Medical Sciences Commons^™

3d Em Uncovers Mitochondrial Network Remodeling In Residual Triple Negative Breast Cancer After Conventional Chemotherapy Treatments, Mariah J Berner, Heather K Beasley, Benjamin Rodriguez, Audra Lane, Steven W Wall, Andrea G Marshall, Zer Vue, Larry Vang, Mokryun L Baek, Mason Killion, Faben Zeleke, Bryanna Shao, Dominique Parker, Autumn Peterson, Julie Sterling Rhoades, Lacey E Dobrolecki, Amber Crabtree, Annet Kirabo, Sepiso K Masenga, Prasanna Katti, Prasanna Venkhatesh, Chandravanu Dash, Michael T Lewis, Antentor Hinton, Gloria V Echeverria

Faculty, Staff and Students Publications

Mitochondria are hubs of metabolism and signaling. We previously demonstrated the importance of mitochondrial structure and function in chemotherapy-refractory triple-negative breast cancer (TNBC). Herein, we present the first 3D analysis of mitochondrial networks in human tumor tissues. Using serial block face scanning electron microscopy, we reconstructed 3,750 mitochondria and 800 lipid droplets (LDs) in naive and residual tumors persisting after conventional chemotherapies in two orthotopic patient-derived xenografts (PDX). Chemotherapies administered as monotherapy or in combination produced residual tumors that harbored mitochondria with significantly increased areas, volumes, and perimeters. We observed substantial reduction of mitochondrial intratumor heterogeneity following all treatments. Further, …

Targeting Arginine Metabolism Overcomes Chemotherapy Resistance In Aggressive-Variant Prostate Cancers, Elavarasan Subramani, Patrick G Pilié, Rebecca Slack-Tidwell, Paul V Viscuse, Xianghong Kuang, Thirukumaran Kandasamy, Dominik Awad, Jenny J Han, Licai Huang, Christine B Peterson, Amado J Zurita, Sumit K Subudhi, Paul G Corn, Rama Soundararajan, Peter Shepherd, Badrajee Piyarathna, Vasanta Putluri, Nagireddy Putluri, Arun Sreekumar, Yuzhuo Wang, Amina Zoubeidi, Iqbal Mahmud, Sara A Martinez, Lin Tan, Philip L Lorenzi, Sreyashi Basu, Sonali Jindal, Padmanee Sharma, Christopher J Logothetis, Timothy C Thompson, Daniel E Frigo, Ana M Aparicio

Faculty, Staff and Students Publications

Aggressive-variant prostate cancers (AVPCs) respond poorly to anti-androgen therapy but show sensitivity to taxane-platinum chemotherapy, though outcomes remain poor. We conducted a phase 2 trial testing induction cabazitaxel plus carboplatin (CabCarb) followed by olaparib maintenance versus observation in men with AVPC. The primary endpoint of improved progression-free survival (PFS) was not met, likely due to the study being underpowered after 38.5% of patients experienced early progression (ChemoPD) prior to randomization. No genomic alterations predicted ChemoPD; however, transcriptomic analysis revealed the enrichment of metabolic pathways, including arginine metabolism, in ChemoPD tumors. These findings were supported by metabolomics data from preclinical models. …

Targeted Inhibition Of Atr Kinase Promotes Antitumor Immunity In Hnscc Through Enhanced Sting Activation And T Cell Function, Fabio Hb Da Costa, Mutsuki Kawabe, Tsung-You Tsai, Kento Okamoto, Mason D Bartels, Sofia Cortes, Ratna Veeramachaneni, Roberto Rangel, Mitchell J Frederick, Vlad C Sandulache, Andrew G Sikora, Jeffrey N Myers, Abdullah A Osman

Faculty, Staff and Students Publications

Objectives: Oral cavity head and neck squamous cell carcinoma (HNSCC) represents a major global health burden, with over 40,000 new cases annually in the United States and >500,000 worldwide. Despite advances in surgery, radiation therapy, chemotherapy, and immunotherapy, overall survival rates have remained largely stagnant over the past three decades, and over half of patients ultimately die from the disease. Although immune checkpoint inhibitors (ICIs) have improved outcomes for a subset of patients with recurrent or metastatic HNSCC, the majority gain limited benefit. Thus, novel therapeutic strategies that enhance responses to immunotherapy are urgently needed. The ATR-CHK1 signaling pathway has …

Neddylation Maintains Oocyte Quality By Stabilizing Mitochondrial Transcription, Avery A Ahmed, Tessa E Steenwinkel, Bethany K Patton, Peixin Jiang, Matthew D Meyer, Jaspreet K Rishi, Mei Leng, Alexander B Saltzman, Elizabeth S Anaya, Momal Sharif, Laurie J Mckenzie, Laura Detti, Anna Malovannaya, Sean M Hartig, Stephanie A Pangas

Faculty, Staff and Students Publications

Age-related decline in oocyte quality increases the risk of infertility, miscarriage, and birth defects. Mitochondrial dysfunction is a key contributor to this decline. Here, we report that oocyte-specific deletion of Uba3, which encodes the catalytic subunit of the E1 NEDDylation-activating complex, causes sterility in mice. Fully grown, germinal vesicle–stage Uba3 conditional knockout oocytes exhibit mitochondrial dysfunction, including elevated reactive oxygen species, impaired oxidative phosphorylation, and depletion of mitochondrially encoded RNA transcripts. Proteomic analysis identified alterations in mitochondrial-associated proteins, including enrichment of mitochondrial matrix and respiratory chain components and reduced abundance of electron transport chain complexes. These defects were associated …

Macrophages As Gatekeepers Of Glioma Progression, Cliona M Rooney, Jasia Mahdi

Faculty, Staff and Students Publications

No abstract provided.

Management Algorithm For Vasoplegic Shock After Cardiac Surgery: An Interdisciplinary Collaboration, Subhasis Chatterjee, Jamel Ortoleva, Rakesh C Arora, Kelci R Dalton, Daniel T Engelman, Natalia Ivascu Girardi, Michael C Grant, Travis J Miles, Marc R Moon, Orlando R Suero, Erica Wittwer, Patrick M Wieruszewski

Faculty, Staff and Students Publications

Background: Vasoplegic shock is distributive shock that follows cardiopulmonary bypass, characterized by hypotension, low systemic vascular resistance, and catecholamine resistance despite preserved or elevated cardiac output. Reported incidence ranges from 5% to 50%. Associated adverse outcomes include acute kidney injury, prolonged intensive care unit stay, and mortality. A single, universally accepted consensus definition is lacking, and few evidence-based best-practice management strategies exist.

Methods: A panel of 12 clinicians-cardiac surgeons, anesthesiologists, intensivists, and pharmacists-from 6 institutions conducted a structured expert review. PubMed and Embase were searched for research studies, including clinical trials, retrospective analyses, and mechanistic studies covering epidemiology, risk factors, …

Placenta Accreta Spectrum Risk In Endometriosis: A Retrospective Cohort Study With Art Subanalysis, Madeline West, Amir Alsaidi, Michael A Belfort, Hendrik A Lombaard, Yamely H Mendez, Christina C Reed, Amir A Shamshirsaz, Jessian L Munoz

Faculty, Staff and Students Publications

No abstract provided.

Detection, Persistence, And Rising Prevalence Of Oncogenic Viruses Revealed By Wastewater Metagenomics, Harihara Prakash, Ryan K Perez, Matt Ross, Michael Tisza, Sara J Javornik Cregeen, Jennifer Deegan, Joseph F Petrosino, Eric Boerwinkle, Justin R Clark, Anthony W Maresso

Faculty, Staff and Students Publications

Oncogenic viruses cause high-risk cancers in humans and are responsible for nearly 20% of all cancer cases worldwide. Currently, very limited data exist in the realm of wastewater-based viral epidemiology (WBE) for cancer-causing viruses, with existing studies using targeted approaches (i.e., PCR-based approaches) that lack genomic resolution. In this study, we used a hybrid-capture approach to detect, filter, and sequence all known oncogenic virus signals from wastewater samples collected over 3 years (May 2022-May 2025) in 16 Texas cities, covering nearly 25% of the state's population. Once sequenced, we used custom computational tools designed for wastewater metagenomics to assign reads …

Pancreatitis Risk Genes Play A Major Role In Pediatric Pancreatitis: Insights From The International Study Group Of Pediatric Pancreatitis: In Search For A Cure, Maisam Abu-El-Haija, Wenying Zhang, Fuchenchu Wang, Gretchen Cress, Brian Dawson, Xiaoping Su, Tyler Thompson, Nicole Kotha, Ankur Chugh, Reuven Zev Cohen, Elissa M Downs, Douglas S Fishman, A Jay Freeman, Cheryl E Gariepy, Matthew J Giefer, Tanja Y Gonska, Phil Greer, Amit S Grover, Andrew Y J Liman, Douglas Lindblad, Quin Y Liu, Asim Maqbool, Jacob A Mark, Brian A Mcferron, Megha S Mehta, Veronique D Morinville, Kenneth Ng, Robert A Noel, Chee Y Ooi, Emily R Perito, Michael Wilschanski, Yuhua Zheng, Ying Yuan, David C Whitcomb, Aliye Uc, Mark Lowe, Consortium For The Study Of Chronic Pancreatitis, Diabetes, And Pancreatic Cancer (Cpdpc)

Faculty, Staff and Students Publications

Background & aims: Clinical data show that genetic variants are significant risk factors for acute recurrent pancreatitis and chronic pancreatitis. To expand the understanding of the role of genetics in acute recurrent pancreatitis and chronic pancreatitis, high-throughput next-generation sequencing of 14 genes was completed in a multicenter pediatric cohort.

Methods: A cross-sectional study involving 944 pediatric patients with acute recurrent pancreatitis or chronic pancreatitis was conducted. CASR, CEL, CFTR, CLDN2, CPA1, CTRC, GGT1, PRSS1, PRSS2, PRSS3, SBDS, SLC26A9, SPINK1, and UBR1 were sequenced. The frequencies of identified variants were compared with frequencies in the genome aggregation database. Group differences were …

Autophagic Flux Blockade Under Hypocapnia Reveals Co2-Sensitive Regulation Of Autophagy-Lysosome Homeostasis, Naghmana Ashraf, Zhen Sun, Jeanine L Van Nostrand

Faculty, Staff and Students Publications

Hypocapnia, a reduction in partial pressure of carbon dioxide (CO2), commonly occurs in clinical contexts such as mechanical ventilation, panic disorder, and brain injury, yet its impact on cellular homeostasis remains poorly understood. Given the central role of autophagy in stress adaptation, we investigated how low CO2 influences autophagic flux and lysosomal function. We found that hypocapnia induces autophagosome accumulation while impairing cargo degradation, indicating a blockade in autophagic flux. This response was accompanied by increased lysosome biogenesis but, paradoxically, reduced autophagosome-lysosome fusion and lysosomal proteolytic activity. Mechanistically, hypocapnia promoted TFE3 dephosphorylation and nuclear translocation, driving transcriptional activation of lysosomal …

Guideline On Stress Echocardiography - 2026, Ana Cristina Camarozano, Salvador Vicente Spina, José Roberto Matos Souza, Marcelo Dantas Tavares De Melo, Daniela Do Carmo Rassi Frota, Silvio Henrique Barberato, Fabio Villaça Guimarães Filho, Harry Acquatella, Vera Márcia Lopes Gimenes, Jorge Alfredo Lowenstein, Ricardo H Pignatelli, José Maria Del Castillo, Joselina Luiza Menezes Oliveira, José Sebastião De Abreu, José Luis De Castro E Silva Pretto, Issam Shehadeh, Alex Dos Santos Felix, Mercedes Maldonado Andrade, Antônio Carlos Sobral Sousa, Maria Estefânia Bosco Otto, Andrea De Andrade Vilela, Pedro Gutierrez Fajardo, Liz Andréa Villela Baroncini, Cristiano Vieira Machado, Fábio Cañellas Moreira, José María Hernández Hernández, Marco Stephan Lofrano Alves, Samira Saady Morhy, Márcio Silva Miguel Lima, Miguel Osman Dias Aguiar, Wilson Mathias Junior, Letícia Dos Santos De Oliveira Rocha, João César Nunes Sbano, Barbara Athayde Linhares Martins Vrandecic, Fabio Roston, Arnaldo Rabischoffsky, Juliana Paixão Etto Rolim, Raphael Aparecido Barreto Da Silva, Guilherme De Rossi, Kamila Fernanda Staszko, Jolie Britt, Marcelo Luiz Campos Vieira

Faculty, Staff and Students Publications

No abstract provided.

Ultrasound-Enabled Refreshable Electrochemical Sensors For Cardiac Biomarker Monitoring, Mayank Garg, Heng Guo, Myeong Namkoong, Elizabeth Zhanov, Connor Malone, Md Saifur Rahman, Ayse Akcan-Arikan, Limei Tian

Faculty, Staff and Students Publications

Cardiac troponin I (cTnI) is the gold-standard biomarker for acute myocardial infarction, yet current laboratory-based high-sensitivity assays require centralized infrastructure, trained personnel, and serial testing, limiting their suitability for real-time or continuous monitoring in resource-limited settings. Point-of-care electrochemical sensors have shown promise for rapid cTnI detection, but their reliance on antibodies as biorecognition elements and redox mediator solutions, and single-use operation restricts practical translation. Here, we report an ultrasound-enabled refreshable electrochemical biosensor for sensitive, stable, and repeatable cTnI monitoring. The device employs a cTnI-specific peptide as the biorecognition element, providing enhanced stability during storage, transport, and operation. Label-free electrochemical impedance …

Macropinocytosis Inhibition Attenuates Profibrotic Responses In Lung Fibroblasts And Pulmonary Fibrosis Models, Ivan O Rosas, Aaron K Mcdowell-Sanchez, Santiago Sanchez, Juan D Cala-Garcia, Alan R Waich Cohen, Elisa Ruiz-Echartea, Scott A Ochsner, Daniel C Kraushaar, Lindsay J Celada, Dandan Sun, Francesca Polverino, Cristian Coarfa, Neil J Mckenna, Konstantin Tsoyi

Faculty, Staff and Students Publications

Idiopathic pulmonary fibrosis (IPF) is a devastating chronic lung disorder with limited treatment options. Macropinocytosis is one of the key cellular processes involved in nutrient consumption from the extracellular environment under stress conditions. Here, we studied the role of macropinocytosis in experimental pulmonary fibrosis models. We found that macropinocytosis is increased in human lung fibroblasts (HLFs) derived from patients with IPF. The inhibition of macropinocytosis with 5-(n-ethyl-n-isopropyl)-amiloride (EIPA) inhibited profibrotic responses in IPF-derived and TGF-β1-stimulated HLFs and reduced pulmonary fibrosis in bleomycin-injured (Bleo-injured) mice. EIPA exerted its antifibrotic effects by regulating amino acid uptake, mammalian target of rapamycin complex 1 …

Deciphering Small Sequence Differences In T Cell Receptor-Antigen Pairing, Yi Han, Yuqiu Yang, James Zhu, Farjana J Fattah, Mitchell S Von Itzstein, Minying Zhang, Casey Bermack, Peixin Jiang, Shailbala Singh, Yanhua Tian, Yifei Hu, Yafang Deng, Xiongbin Kang, Donghan M Yang, Jialiang Liu, Yaming Xue, Chaoying Liang, Indu Raman, Chengsong Zhu, Olivia Xiao, Jonathan E Dowell, Jade Homsi, Sawsan Rashdan, Ke Pan, Shengjie Yang, Mary E Gwin, David Hsiehchen, Yvonne Gloria-Mccutchen, Fangjiang Wu, John V Heymach, Don Gibbons, Junzhou Huang, Chao Cheng, Jianjun Zhang, Cassian Yee, Alexandre Reuben, David E Gerber, Tao Wang

Faculty, Staff and Students Publications

T cells have important functions in development and disease processes through T cell receptor (TCR)-dependent activities. Many tools were developed to predict the binding between TCRs and antigens. However, one of the uncertainties is whether such tools can decipher how small changes in the TCRs or antigenic peptides contribute to binding. We develop a deep learning model, pMTnet-omni, which not only predicts the binding vs. non-binding of TCRs towards pMHCs, but also distinguishes the stronger vs. weaker binding of TCRs similar in sequence. We leverage this capability to interpret the biological rules that govern TCR-antigen pairing. This also enables pMTnet-omni …

Artificial Intelligence In Biomedical Scientific Publishing, Tomasz J Guzik, Victor Aboyans, Stefan Agewall, Steven Bailey, Adrian Baranchuk, Magnus Bäck, Michael Böhm, Robert O Bonow, George W Booz, Giuseppe Boriani, Biykem Bozkurt, Nico Bruining, Davide Capodanno, Çetin Erol, Péter Ferdinandy, Alessia Gimelli, Gerd Heusch, Thomas Kahan, Chim Choy Lang, Gerald Maurer, Robert J Mentz, Marco Metra, Philip Moons, Daniel Piskorz, Massimo Piepoli, Piotr Ponikowski, Alexandra Popma, Bianca Rocca, Juan Sanchis Fores, Philipp Sommer, Rhian M Touyz, Zoltan Ungvari, Pascal Vranckx, Joseph A Hill, Thomas F Lüscher, Filippo Crea

Faculty, Staff and Students Publications

Artificial intelligence is now embedded across the scientific research and publishing ecosystem, influencing discovery, analysis, knowledge translation, authorship, peer review, and editorial workflows. In cardiovascular and biomedical sciences, these developments offer substantial opportunities to accelerate knowledge generation, integrate complex datasets, and improve efficiency and consistency. At the same time, they introduce new risks related to bias, transparency, data integrity, and authorship responsibility, potentially endangering trust in the scientific record. This commentary examines the evolving role of AI in biomedical publishing, with particular attention to generative models and machine learning tools. We review both benefits and limitations, highlight risks such as …

Single-Nucleus Profiling Reveals A Core Disease Signature And Cell Type-Specific Vulnerabilities In Early Rett Syndrome, Yan Li, Ashley G Anderson, Guantong Qi, Sih-Rong Wu, Jean-Pierre Revelli, Hu Chen, Zhandong Liu, Huda Y Zoghbi

Faculty, Staff and Students Publications

Rett syndrome (RTT) is an X-linked neurological disorder caused by MECP2 mutations, creating distinct cellular environments in females (mosaic) versus males (nonmosaic). Despite female patients representing most cases, how mosaicism contributes molecularly to RTT pathogenesis, particularly in presymptomatic stages, remains poorly understood. To address this question, we profiled hippocampal transcriptomes of young female and male RTT mice using bulk and single-nucleus RNA sequencing. We identified a core disease signature of consistently dysregulated genes only in MeCP2− cells across RTT models. Moreover, we uncovered non–cell autonomous effects exclusively in female MeCP2+ excitatory neurons, suggesting that these circuits are more vulnerable early …

Targeted Next-Generation Sequencing Implementation In Eswatini Identifies Rifampicin And Bedaquiline Resistance Undetected By Routine Diagnostic Testing, Debrah Vambe, Alexander Kay, Mangaliso Ziyane, Mdigo Thunzini, Sein Sein Thi, Leonardo De Araujo, Viola Dreyer, Tanja Niemann, Busizwe Sibandze, Sijabu Masina, Andrea Maurizio Cabibbe, Jennifer Furin, Tafadzwa Mazuruse, Lindokuhle Dlamini, Thulani Jele, Bheki Mamba, Gugu Maphalala, Makhosazana Dlamini, Mbongeni Dube, Nomthandazo Lukhele, Daniela Maria Cirillo, Anna Mandalakas, Christoph Lange, Sphiwe Ngwenya, Christian Utpatel, Sindisiwe Dlamini, Stefan Niemann

Faculty, Staff and Students Publications

In Eswatini, multidrug-resistant (MDR) Mycobacterium tuberculosis (Mtb) strains harbouring the rifampicin-resistance (RR) rpoB I491F mutation are missed by routine diagnostics, including GeneXpert MTB/RIF Ultra (Xpert Ultra), line probe assays (LPA), and mycobacterium growth indicator tube (MGIT) phenotypic drug susceptibility testing (pDST). To address this diagnostic gap, Eswatini introduced targeted next-generation sequencing (tNGS) in 2019. We analysed 234 patient samples enrolled from June 2021 to December 2024 with isoniazid and/or rifampicin resistance detected by routine diagnostics, or suspected treatment failure, and obtained detailed clinical and outcome data from 59 patients. tNGS detected RR in 159 strains, of which 101 (64%) carried …

Statewide Multi-Year Wastewater Sequencing Reveals Dual Origins Of Hiv-1 Signal, Justin R Clark, Dylan Chirman, Harihara Prakash, Austen Terwilliger, Marlene Mcneese, Matt Ross, Mike Tisza, Sara J Javornik Cregeen, Loren Hopkins, Jennifer Deegan, Catherine L Troisi, Eric Boerwinkle, Kristina Mena, Fuqing Wu, Jason T Kimata, Marc Johnson, Devon Gregory, Faith E Fletcher, Thomas P Giordano, Anthony W Maresso

Faculty, Staff and Students Publications

Human immunodeficiency virus 1 (HIV-1) is a retrovirus which has infected 90 million people and resulted in over 40 million deaths. Despite advances in diagnostics, treatment, and prophylaxis, HIV-1 continues to spread due to undiagnosed and untreated infections. Traditional monitoring methods are ineffective when access to testing is limited or people do not seek care, particularly given the long period between infection and symptom onset, allowing undetected transmission to continue. Here, we use a hybrid-capture sequencing approach to track HIV-1 signal in municipal wastewater in 15 different cities over nearly 3 years. We obtain near-complete genomic coverage of HIV-1, enabling …

Rare Pediatric Venolymphatic Malformations: Pericardial Cyst Mimickers, Shelby E Walcott, Joseph Burns, Juan Pablo Sandoval Jones, Neil Cambronero, David Brennen, Thomas M Glenn, Betul Yilmaz Furtun

Faculty, Staff and Students Publications

Background: Pericardial cystic masses are rare, and exceedingly so in pediatrics. The clinical course of such masses in children is poorly described.

Case summary: We report 2 cases in 3- and 7-year-old children. Both were initially thought to represent pericardial cysts on imaging, but surgical excision and histopathology confirmed diagnoses of a venolymphatic malformation and an epicardial cyst, respectively. The first patient presented with abdominal pain, and the second patient was asymptomatic. Both recovered well after an uncomplicated surgical intervention.

Discussion: A small number of patients with pericardial masses will have symptoms thought to be related to compression of adjacent …

The Effect Of Hunger On The Likelihood Of Glucose Excursions In Adults With Overweight Or Obesity: Continuous Glucose Monitoring And Ecological Momentary Assessment Observational Study, Byunggul Lim, Phrashiah Githinji, Yue Liao, Jacob Szeszulski, Alexandra L Macmillan Uribe, Rebecca A Seguin-Fowler, Jane Anderson, Chad D Rethorst

Faculty, Staff and Students Publications

Background: Maintaining stable glucose levels is important for metabolic health. Glucose excursions (GEs), which are marked increases in glucose following food intake, have been associated with a higher risk for cardiovascular disease and metabolic dysfunction. Individuals with overweight or obesity who do not have diabetes may still show impaired glucose regulation, as reflected in increased glucose variability. Hunger, as a real-time physiological cue, may be associated with subsequent glucose changes and represents a potential target for just-in-time adaptive interventions.

Objective: This study aimed to investigate the temporal relationship between self-reported hunger and subsequent glucose dynamics, including the likelihood of GE …

Rare Pediatric Venolymphatic Malformations: Pericardial Cyst Mimickers, Shelby E Walcott, Joseph Burns, Juan Pablo Sandoval Jones, Neil Cambronero, David Brennen, Thomas M Glenn, Betul Yilmaz Furtun

Faculty, Staff and Students Publications

Background: Pericardial cystic masses are rare, and exceedingly so in pediatrics. The clinical course of such masses in children is poorly described.

Case summary: We report 2 cases in 3- and 7-year-old children. Both were initially thought to represent pericardial cysts on imaging, but surgical excision and histopathology confirmed diagnoses of a venolymphatic malformation and an epicardial cyst, respectively. The first patient presented with abdominal pain, and the second patient was asymptomatic. Both recovered well after an uncomplicated surgical intervention.

Discussion: A small number of patients with pericardial masses will have symptoms thought to be related to compression of adjacent …

In Vivo Orf Overexpression Screening Identifies Ccn4 As A Regulator Of Glioblastoma Growth Validated Across Multiple Models, Pushan Dasgupta

Faculty, Staff and Students Publications

Despite current multimodal therapies for glioblastoma (GBM), its prognosis remains grim. Thus, a tremendous need exists to identify new genetic drivers that may serve as potential therapeutic targets in glioblastoma (GBM). We describe an in vivo overexpression screening strategy to identify drivers of glioblastoma where we have leveraged TCGA datasets to conduct a functional genomics screen of prioritized open reading frames (ORFs) that are overexpressed and/or amplified in GBM. To interrogate these potential drivers within a more relevant physiological context, the screening was accomplished in vivo in an orthotopic patient-derived glioma stem-like cell (GSC) model. Among 5 positive "hits" from …

Notch1 Acts As A Tumor Suppressor That Induces Early Differentiation In Head And Neck Cancer, Chenfei Huang, Shhyam Moorthy, Qiuli Li, Kazi M Ahmed, Kalil Saab, Defeng Deng, Jiping Wang, Xiayu Rao, Jiexin Zhang, Yuanxin Xi, Jing Wang, Zhiyi Liu, Noriaki Tanaka, David A Wheeler, Eve Shinbrot, Rami Saade, Curtis R Pickering, Tong-Xin Xie, Adel K El-Naggar, Abdullah A Osman, Kunal Rai, Patrick A Zweidler-Mckay, John V Heymach, Lauren A Byers, Faye M Johnson, Vlad C Sandulache, Jeffrey N Myers, Pedram Yadollahi, Mitchell J Frederick

Faculty, Staff and Students Publications

Inactivating NOTCH1 mutations in head and neck squamous cell carcinoma (HNSCC) were described over a decade ago, suggesting a tumor suppressor function - unlike its oncogenic role in other tumors. Today, much debate persists regarding a putative oncogenic role in HNSCC as well, with reports that NOTCH1 signaling drives tumor growth and a cancer stem cell (CSC) phenotype. In this work, comprehensive experiments unequivocally demonstrate that NOTCH1 is a tumor suppressor in HNSCC regardless of mutation or activation status and that it reduces CSC frequency. We developed a signature of NOTCH1 activation showing the pathway is associated with very early …

Structured Telehealth Community Health Worker-Clinician Feedback And Diabetes Outcomes: A Randomized Clinical Trial, Elizabeth M Vaughan, Xiaoying Yu, Amber B Amspoker, Aanand D Naik, Ashok Balasubramanyam, Craig A Johnston, Christi M Ballantyne, Salim S Virani, H Shelton Brown, Kristina Mena, Laura R Porterfield

Faculty, Staff and Students Publications

Importance: Community health workers (CHWs) improve chronic disease management in underserved populations, but scalable integration strategies are limited.

Objective: To evaluate whether a multidimensional intervention incorporating telementored CHWs and a structured participant-CHW-clinician feedback loop can improve diabetes outcomes.

Design, setting, and participants: This 12-month randomized clinical trial was conducted at 3 institutionally and geographically diverse community clinics in Texas between September 1, 2023, and April 30, 2025, and included low-income, uninsured White Hispanic adults with type 2 diabetes identified through clinic databases. Data were analyzed between May 1 and July 31, 2025.

Intervention: Individuals were randomized 1:1 to the intervention …

Development And Preliminary Validation Of Orca-Pd, An Online Rapid Cognitive Assessment For Parkinson Disease: Mixed Methods Study, Avigail Lithwick Algon, Sarah Brisman, Chi-Ying R Lin, William Saban

Faculty, Staff and Students Publications

Background: Traditional in-person neuropsychological tests for Parkinson disease (PD) lack accessibility, scalability, and PD specificity. Mobility impairments hinder access to in-person assessments, and long waiting times for expert evaluation limit scalability. Common tools for cognitive screening, such as the Montreal Cognitive Assessment, are generic and not specific to PD.

Objective: The goal of this study was to address these challenges by leveraging the internet. This study aimed to develop a sensitive tool to detect cognitive impairments in early- to mid-stage PD in an accessible and scalable manner.

Methods: We developed the Online Rapid Cognitive Assessment for Parkinson's Disease (ORCA-PD), a …

Targeted Reflex Rna Sequencing For Enhanced Variant Classification On Exome And Genome Sequencing Improves Patient Outcomes, Xiaonan Zhao, Robert Rigobello, Morgan Driver, Sydney Lau, Mei Ling Chong, Jason Chibuk, Hongzheng Dai, Wilson C W Wu, Christina Peroutka, Laura Famularo, Alexander Y Kim, Bailey Hummel, Sarah Dugan, Tinsley Douglas, Linyan Meng, Fan Xia, Christine M Eng

Faculty, Staff and Students Publications

RNA sequencing (RNA-seq) has been utilized to provide functional evidence regarding the impact of splicing variants. This study explores the utility of targeted reflex RNA-seq to inform classification of predicted splicing variants identified through clinical exome sequencing (ES) and genome sequencing (GS). A retrospective analysis was conducted on consecutive ES/GS cases completed at a single center in which targeted reflex RNA-seq was performed following identification of eligible variants. There were 131 cases (4.1%) that had at least one RNA-seq eligible variant reported, with eight of these cases having two unique eligible variants. Of the 139 eligible variants, 125 were classified …

Safety And Synergy Of Finerenone And Empagliflozin In Lowering Blood Pressure, Rajiv Agarwal, Ricardo Correa-Rotter, Sankar D Navaneethan, Hiddo J L Heerspink, Matthew R Weir, Janet B Mcgill, Amy K Mottl, Masaomi Nangaku, Julio Rosenstock, Peter Rossing, Muthiah Vaduganathan, Charlie Scott, Li Li, Meike Brinker, Csaba P Kovesdy, Jennifer B Green, Johannes F E Mann

Faculty, Staff and Students Publications

Background: This secondary analysis of the CONFIDENCE (combination effect of fInerenone and empagliflozin in participants with chronic kidney disease and type 2 diabetes using a UACR endpoint) trial (REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT05254002) assessed systolic blood pressure (SBP) changes with empagliflozin/finerenone combination therapy versus monotherapy in people with chronic kidney disease and type 2 diabetes across baseline SBP categories. We assessed SBP response predictors and whether early (day 30) SBP changes mediate urinary albumin-to-creatinine ratio reductions.

Methods: Participants (n=800) were stratified by baseline SBP (< 130 mm Hg; ≥130 mm Hg). Outcomes included SBP response (≥10 mm Hg reduction from baseline at day 180) and longitudinal SBP changes, analyzed by linear mixed-effects models and logistic regression. Causal mediation analysis, a secondary exploratory analysis, evaluated the effect of day 30 SBP change on day 180 urinary albumin-to-creatinine ratio reduction.

Results: At baseline, 532 (66%) participants had SBP ≥130 mm Hg; 268 (34%) …

Histone Deacetylase Enzyme Activity Is Not The Universal Anticancer Target Of Hdac Inhibitors, Chaitra Rai, Hang Ruan, Xue Li, Wenbo Li, Hyun-Hwan Jeong, Chengchuang Song, Panpan Liu, Yingjie Chang, Hao Fang, Udhaya Kumar S, Yuxiang Sun, M James You, Dongyin Guan, Zhandong Liu, Leng Han, Xuben Hou, Zheng Sun

Faculty, Staff and Students Publications

Histone deacetylase inhibitors (HDIs) are approved for treating hematologic cancers and are currently being evaluated in hundreds of clinical trials for various cancers and other diseases, although their mechanisms of action remain poorly understood. Here, our unbiased bioinformatics analyses found that, for most cancer types, expression levels or genetic variants of histone deacetylase (HDACs) do not consistently correlate with carcinogenesis, do not predict cancer patient survival, and do not associate with cellular responses to HDIs. Whole-genome CRISPR library screens did not identify HDACs as genes affecting cellular responses to HDIs. Overexpression of dominant-negative Class I HDACs causes similar protein hyperacetylation …

The Aggregated Latent Profile Index: Measuring Person Profile Differentiation Within A Bootstrap-Validated Latent Profile Space, Se-Kang Kim

Faculty, Staff and Students Publications

Multivariate assessment profiles contain two conceptually distinct sources of variation: overall level and profile shape. Existing approaches recover some aspects of this structure, but none jointly establishes the replicability of latent pattern dimensions and provides a principled, population-referenced summary of person profile differentiation independent of overall level. We introduce the Aggregated Latent Profile Index (ALPI), a variance-weighted Euclidean distance that quantifies the degree to which an individual’s profile departs from a flat population reference within a bootstrap-validated latent profile space. ALPI is derived from the Aggregated Latent Profile Space (ALPS), a framework that combines parallel analysis with bootstrap stability diagnostics …

Global Burden Of Drug-Resistant Tuberculosis In Children: A Systematic Analysis For The Global Burden Of Disease Study, Xuhui Liu, Peierdun Mijiti, Lu Xia, Sylvia M Lacourse, Wulan Talafuhan, Alexander W Kay, Yang Yang, Huarui Liu, Dan Ye, Leonardo Martinez, Shuihua Lu, Adong Shen, Anna M Mandalakas, Feng Li, Christoph Lange, Zhen Huang

Faculty, Staff and Students Publications

Background: Paediatric tuberculosis (TB), particularly drug-resistant TB (DR-TB), is associated with significant mortality. However, the global burden of childhood TB remains poorly understood.

Methods: We analysed incident cases, deaths, and age-standardised incidence and mortality rates among children (0-14 years) with multidrug-resistant/rifampicin-resistant tuberculosis (MDR/RR-TB) and extensively drug-resistant tuberculosis (XDR-TB) using the Global Burden of Disease (GBD) 2021 database. Data were stratified by age, sex, region, country, and HIV/AIDS status. Annual and average annual percentage changes were assessed using joinpoint regression analysis. Secondary analyses compared adult and paediatric TB trends in the End TB era and evaluated the potential impact of the …