Objectives/Goals: Male urogenital tract development is influenced by hormonal signals, which may be disrupted by endocrine-disrupting chemicals like lead. This observational study investigates the potential link between lead exposure and hypospadias rates in Puerto Rican boys, focusing on regional hotspots of hypospadias. Methods/Study Population: Lead levels from water plants across Puerto Rico were analyzed using PR Aqueduct and Sewer Authority water quality certificates. Hypospadias rates in seven health regions were obtained from the Puerto Rico Department of Health’s Birth Defects Prevention and Surveillance System. Data were from Puerto Rican boys born to women aged 15 years or older from 2017 to 2022. Rates were calculated using 2020 Census data, and statistical analyses were conducted using Intellectus. Results/Anticipated Results: Significant differences in hypospadias rates and lead levels were found across health regions, with the highest rates observed in Bayamón and Arecibo (5 cases per-100,000 births). Bayamón had the highest average lead concentration (14.33 ppb). A Kruskal–Wallis test showed significant regional variation in lead levels (χ²(6)  =  16.82, p  =  0.010) and hypospadias rates (χ²(6)  =  16.53, p  =  0.011). Post hoc analyses revealed key differences between regions, notably Bayamón and Metro. Discussion/Significance of Impact: These findings suggest a potential spatial link between prenatal lead exposure and hypospadias risk, underscoring the need for targeted public health interventions. Future studies will explore anti-Müllerian hormone expression in lead-exposed Sertoli cells to better understand the biological mechanisms behind these patterns.

Objectives/Goals: Understand the impact of sarcopenia on the main respiratory muscle, the diaphragm (DIAm). We hypothesize that in the DIAm of older (i.e., 24 months) compared to younger (i.e., 6 months) rats, maximum specific force (P0) is reduced, maximum shortening velocity (Vmax) is slower, maximum power output is reduced, and endurance is improved. Methods/Study Population: Mid-costal DIAm strips were excised from 6-month (n = 8; 4 female and 4 male) and 24-month (n = 8; 4 female and 4 male) rats. The DIAm was stimulated using platinum plate electrodes, and mechanical and endurance properties were measured (at 26oC). Results/Anticipated Results: In the DIAm, maximum tetanic formce (P0) decreased by ~35%, maximum velocity of shortening (Vmax) slowed by ~20%, and peak power output was reduced by ~35% in 24-month compared to 6-month rats. During repetitive isovelocity (30% Vmax; approximating peak power output) contractions, endurance (the period during which power output was sustained) of the DIAm was unaffected by aging. Corresponding with previous findings, Discussion/Significance of Impact: The changes in DIAm mechanical performance corresponded to an age-related atrophy of type IIx/IIb muscle fibers. We conclude that force generation and endurance of the DIAm required for breathing motor function is preserved in old age, while DIAm sarcopenia does impair more forceful expulsive airway clearance and voiding behaviors.

Objectives/Goals: In this project, we set out to supplement our existing grant writing workshops with targeted, learner-centered, multimodal training. This method will assist us in moving toward a more equitable training landscape, reaching a wider variety of learners, by freely disseminating these resources. Methods/Study Population: To increase access and impact of training materials for our career development grant writing workshops, we restructured our pre-workshop training videos. We culled expert advice from lengthy recorded lectures into brief (less than 5 minute) how-to videos that target instruction to writing specific sections of an NIH K grant. We then coupled these how-to videos with easy-to-navigate, open access online courses that further illustrate best practices for writing key sections of NIH K grants. These resources were given to registered workshop attendees and made available through a public Canvas course, the Diamond portal, MICHR website, and U-M Innovation Partnerships to disseminate the materials through multiple channels. Results/Anticipated Results: Four online courses and complementary videos were developed over six months, each focusing on a specific section of the NIH K grant proposal. These resources provide targeted instruction for writing the Specific Aims, Candidate Background, Career Development Plan, Career Goals and Objectives, and Mentor Letter. Learners accessed all four of the online courses. Released in January 2024, we continue to gather data on whether learners believe their knowledge about writing successful K grants has increased after using the resources, if they believe the courses have prepared them to write the section of the grant covered, and whether learners would recommend the courses. We will analyze these results to better understand how learners are using and responding to these new resources. Discussion/Significance of Impact: These how-to videos and online courses provide targeted, learner-centered training and fill an important gap by meeting learners where they are and extending the impact of our training beyond our institution. Widely disseminating online interactive training resources is a model we are applying beyond grant writing to other projects.

Objectives/Goals: In mice, it has been shown that loss of Cib2 (calcium and integrin-binding protein 2) results in progressive retinal disease that recapitulates many characteristics of age-related macular degeneration (AMD). This study aims to characterize transcriptional changes in the retinal pigment epithelium (RPE) that underlie this disease process. Methods/Study Population: RPE tissue samples, pooled from 2–3 mice for each biological group, were collected from Cib2-KO and wildtype (WT) mice at two (young) and eight (aged) months of age. Bulk mRNA sequencing was performed using the Illumina HiSeq 4000. Reads were aligned to the UCSC mouse reference genome and quantified using HTSeq. Significant differentially expressed genes (DEGs) between mouse genotype and age groups were assessed using DESeq. CLICK unsupervised clustering followed by gene ontology analysis was performed to identify cellular processes and molecular pathways affected by loss of Cib2 as well as age. Results/Anticipated Results: CLICK analysis revealed several functional pathways that are differentially expressed between sample groups. For example, in both young and aged mice, pathways upregulated in Cib2-KO samples included calcium signaling, RhoA signaling, and integrin signaling. Uniquely downregulated DEGs in young Cib2-KO animals were related to complement and coagulation cascades, LXR/RXR activation (related to lipid synthesis and transport), and phagosomes. Aged Cib2-KO mice displayed the most significant downregulation of genes in the phototransduction pathway, indicating temporal changes in functional pathways that correlate with disease progression. Next steps in analysis include investigating patterns in RPE- and AMD-signature gene sets that may identify molecular pathways more specific to human disease. Discussion/Significance of Impact: Many current studies investigate the role of complement activation, vesicle trafficking, and ion transport as top contributors to AMD development. We identified DEGs paralleling many of these molecular pathways in Cib2-KO mice, highlighting their potential as a model to study age-related RPE pathologies and evaluate therapeutic interventions.

Objectives/Goals: The objective of this project is to develop a tool for evaluating clinical trial (CT) eligibility criteria for demonstrated “gender literacy,” defined as the recognition that biologically assigned “sex” is distinct from personally defined “gender identity,” as a way to quantify the inclusion of gender minority populations. Methods/Study Population: The study is validating an assessment scale that evaluates gender literacy based on CT eligibility criteria (EC). Two health professionals will serve as “coders,” tasked with grading 15 CTs. EC for all CTs will be exported from clinicaltrials.gov. Once trained with using the scale, each coder will give a score for each trial. After this first scoring period, coders will share their scores and experiences using the scale. Coders will be tasked again with grading 15 new CTs. This second scoring period will yield final scores to calculate the inter-rater reliability (IRR), or the extent to which qualitative measurements are consistent and not due to random chance. IRR will be quantified by Cohen’s kappa to validate the scale. Results/Anticipated Results: Cohen’s kappa is on a continuous interval from 0 to 1, where 0 means no agreement and 1 means perfect agreement. It is expected that the Cohen’s kappa for this assessment scale will exceed 0.80. Such validation is necessary to ensure the scale is robust and dynamic for multiple use-cases and consistent across any coder. By having a discussion after the initial scoring period, we can identify confusions or challenges with the scale early on and correct them before the secondary scoring period. In comparing these two coders’ performance, it is expected that the second scores will be more similar, thus a kappa closer to 1. However, if the kappa is low, this may be because gender literacy is a learned skill, through the internalized recognition that gender is truly different from sex. Discussion/Significance of Impact: Systemic barriers and exclusionary language have excluded gender minorities from CT spaces for too long. Tools such as these, paired with standardized language for sex and gender eligibility criteria, will greatly bolster the representation of this population and spark change for a more inclusive future.

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: The goals of this research are to 1) determine the prevalence of perinatal doula services use in Virginia, with a focus on individuals with substance use disorders (SUD), 2) evaluate awareness of doulas among pregnant and postpartum people with SUD, and 3) assess provider knowledge and interaction with doulas for the care of this population. Methods/Study Population: Both quantitative and qualitative methods will be used to evaluate patient and healthcare provider knowledge regarding doula services and the patient–doula–healthcare provider relationship. Surveys and semi-structured interviews will be administered to doulas, pregnant and postpartum women, and healthcare providers in this mixed-methods approach. Information from the Centers for Medicare and Medicaid Services National Provider Identifier (NPI) Registry, and doula training programs will be utilized to recruit doulas for participation. Paper and online recruitment materials will be posted to engage pregnant and postpartum individuals. Healthcare provider recruitment will occur via the NPI Registry along with contacting physicians’ practices. SAS 9.4 and NVivo will be utilized for analysis. Results/Anticipated Results: This proposed research will be an initial assessment of the current state of doula services utilization, mothers’ knowledge of doulas and their purpose, and healthcare providers’ awareness of and partnership with doulas to provide optimal birthing and postpartum experiences to the pregnant and parenting population with and without SUD. Results from this study will be disseminated to community doulas, pregnant people and mothers with substance use disorders, and relevant healthcare providers to decrease barriers to doula care and advocate for consistent, systematic documentation of doula services in the medical record and in public health surveillance systems. Discussion/Significance of Impact: This study will be the first study to assess doula services utilization in Virginia, with a specific focus on pregnant and postpartum women with substance use disorders. This work will support advocacy for improved data capture and utilization regarding doula services in order to reduce barriers to care and improve perinatal outcomes.

Objectives/Goals: To create, train, and evaluate the FAST-PACE (Promoting Academic and Community Engagement) Toolkit that catalyzes academic-community translation science teams during a public health emergency. The toolkit is a road map based on the Research Readiness and Partnership Protocol (R2P2), which was developed from the Flint Water Crisis. Methods/Study Population: A literature review was conducted by the Michigan Institute for Clinical & Health Research Community Engagement (MICHR CE) program and the Community-Based Organization Partners (CBOP), to identify important and common elements in disaster response protocols with a set of key interviews (n = 31) to glean perspectives from community leaders. Key findings were extracted and reviewed to generate guidelines and recommendations for the R2P2 protocol. The co-developed FAST-PACE Toolkit launched its expansion statewide to address emergencies and health disparities of communities in crisis. The iterative process consisted of community report-outs, gathering input from stakeholders, via discussion, and evaluation surveys. The feedback was used to develop, enhance, and tailor the toolkit and training content. Results/Anticipated Results: Data from training (n = 8) of the critical elements of the FAST-PACE Toolkit, which provides guidance for academic and community team members that includes 1) assessing community assets and needs; 2) engaging in clear and bidirectional communication; 3) facilitating transparency and equitable partnering; 4) identifying health equity and justice issues; and 5) conducting the evaluation of research. The training will be disseminated in-person and virtually across the state of Michigan resulting in participants sharing community-identified health issues and social determinants of health to assist MICHR CE to suggest resources to address health impacts. Discussion/Significance of Impact: The FAST-PACE Toolkit borne from the flint water crisis and confounded by other crises used CEnR principles to create a translation science roadmap. It equips communities and collaborating academic institutions across the state to respond to public health crises and fosters equitable translation science partnerships built on respect and trust.

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: Our lab’s novel adoptive cellular therapy (ACT) significantly improves survival in brain tumor models. However, there is a lack of biomarkers to assess immunotherapy responses. Our objective is to use gold nanorods to track hematopoietic stem cell migration, a critical arm of ACT, and validate it as a prognostic biomarker. Methods/Study Population: Hematopoietic stem cells (HSCs) were isolated from the bone marrow of 6-week-old C57BL/6J mice and co-cultured with varying gold nanorod (GNR) concentrations and time points. GNR uptake in HSCs was evaluated with inductive coupled plasma mass spectrometry, two-photon luminescence, and tissue histology. After GNR co-culture, HSC viability and differentiation were quantified with flow cytometry and colony forming unit assays. To evaluate the impact of GNRs on HSC reconstitution, mice received myeloablative total body irradiation and intravenously received GNR-labeled HSCs. Computed tomography (CT) contrast of GNRs will be confirmed through microCT. Lastly, mice will intracranially receive KR158b glioma and GNR-labeled HSC bio-distribution will be measured after ACT and correlated with survival outcomes. Results/Anticipated Results: We have demonstrated that GNRs are readily taken up by HSCs within 30 minutes, and retained within intracellular compartments, via TPL. Incubation of GNRs with HSCs did not significantly alter cell viability or differentiation, supporting the GNR’s favorable biosafety profile. Colony-forming unit assays revealed that GNR incubation did not significantly disrupt the total number of colonies formed and qualitatively, colonies did not demonstrate significant lineage differences. GNR-labeled HSCs demonstrated significant reconstitution after myeloablative total body irradiation in mice. We expect that GNR-labeled HSCs will distribute to the glioma microenvironment and draining lymph nodes, positively correlating with long-term survival after ACT. Discussion/Significance of Impact: GNRs harbored high biosafety and feasibility for tracking HSC migration after ACT. We seek to translate this theranostic tool into the current first-in-human clinical trials at our institution for patients diagnosed with neuroblastoma and diffuse intrinsic pontine glioma to improve immunotherapies against brain malignancies.

Objectives/Goals: Colorectal cancer (CRC) is classified into right-sided, left-sided, and rectal cancer. Clinicopathological and molecular features vary along the colorectum, even within subsites, leading to inconsistencies in identifying relevant biomarkers. We created a CRC metabolome map to explore diagnostic and survival heterogeneity across subsites. Methods/Study Population: A total of 372 patient-matched tumor and normal tissue samples were collected from seven colorectal subsites: cecum (n = 63), ascending colon (n = 44), transverse colon (n = 32), descending colon (n = 28), sigmoid colon (n = 75), rectosigmoid colon (n = 38), and rectum (n = 92). Liquid chromatography–mass spectrometry was used to compare metabolite abundances. Cox proportional hazards regression assessed metabolite impact on survival, adjusted for clinical covariates. Parametric and nonparametric tests were applied to compare the metabolite abundances. An interactive, publicly accessible online platform was developed to allow researchers to explore and generate hypotheses from this data. Results/Anticipated Results: Our study identified 39 and 70 significantly altered metabolites, including bile acids and lysophosphatidylcholines, across tumors and normal mucosa, showing metabolic heterogeneity between CRC subsites. We observed significant linear trends in metabolite gradients from the cecum to the rectum, and it was depended on the disease status. Comparison of tumors to patient-matched normal mucosa revealed metabolite changes exclusive to each subsite. Metabolite differences correlated with survival were unique to each subsite. Additionally, we developed an interactive, publicly accessible CRC metabolome database to share this valuable resource: https://colorectal-cancer-metabolome.com/yale-university. Discussion/Significance of Impact: This study provides the first CRC metabolome map, revealing metabolic differences across colorectal subsites. It challenges the right vs. left CRC classification, highlighting subsite-specific biomarker identification. Findings offer insights for personalized treatments tailored to the tumor type to improve patient outcomes.

Objectives/Goals: Our aim was to identify how the epithelial–mesenchymal transition shields heterogeneous breast tumors against immune attack. Additionally, we endeavored to understand whether our findings were conserved in canine mammary tumors as a translational model for human breast tumors. Methods/Study Population: To understand interactions between quasi-mesenchymal (qM) tumor cells, epithelial (E) tumor cells, and immune cells within heterogeneous breast tumors, we utilized a preclinical mouse model established in our lab. In this system, we can precisely control the proportions of E and qM tumor cells within tumors and study what immune cells infiltrate these tumors in response, using flow cytometry and immunofluorescent staining. Using this model, we have also established cell lines to study E and qM tumor cells in vitro. Finally, we used immunohistochemistry to label immune cells in canine mammary tumors and quantified the presence of these cells in relation to the expression of epithelial and mesenchymal cellular markers. Results/Anticipated Results: We observed that immune suppression within heterogeneous mammary tumors is driven by local, rather than systemic, effects of quasi-mesenchymal (qM) tumor cells. The presence of systemic qM-derived factors does not alter immune cell infiltration nor sensitivity to immunotherapy of epithelial (E) tumors. Furthermore, I found that the local activity of qM-derived factors within heterogeneous tumors induces immune-suppressive changes in surrounding E cells, which protects them against immune attack. Finally, I found that canine mammary tumors with higher proportions of qM tumor cells assemble an immune-suppressive tumor microenvironment, highlighting the translational potential of our findings. Discussion/Significance of Impact: We identified that the epithelial–mesenchymal transition induces immune-suppressive changes in heterogeneous tumors. These findings may reveal novel therapeutic targets for treatment of refractory tumors. Our findings in canine tumors suggest that these mechanisms are conserved across species.

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

Objectives/Goals: 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: 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: Depression is common among people living with HIV (PLWH). This study explored the link between reduced metacognitive awareness and depression in PLWH. It utilized a positive emotion regulation task to compare brain activation during viewing versus upregulating positive emotions. Methods/Study Population: Depressed PLWH (N = 24; mean age  =  53; HAM-D mean  =  19) participated in an emotion regulation task while blood oxygen-level-dependent (BOLD) responses were recorded. In the emotional regulation task, participants were shown the International Affective Picture System (IAPS) a series of positive, negative, and neutral images. Participants were asked to view these images and given instructions to either negatively reappraise (RN) or positively reappraise (RP). In the RP condition, participants were no longer shown the image and asked to upregulate their positive emotional responses associated with it. Ten onset times were included for each trial. Results/Anticipated Results: A one-sample t-test was conducted to analyze contrasts between reappraisal of positive images and viewing positive images (RP > VP). Results showed significantly greater activation in the posterior cingulate and angular gyrus during the RP condition (peak MNI: 18, -52, 34; p < 0.001, uncorrected, k > 10 voxels). In comparing the reappraisal of negative images to viewing negative images (RN > VN), there was increased activation in the right supramarginal gyrus (peak MNI: 50, -28, 22; p < 0.001, uncorrected, k > 10 voxels). When contrasting the reappraisal of positive to negative images (RP > RN), BOLD signals were higher in the left dorsolateral prefrontal cortex (peak MNI: 40, -38, 32; p < 0.001, uncorrected, k > 10 voxels). Discussion/Significance of Impact: Findings underscore that depressed PLWH demonstrates BOLD responses in brain regions linked to appetitive motivation and meta-cognitive awareness during the RP condition which demands more executive resources among those with depression, highlighting the complexity of emotional regulation in this population.

Objectives/Goals: NIH requires researchers submit Data Management and Sharing (DMS) Plans with their grant applications. Librarians developed an assessment tool for the plans and completed a pilot assessment in order to leverage the plans and understand current institutional research data management and sharing. Methods/Study Population: The assessment tool includes questions related to evaluations of DMS Plans as well as questions related to the content of the plans. Evaluation questions were adapted from the Federation of American Societies for Experimental Biology evaluation rubric developed for the DataWorks! Data Management Plan (DMP) Challenge. Fields were added to collect information on the content of DMS Plans, including data type, institutional resources, data repositories, data standards, and data dissemination timelines. The assessment tool was tested in a pilot implementation. Seven library workers were trained and completed paired review samples of 27 DMS Plans (54 evaluations total) in order to test for tool reliability. Results/Anticipated Results: Results include findings on the reliability of the tool as well as preliminary results from an assessment of DMS Plans. Findings on the reliability of the tool include assessments of the paired reviewers for each question included in the tool. Paired reviewers generally agreed, but tended to differ on specific questions, including questions pertaining to the data types generated or used in a research project. Questions with high levels of agreement included subjects of study and code sharing practices. Results on the content of the DMS Plans include information such as data repositories used, data oversight responsibilities, and data and metadata standards employed. Discussion/Significance of Impact: DMS Plans present an opportunity to better understand data management and sharing practices, and good data management supports high-quality, reproducible research. Developing and testing assessment tools for these plans is a key step toward understanding and improving current research data management practices.

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.