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Item Treatment of Metastatic Her2Neu+ Breast Cancer with Oligoprogressive Disease(2024-03-23) Pelton, Sarah; Ayub, Jinan; Kenyon, Taylor; Ramchandani, Muskaan; Newton, ErinBackground Information: In treating metastatic Her2Neu+ breast cancer, trastuzumab-based chemotherapy regimens typically result in fairly durable tumor control. Historically, when there was any disease progression, the systemic therapy was changed, but it has recently been recognized that “oligoprogressive disease” (when only a limited number of metastatic sites progress) might be approached differently. This heterogeneous response to treatment is due to variation in tumor cell phenotypes, which confer drug resistance. Oligoprogressive disease is often treated with local therapy, such as stereotactic body radiotherapy (SBRT), or resection, and determination of optimal treatment regimens remains a challenge. Case Description: We report a case of a 37-year-old, premenopausal female with locally advanced, Her2Neu+ right breast cancer with de novo metastases to the liver and bone. First line systemic therapy was well-tolerated and resulted in disease control. Unfortunately, she had symptomatic progression in her primary breast tumor, which was treated with mastectomy while continuing the same systemic therapy. Later, she developed a painful, right infraclavicular metastasis; surgical resection was ultimately declined due to local edema and the tumor’s proximity to significant neurovasculature. She elected to receive palliative radiation therapy for pain control via SBRT, and her systemic therapy remained unchanged. Currently, she shows no signs of progression and continues to have excellent tolerance of her systemic therapy. Clinical Significance: Oligoprogression is a clinically significant concept for numerous cancers, but the best methods of control have not been elucidated. This case contributes to the limited knowledge base as an example of treating Her2Neu+ breast cancer-associated oligoprogressive disease with local therapy.Item Social Determinants of Health and Clinical Outcomes in Children With Cystic Fibrosis(2024-05-20) de Laosa, Mary; Ayub, Jinan; Bilinski, Sarah; Fultz, Megan; Petit, Rebecca; Chmiel, James; Sanders, DonRationale: Among children with cystic fibrosis (CF), clinical outcomes vary among genetically similar patients, in part due to the contributions of social determinants of health (SDOH). Changes to patient assistance programs and Medicaid re-enrollment requirements may further impact people affected by SDOH. This project aimed to identify socially vulnerable patients and evaluate the impacts of SDOH on clinical outcomes. Methods: From January to July 2023, SDOH questionnaires were distributed to families of children with CF at Riley Hospital for Children. Patients were categorized by SDOH vulnerability and associations with clinical outcomes were analyzed using the Chi-squared test of independence. Results: 193 screeners were analyzed: the mean age was 9.2 years; 53% were males, 2.6% identified as non-White race, 3.6% reported Hispanic ethnicity, 51.6% were enrolled in Medicaid, and 70.5% were taking either ivacaftor or elexacaftor-tezacaftor-ivacaftor (ETI), consistent with the overall CF Center population. Overall, 100 (51.8%) screened positive for at least one SDOH (SDOH+): 60 screened positive for 1, 25 for 2, and 13 for 3+ SDOH. Of the SDOH+ patients, 64% were affected by the medical needs of another family member, 30% by food insecurity, 28% by difficulties affording utilities or rent, 22% by transportation needs, 11% by housing, and 9% by medication costs. In addition, 16 (8.3%) reported being negatively affected by changes to patient assistance programs and 7 (3.6%) by difficulties with Medicaid re-enrollment; 12 (75%) and 3 (43%) of whom were SDOH+, respectively. Of those who were SDOH+, 62% received immediate social work intervention.Mean (SD) FEV1 among SDOH+ patients was 5.8 (5.2)% predicted lower than their 2022 mean, vs 3.5 (5.0)% lower for SDOH- patients, p=0.001. A higher proportion of SDOH+ patients were 35% predicted below their 2022 mean FEV1 (24% vs 13% for SDOH-, p=0.037) and to have been hospitalized for a pulmonary exacerbation in the prior 12 months (21% vs 10% for SDOH-, p=0.030). There were no differences in mean BMI percentile, CFRD, or P. aeruginosa. Conclusions: Half of our CF Center population that completed a questionnaire screened positive for at least one SDOH. Some of these were not previously known by the CF Center team and this information provided opportunities to support families. SDOH+ patients have benefited from support from the multidisciplinary team, which may have mitigated negative impacts on clinical outcomes of insurance/payment assistance program changes. We will continue to routinely track SDOH, and changes to patient assistance programs and Medicaid.Item Investigation of the Oncogenic Properties of Phosphatase of Regenerating Liver 3(2021-04-12) Ayub, Jinan; Amarasinghe, Ovini; Zhang, Zhong-YinPhosphatase regenerating liver (PRL) is an enzymatic phosphatase whose oncogenic properties warrant its investigation as a therapeutic drug target. Specifically, it is well understood that PRL3 overexpression can be directly linked to cancer, as the phosphatase can activate PI3K/AKT pathways and downregulate PTEN levels, promoting metastasis and epithelial-mesenchymal transition (EMT). The purpose of this project was to further investigate mutated PRL3 proteins in order to assess whether mutations, rather than overexpression, of PRL3 can lead to cancer. Furthermore, whether these mutations specifically caused a gain-of-function or loss-of-function in PRL3 activity was examined. This study began by investigating common point mutations associated with PRL3 using the cBioPortal for Cancer Genomics database, through which R138 was identified as the most commonly mutated site. The four most frequent PRL3 mutations were created using QuikChange® site-directed mutagenesis. After sequencing the DNA to confirm mutagenesis, the recombinant proteins were purified to investigate their biochemical properties in vitro, such as their trimerization ability and phosphatase activity. Results indicated the most common mutation, R138C, had similar trimerization ability compared to wild-type PRL3, however, the other three mutants had lower trimerization ability. Interestingly, all four oncogenic mutants showed decreased kinetic activity and lower binding affinity for the pNPP substrate. Although these results imply that these oncogenic mutations are indeed loss-of-function, further in vivo experimentation should be conducted to confirm the applicability of these results in transfected human cell lines.Item Pediatric Postpartum Gallstone Pancreatitis: A Case Study(2023-03-24) Sullivan, Megan; Ayub, Jinan; Jauregui, Alexa; Brian, Gray; Burns, CatherineBackground Hospitalizations in the United States for biliary tract pathology, mainly gallstone disease, affect 0.5% of peripartum and postpartum patients. Complications include significant disability, preterm delivery, and time away from the newborn due to surgery. Symptoms of gallstone pancreatitis are often dismissed as normal peripartum symptoms. Case Presentation A 12-year-old female, 2 months postpartum, presented with 1 day of epigastric pain and vomiting. Labs showed elevated lipase (>2000). Computed Tomography (CT) showed acute pancreatitis, and choledocholithiasis was noted on ultrasound (US). She underwent endoscopic retrograde cholangiopancreatography, followed by laparoscopic cholecystectomy. Review of records revealed 3 previous visits for vomiting and abdominal pain. Gallstones were not suspected due to missed follow-up or suspicion of pregnancy-related diagnoses. Social history was complex due to immigration and socioeconomic status (SES). A 17-year-old female presented similarly, at 2 months postpartum, with epigastric pain. She was discharged with a presumed urinary tract infection. Later diagnostic tests revealed acute pancreatitis (CT) and gallstones (US). After treatment, lipase remained elevated (>6000), but other labs suggested passage of the previously obstructing gallstone. She underwent laparoscopic cholecystectomy. Care was delayed due to insurance barriers. Conclusion Patients <20 years are at greatest risk for postpartum gallstone pathology. This differential should be prioritized in young patients with epigastric or right upper quadrant pain, especially in the presence of risk factors such as low SES. Clinical significance It is typical for gallstone acute pancreatitis to have symptoms prior to presentation, but it is unclear if preceding symptoms in postpartum patients are misdiagnosed and attributed to pregnancy, or if acute presentation is more common. Increased awareness about gallstones in postpartum pediatric patients can mitigate the dangerous sequelae of gallstones including acute pancreatitis.Item Relationship between Neighborhood-Level Socioeconomic Status and Relapsed Pediatric B-Acute Lymphoblastic Leukemia Treated with CAR-T19 Therapy in Indiana(2025-03-29) Ayub, Jinan; Walker, Alyssa; Grischke, Tyra; Garcia, Gloria; Skiles, Jodi; Spiegel, Courtney; Batra, SandeepBackground/Purpose: There is paucity of studies investigating the relationship between socioeconomic status and outcomes for patients receiving chimeric antigen receptor T-cell therapy (CART19) for refractory or relapsed B-ALL. Area Deprivation Index (ADI) serves as a measurement of socioeconomic disadvantage based on theoretical income, education, employment, and quality of housing. Methods: A retrospective chart review of 27 patients with relapsed B-ALL treated with CART19 at a non-profit children’s hospital from 2018-2024 was conducted. Using a public institution’s Neighborhood Atlas database, ADI scores (range 1-10) were recorded for each patient based on ZIP code of residence in Indiana. A low ADI score (0-5) indicates affluence and higher SES, while a high ADI score (6-10) indicates deprivation and a lower SES. Comparisons between groups were done using Chi-square tests for categorical variables. The Kaplan-Meier method was used to analyze relapse free survival (RFS) using the log rank test to compare groups. Results: The patients (age range 2-25 years) were stratified into two groups: low ADI or high SES (≤5, n = 10 (37%); 2.9 ± 1.4; range, 1-5)) and high ADI or low SES (>5, n = 17 (63%); 8.5 ± 1.5; range, 6-10). Seventeen identified as white (63%) and 10 (37%) as Hispanic. Three patients received CART19 infusions twice, and one patient received multiple CART19-directed products. In the high ADI group, 3-month, 6-month, and 1-year RFS post-CART therapy was 82%, 76%, 60% respectively compared to 100%, 71%, 57% in the low ADI group (p=0.9). Conclusion: Most patients who received CART therapy at our tertiary center resided in low SES areas but did not experience worse RFS compared to patients residing in more affluent areas. Further studies with larger sample sizes are needed to better understand the heath inequalities among patients with relapsed leukemia in Indiana and to identify challenges faced by patients from disadvantaged communities with limited resources.Item Effects of siRNA-Mediated PRL2 Knockdowns on Cell Signaling in Pancreatic and Lung Cancer Cell Lines(2021-11-15) Ayub, Jinan; Nguele Meke, Frederick; Zhang, Zhong-YinPhosphatase of regenerating liver (PRL) is an enzymatic phosphatase whose oncogenic properties warrant its investigation as a therapeutic drug target. Of all three variants, PRL2 is the most abundantly expressed in cells and dephosphorylates proteins involved in preventing oncogenesis. A recent publication by Dr. Zhong-Yin Zhang’s lab showed that PRL2 downregulates PTEN by dephosphorylating its Y336 residue, activating ubiquitin-mediated PTEN degradation and increasing the cell’s susceptibility to malignancies. This project investigated if lower PRL2 expression in pancreatic and lung cancer cell lines, which confer high mortality rates, can suppress its oncogenic effects in signaling pathways. In this study, five different pancreatic and lung cancer cell lines, PaCa2, A549, H358, HPAF, and CFPAC, were transiently transfected with small interfering RNA (siRNA) to knockdown PRL2 expression. After 48 hours, the protein expression of ERK/AKT, STAT3, PCNA, PTEN, and PARP in these cells were analyzed on Western blots. The preliminary results were mixed, with only the A549, H358, and PaCa2 cell lines showing the expected increase in PTEN levels. All cell lines showed increased apoptosis, as demonstrated by increased cleaved PARP levels. These results may help determine if disrupting PRL-regulated pathways can prevent pancreatic and lung cancer cell development. In the future, CRISPR-Cas9 will be used to generate PRL2 knockout stable lines, as the signaling studied under transient transfections may be too short-lived to accurately capture the effect of PRL2 loss on cell signaling. Additionally, experiments with mouse xenograft models will be performed to further evaluate tumorigenicity in vivo.Item Creating a Clinic: Review of Demographics and Common Diagnoses at the Crossroads Student Outreach Clinic(2024-05-16) Ayub, Jinan; Sullivan, Megan; Nadeem, Manahil; Wirth, CarrieResearch Objective & Hypothesis This study aims to identify and analyze patient demographics and conditions treated at a new student outreach clinic. We hypothesized the clinic would primarily serve patients who were Spanish-speaking, seeking care for chronic conditions, and had transportation barriers. Background The Crossroads Student Outreach Clinic (SOC) is a free clinic that offers healthcare to underserved patients in the Greater Lafayette area. The clinic is run by IUSM-WL students along with Arnett family medicine residents and faculty. The clinic is made possible through a partnership with IU Health Arnett and occurs at the residency clinic once monthly. Methods & Design Patients completed an intake form self-reporting demographic information, medical history, primary health goals, and barriers to care. Data collection from each patient included chief complaints and diagnoses addressed at the visit. Patients were also given a seven-question quality survey. Categorical data was analyzed using frequency tables and age demographics were analyzed using group frequency tables. Results Since October 2023, 31 patients have been seen. Most patients were aged 30-49 years old (39%), of Hispanic ethnicity (42%), and reported English as their primary language (58%), followed by Spanish (36%). The most common reason for an appointment was a wellness check (42%). The most frequent diagnoses corresponded to the following systems: gastrointestinal (26%), reproductive (26%), psychiatric (23%). The most common diagnoses were hypertension (13%) and depression (13%). Twenty-seven patients completed the survey (87%). Most patients strongly agreed to all questions: ease of appointment scheduling (96%), accessibility via provided transportation (74%), medical competency of staff (93%), respectful treatment (100%), prescription fulfillment (52%), likelihood of recommending to others (93%), and overall satisfaction (85%). Conclusion The Crossroads SOC serves a diverse group of individuals, with many patients seeking preventative care and treatment for chronic conditions. With many appointments consisting of wellness visits, we aim to implement more screening tools, vaccination resources, and point-of-care labs.Item Finding a Parallel to Eisenstein's Criteria over Finite Fields(Butler University, 2019) Heumann, Ryan; Sharma, PremFactoring polynomials over the integers is something that we all learn in high school algebra. Homework assignments are made up of countless polynomials and it is our job to find the factors. Eventually, the polynomials get longer and more difficult and we learn other methods to factor them. The problem becomes harder when you come across a polynomial which you are unable to factor. With certain polynomials like x^2+1, you can easily tell that it cannot be factored over Z. However, other times we are left wondering whether a given polynomial p(x) is factorable over Z at all. Lucky for us, Gotthold Eisenstein, a mathematician, found a sufficient condition for irreducibility over Z.Item Gaps in Rural Healthcare and Technology’s Evolving Role in Addressing Them(Purdue University, 2025-04-17) Heumann, RyanThe gap in mortality rate due to disease between rural and urban communities is substantial and continues to grow. There is no one root cause to this disparity, so there is no simple solution either. In order to even begin to reverse the trend, it is vital to understand the factors that contribute to health outcomes in rural communities. Part of this analysis includes studying where individuals are getting information about their health and healthcare. With the growth of the internet over the last three decades, this landscape has been dynamic. It becomes important to dissect its impact on health behaviors to avoid the same pitfalls as the new era of technology, marked by artificial intelligence, continues to grow exponentially.Item Effects of Functional Movement-Based Myofascial Release Therapy on Shoulder Range of Motion in a Collegiate Pitcher: A Case Report(Indiana University School of Medicine, 2025-01-26) Heumann, Ryan; Waltz, Matt; Garcia-Hosokawa, Marcel; Chlebowski, ArthurStrong, repetitive forces sustained by the shoulder joint during overhead throwing sports can cause alterations in range of motion (ROM) of the joint itself. This change can lead to risk of injury. Currently, there are a number of established therapies to increase ROM and decrease injury risk. This case report covers the use of a form of myofascial release therapy (MRT), and its effect on throwing shoulder ROM and pain in a collegiate baseball player. After twelve sessions of therapy, external rotation increased by 20.64°(16.97%) and internal rotation increased by 19.60°(65.88%). This total increase in ROM provides evidence for a less commonly used therapeutic technique and its possible effect on decreasing risk of injury in overhead throwing athletes.