Digital Commons Network^™

The Role Of Chimeric Antigen Receptor Regulatory T Cells In Promoting Immune Tolerance In Solid Organ Transplantation: Mechanisms And Therapeutic Potential, Maher S. Alwethaynani

Saudi Medical Journal

Solid organ transplantation (SOT) is a life-saving procedure for patients with end-stage organ failure; however, lifelong immunosuppressant use is needed to prevent allograft rejection. These drugs increase the risk of non-Hodgkin lymphoma, liver, kidney, and lung cancers, and heighten susceptibility to oncogenic viruses, including hepatitis B and Epstein-Barr virus. The usage of chimeric antigen receptor (CAR) regulatory T (Treg) cells is a promising approach to induce transplant tolerance while minimizing dependence on immunosuppressants. The CAR Tregs offer the potential to enhance graft survival and quality of life by reducing immunosuppressant-related morbidity and mortality. Despite remarkable progress in transplantation tolerance, challenges …

Meta-Analysis On The Effect Of Tai Chi Chuan On Human Biomechanics And Health From (2021–2025), Bijad S. Alqahtani, Husam A. Almalki

Saudi Medical Journal

Objective: Prior reviews emphasize overall health outcomes of Tai Chi Chuan (TCC) but rarely resolve the biomechanical intermediates (such as Center of Mass (CoM)–Center of Pressure (CoP) control, joint loading) that link practice to clinical function—knowledge that matters for balance, fall risk, and osteoarthritic knee load management. This systematic review and meta-analysis aim to test the null hypothesis that TCC produces no improvement versus comparators in (i) biomechanical stability indices (mediolateral/anterior–posterior CoM–CoP separation; COP Root Mean Square RMS) and (ii) related clinical functions (such as Time up and go (TUG), Berg balance scale (BBS), Western Ontario and McMaster Universities Osteoarthritis …

Developmental Dysplasia Of The Hip In Saudi Arabia And The Gulf Countries: A Genetic Systematic Review Study, Naif Z. Alrashdi, Ahmed M. Almansour, Azfar Jamal

Saudi Medical Journal

Objective: To describe the available research on genetic determinants with special emphasis on the developmental dysplasia of the hip (DDH), in Saudi Arabia and Gulf nations, with reference to the genetic variants, family trend, and environmental factors. Methods: The literature search was conducted in PubMed, Embase, Scopus, Web of Science, and the Saudi Digital Library and Google Scholar through a broad literature search since the beginning of the databases until 2023. Studies that conducted in Saudi Arabia or Gulf countries which evaluated the relationships of genetic factors in DDH were included. Case reports, conference abstracts, and studies that did not …

Exploring Translational Medical Research Progress In G20 Countries: 5-Year Study, Hana A. Alhumud, Fars K. Alanazi, Edward B. Devol

Saudi Medical Journal

Objectives: Biomedical research is crucial for advancing medical knowledge and improving public health. However, the research process is often disjointed and lacks seamless progression, leading to delays and missed opportunities. To address this, the concept of translational research has emerged, focusing on the smooth transition of research results to the next stage of inquiry. Methods: This study analyzed approximately 40,000 research publications from the Web of Science database to identify research activities associated with translational research. Publications from Group of 20 (G20) countries over the past 5 years were examined to explore patterns of research focus and progress in this …

Gadolinium Deposition Concerns In Magnetic Resonance Imaging, Emily Tran

Radiologic Sciences

Purpose To examine how concerns about gadolinium deposition have influenced the use of macrocyclic versus linear contrast agents in magnetic resonance (MR) practice.

Method A structured literature review was conducted using AI-assisted research tools and academic databases to identify recent peer-reviewed original research articles related to gadolinium deposition and contrast agent use patterns in MR. Only studies published between 2020 and 2026 were included.

Results Recent research confirmed that gadolinium can accumulate in human tissues following contrast-enhanced MR examinations. Multiple studies demonstrated that linear gadolinium-based contrast agents are associated with greater levels of tissue retention compared with macrocyclic agents due …

Administrative And Clinical Impacts Of Theranostic Program Expansion In Nuclear Medicine, Karmela Kljajic Pascual

Radiologic Sciences

Purpose To synthesize current evidence on theranostic trials, nuclear medicine clinical workflow models, and organizational readiness, with a focus on how healthcare organizations and medical imaging leaders are adapting to the rapid expansion of theranostic services.

Method A comprehensive search was conducted across Scopus, PubMed, MEDLINE, and Google Scholar. Inclusion criteria required peer‑reviewed articles published between 2002 and 2026 addressing nuclear medicine leadership, theranostic implementation, workflow design, and organizational factors influencing theranostic program development. Exclusion criteria removed editorials, blog posts, and nonpeer‑reviewed sources.

Results Four major themes emerged: workforce and staffing demands, infrastructure and resource requirements, regulatory and administrative pressures, …

Decreased Frequency Of Splenectomy For High-Grade Splenic Injuries Following The Implementation Of An Interventional Radiology Alert Protocol., Maura Kopchak, John Bach, William B Devoe, Brian Dusseau, Katherine A Graham, John Dillis, Thomas Glusich, Jeff Hubartt

OhioHealth Research Institute Articles

Background A vascular interventional radiology (VIR) protocol was initiated at a mature level 2 trauma center on 3/1/2023 to reduce time to vessel puncture to < 60 minutes as per American College of Surgeons (ACS) guidelines. The average time to vessel puncture in the two years prior to protocol initiation was 102 minutes. Following initiation, time to vessel puncture was reduced to 48.2 minutes (p < 0.001). A statistically significant increase in the number of splenic embolizations was noted in the post-protocol group. The primary outcome of the current study was to evaluate if the initiation of a VIR protocol correlated with a statistically significant decrease in splenectomies for high-grade splenic injuries (American Association for the Surgery of Trauma (AAST) grade 3 or higher) in favor of splenic embolization. The secondary outcomes of the study were to assess whether the initiation of the VIR alert protocol improved our rate of splenic salvage, defined as preserved splenic immune function, and if there was a decreased rate of splenectomies across all injury grades. Methods The trauma registry database was queried for all splenic injuries from 1/1/2021 to 9/1/2024. Admission CT scans were used to grade injuries using the AAST Organ Injury Scale. Demographic and clinical characteristics, including severity of illness (ISS), admission INR, age, blood product required pre- and post-intervention, mortality, sex, length of stay, anticoagulant (AC)/antiplatelet (AP) use, mechanism of injury, and need for REBOA (resuscitative endovascular balloon occlusion of the aorta) placement, were collected for all patients. Patients were further broken down into those requiring splenectomy, embolization, or no intervention. Data were analyzed using chi-square and Mann-Whitney U with Jamovi Version 2.3.26.0 (The Jamovi Project, 2023). Results No statistically significant difference was found for clinical or demographic characteristics between groups. Fewer splenectomies and more splenic embolizations were performed in the post-protocol group for high-grade splenic injuries (grade 3), which was statistically significant (p< 0.001). This was also true when all grade splenic injuries were compared (p< 0.001). Conclusion Following the establishment of an institutional VIR alert protocol for active hemorrhage control in trauma patients, more frequent utilization of angioembolization for high-grade splenic injuries was found with a subsequent decrease in splenectomy rate. Implementation of the VIR alert protocol directly correlated with a shift in practice pattern reflecting attempts at splenic salvage for all injury grades.

Hematopoietic Stem And Progenitor Cell Reprogramming During Breast Cancer Progression Promotes Myeloid-Biased Hematopoiesis, Emily Maria Eul

Arts & Sciences Graduate Student Theses and Dissertations

Breast cancer progression is associated with systemic immune dysregulation characterized by the expansion of immunosuppressive myeloid populations that promote tumor progression, metastasis, and resistance to therapy. However, the mechanisms that sustain pathological myeloid expansion remain incompletely understood. In particular, it remains unknown whether solid tumors functionally reprogram hematopoietic stem and progenitor cells (HSPCs) to drive enhanced myeloid output and if bone-derived signals can regulate tumor-associated hematopoietic remodeling. In murine models of primary and metastatic breast cancer, tumor progression induced the remodeling of the hematopoietic compartment, characterized by the expansion of HSPCs, enhanced myeloid differentiation, and systemic accumulation of myeloid populations. …

Non-Enzymatic Hepatic Abhd6 Interacts With Akt-Foxo1 Axis To Regulate Metabolic Health, Guannan Li, Laurence T Maeyens, Jiyuan Yin, Jan-Bernd Funcke, Chanmin Joung, Ruizhen Li, Ziying Xu, Ting Wu, Xin Li, Nisi Jiang, Mbolle Ekane, Maria Paula Lopez, Pengju Cao, Sijia He, Adam B Salmon, S R Murthy Madiraju, Marc Prentki, Juli Bai, James F Nelson, Xianlin Han, Yi Zhu, Shangang Zhao

Children’s Nutrition Research Center Staff Publications

The enzymatic role of ABHD6 in insulin secretion and resistance is well documented. However, its non-enzymatic function, especially its effects on metabolic health, including selective hepatic insulin resistance and metabolic dysfunction-associated steatotic liver disease (MASLD), is poorly understood. To define the role of ABHD6 in liver physiology, we generated liver-specific ABHD6 knockout mice, as well as liver-specific native and enzymatically inactive mutant ABHD6 overexpression mouse models. We demonstrate that non-enzymatic ABHD6 contributes to the regulation of selective hepatic insulin resistance and MASLD progression. Mechanistically, we show that ABHD6 localizes to the nucleus and interacts with Akt/FoxO1 axis to regulate insulin …

Surgeon Health And Well-Being Initiative: A Survey Of General And Orthopedic Surgery Residents' Reports Of Musculoskeletal Pain., Maryam Mohamed, Grace J Kim, Kristen Conrad-Schnetz, Zhan Yang, Mary Carneval

Ambulatory and Primary Care Articles

Background Musculoskeletal (MSK) pain is a well-known risk among surgeons, resulting from the multifactorial physical demands of the occupation. Because of the demands faced by resident surgeons, many individuals find themselves with sometimes debilitating MSK pain. Although these risks are well documented and there have been proposed solutions, there is little discussion on the role that osteopathic manipulative treatment (OMT) can play in relief of MSK pain over time in this population. Objective The purpose of this study is to determine the prevalence and distribution of MSK pain among general and orthopedic surgery residents at Cleveland Clinic Foundation (CCF). Based …

Quantitative Imaging Of Pyruvate Metabolism In A Patient With Anaplastic Thyroid Cancer, James A Bankson, Joshua S Niedzielski, Collin J Harlan, Yunyun Chen, Christopher M Walker, Philip L Lorenzi, Lin Tan, Vikas Kundra, Matthew E Merritt, Mukundan Ragavan, Dawid Schellingerhout, Renjie He, Yao Ding, Sahana Datar, Qing Wang, Christine B Peterson, Clifton D Fuller, Vlad C Sandulache, Stephen Y Lai

Faculty, Staff and Students Publications

Purpose: Magnetic resonance imaging using hyperpolarized (HP) [1-13C]-pyruvate enables assessment of pyruvate metabolism in vivo and offers new insight into metabolic changes in response to cancer therapy. Widely used semi-quantitative metrics of pyruvate metabolism can be affected by physiological factors that are extrinsic to intracellular metabolism. A validated pharmacokinetic (PK) model for analysis of intracellular pyruvate metabolism is needed to enhance the accuracy of quantitative metrics and clinical translation of metabolic MRI using HP pyruvate.

Methods: A PK model with two physical compartments and two chemical pools was developed to analyze the conversion of labeled pyruvate into lactate in vitro. …

The Effect Of Cerebellar Transcranial Direct Current Stimulation On Anxiety, Shivangi Bhardwaj

All-Inclusive List of Electronic Theses and Dissertations

Anxiety is one of the most prevalent mental health disorders in the U.S. Individuals of all ages are affected by anxiety. Therefore, research into anxiety and its potential treatment has constantly been an area of interest. Newer approaches to managing anxiety include non-invasive stimulation techniques, such as Transcranial Direct Current Stimulation (tDCS), because of its accessibility and effectiveness. Past tDCS work typically focused on regions in the frontal lobe. However, tDCS over the cerebellum has not received as much attention compared to the cerebrum, despite recent work demonstrating cerebellar involvement in emotion processing. Thus, a better understanding of how cerebellar …

Source-Specific Nitrate And Nitrite Intake And Bladder Cancer: Findings From The Danish Diet, Cancer And Health Cohort, Dorit W. Erichsen, Cecilie Kyrø, Jörg Schullehner, Susanne Rosthøj, Catherine P. Bondonno, Liezhou Zhong, Ole Raaschou-Nielsen, Pratik Pokharel, Torben Sigsgaard, Peter Fjeldstad Hendriksen, Frederik Dalgaard, Christina Dahl, Jonathan M. Hodgson, Christina C. Dahm, Anja Olsen, Anne Tjønneland, Nicola P. Bondonno

Research outputs 2022 to 2026

Introduction Nitrate and nitrite, present in ground and drinking water, as well as foods, may contribute to bladder cancer through the formation of carcinogenic N -nitrosamines. However, risk likely depends on both the source and endogenous nitrosating factors. Methods Among participants of the Danish Diet, Cancer, and Health Cohort (N = 54,610) with no history of cancer, source-specific nitrate and nitrite intakes (drinking water, plant sources, naturally occurring animal sources, and additive-permitted meat sources) were estimated from national water monitoring data and food frequency questionnaires using food databases. Bladder cancer cases were ascertained through the Danish Cancer Registry. Multivariable-adjusted Cox …

Hyperadhesive Von Willebrand Factor Contributes To Pathogenesis Of Preeclampsia, Yajuan Wang, Chenyu Wang, Katie L Houck, Xiaoli Gao, Yuanyuan Chen, Xin Xu, Xue Zhao, Miguel A Cruz, Shu Zhang, Chester Q Li, Fengxia Xue, Min Li, Swati Shree, Jing-Fei Dong, Cha Han

Children’s Nutrition Research Center Staff Publications

Background: Preeclampsia is the most common complication of pregnancy, significantly affecting maternal and fetal health, and is characterized by placental and systemic endotheliopathy. Patients with preeclampsia have elevated levels of VWF (von Willebrand Factor), which is associated with poor clinical outcomes. However, whether VWF serves as a marker for endotheliopathy or contributes to the pathogenesis of preeclampsia remains poorly understood.

Methods: We investigated the role of hyperadhesive VWF in the development of preeclampsia by studying patients, evaluating mouse models, and performing in vitro experiments.

Results: We show that patients develop VWF- and fibrin-rich thrombosis in the placenta and have significantly …

Indications, Techniques, And Safety Of Cryotherapy And Cryobiopsy Via Flexible Bronchoscopy In Pediatric Patients, Alex J Katz, Haley Haskett, Kubra M Bozkanat, Aoife Corcoran, Lauren M C Grant, Antoinette Wannes Daou, Sin Tran, Esra Caylan, Alfin Vicencio, Dan T Benscoter, Cherie A Torres-Silva, Sara M Zak, Gregory Burg, Lisa R Young, Pelton Phinizy, Shailendra Das, Richard Paul Boesch, Erik B Hysinger, Joseph Piccione

Faculty, Staff and Students Publications

Rationale: Cryotherapy and its diagnostic analogue, cryobiopsy, are emerging techniques via bronchoscopy with a wide range of clinical applications. While the use of cryotherapy and cryobiopsy has been established in adult pulmonary medicine, pediatric data describing the indications, procedural specifics, outcomes, and complications are limited.

Objective: To describe the indications, procedural specifics, outcomes, and complications of cryotherapy and cryobiopsy use in pediatric bronchoscopy.

Methods: A multicenter retrospective observational study was conducted at 5 pediatric hospitals in the United States. Patients aged 0 to 21 years who underwent cryotherapy or cryobiopsy via bronchoscopy between January 2017 and January 2025 were included. …

Hippo Signaling Regulates Cuticle Pigmentation And Dopamine Metabolism In Drosophila, Shelley B Gibson, Samantha L Deal, Ye-Jin Park, Bo Sun, Yanyan Qi, Jung-Wan Mok, Hyung-Lok Chung, Hongjie Li, Shinya Yamamoto

Duncan NRI Faculty and Staff Publications

Pigmentation plays multiple important roles in development, physiology and evolution. Melanization of the insect cuticle requires dopamine as a precursor of melanin and involves key enzymes in dopamine biosynthesis including Tyrosine hydroxylase (TH) and Dopa decarboxylase (Ddc). Some studies have hinted that disruption of the evolutionarily conserved Hippo signaling pathway, which has been primarily studied in the context of tissue growth, may lead to changes in cuticle pigmentation in the fruit fly Drosophila melanogaster. However, to our knowledge, there have not been any systematic investigations into their potential mechanistic links. In this study, we identified that all genes that comprise …

Comparative Effectiveness Of Antiseptic And Antibiotic Irrigation Versus Normal Saline In Infected Total Ankle Arthroplasty: A Systematic Review, Madelaine Adkins, Yahan Wei, Amanda Killeen

School of Podiatric Medicine - Student Research

Introduction: Periprosthetic joint infection (PJI) is a rare but devastating complication following total ankle arthroplasty (TAA). Acute infections are commonly managed with debridement, antibiotics, and implant retention (DAIR), in which irrigation plays a critical role in reducing bacterial burden. Although irrigation protocols have been investigated in total hip and total knee arthroplasty, evidence specific to infected TAA remains unclear. This systematic review evaluated the available literature regarding irrigation practices in the surgical management of infected TAA.

Methods: A systematic review was conducted in accordance with PRISMA guidelines. PubMed and Scopus were search for English-language studies published between December 2005 and …

The Role Of Mitochondria In The Pathogenesis Of Parkinson’S Disease, Oyinkansola Mudasiru, Vivian Etugbo, Bhuvana Lakkasetter, Claudia Biguetti, Reginald Adiele

School of Podiatric Medicine - Student Research

Introduction: Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by the degeneration of the dopaminergic neurons of the substantia nigra that leads to motor and non-motor dysfunctions. Emerging evidence highlights mitochondrial dysfunction as a key factor in PD pathogenesis. This project aims to investigate the pathophysiology of PD, highlighting the involvement of oxidative stress, and examining current and emerging therapeutic approaches aimed at restoring mitochondrial function.

Methodology: A systematic literature review was conducted using PubMed and Google Scholar within the 2004-2024 date range. Keywords included “Parkinson’s disease”, “mitochondrial dysfunction", “oxidative stress”, and neurodegeneration”. Data was extracted regarding …

Genetic Associations With Pulmonary Embolism Among Those With A Deep Vein Thrombosis: The International Network Against Venous Thrombosis Consortium, Susana Lozano-Esparza, Gabrielle E Shakt, Jennifer A Brody, Angel Martinez-Perez, Matthew P Conomos, Marine Germain, Katharine R Clapham, Maris Teder-Laving, Astrid Van Hylckama Vlieg, Anni Kauko, Florian Thibord, Ohanna C L Bezerra, Girish N Nadkarni, Gaëlle Munsch, Therese Haugdahl Nøst, Ellen L Goode, Yuekai Ji, Daniel I Chasman, Alexander P Reiner, Constance Turman, Kerri L Wiggins, Colleen M Sitlani, Juan Carlos Souto, Pamela L Lutsey, Tiffany Bellomo, Estonian Biobank, Million Veteran Program, Ruifang Li-Gao, Aleksi Kristian Winstén, Ming-Huei Chen, Ron Do, Lénaick Gourhant, Kristian Hveem, Sebastian M Armasu, Noémie Saut, Nathan Pankratz, Franco Giulianini, Jeffrey Haessler, Mingyang Song, Robert Olaso, Eric Boerwinkle, Daniel Dochtermann, Jose Manuel Soria, Stephen S Rich, David Smadja, Satoshi Koyama, Frits R Rosendaal, Teemu Niiranen, France Gagnon, Ha My T Vy, Neil Zakai, Catherine Lemarie, Anne Heidi Skogholt, Jean-François Deleuze, James S Pankow, Paul M Ridker, Yuxi Liu, Kenneth M Rice, Saiju Pyarajan, Mary Cushman, Jospeh Emmerich, Bruce M Psaty, Pradeep Natarajan, Andrew D Johnson, Marc A Rodger, Pierre Suchon, Francis Couturaud, Pierre-Emmanuel Morange, Weihong Tang, Charles Kooperberg, Christopher Kabrhel, Maria Sabater-Lleal, David-Alexandre Trégouët, Alisa S Wolberg, Scott M Damrauer, Nicholas L Smith

Children’s Nutrition Research Center Staff Publications

Background: Venous thromboembolism (VTE) includes deep vein thrombosis (DVT) and pulmonary embolism (PE), the latter of which often originates from DVT and can be fatal.

Objectives: The aim of this study was to identify causal genetic factors that alter risk of PE among those with a presumed DVT.

Methods: Using a case-only design of VTE, we conducted meta-analyses of genome-wide association studies (GWASs) in the International Network Against Venous Thrombosis Consortium. Among participants diagnosed with VTE, each study identified those who had a clinically reported PE, with or without a clinically reported DVT; those remaining had isolated DVT. Logistic regression …

Personalizing Modern Heart Failure Therapy In Hfref: Bridging Evidence, Clinical Practice, And Future Perspectives, Ehsan Shahverdi, Amin Shahverdi, Sendooran Shahi, Carsten Schneider, Mathias Lange, Shadi Kamali

Journal of the Saudi Heart Association

Background

Heart failure with reduced ejection fraction (HFrEF) remains a major cause of morbidity, mortality, and healthcare utilization worldwide despite substantial therapeutic advances. Over the past three decades, randomized clinical trials have established four foundational pharmacologic pillars of guideline-directed medical therapy (GDMT): renin–angiotensin system inhibition or angiotensin receptor–neprilysin inhibition, evidence-based beta-blockers, mineralocorticoid receptor antagonists, and sodium–glucose cotransporter 2 inhibitors. However, real-world implementation of these therapies remains suboptimal.

Objectives

To provide a contemporary state-of-the-art review of current evidence supporting GDMT in HFrEF, examine unresolved challenges in sequencing and optimization, and propose a practical phenotype-based framework to support individualized treatment decisions

. …

Neural-Immune-Cardiovascular Axis: From Mechanistic Crosstalk To Therapeutic Targets In Cardiovascular Disease, Junkang Cheng, Shuang Gao, Haowei Zhang, Wei Gao, Zeyuan Mei, Xiaoling Liu, Jocelyn Gao, Chenghu Guo, Guipeng An

Student Papers, Posters & Projects

The neural-immune-cardiovascular axis represents an emerging and highly integrated physiological and pathophysiological concept, describing a complex bidirectional communication network between the nervous, immune, and vascular systems. This review systematically examines the pivotal role of this axis in maintaining cardiovascular homeostasis and in the pathogenesis of cardiovascular diseases. We first provide an overview of the fundamental signaling pathways between the components of this axis. Subsequently, we delve into the specific crosstalk mechanisms within the axis in the context of major cardiovascular conditions, including atherosclerosis, hypertension, and heart failure. A central focus is placed on critically evaluating the potential therapeutic targets and …

Rsv Can Infect The Human Nasal Epithelium Via The Basolateral Route And Shows Distinct Subgroup Infectivity And Basal Cell Tropism, Ashley Murray, Divya Nagaraj, Emily M Schultz, Gina Aloisio, Erin Nicholson, Sarah E Blutt, Vasanthi Avadhanula, Pedro A Piedra

Faculty, Staff and Students Publications

Respiratory syncytial virus (RSV) causes millions of lower respiratory tract infections (LRTIs) in young children, older adults, and immunocompromised populations every year. RSV infection initiates in the upper respiratory tract and can progress to the lower airways, resulting in bronchiolitis, pneumonia, and even death. RSV primarily infects epithelial cells apically, but we hypothesized that basolateral exposure of the respiratory epithelium could provide an alternative mechanism of infection that contributes to LRTI development. Using a human nose organoid-air-liquid interface (HNO-ALI) model, we performed apical and basolateral inoculations with contemporaneous RSV strains (RSV/A/Ontario [RSV/A/ON] and RSV/B/Buenos Aires [RSV/B/BA]) representing the two RSV …

Wellness Literature Review – 2025, Martin Huecker, Brian A. Ferguson

Journal of Wellness

Introduction: Clinician well-being remains a persistent challenge, with ongoing burnout and psychological distress despite efforts by systems and individuals. This Journal of Wellness annual review covers studies published in 2025.

Methods: The Editors searched PubMed and Google Scholar for prospective and interventional studies / clinical trials in humans, with focus on well-being. Authors utilized artificial intelligence (AI)–based large language model (LLM) (ChatGPT, OpenAI^TM) to assist with preliminary identification of relevant studies, however authors noted significant AI-associated errors and outright misrepresentations requiring hand curated product generation and manual PubMed searches.

Literature in Review: We continue to appreciate a shift …

Functional Divergence Of Capicua Isoforms Explains Differential Tissue Vulnerability In Neurological Disease, Hamin Lee, Esmeralda Villavicencio Gonzalez, Elias M Rivera, Mark A Durham, Ronald Richman, Elizabeth H-Y Chu, Kailey Xia, Hu Chen, Zhandong Liu, Surabi Veeraragavan, Binoy Shivanna, Huda Y Zoghbi

Faculty, Staff and Students Publications

Many neurological diseases impact specific brain regions despite widespread expression of the disease-related protein. Spinocerebellar ataxia type 1 (SCA1) primarily affects the cerebellum, though Ataxin-1 (ATXN1) is widely expressed. We previously showed that intensified interaction between mutant ATXN1 and Capicua (CIC) drives SCA1 pathogenesis in the cerebellum, whereas ATXN1 loss augments amyloid β production in the hippocampus and cortex. CIC, however, forms a complex with ATXN1 and its paralog, Ataxin-1-like (ATXN1L), yet knockout of either yields completely different phenotypes. To determine whether this could be due to CIC having two isoforms, we generated mice bearing either the long (CIC-L) or …

Persistent Chemotherapy-Induced Peripheral Neuropathy As A Chronic Cancer Pain Syndrome: Mechanisms, Therapeutic Limitations, And Future Directions, Reed Firestone, Jamin Morrison

Department of Medicine Faculty Papers

Background/Objectives: Chemotherapy-induced peripheral neuropathy (CIPN) is a common, dose-limiting complication of cancer therapy and a major contributor to chronic neuropathic pain among cancer survivors. Although traditionally managed as a treatment-related toxicity, persistent CIPN frequently persists long after chemotherapy completion and is increasingly recognized as a major survivorship and palliative care challenge. This review synthesizes current mechanistic, clinical, and translational evidence and reframes persistent CIPN as a chronic neuropathic cancer pain syndrome. Methods: A narrative review of peer-reviewed literature was conducted using PubMed/MEDLINE, Embase, and the Cochrane Library, supplemented by manual review of key references and clinical guidelines. Emphasis was placed …

Epilepsy-Associated Digenic Variants Affecting An Actin-Mitochondria-Glutamate Pathway Promote Seizure Susceptibility, Shenzhao Lu, Mengqi Ma, Shabab B Hannan, Mingxi Deng, Hu Chen, Zhijian Yu, Lindsey D Goodman, Haein Kim, Yun Zhao, Sandeep Kumar Dubey, Wen-Wen Lin, Xueyang Pan, Debdeep Dutta, Vishnu Anand Cuddapah, Jill A Rosenfeld, Xi Luo, Zhandong Liu, Joshua M Shulman, Hugo J Bellen

Faculty, Staff and Students Publications

Epilepsy affects approximately 50 million people worldwide, yet more than half of individuals with a presumed genetic cause still lack a molecular diagnosis despite the identification of over 1,000 monogenic epilepsy genes. This diagnostic gap is unlikely to be resolved by improved variant detection alone, suggesting that variants affecting the same biological pathway may combine to cause disease. By studying epilepsy-associated actin regulatory genes, we identified a conserved "actin-mitochondria-glutamate (AMG) pathway". We demonstrate that reduced actin polymerization promotes DRP1-mediated mitochondrial fission, increases reactive oxygen species (ROS) levels, and enhances glutamatergic transmission, leading to seizures. The glial innate immune pathway, a …

Premature Ventricular Contractions As A Result Of Subacute Myocarditis In A Professional Football Player, Charlotte Pirquet, Daniel Underberg, Brian Osler, Derek Schwabe-Warf, David Shipon

Department of Medicine Faculty Papers

BACKGROUND: Return-to-play (RTP) decisions for professional athletes with arrhythmias are challenging, particularly when the diagnosis is uncertain.

CASE SUMMARY: A 33-year-old professional football player presented for RTP evaluation of premature ventricular contractions (PVCs) and atypical chest pain. Work-up was significant for fragmented R waves and PVCs on electrocardiogram as well as late gadolinium enhancement on cardiac magnetic resonance imaging. Positron emission tomography scan was normal. These findings suggested possible subacute myocarditis. He elected to rest for 2 to 3 months and was treated with guideline-directed medical therapy. Risk stratification highlighted increased risks associated with late gadolinium enhancement and incomplete genetic …

Combining Menin And Mek Inhibition To Target Poor Prognosis Kmt2a-Rearranged Ras Pathway-Mutant Acute Myeloid Leukemia., Nastassja Scheidegger, Constanze Schneider, Gabriela Alexe, Yi-Cheng Wang, Todd A. Alonzo, Allen Basanthakumar, Wallace A. Bourgeois, Julia Dudkiewicz-Garbicz, Delan Khalid, Lucy A. Merickel, Jennifer A. Perry, Rhonda E. Ries, Silvi Salhotra, Audrey Taillon, Alan S. Gamis, Richard Aplenc, Marian H. Harris, Mark Wunderlich, Scott A. Armstrong, Jessica A. Pollard, Soheil Meshinchi, Yana Pikman, Kimberly Stegmaier

Manuscripts, Articles, Book Chapters and Other Papers

KMT2A-rearranged (KMT2A-r) acute leukemias are especially prevalent in the pediatric population. KMT2A-fusion proteins drive leukemogenic gene expression through an interaction with a chromatin complex that includes the scaffold protein menin, giving rise to aggressive acute leukemias. RAS pathway mutations are also common in pediatric leukemia. In a cohort of 1750 patients enrolled on Children's Oncology Group (COG) trials, we identified RAS pathway mutations in 43% of acute myeloid leukemia (AML) cases. The presence of RAS pathway mutations in KMT2A-r AML was associated with a lower complete remission rate, poor event-free survival and overall survival (OS), and early relapses. Given the …

Bridging Pediatric To Adult Care In Cystinosis: A Scoping Review Of Healthcare Transition Of Care Protocols And A Roadmap For Future Practice., Sanat Subhash, Nicholas Pantelakis, Kyle Backston, Ruhaan Bajpai, Amir Safadi, Brandon Petrovich, Bradley A. Warady, Maria Diaz-Gonzalez De Ferris, Rupesh Raina

Manuscripts, Articles, Book Chapters and Other Papers

Cystinosis is a rare lysosomal storage disorder that affects approximately 1 in 100,000 to 200,000 live births worldwide. Long-term graft success in cystinosis depends on cysteamine adherence and structured multidisciplinary transition, supported by protocols developed by both pediatric nephrologists and hospital organizations. This review explores institutional and regional care models, structured programs such as the RISE protocol and Got Transition's Six Core Elements, and major barriers including adult nephrology expertise, psychosocial stressors, and insurance coverage gaps. Additionally, we explore the impact of digital health tools for their role in supporting cysteamine adherence and maintaining continuity of care. Emerging technologies such …

Biotic Therapies For Irritable Bowel Syndrome: Current Interventions, Gina Wodarczyk, Maria Winte, Diana Mastellone, Termen Singh, Joshua Desipio, Sangita Phadtare

Division of Gastroenterology and Hepatology Faculty Papers

Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder characterized by recurrent abdominal pain and changes in bowel habits without measurable disease processes. Recent research emphasizes the gut-brain-microbiome (GBM) axis and explores how microbiota influence gastrointestinal and central nervous system functions. Here, we first discuss a brief overview of various treatment approaches for IBS, focusing on interventions such as probiotics, prebiotics, or synbiotics that target the GBM axis in adults with IBS. Relevant trials discussed the use of probiotics, prebiotics, or synbiotics.