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  Understanding Barriers in Breast Cancer Screening in Hispanics

  Bryan Benitez, Bryan Lugo Maldonado, Angel M. Lehn, Shirley F. Delair, and Quan P. Ly

  Breast cancer is the most prevalent cancer in the US, with 310,000 new cases annually. However, it is also one of the most preventable cancers through regular mammogram screenings. The primary purpose of this project was to identify the main barriers in screening found among the Hispanic population that were referred by OneWorld Community Health Centers. 212 patients were called from OneWorld to evaluate any barriers they faced in breast cancer screening and how their mammogram experience went. We found that Hispanics were primarily affected by a lack of follow-up in appointments (53.5%), Financial Issues(19.8%), and Lack of Time(19.8%). This gives us an important insight into how to improve screening rates within this at-risk population and the effect of educational level on adherence to physician orders.

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  Tyrphostin (AG-879) Decreases AKT Activation Through NGFR Inhibition in Human Glioblastoma Cell Lines

  Olivia M. Buchweitz, Poonam Yadav, Indumati Ramireddy, Raghupathy Vengoji, Surinder K. Batra, and Nicole Shonka

  Glioblastoma is an aggressive malignant brain cancer with a dismal 5-year survival rate of 6.9%. Despite current treatments – surgical resection, radiation, and chemotherapy – GBM remains incurable, highlighting the urgent need for more effective targeted therapies. Nerve Growth Factor Receptor (NGFR) plays a key role in the maintenance and growth of gliomas and is upregulated during GBM progression. Tyrphostin (AG-879), an inhibitor of TrkA in the NGFR pathway, was investigated in this study. We hypothesized that NGFR contributes to GBM progression by promoting proliferation and its pharmacological targeting will inhibit GBM growth. The objective was to determine the impact of AG-879 on cell proliferation and elucidate the underlying mechanisms of its anti-GBM effects. To evaluate this, U118 GBM cells were split into control and treatment (10µM AG-879) groups and allowed to incubate for 72-hours at 37.5^oC. Afterwards, cell lysate was collected, and Lowry protein estimation was performed. Western Blot analysis was conducted, and membranes were probed with antibodies that targeted β-actin (loading control), phospho-AKT (proliferation marker), and total AKT. Our results demonstrated that AG-879 effectively decreases U118 cell proliferation by inhibiting AKT activation (phospho-AKT) at 10µM. Future studies should evaluate the effect of AG-879 on markers of apoptosis and cell cycle arrest.

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  Barriers to Screening Colonoscopy for Hispanic Patients in Omaha, Nebraska

  Bryan Lugo Maldonado, Angel M. Lehn, Bryan Benitez, Shirley F. Delair, and Quan P. Ly

  Colorectal cancer (CRC) is the second leading cause of cancer death in the United States. Early detection through screening is crucial for reducing mortality rates. However, the Hispanic population in the US are less likely to adhere to CRC screening guidelines. The objective of this study is to identify barriers to screening colonoscopy among Hispanic patients in Omaha, Nebraska. Ninety-two Hispanic patients from OneWorld Community Health Center were interviewed via phone. The survey evaluate sociodemographic characteristics and potential barriers to colonoscopy. From the interviews, the most common barriers identified were lack of follow-up, affecting (16.30%) of patients, lack of insurance (10.87%), and lastly, lack of understanding of the procedure (9.78%). Understanding these barriers to screening colonoscopy in the Hispanic population could increase adherence and potentially reduce the mortality rate.

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  PDAC-cells Differentially Modulate Expression of Neutrophil Serine Proteases and Their Inhibitors

  Sumanas Maram, Reegan Sturgeon, Ridhi Bhola, Ainsley Meyerson, Esther Johnson, and Rakesh K. Singh

  Pro-inflammatory tumors are a defining feature of pancreatic cancer. Infiltrating leukocytes modulate inflammation and aid in PDAC disease progression; this leads them to be therapeutic targets for researchers. Neutrophils, which are pro-tumorigenic, are the most abundant leukocyte in circulation; although past research has indicated that neutrophils aid in tumor progression, the mechanisms behind tumor-associated neutrophils are relatively unknown. One focus of my laboratory is neutrophil serine proteases (NSP), enzymes produced by neutrophils capable of inducing apoptosis. The inhibitors of these NSPs are serine protease inhibitors (serpins), and past research has shown that deficiencies in them have led to high cell mortality, indicating that these serpins and NSPs may modulate apoptosis levels (4). My lab has also shown that neutrophil survival increases with the treatment of PDAC-conditioned media. The specific objective of my project is to understand how PDAC cells modulate the expression of neutrophil serine proteases and their inhibitors. We used cDNA from a mouse promyelocyte neutrophil cell line (MPRO) that was treated with different PDAC-conditioned media. Expression levels of NSP genes (Cathepsin G (CatG), Neutrophil Elastase (NE), and Proteinase 3 (PR3)) and their inhibitors (Serpin b1a, Serpin b6a, and Serpin a1a) were observed using qRT-PCR (1). We observed that for NSPs, the trend indicated greater expression in the gemcitabine-resistant treated cell lines (CD18/HPAF GemR and T3M4 GemR), compared to the parental treated cell lines (CD18/HPAF and T3M4). Additionally, for L3.3 (low metastatic) and L3.6 (high metastatic) treated neutrophils, we see upregulation expression of serine proteases in L3.6 treated cells compared to L3.3 treated cells. In contrast, for NSP inhibitors, the trend indicates greater expression in the parental cell lines than in gemcitabine-resistant cell lines. There is upregulation in both L3.3 and L3.6 cell expression as well. Together, our data suggests that PDAC cells differentially modulate the expression of NSPs and their inhibitors.

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  Serine Protease Inhibitors Enhance Neutrophil Survival

  Ainsley Meyerson, Reegan Sturgeon, Ridhi Bhola, Sumanas Maram, Esther Johnson, and Rakesh K. Singh

  According to the Centers for Disease Control (CDC), cancer is the second leading cause of death in the U.S., with 9.6% of all adults being diagnosed throughout their lifetime. Many of those diagnosed are given low survival rates due to late diagnosis or tumor resistance to chemotherapy. Cancer cells create a pro-inflammatory tumor microenvironment (TME) that supports tumor growth. Neutrophils, key components of this TME, are shown to survive in the TME of some cancers longer than in circulation. Neutrophils produce serine proteases (NSPs), such as cathepsin G (CatG), neutrophil elastase (NE), and proteinase 3 (PR3), which are associated with apoptosis. These can be exploited by tumors to allow for increased neutrophil survival and aid in tumor progression. This study explores the impact of inhibiting NSPs with neutrophil serine protease inhibitors such as tosyl phenylalanyl chloromethyl ketone (TPCK), phenylmethylsulfonyl fluoride (PMSF), and Cathepsin G Inhibitor (CTGI) in a serum-free environment mimicking the TME. We used two neutrophil cell line models (MPRO – mouse and HL-60 – human). Neutrophil proliferation/survival was determined through a WST assay. We observed that increasing NSP inhibitor concentrations enhances cell survival in both MPRO and HL-60 cells, indicating that NSPs and their inhibitors could be a pathway utilized by cancer cells to influence neutrophil phenotype in the TME. This data suggests that targeting NSPs and their inhibitors may offer a promising strategy to disrupt tumor progression.

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  Disrution of 3D Genome Organization Can Explain Alcohol Fetal Spectrum Disorder

  Coralmarie Ortiz Cardona, Joynob Akter Puspo, Stephanie F. Maurina, Ben Nolan, Jordan Rowley, and Christopher Cummings

  Fetal Alcohol Spectrum Disorders (FASD) refers to a range of disorders caused by prenatal alcohol exposure and are characterized by neurodevelopmental impairment with or withoutspecific facial features, congenital anomalies, and poor growth. The spectrum is composed of four diagnostic categories: fetal alcohol spectrum (FAS), partial fetal alcohol spectrum (PFAS), alcohol-related neurodevelopmental disorder (ARND), and alcohol-related birth defects (ARBD). There is no specific diagnostic test or molecular biomarker for FASD, and without one, patients require evaluation through a multidisciplinary team approach. Epigenetics is the study of changes in gene activity that do not involve alterations to the DNA sequence. Alcohol exposure during pregnancy can lead to chromatin modifications like DNA methylation and histone modifications, indicative of an epigenetic mechanism for the FASD phenotype. Chromatin is an epigenetic componentwithin the 3D nuclear space, efficiently packaging the genome while allowing proper expression and replication of the genetic material. 3D Organization of the genome is a property of chromatin and its components, with CTCF acting as a major architectural protein, working jointly with cohesin to generate thousands of high-intensity chromatin loops. We hypothesize that disruption of these loops by prenatal alcohol exposure drives neurodevelopmental defects by altering the expression of genes critical for brain development and function. In this study, we used chromatin immunoprecipitation sequencing (ChIP-seq) and found that alcohol exposure increases the intensity of CTCF loops, and we hypothesize this is through the formation of adducts.

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  The Correlation Between Social Work Encounters and Health Outcomes in Children with Cystic Fibrosis

  Sophia A. St Marie and Heather M. Thomas MD

  Purpose: The objective of this study is to evaluate the impact social workers have on the health of children with cystic fibrosis and to see if an increased number of social work encounters is an indicator of poor health in these children.

  Methods: The electric medical record (EPIC) was used to collect data on 193 patients born between 2000 and 2024 (0 to 23 years). Data from June 1, 2019, to June 1, 2024 (or birth to June 1, 2024) was considered. Physical information, namely age (months and years), mutation (homozygous, heterozygous, or other), BMI (or weight/length) percentile and z-score, %FEV1, modulator (if applicable), visits to CF clinic, outpatient pulmonary exacerbations, and inpatient pulmonary exacerbations was collected. Additionally, social factors: food, housing, or transportation insecurity, education, prior CPS involvement, patient/caregiver mental health (qualitatively and with PHQ-9/GAD-7 (>age 11)), language barriers, and insurance type were taken into account. All values were adjusted for age by months. Statistical analysis by t-test was conducted to check for the significance of the findings.

  Results: When considering the entirety of the data set, it can be deduced that the number of social work visits is suggestive of health. Namely, a high number of social work encounters corresponded to lower BMI and FEV1 (-m), and a higher number of exacerbations (+m). Statistically, however, this is not significant, so we accept the null hypothesis that social work encounters have no significant impact on health markers. In patients with the top 10 most social work encounters, exacerbation trends remain consistent, but FEV1 and BMI trends appear in the inverse (+m). Further research is needed to determine why. Our hypothesis is disproven, perhaps due to social workers improving the health of patients by providing support and resources.

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  Opioid-Induced Changes to Pregnancy Outcomes and Placental Structure in Rat Models

  Ayla Young, Isaac Adediji, Hager Kowash, Vicki Schaal, Gurudutt Pendyala, and Lynda Harris

  Maternal opioid-use disorder (MOUD) is a growing national health problem and the number of affected births quadrupled between 1999 and 2014.¹ MOUD is correlated with abnormal placental trophoblast proliferation and villous vascularization, suggestive of chronic hypoxia and poor vascular integrity.² Such damage to the placenta can be extremely disruptive, not only because of the placenta’s role in providing oxygen to the developing fetus, but also because of the placenta-brain axis, which modulates fetal brain development.³ MOUD may cause neurodevelopmental alterations via direct changes to the fetal brain or via indirect opioid-induced placental dysfunction which disrupts the placenta-brain axis. This study used a rat model of exposure to oxycodone, a commonly prescribed opioid; melatonin was also administered both separately and concurrently with oxycodone to assess its efficacy in reducing the adverse effects from oxycodone. Both oxycodone and melatonin treatments increased the relative area of the placental exchange region, called the labyrinth zone, but only melatonin had a significant impact on the fetal:placental weight ratio and fetal size. Thus, while melatonin increased placental efficiency by expanding the exchange area, the oxycodone-induced placental alterations did not increase placental efficiency. It is likely that these changes were necessary compensations for oxycodone-induced placental damage.