Medical Specialties Commons^™

Immune Checkpoint Therapy Combinations In Adult Advanced Mit Family Translocation Renal Cell Carcinomas, Omar Alhalabi, Jonathan Thouvenin, Sylvie Négrier, Yann-Alexandre Vano, Luca Campedel, Elshad Hasanov, Ziad Bakouny, Andrew W Hahn, Mehmet Asim Bilen, Pavlos Msaouel, Toni K Choueiri, Srinivas R Viswanathan, Kanishka Sircar, Laurence Albiges, Gabriel G Malouf, Nizar M Tannir

Faculty, Staff and Student Publications

Background: There remains a paucity of data regarding the efficacy of immune checkpoint therapy (ICT) combinations ± vascular endothelial growth factor (VEGF) targeted therapy (TT) in translocation renal cell carcinoma (tRCC).

Methods: This is a retrospective study of patients with advanced tRCC treated with ICT combinations at 11 centers in the US, France, and Belgium. Only cases with confirmed fluorescence in situ hybridization (FISH) were included. Objective response rates (ORR) and progression-free survival (PFS) were assessed by RECIST, and overall survival (OS) was estimated by Kaplan-Meier methods.

Results: There were 29 patients identified with median age of 38 (21-70) years, …

Integrative Molecular Subtypes Of Acute Myeloid Leukemia, Qianxing Mo, Seongseok Yun, David A Sallman, Nicole D Vincelette, Guang Peng, Ling Zhang, Jeffrey E Lancet, Eric Padron

Faculty, Staff and Student Publications

No abstract provided.

Impact Of Early Relapse Within 24 Months After First-Line Systemic Therapy (Pod24) On Outcomes In Patients With Marginal Zone Lymphoma: A Us Multisite Study, Narendranath Epperla, Rina Li Welkie, Pallawi Torka, Geoffrey Shouse, Reem Karmali, Lauren Shea, Andrea Anampa-Guzmán, Timothy S Oh, Heather Reaves, Montreh Tavakkoli, Kathryn Lindsey, Irl Brian Greenwell, Emily Hansinger, Colin Thomas, Sayan Mullick Chowdhury, Kaitlin Annunzio, Beth Christian, Stefan K Barta, Praveen Ramakrishnan Geethakumari, Nancy L Bartlett, Alex F Herrera, Natalie S Grover, Adam J Olszewski

Department of Medicine Faculty Papers

Progression of disease within 24 months (POD24) from diagnosis in marginal zone lymphoma (MZL) was shown to portend poor outcomes in prior studies. However, many patients with MZL do not require immediate therapy, and the time from diagnosis-to-treatment interval can be highly variable with no universal criteria to initiate systemic therapy. Hence, we sought to evaluate the prognostic relevance of early relapse or progression within 24 months from systemic therapy initiation in a large US cohort. The primary objective was to evaluate the overall survival (OS) in the two groups. The secondary objective included the evaluation of factors predictive of …

Dna Supercoiling-Induced Shapes Alter Minicircle Hydrodynamic Properties, Radost Waszkiewicz, Maduni Ranasinghe, Jonathan M Fogg, Daniel J Catanese, Maria L Ekiel-Jeżewska, Maciej Lisicki, Borries Demeler, Lynn Zechiedrich, Piotr Szymczak

Faculty, Staff and Students Publications

DNA in cells is organized in negatively supercoiled loops. The resulting torsional and bending strain allows DNA to adopt a surprisingly wide variety of 3-D shapes. This interplay between negative supercoiling, looping, and shape influences how DNA is stored, replicated, transcribed, repaired, and likely every other aspect of DNA activity. To understand the consequences of negative supercoiling and curvature on the hydrodynamic properties of DNA, we submitted 336 bp and 672 bp DNA minicircles to analytical ultracentrifugation (AUC). We found that the diffusion coefficient, sedimentation coefficient, and the DNA hydrodynamic radius strongly depended on circularity, loop length, and degree of …

Elucidating The Impact Of Sos-Response Timing In On Escherichia Coli Survival Following Treatment With Fluoroquinolone Topoisomerase Inhibitors, Stephanie Schofield

Honors Scholar Theses

Antibiotic treatment failure is a public health crisis, with a 2019 report stating that roughly 35,000 deaths occur in the United States yearly due to bacterial infections that are unresponsive to antibiotics (1). One complication in the treatment of bacterial infection is antibiotic persistence which further compromises our battle to effectively treat infection. Bacterial persisters can exist in clonal bacterial cultures and can tolerate antibiotic treatment by undergoing reversible phenotypic changes. They can survive drug concentrations that their genetically identical kin cannot. Some persisters remain in a slow growing state and are difficult to target with current antibiotics. A specific …

Development Of Combination Therapy Strategies To Treat Cancer Using Dihydroorotate Dehydrogenase Inhibitors, Nicholas Mullen

Theses & Dissertations

Cancer cells require supraphysiologic levels of nucleotide triphosphates to fuel their malignant behaviors, including uncontrolled proliferation, immune evasion, metastasis, and therapy resistance. This requirement is met by hyperactive flux through the de novo pyrimidine and de novo purine pathways. Dihydroorotate dehydrogenase (DHODH) is an essential enzyme in the de novo pyrimidine pathway that can be targeted by FDA approved and experimental drug compounds. A robust body of preclinical evidence, encompassing hundreds of independent studies over several decades, demonstrates impressive activity of DHODH inhibitors in animal models of cancer. Paradoxically, however, all clinical trials to date have failed to demonstrate efficacy …

Targeting The Cxcr1/2 Axis In Pancreatic Ductal Adenocarcinoma, Caitlin Molczyk

Theses & Dissertations

Pancreatic ductal adenocarcinoma (PDAC) is notoriously challenging to diagnose and treat. This tumor has an aggressive phenotype and benign clinical features until severe disease dissemination, which makes it too late to eradicate. Although it is only the 10th most common cancer in the United States, it is the fourth leading cause of cancer-related deaths. The treatment options are complicated further due to tumor heterogeneity, meaning not all tumor cells are in the same state phenotypically or epigenetically. They also express cytokines, chemokines, and receptors differently. Here we explore the usage of CXCR1 and CXCR2 and their ligands in PDAC tumor …

Higher Dose Corticosteroids In Patients Admitted To Hospital With Covid-19 Who Are Hypoxic But Not Requiring Ventilatory Support (Recovery): A Randomised, Controlled, Open-Label, Platform Trial, Recovery Collaborative Group

Faculty, Staff and Student Publications

BACKGROUND: Low-dose corticosteroids have been shown to reduce mortality for patients with COVID-19 requiring oxygen or ventilatory support (non-invasive mechanical ventilation, invasive mechanical ventilation, or extracorporeal membrane oxygenation). We evaluated the use of a higher dose of corticosteroids in this patient group.

METHODS: This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]) is assessing multiple possible treatments in patients hospitalised for COVID-19. Eligible and consenting adult patients with clinical evidence of hypoxia (ie, receiving oxygen or with oxygen saturation

FINDINGS: Between May 25, 2021, and May 13, 2022, 1272 patients with COVID-19 and hypoxia receiving no oxygen …

Letter From The Editor: Oata Special Issue 2023, Sara Stiltner

Journal of Sports Medicine and Allied Health Sciences: Official Journal of the Ohio Athletic Trainers Association

Letter from the Editor

Thank you for viewing the OATA Annual Meeting Special Issue of the

Journal of Sports Medicine and Allied Health Sciences:

The Official Journal of the OATA.

This is our 9^th year working in conjunction with the

OATA Annual Meeting to open a new volume of the JSMAHS.

This special issue would not be possible without the Managing Editor, Cole Dearing and the OATA Research and Grant Subcommittee Members who spend time and pour in effort to provide highly critiqued blinded peer review of the OATA Free Communication Abstracts. Those members include: Stacey Busser, Akron University, …

Perceptions Among Athletic Trainers’ Education In Treating Athletes With Attention Deficit Hyperactivity And Autism Disorders, Juliette Mueller, Audrey Wagstaff, Jennifer Walker

Journal of Sports Medicine and Allied Health Sciences: Official Journal of the Ohio Athletic Trainers Association

OBJECTIVE

The purpose of this study was to investigate the education and preparedness of athletic trainers when caring for athletes with Attention.Deficit.Hyperactivity.Disorder (ADHD) and or Autism Spectrum Disorder (ASD).

Athletic Trainers Knowledge And Practices For Sudden Cardiac Death, Brent Mcclure, Chyrsten Gessel, Brittany Peppel

Journal of Sports Medicine and Allied Health Sciences: Official Journal of the Ohio Athletic Trainers Association

OBJECTIVE

Sudden cardiac death (SCD) is one of the leading causes of death in athletics, despite athletic trainers working as first responders for athletic events. The purpose of this study was to assess athletic trainers’ knowledge of SCD, and to analyze perceptions regarding evidence-based practice. This study aimed to answer how the NATA position statement has impacted athletic trainers practice, and to identify potential limitations in implementing best practice.

Unreported Concussions Within Law Enforcement Officers, Bailee Faulkner, Jennifer Walker, Audrey Wagstaff

Journal of Sports Medicine and Allied Health Sciences: Official Journal of the Ohio Athletic Trainers Association

OBJECTIVE

Understand the degree to which concussions go unreported among members of the Law Enforcement community.

Perceived Knowledge And Confidence Of Social Determinants Of Health In College And Secondary School Athletic Trainers, Lauren Redfern, Chyrsten Gessel, Elena Robinson

Journal of Sports Medicine and Allied Health Sciences: Official Journal of the Ohio Athletic Trainers Association

OBJECTIVE

For most athletes, their athletic trainer is the healthcare provider with whom they interact the most while for others, ATs are the only health care professionals they interact with. It is crucial that ATs can assess and implement strategies that account for SDH in athletes. The purpose of this study was to explore the relationship between the number of years certified as an athletic trainer in the college and secondary school settings and perceived knowledge of factors and confidence in the implementation of interventions to address social determinants of health (SDH) when treating patients.

Usage And Influence Of Dietary Supplementation Amongst Adolescent Athletes, Allison Harlow, Jennifer Walker, Aubrey Wagstaff

Journal of Sports Medicine and Allied Health Sciences: Official Journal of the Ohio Athletic Trainers Association

OBJECTIVE The purpose of this study was to investigate the use of dietary supplements or ergogenic aids amongst high school athletes.

The Effect Of Instrument Assisted Soft Tissue Mobilization On Improving Joint Range Of Motion In Active Individuals: A Critically Appraised Topic, Cole E. Dearing, Andrea Cripps, Jenny Toonstra

Journal of Sports Medicine and Allied Health Sciences: Official Journal of the Ohio Athletic Trainers Association

CLINICAL SCENARIO

In all activities that require physical movement, whether in athletics or in other daily tasks, it is important for joints to have adequate range of motion and flexibility. Soft tissue restrictions are very common pathologies in healthcare. Although a decrease in myofascial range of motion can arise from a variety of reasons such as biomechanical deformities, autoimmune diseases, or age, it is often caused by overtraining or musculoskeletal injuries in active populations. Instrument assisted soft tissue mobilization techniques are gaining popularity to assist in treating various soft tissue injuries and musculoskeletal pathologies. The belief is that by applying …

Rates Of Burnout Among Collegiate Athletic Trainers During The Covid-19 Pandemic, Lauren Linn, Jennifer Walker, Audrey Wagstaff

Journal of Sports Medicine and Allied Health Sciences: Official Journal of the Ohio Athletic Trainers Association

OBJECTIVE

The purpose of this study was to investigate the effects of COVID-19 related tasks on the rates of burnout in athletic trainers practicing in the collegiate setting.

Efficacy Of Corrective Exercise On Improving Functional Movement Within The Tactical Population: A Critically Appraised Topic, Sara Stiltner, Adam J. Thompson, Andrea Cripps

Journal of Sports Medicine and Allied Health Sciences: Official Journal of the Ohio Athletic Trainers Association

CLINICAL SCENARIO

Police, fire, emergency medical services, and military personnel encompass a tactical population that is considered an emerging setting in athletic training.Due to the occupational demands within this demographic, these patients are experiencing musculoskeletal injuries and injuries that withhold them from career duties at an alarming rate. One of the main contributors to the incidence of musculoskeletal injury is a lack of functional movement.^1-3 Incorporating corrective functional movement programs should be a primary goal in treating tactical populations.

The Value Of The Vestibular/Ocular Motor Screening (Voms) In Evaluating Adolescent Patients With Concussions, Laura Harris, Kirstin Antonaros, Hayley Cole, Patrick Daniels, Kurtis Gould, Trent Ivey, Alexa Lewis, Alexis Maxwell, Paul Miles

Journal of Sports Medicine and Allied Health Sciences: Official Journal of the Ohio Athletic Trainers Association

OBJECTIVE

To determine the VOMS can differentiate between typical and protracted recoveries in adolescent patients.

A Comparison Of Skill Retention From Two Instructor-Led Bls Cpr Courses, Michelle R. Wilson, Christine Liebrecht

Journal of Sports Medicine and Allied Health Sciences: Official Journal of the Ohio Athletic Trainers Association

OBJECTIVE

CPR skill retention is vitally important on successful resuscitation outcomes. This study examined college students’ retention of Adult CPR skills 6 months following participation in an instructor-led CPR course presented in two different formats.

Injury Rates In Fly-Fishing: An Analysis Of Contributing Factors, Andrea Cripps, Jason Smith, Ian Thomas, Trent Griner

Journal of Sports Medicine and Allied Health Sciences: Official Journal of the Ohio Athletic Trainers Association

OBJECTIVE

The sport of fly-fishing has experienced significant growth since the start of the COVID-19 pandemic. There is very little literature available to quantify injuries associated with the sport of fly-fishing. Previous injury surveillance studies demonstrated certain casting styles and equipment may lead to upper extremity pain or injury. The purpose of this study was to evaluate factors that can contribute to injuries that occur while participating in the sport of fly-fishing.

Attrition And Retention Factors Of Dual-Appointment Athletic Trainers, Elizabeth A. Starns, Mackenzie Starns

Journal of Sports Medicine and Allied Health Sciences: Official Journal of the Ohio Athletic Trainers Association

OBJECTIVE

The factors leading to athletic trainer (AT) job attrition and retention and the impact and on the profession regularly appear in athletic training literature and research. This literature and research found work-life balance, including work-family conflict, burnout, and work factors, such as hours worked and compensation, to be the primary attrition and retention factors for athletic trainers that are currently in traditional athletic training roles or have left the profession^1-14. Similar to athletic trainers, research shows university faculty job attrition, regardless of specialty, is caused by work-life balance, specifically work-family conflict. However, unlike athletic trainers, faculty attrition …

The Effect Of Fatigue On Lower Extremity Joint Kinematics And Performance, Shelley Payne, Sarah Alloto, Joe Wilkins, Ashley Simons

Journal of Sports Medicine and Allied Health Sciences: Official Journal of the Ohio Athletic Trainers Association

OBJECTIVE

ACL injuries are multifactorial in nature meaning they can be the result of faulty biomechanics, individual genetic predisposition, or environmental factors (Alentorn- Geli et al., 2009). A focus of most healthcare professionals including physical therapists and athletic trainers includes the screening for preventable risk factors for non- contact ACL injuries. Preventable risk factors include asymmetry between a person’s limbs, decreased hamstring strength, increased muscle fatigue, decreased landing angle of hip and knee Tlexion, increased valgus landing, and lack of Tlexibility in the hip internal rotators (Brophy, 2021). Given the short and long-term negative consequences of an ACL injury, it …

Differential Degeneration Of Neurons In A Mouse Model Of Canavan Disease, Vibha Chauhan, Quy Nguyen, Jeremy Francis, Paola Leone

Rowan-Virtua Research Day

Canavan disease (CD) is an inherited leukodystrophy caused by inactivating mutations to the glial enzyme aspartoacylase (ASPA). ASPA catabolizes neuronal N-acetylaspartate (NAA) into free acetate and aspartate and loss of this function results in the chronic elevation of non-catabolized NAA and the failure of developmental myelination. Elevated NAA is thought to cause damage to myelin and myelin-producing cells (oligodendrocytes, but the viability of neurons in CD is relatively unexplored. We compare here the progressive degeneration of neurons in two regions of the CD mouse brain, the thalamus and the cortex, distinguished by differing degrees of vacuolation, and show that the …

Swallowing Disrupts Tongue-Jaw Coordination During Chewing In A Rat Model Of Parkinson's Disease, Meejan Palhang, N. Charles, Francois Gould

Rowan-Virtua Research Day

The primary motor symptoms of Parkinson’s disease, including bradykinesia, rigidity, and tremor, are associated with difficulties regulating transitions between motor behaviors due to basal ganglia dysfunction. Chewing and swallowing, which are disordered in most patients with Parkinson’s disease, are two complex motor behaviors which overlap in time and share some neuromuscular components. The objective of this study is to identify how Parkinson’s disease affects the coordination of chewing and swallowing. We hypothesize that as a result of impaired regulation of shift between motor patterns, chewing cycles that occur with a swallow will be more affected that chewing cycles occurring in …

Extravasated Brain-Reactive Autoantibodies Perturb Neuronal Surface Protein Expression In Alzheimer's Pathology, Wardah Bajwa, Mary Kosciuk, Randel L. Swanson, Anuradha Krishnan, Venkat Venkataraman, Robert Nagele, Nimish Acharya

Rowan-Virtua Research Day

Background: Increased blood-brain barrier (BBB) permeability is reported in both the neuropathological and in vivo studies in both Alzheimer’s Disease (AD) and age matched cognitively normal, no cognitive impairment (NCI), subjects. Impaired BBB allows various vascular components such as immunoglobulin G (IgG) to extravasate into the brain and specifically bind to various neuronal surface proteins (NSP), also known as brain reactive autoantibodies (BrABs). This interaction is predicted to further enhance deposition of amyloid plaques.

Hypothesis: Interaction between extravasated BrABs and its cognate NSPs lower the expression of that NSPs in AD patients.

Methods: We selected Western blotting technique to study …

Loss Of Lgr5 Through Therapy-Induced Downregulation Or Gene Ablation Is Associated With Resistance And Enhanced Met-Stat3 Signaling In Colorectal Cancer Cells, Tressie A Posey, Joan Jacob, Ashlyn Parkhurst, Shraddha Subramanian, Liezl E Francisco, Zhengdong Liang, Kendra S Carmon

Faculty, Staff and Student Publications

Leucine-rich repeat-containing, G protein-coupled receptor 5 (LGR5) is highly expressed in colorectal cancer and cancer stem cells (CSCs) that play important roles in tumor initiation, progression, and metastasis. Loss of LGR5 has been shown to enhance therapy resistance. However, the molecular mechanisms that mediate this resistance remain elusive. In this study, we demonstrate conversion of LGR5+ colorectal cancer cells to an LGR5- state in response to chemotherapy, LGR5- targeted antibody-drug conjugates (ADCs), or LGR5 gene ablation led to activation of STAT3. Further investigation revealed increased STAT3 activation occurred as a result of increased mesenchymal epithelial transition (MET) factor receptor activity. …

Insights Into The Formation And Diversification Of A Novel Chiropteran Wing Membrane From Embryonic Development, Neal Anthwal, Daniel J Urban, Alexa Sadier, Risa Takenaka, Simon Spiro, Nancy Simmons, Richard R Behringer, Chris J Cretekos, John J Rasweiler, Karen E Sears

Faculty, Staff and Student Publications

BACKGROUND: Through the evolution of novel wing structures, bats (Order Chiroptera) became the only mammalian group to achieve powered flight. This achievement preceded the massive adaptive radiation of bats into diverse ecological niches. We investigate some of the developmental processes that underlie the origin and subsequent diversification of one of the novel membranes of the bat wing: the plagiopatagium, which connects the fore- and hind limb in all bat species.

RESULTS: Our results suggest that the plagiopatagium initially arises through novel outgrowths from the body flank that subsequently merge with the limbs to generate the wing airfoil. Our findings further …

Twas_Sim, A Python-Based Tool For Simulation And Power Analysis Of Transcriptome-Wide Association Analysis, Xinran Wang, Zeyun Lu, Arjun Bhattacharya, Bogdan Pasaniuc, Nicholas Mancuso

Faculty, Staff and Student Publications

Genome-wide association studies (GWASs) have identified numerous genetic variants associated with complex disease risk; however, most of these associations are non-coding, complicating identifying their proximal target gene. Transcriptome-wide association studies (TWASs) have been proposed to mitigate this gap by integrating expression quantitative trait loci (eQTL) data with GWAS data. Numerous methodological advancements have been made for TWAS, yet each approach requires ad hoc simulations to demonstrate feasibility. Here, we present twas_sim, a computationally scalable and easily extendable tool for simplified performance evaluation and power analysis for TWAS methods.

Software and documentation are available at https://github.com/mancusolab/twas_sim.

Usp36 Promotes Tumorigenesis And Drug Sensitivity Of Glioblastoma By Deubiquitinating And Stabilizing Alkbh5, Guoqiang Chang, Gloria S Xie, Li Ma, Peng Li, Linlin Li, Hope T Richard

Faculty, Staff and Student Publications

Background: ALKBH5 is aberrantly activated and exerts critical roles in facilitating the development of glioblastoma. However, the underlying activation mechanism by which ALKBH5 protein is increased in glioblastoma is not completely understood. Our study aimed to elucidate the signaling pathways involved in mediating ALKBH5 protein stability.

Methods: The contribution of deubiquitinating enzymes (DUB) to the fluctuation of ALKBH5 protein expression was globally profiled with western blot analysis. Mass spectrometry and immunoprecipitation were performed to identify the USP36 and ALKBH5 interaction. The effects of USP36 on the stability of ALKBH5 were detected with in vivo and in vitro ubiquitination assays. Cell …

Igfbp2 Expressing Midlobular Hepatocytes Preferentially Contribute To Liver Homeostasis And Regeneration, Yu-Hsuan Lin, Yonglong Wei, Qiyu Zeng, Yunguan Wang, Chase A Pagani, Lin Li, Min Zhu, Zixi Wang, Meng-Hsiung Hsieh, Natasha Corbitt, Yu Zhang, Tripti Sharma, Tao Wang, Hao Zhu

Faculty, Staff and Student Publications

Although midlobular hepatocytes in zone 2 are a recently identified cellular source for liver homeostasis and regeneration, these cells have not been exclusively fate mapped. We generated an Igfbp2-CreER knockin strain that specifically labels midlobular hepatocytes. During homeostasis over 1 year, zone 2 hepatocytes increased in abundance from occupying 21%-41% of the lobular area. After either pericentral injury with carbon tetrachloride or periportal injury with 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC), IGFBP2+ cells replenished lost hepatocytes in zones 3 and 1, respectively. IGFBP2+ cells also preferentially contributed to regeneration after 70% partial hepatectomy, as well as liver growth during pregnancy. Because IGFBP2 labeling increased …