Objectives/Goals: Lack of comparative data limits research operations quality improvement (QI). The Northwest Participant and Clinical Interactions (NW PCI) Network, a group of 17 unaffiliated university and health system-based research centers, built an operations dashboard to track efficiency and enable multisite QI projects. Methods/Study Population: A Data Governance Working Group was assembled to establish shared data governance, draft nondisclosure (NDA), and data transfer and use agreements (DTUA) suitable across organizations and standardize research operations metric definitions. Sites in the NW PCI Network were recruited to participate in a pilot program to assess data sharing and governance infrastructure, data collection, upload procedures, and data visualization tools. The NW PCI Coordinating Center developed an analytical data dashboard of research operations metrics and conducted semi-structured interviews with participating sites to understand barriers and facilitators of program success. Results/Anticipated Results: Four sites (2 health systems, 2 universities) were recruited for the pilot and reviewed and executed NDAs and DTUAs. Three of the sites have submitted data for a total of 1,405 studies. Of the 24 requested data operations metrics (e.g., study startup, recruitment, implementation, and basic study information), 71% of the metrics were submitted by all three sites (n = 17), 25% were submitted by at least one site (n = 6), and 4% were not submitted by any site (n = 1). Interviews with sites after data submission found areas for improvements (clarification of data definitions, efficiency of data upload process) and positive effects for sites (e.g., process improved insight into own data operations). Discussion/Significance of Impact: Unaffiliated research centers created data governance procedures to enable sharing of operations data. Pilot sites successfully loaded most but not all operations data to the dashboard. Interviews identified process limitations and opportunities for improvement to inform expansion to all NW PCI sites.

Objectives/Goals: To address the manual, time-consuming processes of validating IRB compliance and ensuring the secure delivery of i2b2 data, this project automates compliance checks, streamlines Protected Health Information (PHI) access, and provides timely, secure data availability while reducing administrative burdens and non-compliance risks. Methods/Study Population: This project enhances the i2b2 application to automate compliance processes and facilitate secure data delivery through integration with REDCap. By linking i2b2 with the IRB system, the application performs automatic compliance checks for project requests, verifying GCP and HIPAA certifications, only allowing the release of IRB-approved PHI variables, safeguarding against unauthorized data access. Manual signatures confirm non-automated compliance processes. Once verified, the application automatically creates a REDCap project, assigns user access, and securely delivers data, ensuring compliance with HIPAA regulations. Results/Anticipated Results: The automated system successfully streamlined IRB compliance checks and data delivery for i2b2 requests. Validation of certifications like GCP and HIPAA, now occurs automatically, significantly reducing the risk of non-compliance. Personnel access to data is limited to IRB-approved PHI, ensuring data security and adherence to institutional standards. The integration with REDCap has reduced manual processes, cutting data request processing time to approximately 30 minutes. Researchers and administrative staff experienced a notable decrease in administrative burden, with faster, more efficient access to approved data while maintaining full compliance with IRB and HIPAA regulations. Discussion/Significance of Impact: The lessons learned can be adapted by institutions to improve compliance efficiency and reduce administrative overhead. Implementing similar automation of certification checks and data delivery, sites can enhance data security, minimize errors, and ensure faster, compliant access to research data.

Objectives/Goals: The Clinical Research Education in Genome Science (CREiGS) program was developed to address the need for faculty and trainees conducting biomedical research to gain foundational training in genome science and accelerate the clinical adoption of genomic medicine. CREiGS, funded by NHGRI, offers comprehensive training in genomic analysis and statistical computing. Methods/Study Population: CREiGS targets a diverse pool of medical/doctoral students, postdocs, and faculty from academic institutions nationwide. The hybrid program included an 11-week online phase and a 3-day in-person phase, focusing on genomic science, statistical analysis and R programming, rigor and reproducibility, and engaging diverse populations in genomics research. Advanced special topics lectures included: decision analysis for genomics research, bioethical engagement of indigenous communities in genomics research, elucidating gene networks for advancing human health, etc. Strategies for recruiting diverse participants and ensuring an inclusive learning environment were informed by the Diversity Recruitment External Advisory Board. Participants’ skills were evaluated via pre- and post-course surveys. Results/Anticipated Results: Of 187 participants over 5 cohorts, 68.4% were female and 47.0% from underrepresented groups. The cohort spanned career stages, with 35.3% students, 34.2% postdocs, and 30.4% faculty, most of whom were at the junior level. Competency evaluations showed improvements in all core competencies of the course: (1) independently carrying out small-scale research improvements, (2) confidence collaborating with statisticians, bioinformaticians, and other genome science experts, (3) applying appropriate statistical methods for the analysis of genetics and genomics data, (4) accurately interpreting findings from genome research studies, (5) critiquing the internal/external validity of genome research studies, and (6) effectively engaging diverse populations and community stakeholders. Discussion/Significance of Impact: CREiGS successfully provided inclusive, high-quality, genomic and statistical training, to diverse scientists enhancing their research capacity and methodologic competency. Findings from longer term evaluations examining the contribution of CREiGS to participants’ genome science-related scholarly productivity are forthcoming.

Objectives/Goals: Obesity has been classified as a global epidemic and origin of numerous health issues. The central hypothesis of this study is that psychological measures, DNA methylation, and gene transcription will predict obesity-related outcomes after lifestyle interventions, and such interventions may alter DNA methylation profiles. Methods/Study Population: This study consisted of a randomized-controlled trial examining the effects of lifestyle +/- stress reduction interventions in 285 highly stressed parents with obesity, followed for 2 years. Full participants received nutrition and activity counseling, and were randomized to either a stress reduction intervention or a contact control. Those who otherwise qualified for the study but unable to fully participate were included in a no intervention control group. The intervention consisted of 12 weeks of nutrition and activity counseling +/- 2-hour weekly stress reduction interventions using MBSR and CBT-based strategies. DNA methylation was assessed using Illumina EPIC arrays. Results/Anticipated Results: Using linear mixed models (LMMs), this study will first examine the hypothesis that baseline psychological measures and pre-existing methylation sites associated with obesity and glycemic control (e.g., ABCG1, ATP10A, TXNIP, SREBF1, RNF39, and SOCS3) predict changes in BMI, HOMA-IR, and HgbA1C post-intervention and at 1 and 2 year follow-ups. Using sites that demonstrate statistical significance, we will develop a polymethylation risk score predictor of change in BMI. Next, we will examine the hypothesis that interventions which reduce obesity may also lead to improvements in epigenetic aging using LMMs to determine if changes in BMI or HOMA-IR predict changes in epigenetic age acceleration over the course of the study. Discussion/Significance of Impact: This work examines whether psychological factors and/or epigenetic markers may be used in patient stratification at initiation of treatment, enabling improved treatment selection, fewer years of obesity and decreased risk of comorbidities. This proposal also asks whether lifestyle interventions impact the aging process itself.

Objectives/Goals: Our main objective was to compare 5-year survival and organ function between patients with sickle cell disease (SCD) who underwent hematopoietic cell transplant (HCT) and those who did not undergo HCT. We hypothesized that organ function would be improved in those with SCD who underwent HCT when compared to those who remained on standard therapy. Methods/Study Population: This IRB-approved, retrospective study includes patients with SCD treated at Children’s Healthcare of Atlanta. Cases underwent HCT between 2010 and 2016. They were randomly matched with 2 patients with SCD who did not undergo HCT. Match criteria included age, sex, disease genotype, and disease severity, which was determined by the number of hospitalizations in the 5 years pre-HCT, prior intensive care unit admission, and prior chronic transfusion therapy. Data extracted included SCD treatment, hospitalizations, emergency department visits, and organ function pre-HCT and 1-, 2-, 3-, and 5-years post-HCT. Organ-specific outcomes and overall survival were compared between the two groups using cumulative incidence curves and Kaplan–Meier analyses. Normal FEV1 and FVC in this analysis were >80% predicted. Results/Anticipated Results: Thirty-seven cases who had undergone HCT were matched with 74 controls who continued with standard medical therapy. The median age was 8 years for both groups and 59% were females. The median disease severity score was 2 in both groups. At baseline, 70.3% of the HCT group completed pulmonary function tests (PFTs) compared to 35.1% of the non-HCT group. Of these, 73% in both groups had a normal FEV1. In terms of FVC, 57.7% of HCT patients and 76.9% of non-HCT patients had a normal FVC pre-HCT. At 5 years post-HCT, 56.8% of the HCT group had PFTs completed compared to 21.6% of the non-HCT group. Among these, 85.7% in the HCT group had a normal FEV1 compared to 75% in the non-HCT group, while 90.6% had a normal FVC in the HCT group compared to 75% in the non-HCT group. Two of 37 in the HCT group and 1 of 74 in the non-HCT group died (p = 0.21). Discussion/Significance of Impact: Our data suggest that post-HCT, the proportion of patients falling in the normal range for FEV1 and FVC increases. This increase is not seen in the non-HCT group, indicating that HCT may improve this organ function. There was no difference in survival between the groups, indicating the risk of HCT mortality may not be greater than the risk of living with SCD.

Objectives/Goals: To reduce cervical cancer in the USA, it is essential to identify the reasons underlying the low HPV vaccination rates. This study aims to identify knowledge and beliefs about HPV vaccination among women in rural areas. The knowledge gained from this study will directly lead to developing an education tool tailored specifically for women in rural areas. Methods/Study Population: We conducted a cross-sectional study from November 2022 to July 2023. We recruited women (n  =  141) who visited a mobile health unit in rural North Louisiana. The inclusion criteria were women aged 25–64 years who spoke English, had not undergone a total hysterectomy, and had no history of cervical cancer. Data collected included sociodemographic characteristics, sexual history, awareness and knowledge of HPV infection, cervical cancer, genital warts, and HPV vaccination, the perceived risk of acquiring genital HPV infection and developing cervical cancer, and the willingness to receive an HPV vaccine. Descriptive statistics were used to evaluate participant responses. Written informed consent was obtained before completing the self-administered questionnaire. Results/Anticipated Results: Our findings showed significant gaps in HPV vaccine knowledge and uptake. Approximately 40% of the participants were unaware of the HPV vaccine, 96.5% had never received it, and 91.4% had never been offered it. However, 42% indicated a willingness to consider vaccination if it were offered. Factors influencing their decision to vaccinate against HPV included a family history of cervical cancer (44.7%), having multiple sexual partners (48%), and engaging in unprotected sex (61.7%). Furthermore, there was significant uncertainty surrounding the vaccine, with 65.2% of participants unsure about its safety, 66% unaware of potential health risks, and 47.5% uncertain about its effectiveness in preventing HPV. Discussion/Significance of Impact: Our research emphasizes the need for tailored behavioral interventions to address knowledge gaps about the HPV vaccine. Low HPV vaccination rates in rural areas contribute to health disparities in cervical cancer. Implementing educational interventions in healthcare settings can enhance vaccination rates and mitigate the risk of cervical cancer.

Objectives/Goals: Develop trauma-informed, victim-centered care skills. Foster student-led, translational research on trauma and victim services engage students in public policy and public health engagement support professional growth through research presentation and publication. Methods/Study Population: A review of the 2018–2021 mentorship program that engaged ten graduate students from diverse institutions (seven from San Juan Bautista School of Medicine, one from Interamerican University, one from UPR-Medical Sciences Campus, and one from Ponce Health Sciences University). Students participated in trauma-informed and victim-centered research projects focusing on sexual violence, child abuse, and victim services. They were mentored by Dr. Linda Laras and Dr. Linda Pérez at the Puerto Rico Health Justice Center, receiving hands-on experience through case discussions, literature review, research design, data collection, and presentations at the Start By Believing Symposium. Results/Anticipated Results: From 2018 to 2021, students developed trauma-informed care skills and conducted research on topics such as therapy dogs in courtrooms, victim services, and the impact of child sexual abuse. The results of this mentorship program included a publication in Cureus (10.7759/cureus.13644) and presentations at the Start By Believing Symposium, attended by legal and community professionals. The Fundación Intellectus Sexual Violence Research Scholarship was awarded, and the research earned award winning posters at multiple symposiums, including the SJBSM Interdisciplinary Research Symposium. Discussion/Significance of Impact: This mentorship translates trauma-informed research into real-world applications for sexual violence intervention. Medical students gain practical skills to address trauma in residency, while public health students shape policy. These research efforts have resulted in best practices and policy changes in Puerto Rico.

Objectives/Goals: Engaging interest holders in research is increasingly common, and guidelines include creating engagement plans. A detailed plan may be especially helpful when researchers perceive engagement as difficult or less relevant. We tested whether a study’s translational stage or an investigator’s years of research experience affect their perceptions. Methods/Study Population: Since 2019, the Tufts Clinical and Translational Science Institute Pilot Studies Program required applicants to submit plans to engage interest holders. Applicants in three cohorts responded to a survey about this requirement, including perceived difficulty developing an engagement plan, perceived relevance of engagement, and self-reported years of research experience (≤5, 6–10, and ≥10 years). Two raters assigned translational stage(s) of proposed studies: T0 (basic science), T.5 (pre-clinical to initial human studies), and T1 through T4. Separate analyses were conducted when multistage studies were coded as the earliest vs. latest stage and for individual stage vs. groups of stages (T0/T.5/T1 vs. T2/T3/T4). The Fisher’s exact statistical test was used to assess associations between variables. Results/Anticipated Results: Analyses included 67 participants. Developing an engagement plan was perceived as more difficult for studies at earlier translational stages when those studies were coded as the earliest applicable stage. This significant association held both when stages were grouped as T0/T.5/T1 and T2/T3/T4 (P  =  .03) and when analyzed as a single stage (P  =  .01); however, when studies were coded as the latest applicable stage, there were no significant associations. Similarly, when multistage studies were coded as the earliest applicable stage, engagement was perceived as less relevant for early-stage studies when grouped (P  =  .04), but not for individual stages or when studies were coded as the latest applicable stage. No significant association between years of research experience and perceived difficulty was identified. Discussion/Significance of Impact: Results show that investigators conducting early-stage research perceive more difficulty engaging interest holders, aligning with prior qualitative studies. These investigators may need more evidence of the value added to early-stage studies, targeted and practical training, and funder requirements to establish a culture of engagement.

Objectives/Goals: Our goal was to investigate the associations between parental resilience and parenting behaviors, and their relationship to their offspring’s reward neurocircuitry function; in particular, the reward prediction error (RPE) circuit, a transdiagnostic marker of psychopathology. Methods/Study Population: N = 26 parent–child dyads (children ages 10–14) were recruited. Parents reported on parenting behaviors using the Alabama Parenting Questionnaire (APQ), and resilience using the Connor-Davidson Resilience Scale (CD-RISC). Children performed the Novelty task, a reward learning task, during fMRI scanning. Trial-by-trial RPEs were calculated based on a reinforcement learning model. Brain regions of interest (ROIs) including the nucleus accumbens, anterior putamen, and ventromedial prefrontal cortex were created (regions implicated in RPE representation). Results/Anticipated Results: The APQ parental involvement subscale was associated with increased negative affect tolerance (r = 0.40, p Discussion/Significance of Impact: Findings suggest that parental factors may impact neurocircuitries underlying psychopathology in offspring, and consequently, risk for offspring psychopathology. Interventions designed to increase parental resiliency may reduce risk for psychopathology in offspring, perhaps by increasing parental involvement and neural RPE sensitivity.

Objectives/Goals: Kentucky (KY) is a high priority ending the HIV epidemic state, with high rates of new HIV diagnoses tied to injection drug use. The overall goal of this pilot is to launch sentinel surveillance of bloodborne infections and drug compounds among people who inject drugs (PWID) to monitor trends in near-real time and inform rapid community response. Methods/Study Population: In collaboration with the Clark County, KY, syringe service program (SSP), the pilot study involves two 1-month waves of data collection: enrolling eligible SSP participants and conducting anonymous behavioral surveys, collection of participants’ syringes, laboratory testing of syringes to detect HIV and hepatitis C (HCV), drug residue testing through National Institute of Standards and Technology, and statistical modeling approaches to produce outputs of bloodborne infection and drug detection. Syringes are tested from each enrolled individual for: 1) HIV antibody; 2) HCV antibody; 3) HIV and HCV PCR; 4) HIV antigen; and 5) drug residue. Collaboration with community and PWID stakeholders will identify optimal messaging for reporting results. Results/Anticipated Results: The first wave community-facing pilot was conducted in September–October 2024. 29 survey responses were obtained; median age of the sample is 42 years, 55.2% are gender female; 37.9% reported unstable housing in the past week. Primary drugs of injection reported via survey in the prior month were methamphetamine (62.1%), heroin (13.8%), fentanyl (13.8%), buprenorphine (10.3%), meth and fentanyl in combination (3.4%). PWID reported returning 900 used syringes and a median of 15 per participant visit. At most recent testing, 69.0% reported a positive HCV test; 0% reported a positive HIV test. Some level of drug checking with fentanyl test strips in past month was reported by 51.7%. Initially, 20 syringes were tested for drug compounds; results are pending. HIV and HCV detection testing will be completed by early 2025. Discussion/Significance of Impact: Early results document proof of concept for our sentinel surveillance study; all individuals screened were willing to participate in surveys and syringe collection. New methods to identify risk for disease outbreaks and emerging drugs can inform rapid allocation of prevention resources at a community level, especially where testing is infrequent.

Objectives/Goals: Methicillin-resistant Staphylococcus aureus (MRSA) is a human bacterial pathogen and is classified as a serious threat. MRSA has become resistant to most B-lactam antibiotics (penicillins and cephalosporins). The goal of this study is to identify an antibiotic adjuvant capable of resurrecting B-lactams for the treatment of MRSA infections. Methods/Study Population: A fluorescence-reporter assay was used to screen a compound library. Minimum-inhibitory concentrations were assessed for the compounds against various MSSA and MRSA strains. A common resistance mechanism to B-lactams by MRSA is by the function of the bla operon. One gene in this operon encodes for a B-lactam sensor/signal transducer protein BlaR, the primary target of this study. Inhibition of BlaR by compound 1 (best potentiator of oxacillin) was studied by nano-differential scanning fluorimetry (nanoDSF), surface plasmon resonance (SPR), scanning electron microscopy (SEM), and time-kill assays. Results/Anticipated Results: We identified 80 compound hits from a 1,974-compound NCI library. Twenty-four compounds showed potentiating ability (2- to 4,096-fold decrease in MIC for oxacillin). Seven compounds exhibited melting temperature shifts by nanoDSF of BlaR, indicating binding. SPR determined compound 1 has a binding affinity of 31 micromolar to BlaR-SD. SEM images showed disruption in the S. aureus cell wall on exposure to compound 1 and oxacillin. S. aureus N315 showed 3-log reduction in bacterial count treated with a mixture of compound 1 and oxacillin. Discussion/Significance of Impact: Compound 1 targets BlaR-SD, which restores S. aureus susceptibility to treatment by oxacillin. There are currently few antibiotics available in the clinic capable of treating MRSA infections. The combination hold promise of a treatment option for MRSA.

Objectives/Goals: Skilled clinical research professionals are essential to efficient and effective research teams, but many undergraduate students are not aware of staff-level careers in the field. To address this, the Michigan Institute for Clinical and Health Research launched the Clinical and Health Research Professional (CHRP) Pathways Program. Methods/Study Population: The 10-week hybrid CHRP Pathways Program was piloted in Summer 2024. Undergraduate students interested in research careers were recruited from local universities and community colleges. The program consisted of 8 hours/week of didactic curriculum guided by ECRPTQ competencies and 32 hours/week of mentored work experience on research teams. Classroom activities were completed with participants from a partner program within the university. Surveys were administered at 3 weeks and 10 weeks along with an end-of-program focus group to assess acceptability and self-reported learning outcomes. Results/Anticipated Results: The pilot CHRP Pathways Program enrolled 3 students and was well-received by participating students and mentor research teams. Students agreed that they would recommend the program to their classmates. Students indicated that the program helped them understand the role of a study coordinator, provided insight into research career paths, and helped them form professional relationships. Self-reported confidence levels in a range of research competencies increased. Two students who completed the 10-week program chose to continue working part-time with their research teams while continuing their undergraduate studies. Discussion/Significance of Impact: Experiences like the CHRP Pathways Program provide valuable exposure to staff-level research career opportunities for students engaged in health science studies. They can address an existing workforce gap by equipping college graduates with relevant work experience and basic research competencies.

Objectives/Goals: This study aims to understand the prevalence of trauma in young adults and what sociodemographic factors influence trauma exposure and type of trauma. It also seeks to explore functional connectivity and neural network patterns associated with trauma by analyzing resting state magnetic resonance imaging (MRI) data. Methods/Study Population: Sociodemographic data will be analyzed from participants aged 18–25 years, such as age, gender, race, ethnicity, and highest level of education completed. Trauma exposure will be assessed based on the DSM-5 criteria of trauma through phone screenings and clinical interviews. The data will be categorized based on trauma type and statistical analyses will be conducted to explore potential sociodemographic patterns related to trauma. Additionally, resting-state MRI data will be utilized to identify potential neural correlates of trauma exposure. Results/Anticipated Results: It is anticipated that sociodemographic factors such, race and ethnicity, and highest level of school completed may influence the likelihood of experiencing traumatic events. It is predicted that in the resting-state MRI analysis that there will be altered functional connectivity in trauma exposed young adults in regions such as the amygdala, hippocampus, and prefrontal cortex since those regions are implicated in emotional regulation and stress response. Some changes may also be seen in the default mode network and salience network. Discussion/Significance of Impact: Trauma exposure can alter neural circuitry, leading to emotional processing difficulties and heightened stress response, with lasting effects on mental health and brain development. Prevention efforts and targeted treatments can be guided by identification of affected brain networks and sociodemographic factors that increase trauma risk.

Objectives/Goals: Bacterial dysbiosis has emerged as an accomplice in the progression of many cancers. The pancreas microbiome changes in pancreatic cancer patients. The mechanisms via which components of the microbiome regulate tumor growth is unclear. We seek to determine if bacterial dysbiosis influences cancer cell behavior thereby promoting tumor progression. Methods/Study Population: We performed immunohistochemistry for lipopolysaccharide and observed bacteria preferentially located in close proximity to cancer cells. We utilized an in vitro cell culture system and in vivo mouse models, in the presence and absence of gut bacteria, to assess the effect of bacteria and bacterial metabolites on pro-tumorigenic signaling and transcriptional changes in the cancer cell. We analyzed cancer cells and epithelial cells using RNA sequencing, flow cytometry, and enzyme-linked immunosorbent assay. We also used targeted metabolomics to identify bacterial and cancer cell produced metabolites. Results/Anticipated Results: We found microbial dysbiosis can induce proliferation, an inflammatory response and an increase in tryptophan metabolism via the kynurenine pathway in the pancreatic cancer cell. Along with upregulated expression of IDO1 in vivo, we observe an increase in nicotinic adenine mononucleotide. Also, we observe an increase in nicotinic acid in vitro and nicotinic adenine dinucleotide within the cancer cell compartment in the presence of bacteria and bacteria conditioned media. Due to the critical role in many vital pathways of cell survival, NAD+ production is thought to play a significant role in cancer progression. Nicotinic acid can stimulate NAD production to protect cells from cell death. Discussion/Significance of Impact: Pancreatic cancer is associated with a distinct tumor microbiome and ablation slows disease progression. Our data delineate mechanisms via which microbes modulate the pancreatic cancer cell and provide insight into therapeutic strategies for gut microbial modulation in treating pancreatic cancer.

Objectives/Goals: Opioid use disorder (OUD) in pregnancy and its implications on the maternal-fetal interface has been relatively understudied. Here, we aimed to uncover the impact of maternal OUD on placental structure, function, and inflammatory responses and further stratified our findings by maternal hepatitis C (HCV) infection. Methods/Study Population: To address this knowledge gap, we collected placental tissue from healthy pregnancies (control) and those with opioid use disorder with and without maternal HCV infection. First, placental development was assessed by gross and histological examination of the placenta. Immune cells were then isolated from decidua (maternal) and chorionic villous (fetal) placental tissues, and the frequency and phenotype of immune subsets were determined by flow cytometry. Markers of inflammation, placental perfusion, growth factors, tissue remodeling, and vascularization were measured in placental tissue homogenate by multiplex Luminex assay. Finally, gene expression alterations in placental architecture were assessed by Visium spatial transcriptomics, integrating transcriptomic data with spatial information. Results/Anticipated Results: Our results indicate that maternal OUD impairs placental perfusion/development and is accompanied by increased markers of inflammation in the decidua (IL-1Ra, IL-2, IL-18, IP-10, MIP-1β, and TNFα) and villous (IL-6 and IL-8). Furthermore, markers of angiogenesis and placental development are altered in the decidua, including increased EGF and IL-6Ra, but decreased FLT-1, FLT-4, and bFGF. The abundance of placental immune cells is varied with OUD/HCV, including decreased frequencies of decidual macrophages and NK cells, critical for blood supply to the fetus, and increased abundance of infiltrating maternal macrophages in fetal chorionic villous. Finally, spatial transcriptomics revealed aberrant infiltration of activated immune cells and modified processes associated with inflammation and angiogenesis. Discussion/Significance of Impact: Altogether, these findings suggest a profound impact of maternal OUD with and without maternal HCV infection on the structure, function, and immune landscape of the maternal–fetal interface that can alter fetal development and maturation.

Objectives/Goals: Increasingly, women and people of color are earning PhDs. However, historically underrepresented (HU) degree seekers often follow a “nontraditional” track, pursuing their degree part time, at an older age, and balancing work and family with their studies. Over half of the U.S. PhD students are part time, a feature correlated with candidate diversity. Methods/Study Population: To address this need, the Advancing Diversity and Equity in Pre-doctoral Trainees (ADEPT) program was developed for part-time HU students who do not meet the requirements of the NIH-funded NRSA TL1 program but who offer relevant work and life experience. The program provides individualized navigation and tailored support based on individual student need and career goals, flexible training opportunities, and intentional connections to established, dedicated, and well-trained mentors throughout the predoctoral journey. To better understand their unique needs, we conducted thematic analysis on the notes taken during monthly meetings to explore the challenges our students face and how ADEPT provides support in navigating these challenges. Results/Anticipated Results: Students pursuing a PhD on a part-time basis while balancing other responsibilities, such as caretaking or a full-time job, bring a unique perspective to their graduate education. 5 ADEPT students described how their background or clinical work experience played a crucial role in their decision to pursue a PhD. Themes from the monthly meeting and mentor meeting notes include the challenges of balancing full-time jobs with school, and how they do not experience the cohort effect that a traditional, full-time PhD student would have as a resource. The students reflected on how an individualized culturally sensitive approach was instrumental to their success. Discussion/Significance of Impact: It was initially believed that part-time PhD students were rare. Despite this misconception, we easily recruited students. Students reported their experiences do not reflect the experiences of their full-time peers and their difficulty establishing a peer group, demonstrating the clear need for ADEPT.

Objectives/Goals: The objective of this study is to explore strategies for AI-physician collaboration in diagnosing acute respiratory distress syndrome (ARDS) using chest X-rays. By comparing the diagnostic accuracy of different AI deployment methods, the study aims to identify optimal strategies that leverage both AI and physician expertise to improve outcomes. Methods/Study Population: The study analyzed 414 frontal chest X-rays from 115 patients hospitalized between August 15 and October 2, 2017, at the University of Michigan. Each X-ray was reviewed by six physicians for ARDS presence and diagnostic confidence. We developed a deep learning AI model for detecting ARDS and explored the strengths, weaknesses, and blind spots of both physicians and AI systems to inform optimal system deployment. We then investigated several AI-physician collaboration strategies, including: 1) AI-aided physician: physicians interpret chest X-rays first and defer to the AI model if uncertain, 2) physician-aided AI: the AI model interprets chest X-rays first and defers to a physician if uncertain, and 3) AI model and physician interpreting chest X-rays separately and then averaging their interpretations. Results/Anticipated Results: While the AI model (84.7% accuracy) had higher accuracy than physicians (80.8%), we found evidence that AI and physician expertise are complementary. When physicians lacked confidence in a chest X-ray’s interpretation, the AI model had higher accuracy. Conversely, in cases of AI uncertainty, physicians were more accurate. The AI excelled with easier cases, while physicians were better with difficult cases, defined as those where at least two physicians disagreed with the majority label. Collaboration strategies tested include AI-aided physician (82.4%), physician-aided AI (86.9%), and averaging interpretations (86%). The physician-aided AI approach had the highest accuracy, could off-load the human expert workload on the reading of up to 79% chest X-rays, allowing physicians to focus on challenging cases. Discussion/Significance of Impact: This study shows AI and physicians complement each other in ARDS diagnosis, improving accuracy when combined. A physician-aided AI strategy, where the AI defers to physicians when uncertain, proved most effective. Implementing AI-physician collaborations in clinical settings could enhance ARDS care, especially in low-resource environments.

Objectives/Goals: Mayo Clinic Florida’s Clinical Research Units develop over 200 clinical studies on average annually. Almost 30% of these projects are developed and then are unable to activate due to a variety of operational factors. To increase the success rate, a scoring tool was created to assess the risk associated with the development of these research projects. Methods/Study Population: A project team comprised of members of research administration and physician leadership developed a rapid project management (RPM) scoring tool to assess operational risk factors. The scoring algorithm was embedded into an existing REDCap database, using a combination of identified variables and calculated fields. All noncancer industry sponsor-initiated clinical studies were scored at intake. According to the following categories: enrollment timelines, study team capacity, and previous experience with the Sponsor. Studies with a score greater than the established threshold were referred to physician leadership for transparent discussions with the principal investigator regarding the identified study development-related risks. Results/Anticipated Results: The RPM tool has assessed close to 200 projects since implementation in June 2022. An interim analysis is being conducted of all projects assessed by the RPM tool dating from implementation to May 2024 to compare the outcomes of these studies with the given RPM score. We anticipate based on anecdotal evidence gathered during the course of this pilot project that the RPM tool will show a correlation between risks identified and study outcomes as defined as successful activation of trials, or rationale of project development failures. We anticipate a reduction in the amount of time elapsed and effort expended developing projects with scores reflecting identified project development-related risk factors. Discussion/Significance of Impact: The RPM tool provides an opportunity to allocate resources to studies with the greatest potential for successful activation. In the future, the RPM tool may be used to identify risk factors associated with enrollment and accrual of participants.

Objectives/Goals: 1. Demonstrate the need to apply principles of community-engaged research to various stages of the research process. 2. Outline the process of using CE Studio(s) to redesign an interview guide for service providers of youth involved in the justice system. Methods/Study Population: Service-providers provide a critical lens with which to view the sexual health needs of justice-involved youth. Minimal research describes the unique perspectives of those who work directly with this vulnerable population to address their sexual health needs. The goal of this project is to outline the process of using CE Studio(s) to redesign an interview guide for service providers. The guide is aimed at gathering insight into the knowledge, access, and use of sexual health services for justice-involved youth. Preparation involves the preplanning phase, including the drafting of the interview guide; engagement consists of recruitment and implementation of the CE Studio; and restructuring will outline the application of feedback and finalization of the interview guide. Results/Anticipated Results: During the preparation phase, the researcher was tasked with (1) developing a visual guide to highlight key points of the research study and (2) providing a draft of the tentative interview guide for review prior to the CE Studio session. For the engagement stage, participants were recruited from listservs, community organizations, and word-of-mouth to participate in a session facilitated by a member of the CE Studio team. Lastly, we anticipate that the restructuring phase will not only allow us to use feedback from the CE Studio session to alter the interview guide but provide insight into potential recruitment strategies for the overarching research project. Discussion/Significance of Impact: Leveraging CE Studios to elicit feedback from service providers will provide unique insight into addressing the sexual health needs of justice-involved youth. We expect that the overall CE Studio process and feedback will be integral in eliciting strong qualitative feedback and shaping the implementation of the overall research project.

Objectives/Goals: We aim to establish a systematic approach to distinguish translational science from translational research. Our goal is to create a simple tool that would enable individuals with different backgrounds and levels of expertise to readily determine whether a study truly features translational science. Methods/Study Population: Participants were recruited from a Clinical and Translational Science Award (CTSA) program hub and randomly divided into 2 groups. One group was asked, with minimal guidance, to categorize whether publications described translational science or translational research. The group met to resolve disagreements and identify key indicators and challenges in determining whether a study involves translational science. They provided input on a set of guiding questions intended to facilitate the identification of translational science. The second group did not participate in discussion or tool development. Both groups reviewed a new set of publications, using the tool to guide their assessments. Results/Anticipated Results: Based on publication assessments, we will assess the percent agreement among reviewers in each group for each publication and across the set. We anticipate that the first group will exhibit higher agreement for its second round of review than its first, owing to the benefit of discussion with colleagues and provision of guiding questions. We anticipate that the tool will also promote higher agreement among the second group in their first round of review. We predict that both groups will exhibit high rates of agreement when reviewing with the support of guiding questions. Discussion/Significance of Impact: This study will help us understand interpretations of translational science, a term that has sparked debate and disagreement within CTSA hubs. If successful, the guiding questions will provide CTSAs a tool to improve training, proposal responsiveness, and review for translational science projects.