Medical Specialties Commons^™

Mammographic Density Mediates The Protective Effect Of Early-Life Body Size On Breast Cancer Risk, Marina Vabistsevits, George Davey Smith, Tom G Richardson, Rebecca C Richmond, Weiva Sieh, Joseph H Rothstein, Laurel A Habel, Stacey E Alexeeff, Bethan Lloyd-Lewis, Eleanor Sanderson

Faculty, Staff and Student Publications

The unexplained protective effect of childhood adiposity on breast cancer risk may be mediated via mammographic density (MD). Here, we investigate a complex relationship between adiposity in childhood and adulthood, puberty onset, MD phenotypes (dense area (DA), non-dense area (NDA), percent density (PD)), and their effects on breast cancer. We use Mendelian randomization (MR) and multivariable MR to estimate the total and direct effects of adiposity and age at menarche on MD phenotypes. Childhood adiposity has a decreasing effect on DA, while adulthood adiposity increases NDA. Later menarche increases DA/PD, but when accounting for childhood adiposity, this effect is attenuated. …

Impact Of Renal Cell Carcinoma Molecular Subtypes On Immunotherapy And Targeted Therapy Outcomes, Renée Maria Saliby, Chris Labaki, Tejas R Jammihal, Wanling Xie, Maxine Sun, Valisha Shah, Eddy Saad, M Harry Kane, Soki Kashima, Katherine Sadak, Talal El Zarif, Deepak Poduval, Robert J Motzer, Thomas Powles, Brian I Rini, Laurence Albiges, Sumanta K Pal, Bradley A Mcgregor, Rana R Mckay, Sabina Signoretti, Eliezer M Van Allen, Sachet A Shukla, Toni K Choueiri, David A Braun

Faculty, Staff and Student Publications

Saliby et al. show that a machine learning approach can accurately classify clear cell renal cell carcinoma (RCC) into distinct molecular subtypes using transcriptomic data. When applied to tumors biospecimens from the JAVELIN Renal 101 (JR101) trial, a benefit is observed with immune checkpoint inhibitor (ICI)-based therapy across all molecular subtypes.

The Crosstalk Between Macrophages And Cancer Cells Potentiates Pancreatic Cancer Cachexia, Mingyang Liu, Yu Ren, Zhijun Zhou, Jingxuan Yang, Xiuhui Shi, Yang Cai, Alex X Arreola, Wenyi Luo, Kar-Ming Fung, Chao Xu, Ryan D Nipp, Michael S Bronze, Lei Zheng, Yi-Ping Li, Courtney W Houchen, Yuqing Zhang, Min Li

Faculty, Staff and Student Publications

With limited treatment options, cachexia remains a major challenge for patients with cancer. Characterizing the interplay between tumor cells and the immune microenvironment may help identify potential therapeutic targets for cancer cachexia. Herein, we investigate the critical role of macrophages in potentiating pancreatic cancer induced muscle wasting via promoting TWEAK (TNF-like weak inducer of apoptosis) secretion from the tumor. Specifically, depletion of macrophages reverses muscle degradation induced by tumor cells. Macrophages induce non-autonomous secretion of TWEAK through CCL5/TRAF6/NF-κB pathway. TWEAK promotes muscle atrophy by activating MuRF1 initiated muscle remodeling. Notably, tumor cells recruit and reprogram macrophages via the CCL2/CCR2 axis …

Unveiling The Nexus Of Cellular Quality Control: Exploring The Interplay Between Ribosome-Associated Protein Quality Control And Mitochondrial Quality Control Pathways, Foozhan Tahmasebinia

Biological Sciences Theses and Dissertations

In eukaryotic cells, the intricate interplay between cellular quality control mechanisms is crucial for maintaining homeostasis and safeguarding the integrity of vital processes, spanning from macromolecule synthesis to the renewal of entire cellular organelles.

Disruption of these networks can lead to severe diseases such as metabolic disorders, underscoring the interconnected nature and feedback control mechanisms inherent in biological systems, including cellular quality control systems. This interconnectedness extends to the intricate communication between organelles, enabling coordinated functioning and adaptation to changing cellular conditions, particularly in response to stressors.

While the exact mechanisms governing these communications within cellular quality control systems remain …

Parental Factors Associated With Covid-19 Vaccine Uptake For Children Over 5 Years Of Age In Texas, Paula M Cuccaro, Jihye Choi, Yordanos M Tiruneh, Journey Martinez, Jing Xie, Michelle Crum, Mark Owens, Jose-Miguel Yamal

Faculty, Staff and Student Publications

The COVID-19 vaccine is safe and effective for children, yet parental hesitancy towards vaccinating children against the virus persists. We conducted a telephone-administered weighted survey in Texas to examine parents' sociodemographic factors and medical conditions associated with COVID-19 vaccination intention for parents with unvaccinated children ages 5-17 years. We collected responses from 19,502 participants, of which 4879 were parents of children ages 5-17 years. We conducted multiple logistic regression with Lasso-selected variables to identify factors associated with children's vaccination status and parents' intention to vaccinate their children. From the unweighted sample, less than half of the parents (46.8%) had at …

Inotuzumab Ozogamicin For The Treatment Of Adult Acute Lymphoblastic Leukemia: Past Progress, Current Research And Future Directions, Nicholas J Short, Elias Jabbour, Nitin Jain, Hagop Kantarjian

Faculty, Staff and Student Publications

Inotuzumab ozogamicin (INO) is an anti-CD22 antibody-drug conjugate that was first evaluated in B-cell lymphomas but was subsequently shown to be highly effective in acute lymphoblastic leukemia (ALL). INO improved response rates and survival in a randomized study in adults with relapsed/refractory B-cell ALL, leading to its regulatory approval in the United States in 2017. While the formal approval for INO is as monotherapy in relapsed/refractory ALL, subsequent studies with INO administered in combination with chemotherapy and/or blinatumomab both in the frontline and salvage settings have yielded promising results. In this review, we discuss the clinical development of INO in …

Regulation Of Cerebral Blood Flow Boosts Precise Brain Targeting Of Vinpocetine-Derived Ionizable-Lipidoid Nanoparticles, Xufei Bian, Ling Yang, Dingxi Jiang, Adam J Grippin, Yifan Ma, Shuang Wu, Linchong Wu, Xiaoyou Wang, Zhongjie Tang, Kaicheng Tang, Weidong Pan, Shiyan Dong, Betty Y S Kim, Wen Jiang, Zhaogang Yang, Chong Li

Faculty, Staff and Student Publications

Despite advances in active drug targeting for blood-brain barrier penetration, two key challenges persist: first, attachment of a targeting ligand to the drug or drug carrier does not enhance its brain biodistribution; and second, many brain diseases are intricately linked to microcirculation disorders that significantly impede drug accumulation within brain lesions even after they cross the barrier. Inspired by the neuroprotective properties of vinpocetine, which regulates cerebral blood flow, we propose a molecular library design centered on this class of cyclic tertiary amine compounds and develop a self-enhanced brain-targeted nucleic acid delivery system. Our findings reveal that: (i) vinpocetine-derived ionizable-lipidoid …

Dataset Of Weekly Intra-Treatment Diffusion Weighted Imaging In Head And Neck Cancer Patients Treated With Mr-Linac, Dina M El-Habashy, Kareem A Wahid, Renjie He, Brigid Mcdonald, Samuel J Mulder, Yao Ding, Travis Salzillo, Stephen Y Lai, John Christodouleas, Alex Dresner, Jihong Wang, Mohamed A Naser, Clifton D Fuller, Abdallah Sherif Radwan Mohamed, Joint Head And Neck Radiation Therapy-Mri Development Cooperative

Faculty, Staff and Student Publications

Radiation therapy (RT) is a crucial treatment for head and neck squamous cell carcinoma (HNSCC); however, it can have adverse effects on patients' long-term function and quality of life. Biomarkers that can predict tumor response to RT are being explored to personalize treatment and improve outcomes. While tissue and blood biomarkers have limitations, imaging biomarkers derived from magnetic resonance imaging (MRI) offer detailed information. The integration of MRI and a linear accelerator in the MR-Linac system allows for MR-guided radiation therapy (MRgRT), offering precise visualization and treatment delivery. This data descriptor offers a valuable repository for weekly intra-treatment diffusion-weighted imaging …

The Greenbeard Gene Tgrb1 Regulates Altruism And Cheating In Dictyostelium Discoideum, Mariko Katoh-Kurasawa, Peter Lehmann, Gad Shaulsky

Faculty, Staff and Students Publications

Greenbeard genetic elements encode rare perceptible signals, signal recognition ability, and altruism towards others that display the same signal. Putative greenbeards have been described in various organisms but direct evidence for all the properties in one system is scarce. The tgrB1-tgrC1 allorecognition system of Dictyostelium discoideum encodes two polymorphic membrane proteins which protect cells from chimerism-associated perils. During development, TgrC1 functions as a ligand-signal and TgrB1 as its receptor, but evidence for altruism has been indirect. Here, we show that mixing wild-type and activated tgrB1 cells increases wild-type spore production and relegates the mutants to the altruistic stalk, whereas mixing …

In Football Players With Scaphoid Fractures, How Does Surgical Intervention Compare To A Conservative Intervention For The Outcomes Of Repair? A Critically Appraised Topic, Kaitlin Brun, Meggan Bartok, Caitlin Craig, Ally Smith

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

CLINICAL SCENARIO

Scaphoid injuries are common in high impact or high collision sports with 11% of all hand injuries and 60%-70% of all carpal injuries being attributed to the scaphoid bone. Athletes at the highest risk include males ages 20-24 years of age and those who participate in football, basketball, or ice hockey. Fracture of the scaphoid are often misdiagnosed which increase the chance of a nonunion fracture. Currently most scaphoid fractures are treated either conservatively or with surgical interventions. The increasing knowledge of this injury leads us to question the best treatment options for future football athletes.

Effectiveness Of Kinesio Tape In Treating Low Back Pain: A Critical Appraisal, Stacey Lansky, Sara Stiltner

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

CLINICAL SCENARIO

Low back pain is a musculoskeletal disorder that is expected to affect 80% of the population. ^2,7-8 There are several therapeutic interventions including modalities and rehabilitation exercises that have been used in standard treatment of low back pain to improve pain and disability. ^2,3,5,6,8,9 However, few studies have been done on the effects of Kinesio Tape (KT) on pain and disability in patients with low back pain. It should be a primary goal of clinicians treating patients with low back pain to understand if KT is an appropriate alternative intervention in treating pain and disability associated with low …

Athletic Trainers’ Knowledge And Perceived Ability Of Recognizing And Treating Panic Attacks, Caitlin Hill, Chyrsten Gessel, Jaclyn Tate

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

OBJECTIVE

Mental health is a condition of mental wellness that enables people to manage life's stressors, develop their potential, study and work effectively, and give back to their communities. One mental health condition is anxiety. Anxiety is the expectation of a threat in the future. There are multiple subtypes of anxiety disorders, including panic disorder with or without agoraphobia, generalized anxiety disorder (GAD), social anxiety disorder (SAD), specific phobias, separation anxiety, and panic disorder. This study investigates the relationship between ATs' knowledge and their perceived ability to identify and treat panic attacks.

Scapular Fracture In An Ice Hockey Player, Rachel N. Kornbluth, Art Mccreary, Aaron Lear

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

OBJECTIVE

Ice hockey is a fast and aggressive sport.^1-2 Due to deliberate collisions and fighting, a hard playing surface, and sharp skates, ice hockey players are at high and distinctive risk to injury.^2-5 The way in which ice hockey players collide with, or check, one another, makes the shoulder vulnerable. About 8.6-21.9% of injuries sustained in ice hockey involve the shoulder.⁴ Acromioclavicular joint sprains and anterior glenohumeral dislocations are most common.^1,4-5 This case presents a 25-year-old male collegiate ice hockey player who sustained a recurrent right-sided glenohumeral dislocation after being checked from behind with his arm …

Cpr Knowledge And Skill Retention Among Ncaa Division Iii Athletic Coaches: A Prospective Cohort Study, Allison Hanstine, Jaclyn Tate, Chyrsten Gessel

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

OBJECTIVE

It is crucial for athletic coaches to be proficient in CPR knowledge and skill performance for the health and safety of their athletes. This research aimed to assess CPR knowledge and CPR skill retention five months post-training among athletic coaches. In addition, the study assessed whether the number of years certified in CPR had an association with CPR skill performance scores five months post-training.

The Effectiveness Of Patient Education In A High School Setting, Noah Silvers, Laura L. Harris

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

OBJECTIVE

To compare different types of patient education when recommending best practices for the care of ankle sprains and concussions in adolescents.

Barriers To Implementation Of Post-Concussion Grade Exercise Tests, Tyler Beauregard

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

OBJECTIVE

The purpose of this study was to assess the potential barriers to sports physical therapy and athletic training clinicians implementing graded exertional tests, specifically for their patients following concussion.

Accuracy Of Ottawa Ankle Rules In Adolescent Foot And Ankle Injuries, Kalie Siereveld, Olivia Teague, Laura L. Harris

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

OBJECTIVE

To determine the effectiveness of Ottawa Ankle Rules (OAR) for informing physician referrals secondary to ankle and foot injuries within adolescents.

Quality Improvement Of A Post-Concussion Recovery Protocol, Halle Strege, Kaitlyn Burnham, Laura L. Harris

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

OBJECTIVE

To determine the effectiveness of a post-concussion recovery protocol in an adolescent athletic population.

An Investigation Of Aed Access In One Secondary School, Michelle Skaggs, Laura L. Harris

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

OBJECTIVE

To evaluate the accessibility and time required to retrieve and apply Automated External Defibrillators (AEDs) against established standards.

Athletic Trainer Confidence In The Management Of Abdominal Injuries And Gi Conditions, Emily C. Roberts, Janet E. Simon

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

OBJECTIVE

Inadequate evidence, position statements, clinical practice and post-surgical guidelines challenge athletic trainers’ capabilities to provide care for abdominal injuries and GI conditions.^1-4 The primary objective of this study is to assess athletic trainers’ confidence in the management and treatment of abdominal injuries and GI conditions compared to musculoskeletal injuries.

The Effect Of Task Demands On Decision Making In Dynamic, Sport-Like Virtual Environments, Jeromy Alt, Paula L. Silva, Tehran Davis, Adam W. Kiefer, Ryan Macpherson

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

OBJECTIVE

To determine if level of temporal pressure to arrive at a desired location explains decisions about passability of closing gaps between opponents encountered and how decisions change with task experience.

The Effect Of Ankle Foot Orthotics On Collegiate Athletes’ Sprint Biomechanics, Elizabeth A. Starns, Paige Tucker

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

OBJECTIVE

Carbon composite dynamic response ankle foot orthotics (CCDRAFOs) are lightweight ankle braces originally made to help pathologically involved legs walk more efficiently¹. Since CCDRAFOs are traditionally not used on able-bodied individuals, there is limited information on the effects of CCDRAFOs on sprint performance of able-bodied athletes. However, the technology behind CCDRAFOs effectiveness has been suggested to have ergogenic aid properties^2-5. This study’s purpose was to evaluate the effects of CCDRAFOs on collegiate athletes’ lower extremity biomechanics, specifically ankle and knee joint angles.

Neurocognitive Performance Differences Between Athletes Who Are Deaf Or Hard-Of-Hearing And Athletes Who Are Hearing, Matthew P. Brancaleone, Jaclyn Caccese, James Onate

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

OBJECTIVE

There are over 71,000 college students in the United States who are deaf or hard-of-hearing (D/HoH), with many participating in athletics. Athletes who are D/HoH have similar concussion rates to athletes who are hearing at the collegiate level. Differences in neurocognitive baseline performance between athletes who are D/HoH and athletes who are hearing may exist due to misunderstanding of written English instructions or differences in sensory processing. Therefore, the purpose of this study was to compare neurocognitive performance between athletes who are hearing and athletes who are D/HoH.

Using Standardized Patients As A Tool To Explore Student Critical Thinking, Sara Stiltner, Andrea Cripps

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

OBJECTIVE

Standardized patients (SP) are a tool utilized regularly in athletic training to promote student confidence and independent thinking. SP are widely used in nursing, physical therapy, and in over 80% of medical education programs.¹ The use of SP to supplement student learning and career preparation, in the undergraduate setting has been a validated in increasing student confidence.³ SP’s are a tool that utilize an actor trained to portray a patient who has a specific medical condition or illness and the actor is trained to respond to the students in a consistent manner.^1,2 SP’s allow students the …

Mustang: Multi-Sample Spatial Transcriptomics Data Analysis With Cross-Sample Transcriptional Similarity Guidance, Seyednami Niyakan, Jianting Sheng, Yuliang Cao, Xiang Zhang, Zhan Xu, Ling Wu, Stephen T C Wong, Xiaoning Qian

Faculty, Staff and Students Publications

Spatially resolved transcriptomics has revolutionized genome-scale transcriptomic profiling by providing high-resolution characterization of transcriptional patterns. Here, we present our spatial transcriptomics analysis framework, MUSTANG (MUlti-sample Spatial Transcriptomics data ANalysis with cross-sample transcriptional similarity Guidance), which is capable of performing multi-sample spatial transcriptomics spot cellular deconvolution by allowing both cross-sample expression-based similarity information sharing as well as spatial correlation in gene expression patterns within samples. Experiments on a semi-synthetic spatial transcriptomics dataset and three real-world spatial transcriptomics datasets demonstrate the effectiveness of MUSTANG in revealing biological insights inherent in the cellular characterization of tissue samples under study.

Phenome-Wide Identification Of Therapeutic Genetic Targets, Leveraging Knowledge Graphs, Graph Neural Networks, And Uk Biobank Data, Lawrence Middleton, Ioannis Melas, Chirag Vasavda, Arwa Raies, Benedek Rozemberczki, Ryan S Dhindsa, Justin S Dhindsa, Blake Weido, Quanli Wang, Andrew R Harper, Gavin Edwards, Slavé Petrovski, Dimitrios Vitsios

Faculty, Staff and Students Publications

The ongoing expansion of human genomic datasets propels therapeutic target identification; however, extracting gene-disease associations from gene annotations remains challenging. Here, we introduce Mantis-ML 2.0, a framework integrating AstraZeneca's Biological Insights Knowledge Graph and numerous tabular datasets, to assess gene-disease probabilities throughout the phenome. We use graph neural networks, capturing the graph's holistic structure, and train them on hundreds of balanced datasets via a robust semi-supervised learning framework to provide gene-disease probabilities across the human exome. Mantis-ML 2.0 incorporates natural language processing to automate disease-relevant feature selection for thousands of diseases. The enhanced models demonstrate a 6.9% average classification power …

Mitochondria Regulate Proliferation In Adult Cardiac Myocytes, Gregory B Waypa, Kimberly A Smith, Paul T Mungai, Vincent J Dudley, Kathryn A Helmin, Benjamin D Singer, Clara Bien Peek, Joseph Bass, Lauren Nelson, Sanjiv J Shah, Gaston Ofman, J Andrew Wasserstrom, William A Muller, Alexander V Misharin, G R Scott Budinger, Hiam Abdala-Valencia, Navdeep S Chandel, Danijela Dokic, Elizabeth Bartom, Shuang Zhang, Yuki Tatekoshi, Amir Mahmoodzadeh, Hossein Ardehali, Edward B Thorp, Paul T Schumacker

Faculty, Staff and Student Publications

Newborn mammalian cardiomyocytes quickly transition from a fetal to an adult phenotype that utilizes mitochondrial oxidative phosphorylation but loses mitotic capacity. We tested whether forced reversal of adult cardiomyocytes back to a fetal glycolytic phenotype would restore proliferative capacity. We deleted Uqcrfs1 (mitochondrial Rieske iron-sulfur protein, RISP) in hearts of adult mice. As RISP protein decreased, heart mitochondrial function declined, and glucose utilization increased. Simultaneously, the hearts underwent hyperplastic remodeling during which cardiomyocyte number doubled without cellular hypertrophy. Cellular energy supply was preserved, AMPK activation was absent, and mTOR activation was evident. In ischemic hearts with RISP deletion, new cardiomyocytes …

Casi: A Framework For Cross-Timepoint Analysis Of Single-Cell Rna Sequencing Data, Yizhuo Wang, Christopher R Flowers, Michael Wang, Xuelin Huang, Ziyi Li

Faculty, Staff and Student Publications

Single-cell RNA sequencing (scRNA-seq) technology has been widely used to study the differences in gene expression at the single cell level, providing insights into the research of cell development, differentiation, and functional heterogeneity. Various pipelines and workflows of scRNA-seq analysis have been developed but few considered multi-timepoint data specifically. In this study, we develop CASi, a comprehensive framework for analyzing multiple timepoints' scRNA-seq data, which provides users with: (1) cross-timepoint cell annotation, (2) detection of potentially novel cell types emerged over time, (3) visualization of cell population evolution, and (4) identification of temporal differentially expressed genes (tDEGs). Through comprehensive simulation …

Imaging Features Of Primary Intracranial Sarcoma With Dicer1 Mutation: A Multicenter Case Series, Rami W Eldaya, Richard J Fagan, Samir A Dagher, Angshumoy Roy, Sonika Dahyia, Gregory N Fuller, Max Wintermark, Matthew S Parsons, Thierry A G M Huisman

Faculty, Staff and Student Publications

Primary intracranial sarcoma, DICER1-mutant, is a rare, recently described entity in the fifth edition of the WHO Classification of CNS Tumors. Given the entity's rarity and recent description, imaging data on primary intracranial sarcoma, DICER1-mutant, remains scarce. In this multicenter case series, we present detailed multimodality imaging features of primary intracranial sarcoma, DICER1-mutant, with emphasis on the appearance of the entity on MR imaging. In total, 8 patients were included. In all 8 patients, the lesion demonstrated blood products on T1WI. In 7 patients, susceptibility-weighted imaging was obtained and demonstrated blood products. Primary intracranial sarcoma, DICER1-mutant, …

Evaluation Of Sleep Outcomes After Traumatic Brain Injury In Children Using Questionnaires And Actigraphy, Connie Tran, Sydney Weese, Cydni Williams Md

Student Research Symposium

Traumatic brain injuries are the result of a sudden external blunt force to the brain and can result in long-term complications or death. In pediatrics, it is the leading cause of acute and chronic sleep wake disturbances, as well as cognitive deficits, which can lead to a reduction in the quality of life. These impairments can later result in lowered performance in work and school settings or decreased psychosocial function. Although there is sufficient evidence that traumatic brain injuries contribute to is that it is unknown whether or not sleep wake disturbances contribute to an increase in the mentioned cognitive …