Translational Medical Research Commons^™

A Review Of Sutures And The Prospective Applications Of Nanofiber Technology In Suture Engineering, Hanna Brancaccio, Dominique Hassinger, Vincent Beachley

Rowan-Virtua Research Day

Introduction: Suturing is a method to close surgical or traumatic wounds to promote healing. The ideal suture should have high tensile strength that loses strength at the same rate as the healing tissue gains strength, be easy to handle and form secure knots, induce minimal inflammation, and stretch/recoil according to wound contraction. While there are suture materials available for use in various procedures that fulfill most requirements, no one suture possesses every desirable characteristic, and limitations are still prevalent. Nanofiber geometry has a well-known ability to modulate cell morphology, attachment, gene expression, extracellular matrix production, and macrophage polarization in …

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 …

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.

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 …

Detection Of Alteration In Carotid Artery Volumetry Using Standard-Of-Care Computed Tomography Surveillance Scans Following Unilateral Radiation Therapy For Early-Stage Tonsillar Squamous Cell Carcinoma Survivors: A Cross-Sectional Internally-Matched Carotid Isodose Analysis, Efstratios Koutroumpakis, Mohamed A Naser, Abdallah Sherif Radwan Mohamed, Salman A Eraj, Andrea Jarre, Jay C Shiao, Mona Kamal, Subha Perni, Jack P Phan, William H Morrison, Steven J Frank, G Brandon Gunn, Adam S Garden, Anita Deswal, Jun-Ichi Abe, David I Rosenthal, Elie Mouhayar, Clifton D Fuller

Faculty, Staff and Student Publications

Aim: This study leveraged standard-of-care CT scans of patients receiving unilateral radiotherapy (RT) for early tonsillar cancer to detect volumetric changes in the carotid arteries, and determine whether there is a dose-response relationship.

Methods: Disease-free cancer survivors (>3 months since therapy and age > 18 years) treated with intensity modulated RT for early (T1-2, N0-2b) tonsillar cancer with pre- and post-therapy contrast-enhanced CT scans available were included. Patients treated with definitive surgery, bilateral RT, or additional RT before the post-RT CT scan were excluded. Isodose lines from treatment plans were projected onto both scans, facilitating the delineation of carotid artery …

Characteristics And Outcomes Of Adults Hospitalized With Respiratory Syncytial Virus, Brian S. Shaw, Cara Slaton, Ian P. Murphy, Michael Mcalister, Daniel Egan, Kwabena Ayesu

The University of Louisville Journal of Respiratory Infections

Background: Respiratory syncytial virus (RSV) is a negative sense single-stranded RNA virus (ssRNA) that primarily causes respiratory infections in both children and older adults. We examined clinical characteristics and outcomes of hospitalized adult patients who tested positive for RSV.

Methods: This was a multicenter, retrospective, descriptive study that examined adult patients admitted with a positive RSV test over two years across eight hospitals in Orlando, Florida.

Results: A total of 120 patients were included, of which 88 (73%) were 60 years old and older. Overall, patients with RSV infection were caucasian (62%) with a median age of 70 years and …

Leveraging Clinical Standards To Improve The Translational Relevance Of Therapies For Experimental Spinal Cord Injury, Aaron L. Silverstein

Theses and Dissertations--Neuroscience

Efforts to improve treatment of spinal cord injury (SCI) often use animals to develop effective therapeutics, intending to improve the survival and the quality of life of persons with SCI. Over half of all SCIs in the United States occur at the cervical level and often cause locomotor deficits and life-threatening breathing dysfunction. Thus, my dissertation is focused on this important patient population.

After beginning with a description of translational research and surveying SCI from a clinical standpoint, I turned to describe experimental models of cervical SCI and more detailed neuroimmunological findings relevant to my work. Then, I conducted a …

Fabricating Silver-Ceria Polymer Nanocomposite Scaffolds For Biomedical Therapeutic Applications, Shreya S. Pawar

Honors Undergraduate Theses

Improper healing of bone fractures and limited regeneration of bone following bone tumor resection remain a prevalent complication worldwide. Long-term effects of this include joint instability, limited movement, and arthritis. Bone infections (osteomyelitis), reactive oxygen species (ROS) generation via excessive inflammation, and underlying conditions such as osteoporosis can contribute to suboptimal bone tissue regeneration. ROS accumulation stimulates osteoblast apoptosis, while promoting osteoclast differentiation. These processes inhibit mineralization and osteogenesis. Conventional therapeutics involve the utilization of drugs and bone grafts. However, these approaches pose limitations and can result in subsequent complications. Microbial infections, ROS accumulation, and excessive inflammations are factors that …

Effectiveness Of Fu's Subcutaneous Needling In Pain Management And Rehabilitation: A Narrative Review, Po-En Chiu, Chun-Chang Wu, De-Jian Lu, Zhonghua Fu, Li-Wei Chou

Rehabilitation Practice and Science

Fu’s Subcutaneous Needling (FSN) is a modern needling technique distinct from traditional acupuncture, primarily used for musculoskeletal pain, neuropathic conditions, and emerging applications in rehabilitation. FSN is also designated as a kind of dry needling focusing on deactivating myofascial trigger points. This review categorizes FSN-related studies into case reports, clinical trials, and animal studies, evaluating its therapeutic efficacy, safety, and mechanisms. Case reports suggest that FSN provides rapid pain relief and functional improvement, while clinical trials, including randomized controlled trials (RCTs), support its role in reducing pain and enhancing neuromuscular function despite limitations in sample size and protocol consistency. Animal …

Contributions Of Pathobiological And Translational Science To Understanding And Managing Ischemic Heart Disease: Progress, Impediments, And Future Directions, L Maximilian Buja

The Texas Heart Institute Journal

Key pathobiological components of ischemic heart disease have been identified as follows: (1) In 1970 to 1973, myocardial infarct size was found to be the primary determinant of prognosis after acute myocardial infarction (AMI); (2) in 1973 to 1989, vulnerable coronary artery plaques were found to predispose individuals to coronary plaque disruption and thrombosis, causing major AMI; (3) in 1972, timely coronary reperfusion was demonstrated to limit the size of evolving AMI but with risk of reperfusion injury; and (4) in 1986, myocardial conditioning was found to be a clinically significant modulator capable of delaying AMI progression. Promising cardioprotective strategies …

Defining The Peripheral Plasticity Of Nociceptive Afferents Following Spinal Cord Injury And Physical Therapy Intervention., Morgan Julianna Forston

Electronic Theses and Dissertations

The focus of this dissertation is to explore the peripheral plasticity of nociceptive afferents following spinal cord injury (SCI) and whether it is exacerbated or induced when physical therapy-based muscle stretching, a therapy we have shown to be detrimental to locomotor recovery in rodents, is implemented post-SCI. Chapter I provides a brief introduction on sensory afferents with particular emphasis on nociceptive afferents and their multifaceted role within the peripheral and central nervous systems. Chapter II describes SCI epidemiology and common sensory related complications that occur in patients as well and pharmaco- and physical therapies that are employed post-SCI. Chapter III …

Etanercept, Methotrexate, Or Combined Therapy For Improving Rheumatoid Arthritis Symptoms, Ajith Dupati

Clinical Research in Practice: The Journal of Team Hippocrates

A clinical decision report using:

van der Heijde D, Klareskog L, Rodriguez-Valverde V, et al. Comparison of etanercept and methotrexate, alone and combined, in the treatment of rheumatoid arthritis: two-year clinical and radiographic results from the TEMPO study, a double-blind, randomized trial. Arthritis Rheum. 2006;54(4):1063-1074. https://doi.org/10.1002/art.21655

for a patient with rheumatoid arthritis.

Use Of Empagliflozin As An Adjuvant Treatment For Obstructive Sleep Apnea For A Patient Who Has Not Seen A Physician In Over 40 Years, Andrew Demko

Clinical Research in Practice: The Journal of Team Hippocrates

A clinical decision report using:

Neeland IJ, Eliasson B, Kasai T, et al. The Impact of Empagliflozin on Obstructive Sleep Apnea and Cardiovascular and Renal Outcomes: An Exploratory Analysis of the EMPA-REG OUTCOME Trial. Diabetes Care. 2020;43(12):3007-3015. https://doi.org/10.2337/dc20-1096

for a patient with obstructive sleep apnea who has not seen a physician in over 40 years.

Avaren-Fc, A Novel Immunotherapeutic, Recruits Nk Cells In B16f10 Melanoma Tumor Tissue, Sreevatsa Vemuri, Katarina L Mayer, Nobuyuki Matoba

The Cardinal Edge

Melanoma is the fifth most common cancer in the US, with limited effective immunotherapeutic options available for patients. Avaren-Fc (AvFc) is a novel experimental immunotherapeutic agent with a unique “lectibody” property. It is capable of targeting cancer cells through the selective recognition of high mannose glycans, which are aberrantly overrepresented on the surface of malignant cells. Upon binding to cancer cells, AvFc can interact with circulating effector immune cells equipped with Fc receptors, such as natural killer (NK) cells to induce antibody-dependent cell-mediated cytotoxicity (ADCC) and kill the cancer cells. Previous work has shown that AvFc effectively induces ADCC activity …

Ansa Cervicalis-To-Phrenic Nerve Transfer: Technical Note With Potential Application For Diaphragmatic Reanimation In Patients With High Cervical Spinal Cord Injury, Jonathan Melnick, Mohammadali M. Shoja, Gary B. Schwartz

HCA-NSU MD Research Day

Objective. This study was conducted to determine whether utilization of the superior root of ansa cervicalis (SRAC) as the donor for phrenic nerve (PN) transfer is technically feasible. Background. In patients with high cervical spinal cord injury resulting in diaphragmatic paralysis, another donor, the spinal accessory nerve, has been used successfully to reinnervate the PN and restore diaphragmatic function. Methods. Eight neck sides underwent cadaveric surgery. The sternocleidomastoid muscle was retracted posteriorly, the SRAC and PN were isolated, and the SRAC was cut near its distal end and transposed to the ipsilateral PN as it crossed the anterior scalene muscle. …

The Importance Of Including Maternal Immune Activation In Animal Models Of Hypoxic-Ischemic Encephalopathy, Bailey Collins, Elise A. Lemanski, Elizabeth Wright-Jin

Department of Medicine Faculty Papers

Hypoxic-ischemic encephalopathy (HIE) is a perinatal brain injury that is the leading cause of cerebral palsy, developmental delay, and poor cognitive outcomes in children born at term, occurring in about 1.5 out of 1000 births. The only proven therapy for HIE is therapeutic hypothermia. However, despite this treatment, many children ultimately suffer disability, brain injury, and even death. Barriers to implementation including late diagnosis and lack of resources also lead to poorer outcomes. This demonstrates a critical need for additional treatments for HIE, and to facilitate this, we need translational models that accurately reflect risk factors and interactions present in …

Emerin Deficiency Drives Mcf7 Cells To An Invasive Phenotype, Emily Hansen, Christal Rolling, Matthew Wang, James M Holaska

Rowan-Virtua School of Osteopathic Medicine Departmental Research

During metastasis, cancer cells traverse the vasculature by squeezing through very small gaps in the endothelium. Thus, nuclei in metastatic cancer cells must become more malleable to move through these gaps. Our lab showed invasive breast cancer cells have 50% less emerin protein resulting in smaller, misshapen nuclei, and higher metastasis rates than non-cancerous controls. Thus, emerin deficiency was predicted to cause increased nuclear compliance, cell migration, and metastasis. We tested this hypothesis by downregulating emerin in noninvasive MCF7 cells and found emerin knockdown causes smaller, dysmorphic nuclei, resulting in increased impeded cell migration. Emerin reduction in invasive breast cancer …

The Enzymatic Regulation Of Contraction-Induced Toll-Like Receptor 4 Shedding From C2c12 Myotubes, Rebekah C. Gridley

Health, Exercise, and Sports Sciences ETDs

Stimulated contractions are shown to increase toll-like receptor 4 (TLR4) release from C2C12 myotubes in vitro. The purpose of this study was to determine if the release of TLR4 from myotubes is controlled by proteolytic membrane cleavage. A broad-spectrum metalloprotease inhibitor was used to test this hypothesis in a C2C12 cell culture model, and TLR4 concentrations in the cell culture supernatant were measured via enzyme-linked immunosorbent assay (ELISA) following stimulated myotube contractions.

ELISA analysis revealed TLR4 concentrations below the sensitivity threshold of the ELISA kit for all experimental conditions. In confirming the effectiveness of the electrical pulse stimulation (EPS) treatment, …

Keratin 17 Modulates The Immune Topography Of Pancreatic Cancer, Lyanne Delgado-Coka, Michael Horowitz, Mariana Torrente-Goncalves, Lucia Roa-Peña, Cindy Leiton, Mahmudul Hasan, Sruthi Babu, Danielle Fassler, Jaymie Oentoro, Ji-Dong Bai, Emanuel Petricoin, Lynn Matrisian, Edik Matthew Blais, Natalia Marchenko, Felicia Allard, Wei Jiang, Brent Larson, Andrew Hendifar, Chao Chen, Shahira Abousamra, Dimitris Samaras, Tahsin Kurc, Joel Saltz, Luisa Escobar-Hoyos, Kenneth Shroyer

Kimmel Cancer Center Faculty Papers

BACKGROUND: The immune microenvironment impacts tumor growth, invasion, metastasis, and patient survival and may provide opportunities for therapeutic intervention in pancreatic ductal adenocarcinoma (PDAC). Although never studied as a potential modulator of the immune response in most cancers, Keratin 17 (K17), a biomarker of the most aggressive (basal) molecular subtype of PDAC, is intimately involved in the histogenesis of the immune response in psoriasis, basal cell carcinoma, and cervical squamous cell carcinoma. Thus, we hypothesized that K17 expression could also impact the immune cell response in PDAC, and that uncovering this relationship could provide insight to guide the development of …

Novel Spirocyclic Dimer (Spid3) Displays Potent Preclinical Effects In Hematological Malignancies, Alexandria Eiken

Theses & Dissertations

Chronic lymphocytic leukemia (CLL) is a heterogeneous disease characterized by the accumulation of mature CD5⁺ B-cells in the peripheral blood, bone marrow, and secondary lymphoid tissues (e.g., spleen and lymph nodes).Despite the efficacy of front-line therapies, CLL is still an incurable disease, highlighting the need for development of novel therapeutics and further study of resistance mechanisms. Within the lymph node CLL tumor microenvironment (TME), there is an upregulation of gene signatures associated with B-cell receptor (BCR) and downstream nuclear factor kappa B (NF-κB) signaling compared to CLL cells found within the blood or bone marrow niches. Additionally, BCR signaling …

Therapeutic Effects Of Bet Protein Inhibition In B-Cell Malignancies And Beyond, Audrey L. Smith

Theses & Dissertations

Chronic lymphocytic leukemia (CLL) develops through a combination of intrinsic genetic defects, constitutively active survival/proliferation signaling pathways, and complex microenvironment interactions. Redundant tumor microenvironment (TME) immuno-suppressive mechanisms and epigenetic maintenance of terminal T-cell dysfunction also greatly hinder anti-tumor T-cell responses in CLL. Small-molecule agents targeting the B-cell receptor (BCR) pathway and anti-apoptotic proteins alone or in combination with chemo-immunotherapy have revolutionized the management of CLL, yet there is still a significant need for novel therapeutic strategies to yield durable tumor elimination. Bromodomain and extra-terminal domain (BET) proteins are epigenetic readers that bind to acetyl-lysine residues on histones to regulate gene …

Identifying The Molecular Determinants Of Lung Metastatic Adaptation In Prostate Cancer, Grace M. Waldron

Theses & Dissertations

Prostate cancer (PC) stands as the primary diagnosed cancer in men in the US at approximately 299,010 cases in 2024 and ranks second globally, posing a significant public health challenge. Clinical presentations vary widely, from indolent to aggressive forms, necessitating stage-specific treatment regimens. Understanding its metastatic nature is critical due to the impact of cancer cell dissemination on disease morbidity, with bone and visceral organs serving as key sites of metastasis. Despite bone metastasis being the most common site for metastasis, visceral metastases at sites such as the liver and lungs correlate with poorer survival, emphasizing the role of microenvironmental …

Applications Of Deep Learning With Detecting Intracranial Aneurysms On Ct Angiograms: A Literature Review, Christian Fang, Emily Wang

Rowan-Virtua Research Day

INTRODUCTION

Deep learning is a method of artificial intelligence involving progressively layered neural networks to extrapolate patterns from data to provide predictions. Moreover, given the arduous nature required for examining CT scans for intracranial aneurysms, discovering ways to expedite this process is beneficial. The use of deep learning to evaluate CT angiograms for intracranial aneurysms has been sparsely studied. This literature review aims to determine the accuracy and reliability of deep learning to analyze CT angiograms in patients suspected to have intracranial aneurysms.

METHODS

A qualitative review of literature using PubMed, SCOPUS, and EMBASE was conducted. Inclusion criteria comprised articles …

Evaluating C-Reactive Protein Associated Risk Of Cardiovascular Disease In Patients With Autism Spectrum Disorder, Brandon Cunha, Andrea Iannuzzelli, Rohan Mehra

Rowan-Virtua Research Day

This study examines the relationship between C-reactive protein (CRP) levels and cardiovascular disease (CVD) risk in 293 patients with Autism Spectrum Disorder (ASD) from the Rowan-Virtua Regional Integrated Special Needs Center (RISN Center). Baseline CRP values were gathered from EMR and evaluated for CVD risk. ASD patients have increased prevalence of CVD risk factors, and the literature demonstrates a strong relationship between CRP and CVD risk in this population. Patients were stratified by severity of ASD to investigate potential differences. Severe limitations in EMR data and overall sample size limited the generalizability and significance of this study. Larger scale studies …

Cord Blood-Derived Invariant Natural Killer T Cells As A Platform For Allogeneic Chimeric Antigen Receptor Cell Therapy, Maison Grefe

Dissertations and Theses (Open Access)

Chimeric antigen receptor (CAR) T cells have revolutionized the treatment of hematopoietic malignancies achieving >50% complete response rates in numerous refractory/relapsed B cell malignancies. However, there are challenges that hinder CAR-T efficacy and bar the broader use of this therapy in patients. One approach to address these challenges is to create a safe allogeneic CAR cell product by using cells that do not cause graft versus host disease (GvHD). Invariant natural killer T (iNKT) cells are an ideal candidate as they are restricted to the monomorphic CD1d protein in contrast to HLA restricted αβ-T cells and therefore are safe in …

Interrogating Therapeutic Resistance To Oncogenic Krasg12c-Based Therapies In Colorectal Cancer, Oluwadara Coker

Dissertations and Theses (Open Access)

Colorectal cancer is the second leading cause of cancer-related deaths and the third most common cancer in the United States. Although KRAS is mutated in 50% of patients with metastatic CRC (mCRC), it has historically been a challenging therapeutic target. The recent approval of novel covalent inhibitors selective for KRASG12C mutation have entered the clinic, which has not only marked a major milestone in cancer drug discovery but has also intensified efforts to directly target other KRAS mutations that have also successfully entered the clinic. However, treatment-associated resistance mechanisms have long threatened to attenuate clinical benefit through either adaptive or …

Multiple Daily Injection Insulin Regimen Is An Effective, And More Economical, Alternative To Continuous Insulin Infusion For Type 1 Diabetics, Julia Yee

Clinical Research in Practice: The Journal of Team Hippocrates

A clinical decision report using:

Heller S, White D, Lee E, et al. A cluster randomised trial, cost-effectiveness analysis and psychosocial evaluation of insulin pump therapy compared with multiple injections during flexible intensive insulin therapy for type 1 diabetes: the REPOSE Trial. Health Technol Assess. 2017 Apr;21(20):1-278. https://doi.org/10.3310/hta21200

for a patient with type 1 diabetes.

Avaren-Fc, A Novel Immunotherapeutic, Recruits Nk Cells In B16f10 Melanoma Tumor Tissue, Sreevatsa Vemuri, Katarina Mayer, Nobuyuki Matoba

Posters-at-the-Capitol

Melanoma is the fifth most common cancer in the US, with limited effective immunotherapeutic options available for patients. Avaren-Fc (AvFc) is a novel experimental immunotherapeutic agent with a unique “lectibody” property. It is capable of targeting cancer cells through the selective recognition of high mannose glycans, which are aberrantly overrepresented on the surface of malignant cells. AvFc can interact with circulating effector immune cells equipped with Fc receptors, such as natural killer (NK) cells to induce antibody-dependent cell-mediated cytotoxicity (ADCC) and kill cancer cells. Previous work has shown that AvFc effectively induces ADCC activity against B16F10 cancer cells in vitro …

The Splice Index As A Prognostic Biomarker Of Strength And Function In Myotonic Dystrophy Type 1, Marina Provenzano

Theses and Dissertations

Myotonic dystrophy type 1 (DM1) is a slowly progressive, multisystem disorder caused by a CTG repeat expansion in the DMPK 3’UTR that leads to global dysregulation of alternative splicing. The resulting decline in physical function is slow, and no reliable biomarkers exist for predicting disease progression; however, an RNA mis-splicing biomarker associated with weakness may have utility in predicting functional outcomes. Here we validate the Splice Index (SI) as a potential biomarker of DM1-associated strength and function. Muscle biopsies of the tibialis anterior were collected from DM1-affected individuals at baseline (n = 46) and 3-months (n = 34), along with …

Developing Radiosensitizers To Enhance Radiotherapy In Treating Gastroenteropancreatic Neuroendocrine Tumor, Zeta Chow

Theses and Dissertations--Clinical and Translational Science

Gastroenteropancreatic Neuroendocrine Tumor (GEP-NET) is a heterogeneous group of malignancies arising from multipotent neuroendocrine stem cells in the gastrointestinal tract. The incidence of GEP-NET continues to rise, possibly due to the advancement of imaging and biomarkers available for diagnosis. However, even though the majority of patients are diagnosed with low-grade and localized disease, a significant percentage of patients present with advanced-stage metastatic disease with poor prognosis in months to a few years. These advanced-stage GEP-NET patients can also present with a variety of debilitating symptoms that significantly impact their quality of life. The role of palliative-intent surgery is limited, and …