ABSTRACT IMPACT: Implementing a team science approach with broad engagement from academic researchers, healthcare payers, providers, patients, and community-based organizations is complex, yet critical to implementing evidence into real world settings. OBJECTIVES/GOALS: 1. Participants will be able to deploy novel strategies for creating and training a regional multi-stakeholder consortium to improve the quality and value of healthcare.

2. Participants will be to examine ways in which team science provides holistic sustainable strategies to improve care and outcomes in real-world settings. METHODS/STUDY POPULATION: The Quality & Value Innovation Consortium (QVIC) has created a network of hospitals and other stakeholders (providers, payers, purchasers, patients, community-based organizations, and researchers) to collaborate and innovate on healthcare delivery. This initiative began with a team of a physician researcher, a health services researcher, and a nurse researcher first identifying healthcare systems’ priorities through individual meetings with leadership from 14 regional hospitals. Concurrently, meetings were held with other stakeholders. These interviews identified 32 key quality improvement topics.

Focus groups and surveys reduced these to 11 topics that were then selected for community forums. Through a mixed methods approach, two priority topics were selected for regional implementation. RESULTS/ANTICIPATED RESULTS: The QVIC meetings have prioritized two topics and highlighted novel information sharing across entities, and strategies to address the social determinants of health. The QVIC efforts have been recognized as a community asset for helping build collaboration and partnerships among diverse stakeholders. Ultimately, two regional initiatives, opioid management, and transitions in heart failure care were selected for implementation. Both of these initiatives aim to reduce readmissions by addressing social determinants of health. Implementation strategies and evaluation metrics are being customized for pragmatic integration within each system, utilizing a collaborative team science approach. DISCUSSION/SIGNIFICANCE OF FINDINGS: While the entire country is grappling with the challenge of improving the quality of care, while lowering its costs, Kansas City has modeled a unique culture and strategy for achieving this goal, important for learning health systems and communities.

Objectives/Goals: KSHV is well documented to infect and establish latency in endothelial cells; however, infected cell types in the Kaposi Sarcoma (KS) tumor microenvironment are not well defined. Here, we present the first application of the Lunaphore COMETTM multiplexed immunofluorescence platform for spatial proteomic analyses of KS lesions. Methods/Study Population: Custom antibody panels were validated and optimized for characterization of the TME components, as compared to marginal structures. The Ab panels supported the detection, quantification, and comparison of >15 cell types in regions of interest in the KS tissues in a single automated run. For data analysis, we developed a rule-based decision tree for accurate cell classification and used the resulting cell populations to perform a nearest-neighbor analysis. We assessed spatial proximity among cell types located within, adjacent to, or distal from the areas with a large number of cells expressing KSHV LANA. Results/Anticipated Results: The highest KSHV load was detected in CD34+ cells with or without CD31, consistent with an endothelial progenitor phenotype (EPCs). We also defined 12 cell types with KSHV-LANA detected in <1% of each cell type. Among them, tumor-infiltrating CTLs were proximal to or overlapping with infected EPCs, suggesting they have cytolytic activities. In addition, we observed areas with T-cells detected at high frequency near normal vascular endothelial cells (VECs), indicating immune cell trafficking toward the lesion in these marginal areas. While supporting previous findings that T-cells are not infected by KSHV, our data also revealed areas having high viral Ag load and abnormal vasculature, versus surrounding areas with much lower Ag load, normal vasculature, and robust immune infiltration. Discussion/Significance of Impact: Our approach not only demonstrated its ability to characterize the KS TME at a previously unapproachable level of complexity but has also revealed gaps in lineage assignments in substantial proportions of the tumor, which will be subjected to further characterization.

Objectives/Goals: The goal of this project is to integrate human and animal data to explore the relationship between social participation and cognitive functioning after traumatic brain injury (TBI). Further, we aim to determine whether reduced social participation is not only a consequence of TBI but a potential driver of post-injury cognitive deficits. Methods/Study Population: This study uses a translational framework to examine how social participation influences cognitive outcomes after traumatic brain injury (TBI) using complementary human and animal models. Longitudinal TBIMS data will be analyzed to assess associations between social participation (PART-O: productivity, out and about, social relations) and cognition (BTACT: memory, fluency, reasoning, processing speed) using linear regression (potentially a Random Intercept Cross-Lagged Panel Model to capture bidirectional effects over time). Further, mice with mild, moderate, or severe TBI will be housed in isolated, standard, or enriched social environments. Post-injury cognitive performance (NOR, Y-maze) and neuronal proliferation and survival in the prefrontal cortex and hippocampus will be evaluated. Results/Anticipated Results: We anticipate that both humans and animals with greater social participation will demonstrate superior cognitive performance over time. In the animal model, we further expect that mice housed in social or enriched environments will exhibit reduced cell death and enhanced neuronal survival in the prefrontal cortex and hippocampus compared to socially isolated counterparts. Discussion/Significance of Impact: Together, these findings may inform future rehabilitation strategies that integrate social participation as a core component of cognitive recovery supporting more personalized and multidisciplinary approaches to chronic TBI care.

Objectives/Goals: Our objectives were to determine enteric microbiome characteristics in fluoroquinolone-resistant Enterobacterales (FQRE)-colonized and non-FQRE-colonized hematopoietic cell transplant (HCT recipients, and to understand the enteric microbiome-specific factors associated with the development of FQRE BSI in FQRE-colonized HCT recipients. Methods/Study Population: This was a prospective cohort study of patients undergoing HCT at Weill Cornell Medicine from November 2016 to August 2019. All participants received levofloxacin prophylaxis during post-HCT neutropenia. Stool samples were collected prior to levofloxacin prophylaxis initiation and during the week after HCT. Our overall study population consisted of 26 FQRE-colonized HCT recipients and 69 non-FQRE-colonized HCT recipients. Samples underwent selective quantitative culture for FQRE, as well as 16S rRNA sequencing. Raw sequence data were processed and aligned to a custom SILVA database. Analysis of 16S rRNA sequencing was conducted in R using phyloseq. Results/Anticipated Results: We saw significant differences in microbiome composition in comparing pre-HCT samples from FQRE-colonized HCT recipients to non-FQRE-colonized HCT recipients, including significantly higher relative abundances of Bacteroidales and Enterobacterales in colonized recipients. MaAslin2 demonstrated significantly differential abundance of Bacteroides and Escherichia-Shigella ASVs. We observed a significant decrease in Enterobacterales relative abundance in non-FQRE-colonized recipients after HCT, but no such change in FQRE-colonized recipients. FQRE-colonized recipients who developed FQRE BSI had a lower relative abundance of Bacteroidales as compared to those who did not. No significant difference in FQRE colonization density as measured by quantitative FQRE stool culture was observed. Discussion/Significance of Impact: FQRE-colonized HCT recipients represent a unique subgroup of HCT recipients. Colonized HCT recipients with FQRE BSI had lower relative abundance of Bacteroidales compared to those without BSI. Further work is needed to determine the mechanism behind this association and to further characterize the microbiome in this subgroup of HCT recipients.

OBJECTIVES/GOALS: Our objective is to characterize excitatory, inhibitory, and neuromodulatory components of the voluntary motor command at the level of the spinal motoneuron in people with multiple sclerosis (MS). This information will provide insight into neural mechanisms of motor dysfunction and their heterogeneity among patients with MS. METHODS/STUDY POPULATION: Due to advances in high-density surface EMG (HDsEMG) decomposition and the recent development of a paradigm for reverse engineering of motor unit population discharge, we can feasibly estimate aspects of excitatory, inhibitory, and neuromodulatory components of the voluntary motor command in humans on a person-specific basis. We tested 11 ambulatory patients with MS and mild-moderate disability. We recorded HDsEMG from tibialis anterior (TA) and soleus (SOL) during isometric plantarflexion and dorsiflexion, performed as slow triangle contractions. EMG was decomposed into motor unit spike trains using blind source separation. We calculated a number of motor unit variables, most notably delta-F, which estimates motoneuron excitability and the balance of neuromodulatory and inhibitory inputs. RESULTS/ANTICIPATED RESULTS: There were consistent differences in MS patients vs. controls. For TA, values were decreased for delta-F (3.9 vs. 5.9 pps), initial firing rate acceleration (5.8 vs. 7.1 pps), firing rate range (9.3 vs. 11.9 pps), and max firing rate (12.3 vs. 15.0 pps). SOL had more modest decreases in delta-F (3.0 vs. 3.8 pps) and firing rate range (4.8 vs. 5.6 pps). Self-sustained firing was longer for MS patients. Within a patient, abnormalities in motor unit variables were not consistent across muscles and legs. Interestingly, there were several abnormalities in the patients with a normal clinical motor exam, indicating that perhaps our measures are sensitive to subclinical changes in processing of voluntary motor commands. DISCUSSION/SIGNIFICANCE: Excitatory, inhibitory, and neuromodulatory components of the voluntary motor command must be appropriately balanced for skilled motor output. This study is the first to characterize how they are disrupted in MS, providing foundational information to inform the development of mechanistically-based rehabilitation interventions.

Objectives/Goals: This study examines associations between childhood violence exposure, accelerated biological aging, and adolescent depression using DNA methylation-based epigenetic clocks. Findings aim to identify biomarkers for early detection, guide interventions, and address youth mental health disparities. Methods/Study Population:Data from the Future of Families and Child Wellbeing Study (N = 4,898), a diverse urban U.S. cohort, were analyzed. Childhood violence exposure, assessed using the Parent-Child Conflict Tactics Scale, included measures of physical, emotional, and psychological aggression and neglect. Biological aging at age 15 was evaluated using second-generation epigenetic clocks derived from saliva DNA methylation patterns, while depressive symptoms were measured with the CES-D scale. Multiple linear regression models tested associations between early violence exposure, epigenetic aging, and depressive symptoms, adjusting for socioeconomic status, caregiver mental health, and other key covariates. Results/Anticipated Results: Preliminary results suggest that early violence exposure may be linked to accelerated biological aging and depressive symptoms during adolescence, a critical developmental period. Epigenetic clocks offer an objective method for identifying high-risk youth, complementing mental health evaluations. With further validation and participatory action research, these findings could guide the development of biomarkers for longitudinal testing in school-based screenings and community health programs. These tools aim to be accessible, culturally relevant, and tailored to diverse populations, enhancing early detection, informing personalized interventions, and supporting scalable clinical applications. Discussion/Significance of Impact: This study explores links between early adversity, biological aging, and mental health, advancing understanding of adolescent depression. Epigenetic biomarkers could improve risk detection and guide tailored interventions in schools and community settings, enhancing access and reducing disparities.

OBJECTIVES/GOALS: It has been previously shown that pediatric high-grade glioma (pHGG) survival is different between sexes. We set out to find out whether there are sex-specific differences in the genomic landscapes of pHGG that may underlie this sex disparity. METHODS/STUDY POPULATION: We downloaded Illumina 450k DNAm data from ArrayExpress and GeneExpressionOmnibus. The minfi package was used to process raw DNAm data. Sex chromosomes and CpGs that are common SNPs were removed. Surrogate variables (SVs) were estimated via the sva Bioconductor package. Differentially methylated CpGs were identified by fitting a multiple linear regression model for the DNAm level at each CpG, with independent variables being sex (a binary variable) and the estimated SVs. RNAseq data was downloaded from Cavatica, and differential gene expression analysis was carried out via the DESeq2 package. RESULTS/ANTICIPATED RESULTS: In the pediatric glioblastoma (GBM) DNAm data [58 female & 91 male IDH wt samples; ages 0.1–21 yrs;], we found 7,371 differentially methylated cytosines (DMCs) at FDR≤0.05. Of the DMCs, 289 had DNAm differences between male and female samples ≥10%. The majority of probes (68%) were in CpG islands, shelves, or shores. We also found 4 differentially methylated regions (DMRs) between sexes (FWER≤0.1). In the adult GBM DNAm samples [32 F & 32 M IDH wt samples; ages 22–75 yrs], we found only 117 DMCs at FDR≤0.05, and no DMRs. In the RNAseq dataset [68 F & 54 M pHGG samples, ages 0.08–30.6 yrs], we found 383 differentially expressed genes (at FDR≤0.05), and 16 of them (4%) overlapped a DMC. DISCUSSION/SIGNIFICANCE OF IMPACT: Our findings demonstrate that pHGG exhibits sex-specific methylome differences. Interestingly, this difference is greater in the pediatric population as compared to adults. The pHGG transcriptome also differs by sex, which may be related to differential DNAm in a minority of cases.

OBJECTIVES/SPECIFIC AIMS: Drugs to attenuate aortic growth are usually not initiated in patients with Marfan syndrome until aortic dilation is already present. Therefore, we measured the impact of drugs (the renin-angiotensin system inhibitors losartan and enalapril) on survival and thoracic aortic growth in a mouse model of Marfan syndrome when extensive aortic dilation was already present. METHODS/STUDY POPULATION: Male and female fibrillin-1 hypomorphic (FBN1 mgR/mgR) mice (n=10-12/group) were stratified into treatment groups by aortic diameter at 6 weeks of age to ensure an equivalent average aortic diameter in each group at the start of the study. Osmotic mini pumps filled with PBS (vehicle), enalapril (2 mg/kg/d), or losartan (20 mg/kg/d) were implanted subcutaneously into mice after stratification. Mini pumps infusing drug or vehicle were replaced every 4 weeks for a total duration of 12 weeks. Wild type littermates (n=10) were infused with PBS as a negative control to the Marfan mouse model. Ascending aortic diameters from male and female FBN1 mgR/mgR mice and their wild type littermates were assessed by ultrasound every 4 weeks from 6 to 18 weeks of age. Aortic diameters were measured luminal edge to luminal edge during diastole. RESULTS/ANTICIPATED RESULTS: 6 week old FBN1 mgR/mgR mice exhibited significantly dilated ascending thoracic aortas at study initiation compared to their wild type sex-matched littermates (in males: FBN1 mgR/mgR = 1.87 +/− 0.07mm, wild type = 1.23 +/− 0.07mm; p <0.001) (in females: FBN1 mgR/mgR = 1.56 +/− 0.07mm, wild type = 1.18 +/− 0.07mm; p <0.001). Baseline mortality of FBN1 mgR/mgR mice infused with PBS was 36% in male and 22% in female mice at the time of study termination. Within sex-matched mgR littermates, there was no significant difference in survival between groups treated with PBS, enalapril, or losartan after 12 weeks (p=0.224 for males, p=0.094 in females). In the same groups, no significant difference in maximum ascending aortic diameter was detected after treatment for 12 weeks (in males: PBS=2.69 +/− 0.19 mm, enalapril=2.04 +/− 0.27 mm, losartan=2.42 +/− 0.28 mm; p=0.24) (in females: PBS = 1.92 +/− 0.13, enalapril=1.89 +/− 0.31, losartan=1.98 +/− 0.17; p=0.86). Furthermore, aortic diameters in the FBN1 mgR/mgR mice were found to demonstrate sexual dimorphism. DISCUSSION/SIGNIFICANCE OF IMPACT: This research shows that losartan is not effective when administered after significant thoracic aortic dilation has already occurred in FBN1 mgR/mgR mice. This has important translational implications because losartan is usually not started in patients with Marfan syndrome until significant aortic dilation is already present. Therefore, more research needs to be done to determine the critical time period within which this medicine will be effective if given to patients. In addition, this research demonstrates that male FBN1mgR/mgR mice have a significantly larger aortic diameter than female FBN1mgR/mgR mice. This sexual dimorphism has recently been observed in patients with Marfan syndrome as well. Additional studies for understanding the mechanism underlying this sexual dimorphism have the potential to elucidate new therapeutic approaches for aortic disease.

OBJECTIVES/GOALS: While mutant TP53 is an attractive therapeutic target in TNBC, attempts to target the mutant p53 protein directly have failed. Thus, we aim to identify pathways critical for the survival of TP53 mutant cells that can be targeted in TNBC. We have identified Kif11 as one such target and aim to further investigate its function in TP53 mutant TNBC. METHODS/STUDY POPULATION: We conducted a dual in silico/in vivo screen that identified Kif11 inhibition as preferentially inhibiting the growth of TP53 mutant TNBC. We obtained data on TP53 mutational status, KIF11 mRNA expression levels, and clinical characteristics from TCGA, METABRIC, and CCLE datasets. We treated breast cancer cell lines with the KIF11 inhibitor SB-743921. Cell counts were obtained through staining with DAPI or Hoechst and imaging on the ImageXPress PICO. We detected cell death by DRAQ7 staining and flow cytometry analysis following Annexin V-PI staining. To investigate mitotic spindle organization, we performed immunofluorescent staining with an anti-tubulin antibody and DAPI co-staining. Cell cycle analysis was performed through flow cytometry. RESULTS/ANTICIPATED RESULTS: KIF11 is highly expressed in TP53 mutant and TNBC clinical samples. High KIF11 expression is associated with poorer clinical outcomes. Kif11 inhibition suppresses growth of both TP53 mutant and wild-type breast cancer cells, but preferentially induces the death of TP53 mutant cells as detected by DRAQ7 and Annexin V/PI staining. Kif11 inhibition induces a G2-M block and growth inhibition in TP53 wild-type cells. On the other hand, following treatment with the Kif11 inhibitor SB-743921, TP53 mutant cells undergo mitotic spindle dysfunction leading to the formation of multinucleated cells and cell death. DISCUSSION/SIGNIFICANCE: These results demonstrate that Kif11 is a promising therapeutic target in aggressive, TP53 mutant TNBCs. Kif11 inhibitors, including SB-743921, have been tested in human trials, and are well tolerated, but it is unclear which patients would most benefit. Our studies show that Kif11 inhibitors may be most useful in patients with TP53 mutant TNBCs.

Effective mentoring is a key mechanism propelling successful research and academic careers, particularly for early career scholars. Most mentoring programs focus on models pairing senior and early career researchers, with limited focus on peer mentoring. Peer mentoring may be especially advantageous within emerging areas such as implementation science (IS) where challenges to traditional mentoring may be more prevalent. This special communication highlights the value of peer mentoring by describing a case study of an early career IS peer mentoring group. We delineate our curriculum and structure; support and processes; and products and outcomes. We highlight important group member characteristics to consider during group formation and continuation. The group’s long-term (6 years) success was attributed to the balance of similarities and differences among group members. Members were in a similar career phase and used similar methodologies but studied different health topics at different institutions. Group members gave and received instrumental and psychosocial support and shared resources and knowledge. Peer mentoring can serve an important function to provide emotional, logistical, and professional development support for early career scholars. Our case study highlights strategies to foster peer mentoring groups that provide a generalizable blueprint and opportunity for improved outcomes for early career professionals.

Social media offers research teams new opportunities for outreach and study recruitment; however, research teams often need guidance and tools on how to use social media to effectively recruit for their clinical trials. To address this gap, the Recruitment Innovation Center (RIC) developed a new, comprehensive toolkit informed by community feedback and extensive RIC experience. The toolkit contains guidance and considerations for using social media to recruit clinical trial participants, including best practices, platform-specific strategies, and customizable templates. This paper details the creation and contents of this new, free resource.

This in-depth analysis illuminates a translational journey of a community-university research collaboration that examined health disparities among incarcerated pregnant women and spanned the translational spectrum, with the initial collaboration in 2011 paving the way for consequent research grants, publications, practices, programs, and legislation passed years later. The case study utilized data from interviews with research stakeholders, institutional and governmental sources, peer-reviewed publications, and news stories. Identified research and translational challenges included cultural differences between research and prison system; the prison system’s lack of transparency; politics of using and translating research to policy change; and issues of capacity, power, privilege, and opportunity when doing community-engaged research/science. Among the facilitators of translation were the Clinical and Translational Science Award and institutional support; engagement of key stakeholders and influencers; authentic collaboration and team science; researchers as translation catalysts; pragmatic scientific approach; and policies and legislative activities. The research contributed to a variety of community and public health, policy/legislative, clinical/medical, and economic benefits. The case study findings enhance our understanding of translational science principles and processes leading to improved wellbeing and serve as a call for advancing the research agenda addressing health disparities related to criminal and social justice issues.

OBJECTIVES/SPECIFIC AIMS: The purpose of this case series is to show how helping parents instill a non-restrictive, structure-based (i.e., authoritative) approach to feeding is useful in addressing family food conflicts in a clinical child obesity treatment program. METHODS/STUDY POPULATION: Case reports are presented for 3 young children (two 8-year-old males and one 7-year-old female) with obesity (BMI ≥ 95th percentile for age and sex). Patients underwent family-based treatment at Brenner FIT® (Families In Training), an interdisciplinary tertiary weight management clinic. RESULTS/ANTICIPATED RESULTS: All patients experienced a period of rapid weight gain and/or severe onset obesity. Parents reported a combination of problematic eating behaviors (e.g., sneaking food, frequent complaints of hunger, vomiting from rapid consumption). Families implemented structure-based feeding with a meal-snack schedule and allowed children to eat until they were full from the food provided at meal-snack times. BMI z-score decreased from 2.19 to 2.07 in patient 1 and from 2.43 to 2.09 in patient 2 (follow-up weight was not available for patient 3). DISCUSSION/SIGNIFICANCE OF IMPACT: The improvements observed by our clinical program after families lifted restriction and instituted authoritative feeding is anecdotal evidence for the ecological validity of existing empirical work. Randomized controlled trials are needed to examine causality.

OBJECTIVES/GOALS: Leigh Syndrome, French Canadian-Type (LSFC) is a neurometabolic disorder caused by mutation of mitochondria-related gene, LRPPRC. White matter lesions and demyelination in central nervous system are common in LSFC. LRPPRC is enriched in myelinating glial cells, yet its role is not known. Our goal is to elucidate its mechanistic role in myelination. METHODS/STUDY POPULATION: We crossed C57BL/6N mice bearing a LRPPRC-loxP allele with mice bearing a Plp-CreERT2 allele. Mice with the Plp-CreERT2 allele expresses a tamoxifen-inducible Cre under the control of the Plp promoter, which drives expression in oligodendrocytes. Using these strains, we can target the deletion of LRPPRC, via tamoxifen injection, in both newly formed myelin and mature myelin. Plp-CreERT2; LRPPRCL/L (LRPPRC-KO) or control littermate mice will be injected for LRPPRC deletion at developmental and maturation stages of myelin. Immunofluorescence and electron microscopy of isolated brain tissues will be used for myelin integrity analysis. Cognitive functions of the mice will be measured via behavioral tests. Lastly, we will submit tissues for lipidomic analyses to observe any lipid metabolite variation. RESULTS/ANTICIPATED RESULTS: Behavioral and motor defects would be expected in LRPPRC-KO mice performing in cognitive function tasks across myelin maturation stages. Electron microscopy-based structure analysis of optic nerve, corpus callosum, and spinal cord should reveal thin or loss of myelin on the axons of LRPPRC-KO compared to control. Immunofluorescence staining of major myelin structural proteins, including myelin proteolipid protein (PLP), myelin basic protein (MBP), and myelin-associated glycoprotein (MAG) would be expected have lower levels in LRPPRC deficient tissues. Since myelin is a lipid-rich species, we would also expect lipid concentrations to be affected. LRPPRC-KO lipidomic analyses of myelin-related lipids should depict lower levels in comparison to control, which would imply dysfunctional lipid metabolism. DISCUSSION/SIGNIFICANCE: There are limited studies in ameliorating neural deficits caused by LS and LSFC. Successful completion of this project would help elucidate the functions of LRPPRC in myelination and lipid metabolism and potentially provide insights for developing novel therapeutic strategies for alleviating the demyelination and neural deficits in LSFC.

OBJECTIVES/GOALS: We use a tissue engineered, biomimetic, 3D model to study the pathogenesis of breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) by comparing the effect of silicone implant shell on proliferation of patient-derived BIA-ALCL to its precursor T cells within the breast microenvironment. METHODS/STUDY POPULATION: Patient-derived breast tissue was processed for component adipocytes, ductal organoids, and stromal vascular fraction. These were suspended within 50 µl of 0.3% type I collagen matrix to which was added 200,000 cells/mL of either patient-derived BIA-ALCL cells or T progenitor cells. These were then plated into 6mm wells. As a control, both BIA-ALCL cells and T progenitor cells were suspended within type I collagen alone at the same seeding density without breast components. Before plating, wells were lined circumferentially with either textured, smooth, or no implant shell. These were 1cm by 2cm pieces dissected from the whole implant. Wells were imaged using confocal microscopy over 8 days. RESULTS/ANTICIPATED RESULTS: Unstimulated T progenitor cell count showed no significant increase in any of the conditions tested. The change in cell count over 8 days was 3.85% in each condition (p = 0.3352). A Tukey’s multiple comparison test comparing each condition revealed no significant increase in cell count over 8 days for all six conditions. Notably, our previous studies have shown proliferation of BIA-ALCL cells to be significantly more robust in the biomimetic platform compared to collagen-only groups, regardless of implant shell type (p < 0.01). BIA-ALCL cells grew nearly 30% faster in textured and smooth shell biomimetic groups compared to biomimetic wells lacking implant shell. DISCUSSION/SIGNIFICANCE OF IMPACT: Towards elucidating BIA-ALCL’s etiopathology, we show that silicone implant shell has a significant effect on proliferation of BIA-ALCL cells, but not their precursor T cells. If breast implant silicone shell is not a sufficient stimulus for T cell proliferation, co-stimulatory factors are required.

ABSTRACT IMPACT: Evaluate the accuracy of applying a predictive algorithm using clinical measures only in persons with stroke in the US. OBJECTIVES/GOALS: PREP2 is an algorithm, that predicts UL functional capacity at 3 months post stroke from measures taken within the first week.(1, 2) Despite its accuracy and ease of use, challenges arise of applying PREP2 in the US. The objective of this study was to evaluate the accuracy of PREP2 using only clinical measures in persons with stroke in the US. METHODS/STUDY POPULATION: Individuals with first-ever stroke were recruited from a local hospital and followed longitudinally, as part of an ongoing observational cohort. Variables captured within two weeks of stroke and entered into the algorithm were: age, SAFE score(1-3) and NIH Stroke Scale(4) total score. The algorithm classifies individuals into one of four expected categories: excellent, good, limited, or poor. The dependent variable was the predicted category of UL functional capacity as defined by ranges of the 3-month Action Research Arm Test score.(5) Accuracy, specificity, sensitivity, positive predictive value (PPV), and negative predictive value (NPV) of the algorithm, were calculated using a 4x4 contingency table. Other statistics analyzed include demographic characteristics and a weighted kappa for the algorithm. RESULTS/ANTICIPATED RESULTS: Data from 49 individuals were analyzed (57% male, 88% ischemic stroke, age = 65±8.56 years). Expected categorization matched observed categorization in 29/49 subjects, with the overall accuracy of the algorithm of 59% (95% CI = 0.44-0.73). The sensitivity of the algorithm was low except for the excellent category (0.95). Specificity was moderate to high for good (0.81), limited (0.98), and poor (0.95) categories. PPV was low for all categories and NPV was high for all categories except the good category. Additional results including weighted kappa and inaccuracy of predictions to be presented. DISCUSSION/SIGNIFICANCE OF FINDINGS: PREP2 algorithm, with clinical measures only, is better than chance (chance = 25% for each of the 4 categories) alone at predicting a category of UL capacity at 3 months post stroke. PREP2 is a simple tool that facilitates evaluation of eventual UL outcome from measures routinely captured after a stroke within most healthcare settings in the US.

OBJECTIVES/GOALS: Traumatic interpersonal experiences are associated with higher rates of chronic pain, increased pain severity and poorer functioning. The objective of this ongoing project is to obtain prevalence rates for various forms of interpersonal trauma among individuals with chronic pain, and to explore the potential mediating effect of heightened sensory and social sensitivity on the experience of pain. METHODS/STUDY POPULATION: Patients at Michigan Medicine between the ages of 18 and 65 complete an online survey. Patients are being recruited through a tertiary-care, outpatient pain clinic, as well as through an online health research portal. We aim to recruit 700 participants; we currently have 59.6% of our goal (n = 417). Participants also have the option to be included in a registry from which we can recruit for future studies. Approximately 85% of our participants have agreed to be in the registry. RESULTS/ANTICIPATED RESULTS: Preliminary data show that, of the 263 (63.4%) participants for whom data on chronic pain is available, 167 (63.5%) report chronic or persistent pain over the previous 3 months. Of these, 54% reported some form of childhood abuse or neglect. Approximately 41% reported four or more adverse childhood experiences. Additionally, of the 122 participants (73%) who were in a current romantic relationship, 20% reported some form of physical violence victimization from their romantic partner. We anticipate that interpersonal trauma will be associated with poorer perceptions of social relationships, higher sensory sensitivity, and higher perceived stress. DISCUSSION/SIGNIFICANCE OF IMPACT: The PASE Project parent study will be used to better understand prevalence rates for various forms of interpersonal trauma in our chronic pain population. Future analyses and studies will explore alternative pathways linking interpersonal trauma to the experience of pain through sensory and social sensitivity, which will inform interventions aimed at reducing pain among patients with a history of trauma.