OBJECTIVES/GOALS: Selinexor is a novel XPO1 inhibitor that blocks nuclear export, thus impairing DNA repair and causing apoptosis. Our goal was to conduct preclinical and clinical studies to test our hypothesis that selinexor’s efficacy is boosted by priming with temozolomide and is associated with a tissue biomarker. METHODS/STUDY POPULATION: We leveraged a team science approach through the NCI Cancer Therapy Evaluation Program (CTEP) to design preclinical experiments, develop a novel RNAseq analysis pipeline, and use pre-existing clinical experience to open an early phase clinical trial for recurrent glioblastoma. Team members included a CTEP medical officer, cancer biologist, pharmacist, industry scientist, translational scientist, and early career clinician scientist mentored by an expert clinician scientist. Based on preclinical results, participants in the clinical trial experimental arm will receive sequential temozolomide 150mg/m2 on days 1-5 and a starting dose of selinexor 60mg on days 8 and 15 of a 28-day cycle. Participants in the control arm will receive monotherapy temozolomide. RESULTS/ANTICIPATED RESULTS: Sequential treatment of U87 cells and intracranial xenografts had superior DNA damage (É£H2A.X, cleaved PARP) and overall survival compared to combination or single-agent (HR 0.25 [95% CI, 0.07-0.84]; p=0.01, log-rank). We used the top-scoring gene pair method to identify an RNAseq signature associated with response to selinexor. We then designed a trial for first recurrent MGMT methylated glioblastoma. Primary objectives are safety and preliminary efficacy. Secondary objectives are overall response rate, efficacy, and validation of a molecular signature. Phase 1 dose finding (n=12) will be followed by a randomized phase 2 (n=72); using proportional hazards regression, RHR 0.5 with p DISCUSSION/SIGNIFICANCE: The NCI CTEP Project Team employs team science as a framework to successfully develop multidisciplinary collaborations, build investigator trial experience, and lead the way to future research opportunities. Our trial addresses a significant unmet need to offer novel therapies and molecular biomarkers in glioblastoma.

Objectives/Goals: Novel therapeutics to control Staphylococcus aureus (S. aureus) infections are needed for people with cystic fibrosis (CF, PwCF). In this study, our objective is to determine if the pharmacologic MEK1/2 inhibitor compound ATR-002 can restrict the growth of S. aureus clinical isolates and modulate infection in a murine model of S. aureus infection. Methods/Study Population: To evaluate the anti-inflammatory effects of ATR-002 on human macrophages, cells were stimulated with TLR2 agonists FSL1 or Pam3CSK4 with a dose range of ATR-002, and secretion of proinflammatory cytokines were measured by ELISA. To determine the direct antibacterial effect of ATR-002, minimum inhibitory concentration (MIC) assays were performed with the community-associated methicillin-resistant S. aureus strain USA300 and 40 S. aureus isolates from PwCF. To validate our results in vivo, mice were provided i.p. treatment with either vehicle, the MEK1/2 inhibitor compound PD0325901 (20 mg/kg), or ATR-002 (10 mg/kg) prior to intranasal infection with 1x10^7 CFU of USA300. Bacterial burdens at 4- and 24-hour post-infection (p.i.) and inflammatory cell recruitment at 24 hours p.i. were quantified. Results/Anticipated Results: Macrophages treated with ATR-002 exhibited a dose-dependent decrease in secretion of proinflammatory cytokines TNF and IL-8 following TLR stimulation. Our studies identified that ATR-002, but not PD0325901 or other MEK1/2 inhibitors, had direct antibacterial effects, and ATR-002 had an MIC range of 8 to above 64 ug/mL on CF S. aureus isolates. In the murine pulmonary infection model, delivery of ATR-002 and PD0325901 significantly prevented infection-induced loss of body mass and decreased neutrophil inflammation. However, when bacterial burdens were quantified 4-hours p.i., only ATR-002 treatment reduced lung bacterial burden compared to vehicle or PD0325901-treated groups. Discussion/Significance of Impact: These results are the first demonstration of the in vivo anti-inflammatory and antibacterial effects of ATR-002. Our results further demonstrate that ATR-002 exhibits direct antibacterial effects across a collection of clinical isolates of S. aureus. Future studies will continue to investigate the therapeutic potential of ATR-002.

OBJECTIVES/GOALS: The objective of our research is to define unique molecular and immune markers in benign breast tissue to better identify women at risk of node-positive breast cancer (BC). The goal of the work is to improve individualized risk assessment, to guide targeted prevention and screening recommendations, and to reduce disease incidence and mortality. METHODS/STUDY POPULATION: From the Mayo Clinic’s Benign Breast Disease (BBD) cohort, we matched women who developed node-positive breast cancer after a BBD biopsy (cases; n=42) with women who remained cancer-free (controls; n=37), considering patient age and biopsy date. We used NanoString gene expression profiling to identify differentially expressed genes (DEGs) between cases and controls. We optimized a multiplex immunofluorescence (mIF) approach to simultaneously detect multiple markers within single FFPE tissue slides to correlate cells expressing DEGs in relation to innate and adaptive immune effectors. We used tissue segmentation, cell phenotyping, and spatial relationships to define molecular and immune differences between cases and controls. RESULTS/ANTICIPATED RESULTS: We discovered higher gene expression levels of IRF8 (interferon regulatory factor 8, a factor involved in immune cell differentiation) in controls as compared to cases (p = 0.0024) and found that IRF8 expression is also associated with longer cancer onset times among cases (p = 0.0012). Our pilot mIF experiments revealed higher frequencies of CD4+, CD8+, CD68+, CD20+ and CD11c+ cells in controls compared to cases. We predict that higher IRF8 expression and increased frequencies of immune cells in BBD biopsies indicate a proactive immune environment that may act to prevent cancer development. Furthermore, we predict that our analyses of the spatial localization of these markers by mIF may offer further predictive insight. DISCUSSION/SIGNIFICANCE: Deciphering the relationship between immune alterations in BBD and risk of node positive BC has the potential to improve individualized risk prediction. These insights will foster improved surveillance and informed screening and prevention, ultimately reducing BC incidence and mortality.

OBJECTIVES/GOALS: The goal of U-LINK is to bring together diverse scholars from multiple disciplines to address complex and challenging problems in healthcare, climate change, social equity, and community, through innovative team science, and aligned with the University of Miami’s strategic plans. METHODS/STUDY POPULATION: The U-LINK program has supported developmental and implementation projects through a competitive selection process. Developmental funding was intended for teams to develop and refine ideas and to become established as an effective team. Additional funding was provided to teams to advance their projects by conducting data collection and feasibility testing. In addition, U-LINK has supported fellowship for pre-doctoral and affiliated doctoral trainees. Team science training was provided to all teams through didactic lectures and hands-on training. Teams were tracked longitudinally by using surveys and bibliometrics to measure success and impact including scholarly output and follow on funding. Network analysis was performed to analyze research collaboration networks before and after ULINK funding. RESULTS/ANTICIPATED RESULTS: U-LINK has funded pilot programs and initial phases for 57 projects and 13 fellowships in the last three years. Over 400 individuals on teams from 16 schools/academic units collaborated on these projects on topics such as resilience, climate change, social equity and societal challenges, health, and impact of recent legislation on LGBTQ+ community. While data collection and analysis are ongoing, initial results show successful outcomes from U-LINK projects including publications and $29.5m in follow-on external funding. We anticipate network analysis to demonstrate increased and continued multi-disciplinary collaborations among U-LINK teams through co-authorship networks and increase in collaborative grants being submitted and/or funded. DISCUSSION/SIGNIFICANCE: The University of Miami’s U-LINK program has demonstrated success in forming interdisciplinary teams that have produced real-world solutions to complex problems by harnessing the inherent diversity and strength across UM’s programs.

Objectives/Goals: Conventional magnetic resonance imaging (MRI) methods are unable to visualize bone comparable to computed tomography (CT). Radiation therapy can result in post-treatment complications, such as osteoradionecrosis (ORN). We aim to integrate black bone (BB) MRI into routine follow-up MRI scans as an alternative to CT to monitor the development of ORN. Methods/Study Population: We assess the CT, T2-weighted (T2W), and BB MRI scans of 21 head and neck cancer patients without active ORN. All images are acquired within 4 weeks of each other to minimize anatomical variability. The mandibles are manually segmented on each image, and the MR images are registered to the CT to map the CT contour onto the MR images for comparison. Image segmentation evaluation metrics, including dice similarity coefficient (DSC), mean distance to agreement (MDA), and Hausdorff distance (HD), assess for spatial differences between each MRI sequence, using CT as reference standard. DSC measures contour volume, while MDA and HD assess the differences in contour boundaries, with HD sensitive to outliers. We employ a Wilcoxon signed-rank test using a significance value of p≤0.05 to assess for statistical significance. Results/Anticipated Results: Using metrics widely accepted in biomedical research, we assess the performance of BB to visualize mandible against its conventional T2W MRI counterpart when compared to CT. Black bone has a significantly different DSC (median=0.878, IQR=0.0397) than T2W (median=0.806, IQR=0.0876; p<0.0001), indicating high volumetric overlap between contours on BB and CT. Black bone has a significantly different MDA (median=0.0731mm, IQR=0.0227mm) than T2W (median=0.119mm, IQR=0.0697; p<0.0001), indicating high agreement between contour boundaries on BB and CT. Black bone has a significantly different HD (median=0.649mm, IQR=0.211mm) than T2W (median=1.80, IQR=0.933; p<0.0001), indicating a submillimeter difference between contour boundaries, including outliers, on BB and CT. Discussion/Significance of Impact: Our results exhibit BB as a promising non-ionizing alternative to CT for bony visualization compared to conventional MRI. BB has potential to detect early anatomical changes in bone, providing a standardized assessment of ORN. This can improve our dose–response understanding of post-treatment toxicities, refining radiation treatment planning.

Objectives/Goals: Ovarian cancer is the most lethal gynecologic cancer with emergence of recurrent and resistant disease being frequent. We sought to identify novel ways to effectively kill chemotherapy-resistant forms of ovarian cancer and to prevent recurrence following curative intent with surgical and adjuvant regimens. Methods/Study Population: Our group identified CTPS1 as a novel dependency in triple negative breast cancer (TNBC) and ovarian cancer. We found CTPS1 was highly expressed in breast and ovarian tumor tissues and therapy-resistant models. We demonstrated siRNA knockdown of CTPS1 reduced proliferation in sensitive and resistant cell lines. In collaboration with Step Pharma, who developed the first CTPS1 inhibitor (STP938), we performed genome-wide CRISPR KO screens on STP938-sensitive and -resistant cells. Top synthetic lethal hits identified included TSC1, TSC2, and PPP2R2A. Synergy assays were conducted with STP938 in combination with mTOR inhibitors (Everolimus, Sirolimus, and Temsirolimus) and the PPP2R2A inhibitor LB-100 to evaluate the therapeutic benefit of combination therapies. Results/Anticipated Results: We identified CTPS1 as a novel vulnerability in many ovarian cancer cell line models, including models of chemotherapy and/or PARP inhibitor resistance. The first-in-class CTPS1 inhibitor (STP938) was shown to be a highly effective anticancer agent in sensitive and resistant forms of ovarian cancer, both in vitro and in vivo. Genome-wide CRISPR KO screens identified central components of the mTOR pathway (TSC1 and TSC2), as well as PPP2R2A, as synthetic lethal targets in the setting of STP938 exposure. We anticipate that combinatorial treatment of mTOR inhibitors and PP2R2A inhibitors with STP938 will further enhance efficacy and reduce the risk of recurrence when used in the adjuvant treatment of ovarian cancer patients. Discussion/Significance of Impact: This study will validate synthetic lethal interactions from our CRISPR screen, reveal genes that could be mutated in ovarian cancer patients that may be driving resistance to STP938, and uncover combination therapies that can be used to increase efficacy in ovarian cancer patients treated with STP938.

Objectives/Goals: The Never-in-mitosis A-related (NEK) kinases are a family of 11 poorly explored kinases that play varying roles in cellular processes. Aberrant NEK activity is implicated in various human diseases, including cancer. We hypothesize that NEK9 drives triple-negative breast cancer (TNBC) motility. Methods/Study Population: Baseline NEK9 expression was determined across five breast cancer and three non-breast cancer cell lines by immunoblot. We expanded the analysis to six additional TNBC cell lines. To determine the impact of NEK9 on TNBC biology, we evaluated the effects of NEK9 pharmacological inhibition with novel inhibitor BA 03-53-11 (BA) at 0µM, 0.5µM, 1µM, and 2µM. We treated TNBC cell lines MDA-MB-231, BT-549, HS578T, and TNBC patient-derived cell line TUBcX-4IC and performed functional assays to assess impacts on cell motility (scratch assay), viability (crystal violet staining), and proliferation (Ki-67 staining). Results/Anticipated Results: NEK9 levels were elevated in the TNBC cell line compared to other breast cancer subtypes, osteosarcoma, and non-cancerous cells. Additionally, NEK9 protein expression was variable across TNBC cell lines. While pharmacological NEK9 inhibition did not significantly alter TNBC cell viability or proliferation, we observed that NEK9 inhibition suppressed cell motility in TNBC cells compared to vehicle control. Taken together, these preliminary results support a role for NEK9 in regulating TNBC progression. Our ongoing studies aim to test NEK9-mediated motility and proliferation in additional TNBC cell lines and evaluate NEK9 as a therapeutic target for this aggressive breast cancer subtype. Discussion/Significance of Impact: TNBC is an aggressive form of breast cancer that lacks targeted therapies. Because aberrant kinase activity underpins oncogenic transformation, kinase inhibitors have emerged as ideal therapeutic agents. Elucidation of NEK9 function in TNBC is essential for the development of novel therapeutics.

OBJECTIVES/GOALS: * Patients with skin of color (SOC) are disproportionately affected by systemic lupus erythematosus (SLE) and cutaneous lupus erythematosus (CLE). In this study, we aim to address this disparity and characterize the real-world efficacy and tolerability of anifrolumab in CLE patients using validated disease activity instruments. METHODS/STUDY POPULATION: This single-center, prospective observational cohort study includes SLE patients with severe or refractory CLE who have received ≥ 1 dose of anifrolumab. Cutaneous disease activity is assessed periodically at 2, 6, 9, 12, and 18 months using the Cutaneous Lupus Disease Area and Severity Index (CLASI). Adverse events and concurrent treatments are also routinely evaluated. To date, 22 patients have been enrolled, with 6-month follow-up data available for 15. At the time of anifrolumab initiation, 95% of participants had discoid LE (DLE), 60% had mucosal DLE, and 13% had subacute CLE. Nine patients identified as SOC, two as White, and four did not report race/ethnicity. RESULTS/ANTICIPATED RESULTS: A Friedman test showed statistically significant changes over time in CLASI activity score (CLASI-A) (χ2(2) =20, p<0.0001) (Figure 1) and CLASI damage score (CLASI-D) (χ2(2) =9.5789, p=0.0083) (Figure. To estimate effect sizes, we employed linear mixed models, which demonstrated statistically significant reductions in the CLASI-A score from baseline by an average of 14 points at 2 months (p<0.001) and 18 points at 6 months (p<0.001); notably, a reduction in CLASI-A of 4 is considered clinically meaningful. At 2 months, 20% of patients experienced a 50% or more reduction in CLASI, which increased to 60% of patients at 6 months. Patients on systemic corticosteroids could taper off. Adverse events were minimal and did not lead to treatment discontinuation. Fig. 1:[blob:https://acts.slayte.com/045319b4-7272-4351-a771-78ba9ee57f5c] Fig. 2:[blob:https://acts.slayte.com/67df7653-0cd8-4e8e-a3e1-d5c565b19dce] DISCUSSION/SIGNIFICANCE: As SOC patients with CLE have significant potential for permanent pigmentary alternations, early treatment is imperative. Effective treatments for refractory CLE are elusive. Our study represents the largest single-center cohort of CLE patients treated with anifrolumab and suggests that it is a promising therapeutic option for patients with SOC.

OBJECTIVES/GOALS: This study aimed to investigate the mechanistic effects of the omega-6-derived eicosanoid 12-HETrE on platelets of cardiovascular patients at risk for a recurrent cardiovascular event triggered by thrombosis. 12-HETrE negatively regulates platelet reactivity through binding to the prostacyclin receptor in platelets. METHODS/STUDY POPULATION: Healthy donors were recruited from the Ann Arbor community and the University of Michigan Medicine Center. Cardiovascular patients with elevated cardiovascular risk were recruited from the Cardiac Catheterization Laboratory at Michigan Medicine Hospital. All subjects were recruited under study protocols approved by the University of Michigan IRB. Healthy donors were matched with the cardiovascular patients regarding age, sex, race, and BMI. Whole blood was collected via venipuncture into vacutainers containing sodium citrate. Platelets were isolated via serial centrifugation and treated ex vivo with vehicle control, 12-HETrE, or Iloprost. RESULTS/ANTICIPATED RESULTS: Based on our previous studies, we chose to treat platelets ex vivo with 25uM of 12-HETrE for 10 minutes. Using platelets of healthy donors, we have shown that treatment with 25uM of 12-HETrE for 10 minutes inhibited platelet aggregation and activation, and activated protein kinase A, suggesting activation of the prostacyclin receptor. We conducted a preliminary study to demonstrate that ex vivo treatment of 12-HETrE regulated signaling pathways in platelets such as cell-to-cell interaction, platelet activation and cytoskeleton rearrangements. In this study, we have demonstrated that treatment with 12-HETrE regulated receptors and intraplatelet proteins in platelets of cardiovascular patients. Furthermore, these proteins are involved in critical pathways in the platelet. DISCUSSION/SIGNIFICANCE: Dual antiplatelet therapy has significantly decreased mortality due to thrombotic events. However, cardiovascular events triggered by thrombosis persist as the leading cause of death in the US. This study may uncover key regulators to be targeted for the long-term goal of providing additional protection to reduce future incidence of thrombosis.

OBJECTIVES/SPECIFIC AIMS: Helping researchers assess and effectively translate innovations into healthcare improvements is a complex process (Terry et. al., 2013). The Clinical Translational Science Awards (CTSA)—supported by the National Institute of Health (NIH) under the auspices of the National Center for Advancing Translational Sciences (NCATS)— provide the resources and support needed to strengthen our nation’s clinical and translational research (CTR) enterprise. In 2008, Stanford University was awarded a CTSA from the NIH, establishing Spectrum (the Stanford Center for Clinical and Translational Research and Education). Under the Spectrum umbrella, the Byers Center for Biodesign manages the MedTech Pilot Program with the goal of translating discoveries into novel health technologies that address important unmet health needs. The MedTech Pilot Program is an innovative funding mechanism that seeks to (1) stimulate clinical translational research, (2) help promising projects bridge the gap between the bench and the patients’ bedside, and (3) encourage collaborative, transdisciplinary work. Specifically, the Pilot Program offers up to $50,000 to support projects involving medical devices and mobile technologies used for (1) therapeutic applications and (2) device-based patient-specific (or POC) diagnostic applications. This analysis of the MedTech Pilot Program will: 1) describe the Program’s structure and process; 2) highlight the intensive, hands-on mentorship and practical guidance awardees receive that enables them to more efficiently and effectively advance their projects toward patient care; and 3) characterize the progress of the 36 funded projects. METHODS/STUDY POPULATION: Key elements of the Pilot Program’s infrastructure and mentoring processes as they relate to project outcomes were identified. Additionally, outcomes data were collected from two sources: (1) annual survey of Pilot Awardees and (2) publicly available information relevant to the pilot projects. RESULTS/ANTICIPATED RESULTS: The Pilot Program’s framework and infrastructure has supported a diverse group of transdisciplinary projects. These projects were evaluated using both traditional and non-traditional metrics (e.g., patents, startups, publications). The initial investment of $1.5 million to fund 36 projects has led to over $88 million dollars in additional funding. Additionally, taking full advantage of the expertise in Silicon Valley, strong mentorship has helped advance projects along the clinical and translational path. DISCUSSION/SIGNIFICANCE OF IMPACT: The Pilot Program has benefited Stanford innovators and researchers by providing seed funding to help promising projects bridge the gap between the bench and the bedside. The intensive, hands-on mentorship, early pilot funding, and practical guidance pilot awardees receive effectively help translate their technologies into patient care.

Objectives/Goals: People with insulin-treated diabetes face hypoglycemia risk due to imperfect insulin replacement and impaired counterregulation. We identified the dopamine antagonist, metoclopramide, as a potential treatment. Hypothesis: Treatment with metoclopramide will prevent the development of impaired counterregulatory response to hypoglycemia. Methods/Study Population: In a pre-clinical model, diabetes was induced in 10-week-old Sprague-Dawley rats with streptozotocin (STZ, 65 mg/kg IP). Rats were divided into three groups: 1) diabetic controls (STZ+RS, n = 6), 2) recurrent hypoglycemia (STZ+RH, n = 7), and 3) recurrent hypoglycemia + metoclopramide (STZ+RH+MET, 3 mg/kg IP, n = 7). After 3 days, all rats underwent a hyperinsulinemic (50 mU/kg/min) and hypoglycemic (~45 mg/dl) clamp. In the clinical trial, adults with Type 1 diabetes (age 20–60, ≥5 years duration) were enrolled in a phase II, double-blinded, placebo-controlled trial. Awareness status was assessed via Gold score, and subjects maintained drug regimens and underwent two hyperinsulinemic-hypoglycemic clamps (where blood glucose was lowered to 100, 65, 55, and 45 mg/dl) to assess counterregulation. Results/Anticipated Results: In the pre-clinical model, glucose infusion rates (GIR) to maintain hypoglycemia were higher in STZ+RH (27±0.9 mg/kg/min) than STZ+RS (19±0.8 mg/kg/min, p Discussion/Significance of Impact: Metoclopramide improves glucoregulatory, sympathoadrenal, and counterregulatory responses to hypoglycemia in pre-clinical models, suggesting dopaminergic regulation. While clinical data are still blinded, increased epinephrine and growth hormone responses suggest treatment may preserve or restore counterregulation.

The Deep South has the highest prevalence of obesity, diabetes, and hypertension in the United States, with marked disparities by race, socioeconomic status, and rurality. Addressing these disparities requires not only effective interventions, but also a translational science workforce equipped to design, implement, and scale solutions in real-world settings. The Forge AHEAD Center was established to improve cardiometabolic health outcomes across the Deep South by advancing both research and scientific workforce development. As a central component of this mission, the Center has developed the “Pilot Plus” model, an integrated framework that combines pilot funding with structured training in translational science, multidisciplinary team-based mentorship, and embedded community engagement. Early-stage investigators are supported through coordinated access to methodological expertise, including dissemination and implantation science and assessment of social determinants of health, while community stakeholders are incorporated into the research process. By aligning funding, training, and infrastructure within a single program, the Pilot Plus model addresses fragmentation in traditional research development approaches and expands access to critical resources across institutions. This model provides an adaptable framework for strengthening translational research capacity and developing a cadre of demographically varied investigators prepared to advance health outcomes in regions with a high burden of chronic disease

OBJECTIVES/SPECIFIC AIMS: Patients with undiagnosed obstructive sleep apnea (OSA) will often present to an otolaryngologist with symptoms of chronic rhinosinusitis (CRS). Differentiating CRS from OSA may help obviate unnecessary and costly work-up for CRS. This study analyzes symptom profiles of such patients to help identify which require polysomnography. METHODS/STUDY POPULATION: This is a three-year retrospective analysis of adult patients seen in an academic practice with a rhinologic chief complaint. The 22-Item Sinonasal Outcomes Test (SNOT-22) survey, which is a validated patient-reported outcome measure widely adopted for CRS featuring a symptom scale of 1 (least severe) to 5 (most severe), was completed by patients with untreated OSA confirmed on polysomnography without CRS (OSA group) and a control group of CRS patients (CRS group). Results were compared using Chi-square test (categorical) and Wilcoxon rank-sum test (continuous) with Bonferroni correction, and multiple logistic regression. RESULTS/ANTICIPATED RESULTS: 43 patients were included in the OSA group [mean apnea-hypopnea index: 27.9 (SD: 21.2)] and 124 patients were included in the CRS group. The CRS group demonstrated significantly higher scores in nasal (p < 0.001), extra-nasal (p < 0.001) and ear/facial symptom domains (p = 0.001) while the OSA group reported higher psychological (p = 0.028) and sleep symptom domain scores (p = 0.052). As for the cardinal symptoms of CRS, nasal discharge and loss of smell were significantly higher in the CRS group (both p < 0.001), whereas facial pain (p = 0.117) and nasal obstruction (p = 0.198) were not significantly different between the two groups. After adjustment, for every 1-point increase in a patient’s score for ear pain, thick nasal discharge and loss of smell or taste, their odds of having CRS increased by a factor of 3.18 [(95% CI 1.61-6.29), p = 0.001], 1.60 [(95% CI 1.22-2.10], p = 0.001] and 1.36 [(95% CI 1.04-1.78), p = 0.025], respectively, compared to having OSA. OSA patients were more likely to choose a sleep-related symptom as a “most important complaint” (MIC) (p < 0.001). Facial pain and nasal obstruction were the most common MIC in the rhinologic domain for OSA patients, whereas thick nasal discharge and post-nasal discharge were the most common MIC for CRS patients. DISCUSSION/SIGNIFICANCE OF IMPACT: For patients presenting with rhinologic symptoms, the SNOT-22 can help identify those with undiagnosed OSA. OSA should be suspected in patients with sleep and psychological dysfunction as their primary complaints without the significant nasal drainage and anosmia that characterizes CRS.

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

OBJECTIVES/GOALS: Women with diabetes (DM) have higher rates of unplanned pregnancy and pregnancy complications, indicating a need for DM-specific counseling. Our aim is to use the Health Belief Model (HBM), widely applied to DM interventions, to create a conceptual model of contraceptive decision-making for women with DM. METHODS/STUDY POPULATION: Our convergent mixed methods study integrates quantitative survey data and qualitative interview data from women aged 18-50 with DM. We will interview until theoretical saturation is achieved. Descriptive statistics will be calculated to summarize demographics, health history, and contraceptive use and knowledge. Using a grounded theory approach, qualitative analysis will be conducted by JW and EJ with special focus on exploring HBM constructs. A joint display will be used to integrate key quantitative variables by qualitative themes. Finally, we will aim to implement these HBM constructs within the context of contraceptive decision-making for women with DM. RESULTS/ANTICIPATED RESULTS: To date, we have interviewed 16 women with average age of 35 and an equal mix of type 1 vs. type 2 DM and those who identify their health as poor/fair vs. good/very good. The following HBM domains have emerged as relevant to contraceptive decision-making: perceived threats, perceived barriers, cues to action and self-efficacy. An analysis of the cues to action domain suggests that patients’ responses to provider counseling are substantially dependent on provider tone and awareness of patient context. Effective cues were delivered supportively with focus on health promotion, while ineffective cues focused on adverse outcomes or were delivered to women not at risk of pregnancy. DISCUSSION/SIGNIFICANCE OF IMPACT: The application of the HBM to contraceptive decision making among women with DM will provide insight into critical factors that inform both patient and provider attitudes and behaviors and can be targeted for future interventions to reduce unplanned pregnancy in this vulnerable population.