. An expert panel of clinical microbiology trainees, medical microbiologists, trainees, and site leads from five University of Toronto-affiliated microbiology labs was assembled. Initial insights were gathered through surveys and a comprehensive scoping review of the literature. The study involved two rounds of feedback, a SurveyMonkey-based survey, with a defined consensus of 75% agreement among participants. Followed by an implementation survey conducted through REDCap to assess how these QIs were adopted in practice and identify barriers to implementation. Results/Anticipated Results: The study achieved consensus on nine high-impact quality indicators, including blood culture volume and contamination rates, cerebrospinal fluid transport time, and turnaround times for Gram stain results. Blood culture contamination and positivity rates garnered the highest agreement, at 100% and 91%, respectively. While some indicators were widely accepted and implemented, others faced resistance due to feasibility concerns. The study also identified significant variability in the level of adoption across the participating laboratories, pointing to operational challenges and the need for further efforts to address these barriers. Discussion/Significance of Impact: This study highlights the importance of QI harmonization in improving lab services and patient safety. It reveals challenges in standardizing practices but promotes uniformity in QIs, laying the groundwork for better inter-lab collaboration, consistent outcomes, and improvements in microbiology.

Objectives/Goals: Youth with IBD have preventive, psychosocial, and acute care needs beyond those of peers, yet receipt of services does not match those needs. Our objectives are to assess the feasibility of (1) an individualized care plan intervention to improve perceived and measured care quality and (2) a pragmatic trial design embedded in pediatric IBD practice. Methods/Study Population: This is a pilot rollout-design randomized trial (n = 60) at a regional academic medical center. Eligible patients are 13–19 years old with IBD for at least 3 months and scheduled for a follow-up visit during the trial. Research staff recruits from one cluster at a time until goal enrollment (14–16). Enrollees are randomized 1:1 to intervention (MyIBD now) or control (MyIBD after the trial). MyIBD combines a tabular summary of individualized acute, chronic, and preventive care needs with nurse facilitator support for patients to use the information. Surveys at baseline, 6 and 12 months measure care quality (Patient Assessment of Chronic Illness Care scale, vaccines, health services) and patient self-management skills (Partners in Health scale). Implementation outcomes are collected via chart review. Results/Anticipated Results: To date, 44 subjects have been randomized. Among subjects, the mean age is 16 years; 73% have Crohn’s disease, 77% have commercial insurance, 75% receive anti-TNF therapy, and 14% live in a rural area. Mean baseline perceived care quality (PACIC scale) is 76.9 (sd 16.3; out of 100); mean baseline perceived self-management skill (PIH scale) is 78.1 (sd 13.4; out of 96). On objective care quality measures, 59% have completed the HPV vaccine series, 32% have received an additional pneumonia vaccine; in the past year 68% have had a screening for mood disorders, 20% an emergency department visit for IBD, and 18% an IBD hospitalization. To date, the IBD clinical team has achieved 100% completion (intervention subjects receive MyIBD plus nurse facilitation) and 0% contamination (control subjects inappropriately receive MyIBD). Discussion/Significance of Impact: Study results to date support the feasibility of the pragmatic, embedded trial design and indicate opportunities for improvement in care quality as perceived by patients and as measured by common preventive and acute care quality indicators. An individualized care plan supported with nurse facilitation may improve pediatric IBD care quality.

Objectives/Goals: To design and implement programming that better prepares graduate students for diverse roles in a variety of workforce environments, our study models the training landscape and programming needs of graduate students in behavioral, clinical, and biomedical graduate programs at a large Midwestern school of medicine and public health. Methods/Study Population: We conducted six focus groups (two graduate program manager focus groups and four graduate student focus groups), to assess the programming, career development, and training needs of graduate students. Using a grounded theory approach, we first engaged in open coding of a sample of transcripts. After developing a codebook, we continued with an iterative coding process interspersed with coder meetings to discuss emerging and changing codes. Using the framework of landscape analysis allowed our coding and modeling to go beyond graduate student needs and study the varying relationships and contexts that impact graduate students throughout their training, such as relationship to supervisor or institutional policies. Results/Anticipated Results: Preliminary results indicate that students wrestle with their status as both students and workers. Specifically, conflict arises between graduate and supervisor expectations around time spent in class, lab, and other career development activities based on these divergent roles. Students and program managers also note the disparities that arise from the university’s lack of standard, formalized policy on labor issues, such as paid leave. Data also suggest that students on training grants note the difference in access to career development resources compared to colleagues. In many cases, students themselves coordinate ad hoc programming to better suit their career and professional development needs, although this work is not a required aspect of their training. Discussion/Significance of Impact: We characterize current graduate training landscapes, which continue to shift as graduate student bodies diversify, unionize, and express interest in increasingly varied biomedical careers. Data from multiple perspectives facilitate creating, implementing, and evaluating supportive training programs that meet identified student needs.

Objectives/Goals: To identify the genomic mechanisms underlying cross-species regulation of longevity among mammals and birds and to characterize the impact of those conserved pathways on human aging. More broadly, this study aims to develop a novel evolutionary approach to understand the genetics of complex traits. Methods/Study Population: High-quality genome sequences for 194 bird species and 295 mammal species with reliable longevity and body size data were obtained from publicly available resources. The data include coding sequence alignments of 16,863 mammalian and 14,565 avian one-to-one orthologous genes. Gene-wise relative evolutionary rates (RERConverge) and maximum likelihood phylogenetics (PAML) were computed to assess for evidence of purifying selection and positive selection for longevity. As part of ongoing analysis, human orthologs of selected results will be examined in the UK Biobank for validation. Results/Anticipated Results: Preliminarily, we have found a signal of concordant positive selection between two classes of vertebrates separated by hundreds of millions of years. Several genes show signals of positive selection in long-lived species of both birds and mammals. Ongoing work focuses on elucidating the relationship between relative evolutionary rates and positive selection, the overlap in selection signature between long-lived animals with large body sizes and those who are exceptionally long lived for their body size, and further elaborating on convergence between mammals and birds. Discussion/Significance of Impact: Currently, most scientific knowledge about aging is from experiments on short-lived model organisms. By systematically studying the genomes of long-lived mammals and birds, we aim to develop a new method for studying complex traits and uncover novel insights into the mechanisms of longevity.