Investigative Techniques Commons^™

Uncovering The Pml::Rara Fusion In Cytogenetically Cryptic And Fish-Negative Acute Promyelocytic Leukemia-A Case Report And Comprehensive Literature Review, Busra Delikkaya, Jaime Eberle-Singh, Arianna Morton, Jerald Gong, Jinglan Liu

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

The PML::RARA fusion resulting from t(15;17) is the genetic hallmark of acute promyelocytic leukemia (APL), typically detected by cytogenetics and/or fluorescence in situ hybridization (FISH) studies. Rarely, APL patients present with normal cytogenetics and FISH findings, complicating diagnosis and delaying life-saving therapy. We report a 23-year-old male with clinical, morphologic and immunophenotypic features consistent with APL but negative for FISH studies. Despite prompt initiation of all-trans retinoic acid (ATRA) based on clinical suspicion, the patient succumbed to intracranial hemorrhage. Quantitative reverse transcriptase PCR (qRT-PCR) confirmed a long isoform PML::RARA fusion. A review of 34 published cytogenetics- and FISH-negative cases since …

Enhancing Cataract Surgery Outcomes: Optimal Use Of Pre- And Post-Operative Eye Drops, Keith Skolnick M.D., Anu Valiaveedu

Mako: NSU Undergraduate Student Journal

Many preoperative and postoperative cataract patients struggle with comprehending the use of prescription medication as directed. Language barriers and low health literacy levels are major factors contributing to improper use of prescriptions. To increase patients comprehension, the Fort Lauderdale Eye Institute employed an educational intervention consisting of a live presentation and an instructional video. Results found that 44% of patients were hesitant to ask questions to clinical staff, 32% felt overwhelmed, and nearly 70% lacked confidence in using their prescribed eye drops. Following the intervention, 91% of patients reported increased confidence in their medications, and most indicated that the video …

Development Of Emerin Mrna Lipid Nanoparticles To Rescue Myogenic Differentiation., Nicholas Marano, Liza Elif Guner, Rachel S Riley, James M Holaska

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Emery-Dreifuss muscular dystrophy 1 (EDMD1) arises from mutations in EMD. Most EDMD1 patients lack detectable emerin expression. They experience symptoms such as skeletal muscle wasting, joint contractures, and cardiac conduction defects. Currently, physicians rely on treating patient symptoms without addressing the underlying cause-lack of functional emerin protein. Thus, there is a need for therapeutic approaches that restore emerin protein expression to improve patient outcomes. One way would be to deliver emerin mRNA or protein directly to affected tissues to restore tissue homeostasis. Here, we evaluated the utility of lipid nanoparticles (LNPs) to deliver emerin mRNA to diseased cells. LNPs …

Quantile Index Predictors Using R Package Hyper.Gam, Tingting Zhan, Misung Yi, Inna Chervoneva

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

MOTIVATION: Evaluation of single-cell protein expression from immunohistochemistry images is used increasingly in biomedical research. Many proteins are used solely for phenotyping cells in the tumor microenvironment. Other proteins with meaningfully quantitative expression levels provide so-called functional protein biomarkers. There is still a limited number of methods and software tools available for utilizing the entire distributions of single-cell expression levels.

RESULTS: We present the R package hyper.gam, providing a supervised learning framework for deriving biomarkers based on single-cell distribution quantiles. The single-cell data are first converted into sample quantile functions, which are then used as predictors in scalar-on-function regression models …

Elevated Nr2f1 Underlies The Persistence Of Invasive Disease After Treatment Of Braf-Mutant Melanoma, Manoela Tiago, Timothy J. Purwin, Casey D. Stefanski, Renaira Oliveira Da Silva, Mitchell E. Fane, Yash Chhabra, Jelan I. Haj, Jessica L. F. Teh, Rama Kadamb, Weijia Cai, Sheera Rosenbaum, Vivian Chua, Nir Hacohen, Michael A. Davies, Jessie Villanueva, Inna Chervoneva, Ashani T. Weeraratna, Dan A. Erkes, Claudia Capparelli, Julio A. Aguirre-Ghiso, Andrew E. Aplin

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Despite the success of targeted inhibitors in cutaneous melanoma, therapeutic responses are limited by the aged tumor microenvironment and drug-tolerant residual cells. Given the similarities between drug tolerance and cellular dormancy, we studied the dormancy marker, nuclear receptor subfamily 2 group F member 1 (NR2F1), in response to BRAF-V600E inhibitors (BRAFi) plus MEK inhibitors (MEKi) in BRAF-mutant melanoma models. Transcriptomic analysis of melanoma patient samples treated with BRAFi + MEKi showed increased NR2F1. NR2F1 was highly expressed in the drug-tolerant invasive cell state of minimal residual disease in patient-derived and mouse-derived xenografts on BRAFi + MEKi. NR2F1 over-expression was sufficient …

5-Ht Receptors: Pharmacology And Functional Selectivity, Benjamin R. Cummins, Gerald B. Billac, David E. Nichols, Charles D. Nichols

School of Medicine Faculty Publications

Serotonin 5-HT receptors were one of the first serotonin receptors to be pharmacologically characterized. In mammals, they are expressed throughout the body in nearly every cell and tissue type, with the highest density in cortical layer V of the brain. They are involved in several aspects of normal physiological processes and behaviors and have been implicated in the etiology of neuropsychiatric diseases such as schizophrenia. Atypical antipsychotics have targeted blockade of 5-HT receptors as part of their therapeutic mechanism. More recently, 5-HT receptors have come to prominence for their role as the primary target for psychedelic drugs, which activate this …

Zonal Hepatocellular Responses To Acute Ethanol: Impacts On Mitochondrial Function And Metabolism, Matthew T. Savoca

MUSC Theses and Dissertations

Background: Ethanol (EtOH) consumption causes hepatocellular mitochondrial depolarization (mtDepo) and mitophagy. Here, the Aims were to develop techniques to characterize sublobular hepatocellular metabolism and the distribution of mtDepo and mitophagy after acute EtOH. Methods: Wildtype and GFP-LC3 transgenic mice were treated with EtOH or vehicle and administered the covalently labeling mitochondrial membrane potential (ΔΨ) reporter, MitoTracker Red (MTR), and/or the non-covalent ΔΨ reporter, rhodamine 123 (Rh123), prior to intravital imaging, liver fixation, or hepatocyte isolation. After in vivo MTR, hepatocytes were isolated and sorted. Enrichment in E-cadherin (ECAD) and cytochrome P4502E1 in periportal (PP) and pericentral (PC) hepatocytes, respectively, validated …

Hexasodium Fytate (Snf472 Or Csl525) Inhibits Ectopic Calcification In Various Pseudoxanthoma Elasticum And Calcinosis Cutis Animal Models, Miguel Ferrer, Maria Pérez-Ferrer, Marc Blasco, Ida Jacobs, Qiaoli Li, Olivier Vanakker, Lisa Dangreau, Andrea López, Gianluca Malagraba, Firas Bassissi, Joan Perelló, Carolina Salcedo

Department of Biochemistry and Molecular Biology Faculty Papers

Background/Objectives: Ectopic calcification is a pathological condition characterized by the mineralization of soft tissues due to the deposition of calcium phosphate crystals. Hexasodium fytate (CSL525, previously known as SNF472) is a crystallization inhibitor being developed for the treatment of ectopic calcification-related disorders. Our aim was to investigate CSL525 for the treatment of soft-tissue calcification disorders in animal models of pseudoxanthoma elasticum and calcinosis cutis. Methods: In a first study, abcc6^-/- zebrafish larvae were exposed to 1 mM CSL525 for 7 days or kept under the same conditions without CSL525, and spinal mineralization was quantified. In a second study, abcc6 …

Molecular Subtyping Of Hypertensive Disorders Of Pregnancy, Michal Elovitz, Elaine Gee, Nathaniel Delaney-Busch, Alison Moe, Mitsu Reddy, Arkady Khodursky, Johnny La, Ilma Abbas, Kay Mekaru, Hunter Collins, Farooq Siddiqui, Rory Nolan, Rupsa Boelig, Daniel Kiefer, Pamela Simmons, George Saade, Antonio Saad, Ebony Carter, Thomas Mcelrath, Stephen Quake, Mark Depristo, Carrie Haverty, Manfred Lee, Eugeni Namsaraev, Vincenzo Berghella, Ai-Ris Collier, Antonia Frolova, Esther Park-Hwang, Luis Pacheco, Elizabeth Sutton, Maneesh Jain, Kara Rood, William A Grobman, Joseph Biggio, Cynthia Gyamfi-Bannerman, Arun Jeyabalan, Morten Rasmussen

Department of Obstetrics and Gynecology Faculty Papers

Hypertensive disorders of pregnancy (HDP), including preeclampsia, affect 1 in 6 pregnancies, are major contributors to maternal morbidity and mortality, yet lack precision medicine strategies. Analyzing transcriptomic data from a prospectively-collected diverse cohort (n = 9102), this study reveals distinct RNA subtypes in maternal blood, reclassifying clinical HDP phenotypes like early/late-onset preeclampsia. The placental gene PAPPA2 strongly predicts the most severe forms of preeclampsia in individuals without pre-existing high risk factors, months before symptoms, and its overexpression correlates with earlier delivery in a dose-dependent manner. Further, molecular subtypes characterized by immune genes are upregulated in less severe forms of HDP. …

Editorial: Old Drugs: Confronting Recent Advancements And Challenges, Anna Wiktorowska-Owczarek, Diego Iacono, Magdalena Jasińska-Stroschein

Department of Neurology Faculty Papers

No abstract provided.

Prodrug Activation In Malaria Parasites Mediated By An Imported Erythrocyte Esterase, Acylpeptide Hydrolase (Apeh), Sesh A. Sundararaman, Justin J. Miller, Ellora C. Daley, Kelsey A. O'Brien, Paulina Kasak, Abigail M. Daniels, Rachel L. Edwards, Kenneth M. Heidel, Darean A. Bague, Madeleine A. Wilson, Andrew J. Koelper, Elexi C. Kourtoglou, Alex D. White, Sloan A. August, Georgia A. Apple, Regis W. Rouamba, Anthony J. Durand, John J. Esteb, Florian L. Muller, R. Jeremy Johnson, Geoffrey C. Hoops, Cynthia S. Dowd, Audrey R. Odom John

College of Health Professions Faculty Papers

The continued emergence of antimalarial drug resistance highlights the need to develop new antimalarial therapies. Unfortunately, new drug development is often hampered by undesirable drug-like properties of lead compounds. Prodrug approaches temporarily mask undesirable compound features, improving bioavailability and target penetration. We have found that lipophilic diester prodrugs of phosphonic acid antibiotics, such as fosmidomycin (Fsm), exhibit significantly higher antimalarial potency than their parent compounds [R.L. Edwards et al., Sci. Rep. 7, 8400 (2017)]. However, the activating enzymes for these prodrugs were unknown. Here, we show that an erythrocyte enzyme, acylpeptide hydrolase (APEH), is the major activating enzyme of multiple …

5-Hydroxymethylcytosine Sequencing Of Plasma Cell-Free Dna Identifies Epigenomic Features In Prostate Cancer Patients Receiving Androgen Deprivation Therapies, Qianxia Li, Chiang-Ching Huang, Shane Huang, Yijun Tian, Jinyong Huang, Amirreza Bitaraf, Xiaowei Dong, Marja T. Nevalainen, Manishkumar Patel, Jodie Wong, Jingsong Zhang, Brandon J Manley, Jong Y. Park, Manish Kohli, Elizabeth M. Gore, Deepak Kilari, Liang Wang

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

BACKGROUND: We evaluated whether 5hmC signatures in cell-free DNA (cfDNA) are associated with treatment failure to androgen-deprivation therapies (ADT) among men with hormone-naive prostate cancer.

METHODS: We collected a total of 139 serial plasma samples from 55 prostate cancer patients receiving ADT at 3 time points including baseline (before initiating ADT, n = 55); 3 months (after initiating ADT, n = 55); and disease progression (n = 15) within 24 months or 24 months if no progression was detected (n = 14). We used selective chemical labeling sequencing to quantify 5hmC abundance across the genome and Kaplan-Meier analysis to assess …

Emerging Technologies For Forensic Genetic Identification, Lilly Llanos

Senior Honors Theses

There are many new innovations in forensic science that are being developed for the identification of biological evidence. These techniques include next-generation DNA sequencing, DNA phenotyping, and forensic genetic genealogy. This thesis will explore each, as well as newer applications of proteomics. The methodologies, reliability, practicality of cost and training, moral implications, and past research of each will be discussed. Finally, some ideas for future research and steps to drive growth and greater understanding will be suggested. This will encourage further innovations and the increased acceptance of forensic evidence in court. Each method was found to have both advantages and …

Antiseizure Medications And Their Differing Effects On Cardiovascular Risk, Aleena Abbasi, Bassil Abbasi, Scott Mintzer, Carla Lopinto-Khoury

Department of Neurology Faculty Papers

This review discusses the differing effects of enzyme-inducing and non-inducing antiseizure medications on cardiovascular risk and their implications for the management strategies of epilepsy patients. Traditional risk markers, including low density lipoprotein, high density lipoprotein and triglycerides, can be altered by both enzyme induction and inhibition. Other markers of vascular risk, including c-reactive protein, non-high-density lipoprotein and homocysteine, are affected by antiseizure medications, although adults and children may have different responses. The overall atherosclerotic risk picture is more complex due to indirect effects such as neuroendocrine function and the metabolic syndrome. Large scale data shows an evolving understanding of cardiovascular …

Bloom: Behavioral Learning And Outcome Observation In Microbes, Sean Sarwar Haque, Luke Compton Wharton, Ming Lin, Razvan Voicu

Symposium of Student Scholars

Understanding how pathogens respond to physical changes in their environment is crucial for developing effective treatments and preventative measures. Current research often relies on static models or experimental data that either fail to capture the dynamic interactions within cellular environments or are not generalizable to other types of pathogens. This project aims to address this gap by creating a comprehensive cell simulation that models pathogens and their response to chemical, physical, and physiological changes. The proposed solution is a simulation that integrates biological data and computational modeling to replicate the behavior of pathogens in real time as they are affected …

Escape From Diabetes, J E. Jochum, J Carmack, J Toon

Clinical Practice in Athletic Training

Introduction: In the past decade, interprofessional education (IPE) to promote interprofessional collaborative practice has become an integral component of pre-licensure education in the health professions. Research shows that IPE activities involving problem-solving in patient care that requires cooperation and communication among the professions is most effective. An effective activity to meet interprofessional competencies is the use of escape rooms. Escape rooms are team-based games where groups of individuals solve puzzles to accomplish a specific goal, typically in a limited amount of time. There are many benefits to using escape rooms in education, including promoting problem-solving, teamwork, and creativity, improving focus …

Modification Of Ergonomics For A World-Class Brass Instrumentalist With A Congenital Limb Difference: Level 3 Case, O G. Newhouse

Clinical Practice in Athletic Training

Background: A drum and bugle corps is a musical marching organization that consists of approximately 160 brass, percussion, and color guard performers. There are currently twenty-one drum corps organizations at the world-class level that compete. Organizations learn their 8–10-minute show in the late spring and begin traveling the country performing and competing in the early summer until August. Rehearsal days can be up to 10 hours of practice including visual and music. It has been reported that the incidence of upper limb pain is higher in those who have longer practice times, in which is a symptom of overuse. These …

The Effects Of A Joint Reduction Trainer On Confidence Levels In Professional Athletic Training Students, T Franklin, S Hacherl

Clinical Practice in Athletic Training

Introduction: Dislocations are common injuries managed by athletic trainers, yet athletic training students are unlikely to practice reduction techniques during clinical experiences. Current standards set by the Commission on Accreditation of Athletic Training Education require accredited programs to prepare students to manage patients with dislocations, including joint reductions. Research indicates the use of simulation techniques, such as joint reduction simulators, in education can fill clinical experience gaps and improve student confidence and skills. Shoulder dislocations make up nearly 50% of dislocations with several reduction techniques identified in the current literature. The use of a joint reduction simulator may provide athletic …

Barriers To The Implementation Of The Amsterdam 2022 Statement In The Secondary School Setting, L Torres, J L. Baldari, F A. Gardin, A M. Price

Clinical Practice in Athletic Training

Introduction: The Amsterdam 2022 International Consensus Statement on Concussion in Sport provides a summary of contemporary best practice recommendations for healthcare providers who are involved in the care of athletes at risk of sport-related concussion (SRC). Given that athletic trainers (ATs) have a professional responsibility to continually educate themselves on topics of great importance to the population that they care for, such as SRC management, it is reasonable to expect them to evolve their concussion management protocols to better align themselves with the recommendations found this statement. The purpose of this study was to identify the barriers associated with the …

Using Ai-Generated Scenarios To Enhance Learning Of The Emergency Assessment Process, D Cobble, L Schroeder, J Vaughn, S Ford

Clinical Practice in Athletic Training

Introduction: Rigorous accreditation standards require students to demonstrate competency in various clinical proficiencies through clinical practice or simulation-based educational activities. Therefore, simulation has become an integral component of athletic training education, as scenarios can provide realistic and reproducible experiences for all students. To that end, our study had two primary objectives: investigate the ability of artificial intelligence (AI) to generate accurate and realistic athletic training simulation scenarios and evaluate AI's effectiveness in teaching and reinforcing the emergency assessment process through student-created scenarios. Methods: Phase one, AI developed three different scenarios for patients experiencing (1) an ovarian cyst, (2) a hypoglycemic …

Athletic Trainer Compensation Characteristics, J P. Young, K Ef Mair, L E. Eberman

Clinical Practice in Athletic Training

Introduction: Athletic trainers (ATs) are integral to healthcare yet face ongoing challenges that affect job satisfaction and retention. Factors such as long work hours, low pay, and work-family conflict contribute to dissatisfaction and a desire to leave the profession. Salary disparities and lack of administrative support are key factors impacting professional fulfillment and career longevity. Identifying how compensation influences job satisfaction is essential for improving retention and advancing the profession. Our study aimed to examine the compensation characteristics of ATs and determine the key factors that predict gross income. Methods: A cross-sectional, web-based survey was conducted. The survey was validated …

Clinat: In Service To Athletic Training Scholarship, Lindsey Eberman, Matthew J. Rivera

Clinical Practice in Athletic Training

To be of service to others means to help others without expecting anything in return. The ClinAT, or Clinical Practice in Athletic Training journal, is an online, open-access outlet for the dissemination of practice-based research in health care, and a donation of time, effort, and energy to the profession of athletic training. In 2018, when Indiana State University created its first issue of ClinAT, we were a faculty of 3 with 5 PhD students supporting the journal, one of whom was wholly dedicated to the effort. As the higher education landscape has changed, and the roles and responsibilities of our …

Exploring The Vitality Of Athletic Training: Insights Into Professional Identity, Commitment, And Retention, L E. Eberman, M J. Rivera, K E. Games, M J. Drescher, J P. Young, J Clifton-Gaw, K Condrey, H Mccarn, N Mondelli, X Yuan

Clinical Practice in Athletic Training

Introduction: The confluence of fluctuating retention, fewer students entering professional programs, and the profession’s identity crisis (conflict between being a sports profession or a health profession) has created a serious question about the vitality of the athletic profession. However, research on the vitality of the profession has often focused on singular variables influencing professional identity, burnout, and commitment. The purpose of this project was to explore multiple factors influencing the vitality of the profession across professional identity and commitment in athletic training. Methods: We used a convergent parallel mixed-methods design, including surveys and interviews with athletic training students and athletic …

Title: Professional Socialization And Development Of Athletic Training Professional Program Directors, N A. Wilkins, K D. Pagnotta, L Kunkel, S David, A B. Thrasher

Clinical Practice in Athletic Training

Introduction: The role of Program Directors (PD) has vastly expanded over the last decade to meet the evolving demands of athletic training education and higher education. While specific responsibilities such as programmatic planning and accreditation maintenance are directly outlined in accreditation standards, PDs often assume additional institutional and programmatic responsibilities that now include recruitment and retention efforts, mentorship of faculty and students, curriculum design and mapping, and other administrative tasks. Previous research demonstrates athletic training faculty have little formalized training in administrative roles, and Coordinators of Clinical Education (CCEs) desired more support and development for that role. Little research exists …

Preceptor Development: Identifying The Best Modality For Building Clinical Educators, G W. Cohen, R M. Lopez, A J. Tritsch

Clinical Practice in Athletic Training

Introduction: Preceptor training and development are not standardized within the athletic training profession. The Commission on Accreditation of Athletic Training Education (CAATE) requires that Athletic Training Programs provide an ongoing education plan for preceptors to promote a constructive learning environment for students. However, with the rapid expansion of clinical education opportunities outside of institutions' immediate area, programs must identify how to reach all their preceptors and uphold their programmatic expectations for clinical educators. Methods: The investigators conducted a cohort pre-test-post-test design study. A preceptor development program (PDP) was created and grounded in the theory of gamified learning and adult learning …

Adolescent Femoral Neck Fractures: A Case Study On Initial Surgical Intervention, Avascular Necrosis Development, And Subsequent Total Hip Arthroplasty, K A. Fisher

Clinical Practice in Athletic Training

Background: The patient sustained a femoral neck fracture at the age of 13 after slipping and falling in his home. He was seen in the Emergency Department the same day and underwent a closed reduction and percutaneous pinning procedure the following morning. Ten weeks after returning to full weightbearing, and 13.5 weeks after his initial fracture, he developed stress fractures of the medial distal femoral and proximal tibial metaphyses. He experienced gradual worsening of hip pain and difficulty with ambulation between 11 to 13 months post-closed reduction and percutaneous pinning (CRPP). Avascular necrosis and collapse of the femoral head was …

Musculoskeletal Tumors Disguised As Orthopedic Injuries: A Case Report, A Summers

Clinical Practice in Athletic Training

Background: Musculoskeletal tumors are relatively rare, accounting for only 0.2 to 0.5% of all malignancies across all age groups. More specifically, Pigmented Villonodular Synovitis, a type of musculoskeletal tumor, has an incidence rate of 1.8 cases per one million people in a population. This benign, proliferative disease is a type of tenosynovial giant cell tumor that can affect the soft tissue lining of joints, bursae, and tendon sheaths. These joint-related tumors often present with an insidious onset and non-specific physical exam findings. Therefore, they are often mistaken for other, more common orthopedic injuries, making them difficult to diagnose. Patient Information: …

Strength Assessment Protocol In Pre-Professional Ballet Dancers, Simona Di Nardo, Ivan Mascio

Clinical Practice in Athletic Training

Purpose: This research project aimed to investigate the effects, particularly regarding the ability to generate force, that could emerge following a ballet class. The purpose of the study was to support the thesis that low levels of fitness and performance in professional and amateur dancers, should be considered a significant gap that needs to be addressed. Larger will be the gap and bigger will be the demand of a dancer to be prepared athletically. While the shorter the gap and more efficient the artistic side of the dance performance will be. As a result, a stronger and healthier body will …

Prevalence, Perceptions, And Attitudes Of Accommodation For Students With Disabilities In Athletic Training Education Programs, T J. Babcock, L E. Eberman

Clinical Practice in Athletic Training

Introduction: Disability accommodation has been widely researched in healthcare education programs, including medical doctor (MD), doctor of osteopathy (DO), and physical therapy (PT). However, little research has been conducted on classroom and clinical education accommodation in athletic training education. The purpose of this study was to explore these settings and gain an understanding of student experiences with accommodation in athletic training education programs. This project was deemed exempt by Indiana State University’s Institutional Review Board. Methods: A cross-sectional 24-question survey was developed and adapted from prior qualitative research on accommodation in physical therapy education. Emails containing a link to the …

The Financial Stresses That Affect Athletic Training Students: A Qualitative Investigation, C Kuehner-Boyer, E León Zaragoza

Clinical Practice in Athletic Training

Introduction: A recent survey examining barriers that affect athletic training students found that financial-related barriers created significant stress for students in professional athletic training programs. The need to work while attending a professional athletic training program was the highest reported barrier with 54.82% of respondents indicating that this was a barrier for them during their program. Beyond the overall reporting rate, the need to work while completing a professional athletic training program was indicated by athletic training students to be the barrier that they encountered the most frequently with respondents reporting that this was a stress for them between monthly …