bluuebunny/crossref_metadata_2025 huggingface dataset:
238 The association between quitting electronic cigarette use in pregnancy and the risk of preterm birth and low birth weight
Authors: Ammar Lin , Tindle Hilary A. , Nian Hui , Yu Chang , Snyder Brittney M , Miller Angela M. , Ryckman Kelli , Hartert Tina V. , Wu Pingsheng
Published: April 2022

OBJECTIVES/GOALS: Nearly half of mothers who report electronic (e)-cigarette use during pregnancy believe e-cigarettes are less harmful than traditional cigarettes. We aim to determine the association of quitting e-cigarette use in pregnancy with the risk of preterm birth and low birth weight. METHODS/STUDY POPULATION: We conducted a cross-sectional study of women participating in the Pregnancy Risk Assessment Monitoring System and with live singleton birth during 2016-2019. Women were classified based on their e-cigarette use: before pregnancy only (quitters), last three months of pregnancy only (initiators), at both times (sustained users), and neither time (non-users). We used a modified Poisson regression to determine the association between quitting e-cigarette use and preterm birth (<37 weeks) and low birth weight (<2,500 grams) adjusting for demographic, social-economic, and behavior-related risk factors. Analyses were weighted to account for the survey design and non-response. RESULTS/ANTICIPATED RESULTS: Based on 150,950 women who responded to the survey, there were estimated 2.9% quitters, 0.2% initiators, 1.0% sustained users, and 95.9% non-users in the U.S. Compared to sustained e-cigarette users, quitters had a similar risk in preterm birth (adjusted risk ratio [ARR]: 0.84, 95% confidence interval [CI]: 0.65, 1.08) and a significantly reduced risk in low birth weight (ARR: 0.77, 95%CI: 0.61, 0.97) adjusting for traditional cigarette use, age, race/ethnicity, education, marital status, family income, prior preterm birth, prior live births, BMI prior to pregnancy, pregnancy weight gain, kotelchuck index, multivitamin use, drinking prior to pregnancy, year of birth, and residential state. DISCUSSION/SIGNIFICANCE: As FDA authorizes the sales of certain e-cigarettes, women smokers may switch to e-cigarettes, believing they are reducing harm. Our study shows that quitting e-cigarette use is associated with a reduction of low birth weight. Clear messaging is needed to help women cease e-cigarette use in pregnancy.
245 Likelihood of live birth following fertility preserving treatment among reproductive-age women diagnosed with gynecologic malignancies or pre-malignancies
Authors: Yu Ruoxi , Christianson Mindy S. , Beavis Anna L. , Stone Rebecca L. , Hopkins Johns
Published: April 2022

OBJECTIVES/GOALS: To determine the impact of fertility preserving treatment (FPT) on likelihood of live birth in a cohort of reproductive-age women (18-45 y) after diagnosis of gynecologic malignancy or pre-malignancy METHODS/STUDY POPULATION: We performed a retrospective cohort study of women ages 18-45 seen by gynecologic oncologists for newly diagnosed cervical cancer (CC), endometrial intraepithelial neoplasia (EIN) or endometrial cancer (EC), and borderline ovarian tumor (BOT) or invasive ovarian cancer (OC) at an academic center from 2015-2019, excluding women who completed childbearing. Our primary outcome was live birth after diagnosis and our exposure was FPT defined as services received by reproductive endocrinology and infertility specialists. We performed Pearsons Chi-squared and log binomial regression to assess association between live birth and FPT with adjustment for patient demographic and disease factors. RESULTS/ANTICIPATED RESULTS: Out of 220 women (median age 36 y), most were White (54% vs. 25% Black) and 37% percent were diagnosed with BOT/OC (vs. 35% EIN/EC; 28% CC). After diagnosis of disease, 19% of women (n=41) had documented FPT and 8% of women (n= 17) had a live birth. By the end of follow-up, 6% of women who did not receive FPT had a live birth (n=11/178) compared to 15% of those who did (n=6/40, p=0.12). In univariate regression, women who received FPT were 2.4 times more likely to have a live birth after disease diagnosis that those who did not receive FPT (p-value = 0.06). However, after adjusting for age at diagnosis, relationship status, disease stage and disease type, the association between FPT and live birth was less robust (RR = 1.4, p-value = 0.6). DISCUSSION/SIGNIFICANCE: In this study, a minority of women had FPT or live births. Our data suggest that FPT benefit should be considered in context of age, relationship status, and disease characteristics for reproductive-age women diagnosed with gynecologic malignancies. Given the complexity, women should be offered referral for consultation with a fertility specialist.
261 Engineering Synthetic Scaffolds to Achieve Periodontal Ligament Cell-Mediated Tissue Regeneration
Authors: Fraser David , Benoit Danielle
Published: April 2022

OBJECTIVES/GOALS: Autologous periodontal ligament cells (PDLCs) are a promising tool for rebuilding tooth-supporting (periodontal) tissues but require scaffolds that enable delivery while maintaining PDLC bioactivity. The goal of this study was to design a synthetic hydrogel that fulfilled these criteria to support clinical translation of PDLC delivery. METHODS/STUDY POPULATION: Hydrogels were formed using poly(ethylene glycol) (PEG) polymers and synthetic peptides. PDLCs were isolated from human 3rd molars following informed consent and were cultured using established techniques. Integrin-binding peptides were utilized to promote specific PDLC behaviors, testing PDLCs from 3 human donors in a design of experiments (DOE) approach. Two promising hydrogel designs, identified in the DOE, were selected for validation testing using PDLCs from 3 additional donors. Finally, a small animal model for hydrogel-mediated PDLC delivery was used to determine if benchtop outcomes could predict in vivo tissue regeneration. RESULTS/ANTICIPATED RESULTS: Hydrogel scaffolds maintained high PDLC viability and controlled differentiation of each donor’s PDLCs based on differential presentation of integrin-binding peptides RGD and GFOGER. Two hydrogel designs were selected that optimized either PDLC alkaline phosphatase (ALP) activity or matrix mineralization, outcomes typically associated with cementum and bone formation. ALP activity-optimized hydrogels displayed enhanced PDLC pyrophosphate regulation while mineralization-optimized hydrogels promoted PDLC osteogenic differentiation. When used to deliver PDLCs to periodontal defects, both ALP activity-optimized and mineralization-optimized hydrogels stimulated new cementum formation with inserting PDL fibers, while mineralization-optimized hydrogels promoted enhanced bone formation. DISCUSSION/SIGNIFICANCE: Numerous challenges remain for translating PDLC regenerative potential to clinical practice. This study demonstrates that a synthetic hydrogel scaffold could overcome certain barriers, including controlling PDLC bioactivity with a simplified fabrication and delivery scheme, and may be a promising scaffold for periodontal tissue regeneration.
272 A Longitudinal, Multi-Method, Pilot Triangulation of Family Intensive Care Unit Syndrome
Authors: Pignatiello Grant , Hickman Ronald L.
Published: April 2022

OBJECTIVES/GOALS: The objectives of this study are to: 1) Examine the feasibility of using concurrent multi-methodology to quantify the affective, decisional, physical symptom domains of Family Intensive Care Unit Syndrome. 2) Describe the associations between the Family Intensive Care Unit Syndrome symptom domains (affective, decisional, physical). METHODS/STUDY POPULATION: Using a repeated-measures, correlational design, we recruited surrogate decision makers of incapacitated, mechanically ventilated patients within four adult intensive care units at a tertiary medical center in northeast Ohio. We collected baseline data (T1) after obtaining informed consent and follow-up data three (T2) and seven (T3) days post-baseline. We used self-report instruments, behavioral tasks, and accelerometry to measure affective (anxiety & depression), decisional (working memory ability & decision fatigue), and physical (sleep quality & sleep disturbance), symptom domains. For objective 1, we computed completion percentages of each
time-point and overall compliance with wearing the accelerometer device. For objective 2, we inspected Spearman correlations. RESULTS/ANTICIPATED RESULTS: We recruited and collected baseline data (T1) for 33 participants. Nineteen participants completed the T2 interview and twenty participants completed T3. Eight participants wore the accelerometer device for less than 72 hours and 15 wore the accelerometer for the full study period. At baseline, the physical symptoms (sleep quality & disturbance) were strongly correlated with the affective (anxiety & depression) symptoms, all of which were moderately correlated with one decisional symptom (decision fatigue). One cognitive symptom (working memory dysfunction), was weakly associated with the affective and physical symptom domains, and moderately correlated with the other cognitive symptom (decision fatigue) These associative trends were maintained within and between each time point. DISCUSSION/SIGNIFICANCE: This study identifies potential opportunities for examining the various symptom domains of Family Intensive Care Unit Syndrome. The associations between the domains are consistent with the extant literature, and highlights the need for supportive interventions that mitigate affective and physical symptoms that can compromise decision-making.
276 Bilirubin Oxidative Products as Predictive Biomarkers of Cerebral Vasospasm: A Pilot Study
Authors: Byer Stefano H , Goswami Shweta , Gordon Wes , Abraham Michael G
Published: April 2022

OBJECTIVES/GOALS: Our aim is to understand the role bilirubin oxidation products play in the development of cerebral vasospasm in patients with subarachnoid hemorrhage. We aim to evaluate the time course of bilirubin, HO-1, and SOD1 in relation to the subsequent development of vasospasm in to establish predictors of vasospasm development. METHODS/STUDY POPULATION: Prospective cohort observational study involving collection of CSF samples of pts admitted to KU NeuroICU with SAH and placement of EVD. CSF will be extracted from the EVD of patients on the day of placement of the EVD, and then each subsequent day for a total of 10 days. Bilirubin concentration will be determined by means of spectrophotometry. HO-1 will be measured using a commercially available ELISA kit. Cu/Zn-Superoxide Dismutase will be measured using a commercially available ELISA kit. A review of patients chart will then be performed following discharge from hospital to determine if a diagnosis of vasospasm was made, details of the vasospasm (i.e. symptoms, severity), as well as to obtain demographic data and events occurring during patients admission that could confound statistical analysis. RESULTS/ANTICIPATED RESULTS: First: we will investigate the feasibility of collecting serial CSF samples and processing them for target analyte quantification. We predict that the protocol will yield quality data that will result in insight on the pathophysiology of cerebral vasospasm. Second: we will characterize the changes in target CSF bilirubin breakdown analytes over 10 days. From this we hypothesize that as bilirubin oxidation increases, the propensity for cerebral vasospasm will also increase. DISCUSSION/SIGNIFICANCE: If there is a clear correlation between formation of bilirubin and increase in HO-1, and SOD1, with the clinical signs of vasospasm, this could be used as a biomarker for not only identifying patients at risk for developing these complications but also a means to follow the effectiveness of potential therapies.
279 “It just seems like people are talking about menopause, but nobody has a solution”: A qualitative exploration of menopause experiences and preferences for weight management among Black women
Authors: Marlatt Kara , Kracht Chelsea L. , Romain Jessica St. , Hardee Julie C. , Santoro Nanette , Redman Leanne M. , Marlatt Kara L.
Published: April 2022

OBJECTIVES/GOALS: A qualitative study was performed to characterize experiences of Black and White women going through menopause, as well as identify barriers and facilitators for participating in a lifestyle program targeting weight management during menopause. This abstract includes data from Black women. Results from White women will be available by ACTS 2022. METHODS/STUDY POPULATION: Perimenopausal and postmenopausal Black women with a self-reported desire to lose or maintain weight during menopause participated in a total of six focus groups. Women were asked about their past experiences with diet, exercise, and weight management; their menopause experiences; as well as specific components and considerations for developing a lifestyle program for weight management. Thematic analysis was conducted on coded transcripts and four main themes emerged, each containing three to seven subthemes. RESULTS/ANTICIPATED RESULTS: Twenty-seven Black women (age 54Â±4 years, BMI 35.1Â±9.0 kg/m2) were enrolled. Overall, women felt unprepared for the changes they experienced during menopause and had difficulty maintaining or losing weight. While women were receptive to trying different diets and exercises, they wanted a diet that was flexible with their lifestyle and exercises that considered their existing health status. Women were also interested in learning about menopause alongside other women, stating that medical professionals did not provide them with adequate information or help. Social support, accountability, and seeing results were perceived critical to achieve long-lasting behavioral change. DISCUSSION/SIGNIFICANCE: Women were interested in receiving menopause information and improving their overall health as part of a lifestyle program during menopause. Associating with other women affected by menopause will allow for the creation of more sustainable lifestyle programs during menopause.
286 Disparities in the Management of Low-Risk Febrile Infants: An Interim Feasibility Report
Authors: Gutman Colleen K , Aronson Paul , Lion K. Casey , Fisher Carla , Patterson Mary , Fernandez Rosemarie
Published: April 2022

OBJECTIVES/GOALS: Well-appearing febrile infants are a model for exploring communication, bias, and health disparities in the pediatric emergency department (ED). Using mixed methods, we will perform an in-depth analysis of disparities and shared decision making, a potentially modifiable driver of inequities. METHODS/STUDY POPULATION: We will conduct a multicenter cross-sectional chart review study of well-appearing febrile infants 29-60 days old treated in the ED and apply multivariable logistic regression to assess the association between 1) race/ethnicity and 2) limited English proficiency with the primary outcome, discharge to home without lumbar puncture and without antibiotics (standard of care). We will concurrently perform an interpretive study using purposive sampling to conduct interviews with: 1) minority parents of febrile infants and 2) ED physicians. By capturing dyadic data, we will triangulate perspectives to elucidate disparities and bias that can emerge in the shared decision making process. RESULTS/ANTICIPATED RESULTS: Forty member institutions of the Pediatric Emergency Medicine Collaborative Research Committee are participating, providing a projected cohort of 3000 infants. In the 6 months since site recruitment, 235 eligible infants have been entered into the dataset (43% minority race/ethnicity, 6% language other than English), 61% of whom received the primary outcome. Chart review has the benefits of 1) ensuring exclusion of ill infants, 2) providing data on interpreter use that is unavailable in administrative datasets, and 3) allowing an analysis of shared decision making. These findings will inform an interpretive study of parent and provider experiences of bias in shared decision making. DISCUSSION/SIGNIFICANCE: We demonstrate the feasibility of a large-scale manual chart review to analyze disparities within a shared decision making context. Partnered with qualitative scholarship, this research will support the development of communication interventions to mitigate implicit bias in the clinical encounter.
292 Fibromyalgianess and Glucocorticoid Persistence Among Patients with Rheumatoid Arthritis
Authors: Wallace Beth , Moore Meriah N. , Heisler Andrew C. , Muhammad Lutfiyya N. , Song Jing , Clauw Daniel J. , Bingham Clifton O. , Bolster Marcy B. , Marder Wendy , Neogi Tuhina , Wohlfahrt Alyssa , Dunlop Dorothy D. , Lee Yvonne C.
Published: April 2022

OBJECTIVES/GOALS: Over 30% of patients with rheumatoid arthritis (RA) exhibit fibromyalgianess, a symptom cluster associated with increased pain sensitivity. Up to half of RA patients use oral glucocorticoids (GCs) long-term despite their known, dose-dependent toxicity. We examined the association between fibromyalgianess and oral GC persistence in RA patients. METHODS/STUDY POPULATION: We used data from the Central Pain in Rheumatoid Arthritis (CPIRA) cohort to follow participants with active RA on oral prednisone who initiated a new disease-modifying anti-rheumatic drug. We measured fibromyalgianess using the Fibromyalgia Survey Questionnaire (FSQ), previously shown to correlate with key fibromyalgia features often superimposed upon RA. We stratified fibromyalgianess severity as follows: FSQ<8 low, 8-10 moderate, >10 high/very high. We defined GC persistence as GC use at 3 month followup visit. We assessed the association between baseline fibromyalgianess (exposure) and GC persistence at followup (outcome) using multiple logistic regression, adjusted for demographics, RA duration, serostatus, and inflammatory activity measured by swollen joint count and C reactive protein. RESULTS/ANTICIPATED RESULTS: Of 97 participants on prednisone at baseline, 65% were taking prednisone at follow-up. Fifty-seven percent of participants with low baseline fibromyalgianess had persistent GC use, compared to 84% with high or very high fibromyalgianess. After adjustment as outlined above, participants with high/very high baseline fibromyalgianess remained more likely to be on prednisone at follow-up, relative to those with low fibromyalgianess (OR 4.99 [95% CI 1.20 – 20.73]). DISCUSSION/SIGNIFICANCE: In this cohort of patients with active RA, high fibromyalgianess is associated with persistent GC use, independent of inflammatory activity. This finding suggests non-inflammatory pain related to fibromyalgianess may be misclassified as inflammatory pain related to RA disease activity.
302 Abaloparatide as a novel therapy for posttraumatic osteoarthritis
Authors: Landgrave Samantha H. , Ishii Toru , Maynard Robert , Wu Andrew , Godfrey Dana , Manes Terrin , Butler Veronica , Villani David , Hendesi Honey , Frank Rachel , Iyer Srividhya , Payne Karin , Adams Douglas J. , Favazzo Lacey , Lanske Beate , Zuscik Michael J.
Published: April 2022

OBJECTIVES/GOALS: Osteoarthritis (OA) is a cartilage destroying disease. We are investigating abaloparatide (ABL) activation of parathyroid hormone receptor type 1 (PTH1R), which is expressed by articular chondrocytes in OA. We propose ABL treatment is chondroprotective in murine PTOA via stimulation of matrix production and inhibition of chondrocyte maturation. METHODS/STUDY POPULATION: 16-week-old C57BL/6 male mice received destabilization of the medial meniscus (DMM) surgery to induce knee PTOA. Beginning 2 weeks post-DMM, 40 Î¼g/kg of ABL (or saline) was administered daily via subcutaneous injection and tissues were harvested after 6 weeks of daily injections and 8 weeks after DMM surgery. Harvested joint tissues were used for histological and molecular assessment of OA using three 5 Î¼m thick sagittal sections from each joint, 50 Î¼m apart, cut from the medial compartment of injured knees. Safranin O/Fast Green tissue staining and immunohistochemistry-based detection of type 10 collagen (Col10) and lubricin (Prg4) was performed using standard methods. Histomorphometric quantification of tibial cartilage area and larger hypertrophic-like cells was performed using the Osteomeasure system. RESULTS/ANTICIPATED RESULTS: Safranin O/Fast Green stained sections showed a decreased cartilage loss in DMM joints from ABL-treated versus saline-treated mice. Histomorphometric analysis of total tibial cartilage area revealed preservation of cartilage tissue on the tibial surface. Immunohistochemical analyses showed that upregulation of Col10 in DMM joints was mitigated in the cartilage of ABL-treated mice, and chondrocyte expression of Prg4 was increased in uncalcified cartilage areas in ABL-treated group. The Prg4 finding suggests a matrix anabolic effect that may counter OA cartilage loss. Quantification of chondrocytes in uncalcified and calcified tibial cartilage areas revealed a reduction in the number of larger hypertrophic-like cells in ABL treated mice, suggesting deceleration of hypertrophic differentiation. DISCUSSION/SIGNIFICANCE: Cartilage preservation/regeneration therapies would fill a critical unmet need. We demonstrate that an osteoporosis drug targeting PTH1R decelerates PTOA in mice. ABL treatment was associated with preservation of cartilage, decreased Col10, increased Prg4, and decreased number of large hypertrophic-like chondrocytes in the tibial cartilage.
310 Transcriptomics for gallbladder cancer prognosis
Authors: Jackson Linsey , Allotey Loretta K. , Valles Kenneth , Oliver Gavin R. , Nair Asha , Obrien Daniel R. , Graham Rondell P. , Borad Mitesh J , Athreya Arjun , Roberts Lewis R.
Published: April 2022

OBJECTIVES/GOALS: Recent research has attempted to identify diagnostic, prognostic, and predictive biomarkers, however, currently, no biomarkers can accurately diagnose GBC and predict patients prognosis. Using machine learning, we can utilize high-throughput RNA sequencing with clinicopathologic data to develop a predictive tool for GBC prognosis. METHODS/STUDY POPULATION: Current predictive models for GBC outcomes often utilize clinical data only. We aim to build a superior algorithm to predict overall survival in GBC patients with advanced disease, using machine learning approaches to prioritize biomarkers for GBC prognosis. We have identified over 80 fresh frozen GBC tissue samples from Rochester, Minnesota, Daegu, Korea, Vilnius, Lithuania, and Calgary, Canada. We will perform next-generation RNA sequencing on these tissue samples. The patients clinical, pathologic and survival data will be abstracted from the medical record. Random forests, support vector machines, and gradient boosting machines will be applied to train the data. Standard 5-fold cross validation will be used to assess performance of each ML algorithm. RESULTS/ANTICIPATED RESULTS: Our preliminary analysis of next generation RNA sequencing from 18 GBC tissue samples identified recurrent mutations in genes enriched in pathways in cytoskeletal signaling, cell organization, cell movement, extracellular matrix interaction, growth, and proliferation. The top three most significantly altered pathways, actin cytoskeleton signaling, hepatic fibrosis/hepatic stellate cell activation, and epithelial adherens junction signaling, emphasized a molecular metastatic and invasive fingerprint in our patient cohort. This molecular fingerprint is consistent with the previous knowledge of the highly metastatic nature of gallbladder tumors and is also manifested physiologically in the patient cohort. DISCUSSION/SIGNIFICANCE: Integrative analysis of molecular and clinical characterization of GBC has not been fully established, and minimal improvement has been made to the survival of these patients. If overall survival can be better predicted, we can gain a greater understanding of key biomarkers driving the tumor phenotype.
311 Rib Fractures in Geriatric Trauma: A Review of 1,037 Cases at a Single Level I Trauma Center
Authors: Sheppard Forest , Mack Joseph D. , Falank Carolyne , Morse Bryan C , Cullinane Daniel C , Rappold Joseph F , Ontengco Julianne , Ciraulo David
Published: April 2022

OBJECTIVES/GOALS: Rib fractures are common traumatic thoracic injuries and are associated with high rates of morbidity and mortality. In those age â‰¥ 65, the rate of these complications double. This study sought to identify the extent to which injury-related predictors influence clinical outcomes in geriatric patients with rib fractures. METHODS/STUDY POPULATION: A retrospective 5-year review was performed of a single Level 1 Trauma center registry. Geriatric patients (â‰¥65 years of age) diagnosed with rib fractures from January 1, 2014 to December 31, 2019 were included. The primary outcome of interest was in-hospital mortality. Secondary outcomes included hospital and intensive care unit length of stay (HLOS and ICU LOS, respectively) and discharge disposition, as a surrogate for loss of independence. Further, subgroup analysis based on number of rib fractures (i.e. <4 and â‰¥4 rib fractures) was performed. RESULTS/ANTICIPATED RESULTS: 2,134 adult trauma patients were admitted with at least one rib fracture. Of these, 1,037 (49%) were â‰¥ 65 years old. This cohort had a mean age of 78.6 years old, injury severity score (ISS) of 11.4, HLOS of 7.4 days and 29% required ICU care with mean ICU LOS of 1.9 days. Only 36% were discharged home compared to 64% who were discharged to a care facility and thus had a loss of independence. Overall mortality was 6.3%. Compared to survivors, non-survivors had a higher ISS (19.3 vs. 10.8, p = < 0.0001) and longer ICU LOS (7.1 vs. 6.5 days, p = 0.04). Analysis based on number of rib fractures showed that those with â‰¥4 rib fractures had significantly higher mortality (8% vs. 4%, p = 0.008), longer HLOS (8.7 vs. 6.1 days, p < 0.0001), longer ICU LOS (2.6 vs. 1.3 days, p < 0.0001), and significantly lower discharge to home (32% vs. 39%, p = 0.02). DISCUSSION/SIGNIFICANCE: To our knowledge, this is the largest single-center study of geriatric patients with rib fractures. In this study, the observed mortality in patients â‰¥65 years of age was 6.3% which represents a lower mortality rate than historically reported. Despite this, only 36% were able to be discharged directly to home.
313 Biobehavioral predictors of dose-limiting toxicities of cancer therapy: Identification of areas for preventative intervention
Authors: Thornton Clifton P. , Ruble Kathy
Published: April 2022

OBJECTIVES/GOALS: This presentation outlines a novel approach to evaluating multiple risk factors for the development of dose-limiting toxicities in adolescents and young adults with cancer. This is the first to evaluate biobehavioral predictors originally identified in animal models in clinical human studies. METHODS/STUDY POPULATION: Adolescents and young adults (AYAs) have seen the slowest improvements in cancer survival and have some of the highest rates of dose-limiting mucositis (mouth sores). AYAs receiving chemotherapy with a significant chance of dose-limiting mucositis were recruited for a prospective study. Baseline perceived psychologic stress levels and inflammatory markers were collected at the time of chemotherapy administration and participants completed a daily assessment of mucositis for 14 days following chemotherapy. Logistic regression will be used to evaluate stress and inflammation as predictors of mucositis and Sobels testing will evaluate the role of inflammation as mediators in this relationship. RESULTS/ANTICIPATED RESULTS: We anticipate that, as seen in animal models, stress and inflammation will predict mucositis development. First, we hypothesize that stress levels and inflammatory markers will have a direct correlation and that the level of inflammation at the time of chemotherapy administration will predict mucositis incidence and severity. Through mediation testing, we hypothesize that inflammatory markers will explain a significant amount of the variance in mucositis also explained by stress, identifying inflammation as a mediator in this relationship. In all, we expect that stress and inflammation both predict mucositis development and will be identified as important modifiable factors that can be altered to reduce the risk of toxicity development during cancer therapy. DISCUSSION/SIGNIFICANCE: This work intends to evaluate predictors of chemotherapy-related toxicity development in AYAs with cancer and identify areas of intervention that will reduce toxicity profiles and close the gap in cancer survival for AYAs. Findings are applicable to biomedical, nursing, and psychosocial professionals and will inform future, large clinical studies
316 Frontal-cerebellar EEG source localization and functional connectivity as predictors of Alzheimer’s disease-related cognitive decline
Authors: Paitel Elizabeth R. , Nielson Kristy A.
Published: April 2022

OBJECTIVES/GOALS: Novel EEG source localization and functional connectivity will assess frontal and cerebellar activity as predictors of subsequent memory and executive functioning (EF) decline in healthy, asymptomatic older adults who carry the Apolipoprotein-E Îµ4 allele (Îµ4+), which conveys up to 12x increased risk for Alzheimers disease (AD). METHODS/STUDY POPULATION: Healthy, cognitively intact Îµ4+ older adults (n = 23; ages 65-89) completed neuropsychological testing (focus on memory and EF) and EEG at Time 1, returning an average of one year later for neuropsychological retesting. EEG data during successful stop-signal inhibitory control trials will be used for advanced source localization and functional connectivity, with a focus on frontal and cerebellar regions of interest (ROIs). Source analyses will focus on the N200 time window (~200-350ms) to assess conflict processing and P300 (~300-550ms) for performance evaluation. Connectivity analyses are frequency-based, and will focus on theta band connectivity to assess conflict processing and delta to assess performance evaluation. RESULTS/ANTICIPATED RESULTS: Using hierarchical linear regression models, the magnitude of source activation within ROIs and connectivity metrics between ROIs will be used to predict residualized change in memory and executive function metrics between Time 1 and Time 2. We anticipate that 1) greater, compensatory activation in frontal ROIs during the N200 window, and 2) less cerebellar activation during P300, will predict memory and executive decline over the retest interval. Decline will also be predicted by 3) greater inter-hemispheric frontal connectivity in the theta band (conflict processing) and 4) less frontal-cerebellar delta connectivity (performance evaluation). DISCUSSION/SIGNIFICANCE: At most, ~50% of Îµ4 carriers will develop AD. Thus, identifying which carriers will decline is crucial to enabling successful, early intervention. Cerebellar dysfunction and impaired connectivity may be among the earliest indicators of incipient AD. Cutting-edge cerebellar EEG may enable an accessible option for early discernment of AD risk.
331 A Machine Learning-based Pharmacogenomic Association Study of Major Adverse Cardiovascular Events (MACEs) in Caribbean Hispanic Patients on Clopidogrel
Authors: Arroyo Luis A. Rosario , Rosario-Arroyo Luis , Roman-Rodriguez Krystal S , Gonzalez-Lebron Carola F , Santiago Ednalise , Monera-Paredes Mariangeli , Feliu-Maldonado Roberto A. , Roche-Lima Abiel , Duconge Jorge
Published: April 2022

OBJECTIVES/GOALS: To summarize baseline characteristics and risk factors for major adverse cardiovascular events (MACEs) and develop a prediction model by testing the association between genetic variants and MACEs in Caribbean Hispanic patients on clopidogrel using machine-learning (ML) techniques. METHODS/STUDY POPULATION: This is a secondary analysis of available clinical and genomic data from an existing database of 600 Caribbean Hispanic cardiovascular (CV) patients on clopidogrel. MACEs is defined as the composite of all-cause death, myocardial infarction, stroke and stent thrombosis over 6 months. Dataset is divided into training (60%) and testing (40%) sets, respectively. Two different supervised ML approaches (i.e. multiclass classification and regression algorithms) are applied to the study dataset using Python v3.5 and WEKA, and tested by receiver operating curve (ROC) analysis. A case-control association analysis between MACEs at 6 months and genotypes is performed by using chi-squared test. RESULTS/ANTICIPATED RESULTS: Average age of participants was 68 years-old, 55% males, with high prevalence of risk factors (i.e., overweight: 28.4 kg/m2; hypertension: 83.8%; hypercholesterolemia: 71.9% and diabetes: 54.8%). MACEs rate is 13.8%, with 33.5% resistant to clopidogrel. Logistic regression, KNN and gradient boosting showed the best performance, as suggested by ROC analysis and AUC CV scores of 0.6-0.7. A significant association between MACE occurrence and â‰¥3 risk alleles was found (OR=8.17; p=0.041). We anticipate that these genetic variants (CYP2C19*2, rs12777823, PON1-rs662, ABCB1-rs2032582, PEAR1-rs12041331) will uniquely contribute to clopidogrel resistance and MACEs in Caribbean Hispanics. DISCUSSION/SIGNIFICANCE: Our findings help address in part the long-standing problem of excluding minorities from research, which entails a gap of knowledge about clopidogrel pharmacogenomics in Puerto Ricans. This study provides a possible ML model that integrates clinical and pharmacogenomics for MACE risk estimation.
332 Association of sphingolipid de novo synthesis with airway response to magnesium
Authors: Heras Andrea , Worgall Stefan , Perez-Zoghbi Jose
Published: April 2022

OBJECTIVES/GOALS: MgSO4 is a frequently used to treat asthma exacerbations. Its role in the management of pediatric asthma remains controversial. Our objective is to demonstrate that the response of the small (peripheral) airways depends on airway de novo sphingolipid synthesis, clinically and experimentally. The small airways are the main site of asthma pathology. METHODS/STUDY POPULATION: We investigated airway reactivity in response to MgSO4 in murine small airways and children 1. Precision-cut lung slices (PCLS): Using heterozygous knockouts mice of one of the Sptlc2 subunit of the serine palmitoyl-CoA transferase (SPT) which results in reduced tissue sphingolipid levels compared to wild-type control littermates (Sptlc2+/+). We compared small airway dilation to MgSO4 in Sptlc2+/- and Sptlc2+/+ mice. This was assessed by directly visualization of small airway contractility in PCLS from Sptlc2+/- mice using video phase-contrast microscopy 2. Clinical response to MgSO4 in children by using a respiratory score before and after the treatment. The response to MgSO4 was the correlated to asthma-associated 17q21 specific single nucleotide polymorphisms (SNPs) from DNA isolated from buccal swabs RESULTS/ANTICIPATED RESULTS: Sphingolipid-mediated activity alters magnesium response in small airways. We assessed whether downregulation of SPT could lead to alterations in MgSO4-induced small airway dilation and in MgSO4 responsiveness in mouse tracheal rings and found that the magnesium-induced relaxation of airways pre-contracted with methacholine was impaired in Sptlc+/- mice compared to the control group (p=<0.05) Clinical response to MgSO4 in children with status asthmaticus. A respiratory score was assessed in a cohort of 5 to 21-year-old who received IV MgSO4. An increase of 3 or more points was considered positive. Only 32% of the patients showed a favorable improvement to the medication, showing variability of response between individuals. The correlation of sphingolipid-deficient SNPs and MgSO4 responsiveness is ongoing DISCUSSION/SIGNIFICANCE: This suggest that decreased SPT activity in the respiratory track alters the response of the airways to magnesium. Connecting decreased de novo SL synthesis to alterations in cellular magnesium homeostasis provides a mechanistic link to differential airway reactivity to MgSO4 in pediatric asthma management.
337 Innovation Opportunities within Lymphedema
Authors: Plona Zachary , Ngao Lina , Monteagudo Benjamin , Hutchinson Hunter , Schultz Jennifer , Yazdi, PhD, MBA Youseph , Acharya Soumyadipta
Published: April 2022

OBJECTIVES/GOALS: Lymphedema is a chronic, debilitating disease characterized by progressive swelling due to lymphatic dysfunction. Lymphedema affects 5+ million people in the US, commonly as a consequence of cancer treatment. We identified the most relevant needs within lymphedema based on clinical impact, commercial viability, and technological feasibility. METHODS/STUDY POPULATION: A narrative review of lymphedema management was performed through a combination of literature review via English language PubMed, landscape determination for current solutions and primary ethnography. Lymphedema-focused physicians, patients, physical therapists and researchers were interviewed on Needs were identified and clustered based on common themes. These clusters were further refined through an iterative process of systematic scoring and expert evaluation. Clusters were evaluated on their potential for clinical and commercial impact as well as technical feasibility. RESULTS/ANTICIPATED RESULTS: General clusters identified included improved diagnostic modalities, curative treatment, disease knowledge among non-specialized clinicians and increased insurance coverage. 3 primary needs were determined to represent the best opportunities for technological innovation. There is a need for a quantitative method of evaluating lymphedema. This would allow for both improved tracking of progression for patients undergoing conservative management, and for better evaluation of surgical outcomes. Oncologists and surgeons need a method of prophylaxis in order to decrease the rate of lymphedema development following cancer treatment. Physicians need a method for early diagnosis of subclinical lymphedema to enable early intervention through proactive screening rather than reactive management. DISCUSSION/SIGNIFICANCE: Increasingly medical device design has moved towards a “bedside to benchtop” model where technology development is targeted based on critical needs within the clinical environment. Identification of these critical needs will serve as to guide future technological innovation in creating clinically impactful advancements.
352 Computational methods for predicting drug combinations for targeting KRAS mutations relevant to non-small cell lung cancer
Authors: Bruggemann Liana , Falls Zackary , Mangione William , Mahajan Supriya , Samudrala Ram
Published: April 2022

OBJECTIVES/GOALS: Our goal is to develop a cost-effective approach for precision medicine treatment by providing computational predictions for new uses of currently available FDA approved, and experimental drugs for NSCLC. METHODS/STUDY POPULATION: Cell Lines: A549 (ATCC- CCL-185) Human epithelial Lung Carcinoma cells, H1792 (ATCC-CRL-5895) Human Lung Carcinoma cells. In Vitro Cytotoxicity Assay: A VybrantÂ® MTT Cell Proliferation Assay was used. Colony Formation Assay: NCI-H1792, A549 cells were seeded at a density of 500 cells/ dish, then treated with ARS-1620, Osimertinib. The Computational Analysis of Novel Drug Opportunities (CANDO): Â Herein, we employed the bioanalytic docking (BANDOCK) protocol within CANDO to calculate the compound-protein interaction scores for a library of 13,218 compounds from DrugBank against a library of 5,317 protein structures from the Protein Data Bank, resulting in a proteomic interaction signature for each compound, and identified Osimertinib as the most likely EGFR/ErbB inhibitor to synergize with ARS-1620. RESULTS/ANTICIPATED RESULTS: ARS-1620 and Osimertinib in combination displays potent anti-tumor activity as evident by a decrease in cell viability with cytotoxicity assays, as well as reduced number of colonies in the colony formation assay for both A549 and H1792 cells. By using CANDO, and cross-referencing the obtained rankings with known experimental information, we have obtained drug predictions within the context of precision medicine. Our preliminary data indicates that EGFR inhibitor Osimertinib may be most structurally similar to KRAS G12C inhibitors overall, compared to other ErbB/ EGFR inhibitors. Validations with human cancer cell lines A549 and H1792 have confirmed that Osimertinib in combination with KRAS G12C inhibitor ARS-1620 may exhibit a synergistic effect in decreasing cellular proliferation and colony formation. DISCUSSION/SIGNIFICANCE: This suggests that this innovative drug combination therapy may help improve treatment outcomes for KRAS G12C(H1792) and KRASG12S(A549) mutant cancers. Cell migration and cell invasion studies in response to treatment with Osimertinib and ARS-1620 are currently ongoing.
377 Mapping Clinical Trial Outcome Measures for Atopic Dermatitis
Authors: Naumov Nicholas , Pacifici Eunjoo
Published: April 2022

OBJECTIVES/GOALS: Atopic Dermatitis (AD) affects 10% of people globally and is studied widely in clinical trials. However, clinical outcomes assessment (COA) for AD are not standardized, hindering easy comparisons across different studies. This study examines AD studies to identify the most used COAs. METHODS/STUDY POPULATION: Clinicaltrials.gov was searched to identify AD trials conducted between 2011 and 2021. Ongoing and completed trials were classified according to the therapeutic modality: Biologic, Immunosuppressive, or Other (botanicals and antibiotics). Further, AD trials were examined to determine which of the COAs listed in the FDA compendium issued in 2021 were included: the Investigators Global Assessment (IGA), the Eczema Area and Severity Index (EASI-75), and the Pruritus Numeric Rating Scale (NRS). The results were analyzed to determine which COA is most frequently used and if there were differences across therapeutic modalities or trial phases. RESULTS/ANTICIPATED RESULTS: Across a total of 50 AD trials registered in clinicaltrials.gov, EASI-75 was the most used COA; the item was included in 12 of 16 biologics, 5 of 14 immunosuppressives, and 7 of 20 other products. Moreover, AD trials of biologics included more of the FDA-suggested COAs than those studying other modalities. There were also differences across the clinical trial phases in that most phase III AD trials (83.33%, n=8) included two of the three COAs listed (IGA and EASI-75) compared to less than half of phase I/II trials (vs. 43.75%, n=32). DISCUSSION/SIGNIFICANCE: Findings from this study indicate a lack of COA harmonization across AD trials, impeding comparative analysis of the trial results. Establishing a common standard for COA would foster communication and transparency among key stakeholders including researchers, healthcare providers, and patients.
390 Adaptation and Evaluation of Guideline-Based Family-Based Behavioral Treatment for Overweight and Obesity in Childhood Survivors of Acute Lymphoblastic Leukemia (ALL)
Authors: Jakubiak Jessica , Wilfley Denise , King Allison , Hayashi Robert J.
Published: April 2022

OBJECTIVES/GOALS: Childhood survivors of ALL are at considerable risk for late effects which are exacerbated by excess weight. The proposed study involves the adaption and evaluation of the first empirically supported intervention for childhood survivors of ALL that is consistent with all national recommendations for the treatment of childhood obesity. METHODS/STUDY POPULATION: The proposed intervention will be adapted from family-based behavioral weight loss treatment (FBT) a multicomponent intervention which targets diet, activity, behavioral skills, parenting, and social facilitation among children and their parents. The Framework for Reporting Adaptations and Modifications-Enhanced structure (FRAME), a dissemination and implementation framework, will guide the adaptation, allowing for the incorporation of feedback previously gathered from key stakeholders. A single-arm, non-randomized trial of the adapted intervention will then be conducted to evaluate its acceptability, feasibility, and preliminary indications of efficacy including measures of relative weight change and associated health-related behaviors among 40 childhood ALL survivors and their families. RESULTS/ANTICIPATED RESULTS: Self-reported feedback from families at the end of treatment (EoT) is anticipated to demonstrate that this intervention will be regarded as both acceptable and feasible. Other measures of feasibility will include attendance and retention rates, which are expected to reflect to those of previous FBT trials (92% and 85%, respectively). Preliminary indications of the efficacy of the adapted intervention will be investigated through the comparison of a series of measurements taken at both baseline and EoT. Changes in relative weight will be assessed and are expected to meet a previously established range of clinically meaningful reduction in child percent overweight of 9 units or more. Improvements in dietary intake, physical activity, and health related quality of life are also anticipated. DISCUSSION/SIGNIFICANCE: Knowledge gained from the implementation of the first evidence-based intervention adapted for childhood survivors of ALL will be critical to the justification of a larger-scale, randomized controlled trial and holds promise to effectively modify the risk for chronic disease among a vulnerable population.
401 Eliminating System xc- Signaling Between Astrocytes and Neurons Selectively Impairs Complex Cognition
Authors: Simand Gregory , Simand Gregory J. , Hess Evan , Kong Linghai , Raddatz Nicholas J. , Hurley Matthew M , Maunze Brian , Choi SuJean , Geurts Aron M. , Baker David A.
Published: April 2022

OBJECTIVES/GOALS: We aim to determine whether non-neuronal, non-synaptic glutamate signaling mechanisms can be targeted to produce highly specific, narrow changes in brain function that would benefit CNS disorders. To do this, we investigated cognitive changes produced through manipulating the activity of the astrocytic glutamate release mechanism system xc-. METHODS/STUDY POPULATION: System xc- (Sxc) activity was eliminated by mutating the gene Slc7a11 through pronuclear injection of zinc-finger nucleases into Sprague Dawley rat embryos to create a line of rats lacking Sxc (MSxc rats). To confirm a lack of Sxc activity, we verified that tissue from MSxc rats had a complete lack of xCT, which is the regulatory subunit of Sxc that is encoded by Slc7a11. We also verified that astrocyte cultures generated from MSxc tissue lacked cystine-evoked glutamate release. Next, we measured development (body weight), CNS regulation of metabolism, and other indicators of generalized, non-specific brain function as well as behaviors that are reliant on executive function, such as cognitive flexibility, impulse control, decision-making, and response inhibition. RESULTS/ANTICIPATED RESULTS: Eliminating Sxc was not lethal and did not impair development or produce widespread changes in brain function as is commonly observed when deleting other glutamate mechanisms. MSxc rats did not differ from wildtype in growth rate, central regulation of metabolism as reflected by absolute or diurnal changes in core body temperature, locomotor activity in a familiar or novel environment, or simple forms of cognition such as novel object recognition, or operant responding (food and cocaine-reinforced). In contrast, behaviors that rely on executive function were impaired. MSxc rats displayed deficits in cocaine reinstatement and attentional set-shifting. We anticipate MSxc rats to also show impairments in decision-making in the rat gambling task and response inhibition in the stop-signal reaction time task. DISCUSSION/SIGNIFICANCE: Eliminating Sxc activity in rats produced deficits in behaviors reliant on executive function without impacting development or simple brain function. These results highlight the potential of targeting Sxc to enhance cognition without generating therapeutically limiting adverse effects resulting from non-specific changes in brain function.