OBJECTIVES/GOALS: The major obstacle to an effective cure or remission for HIV infection is the integration of HIV into the genome of long-lived resting cells which constitute the so-called viral reservoir. With this study we want to elucidate the changes of the gut-associated HIV reservoir at different stages of viral suppression METHODS/STUDY POPULATION: Recent studies have shown that after long-term (>7 years) clinical suppression of peripheral HIV RNA, the circulating viral reservoir does not seem to decline further and, in fact may expand. The gastrointestinal associated lymphoid tissue (GALT) harbors by far the largest fraction of the latently infected cells, however not much is known about its changes over time.We thus quantified the HIV viral reservoir in the GALT by identifying HIV viral transcripts via 10X single-cell RNA sequencing at two GALT-sites in five PWH and compared the amount of HIV RNA found in the group of PWH with early (< 7years) vs late (> 7years) peripheral virological suppression (plasma HIV RNA <20copies/mL). RESULTS/ANTICIPATED RESULTS: Study participants had been diagnosed with HIV infection for a median (IQR) of 31 (32-34) years and had consistently undetectable peripheral blood HIV RNA for the previous 8 (4-15) years. In PWH with consistent viral suppression < 7yrs, 4 (2-6) HIV transcripts were identified in the ileum and 25 (13 – 38) in the colon. In PWH with consistent viral suppression > 7yrs, 0 (0-4) HIV transcripts were identified in the ileum and 7 (14-11) in the colon. Based on these preliminary results we plan to expand our cohort and confirm these results using Proviral DNA quantification. We anticipate that the viral decay in the GALT will follow a slower dynamic than what has been reported for the peripheral blood achieving a steady state after more than 7 years of peripheral viral suppression. DISCUSSION/SIGNIFICANCE: Despite the remarkable progress the survival and quality of life of PWH, after forty years from its first discovery, HIV infection remains uncurable. Considering its critical role, efforts are needed to better understand the dynamics of the GALT-associated HIV reservoir.

Objectives/Goals: Institutional clinical trial accrual metrics and associated monitoring practices are insufficiently characterized and lack consistency. We aim to assess current metrics and methodologies to inform the development of a tool and recommendations that institutions can use to strengthen monitoring capabilities and enhance trial performance. Methods/Study Population: We designed a survey to assess how CTSA institutions measure and monitor clinical trial accrual, including the types of data elements captured, collection methods, and institutional responses to low accrual. Existing survey instruments were reviewed to inform the development of an initial survey. Subject matter experts were consulted on survey questions, sampling strategies, and administration methods. The finalized survey will be distributed to representatives from CTSA institutions. Findings will inform the development of a self-evaluation tool and recommendations to identify gaps and support institutions in strengthening accrual monitoring practices. Results/Anticipated Results: We will disseminate the final survey to CTSA institutions in 2026. We anticipate variability in accrual metrics and monitoring practices within and across institutions nationally. Discussion/Significance of Impact: Further work is needed to establish consistent definitions, collection methods, and reporting frameworks to improve accrual evaluation and address trial pipeline challenges. Without standardization, harmonizing trial data across sites is difficult, limiting opportunities for shared learning.

Objectives/Goals: Accurately stratifying patients with clinically isolated syndrome by risk of developing multiple sclerosis is of great clinical importance. Though numerous prediction models attempt to achieve this goal, no systematic review exists to independently evaluate these models. We aim to systematically identify and assess the risk of bias in all such models. Methods/Study Population: Studies developing or validating prediction models to assess risk of developing MS in patients with CIS who are not receiving an MS-indicated disease-modifying therapeutic will be identified via a systematic literature search. Studies will be evaluated for overall risk of bias using PROBAST (Prediction model Risk Of Bias Assessment Tool). Briefly, data sources, predictor, and outcome definition and assessment, applicability, and analysis will be assessed for each model in each identified study, and an overall risk of biased judgment will be assigned. Identified studies, predictors incorporated, results, and risk of bias assessment with accompanying rationale will be summarized in the final report. Results/Anticipated Results: Based on an initial exploratory search, we anticipate that most, if not all, identified prediction models will have high risk of bias. We anticipate that many studies will have limited applicability due to the use of outdated diagnostic criteria for definition of outcomes, or high risk of bias concerns originating from their analysis due to insufficient volume of included participants or poor model validation practices. We further anticipate that most, if not all, of the identified prediction models will have limited potential to be translated to use in a clinical setting. Discussion/Significance of Impact: Understanding how to identify patients with high-risk CIS may inform and improve clinician treatment decisions, patient outcomes, and future research study design. This work may also reveal flaws in current prediction models for CIS, opening new avenues of research and prompting development of improved prognostic models for patients with CIS.

OBJECTIVES/GOALS: The new Kidney Allocation System (KAS) was implemented in 2014 and it is not fully understood how its changes to patient incentives may have impacted dialysis facility waitlisting rates. We examine differences in facility performance and how such differences may have been impacted by this policy change. METHODS/STUDY POPULATION: We used Dialysis Facility Report data from 2011 to 2017 to study waitlisting rates at 3,392 dialysis facilities in the US, using waitlisting counts in the numerator, and the total number of ESRD patients in a facility as the denominator. We examined changes in waitlisting rates over by year at the facility, regional, and national level, and report national trends in waitlisting pre- and post-KAS. Facilities were stratified based on waitlisting rate in 2011 and then we examined whether each facility moved into a higher or lower quartile or stayed in the same quartile in 2017. RESULTS/ANTICIPATED RESULTS: Among n = 3,392 dialysis facilities, the average change in dialysis facility waitlisting rates from 2011 to 2017 was −4.74 percentage points (range -54.4% to 42.3%). Average change in dialysis facility waitlisting rates from 2011 to 2014 was −0.57 percentage points while the average change in dialysis facility waitlisting rates from 2014 to 2017 was −4.17 percentage points. Half of facilities in the 2011 lowest quartile remained in the lowest quartile in 2017; 45% of facilities in the top 2011 quartile dropped into a lower quartile. The middle 2 quartiles were fairly evenly split between worsening, improving, and not changing. DISCUSSION/SIGNIFICANCE OF IMPACT: Average waitlisting rates have declined since KAS implementation. Many facilities switched quartiles from 2011-17 suggesting that facility waitlisting rates are unstable over time. The decline in waitlisting rates post-KAS suggests that new allocation rules may be discouraging patients and/or providers from getting ESRD patients waitlisted.

OBJECTIVES/SPECIFIC AIMS: The study aims to determine the baseline knowledge, attitudes and practices of the professionals (i.e., doctors and nurses) that provide the end-of-life care at an acute community hospital. By obtaining information on what is known, what is believed and what is done by doctors and nurses in end-of-life care, we can identify needs, problems, barriers and possible solutions. METHODS/STUDY POPULATION:. Develop a questionnaire in Spanish addressing knowledge, attitudes and practices about end-of-life care in an acute hospital, define the survey objectives, and develop the survey protocol. o To validate the pertinence and usefulness of each questionnaire item, a panel of experts in palliative and end-of-life care will be consulted. o To finalize the questionnaire, it will be pre-tested with a small number of healthcare providers randomly selected from the survey’s intended population. Implement the questionnaire to doctors/nurses providing direct end-of-life care by purposeful sampling at an acute community hospital. o Beforehand, survey interviewers will be recruited and trained. Perform quantitate and qualitative analyses o Answers to closed-end questions and quantitative data will be tallied using Microsoft Excel and analyzed using STATA statistical software. o Relationship between the participant’s characteristics and their knowledge, attitudes and practices will be assessed using chi-square test. o Answers to open-ended questions in the questionnaire will be collected, analyzed based on their content, and placed in more comprehensive categories by NVivo software. RESULTS/ANTICIPATED RESULTS: It is expected to capture variations and/or consistencies in the amount of knowledge, the type of attitudes and the actual practices among and within physicians and nurses on end-of-life care in a community acute hospital. DISCUSSION/SIGNIFICANCE OF IMPACT: The proposed research is expected to contribute key information from the perspectives of physicians and nurses who deliver end-of-life care in an acute community hospital in Puerto Rico. This contribution is significant because it will serve as the platform to develop culturally-appropriate educational/training materials and, subsequently, implement culturally-responsive guidelines for the care of seriously ill Hispanics, with the expectation of improving their quality of life, and perhaps reducing their medical care costs.

OBJECTIVES/GOALS: The goal of this project is to characterize the efficacy of FOXA2 as a potential biomarker for patients with metastatic castrate-resistant prostate adenocarcinoma (CRPC) before transitioning to neuroendocrine prostate cancer (NEPC). NEPC currently has no therapeutic options and poor mechanistic understand of its origins. METHODS/STUDY POPULATION: In our study, we have utilized a multi-omics approach to characterize the potential efficacy of FOXA2 as a prognostic biomarker in numerous patient-derived castrate-resistant prostate cancer (CRPC) models. We have performed ATAC-, ChIP-, RNA-seq and proteomics to fully characterize where FOXA2 is binding genome-wide, how FOXA2 alters chromatin accessibility dynamics, identify regulatory gene targets of FOXA2, and identify FOXA2 protein-protein interactors. We have supported these findings using publicly available data from independent CRPC and NEPC patient cohorts and prostate cancer cell models. RESULTS/ANTICIPATED RESULTS: Our findings show that FOXA2 overexpression suppressed androgen signaling and promoted progression to a NEPC phenotype under short- and long-term androgen deprivation conditions, respectively. Further, FOXA2 redirected the chromatin accessibility landscape to be consistent with an NEPC gene expression program, including increased chromatin accessibility for key NEPC transcription factors. FOXA2 ChIP-seq showed FOXA2 to be bound at known NEPC driver genes and epigenetic modifiers across multiple stages of prostate cancer progression. Lastly, we discovered that FOXA2 physically interacts with key NEPC TFs and epigenetic regulators, suggesting that these FOXA2 physical interactions are required for NEPC progression. DISCUSSION/SIGNIFICANCE: This project will determine the efficacy of FOXA2 as a biomarker in advanced prostatecancer samples, which will translate as a potentially useful tool for clinicians to use for treatment of advanced prostate cancer patients.

The All of Us Research Program is an historic effort to gather data over 10+ years from one million or more people living in the United States to accelerate research and advance precision medicine. There is a particular focus on populations historically underrepresented in biomedical research who are often served by Federally Qualified Health Centers (FQHCs). However, FQHCs face significant challenges in participating in research. This paper addresses three common barriers faced by FQHCs and describes a management model that was used to support a group of FQHCs participating in the All of Us Research Program. Specifically, the paper addresses the challenges of building FQHC research capacity to operationalize and manage research activities, transforming and sharing Electronic Health Records and other data, and recruiting and retaining research participants. The central coordination management model, which was used to support the FQHCs, is a generalizable framework and can serve as an exemplar of how to engage FQHCs in other longitudinal research efforts. To date, the FQHCs have enrolled more than 10,000 participants in the All of Us Research Program. Their success is an indicator that with the proper support, FQHCs can successfully implement a complex biomedical research program in the context of their health centers.

Commercializing biomedical discoveries is a challenging process for many reasons. However, Academic Medical Centers (AMC) that have teaching, patient care, research, and service engrained in their mission are well poised to host these discoveries. These academic discoveries can lead to improvement in patient health and economic development if supported to cross the “valley of death” through institutional assistance, by providing guidance, gap funding and product development expertise. Colorado has a vibrant local startup ecosystem, state support for commercialization and entrepreneurship as well as critical mass of product development expertise. University of Colorado Anschutz Medical Campus, as a major AMC, is an engine for growth for the region. This article discusses innovation efforts at the University of Colorado Anschutz Medical Campus as a case study, which is built around two major efforts: the CCTSI and CU Innovations. I-Corps at CCTSI and the SPARK|REACH program of CU Innovations have been instrumental in fostering innovation, commercialization, and entrepreneurship on the campus.

Cathleen Kane, NYU Karen Cielo, UIC Paul Duguid, Arkansas Mendy Dunn, Florida Maryam Gholami, UCSD Kristi Holmes, Northwestern Joe Hunt, Indiana Patricia Moussatche, Stanford Christy Navarro, UC Davis Brittney Jackson Patterson, Wake Forest Alfred Vitale, Mayo Jennifer Croker, UAB – confirmed. Objectives/Goals: Over the past few years, there has been debate and confusion about the definition of Translational Science (TS) versus Translational Research (TR). The CTSA Administrators met in 2024 to discuss how to better define TS versus TR and create a useful product for the consortium. Methods/Study Population: The Administrators brainstormed best practices and discussed what products could be developed to clarify these concepts. A committee formed to create a useful product for the consortium. An editable document was shared by email and discussed at the December 2024 and February 2025 Administrators meeting to crowdsource existing assets. This process was repeated with the NCATS QA/QC Group, CTSA Evaluators, Workforce Development Enterprise Committee, and Communications Consortium Committee between May and July 2025. The team collects 87 entries from 31 CTSA hubs. Members of the committee reviewed and curated the entries for relevance, accuracy, duplication, and completeness. Results/Anticipated Results: The final work product will be deposited on the Coordination, Communication, and Operations Support (CCOS) website for long-term storage. This site provides a password-protected, stable home for this resource. To help improve the usefulness of this resource, documents available as pdfs are downloaded into a database, so they can be found even if their URLs change. In addition, the name of the institution, person, and email address contributing the resource was included with each item. Discussion/Significance of Impact: The authors’ hope this resource will provide the clinical and translational science community with materials to educate and clarify the meaning of TS and TR, and how each contributes to scientific advances that improve health for everyone.

OBJECTIVES/GOALS: Electronic cigarettes have become increasingly popular, with various combustion products generated in the process. Dihydroxyacetone (DHA), a carbohydrate made during the heating process. Exposures may reach high micromolar to low millimolar doses of DHA per day and no studies have been done to understand the effects of DHA in the heart. METHODS/STUDY POPULATION: Here, we examine if DHA contributes to these using rat cardiomyocytes, H9c2 cells, and rat cardiac tissues to DHA evaluating metabolic and mitochondrial effects. Using the cells, we will investigate metabolic and mitochondrial pathways using Seahorse, protein expression changes in nutrient sensing pathways, and understand dose-dependent effects of DHA in the heart. Metabolite pools will also be evaluated to understand the changes promoted by DHA. Oxidative stress as previously observed in other cell models will also be measured. Key findings in the cardiac cells will be investigated in the cardiac tissues exposed to DHA. RESULTS/ANTICIPATED RESULTS: We have previously shown DHA induces oxidative stress, metabolic changes, and mitochondrial dysfunction in various cell line models. Interestingly, these effects are highly cell-type dependent. E-cigarettes are known to have toxic cardiac effects, including arterial stiffness, endothelial dysfunction, vascular injury, and oxidative stress. Changes in glycolytic, fatty acid synthesis, and the citric acid cycle enzymes and metabolites were found in the H9c2 cells. We also observed increased mitochondrial ROS and fuel changes due to DHA exposure. In DHA exposed cardiac tissues, we observed oxidative stress and mitochondrial fission and fusion dynamics altered. DISCUSSION/SIGNIFICANCE: These data suggest further study at physiologically relevant doses is warranted to understand how DHA inhaled impacts the long-term health of vapers. As well as the regulation of DHA in e-cigarettes as it has been deemed as safe for topical applications and warned against inhalation.

OBJECTIVES/GOALS: To assess labels of drugs approved for Type 2 Diabetes (T2D) for the inclusion of geriatric sub-population data (ages 65-74, 75-84, ≥85) since January 1, 2013, in accordance with international guidance and US regulations in recognition of an aging populations and global demographics. METHODS/STUDY POPULATION: Utilizing FDA Guidance for Industry: Labeling for Human Prescription and Biological Products - Implementing the Physician’s Labeling Rule (PLR) Content and Format Requirements and the International Council for Harmonization of Technical Requirements (ICH) E7 guidance “Studies in Support of Special Populations: Geriatrics” as reference for assessing labels. The Center for Drug Evaluation and Research (CDER) new drugs/biologic approvals database was filtered for drugs approved between Jan. 1, 2013 and Dec. 31, 2022 with approved T2D indications. Examined original drug labels and supplements from Drugs@FDA for geriatric use efficacy and safety wording in Section 8.5 (Use in Specific Populations, Geriatric Use), for labels. Subpopulation data in labeling for ages 65-74, 75-84, and ≥85 was analyzed. RESULTS/ANTICIPATED RESULTS: Seven T2D drugs (Trulicity, Tresiba, Adlyxin, Ozempic, Steglatro, Kerendia, Mounjaro) approved within the specified time period were analyzed. In the current examination, all labels contain information regarding efficacy differences between ages 65+ and 75+, however, none contain information on efficacy for ≥85 populations. Four of the seven drugs have been updated with increased data from further efficacy trials for older adults conducted after initial approval. The remaining three drugs have only been reworded, or not changed at all, with no further efficacy trials conducted. DISCUSSION/SIGNIFICANCE: This research shows the gap in representation of older adults in clinical trial data and T2D drugs’ labeling. Despite having a higher usage of T2D drugs compared to the general population, older adults and especially the oldest-old (≥85) are underrepresented. Additional demographic requirements ensuring diversity in clinical trials is needed.

OBJECTIVES/GOALS: The purpose of this study was to investigate how suggestibility and social susceptibility relate to alcohol use in young adult non-dependent alcohol users, and the role of trait anxiety in this relationship. We hypothesized that greater trait anxiety would be associated with higher levels of alcohol misuse, and this would be mediated by suggestibility. METHODS/STUDY POPULATION: Study participants enrolled in the NIAAA screening and assessment protocol completed questionnaires on suggestibility, anxiety, and alcohol use. The Multidimensional Iowa Suggestibility Scale (MISS) is a 95-question self-report assessment of suggestibility. Trait anxiety is assessed with the State Trait Anxiety Inventory-Trait (STAI-T). Alcohol measures included the Alcohol Use Disorder Identification Test (AUDIT). Structured Clinical Interviews for DSM-IV or DSM-5 disorders were conducted, and non-dependent participants (N = 113) were considered. A median split was conducted (median age = 35.1 years), with the focus of this study on the younger individuals (N = 55). RESULTS/ANTICIPATED RESULTS: Initial analyses showed that suggestibility, alcohol misuse, and trait anxiety all had significant positive correlations with one another. To better understand the relationship of peer influence, specifically, with drinking and anxiety, MISS subscale of Peer Conformity was analyzed. MISS total score and Peer Conformity were positively correlated with AUDIT Total as well as STAI-T Score. STAI-T Score was additionally positively correlated with AUDIT Total (all p2 = 0.222). We also looked at Peer Conformity in place of MISS Total (R2 = 0.213). In both models, only suggestibility measures were significant predictors of harmful alcohol use (p<0.01). DISCUSSION/SIGNIFICANCE OF IMPACT: In young social drinkers, there were significant positive associations between suggestibility, risky alcohol use, and trait anxiety. These results suggest that suggestibility may be a modifiable risk factor for risky alcohol consumption. Future directions include using mediation models to explore the associations between suggestibility, anxiety, and alcohol misuse.

OBJECTIVES/SPECIFIC AIMS: This study aims to understand the potential immunomudualtory effect of APOL1 variants in auto-antigen activated myeloid cells by assessing lysosomal integrity in activated cells expressing APOL1. The primary stimuli were: 1. ssRNA hY3 as a proxy for the Ro immune complex; 2. in an bulk RNA seq model, interferon-response gene, Siglec 1, as a read out of interferon activity. The primary outcomes were: 1. Myeloid cell APOL1 expression both in primary macrophage cultures and ex-vivo patient derived macrophages; 2. Lysosome integrity as measured by fluorescence intensity of lysotracker dye on light microscopy. METHODS/STUDY POPULATION: All recruited subjects provided written informed consent as per the NEW YORK UNIVERSITY Division of Rheumatology-wide Specimen and Matched Phenotype Linked Examination (SAMPLE) protocol. Subjects were African American; SLE subjects met 4 American College of Rheumatology criteria for SLE. Healthy donor monocytes representing each genotype in duplicate (reference allele: G0/G0; heterozygote variant: RV/G0; and homozygote variant RV/RV) were cultured with GM-CSF to yield macrophages which were incubated in serum free media or with hY3 ssRNA (TLR 7/8 agonist) to yield inflammatory M1 macrophages. Fold increase of APOL1 in untreated vs hY3 treated macrophages was measured using qPCR. Live cells were then cultured on glass chamber slides with DNA dye, DAPI, and Lysotracker red, a fluorescent dye that stains acidic lysosomes. As a proof of concept, interferon response gene, Signlec1, and APOL1 transcriptional activity in peripheral blood monocytes (PBMCs) were measured and correlated in 17 SLE patients by RNA seq. RESULTS/ANTICIPATED RESULTS: Regardless of genotype, hY3 increased APOL1 expression by 29 (+/−18.4) fold (P = 0.007 vs no treatment). Genotyping of the qPCR product showed concordance with the chromosomal DNA with the RV heterozygotes expressing both alleles. To examine lysosomal membrane integrity, live hY3-treated macrophages were stained with lysosotracker dye and fluorescence intensity was measured. Compared to reference allele carrying macrophages, each additional variant allele corresponded with a lesser degree of lysosome compartment staining. In SLE PBMCs, we found that APOL1 was highly expressed, and significantly correlated with Siglec1 (F=10.5; P = 0.005) supporting an association between circulating interferons and APOL1 accumulation in monocytes. DISCUSSION/SIGNIFICANCE OF IMPACT: Given that the “cytokine milieu” in SLE elicits APOL1 expression, induces inflammatory cell metabolic rewiring, and stimulates autophagy thereby exposing defects in autophagic flux, this gene-environment interaction may underpin the relationship between chronic inflammation and heightened APOL1 polymorphism-attributed cardiovascular risk. These data support further inquiry into the intersection between chronic autoimmunity and APOL1’s functional role in the vascular microenvironment. The in vitro studies herein extend our prior work by demonstrating a mechanistic link between SLE-associated inflammation, APOL1 risk variant status and CVD via a lysosomal defect which converges on common autophagic and metabolic pathways in mononuclear cells.

Objectives/Goals: The goal of this project was to engineer 3D lung models by embedding human epithelial cells and fibroblasts within hybrid-hydrogels containing human decellularized extracellular matrix (dECM) from healthy and fibrotic lungs. This platform will enable us to study cell–matrix interactions involved lung fibrosis pathogenesis. Methods/Study Population: To incorporate dECM into hybrid-hydrogels it must be digested and functionalized. We determined the best conditions for pepsin digesting dECM from healthy and fibrotic human lung by collecting samples every 12 hours up to 96 hours and measuring total protein (BCA assay), total amine concentration (ninhydrin assay), and protein fragment size (SDS PAGE). Next, several molar excesses of Traut’s reagent were tested and functionalization was verified by comparing amine content (ninhydrin assay) to thiol content (Ellman’s assay). Hydrogel stiffness was measured initially and after stiffening using parallel-plate rheology. Results/Anticipated Results: The dECM was successfully pepsin-digested, with the 48-hour time point yielding the highest free amine levels. A 75-molar excess of Traut’s reagent was best for converting free amines to thiols. Dynamic stiffening allowed the creation of hybrid-hydrogels mimicking both healthy (1–5 kPa) and fibrotic (>10 kPa) lung microenvironments. We anticipate that this model will demonstrate differential fibroblast activation based on hybrid-hydrogel dECM source (healthy or fibrotic), microenvironmental stiffness, and cell source (healthy or fibrotic). Validation of this 3D co-culture system could accelerate drug discovery by providing a more accurate in vitro platform for high-throughput screening. Discussion/Significance of Impact: This work advances pulmonary fibrosis modeling by creating human dECM-based hydrogels that recapitulate the cellular and mechanical microenvironment of healthy and diseased lung, potentially enabling us to uncover novel therapeutic targets and improving drug efficacy testing in vitro.

OBJECTIVES/GOALS: Specific aims are to: (Qualitative aim) Develop a new measure of cancer-related self-efficacy in partners (BCSES-P) and obtain feedback on the items (Quantitative) Evaluate the psychometric properties of the BCSES-P including: dimensionality, factor analysis, and construct validity assessing the relationships posited METHODS/STUDY POPULATION: 2-Phase Approach: 1) Item development and 1) Item testing Phase 1 Stage 1: Literature review to identify additional covariates Stage 2: Focus groups and individual interviews to determine partners’ needs Sample size: 20 partners (18 years of age or older, identifying as being in a committed relationship with a BCS) Design: cross-sectional, qualitative interviews Stage 3: Develop candidate items Stage 4: Cognitive interviews Stage 5: Finalize items with research team Phase 2 Preliminary psychometric testing Dimensionality Internal consistency reliability Construct validity Sample size: 150 partners Design: cross-sectional, online survey RESULTS/ANTICIPATED RESULTS: The BCSES-P will be unidimensional as assessed by exploratory factor analysis. The BCSES-P will demonstrate an internal consistency coefficient of 0.70 or above. Construct validity of the BCSES-P will be demonstrated by support of the following theoretical relationships: Cancer-related self-efficacy will be positively related to marital satisfaction and sexual functioning (social well-being) and the distal outcome, overall QoL. Cancer-related self-efficacy will be negatively related to fatigue (physical well-being), fear of recurrence, depression, and anxiety (psychological well-being). DISCUSSION/SIGNIFICANCE OF IMPACT: Findings will guide intervention development to improve partners’ quality of life The BCSES-P will be the first scale to measure partners’ cancer-related self-efficacy. This study will highlight a holistic approach to studying the long-term effects of breast cancer on partners.

Objectives/Goals: This study tests how fiber microstructural integrity and myelination levels within the cingulum connectome are associated with information processing speed (IPS) in relapsing-remitting multiple sclerosis (RRMS). We investigate the functional impact of structural coherence, myelin content, and white matter hyperintensities (WMH) load on IPS. Methods/Study Population: Data from 63 RRMS and 25 healthy controls (HC) were used. We hypothesize that the structural integrity of the cingulum bundle and its structural network – or connectome – is distinctly associated with IPS function in people with RRMS (vs. HC) due to myelin-related plasticity across the wiring. Using diffusion spectrum imaging and high-resolution tract segmentation, we constructed individualized white matter connectomes. Diffusion quantitative anisotropy (QA) and myelin fractions (MWF) were used to quantify structural coherence and myelination. WMH load was measured with T2-FLAIR imaging. Bayesian–Pearson correlations, mixed-linear, and moderation models explored how fiber-specific QA, MWF, and WMH load relate to IPS function in RRMS, as measured by Symbol Digit Modalities Test (SDMT). Results/Anticipated Results: We theorize that (1) QA in the cingulum connectome correlates with SDMT performance dimensionally, indicating that structural coherence in the white matter supports IPS function among both groups; (2) increased myelination will strengthen the positive association between QA and SDMT scores, suggesting that connectome-specific myelin content facilitates IPS; (3) conversely, WMH load within the cingulum connectome is expected to inversely correlate with SDMT scores, reflecting the detrimental impact of lesion burden on IPS function; (4) myelination in specialized tracts within the cingulum connectome play a compensatory role to support IPS function in the RRMS group. These investigations can offer a mechanistic clue to potential neuroplastic targets for cognitive interventions in MS. Discussion/Significance of Impact: By linking white matter integrity to cognitive function at the connectome level, this study can support neuroregenerative strategies to mitigate cognitive burden in RRMS. Our findings may advance understanding of how structural coherence, tract myelination, and WMH affect IPS, shaping personalized prognostic and therapeutic interventions.