Digital Commons Network^™

Development Of A Rabbit Human Glioblastoma Model For Testing Of Endovascular Selective Intra-Arterial Infusion (Esia) Of Novel Stem Cell-Based Therapeutics, Peter Kan, Visish M Srinivasan, Joy Gumin, Roberto Garcia, Stephen R Chen, Jeremiah N Johnson, Dalis E Collins, Melissa M Chen, Daniel Ledbetter, Jason Huse, Zean Aaron Evan Luna, Ariadna Robledo, Viren Vasandani, Abhijit Rao, Sanjay K Singh, Elizabeth J Shpall, Juan Fueyo, Candelaria Gomez-Manzano, Frederick F Lang

Faculty, Staff and Student Publications

BACKGROUND: Endovascular selective intra-arterial (ESIA) infusion of cellular oncotherapeutics is a rapidly evolving strategy for treating glioblastoma. Evaluation of ESIA infusion requires a unique animal model. Our goal was to create a rabbit human GBM model to test IA infusions of cellular therapies and to test its usefulness by employing clinical-grade microcatheters and infusion methods to deliver mesenchymal stem cells loaded with an oncolytic adenovirus, Delta-24-RGD (MSC-D24).

METHODS: Rabbits were immunosuppressed with mycophenolate mofetil, dexamethasone, and tacrolimus. They underwent stereotactic xenoimplantation of human GBM cell lines (U87, MDA-GSC-17, and MDA-GSC-8-11) into the right frontal lobe. Tumor formation was confirmed on …

Dimerization Of The 4ig Isoform Of B7-H3 In Tumor Cells Mediates Enhanced Proliferation And Tumorigenic Signaling, Margie N Sutton, Sarah E Glazer, Riccardo Muzzioli, Ping Yang, Seth T Gammon, David Piwnica-Worms

Faculty, Staff and Student Publications

B7-H3 (CD276) has two isoforms (2Ig and 4Ig), no confirmed cognate receptor, and physiological functions that remain elusive. While differentially expressed on many solid tumors correlating with poor survival, mechanisms of how B7-H3 signals in cis (tumor cell) versus in trans (immune cell co-regulator) to elicit pro-tumorigenic phenotypes remain poorly defined. Herein, we characterized a tumorigenic and signaling role for tumor cell-expressed 4Ig-B7-H3, the dominant human isoform, in gynecological cancers that could be abrogated upon CRISPR/Cas9 knockout of B7-H3; tumorigenesis was rescued upon re-expression of 4Ig-B7-H3. Size exclusion chromatography revealed dimerization states for the extracellular domains of both human 4Ig- …

Video Endoscopy As Big Data: Balancing Privacy And Progress In Gastroenterology, Eugenia N. Uche-Anya, Sara Gerke, Tyler M. Berzin

Faculty Scholarly Works

Tens of millions of gastrointestinal (GI) endoscopy videos and images are generated annually in the United States (¹). A single 15-minute endoscopic procedure, recorded at 30 frames per second, generates approximately 27,000 high-definition images, representing a treasure trove of potential data. In the era of artificial intelligence (AI) and machine learning (ML), this data stream will not only fuel innovative and clinically impactful research in gastroenterology for both academic and commercial purposes, but also introduce ethical and legal concerns that merit consideration. Gastroenterologists are now faced with navigating new questions around data privacy and data ownership that have …

Heat Shock Factor 1 Directly Regulates Transsulfuration Pathway To Promote Prostate Cancer Proliferation And Survival, J Spencer Hauck, David Moon, Xue Jiang, Mu-En Wang, Yue Zhao, Lingfan Xu, Holly Quang, William Butler, Ming Chen, Everardo Macias, Xia Gao, Yiping He, Jiaoti Huang

Faculty, Staff and Students Publications

There are limited therapeutic options for patients with advanced prostate cancer (PCa). We previously found that heat shock factor 1 (HSF1) expression is increased in PCa and is an actionable target. In this manuscript, we identify that HSF1 regulates the conversion of homocysteine to cystathionine in the transsulfuration pathway by altering levels of cystathionine-β-synthase (CBS). We find that HSF1 directly binds the CBS gene and upregulates CBS mRNA levels. Targeting CBS decreases PCa growth and induces tumor cell death while benign prostate cells are largely unaffected. Combined inhibition of HSF1 and CBS results in more pronounced inhibition of PCa cell …

Preclinical Repurposing Of Sitagliptin As A Drug Candidate For Colorectal Cancer By Targeting Cd24/Ctnnb1/Sox4-Centered Signaling Hub, Jing-Wen Shih, Alexander T H Wu, Ntlotlang Mokgautsi, Po-Li Wei, Yan-Jiun Huang

Faculty, Staff and Student Publications

Despite significant advances in treatment modalities, colorectal cancer (CRC) remains a poorly understood and highly lethal malignancy worldwide. Cancer stem cells (CSCs) and the tumor microenvironment (TME) have been shown to play critical roles in initiating and promoting CRC progression, metastasis, and treatment resistance. Therefore, a better understanding of the underlying mechanisms contributing to the generation and maintenance of CSCs is crucial to developing CSC-specific therapeutics and improving the current standard of care for CRC patients. To this end, we used a bioinformatics approach to identify increased CD24/SOX4 expression in CRC samples associated with poor prognosis. We also …

Novel Textbook Outcomes Following Emergency Laparotomy: Delphi Exercise, David N Naumann, Aneel Bhangu, Adam Brooks, Matthew Martin, Bryan A Cotton, Mansoor Khan, Mark J Midwinter, Lyndsay Pearce, Douglas M Bowley, John B Holcomb, Ewen A Griffiths, Beacon Collaborative

Faculty, Staff and Student Publications

Background: Textbook outcomes are composite outcome measures that reflect the ideal overall experience for patients. There are many of these in the elective surgery literature but no textbook outcomes have been proposed for patients following emergency laparotomy. The aim was to achieve international consensus amongst experts and patients for the best Textbook Outcomes for non-trauma and trauma emergency laparotomy.

Methods: A modified Delphi exercise was undertaken with three planned rounds to achieve consensus regarding the best Textbook Outcomes based on the category, number and importance (Likert scale of 1-5) of individual outcome measures. There were separate questions for non-trauma and …

Postoperative Systemic Inflammatory Response Syndrome Predicts Increased Mortality In Patients After Elective Craniotomy, Liyuan Peng, Qi Gan, Yangchun Xiao, Jialing He, Xin Cheng, Peng Wang, Lvlin Chen, Tiangui Li, Yan He, Weelic Chong, Yang Hai, Chao You, Fang Fang, Yu Zhang

Department of Medical Oncology Faculty Papers

Introduction: Patients undergoing craniotomy are at high risk of perioperative morbidity and mortality due to excessive inflammatory responses. The purpose of the present study is to evaluate the prognostic utility of postoperative systemic inflammatory response syndrome (SIRS) in patients undergoing craniotomy.

Methods: We performed a retrospective cohort study of patients who underwent craniotomy between January 2011 and March 2021. SIRS was diagnosed based on two or more criteria (hypo-/hyperthermia, tachypnea, leukopenia/leukocytosis, tachycardia). We used univariate and multivariate analysis for the development of SIRS with postoperative 30-day mortality.

Results: Of 12,887 patients who underwent craniotomy, more than half of the patients …

Targeting Dna Repair And Survival Signaling In Diffuse Intrinsic Pontine Gliomas To Prevent Tumor Recurrence, Monika Sharma, Ivana Barravecchia, Robert Teis, Jeanette Cruz, Rachel Mumby, Elizabeth K Ziemke, Carlos E Espinoza, Varunkumar Krishnamoorthy, Brian Magnuson, Mats Ljungman, Carl Koschmann, Joya Chandra, Christopher E Whitehead, Judith S Sebolt-Leopold, Stefanie Galban

Faculty, Staff and Student Publications

Therapeutic resistance remains a major obstacle to successful clinical management of diffuse intrinsic pontine glioma (DIPG), a high-grade pediatric tumor of the brain stem. In nearly all patients, available therapies fail to prevent progression. Innovative combinatorial therapies that penetrate the blood-brain barrier and lead to long-term control of tumor growth are desperately needed. We identified mechanisms of resistance to radiotherapy, the standard of care for DIPG. On the basis of these findings, we rationally designed a brain-penetrant small molecule, MTX-241F, that is a highly selective inhibitor of EGFR and PI3 kinase family members, including the DNA repair protein DNA-PK. Preliminary …

Serine Synthesis Via Reversed Shmt2 Activity Drives Glycine Depletion And Acetaminophen Hepatotoxicity In Masld, Alia Ghrayeb, Alexandra C Finney, Bella Agranovich, Daniel Peled, Sumit Kumar Anand, M Peyton Mckinney, Mahasen Sarji, Dongshan Yang, Natan Weissman, Shani Drucker, Sara Isabel Fernandes, Jonatan Fernández-García, Kyle Mahan, Zaid Abassi, Lin Tan, Philip L Lorenzi, James Traylor, Jifeng Zhang, Ifat Abramovich, Y Eugene Chen, Oren Rom, Inbal Mor, Eyal Gottlieb

Faculty, Staff and Student Publications

Metabolic dysfunction-associated steatotic liver disease (MASLD) affects one-third of the global population. Understanding the metabolic pathways involved can provide insights into disease progression and treatment. Untargeted metabolomics of livers from mice with early-stage steatosis uncovered decreased methylated metabolites, suggesting altered one-carbon metabolism. The levels of glycine, a central component of one-carbon metabolism, were lower in mice with hepatic steatosis, consistent with clinical evidence. Stable-isotope tracing demonstrated that increased serine synthesis from glycine via reverse serine hydroxymethyltransferase (SHMT) is the underlying cause for decreased glycine in steatotic livers. Consequently, limited glycine availability in steatotic livers impaired glutathione synthesis under acetaminophen-induced oxidative …

Pediatric Medical Subspecialist Use In Outpatient Settings, Christopher B Forrest, Candice P Chen, Eliana M Perrin, Christopher J Stille, Ruth Cooper, Katherine Harris, Qian Luo, Mitchell G Maltenfort, Lauren E Parlett

Faculty, Staff and Student Publications

Importance

A first step toward understanding whether pediatric medical subspecialists are meeting the needs of the nation’s children is describing rates of use and trends over time.

Objectives

To quantify rates of outpatient pediatric medical subspecialty use.

Design, Setting, and Participants

This repeated cross-sectional study of annual subspecialist use examined 3 complementary data sources: electronic health records from PEDSnet (8 large academic medical centers [January 1, 2010, to December 31, 2021]); administrative data from the Healthcare Integrated Research Database (HIRD) (14 commercial health plans [January 1, 2011, to December 31, 2021]); and administrative data from the Transformed Medicaid Statistical Information …

Cell Cycle Arrest Induces Lipid Droplet Formation And Confers Ferroptosis Resistance, Hyemin Lee, Amber Horbath, Lavanya Kondiparthi, Jitendra Kumar Meena, Guang Lei, Shayani Dasgupta, Xiaoguang Liu, Li Zhuang, Pranavi Koppula, Mi Li, Iqbal Mahmud, Bo Wei, Philip L Lorenzi, Khandan Keyomarsi, Masha V Poyurovsky, Kellen Olszewski, Boyi Gan

Faculty, Staff and Student Publications

How cells coordinate cell cycling with cell survival and death remains incompletely understood. Here, we show that cell cycle arrest has a potent suppressive effect on ferroptosis, a form of regulated cell death induced by overwhelming lipid peroxidation at cellular membranes. Mechanistically, cell cycle arrest induces diacylglycerol acyltransferase (DGAT)-dependent lipid droplet formation to sequester excessive polyunsaturated fatty acids (PUFAs) that accumulate in arrested cells in triacylglycerols (TAGs), resulting in ferroptosis suppression. Consequently, DGAT inhibition orchestrates a reshuffling of PUFAs from TAGs to phospholipids and re-sensitizes arrested cells to ferroptosis. We show that some slow-cycling antimitotic drug-resistant cancer cells, such as …

Immunotherapy Serum Mixing: 2023 Best Practice Changes, Eyas Abla Md, Paul Faybusovich Do, Matthew Lies, Mallory Mondloch

Nursing Posters

Background Story:

CentraCare - Plaza Allergy & Asthma Clinic compounds immunotherapy serum with advanced training of licensed nurses. Effective November 1, 2023, USP (797) Pharmaceutical Compounding guidelines were updated and endorsed by the American Academy of Allergy, Asthma & Immunology (AAAI). The Allergy Clinic completed a gap analysis to determine what process needed to change to comply with these latest guidelines.

Antimicrobial Activity Of Gallium(Iii) Compounds: Pathogen-Dependent Targeting Of Multiple Iron/Heme-Dependent Biological Processes, Seoung-Ryoung Choi, Mohammed A. Hassan, Bradley E. Britigan, Prabagaran Narayanasamy

Journal Articles: Pathology and Microbiology

Metals play vital roles in biological systems, with iron/heme being essential for cellular and metabolic functions necessary for survival and/or virulence in many bacterial pathogens. Given the rise of bacterial resistance to current antibiotics, there is an urgent need for the development of non-toxic and novel antibiotics that do not contribute to resistance to other antibiotics. Gallium, which mimics iron, has emerged as a promising antimicrobial agent, offering a novel approach to combat bacterial infections. Gallium does not have any known functions in biological systems. Gallium exerts its effects primarily by replacing iron in redox enzymes, effectively inhibiting bacterial growth …

A Mindfulness Approach To Regulate Depressive-Associated Emotional Eating, Jillian G. Montefusco

Doctor of Nursing Practice Scholarly Projects

Background: Depression affects 350 to 500 million people globally, with depressive-associated emotional eating (DAEE) impacting approximately 43.5% of these individuals. Depressive-associated emotional eating contributes to obesity through poor dietary choices and weight gain, leading to the projection that by 2048 all United States citizens will be overweight or obese.

Local Problem: At a Chicago weight loss center, the Emotional Appetite Questionnaire screened 75 patients, revealing that 56% (N = 42) ate more during sadness, boredom, and loneliness, and 50.7% (N = 38) ate more during depression, indicating significant DAEE.

Methods: This quasi-experimental quality improvement project uses a pre- and post-evaluation …

Treatment And Diagnosis Of Pulmonary Emboli In Ct, Jacob Gardner

Student Research Poster Presentations 2024

This research project elaborates on the diagnosis and treatment of pulmonary emboli, and how computed tomography can provide a quick and accurate diagnosis. Statistics, symptoms, computed tomography pulmonary angiography protocol, and pulmonary emboli radiographic appearance are also discussed to provide information on how a diagnosis is achieved and which treatment is used. Pulmonary emboli are a life-threatening condition that, if untreated, can potentially be fatal. Pulmonary emboli are the third most frequently occurring cause of cardiovascular death behind a stroke and myocardial infarction. Deaths in the United States from pulmonary emboli are approximately 300,000 deaths per year. In addition, 5-10% …

Increasing The Efficacy Of Actinomycin D With Resveratrol In Aerodigestive Tract Cancers, Lukmon Morenikeji Raji

Theses, Dissertations and Capstones

Chemotherapy poses a significant challenge for cancer patients due to drug-associated toxicity, which often results from their effects on both healthy (normal) and cancerous cells. While various options aim to reduce toxicity and optimize beneficial effects, a comprehensive solution remains elusive. Cyclotherapy is one such approach developed to protect normal cells from the toxic effects of chemotherapy drugs. The basic principle underlying cyclotherapy is p53- dependent cell cycle arrest of normal cells while killing cancer cells via a p53-independent mechanism using a second drug. In our research, we investigated the inhibitory effects of a combination of two low-dose anticancer drugs, …

Dual Gallium Drug Treatment Against Carbapenem-Resistant Klebsiella Pneumoniae: Efficacy And Potential Mechanism(S) Of Action And Resistance, Zachary Scott, Seoung-Ryoung Choi, Bradley E. Britigan, Prabagaran Narayanasamy

Journal Articles: Pathology and Microbiology

Klebsiella pneumoniae (KLP) is a Gram-negative pathogen that can be highly antibiotic-resistant. Our group has worked with gallium-based compounds as a means of treating bacterial infections. Here the possible mechanism is investigated for dual therapy comprised of gallium nitrate (Ga(NO₃)₃) and gallium protoporphyrin (GaPP) on KLP. It is found that in vitro the combination of Ga(NO₃)₃ and GaPP is synergistic against KLP. The in vivo efficacy is of the dual therapy is additionally tested by treating pulmonary KLP infections in mice. Much greater effectiveness are observed in bacterial clearance and survival of mice …

Infectious Causes Of Cavernous Thrombosis: A Rare Case Of Mastoiditis, Koshin Ahmed, Suresh Antony

Central & West Texas GME Research Day 2024

No abstract provided.

Navigating Social Media In Healthcare: Implications, Challenges, And Guidelines For Physicians, Charles F. Clinton, Logan Brown, Bhuvaneshwari Muchandi, José Ignacio González Martínez, Candler Boyett

South Atlantic Division GME Research Day 2024

No abstract provided.

Increased Confidence And Knowledge Of Long-Acting Injectable Antipsychotics In Nursing, Improving The Timeliness To Intervention, Barbara Gracious, Marc Macaluso, Haryashpal Bhullar

South Atlantic Division GME Research Day 2024

No abstract provided.

Non-Commercial Ultrasound Transmission Gels: A Scoping Review, Edward Hu, Justin Le, Janae Fry, Taryn Hoffman, Martin Wegman

South Atlantic Division GME Research Day 2024

No abstract provided.

The Benefits Of Medical Tetrahydrocannabinol On Glaucoma, Hunter Kane

Theses, Dissertations and Capstones

Introduction: This paper explores the potential therapeutic benefits of medical Tetrahydrocannabinol (THC) on glaucoma management, particularly in terms of intraocular pressure (IOP) reduction, ocular blood flow, and symptom management. Glaucoma, characterized by increased IOP and progressive optic nerve damage, is a leading cause of irreversible blindness. Current treatments focus on IOP control but may have inadequate efficacy or intolerable side effects, necessitating alternative approaches such as medical THC.

Methods: The study hypothesis posited that medical THC could significantly reduce IOP, enhance ocular blood flow, and improve symptom management in glaucoma patients. To test this hypothesis, a literature review supplemented by …

The Measure Of Efficiency And Effectiveness When Using Artificial Intelligence (Ai) In Radiology, Jordan Watts

Theses, Dissertations and Capstones

Introduction: The use of artificial intelligence in radiology has helped radiologists identify patterns and abnormalities in medical images to diagnose and treat patients. Deep learning and machine learning algorithms have been used to assist physicians in detecting features that are not noticeable to the human eye. The FDA has approved almost 400 AI algorithms for radiology and estimated that the market for AI in medical imaging would grow from $21.48 billion in 2018 to $264.85 billion in 2028.

Purpose of the Study: The purpose of this research was to evaluate the use of artificial intelligence in radiology to determine its …

Individualizing Patient Education To Reduce Heart Failure Readmissions, Melissa M. Andersen

Doctor of Nursing Practice (DNP) Scholarly Projects - Archive

Background: Heart failure (HF) is a chronic condition with high readmission rates, often due to inadequate patient knowledge about home care and symptom management. Individualized patient education combined with standardized approaches could improve patient outcomes.

Objective: This project’s goal was to determine if using individual patient knowledge to create a personalized education along with standard HF education would improve patient HF knowledge, improve home management and decrease HF readmission rates.

Methods: This pilot quality improvement (QI) project was conducted in an acute care hospital using a convenience sample of 29 patients admitted due to a HF exacerbation using pre-posttest design. …

Wilson’S Disease: A Late-Onset Presentation Of Polyneuropathy, He Wang, Austin Goff, Nathan Lowe, Sanaz Siran

Far West Division GME Research Day 2024

No abstract provided.

The Sense Of Safety Theoretical Framework: A Trauma-Informed And Healing-Oriented Approach For Whole Person Care, Kurt C. Stange

Faculty Scholarship

Objectives: This research describes four aspects of the development of the Sense of Safety Theoretical Framework for whole person care: exploring the meaning of the phrase “sense of safety”—the whole person language; the range of human experience that impacts sense of safety—whole person scope; the dynamics that build sense of safety—the healing goals; and the personal and cross-disciplinary trauma-informed practitioner skills and attitudes that facilitate sense of safety. Methods: This qualitative participatory study was conducted in two phases. Researchers iteratively explored the concept of sense of safety using focus groups and semi-structured interviews. Overarching research questions were: “Does the transdisciplinary …

A Comparative Analysis Of Costs Associated With Assisted Reproductive Technology; Invitro Fertilization Of Singleton, Twin, And Multiple Gestations Compared To Non-Invitro Fertilization Singleton Gestations, Ruth Arthur-Asmah

MUSC Theses and Dissertations

This study examines IVF and non-IVF costs associated with prenatal, delivery, and postpartum care using claims data from Merative MarketScan Commercial and Encounter data from 2018-2020 to understand the costs associated with respective IVF singleton, twin, and multiple gestations, as compared to non-IVF singleton gestations. These patients identified as females at birth, were continuously enrolled in private insurance, and have not experienced termination of pregnancy. The Student T-test was performed on continuous variables, and logistic regression was performed on binary variables with the overall outcome variables being cost, IVF, and non-IVF, controlling for age. The cost data was gamma log …

Metarnn: Differentiating Rare Pathogenic And Rare Benign Missense Snvs And Indels Using Deep Learning, Fang Li, Zenan Sun, Ahmed Abdelhameed, Tiehang Duan, Laila Rasmy, Xinyue Hu, Jianping He, Yifang Dang, Jingna Feng, Jianfu Li, Yichen Wang, Tianchen Lyu, Naomi Braun, Si Pham, Michael Gharacholou, Delisa Fairweather, Degui Zhi, Jiang Bian, Cui Tao

Faculty, Staff and Student Publications

BACKGROUND: Effective management of dual antiplatelet therapy (DAPT) following drug-eluting stent (DES) implantation is crucial for preventing adverse events. Traditional prognostic tools, such as rule-based methods or Cox regression, despite their widespread use and ease, tend to yield moderate predictive accuracy within predetermined timeframes. This study introduces a new contrastive learning-based approach to enhance prediction efficacy over multiple time intervals.

METHODS: We utilized retrospective, real-world data from the OneFlorida + Clinical Research Consortium. Our study focused on two primary endpoints: ischemic and bleeding events, with prediction windows of 1, 2, 3, 6, and 12 months post-DES implantation. Our approach first …

Predicting Endothelium-Dependent Diastolic Function (Fmd)And Its Correlation With The Degree Of Coronary Artery Disease (Cad) And Plaque Vulnerability For Cardiovascular Events, Guangming Zhang, Jing Yang, Hanghang Xing, Hongning Yin, Guoqing Gu

Faculty, Staff and Student Publications

OBJECTIVE: This study aims to investigate the correlation between vascular endothelium-dependent diastolic function (FMD) and the degree of coronary artery disease (CAD), plaque vulnerability, and its predictive value for cardiovascular events.

METHODS: Initially, patients (n=100) who were admitted from January 2020 to January 2021 and intended to undergo percutaneous coronary intervention (PCI) were selected. Further, FMD in all patients was determined before the procedure and divided into a high-FMD group (≥4.2%) and a low-FMD group (

RESULTS: No significant differences were observed concerning general information, number of coronary arteries-associated branches, lesion type, involvement of the left main stem (LM), the …

Cancer Survivorship Care In The United States At Facilities Accredited By The Commission On Cancer, Julia Stal, Kimberly A. Miller, Timothy W. Mullett, Judy C. Boughey, Amanda B. Francescatti, Elizabeth Funk, Heidi Nelson, David R. Freyer

Markey Cancer Center Faculty Publications

IMPORTANCE Since 2021, American College of Surgeons Commission on Cancer (CoC) accreditation standards require providing a survivorship program for patients with adult-onset cancer treated with curative intent. Since more than 70% of all patients with cancer in the US are treated at CoC-accredited facilities, this presents an opportunity for a landscape analysis of survivorship care availability.

OBJECTIVE To determine the prevalence, types, and outcomes of cancer survivorship services at CoC-accredited facilities.

DESIGN, SETTING, AND PARTICIPANTS This survey study used an anonymous, online, cross-sectional survey conducted from May 4 to 25, 2023. Participants were CoC-accredited facilities in the US representing diverse …