Digital Commons Network^™

Nf2 Loss-Of-Function And Hypoxia Drive Radiation Resistance In Grade 2 Meningiomas, Bhuvic Patel, Sangami Pugazenthi, Collin W English, Vijay Nitturi, Shree S Pari, Tatenda Mahlokozera, William A Leidig, Hsiang-Chih Lu, Alicia Yang, Kaleigh Roberts, Patrick Desouza, Kyle P Mcgeehan, Diane D Mao, Namita Sinha, Joseph E Ippolito, Sonika Dahiya, Allegra Petti, Hiroko Yano, Tiemo J Klisch, Akdes S Harmanci, Akash J Patel, Albert H Kim

Duncan NRI Faculty and Staff Publications

Background: World Health Organization Grade 2 meningiomas (G2Ms) often recur and resist therapies. Grade 2 meningiomas with histopathological necrosis have been associated with worse local control (LC) after radiation therapy, but the drivers and biomarkers of radiation resistance in G2Ms remain unknown.

Methods: We performed genetic sequencing and histopathological analysis of 113 G2Ms and investigated the role of genetic and microenvironmental factors on clonogenic survival after ionizing radiation. We performed transcriptional profiling of our in vitro model and 18 human G2M tumors by bulk RNA sequencing as well as 8 G2Ms by single nuclei RNA sequencing.

Results: NF2 loss-of-function (LOF) …

Cardiac Autonomic Dysfunction In Patients With Cancer: Exploring The Role Of Physical Exercise, Anita Borsati, Linda Toniolo, Christian Ciurnelli, Francesco Bettariga, Silvia Teresa Riva, Paolo Frada, Lorenzo Belluomini, Ilaria Trestini, Daniela Tregnago, Jessica Insolda, Marco Sposito, Federico Schena, Michele Milella, Robert U. Newton, Sara Pilotto, Alice Avancini

Research outputs 2022 to 2026

Purpose: Cardiovascular diseases are a leading cause of non-cancer mortality among patients with cancer, with cardiac autonomic dysfunction identified as a significant predictor of future cardiovascular conditions. Despite the importance of autonomic dysfunction as a prognostic marker being well-established in healthy individuals and other chronic conditions, its role in patients with cancer remains underexplored. This narrative review aims to synthesize existing literature on the role of cardiac autonomic dysfunction in patients with cancer and explore the potential of physical exercise as a non-pharmacological intervention to modulate the autonomic nervous system positively. Methods: This review examines methods for assessing cardiac autonomic …

The Evolution Of Sprinting Performance: Technological And Regulatory Influences From 1976 To 2024, Dariusz Tadeusz Skalski, Magdalena Prończuk, Kinga Łosińska, Ewelina Lulińska, Joanna Motowidło, Petr Stastny, Adam Maszczyk, Grzegorz Trybek

Baltic Journal of Health and Physical Activity

Background: This study examines the progression of sprinting performance across the 100m, 200m, and 400m events from 1976 to 2024, highlighting the influence of technological advancements and regulatory changes. Over the past decades, sprinting has been significantly shaped by developments in track surfaces, footwear technology, training methodologies, and regulatory frameworks. Understanding these factors is essential for assessing how sprint times have evolved and what future trends might emerge. Materials and methods: Utilizing a comprehensive dataset from international athletics federations, this research applies time series analysis, regression modeling, and variance testing to assess trends, gender disparities, and performance variability. Data sources …

Navigating Crisis: A Qualitative Exploration Of Parents' Journeys With Suicidal Adolescents In Australian Emergency Departments, Demee Rheinberger, Lauren Mcgillivray, Fiona Shand, Sally Ann Pollard, Susanne Oliver Armstrong, Julia Lessing, Katherine Boydell

The Qualitative Report

Rates of emergency department (ED) presentations for suicide crisis (thoughts, feelings, plans and behaviours) in adolescents are increasing. Parents play a key role in supporting adolescents during and after the ED presentation, however little is known about parental experiences in the ED. Interviews with 20 parents from across Australia were undertaken to help understand this experience. A reflexive thematic analysis was conducted, resulting in three themes which explore the impact of the suicide crisis and ED presentation on the parents’ sense of identity. First, parents’ identity was threatened as they were faced with the juxtaposition between the role of protector …

Development Of A Novel Biomarker Platform For Profiling Key Protein-Protein Interactions To Predict The Efficacy Of Bh3-Mimetic Drugs, Andrew J Kinloch, Faiyaz Rahman, Bahriye Karakas, Muhammad Shahid, Bora Lim, Stephanie J Bouley, James A Walker, Erinna F Lee, Walter D Fairlie, Kevin R Kelly, Michael H Cardone

Faculty, Staff and Student Publications

One of the hallmarks of cancer cells is their failure to respond to the cellular mechanism of apoptosis. The B-cell lymphoma 2 (BCL-2) family of proteins regulate apoptosis. Their ability to do so can be measured using several methods that in turn anticipate the fate of the cancer cell in response to apoptosis-inducing treatment. These assays ultimately identify the readiness of the cancer cell to undergo apoptosis, which is referred to as the mitochondrial priming state. These metrics, however, have been challenging to implement in the clinic.

Anti-Viral Cd8 Central Memory Veto Cells As A New Platform For Car T Cell Therapy, Wei-Hsin Liu, Anat Globerson Levin, Assaf Lask, Galit Horn, Tova Waks, Bar Nathansohn Levi, Irit Milman Krentsis, Einav Shoshan, Xiaohua Su, Maksim Mamonkin, Richard E Champlin, Yair Reisner, Esther Bachar Lustig

Faculty, Staff and Student Publications

Central memory CD8 T cells exhibit marked veto activity enhancing engraftment in several mouse models of T cell-depleted bone marrow (TDBM) allografting. Graft-versus-host disease (GVHD) can be prevented by stimulation of mouse or human memory CD8 T cells against their cognate antigens under cytokine deprivation, in the early phase of culture followed by further expansion with IL21, IL15, and IL7. Thus, human anti-viral CD8 central memory veto T cells generated from CMV and EBV-positive donors are currently evaluated in a clinical trial at MD Anderson Cancer Centre (MDACC). Results in 15 patients indicate a low risk of GVHD. Considering that …

Colorectal Cancer And The Risk Of Mortality Among Individuals With Suicidal Ideation, Srikanta Banerjee, Jagdish Khubchandani, Stanley Nkemjika

Department of Psychiatry and Human Behavior Faculty Papers

Suicide is a major public health problem that has grown at alarming rates in the last two decades. Colorectal cancer (CRC) is one of the most common causes of cancer deaths in the United States in both males and females. However, the influence of suicidal ideation (SI) on the association between CRC and risk of mortality has not been well examined.

METHODS: For this study, the 2005-2018 National Health and Nutrition Examination Survey (NHANES), a nationally representative survey of United States adults aged 20 years or older, was utilized. CRC survivorship was determined from self-reported data on CRC, and mortality …

The Tweak/Fn14 Signaling Mediates Skeletal Muscle Wasting During Cancer Cachexia, Meiricris Tomaz Da Silva, Anirban Roy, Anh Tuan Vuong, Aniket S Joshi, Cristeena Josphien, Meghana V Trivedi, Sajedah M Hindi, Vihang A Narkar, Ashok Kumar

Faculty, Staff and Student Publications

Cancer cachexia is a multifactorial syndrome characterized by progressive skeletal muscle wasting. The TWEAK-Fn14 system regulates muscle mass in diverse conditions. However, its role in the regulation of muscle mass during cancer cachexia remains less understood. Here, we demonstrate that the levels of Fn14 are induced in skeletal muscle of multiple mouse models of cancer cachexia. Muscle-specific deletion of Fn14 reduces myofiber atrophy in mouse models of pancreatic and lung cancer cachexia. Silencing of Fn14 in KPC pancreatic cancer cells prior to their implantation in mice attenuates tumor growth without affecting myofiber size. Muscle-specific deletion of Fn14 reduces the gene …

Neovascular Pruning By Ido1 Inhibitors Can Potentiate Immunogenic Cytotoxicity Of Ischemia-Targeted Agents To Synergistically Enhance Anti-Pd-1 Responsiveness, Shih-Chun Shen, Souvik Dey, James B. Duhadaway, Erika Sutanto-Ward, Maurice T. Hampton, Serguei V. Kozlov, George C. Prendergast, Alexander J. Muller

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND: Strategies for deploying indoleamine 2,3-dioxygenase 1 (IDO1)-targeted therapies for use against cancer have focused on IDO1's role in promoting peripheral immune tolerance that shields tumors from effector T cells. However, preclinical investigation of both primary and metastatic tumor development in the lungs has uncovered a previously unappreciated role for IDO1 in directing a counterregulatory response to interferon (IFN)-γ that realigns the local inflammatory environment to promote tumor neovascularization. Understanding how to therapeutically leverage the ability of IDO1 inhibitors to subvert inflammatory neovascularization within the tumor microenvironment has potential ramifications for future clinical development of these compounds.

METHODS: Pulmonary metastases …

Secreted Phosphoprotein 1 In Lung Diseases, Hongli Liu, Cristian Coarfa, Arzoo N Charania, Jennifer L Larson-Casey, Ivan O Rosas, Chao He

Faculty, Staff and Students Publications

Secreted phosphoprotein 1 (SPP1), also known as osteopontin (OPN) or early T lymphocyte activation protein 1 (ETA-1), is a multifunctional protein involved in numerous biological processes, including immune modulation, stress response, and tissue remodeling. The role of SPP1 in interstitial lung diseases (ILDs) has become an area of increasing interest, given its elevated expression in various ILDs such as idiopathic pulmonary fibrosis (IPF), connective tissue disease-associated ILD (CTD-ILD), and pneumoconiosis, especially with recent data derived from single-cell RNA sequencing. In addition to ILDs, SPP1 has been implicated in infectious granulomatous lung diseases, lung and pleural malignancies, airway diseases, and COVID-19. …

Integrating Radiogenomics And Machine Learning In Musculoskeletal Oncology Care, Rahul Kumar, Kyle Sporn, Akshay Khanna, Phani Paladugu, Chirag Gowda, Alex Ngo, Ram Jagadeesan, Nasif Zaman, Alireza Tavakkoli

Department of Medicine Faculty Papers

Musculoskeletal tumors present a diagnostic challenge due to their rarity, histological diversity, and overlapping imaging features. Accurate characterization is essential for effective treatment planning and prognosis, yet current diagnostic workflows rely heavily on invasive biopsy and subjective radiologic interpretation. This review explores the evolving role of radiogenomics and machine learning in improving diagnostic accuracy for bone and soft tissue tumors. We examine integrating quantitative imaging features from MRI, CT, and PET with genomic and transcriptomic data to enable non-invasive tumor profiling. AI-powered platforms employing convolutional neural networks (CNNs) and radiomic texture analysis show promising results in tumor grading, subtype differentiation …

Biallelic Loss-Of-Function Variant In Minpp1 Causes Pontocerebellar Hypoplasia With Characteristic Severe Neurodevelopmental Disorder, Aljazi Al-Maraghi, Rulan Shaath, Katherine Ford, Waleed Aamer, Jehan Alrayahi, Sura Hussein, Elbay Aliyev, Nourhen Agrebi, Muhammad Kohailan, Satanay Z Hubrack, Sasirekha Palaniswamy, Adam D Kennedy, Karen L Debalsi, Sarah H Elsea, Ruba Benini, Tawfeg Ben-Omran, Bernice Lo, Ammira S A Akil, Khalid A Fakhro

Faculty, Staff and Students Publications

Pontocerebellar hypoplasia (PCH) encompasses a group of autosomal recessive neurodegenerative disorders marked by cerebellar and pontine atrophy. Multiple subtypes of PCH have been identified, among which the rare subtype PCH type 16 is caused by MINPP1 genetic variants. MINPPI encodes an enzyme essential for inositol polyphosphate dephosphorylation, regulating calcium and iron homeostasis. We conducted genome sequencing on a proband from the consanguineous family, who presented with a severe neurodegenerative disorder, to identify the underlying cause of disease. A comprehensive clinical assessment in addition to neuroradiological findings are described. We performed the functional validation of the identified variant and conducted untargeted …

Socioeconomic Disparities In Breast Cancer Survival: Examining Potential Mediator Role Of Oncotype Dx(Odx) Test And Stage At Diagnosis Among Hr+/Her2- Breast Cancer Women, Pratibha Shrestha, Qingzhao Yu, Edward S. Peters, Edward Trapido, Mei Chin Hsieh, Tekeda Ferguson, Quyen D. Chu, Xiao Cheng Wu

School of Public Health Faculty Publications

Background: Women with a lower socioeconomic status (SES) have an increased risk of dying from breast cancer (BC) than those with a higher SES. The association of SES with BC survival may be partially mediated by factors such as Oncotype DX (ODX) testing and stage at diagnosis. This study aims to examine SES disparities in survival among HR+/HER2- BC women and to quantify the mediating effects of the ODX test and stage. Methods: We used data from the Louisiana Tumor Registry to identify women aged 20–90 years diagnosed with stage I–II in 2011–2014 and stage I–III in 2015–2017 HR+/HER2- BC …

Circulating Tumor Dna Monitoring And Blood Tumor Mutational Burden In Patients With Metastatic Solid Tumors Treated With Atezolizumab, Charles Swanton, Russell W Madison, Candice Francheska B Tambaoan, Funda Meric-Bernstam, Christopher J Sweeney, Razelle Kurzrock, Howard A Burris, David R Spigel, Hanna Tukachinsky, Jason Hughes, Julia Malato, Bongin Yoo, Tania Szado, Cheryl Schwab, Lincoln W Pasquina, Amaya Gasco, Katja Schulze, Claire F Friedman

Faculty, Staff and Student Publications

Immune checkpoint inhibitors are important for treatment across tumor types but are not universally effective in controlling disease. Early understanding of tumor response, or lack thereof, can inform treatment decisions. This study evaluates changes in circulating tumor DNA (ctDNA) and blood tumor mutational burden (bTMB) for associations with response to programmed cell death 1 ligand 1 (PD-L1) blockade. We sequenced cell-free DNA collected at the start of therapy, on treatment, and at the end of therapy for 153 patients treated with atezolizumab as part of the pan-tumor MyPathway study (NCT02091141). ctDNA tumor fraction (TF) and bTMB were assessed …

Impact Of A Sepsis Quality Improvement Initiative On Clinical And Operational Outcomes, Christopher B. Thomas, Benjamin Wyler, Claude M. D’Antonio, Mark Laperouse, Shannon Alwood, Kristen Richard, Alyse Grantham, Roya Sheybani, Matt G. Sorrells, Wei Jien Tan, James W. Teague, Hollis O’Neal, Tonya Jagneaux

School of Medicine Faculty Publications

Background/Objectives: Sepsis is a costly and life-threatening condition caused by a dysregulated host response to infection. Lack of a reliable, timely diagnostic for sepsis leads to under- and overdiagnosis, suboptimal outcomes, and strained hospital resources. Our Lady of the Lake Regional Medical Center (OLOLRMC) implemented a sepsis learning health program to evaluate and improve outcomes through standardized ED workflows and the incorporation of a novel sepsis diagnostic test. Methods: We report the results of the first year of experience following the implementation of the learning health initiative and sepsis testing. Data from the Epic EHR were analyzed across two groups: …

Genetic Factors Associated With Myocardial Infarction In Saudi Arabia, Abdullah Saeed, Abdullah Alshafea, Hussain Aldaghaies, Abdullatif Saeed, Abdulrahman Alshehri

Journal of the Saudi Heart Association

Introduction:

Myocardial infarction (MI) is one of the leading causes of mortality in Saudi Arabia, with individuals sharing genetic, lifestyle, and environmental risk factors. The present investigation aimed to review the literature on genetic susceptibility to MI among Saudi individuals, with a specific emphasis on genome-wide association studies (GWAS) for coronary artery disease (CAD) and MI. Studies have revealed the relationship between polymorphisms in genes such as proprotein convertase subtilisin/kexin type 9 (PCSK9), cholesteryl ester transfer protein (CETP), and cyclin-dependent kinase inhibitor 2B antisense RNA 1 (CDKN2B-AS1), which are involved in lipid metabolism, inflammation, and endothelial function.

Methods:

This PROSPERO-registered …

Antibiofilm Properties Of 4-Hydroxy-3-Methyl-2-Alkenylquinoline, A Novel Burkholderia-Derived Alkaloid, Mckinley D Williams, Taylor R Sweeney, Sabrina Trieu, Ravi Orugunty, Abdelahhad Barbour, Fereshteh Younesi, Michael Glogauer, Nopakorn Hansanant, Ronald Shin, Shi-En Lu, Kevin Cao, Abraham Tenorio, Sigmund J Haidacher, Anthony M Haag, Thomas D Horvath, Leif Smith

Faculty, Staff and Students Publications

Biofilms are an important colonization mechanism employed by several microbial species to better establish themselves and monopolize the acquisition of resources across different environs. Some bacteria have evolved specialized metabolites that, when secreted, disrupt the formation and stability of biofilms generated by competing heterospecies, providing the producing organism with an ecological advantage. Soil-derived species are probable candidates for the identification of such compounds, given the intense level of competition that occurs within the terrestrial ecosystem. The MS14 strain of Burkholderia contaminans isolated from soil in Mississippi has previously been shown to produce antimicrobial compounds like occidiofungin and ornibactin. In this …

Unpacking Violence: Examining Socioeconomic, Psychological, And Genetic Drivers Of Gun-Related Homicide And Potential Solutions, John Menezes, Kavita Batra

Department of Plastic Surgery Faculty Research

Background: Gun-related homicide remains a persistent public health crisis in the United States, with over 48,000 firearm-related deaths reported in 2022, including 19,651 homicides and 27,032 suicides. Despite frequent calls for tighter gun control, firearm access alone does not explain the complexity of violence. Objective: This commentary aims to unpack the socioeconomic, psychological, and biological drivers of gun-related homicide and propose integrative, evidence-based solutions that extend beyond legislative reform. Methods: We synthesized data from peer-reviewed literature, national crime and health databases (e.g., Centers for Disease Control and Prevention and Federal Bureau of Investigation), and international reports. We examined patterns related …

Portal Vein Obstruction In Pediatric Liver Transplant Patients: An Evaluation Of Self-Reported Management Practices., Lydia Sieben, Bader A. Alfares, Ruben H. De Kleine, Barbara E. Wildhaber, Thomas Casswall, Greg Nowak, Martin Delle, Denise Aldrian, Valeria Berchtold, Georg F. Vogel, Piotr Kaliciński, Malgorzata Markiewicz-Kijewska, Adam Kolesnik, Jesús Quintero, María Mercadal Hally, Mauricio Larrarte King, Paolo Marra, Michela Bravi, Domenico Pinelli, Mureo Kasahara, Seisuke Sakamoto, Hajime Uchida, Vidyadhar Mali, Marion Aw, Stéphanie Franchi-Abella, Emmanuel Gonzales, Florent Guérin, Guillermo Cervio, Julia Minetto, Sergio Sierre, Martín De Santibañes, Victoria Ardiles, Jimmy Walker Uño, Helen Evans, David Duncan, John Mccall, Steffen Hartleif, Ekkehard Sturm, Jai V. Patel, Marumbo Mtegha, Raj Prasad, Cristina T. Ferreira, Luiza S. Nader, Marco Farina, Catalina Jaramillo, Manuel I. Rodriguez-Davalos, Peter Feola, Amit A. Shah, Phoebe M. Wood, Michael R. Acord, Ryan T. Fischer, Bhargava Mullapudi, Richard J. Hendrickson, Rajeev Khanna, Viniyendra Pamecha, Amar Mukund, Khalid Sharif, Girish Gupte, Simon Mcguirk, Gilda Porta, Winita Hardikar, Marco Spada, Tommaso Alterio, Giuseppe Maggiore, Marisa Beretta, Rudi A J Dierckx, Reinoud P H Bokkers, Hubert P J Van Der Doef, Portal Registry Investigators

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND AND AIMS: Portal vein obstruction (PVO) is a known complication after pediatric liver transplantation (pLT). Effective management strategies are crucial in improving patient outcomes. This study investigated the various practice patterns related to PVO management to clarify the degree of consensus on the diverse facets of care involved in addressing PVO after pLT.

METHODS: A self-reported evaluation was conducted using a scanned, paper-based survey among specialized pLT centers participating in the Portal vein Obstruction Revascularization Therapy After Liver transplantation (PORTAL) registry. The survey consisted of 30 questions covering the current practices regarding PVO, including experience, team composition, follow-up and …

Revisiting Traumatic Intracerebral Hemorrhage In The Context Of Enrich: Illustrative Cases, Erik Werheim, Brendan Mcshane, Zachary Sokol, Theodore Hannah, Robert Ziechmann, Phillip Villaneuva

Department of Surgery Faculty Papers

BACKGROUND: Traumatic intracerebral hemorrhage (tICH) is a common form of intracranial hemorrhage after traumatic brain injury (TBI). The role of surgical intervention in tICH remains a subject of discussion. Recent trials, such as Early Minimally Invasive Removal of Intracerebral Hemorrhage (ENRICH), have shown the efficacy of minimally invasive clot evacuation for non-tICH for hemorrhages with volumes of 30-80 mL. The generalizability of ENRICH to tICH remains unclear; however, it demonstrates the need for rigorous studies evaluating the efficacy of surgical intervention in tICH versus medical management.

OBSERVATIONS: Here the authors present 2 cases of tICH, both in the dominant temporal …

Extracorporeal Membrane Oxygenation For Systemic Lupus Erythematosus: An Elso Registry Analysis, Maria Pereira, Danielle Guffey, Katherine Doane, Eyal Muscal, Carla Levin, Peter Rycus, Marc Anders, Andrea Ontaneda

Faculty, Staff and Students Publications

The success of extracorporeal membrane oxygenation (ECMO) in treating Systemic Lupus Erythematosus (SLE) and the risk factors associated with mortality remain uncertain. Methods: We describe the survival outcomes at discharge of the largest SLE cohort on ECMO support. We performed a retrospective cohort study of the Extracorporeal Life Support Organization registry database from 2012 to 2022. Pediatric and adult survivor groups were analyzed using descriptive statistics for the primary study outcome of survival to hospital discharge. Risk predictors for survival were determined by logistic regression.Results: We included 48 children and 368 adults with SLE. Overall, 198 patients (54%) survived …

Hand Hygiene Roles, Challenges, And Intervention Feedback From School Staff: A Qualitative Analysis, Belize, 2022-2023, Anh N Ly, Christina Craig, Dian Maheia, Yolanda Gongora, Vickie Romero, Rosalva Blanco, Allison Lino, Kelsey Mcdavid, Allison Stewart, Victoria Trinies, Alexandra Medley, Francis Morey, Russell Manzanero, Matthew Lozier, Kristy O Murray

Faculty, Staff and Students Publications

Hand hygiene (HH) in school settings can reduce the spread of infectious diseases and student absenteeism due to illness. During the COVID-19 pandemic, the World Health Organization recommended HH as a public health measure to prevent disease transmission. Understanding school staff's experiences with school-based programs is important for future program development and improvement. As part of a mixed-methods study, we conducted in-depth interviews in March 2022 with school administrators and teachers at 12 primary schools in Belize, selected based on high gaps in HH resources, to understand HH responsibilities, supplies, and challenges. An intervention was implemented to increase HH knowledge …

Cone Beam Ct Dose Optimisation: A Review And Expert Consensus By The 2022 Estro Physics Workshop Igrt Working Group, Lydia J. Wilson, Andria Hadjipanteli, Daniella E. Østergaard, Evelien Bogaert, Kirstie F. Brown, Rianne Dejong, James Earley, Magali Edouard, Marina Khan, Josh Lindsay, Jessica Van Der Himst, George X. Ding, Tim Wood, Marianne C. Aznar, Nuria Jornet, Georgios Ntentas

Department of Radiation Oncology Faculty Papers

Image guided radiotherapy (IGRT) using kilovoltage cone-beam CT (CBCT) has become an indispensable tool to ensure the geometric accuracy of radiotherapy treatment delivery. Although significant technical advances have been made in reducing imaging dose, the repeated imaging procedures can still accumulate significant dose to healthy tissues. Despite the widespread use, we still lack clear guidance for optimisation and widely accepted frameworks for evaluating the quality and suitability of CBCT imaging protocols. To address this gap, the 2022 European Society for Radiotherapy and Oncology (ESTRO) Physics Workshop focused on image-quality and imaging-dose optimisation for IGRT using CBCT. This publication represents a …

Low Cd25 In Alk+ Anaplastic Large Cell Lymphoma Is Associated With Older Age, Thrombocytopenia, And Increased Expression Of Surface Cd3 And Cd8, Shuyu E, L Jeffrey Medeiros, Hong Fang, Shaoying Li, Guilin Tang, Sa A Wang, Wei Wang, C Cameron Yin, M James You, Swaminathan P Iyer, Luis Malpica, Lianqun Qiu, Zhenya Tang, Qing Wei, Pei Lin, Jie Xu

Faculty, Staff and Student Publications

Background/objectives: Anaplastic lymphoma kinase (ALK)-positive (+) anaplastic large cell lymphoma (ALCL) is known to express CD25, but its significance has not been well studied.

Methods: In the present study, we identified 54 ALK+ ALCL patients with CD25 results available and investigated the significance of CD25 expression levels.

Results: Forty-two (78%) cases had high CD25 expressions, whereas low CD25 expressions were found in 12 (22%) cases. Compared with ALK+ ALCL patients with CD25-high neoplasms, patients with CD25-low neoplasms were older (median: 40 years vs. 29 years, p = 0.01) and more often had thrombocytopenia (40% vs. 0%, p = 0.02). Between …

Targeting Neuronal Nitric Oxide Synthase (Nnos) As A Novel Approach To Enhancing The Anti-Melanoma Activity Of Immune Checkpoint Inhibitors, Anika R. Patel, Shirley Tong, Kate Alison Lozada, Amardeep Awasthi, Richard B. Silverman, Jennifer Totonchy, Sun Yang

Pharmacy Faculty Articles and Research

Background and Objectives: Neuronal nitric oxide synthase (nNOS) overexpressed in melanoma plays a critical role in disease progression. Our previous studies demonstrated that nNOS inhibitors exhibited potent anti-melanoma activity and regulated PD-L1 expressions in the presence of interferon-gamma (IFN-γ). However, the role of nNOS in the melanoma immune response has not been well defined. Methods: Changes in gene expression profiles after nNOS inhibitor treatment were determined by transcriptomic analysis. A melanoma mouse model was used to determine the effects of nNOS inhibition on peripheral T cells and the in vivo anti-tumor activity of combining nNOS inhibitors with immune …

Thsd1 Is A Multifaceted Regulator In Health And Disease, Mengjun Dai, Kuizhi Qu, Sophie Liu, Zhen Xu, Yan-Ning Rui

Faculty, Staff and Student Publications

Thrombospondin Type 1 Domain-Containing Protein 1 (THSD1) is a transmembrane protein increasingly recognized for its critical roles in vascular biology and disease pathogenesis. Initially identified as a marker of hematopoietic stem and endothelial cells during embryogenesis, THSD1 has since been implicated in a wide spectrum of physiological and pathological processes. This paper consolidates current knowledge on THSD1, with a focus on its roles in vascular integrity, perinatal disorders, and tumorigenesis. In vascular systems, THSD1 promotes focal adhesion assembly and suppresses autophagy-mediated adhesion turnover, thereby stabilizing endothelial attachment and maintaining barrier function. Genetic and functional studies support its protective role against …

A Semiclassical Model Of The Immediate Temperature Distribution Surrounding The Track Of Heavy Ions With Therapeutic Energies, Martin Rädler, Niayesh Afshordi, Reza Taleei, Katia Parodi, Ramin Abolfath, Julie Lascaud

Department of Radiation Oncology Faculty Papers

Objective. Spikes of high temperature and pressure are created in the vicinity of heavy ions, especially at the Bragg peak. The expected subsequent thermoacoustic effects are however not well understood. In particular, the distribution of the densely packed primary interactions has not been considered in molecular dynamics (MDs) simulations or shock wave solutions. In this work, we derive a dedicated model to describe the primary interactions and their radial distribution, applicable to the modeling of acoustic and thermodynamic effects at the nanoscale. Approach. Starting from first principles, we assemble a semiclassical model of the energy loss of the primary heavy …

The Effect Of Celecoxib And Mumab911 On Strain Adaptive Bone Remodeling And Fracture Repair In Female Mice: Implications For Rapidly Progressive Osteoarthritis, Nicholas Ruggiero, Alexandra Ciuciu, Ashkan Sedigh, Ibtesam Rajpar, David Shelton, Patrice Belanger, Kathryn Gropp, John A. Collins, Theresa A. Freeman, Ryan E. Tomlinson

Department of Orthopaedic Surgery Faculty Papers

Debilitating pain is the primary clinical feature of osteoarthritis (OA) that drives the enormous healthcare costs. Osteoarthritis-related pain is often treated with non-steroidal anti-inflammatory drugs (NSAIDs), which effectively relieve pain and inflammation by inhibition of prostaglandin synthesis. Antibodies directed against nerve growth factor (NGF) were tested some time ago as an alternative potential analgesic for musculoskeletal pain, including osteoarthritis-related pain. Unfortunately, clinical development of these drugs was put on hold due to adverse outcomes - primarily rapidly progressive osteoarthritis. Both prostaglandin synthesis and NGF have been implicated as critical mediators of strain adaptive bone remodeling, which may play a role …

Personalizing Neoadjuvant Chemotherapy Regimens For Triple-Negative Breast Cancer Using A Biology-Based Digital Twin, Chase Christenson, Chengyue Wu, David A Hormuth, Jingfei Ma, Clinton Yam, Gaiane M Rauch, Thomas E Yankeelov

Faculty, Staff and Student Publications

Despite advances triple negative breast cancer treatment, ~50% of patients will not achieve a pathological complete response prior to surgery with standard of care neoadjuvant therapy (NAT). We hypothesize that personalized regimens for NAT could significantly improve patient outcomes, which we address with a patient-specific digital twin framework. This framework is established by calibrating a biology-based model to longitudinal magnetic resonance images with approximate Bayesian computation. We then apply optimal control theory to either (1) reduce the final tumor cell number with equivalent dose, or (2) reduce the total dose of NAT with equivalent response. For (1), the personalized regimens …

Neuroanatomical And Morphometric Differences In Children Who Stutter, Mohammad A. Khan

Honors Scholar Theses

Childhood-Onset Fluency Disorder commonly known as stuttering is a neurodevelopmental speech disorder characterized by disruptions in speech fluency. While genetic and neurobiological factors are implicated, the structural brain differences underlying stuttering remain unclear. This study investigated neuroanatomical alterations in children who stutter (CWS) compared to typically fluent children (TFC), focusing on gray matter volume, cortical thickness, and surface area in speech-related regions; the Inferior Frontal Gyrus, Middle Temporal Gyrus, and Pre-motor Operculum. High-resolution MRI data from 100 children (48 CWS, 52 TFC) aged 3–12 years were analyzed using FreeSurfer. Group comparisons revealed no statistically significant differences in cortical thickness, surface …