Medicine and Health Sciences Commons^™

Investigating The Neuronal Role Of The Proteasomal Atpase Subunit Gene Psmc5 In Neurodevelopmental Proteasomopathies, Sébastien Küry, Janelle E Stanton, Geeske M Van Woerden, Amélie Bosc-Rosati, Tzung-Chien Hsieh, Lise Bray, Marielle Oloudé, Cory Rosenfelt, Marie Pier Scott-Boyer, Victoria Most, Tianyun Wang, Jonas J Papendorf, Charlotte De Konink, Wallid Deb, Virginie Vignard, Maja Studencka-Turski, Thomas Besnard, Anna M Hajdukowicz, Franziska G Thiel, Sophie Wolfgramm, Laëtitia Florenceau, Silvestre Cuinat, Sylvain Marsac, Yann Verrès, Audrey Dangoumau, Léa Poirier, Ingrid M Wentzensen, Annabelle Tuttle, Cara Forster, Johanna Striesow, Richard Golnik, Damara Ortiz, Laura Jenkins, Jill A Rosenfeld, Alban Ziegler, Clara Houdayer, Dominique Bonneau, Erin Torti, Amber Begtrup, Kristin G Monaghan, Sureni V Mullegama, Catharina M L Nienke Volker-Touw, Koen L I Van Gassen, Renske Oegema, Mirjam S De Pagter, Katharina Steindl, Anita Rauch, Ivan Ivanovski, Kimberly Mcdonald, Emily Boothe, Andrew Dauber, Janice Baker, Noelle Andrea V Fabie, Raphael A Bernier, Tychele N Turner, Siddharth Srivastava, Kira A Dies, Lindsay C Swanson, Carrie Costin, Alali Abdulrazak, Rebekah K Jobling, John Pappas, Rachel Rabin, Dmitriy Niyazov, Anne Chun-Hui Tsai, Karen Kovak, David B Beck, May Christine V Malicdan, David R Adams, Lynne Wolfe, Rebecca D Ganetzky, Colleen C Muraresku, Davit Babikyan, Zdeněk Sedláček, Miroslava Hančárová, Andrew T Timberlake, Hind Al Saif, Berkley Nestler, Kayla King, M J Hajianpour, Gregory Costain, D'Arcy Prendergast, Chumei Li, David Geneviève, Antonio Vitobello, Arthur Sorlin, Christophe Philippe, Tamar Harel, Ori Toker, Ataf Sabir, Derek Lim, Mark J Hamilton, Lisa J Bryson, Elaine Cleary, Sacha Weber, Trevor L Hoffman, Anna M Cueto-González, Eduardo F Tizzano, David Gómez-Andrés, Marta Codina-Solà, Athina Ververi, Efterpi Pavlidou, Alexandros Lambropoulos, Kyriakos Garganis, Marlène Rio, Jonathan Levy, Sarah J Langas, Anne M Mcrae, Mathieu K Lessard, Maria Daniela D'Agostino, Isabelle De Bie, Meret Wegler, Rami Abou Jamra, Susanne B Kamphausen, Viktoria Bothe, Lorraine Potocki, Eric Olinger, Yves Sznajer, Elsa Wiame, Michelle L Thompson, Molly C Schroeder, Catherine Gooch, Raphael A Smith, Arti Pandya, Larissa M Busch, Uwe Völker, Elke Hammer, Kristian Wende, Benjamin Cogné, Bertrand Isidor, Jens Meiler, Clémentine Ripoll, Stéphanie Bigou, Frédéric Laumonnier, Peter W Hildebrand, Evan E Eichler, Kirsty Mcwalter, Peter M Krawitz, Florence Roux-Dalvai, Ype Elgersma, Julien Marcoux, Marie-Pierre Bousquet, Arnaud Droit, Jeremie Poschmann, Andreas M Grabrucker, Francois V Bolduc, Stéphane Bézieau, Frédéric Ebstein, Elke Krüger

Faculty, Staff and Students Publications

Neurodevelopmental proteasomopathies are a group of disorders caused by variants in proteasome subunit genes, that disrupt protein homeostasis and brain development through poorly characterized mechanisms. Here, we report 26 distinct variants in PSMC5, encoding the AAA⁺ ATPase subunit PSMC5/RPT6, in individuals with syndromic neurodevelopmental conditions. Combining genetic, multi-omics and biochemical approaches across cellular models and Drosophila, we unveil the essential role of proteasomes in sustaining key cellular processes. Loss of PSMC5/RPT6 function impairs proteasome activity, leading to protein aggregation, disruption of mitochondrial homeostasis, and dysregulation of lipid metabolism and immune signaling. It also compromises synaptic balance, neuritogenesis, and neural progenitor …

Transcription-Replication Collisions Trigger High-Fidelity Replication Reset, Matthew B Cooke, Kobie T Welch, Laura Deus Ramirez, Katelin M Hagstrom, Alice X Wen, Jennifer A Halliday, Susan M Rosenberg, Christophe Herman

Faculty, Staff and Students Publications

Double-stranded DNA ends arise from external agents or cellular processes like transcription-replication collisions (TRCs), threatening genome stability. Here, we performed genomic CRISPRi screens to uncover DNA end formation factors in Escherichia coli. We discovered that translation-transcription decoupling causes DNA end formation through a TRC-dependent pathway, which is lethal when DNA end processing by RecBCD is disrupted, but not when recombination is disrupted. We find that TRCs cause replisome stalling followed by "rear-ending" from trailing replisomes which generates free DNA ends, rather than strand breaks. Surprisingly, these DNA ends are resolved through a process we call "replication reset", where the stalled …

Waiting Room And Hallway Care For Older Adults: A Qualitative Study With Emergency Nurses And Technicians, Sarah J Nessen, Ari B Friedman, Annika R Bhananker, K Jane Muir, Anita N Chary

Faculty, Staff and Students Publications

Background: Emergency Department (ED) crowding places older ED patients at risk for adverse outcomes. Crowding often necessitates ED waiting room and hallway care, but there has been limited research on approaches to care for older adults in these settings. Frontline clinician insights can inform best practices for older adults in the context of the ongoing ED crowding crisis. Our objective was to describe the experiences of emergency nurses and technicians in providing waiting room and hallway care for older adults.

Methods: This qualitative study used individual, semi-structured interviews with a purposive sample of 20 ED nurses and technicians at a …

Multimodal Cardiac Imaging Of Immune-Mediated Complications Post Heart Transplantation: A Contemporary Review, Bruno Bezerra Lima, Tam T Doan, Atilla Feher, James C Wilkinson, Marvin W Kronenberg, Chloe Carr, Malek Nayfeh, Tania Ruiz, Luke L Laws, Melissa Lou Silva, John A Wells, Leandro Slipczuk, Emily T Lippincott, John J Carr, Kaushik Amancherla, Cameron Henry, David Parra, Kelly Schlendorf, Quinn S Wells, Sean G Hughes, Jonathan Soslow

Faculty, Staff and Students Publications

Heart transplantation significantly enhances survival and quality of life for patients with end-stage heart failure. Despite advances in surgical and postoperative care, immune-mediated complications, acute graft rejection and cardiac allograft vasculopathy (CAV), remain major barriers to long-term success. Acute rejection predominantly affects early posttransplant survival, whereas CAV becomes a leading cause of mortality in later years. The gold standards for diagnosis, endomyocardial biopsy for rejection and coronary angiography for CAV, are invasive and imperfect. Noninvasive multimodality imaging is increasingly used to complement or, in selected scenarios, defer invasive testing. Echocardiography with strain detects early myocardial dysfunction when ejection fraction is …

Strengthening Implementation Science Research To Improve Adolescent And Young Adult Hiv-Prevention And Care In Sub-Saharan Africa: Patc3h-In, Geri R Donenberg, Ucheoma Nwaozuru, Sylvia Adebajo, Joseph D Tucker, Juliet Iwelunmor, Lisa M Kuhns, Brenda Gati Mirembe, Lisa Hightow-Weidman, Brian Zanoni, Tapiwa A Tembo, Maria Felix Lupogo, Franklin Yates

2020-Current year OA Pubs

BACKGROUND: Despite significant progress in HIV prevention and treatment, uptake of evidence-based interventions among adolescents and young adults (AYA), particularly in low- and middle-income countries (LMICs), remains low. Implementation research can optimize strategies to enhance reach, uptake, and equitable access to these innovations. The Prevention and Treatment through a Comprehensive Care Continuum for HIV-affected Adolescents in Resource-Constrained Settings Implementation Science Network (PATC

METHODS: The PATC

RESULTS: The PATC

CONCLUSIONS: The PATC

CLINICAL TRIAL NUMBER: Not Applicable.

Successful Implementation Of Stroke Risk Screening For Sickle Cell Anemia In The Displace Study: Results Of A Cluster Randomized Trial, Alyssa M Schlenz, Monica L Hulbert, Et Al.

2020-Current year OA Pubs

BACKGROUND: Stroke risk screening using transcranial Doppler (TCD) is a critical evidence-based tool for children with sickle cell anemia (SCA) that has been poorly implemented in the United States. The Dissemination and Implementation of Stroke Prevention Looking at the Care Environment (DISPLACE) study was designed to improve rates of stroke risk screening for SCA using interventions informed by an extensive multi-level barriers and facilitators assessment. This report describes the final outcomes of a large, randomized implementation trial comparing two intervention arms: 1) an application designed to track TCD implementation, ProviderMinder™, versus 2) ProviderMinder™ plus a single coordinator intervention. All sites …

Clinical And Implementation Outcomes Of An Antimicrobial Stewardship Intervention For Rapid Blood Culture Diagnostics, Monica Abdelnour, Christine R Lockowitz, Evan E Facer, Andrew Atkinson, Sara Malone, Virginia R Mckay, Rebekah E Dumm, Alexander S Plattner, Matthew M Sattler, Jason G Newland

2020-Current year OA Pubs

OBJECTIVE: To evaluate the clinical and implementation outcomes of an antimicrobial stewardship program (ASP) intervention to improve antibiotic therapy for a rapid diagnostic test (RDT) for bloodstream infections (BSIs).

DESIGN: Retrospective pre and postintervention study.

SETTING: Single pediatric tertiary center from August 2022 to May 2024.

PARTICIPANTS: Patients presenting with a positive blood culture accompanied by the Verigene (VG) Gram-positive Blood Culture Nucleic Acid (BC-GP) assay. Implementation outcomes surveys were completed by infectious diseases (ID) clinicians and non-ID clinicians.

METHODS: We implemented a 24 hours a day, 7 days a week (24/7) ASP intervention to improve response to BC-GP assay …

Molecular Basis Of Nfib-Mediated Regulation Of Oncogenic Transcription, Ci Zhu, Ding Xiao, Yueyu Wang, Hong Han, Chengxiao Qin, Shuang Liu, Xi Chen, Hejin Xiao, Xin Chen, Junfeng Shi, Juyu Tang, Jie Shen, He Song

2020-Current year OA Pubs

The Nuclear Factor I (NFI) family of transcription factors orchestrates key regulatory programs in development, differentiation, and metabolism, with dysregulation implicated in diverse pathological conditions, including cancer. Among the paralogs, NFIB has emerged as an oncogenic driver in multiple tumor types, yet the mechanisms through which it engages DNA and directs oncogenic transcriptional programs remain undefined. Here, using cancer cells with high NFIB expression, we demonstrate that NFIB promotes malignant phenotypes, as CRISPR-Cas9 knockout impairs proliferation, migration, and invasion. Transcriptomic profiling reveals that NFIB regulates a cancer-enriched gene network that includes FGFR3 and PDGFRB. Biophysical analyses show that NFIB, including …

Cognitive Testing Of Candidate Items In A Wellbeing Measure Developed For Aboriginal And Torres Strait Islander Peoples, Alana Gall, Gail Garvey, Kate Anderson, Abbey Diaz, Kirsten Howard

Journal of the Australian Indigenous HealthInfoNet

Purpose Health and wellbeing for Aboriginal and Torres Strait Islander peoples is poorly understood, due to commonly used measures of quality of life and wellbeing not aligning with their collectivist worldviews. The need to develop a wellbeing measure, grounded in the aspects of life that Aboriginal and Torres Strait Islander people identify themselves as important, was therefore a priority. The current study aimed to cognitively assess the face and content validity of a new wellbeing measure under development for Aboriginal and Torres Strait Islander adults. Methods We employed a qualitative cross-sectional cohort design. Forty-nine unique draft wellbeing statements underwent cognitive …

Quality Improvement Project: Effects Of Ongoing Clinical Education Training On Nursing Faculty’S Self-Efficacy In Clinical Education, Sarah Ferguson

Doctor of Nursing Practice Projects

Clinical education is essential for bridging theory and practice in nursing education, yet many clinical instructors transition from expert bedside nurses to novice educators without adequate orientation and training. This quality improvement project examined the effects of ongoing clinical education training on nursing faculty self-efficacy at a satellite nursing school in North Texas. This project, guided by Patricia Benner’s Novice to Expert framework and Lewin’s change model, aimed to determine whether continuous professional development throughout the term would increase clinical faculty confidence compared to standard onboarding alone. A descriptive pre/post design was used, with the Clinical Nursing Teacher Self-Efficacy Scale …

Current Status And Future Directions For The Use Of Artificial Intelligence In Pediatric Critical Care Nephrology, Sameer Thadani, Christopher M Horvat, Christin Silos, Bronwyn Sutherland, Kristin Dolan, Jin Chen, Ayse Akcan-Arikan, Javier A Neyra

Library Staff Publications

Artificial intelligence (AI) has the potential to significantly improve the practice of medicine. However, its application in pediatric critical care nephrology remains underdeveloped. This scoping review investigates the current state of AI/machine learning (ML) algorithms developed and implemented in the field of pediatric critical care nephrology over more than two decades (2000-2024). We identified 24 articles related to commonly encountered pathologies including acute kidney injury (AKI), electrolyte and acid-base imbalances, fluid management, and dialysis. Twenty (80%) of these articles focused on AKI (prediction and/or detection) and only two articles (4%) investigated the impact of implemented AI/ML models on clinical care …

Possible Involvement Of Keratinocyte-Derived Microvesicle Particles In Human Photosensitivity Disorders, Risha Annamraju, Madison S. Owens, Anita Thyagarajan, Danielle A. Corbin, Catherine M.T. Sherwin, Jade Bryant, Garrett W. Fisher, Winston R. Owens, Alycia Ketter, Craig A. Rohan, Michael G. Kemp, Robyn K. Crow, Jeffrey B. Travers

Pediatrics Faculty Publications

BACKGROUND: Previous murine studies have implicated acid sphingomyelinase-(aSMase) generated subcellular microvesicle particles (MVP) in photosensitivity. Objective: The current double-blinded placebo-controlled studies examined if a single localized ultraviolet B radiation (UVB) treatment generated more MVP in human subjects with self-identified photosensitivity versus normal controls. A topical 4% formulation of the aSMase inhibitor imipramine applied immediately after UVB blocked the MVP release and erythema responses. Erythema responses at 24 and 72 h in response to multiple UVB fluences and minimal erythema doses (MED) at 24 h and effects of imipramine were also tested.

RESULTS: Small cohorts of 10 adult self-identified photosensitive subjects …

Quality Improvement Project: Improving Providers’ Self-Efficacy In Facilitating Mat Usage Through Educational Training, Joshua W. Moore

Doctor of Nursing Practice Projects

Opioid Use Disorder (OUD) and Alcohol Use Disorder (AUD) are common diseases treated in detox facilities around the world. Medication-assisted treatment (MAT) is the most effective treatment for OUD and AUD. Despite the need for MAT, many providers do not prescribe lifesaving medications due to a lack of knowledge and confidence. The purpose of this quality improvement project at a local detox facility is to answer the question: What effect on providers’ self-efficacy in facilitating MAT usage upon discharge does educational training have? Under the Social Cognitive Theory (SCT), self-efficacy was targeted using the Plan-Do-Study-Act (PDSA) change model. The aim …

Exploring Future Educators’ Roles In Classroom Aac Use: Insight Into Knowledge, Skills, And Attitudes, Katrina M. King

Honors College Theses

The United States public school system requires the provision of a free and appropriate public education (FAPE) in the least restrictive environment (LRE) for qualifying students with disabilities (U.S. Department of Education, n.d.). Speech, language, and hearing related disabilities are among the qualifying categories (U.S. Department of Education, n.d.). Students with these disabilities may have complex communication needs (CCN), or significant limitations in their speech, language, and communication abilities (Communication Rights Australia, 2018). Augmentative and alternative communication (AAC), a type of assistive technology, offers support for these students, however, several barriers inhibit full communicative participation (American Speech-Language-Hearing Association [ASHA], n.d.-a). …

Single-Cell Transcriptomic Analysis Of Peripheral Blood Mononuclear Cells Reveals Key Immune Responses In St-Segment Elevation Myocardial Infarction, Zheng Zhang, Shengfang Wang, Yahui Liu, Gaohan Li, Qianqian Cheng, Wei Yang, Gan-Xin Yan, Chuanyu Gao

Department of Medicine Faculty Papers

BACKGROUND: Inflammation plays a crucial role in the pathogenesis of ST-segment elevation myocardial infarction (STEMI). However, the precise immunological mechanisms remain incompletely understood. Single-cell RNA sequencing (scRNA-seq) provides a powerful approach to dissect immune cell heterogeneity and dynamic changes at single-cell resolution.

METHODS: Peripheral blood mononuclear cells (PBMCs) were collected from 7 STEMI patients (within 6h after primary percutaneous coronary intervention) and 3 healthy controls. Single-cell suspensions were prepared and subjected to scRNA-seq using the 10x Genomics Chromium platform and Illumina NovaSeq 6000. Data were processed using Cell Ranger and analyzed with Seurat for quality control, clustering, and annotation. Differentially …

Bilateral Endogenous Fungal Endophthalmitis Following Elective Surgical Abortion: A Single Center Case Series, Viet Q. Chau, Jesse D. Sengillo, Flavius A. Beca, Julia L. Hudson, Thomas A. Albini, Harry W. Flynn

Wills Eye Hospital Papers

BACKGROUND: To describe the clinical features and management of three cases of bilateral endogenous fungal endophthalmitis following elective surgical abortion performed at the same outpatient surgical center.

METHODS: Case series.

OBSERVATIONS: Three immunocompetent women presented with vision loss days to weeks following elective surgical abortions performed at a single outpatient clinic. Initial visual acuities ranged from 20/20 to 20/300. Fundoscopic examination revealed multiple white round chorioretinal lesions with vitreous infiltration bilaterally in all three patients. Vitreous tap samples were obtained for culture and broad-spectrum intravitreal antimicrobials were administered. Despite negative cultures and systemic workup, the clinical presentation was consistent with …

Ash Sickle Cell Disease Cpkd Guidelines Report, Robert I. Liem, Madeleine Verhovsek, Ted Wun, Sophie Lanzkron

Cardeza Foundation for Hematologic Research

No abstract provided.

Exploring The Experiences Of Bahamian Men Diagnosed With Hypertension And Medication Adherence, Bianca Edwards

Walden Dissertations and Doctoral Studies

Hypertension (HTN) is associated with significant health complications, including stroke, myocardial infarction, heart failure, and kidney disease. Despite advances in the treatment and management of HTN, a lack of medication adherence contributes to the persistence of HTN-related morbidity and mortality affecting men in The Bahamas. The purpose of this qualitative descriptive phenomenological study, guided by Pender’s health promotion model and Bandura’s social cognitive theory, was to explore the lived experiences of Bahamian men diagnosed with hypertension regarding their adherence to prescribed medications. Using Giorgi’s descriptive phenomenological method, in-depth, semistructured interviews were conducted with 11 participants. Data were analyzed through repeated …

Impact Of Community Factors On Naloxone Overdose Reduction In Ohio, Theophilus Oduro Frimpong

Walden Dissertations and Doctoral Studies

The opioid crisis in Ohio, driven by fentanyl, persists due to inequitable access to naloxone despite its proven effectiveness. This study examined how socioeconomic status (SES), race/ethnicity, population density, and hospital availability per capita predicted naloxone overdose reversals (dependent variable) in Ohio. Social-ecological theory guided this quantitative historical correlational analysis of Ohio’s Project DAWN index data (N = 5,280). Inclusion criteria included individuals ages 18 to 65 with naloxone-related overdose reversals (dependent), naloxone distribution (moderator), and community factors (independent). Multiple linear regression results showed that SES (p >.50), race/ethnicity (% White, p = .588; % Black, p = .495; % …

Field Validation Of Multiple Species Distribution Models Shows Variation In Performance For Predicting Aedes Albopictus Distributions At The Invasion Edge, Anna V. Shattuck, Brandon D. Hollingsworth Ph.D., Jared Skrotzki, Scott R. Campbell, Christopher L. Romano, Courtney C. Murdock

Faculty Publications

Background

Climate and land use changes have resulted in range expansion of many species. In this shifting disease landscape, it is important to leverage tools that can predict the distributions of invading vectors to target surveillance and control efforts and identify at-risk populations. Species distribution models (SDMs) are used to predict ranges of invasive species; however, invasive species often violate assumptions of equilibrium and niche conservatism. Moreover, these studies are rarely validated using independent data.

Methods 

We use long-term surveillance data for Aedes albopictus, a highly invasive mosquito capable of transmitting several arboviruses, at its range edge to evaluate a …

Optimizing Lower Intensity Triplet Therapy In Acute Myeloid Leukemia: A Practical Guide, Wei-Ying Jen, Curtis A Lachowiez, Jennifer Marvin-Peek, Jessica K Altman, Musa Yilmaz, Jacqueline S Garcia, Yasmin Abaza, Nicholas J Short, Joshua F Zeidner, Naval G Daver, Andrew H Wei, Ghayas C Issa, Courtney D Dinardo

Faculty, Staff and Student Publications

Venetoclax-based doublets with azacitidine or low dose cytarabine are the standard of care for the treatment of acute myeloid leukemia (AML) in older patients or those unfit for intensive chemotherapy. However, some patients do not attain complete remission, and over time, most patients relapse. Frontline triplet therapy incorporating a targeted therapy (FLT3, IDH or menin inhibitor) is an emerging treatment concept under investigation for this population. Initial triplet regimens have yielded encouraging composite complete remission and measurable residual disease negativity rates, enabling the transition to allogeneic stem cell transplantation for eligible patients. While effective, triplets are associated with myelosuppression and …

Advances In Artificial Intelligence For Glioblastoma Radiotherapy Planning And Treatment, Reid Master, Nesha Rubin, James Sampson, Kamlesh K Yadav, Shruti Pandita, Aria Sabbagh, Anika Krishnan, Patrick J Silva, Kenneth S Ramos, Vincent Gregoire, Nikos Paragios, Sunil Krishnan, Tej K Pandita

The Brown Foundation: Institute of Molecular Medicine

Glioblastoma is an aggressive central nervous system tumor characterized by diffuse infiltration. Despite substantial advances in oncology, survival outcomes have shown little improvement over the past three decades. Radiotherapy remains a cornerstone of treatment; however, it faces several challenges, including considerable inter-observer variability in clinical target volume delineation, dose constraints associated with adjacent organs at risk, and the persistently poor prognosis of affected patients. Recent advances in artificial intelligence, particularly deep learning, have shown promise in automating radiation therapy mapping to improve consistency, accuracy, and efficiency. This narrative review explores current auto segmentation frameworks, dose mapping, and biologically informed radiotherapy …

Deep Learning Reveals How Cells Pull, Buckle, And Navigate Fibrous Environments, Abinash Padhi, Arka Daw, Atharva Agashe, Medha Sawhney, Maahi M Talukder, Mehran M H Pour, Mohammad Jafari, Guy M Genin, Farid Alisafaei, Sohan Kale, Anuj Karpatne, Amrinder S Nain

2020-Current year OA Pubs

Cells in tissues navigate fibrous environments fundamentally differently than they do on flat substrates, but the establishment of cell forces in physiological fibrous settings remains poorly understood. Although factors such as the stiffness of the extracellular matrix (ECM) are known to drive behaviors, including cell motility on flat nonfibrous substrates, the interplay between fiber architecture and stiffness in fibrous ECM is not known. Here, we find that in fibrous environments, the directionality of mechanical forces overrides ECM stiffness as the primary regulator of contractility in migrating cells. Using an approach combining phase microscopy with deep learning to map forces in …

Mitochondrial Iron Transport Via Mfrn1 Is Required For Erythroid Cell Cycle Progression, Mark Perfetto, Aidan Danoff, Muhammad Ishfaq, Heidi Monroe, Aiden Mohideen, Meilin Chen, Jesus Tejero, Amber N Stratman, Satoshi Okawa, Yvette Y Yien

2020-Current year OA Pubs

Iron metabolism drives key erythropoietic processes, including hemoglobinization, survival, and proliferation. Here, we developed in vivo methods to interrogate how iron regulates erythropoiesis and report that mitochondrial iron transport via mitoferrin-1 (MFRN1) is essential for erythroid cell cycle progression. mfrn1 embryos had severely decreased erythroid cell number caused by cell cycle arrest at G2/M. They had enlarged nuclei, suggesting a mitotic defect. Iron supplementation rescued the cell cycle defect, implicating mitochondrial iron deficiency as its cause. In contrast, fpn1 mutants, anemic from systemic iron deficiency, had less severe decreases in erythroid mitochondrial iron than mfrn1 mutants and no proliferative defects. …

Targeting The Hepatic Circadian Clock Concomitant With Tyrosine Kinase Inhibition Reverses Late-Stage Hepatocellular Carcinoma, Baharan Fekry, Savera Aggarwal, Rachel Van Drunen, Rafael Bravo, Andy Escalante, Constance Atkins, Sheng Pan, Zheng Chen, Kai Sun, David R Hall, Mamoun Younes, Kristin Eckel-Mahan

Faculty, Staff and Student Publications

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths. Most patients present at advanced stages, and the effectiveness of tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors is constrained by limited patient response. A subset of HCC shows elevated expression of the promoter 2 ("P2")-driven hepatocyte nuclear factor 4 alpha (HNF4α) isoform, which directly transcriptionally represses the circadian brain and muscle ARNT-like protein 1 (BMAL1) transcription factor. This subtype of HCC is robustly inhibited by the plant-based flavonoid nobiletin (NOB), a circadian-fortifying compound. Using patient-matched human HCC and serum, we show that BMAL1-deficient HCC shows exaggerated carnitine palmitoyl transferase …

Patient-Reported Outcomes After Ipsilateral Radiation Therapy For N2b Tonsillar Squamous Cell Carcinoma, Chike O Abana, Adam S Garden, G Brandon Gunn, Gregory M Chronowski, Abdallah S R Mohamed, Andrew J Frankart, Natalie Geier, Houda Bahig, Carly E A Barbon, Kate Hutcheson, Vinita Takiar, Clifton D Fuller, Steven J Frank, David I Rosenthal, Jack Phan

Faculty, Staff and Student Publications

Background: Previous studies have reported excellent disease control and survival in patients with well-lateralized, American Joint Committee on Cancer (AJCC)-7 T1-2N2b tonsillar squamous cell carcinoma (SCC). The reduced treatment volume is associated with lower rates of physician-assessed toxicity. Patient-reported outcomes (PROs) have been proposed as a similarly reliable measure, but the body of literature is limited for unilaterally treated patients. Our goal was to review PROs of such patients who had reduced treatment volumes.

Methods: We reviewed PROs of patients with AJCC-7 T1-2N2b disease treated with ipsilateral radiation therapy (RT), with or without surgery or chemotherapy before RT. PROs were …

Coordinated Transfer Of Dna Between Pol Θ And Pol Δ Resets Microhomology Choice During Double-Strand Break Repair, Yuzhen Li, Mark Returan, Adele T Guerin, April M Averill, Dorcas Oladapo, Sylvie Doublié, Richard D Wood

Faculty, Staff and Student Publications

DNA polymerase theta (Pol θ)-mediated end joining (TMEJ) initiates DNA double-strand break repair by using short homologies (microhomologies) between single-stranded DNA tails. This repair process is particularly important in cancer cells defective in homologous recombination. The exonuclease function of DNA polymerase delta (Pol δ) has been identified as an essential component for TMEJ, functioning to remove unpaired bases flanking a microhomology (MH). It is not known if the exonuclease removes all unpaired bases at once and how this removal might affect subsequent MH selection. Here, we reconstituted a functional TMEJ repair process using purified human Pol θ and Pol δ. …

Botulinum Toxin Combined With Robot-Assisted Therapy For Post-Stroke Spasticity: A Systematic Review, Salvatore Facciorusso, Stefania Spina, Mirko Filippetti, Rajiv Reebye, Gerard E Francisco, Andrea Santamato

Faculty, Staff and Student Publications

Background: Post-stroke spasticity limits motor recovery and independence. Combining botulinum toxin type-A (BoNT-A) injection with intensive, task-specific robot-assisted therapy (RAT) might enhance neuroplasticity and functional gains, but its additive effect and optimal timing are uncertain. (

Methods: We systematically searched major medical databases and trial registries up to April 2025 for randomized controlled trials in adults with post-stroke spasticity comparing botulinum toxin type-A injection plus RAT with toxin injection plus conventional therapy, or RAT alone with RAT combined with toxin injection. Risk of bias was assessed using the RoB 2 tool, and findings were synthesized narratively.

Results: Seven trials ( …

Improving Dynamic Balance And Gait Adaptation With Ischemic Conditioning Post-Stroke, Stephanie Christine Wolfe

Dissertations (1934 -)

The purpose of this dissertation was to quantify the benefits of ischemic conditioning on reactive balance responses and gait adaptation during treadmill walking in chronic stroke survivors. Reactive balance and gait adaptations are believed to be limited in this population. Ischemic conditioning is an emerging adjunct to physical therapy that improves motor function post-stroke via improvements in strength, voluntary muscle activation, walking speed, and fatigability. Here, we quantified how ischemic conditioning could impact performance of a more complex task: altering gait to meet various perturbing conditions. Specifically, we quantified mediolateral margin of stability in response to lateral cable pulls (both …

Fraud Detection And Explanation In Medical Claims Using Gnn Architectures, Reem Muhammad, Dina Tbaishat, Amril Nazir, Seif Yacoub, Mustafa Abdulrazek, Mohamed Ahmed Abo El-Enen, Ahmed T. Sahlol

All Works

This paper addresses the critical challenge of fraud detection in medical insurance claims-a pervasive issue causing significant financial losses in healthcare-using Graph Neural Networks (GNNs). Given the intricate nature of healthcare data, traditional fraud detection methods do not inherently capture the complex relationships and patterns among different entities. We explore the potential of GNNs to effectively identify fraudulent claims by modeling the interactions among various entities-such as patients, healthcare providers, diagnoses, and services-as a heterogeneous graph. We employ two state-of-the-art heterogeneous GNN architectures, HINormer (Heterogeneous Information Network Transformer) and HybridGNN, along with a modified homogeneous GNN, RE-GraphSAGE (GraphSAGE Graph Sample …