Medicine and Health Sciences Commons^™

Tfeb Drives Mtorc1 Hyperactivation And Kidney Disease In Tuberous Sclerosis Complex, Nicola Alesi, Damir Khabibullin, Dean M Rosenthal, Elie W Akl, Pieter M Cory, Michel Alchoueiry, Samer Salem, Melissa Daou, William F Gibbons, Jennifer A Chen, Long Zhang, Harilaos Filippakis, Laura Graciotti, Caterina Miceli, Jlenia Monfregola, Claudia Vilardo, Manrico Morroni, Chiara Di Malta, Gennaro Napolitano, Andrea Ballabio, Elizabeth P Henske

Duncan NRI Faculty and Staff Publications

Tuberous Sclerosis Complex (TSC) is caused by TSC1 or TSC2 mutations, leading to hyperactivation of mechanistic target of rapamycin complex 1 (mTORC1) and lesions in multiple organs including lung (lymphangioleiomyomatosis) and kidney (angiomyolipoma and renal cell carcinoma). Previously, we found that TFEB is constitutively active in TSC. Here, we generated two mouse models of TSC in which kidney pathology is the primary phenotype. Knockout of TFEB rescues kidney pathology and overall survival, indicating that TFEB is the primary driver of renal disease in TSC. Importantly, increased mTORC1 activity in the TSC2 knockout kidneys is normalized by TFEB knockout. In TSC2-deficient …

Using Interprofessional Collaboration To Bridge Athletic Training And Strength And Condition Programs In High School Settings To Reduce Injuries, Craig Hermans

Doctoral Dissertations and Projects

The purpose of this practicum is to identify the differences between between the athletic training professional and the strength and conditioning professional in a school which may cause barriers in using interprofessional collaboration. Currently, the rate of reinjury in a student-athlete population is quite high due, in part, to the different focuses between athletic trainers and that of strength and conditioning coaches. This practicum prepares a compiled review of the literature of research as well as independent research evaluating the student/athletes’ recovery from injury in relation to reinjury. The findings from the research serve a purpose to establish a deeper …

Correlation Between Melphalan Chemotherapy With Longitudinal Global Strain Indices Of The Left Ventricle In Multiple Myeloma Patients: A Velocity Vector Imaging (Vvi) Echocardiography Study, Liaosadat Mirsafaee, Mohammad Dehghani Firouzabadi, Sayeh Parkhideh, Hassan Vahidnezhad, Fatemeh Dehghani Firouzabadi, Maryam Arab, David M. Yousem, Mersedeh Karvandi

Jefferson Institute of Molecular Medicine Papers and Presentations

Multiple myeloma (MM) is characterized by the neoplastic proliferation of plasma cells, leading to the production of monoclonal immunoglobulins. High-dose chemotherapy with autologous stem cell transplant has been used in the treatment of patients with MM (1). Melphalan (L-phenylalanine nitrogen mustard) is one of the most effective chemotherapeutic drugs in the treatment of MM (2). The side effects of melphalan include anemia, nausea, vomiting, allergic reactions, oral ulcers, nephrotoxicity, and arrhythmia at high doses (3). The effect of this drug on cardiac mechanics and heart damage is not well established, as previous studies have only focused on the electrocardiographic and …

Commentary: A Patient-Specific Lower Extremity Biomechanical Analysis Of A Knee Orthotic During A Deep Squat Movement, Christine Dailey Walck

Publications

The recent study by Walck et al., titled “A Patient-Specific Lower Extremity Biomechanical Analysis of a Knee Orthotic during a Deep Squat Movement,” provides a novel insight into the biomechanical impacts of knee orthotics, particularly the non-linear spring-loaded (NLSL) knee joint orthosis (KJO)1 . This commentary aims to delve into the implications, interpretations, and evaluations of the findings, contextualizing them within the broader discourse on knee orthotics.

Gastric Lipomas: A Case Series And Review Of The Literature, Simone A. Jarrett, Sahana Tito, Matthew Chan, Dominic E. Jarrett, Kevin B. Lo, Richard Depalma

Einstein Health Papers

INTRODUCTION: The purpose of this case series was to review a rare subset of tumors known as gastric lipomas, which are typically found incidentally. The motivation for this study arose from the identification of 2 cases within our institution in a short period.

CASE PRESENTATION: The study involved a review of the diagnosis and management of 2 patients presenting with gastric lipomas at our institution after symptoms of gastrointestinal bleeding. With the advent of new radiologic investigations such as computed tomography and magnetic resonance imaging and advances in endoscopy, there are new approaches to identifying and managing these tumors. On …

Quantifying 3d Mr Fingerprinting (3d-Mrf) Reproducibility Across Subjects, Sessions, And Scanners Automatically Using Mni Atlases, Andrew Dupuis, Yong Chen, Jessie E.P. Sun, Chaitra Badve, Dan Ma, Mark A. Griswold, Rasim Boyacioglu

Researchers, Instructors, & Staff Scholarship

Purpose: Quantitative MRI techniques such as MR fingerprinting (MRF) promise more objective and comparable measurements of tissue properties at the point-of-care than weighted imaging. However, few direct cross-modal comparisons of MRF's repeatability and reproducibility versus weighted acquisitions have been performed. This work proposes a novel fully automated pipeline for quantitatively comparing cross-modal imaging performance in vivo via atlas-based sampling. Methods: We acquire whole-brain 3D-MRF, turbo spin echo, and MPRAGE sequences three times each on two scanners across 10 subjects, for a total of 60 multimodal datasets. The proposed automated registration and analysis pipeline uses linear and nonlinear registration to align …

Prediction Of Hydrogel Degradation Time Based On Central Composite Design, Ying Wang, Deji Liu, Ruiquan Liao, Guangming Zhang, Manlai Zhang, Xiaohui Li

Faculty, Staff and Student Publications

In this study, a self-degrading hydrogel was formed by free-radical-initiated copolymerization, which can be used for oil and gas well strip pressure operations. Fourier transform infrared spectroscopy (FTIR), nuclear magnetic resonance (1H NMR), scanning electron microscopy (SEM), and thermogravimetry-mass spectrometry (TGA-MS) were used to study the reaction mechanism as well as the microstructure of the gels. Then, the effects of the four factors and their interactions on gel degradation time were determined by central composite design (CCD). Then, the effects of copolymer concentration, cross-linker, initiator, and reaction temperature and their interactions on gel degradation time were determined by central composite …

Toward Standardization, Harmonization, And Integration Of Social Determinants Of Health Data: A Texas Clinical And Translational Science Award Institutions Collaboration, Catherine K Craven, Linda Highfield, Mujeeb Basit, Elmer V Bernstam, Byeong Yeob Choi, Robert L Ferrer, Jonathan A Gelfond, Sandi L Pruitt, Vaishnavi Kannan, Paula K Shireman, Heidi Spratt, Kayla J Torres Morales, Chen-Pin Wang, Zhan Wang, Meredith N Zozus, Edward C Sankary, Susanne Schmidt

Faculty, Staff and Student Publications

INTRODUCTION: The focus on social determinants of health (SDOH) and their impact on health outcomes is evident in U.S. federal actions by Centers for Medicare & Medicaid Services and Office of National Coordinator for Health Information Technology. The disproportionate impact of COVID-19 on minorities and communities of color heightened awareness of health inequities and the need for more robust SDOH data collection. Four Clinical and Translational Science Award (CTSA) hubs comprising the Texas Regional CTSA Consortium (TRCC) undertook an inventory to understand what contextual-level SDOH datasets are offered centrally and which individual-level SDOH are collected in structured fields in each …

Differences In Provider Hepatitis C Virus Screening Recommendations By Patient Risk Status, Alfu Laily, Robert Duncan, Kaitlyn M. Gabhart, Lauren D. Nephew, Shannon M. Christy, Susan T. Vadaparampil, Anna R. Giuliano, Monica L. Kasting

Purdue University Libraries Open Access Publishing Fund

Providers’ recommendation is among the strongest predictors to patients engaging in preventive care. Therefore, the aim of this study was to compare providers’ Hepatitis C Virus (HCV) screening recommendation quality between high-risk and average-risk patients to determine if providers are universally recommending HCV screening, regardless of risk behaviors. This cross-sectional survey of 284 Indiana providers in 2020 assessed provider characteristics, HCV screening recommendation practices (strength, presentation, frequency, timeliness), self-efficacy, and barriers to recommending HCV screening. T-test and Chi-square compared recommendation practices for high-risk and average-risk patients. Prevalence ratios were calculated for variables associated with HCV recommendation strength comparing high-risk and …

Common Heart Failure With Preserved Ejection Fraction Animal Models Yield Disparate Myofibril Mechanics, Axel J. Fenwick, Vivek P. Jani, D. Brian Foster, Thomas E. Sharp, Traci T. Goodchild, Kyle Lapenna, Jake E. Doiron, David J. Lefer, Joseph A. Hill, David A. Kass, Anthony Cammarato

School of Medicine Faculty Publications

No abstract provided.

Exploring The Relationship Between Staffing And Long-Term Care Worker Mental Health, Matthew R. Trombley

Doctoral Dissertations and Projects

This research delves into the relationship between staffing levels during a crisis in the healthcare workforce and the mental well-being of long-term care workers, with a specific focus on variables such as burnout, compassion fatigue, and compassion satisfaction. With increasing workforce shortages, the attention to providing quality care during this tumultuous period has become increasingly urgent. There has been scarce empirical research that has explicitly sought to comprehend the connection between staffing levels and the mental health of long-term care professionals. This study was designed as a non-experimental, quantitative correlational investigation, aiming to understand the intricate dynamics between patient-to-staff ratios …

Effectiveness Of Emotionally Focused Therapy (Eft) With Chinese Couple Clients: From The Chinese Eft Therapists' Cultural Lens, Yifan Wang

Doctoral Dissertations and Projects

The purpose of this phenomenological study is to understand the Chinese EFT (Emotionally Focused Therapy) therapists’ experiences of working with Chinese couples in EFT sessions, as well as to discover how the cultural factors play a role in the effectiveness of EFT use with Chinese couples. This study was conducted by finding out 10 EFT-oriented therapists and analyzing via online interviews their experiences of working with Chinese couples. The theories guiding this study are based on Emotionally Focused Therapy (EFT). One of the founding therapists of this approach is Dr. Sue Johnson. EFT is heavily influenced by attachment theory, which …

Burnout Triggers In The Novice Registered Nurse, Sharon K. Nguyen

Doctoral Dissertations and Projects

Nurse burnout has been strongly associated with decreased patient satisfaction and reduced retention rates in the novice registered nurse. This phenomenon is exacerbating the already rising global nursing shortage. A strong correlation is established between novice registered nurses who endure repeated or multiple triggers, such as unsafe staffing ratios, inadequate preceptorship, and ineffective leadership to those who succumb to burnout. Burnout is a significant problem in the United States, impacting how healthcare is perceived by the public. In 2019 there were more than six million nurses, making up the largest segment of the healthcare population and directly affecting the safety …

Medication Errors In Hospitals, Isata Jalloh

Doctoral Dissertations and Projects

In hospitals, the issue of medication errors poses a serious problem, often leading to substantial health complications and, in some cases, even deaths among hospitalized as well as discharged patients. This health challenge not only imposes a substantial financial burden on patients, insurance providers, and Federal/State governments but also contributes to elevated healthcare expenses, hindering the effective allocation of resources to address other healthcare issues. Understanding the triggers of medication errors in hospitals is critical in solving this problem. The purpose of this integrative review is to determine the causes/triggers of medication errors in hospitals. This review will highlight the …

Experience Of Clinical Judgment Among Senior Associate Degree Nursing Students: A Transcendental Phenomenological Study, Hollie Bell Elmore

Doctoral Dissertations and Projects

This transcendental phenomenological study aimed to understand the experience of clinical judgment for senior associate degree nursing students at a rural community college. The students completed a 60-minute simulation involving the cardiac system and debriefed after the active simulation. The theory that guided this study was David Kolb’s experiential learning theory, which defines the learning process as creating knowledge through transforming experience. Because the experiential learning theory is flexible, it can be readily applied to many disciplines such as nursing. This theory also helped to incorporate Tanner’s Clinical Judgment Model. Data for this transcendental qualitative study were collected using semi-structured …

Shaping The Future Of Global Access To Safe, Effective, Appropriate And Quality Health Products, Raffaella Ravinetto, Rodrigo Henriquez, Prashant N Srinivas, Hazel Bradley, Renier Coetzee, Theresa J Ochoa, Jean Claude Semuto Ngabonziza, Jean-Baptiste Mazarati, Wim Van Damme, Remco Van De Pas, Nico Vandaele, Els Torreele

Faculty, Staff and Student Publications

No abstract provided.

Cd36 Regulates Factor Viii Secretion From Liver Endothelial Cells, Paula Reventun, Pablo Toledano-Sanz, Nunzio Alcharani, Maria Viskadourou, Alanna C Morrison, Maria Sabater-Lleal, Alisa S Wolberg, Paul S De Vries, Nicholas L Smith, William O Osburn, Marios Arvanitis, Charles J Lowenstein

Faculty, Staff and Student Publications

No abstract provided.

Examining Factors Associated With The Use Of Community Food Resources: An Application Of The Andersen Model To Inform Future Interventions, Abiodun T. Atoloye, Oluyemisi Akinsola, Melissa Murillo

Nutrition, Dietetics, and Food Sciences Faculty Publications

The role of the food environment in shaping nutrition and health has gained substantial attention from policymakers, public health researchers, and advocacy groups. To promote equities in food access and nutrition outcomes, understanding factors linked with the utilization of local community food resources is crucial. Using Andersen’s service utilization model, we explained how adults use their neighborhood food resources. In a cross-sectional study design, an online survey was conducted in REDCap Version 13.4.0 via the Amazon Mechanical Turk (MTurk) involving 1830 adults with a mean age of 37.9 ± 12.1 years. Participants answered questions on predisposing, enabling, and need factors …

Cell Membrane-Anchored And Tumor-Targeted Il-12 T-Cell Therapy Destroys Cancer-Associated Fibroblasts And Disrupts Extracellular Matrix In Heterogenous Osteosarcoma Xenograft Models, Jiemiao Hu, Alexander J Lazar, Davis Ingram, Wei-Lien Wang, Wendong Zhang, Zhiliang Jia, Dristhi Ragoonanan, Jian Wang, Xueqing Xia, Kris Mahadeo, Richard Gorlick, Shulin Li

Faculty, Staff and Student Publications

Background: The extracellular matrix (ECM) and cancer-associated fibroblasts (CAFs) play major roles in tumor progression, metastasis, and the poor response of many solid tumors to immunotherapy. CAF-targeted chimeric antigen receptor-T cell therapy cannot infiltrate ECM-rich tumors such as osteosarcoma.

Method: In this study, we used RNA sequencing to assess whether the recently invented membrane-anchored and tumor-targeted IL-12-armed (attIL12) T cells, which bind cell-surface vimentin (CSV) on tumor cells, could destroy CAFs to disrupt the ECM. We established an in vitro model of the interaction between osteosarcoma CAFs and attIL12-T cells to uncover the underlying mechanism by which attIL12-T cells penetrate …

Effects Of Kras Genetic Interactions On Outcomes In Cancers Of The Lung, Pancreas, And Colorectum, Isabella N Grabski, John V Heymach, Kenneth L Kehl, Scott Kopetz, Ken S Lau, Gregory J Riely, Deborah Schrag, Rona Yaeger, Rafael A Irizarry, Kevin M Haigis

Faculty, Staff and Student Publications

Background: KRAS is among the most commonly mutated oncogenes in cancer, and previous studies have shown associations with survival in many cancer contexts. Evidence from both clinical observations and mouse experiments further suggests that these associations are allele- and tissue-specific. These findings motivate using clinical data to understand gene interactions and clinical covariates within different alleles and tissues.

Methods: We analyze genomic and clinical data from the AACR Project GENIE Biopharma Collaborative for samples from lung, colorectal, and pancreatic cancers. For each of these cancer types, we report epidemiological associations for different KRAS alleles, apply principal component analysis (PCA) to …

Synthetic Oct-A Blood Vessel Maps Using Fundus Images And Generative Adversarial Networks, Ashanul Haque, Mohd Wajid Ali Khan, Khalaf M Alenezi, Raoudha Soury, Muhammad S Khan, Shahzaib Ahamad, Md Mushtaque, Dinesh Gupta

Faculty, Staff and Student Publications

The design and development of new small-molecule glycation inhibitors are essential for preventing various chronic diseases, including diabetes mellitus, immunoinflammation, cardiovascular, and neurodegenerative diseases. 4-Thiazolidinone or thiazolidine-4-one is a well-known heterocyclic compound with the potential to inhibit the formation of advanced glycation end products. In the present work, we report the synthesis and characterization of four new 5-arylidene 3-cyclopropyl-2-(phenylimino)thiazolidin-4-one (1–4) compounds and their human serum albumin glycation inhibitory activity. One of the compounds 5-(2H-1,3-benzodioxol-5-ylmethylidene)-3-cyclopropyl-2-(phenylimino)-1,3-thiazolidin-4-one (3) showed potent inhibition in the synthesis of initial, intermediary, and final products of glycation reactions. Besides, conformational …

Hypoxia-Activated Prodrug And Antiangiogenic Therapies Cooperatively Treat Pancreatic Cancer But Elicit Immunosuppressive G-Mdsc Infiltration, Arthur Liu, Seth T Gammon, Federica Pisaneschi, Akash Boda, Casey R Ager, David Piwnica-Worms, David S Hong, Michael A Curran

Faculty, Staff and Student Publications

We previously showed that ablation of tumor hypoxia can sensitize tumors to immune checkpoint blockade (ICB). Here, we used a Kras+/G12D TP53+/R172H Pdx1-Cre-derived (KPC-derived) model of pancreatic adenocarcinoma to examine the tumor response and adaptive resistance mechanisms involved in response to 2 established methods of hypoxia-reducing therapy: the hypoxia-activated prodrug TH-302 and vascular endothelial growth factor receptor 2 (VEGFR-2) blockade. The combination of both modalities normalized tumor vasculature, increased DNA damage and cell death, and delayed tumor growth. In contrast with prior cancer models, the combination did not alleviate overall tissue hypoxia or sensitize these KPC tumors to ICB therapy …

Pearls & Oy-Sters: Cacna1a-Related Paroxysmal Tonic Upgaze With Ataxia Responsive To Acetazolamide, Steven M Lazar, Farida Abid

Faculty, Staff and Students Publications

A 9-month-old male infant was evaluated for sudden onset of paroxysmal episodes of forced, conjugate upward eye deviation. Extensive in-hospital evaluation including electrophysiology and neuroimaging studies were reassuring against seizures or a structural abnormality. Given the clinical presentation of sudden onset intermittent upward eye deviations, downbeating saccades, associated ataxia, and typical development, a clinical diagnosis of paroxysmal tonic upgaze (PTU) with ataxia was made. Targeted genetic testing of CACNA1A was performed, which revealed a variant of undetermined significance, which was later classified as a de novo pathogenic variant after protein modeling and parental testing performed. Off-label use of oral acetazolamide …

Correction: Mechanisms Of Ferroptosis And Targeted Therapeutic Approaches In Lymphoma, Tiantian Yu, Zijun Y Xu-Monette, Li Yu, Yong Li, Ken H Young

Faculty, Staff and Students Publications

No abstract provided.

Retrospective Analysis Of The Impact Of High- And Low-Quality Donor Livers For Patients With High-Acuity Illness, Ron K Varghese, Greta E Handing, Ashley E Montgomery, Abbas A Rana, John A Goss

Faculty, Staff and Students Publications

BACKGROUND Patients with high-acuity liver failure have increased access to marginal and split liver options, owing to historically high waitlist mortality rates. While most research states that donor liver quality has no impact on patients with high-acuity illness, there have been inconsistencies in recent research on how liver quality impacts post-transplant outcomes for these patients. We aimed to quantify donor liver quality with various post-transplantation patient outcomes for patients with high-acuity illness. MATERIAL AND METHODS Using the liver donor risk index (LDRI), model for end stage liver disease (MELD), and clinically relevant recipient factors, we used multivariate logistic regression to …

Overcoming Resolution Attenuation During Tilted Cryo-Em Data Collection, Sriram Aiyer, Philip R Baldwin, Shi Min Tan, Zelin Shan, Juntaek Oh, Atousa Mehrani, Marianne E Bowman, Gordon Louie, Dario Oliveira Passos, Selena Đorđević-Marquardt, Mario Mietzsch, Joshua A Hull, Shuichi Hoshika, Benjamin A Barad, Danielle A Grotjahn, Robert Mckenna, Mavis Agbandje-Mckenna, Steven A Benner, Joseph A P Noel, Dong Wang, Yong Zi Tan, Dmitry Lyumkis

Faculty, Staff and Students Publications

Structural biology efforts using cryogenic electron microscopy are frequently stifled by specimens adopting "preferred orientations" on grids, leading to anisotropic map resolution and impeding structure determination. Tilting the specimen stage during data collection is a generalizable solution but has historically led to substantial resolution attenuation. Here, we develop updated data collection and image processing workflows and demonstrate, using multiple specimens, that resolution attenuation is negligible or significantly reduced across tilt angles. Reconstructions with and without the stage tilted as high as 60° are virtually indistinguishable. These strategies allowed the reconstruction to 3 Å resolution of a bacterial RNA polymerase with …

Multiple Pathways For Glucose Phosphate Transport And Utilization Support Growth Of Cryptosporidium Parvum, Rui Xu, Wandy L Beatty, Valentin Greigert, William H Witola, L David Sibley

2020-Current year OA Pubs

Cryptosporidium parvum is an obligate intracellular parasite with a highly reduced mitochondrion that lacks the tricarboxylic acid cycle and the ability to generate ATP, making the parasite reliant on glycolysis. Genetic ablation experiments demonstrated that neither of the two putative glucose transporters CpGT1 and CpGT2 were essential for growth. Surprisingly, hexokinase was also dispensable for parasite growth while the downstream enzyme aldolase was required, suggesting the parasite has an alternative way of obtaining phosphorylated hexose. Complementation studies in E. coli support a role for direct transport of glucose-6-phosphate from the host cell by the parasite transporters CpGT1 and CpGT2, thus …

Clinical Outcomes Of Older And Younger Patients Treated With Loncastuximab Tesirine In The Lotis-2 Clinical Trial, Mehdi Hamadani, Brad Kahl, Et Al.

2020-Current year OA Pubs

No abstract provided.

Integrating Genetic Regulation And Single-Cell Expression With Gwas Prioritizes Causal Genes And Cell Types For Glaucoma, Andrew R Hamel, Wenjun Yan, John M Rouhana, Aboozar Monovarfeshani, Xinyi Jiang, Puja A Mehta, Jayshree Advani, Yuyang Luo, Qingnan Liang, Skanda Rajasundaram, Arushi Shrivastava, Katherine Duchinski, Sreekar Mantena, Jiali Wang, Tavé Van Zyl, Louis R Pasquale, Anand Swaroop, Puya Gharahkhani, Anthony P Khawaja, Stuart Macgregor, Rui Chen, Veronique Vitart, Joshua R Sanes, Janey L Wiggs, Ayellet V Segrè

Faculty, Staff and Students Publications

Primary open-angle glaucoma (POAG), characterized by retinal ganglion cell death, is a leading cause of irreversible blindness worldwide. However, its molecular and cellular causes are not well understood. Elevated intraocular pressure (IOP) is a major risk factor, but many patients have normal IOP. Colocalization and Mendelian randomization analysis of >240 POAG and IOP genome-wide association study (GWAS) loci and overlapping expression and splicing quantitative trait loci (e/sQTLs) in 49 GTEx tissues and retina prioritizes causal genes for 60% of loci. These genes are enriched in pathways implicated in extracellular matrix organization, cell adhesion, and vascular development. Analysis of single-nucleus RNA-seq …

The Immune System And Metabolic Products In Epilepsy And Glioma-Associated Epilepsy: Emerging Therapeutic Directions, Shashwat Tripathi, Cody L Nathan, Matthew C Tate, Craig M Horbinski, Jessica W Templer, Joshua M Rosenow, Timothy L Sita, Charles D James, Benjamin Deneen, Stephen D Miller, Amy B Heimberger

Faculty, Staff and Students Publications

Epilepsy has a profound impact on quality of life. Despite the development of new antiseizure medications (ASMs), approximately one-third of affected patients have drug-refractory epilepsy and are nonresponsive to medical treatment. Nearly all currently approved ASMs target neuronal activity through ion channel modulation. Recent human and animal model studies have implicated new immunotherapeutic and metabolomic approaches that may benefit patients with epilepsy. In this Review, we detail the proinflammatory immune landscape of epilepsy and contrast this with the immunosuppressive microenvironment in patients with glioma-related epilepsy. In the tumor setting, excessive neuronal activity facilitates immunosuppression, thereby contributing to subsequent glioma progression. …