Translational Medical Research Commons^™

Elucidating The Multi-Omics Of Early-Onset Colorectal Cancer, Jumanah Alshenaifi

Dissertations and Theses (Open Access)

The incidence and mortality rates of sporadic early-onset colorectal cancer have increased in recent decades, but there is no clear etiological basis for this trend. EOCRC is commonly defined as colon and rectal cancers diagnosed before the age of 50 years. The rising incidence of EOCRC has made it the second most common cancer and the third leading cause of cancer death in this age group. The rising incidence of EOCRC is also documented internationally in more than 20 countries across different continents. Clinically, EOCRC has a distinct, more aggressive clinical profile than LOCRC. While approximately 15% of EOCRC cases …

An Investigation Into The Potential Of Cell Therapies For Acute Myeloid Leukemia (Aml) Treatment, Amanda Eckstrom

Dissertations and Theses (Open Access)

Despite recent advances in acute myeloid leukemia (AML) treatment, curative rates remain poor with high rates of relapse and many patients are unable to tolerate the intensive chemotherapy standard of care regimen. Cell therapies have shown great success against hematologic malignancies but face several challenges including treatment-related toxicities and human-leukocyte antigen (HLA) matching. Natural killer (NK) cells and gamma delta (γδ) T cells offer alternative effector cell options for cell therapies that do not require HLA-matching and have shown low toxicity in previous studies. In this project, we sought to evaluate FT538 induced pluripotent stem cell-derived NK (iPSC-NK) and donor-derived …

Toward The Application Of Natural Language Processing In Electronic Health Record Analysis For Taxonomy Development, Latoya Mcdonald

All Dissertations

Electronic health records (EHRs) are pivotal resources for nurse practice because they increase the timeliness and reliability of patient information at the point of care and support access by multiple healthcare providers and the individual patients themselves. However, it is widely recognized that data extraction from EHRs is challenging due to the variability in the language used in clinical care notes and the lack of standardized terminology across healthcare systems. The broad objective of this dissertation is to develop taxonomy-based classification models for nursing care by applying feature engineering approaches to EHRs that include nursing care of ostomy patients following …

Jeremy Bentham Will See You Now, Kevin Suiter

Clinical Research in Practice: The Journal of Team Hippocrates

A discussion of remote patient monitoring through the lens of Jeremy Bentham's Panopticon

Clinical Decision-Making And Artificial Intelligence: The Role Of Large Language Models In Medicine, Richa Bhasin, Wassim El-Sayed, Kassim Salami, Mura Abdul-Nabi, Ahmed Elashmawy, M. Ellis Jaruzel Ii

Clinical Research in Practice: The Journal of Team Hippocrates

A clinical decision report using:

Goh E, Gallo R, Hom J, et al. Large Language Model Influence on Diagnostic Reasoning: A Randomized Clinical Trial. JAMA Netw Open. 2024;7(10):e2440969. https://doi.org/10.1001/jamanetworkopen.2024.40969

to explore the role of artificial intelligence in clinical settings.

Paradigm Shifts: Efficacy Of Cabg For Diabetic Patients With Coronary Artery Disease And Prior Pci, And The Utility Of Artificial Intelligence In Clinical Decision-Making, Jacob Mallad, Kevin Suiter, Mahdi Mahmoud, Sidney Caudell, Richard Lewandowski, Hazem Alata, Bethany Lyche, Zarin Kothari

Clinical Research in Practice: The Journal of Team Hippocrates

A clinical decision report using:

Thielmann M, Neuhäuser M, Knipp S, et al. Prognostic impact of previous percutaneous coronary intervention in patients with diabetes mellitus and triple-vessel disease undergoing coronary artery bypass surgery. J Thorac Cardiovasc Surg. 2007;134(2):470-476. https://doi.org/10.1016/j.jtcvs.2007.04.019

for a patient with prior coronary artery catheterization being referred for surgical intervention, and a clinician encountering a nonexistent clinical reference hallucinated by a large language model.

Paradigm Shifts In Medicine, David Meza, James Peter Meza

Clinical Research in Practice: The Journal of Team Hippocrates

Implications for history of science, scientific revolutions and paradigm shifts in the context of rapidly developing artificial intelligence.

Life Course Analysis: How Social Needs And Family Dynamics Impact Clinical Decision-Making, Vito Agrusa, Laila N. Abdallah, Bryen Turco

Clinical Research in Practice: The Journal of Team Hippocrates

The authors explore Life Course Analysis and how social needs (including pet care), changing demographics, and loneliness affect inpatient hospitalization and clinical decision making.

Off-Label Long-Term Use Of Phentermine For Weight Management, Monique Morin, Yamini Pandey, Sarah Bdeir, Rumyah Rafique, Taim-Allah Al-Jarrah, Ali Farhat

Clinical Research in Practice: The Journal of Team Hippocrates

A clinical decision report using:

Hendricks EJ, Greenway FL, Westman EC, Gupta AK. Blood pressure and heart rate effects, weight loss and maintenance during long-term phentermine pharmacotherapy for obesity. Obesity. 2011;19(12):2351-2360 https://doi.org/10.1038/oby.2011.94

for a patient struggling at the intersection of weight loss and financial instability.

Indeterminate Benefit Of Long-Term Beta-Blocker Use After Acute Myocardial Infarction For Some Patients, Logan S. Thayer, Khush Hussain, Nicholas Apostolakis, Gretchen Swift, Arifbillah Sarowar, Mohammad Al-Hadidi, Scott Yaekle

Clinical Research in Practice: The Journal of Team Hippocrates

A clinical decision report using:

Yndigegn T, Lindahl B, Mars K, et. al., Beta-blockers after myocardial infarction and preserved ejection fraction. N Engl J Med. April 7 2024;390:1372-1381. https://doi.org/10.1056/NEJMoa2401479

for a patient showing 55% left ventricular ejection fraction after myocardial infarction.

Tobacco Smoke Exposure Is A Driver Of Altered Oxidative Stress Response And Immunity In Head And Neck Cancer, Yang Li, Pedram Yadollahi, Fonma N Essien, Vasanta Putluri, Chandra Shekar R Ambati, Karthik Reddy Kami Reddy, Abu Hena Mostafa Kamal, Nagireddy Putluri, Lama M Abdurrahman, Maria E Ruiz Echartea, Keenan J Ernste, Akshar J Trivedi, Jonathan Vazquez-Perez, William H Hudson, William K Decker, Rutulkumar Patel, Abdullah A Osman, Farrah Kheradmand, Stephen Y Lai, Jeffrey N Myers, Heath D Skinner, Cristian Coarfa, Kwangwon Lee, Antrix Jain, Anna Malovannaya, Mitchell J Frederick, Vlad C Sandulache

Faculty, Staff and Student Publications

Background: Exposomes are critical drivers of carcinogenesis. However, how they modulate tumor behavior remains unclear. Extensive clinical data show cigarette smoke to be a key exposome that promotes aggressive tumors, higher rates of metastasis, reduced response to chemoradiotherapy, and suppressed anti-tumor immunity. We sought to determine whether smoke itself can modulate aggressive tumor behavior in head and neck squamous cell carcinoma (HNSCC) through reprogramming of the cellular reductive state.

Methods: Using established human and murine HNSCC cell lines and syngeneic mouse models, we utilized conventional western blotting, steady state and flux metabolomics, RNA sequencing, quantitative proteomics and flow cytometry to …

Socioeconomic And Demographic Factors In Genetic Testing Utilization Among Advanced Prostate Cancer Patients: A Retrospective Single-Institution Study, Alexandra T. Skowron Ms, Karen Childers, Courtney M. Rose Ms, Kyle C. Mcelyea Md, Avery K. Supernois Bs, Yousuf Hussain, Mohammed Baseer Ms, Sunita Ghosh Phd, Clara Hwang Md

Medical Student Research Symposium

Introduction

Germline genetic testing in patients with advanced prostate cancer (PCa) is underutilized. Socioeconomic and demographic factors are hypothesized to affect low rates of testing, but causality has not been established. This single institution, retrospective study aimed to understand what barriers may affect germline genetic testing for PCa patients.

Methods

The Henry Ford Health (HFH) tumor registry was queried for new diagnoses of stage 3, 4A and 4B PCa from 2017-2022. Census tract levels were assigned using patient addresses and neighborhood-based geocoding was completed for Median household income (gMHI) and Social vulnerability index (SVI). gMHI and SVI were divided into …

Longitudinal Changes In Aerodigestive Responses To Varying Nipple Properties In Infant Pigs, François D H Gould, Christopher Mayerl, Khaled Adjerid, Jessica Reibel, Nichole Charles, Chloe Edmonds, Rebecca Z German

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Coordination of respiration and swallowing is critical for survival in infant mammals and changes throughout infant maturation. Infants show sensorimotor feeding responses to changes in physical properties of nipples. Commercial nipples are promoted as improving aerodigestive coordination. However, it is unknown how nipple properties influence coordination of respiration and swallowing. Furthermore, how infant-nipple interactions change throughout maturation is not well understood. We designed and manufactured four silicone nipples of the same shape that varied in two parameters: nipple opening diameter and nipple stiffness. We used our validated infant pig model to test the impact of nipple parameters on aerodigestive coordination …

Strategies To Improve Antibody-Mediated Protection Against Herpes Simplex Virus Infections, Matthew D. Slein

Dartmouth College Ph.D Dissertations

No efficacious vaccine exists for herpes simplex virus and the global burden of disease remains high. Antibodies can serve as potent therapeutics to protect high risk populations such as neonates. Although rare, neonatal HSV (nHSV) infections can result in significant mortality and lifelong neurological morbidity even with antiviral therapy. While HSV-specific maternally derived antibodies significantly reduce the risk of neonatal disease in humans, the mechanisms by which they mediate protection have yet to be described. Using a mouse model of neonatal HSV (nHSV) infections we aimed to determine the mechanisms of antibody-mediated protection using monoclonal antibodies (mAbs) targeting two of …

Serum Metal Ion Levels In Patients Undergoing Revision Should Arthroplasty, Rishi Chatterji, Brandon Fisher, Avianna Elizabeth Arapovic, Yuying Xing, J Michael Wiater

Conference Presentation Abstracts

INTRODUCTION: Shoulder arthroplasty systems are transitioning towards more modular prosthesis options with the goal of reducing complication profiles and increasing range of motion. Modularity may increase the potential for fretting, corrosion, and subsequent release of metal ions. These events have been associated with adverse reactions in hip and knee arthroplasty, but not in the setting of revision shoulder arthroplasty. The purpose of this study was to identify associations between implant designs, metallurgy, patient characteristics, and serum metal ion levels in patients undergoing revision shoulder arthroplasty. METHODS: 51 patients that underwent revision shoulder arthroplasty were retrospectively reviewed based on prospectively collected …

Leveraging Large Language Models For Knowledge-Free Weak Supervision In Clinical Natural Language Processing, Enshuo Hsu, Kirk Roberts

Faculty, Staff and Student Publications

The performance of deep learning-based natural language processing systems is based on large amounts of labeled training data which, in the clinical domain, are not easily available or affordable. Weak supervision and in-context learning offer partial solutions to this issue, particularly using large language models (LLMs), but their performance still trails traditional supervised methods with moderate amounts of gold-standard data. In particular, inferencing with LLMs is computationally heavy. We propose an approach leveraging fine-tuning LLMs and weak supervision with virtually no domain knowledge that still achieves consistently dominant performance. Using a prompt-based approach, the LLM is used to generate weakly-labeled …

Gatad2b O-Glcnacylation Regulates Breast Cancer Stem-Like Potential And Drug Resistance, Giang Le Minh, Jessica Merzy, Emily Esquea, Nusaiba Ahmed, Riley Young, Ryan Sharp, Tejsi Dhameliya, Bernice Agana, Mi-Hye Lee, Jennifer Bethard, Susana Comte-Walters, Lauren Ball, Mauricio Reginato

Kimmel Cancer Center Faculty Papers

The growth of breast tumors is driven and controlled by a subpopulation of cancer cells resembling adult stem cells, which are called cancer stem-like cells (CSCs). In breast cancer, the function and maintenance of CSCs are influenced by protein O-GlcNAcylation and the enzyme responsible for this post-translational modification, O-GlcNAc transferase (OGT). However, the mechanism of CSCs regulation by OGT and O-GlcNAc cycling in breast cancer is still unclear. Analysis of the proteome and O-GlcNAcome, revealed GATAD2B, a component of the Nucleosome Remodeling and Deacetylase (NuRD) complex, as a substrate regulated by OGT. Reducing GATAD2B genetically impairs mammosphere formation, decreases expression …

Reconstitution Of Mirna-205 In Docetaxel Resistant Prostate Cancer Cells: A Nanotherapeutic Approach, Neeraj Chauhan, Eswara Naga Hanuma Kumar Ghali, Rahul Tiwari, Iris Enriquez, Rajasekhar Baru, Subhash C. Chauhan, Murali M. Yallapu

Research Symposium

Background: Prostate cancer (PrCa) is the second most diagnosed cancer and cause of death in men globally. Docetaxel (Dtxl) based first line chemotherapy is the main available therapeutic choice for PrCa patients. However, most (almost all) patients develop resistance to Dtxl treatment, making it difficult to treat such patients with no effective adjuvant therapy. Although cabazitaxel may be used to treat these patients, it is associated with many severe side effects including low white blood cells and allergic reactions. Therefore, finding an alternative strategy to reduce Dtxl resistance is of high importance for treating PrCa. miR-205 is a widely studied …

Developing Ship On-Chip Strategy Of Transporting Theranostic Radionuclides For Rapid And Efficient Radiopharmaceutical Production, Mai Lin, Robert Ta, Mark Mc Veigh, Joseph Lapka, Don Nolting, Leon Marcel Bellan, William Charlton, H. Charles Manning

Research Symposium

Introduction: Radiopharmaceuticals play a critical role in cancer diagnosis, staging, and therapy. Recent successes in radiotheranostics (which utilize targeted radiopharmaceutical pairs for both diagnosis and therapy) have led to improved outcomes in challenging clinical settings, such as neuroendocrine tumors and prostate cancer. Despite the tremendous potential, development of new radiopharmaceutical agents and widespread distribution is hampered by the extreme costs associated with production and delivery. Most hospitals require a substantial investment in facility and operational equipment for radiosynthesis that in turn limits the development of radiopharmaceuticals and their impact on precision medicine. Herein, we describe a simple and inexpensive microfluidic …

Roles Of Mir-223 In Platelet Function And High On-Treatment Platelet Reactivity: A Brief Report And Review, Shayan Askari, Lawrence E. Goldfinger

Cardeza Foundation for Hematologic Research

BACKGROUND: Platelets are highly enriched in microRNAs (miRNAs), which are genomically encoded 19-25 nucleotide non-coding RNAs that target complementary mRNAs through total or near-total base pairing. MiR-223 is among the most abundant miRNAs in human and murine platelets, but despite ongoing investigations in recent years, miR-223 roles in platelet physiology and its putative roles in high on-treatment platelet reactivity (HTPR) remain controversial, as studies showed varying findings.

OBJECTIVES: In the current hybrid review/report, we aim to compare studies that investigated miR-223 in platelet function and HTPR. Additionally, we briefly report our own findings on murine miR-223-deficient platelets.

METHODS: We have …