Medical Specialties Commons^™

Plasma Lipidome Dysregulation In Frontotemporal Dementia Reveals Shared, Genotype-Specific, And Severity-Linked Alterations., Yohannes A Ambaw, Peter A Ljubenkov, Shubham Singh, Abdi Hamed, Sebastian Boland, Adam L Boxer, Tobias C Walther, Robert V Farese

Duncan NRI Faculty and Staff Publications

Introduction: Biomarkers are essential for monitoring the progression of frontotemporal dementia (FTD). Although dysregulated brain lipid metabolism, particularly sphingolipids enriched in the nervous system, is a key feature of neurodegeneration, plasma lipids remain underexplored as biomarkers compared to imaging and serum proteins.

Methods: We examined plasma lipidomes using liquid chromatography-tandem mass spectrometry (LC-MS/MS) from individuals carrying pathogenic variants linked to autosomal dominant FTD (GRN, C9orf72, MAPT) and non-carriers.

Results: FTD subjects exhibited increased plasma levels of gangliosides (GM3(d18:1_16:0), GM3(d18:1_24:1)), ceramide Cer(d18:1_23:0), and select polyunsaturated triacylglycerols. In contrast, phosphatidylethanolamine (PE(18:0_24:0) and sphingomyelin (SM(38:0) were reduced. Subtype-specific changes included elevated glucosylsphingosine (GlcSph(d18:1) …

Predicting Clinical Success Of Ct-Based Functional Drained Liver Volume Assessment In Malignant Biliary Obstruction, Ethan Y Lin, Bruno C Odisio, Koustav Pal, Iwan Paolucci, Ryan P Kempen, Nicolas Cardenas, Paige Reed, Ketan Y Shah, Ahmed Awad, Rahul A Sheth, David Fuentes, Alda Tam

Faculty, Staff and Student Publications

Purpose

To compare the predictive accuracy of subjective versus objective assessment of three-dimensional functional drained liver volume (fDLV) for clinical success after percutaneous transhepatic biliary drainage (PTBD).

Materials and Methods

This retrospective study included patients with malignant biliary obstruction and hyperbilirubinemia who underwent de novo PTBD between January 2016 and February 2017. Clinical success was defined as achieving total bilirubin level less than 1.8 mg/dL (30.8 μmol/L) within 30 days after PTBD. Seven interventional radiologists independently categorized subjective fDLV into four groups: less than 30%, 30%–50%, 51%–75%, and greater than 75% of the total liver volume. Objective fDLV was calculated …

Mechanisms Underlying Treatment-Resistant Depression: Exploring Sex-Based Biological Differences, Francisco E R Da Silva, Atakan Yucel, Antonio P M Menezes, Ana C Ruiz, Marcela C Carbajal Tamez, Tatiana Barichello, Giselli Scaini, Joao Quevedo

Faculty, Staff and Student Publications

Treatment-resistant depression (TRD) represents a severe and complex subtype of major depressive disorder (MDD), affecting approximately 30% of patients who fail to respond adequately to multiple standard antidepressant therapies. While the pathophysiology of TRD remains incompletely understood, emerging evidence suggests that sex-based biological differences might influence its onset, progression, and treatment response. Women are disproportionately affected by depression and are more likely to experience residual symptoms and treatment resistance, potentially due to hormonal fluctuations, immune system differences, and variations in brain circuitry and neuroplasticity. This narrative explores the current literature on the mechanisms underlying TRD, with a particular emphasis on …

Risk Of Second Primary Lung Cancer Among Cancer Survivors Stratified By The Site Of First Primary Cancer And The Lung Cancer Screening Eligibility Status, Sara Nofal, Edwin J Ostrin, Jianjun Zhang, Jia Wu, Paul Scheet, Mara B Antonoff, John V Heymach, Iakovos Toumazis

Faculty, Staff and Student Publications

Personal history of cancer is an independent risk factor for developing lung cancer. However, it is not considered in the current US lung cancer screening (LCS) guidelines. In this study, we assessed the risk of developing lung cancer among cancer survivors across 24 different sites of first primary cancer stratified by their LCS eligibility status. Using data from the Patient History Database at the University of Texas MD Anderson Cancer Center, we calculated and compared the cumulative incidence of second primary lung cancer, the overall and the LCS eligibility status-specific, stratified by the site of first primary cancer among cancer …

Spatial Colocalization And Molecular Crosstalk Of Myofibroblastic Cafs And Tumor Cells Shape Lymph Node Metastasis In Oral Squamous Cell Carcinoma, Ken Furudate, Shuya Kasai, Tadashi Yoshizawa, Yuya Sasaki, Kohei Fujikura, Shintaro Goto, Ryohei Ito, Koki Takagi, Tomoyuki Tanaka, Hiroshi Kijima, Kosei Kubota, Ken Itoh, Wataru Kobayashi, Koichi Takahashi

Faculty, Staff and Student Publications

Lymph node metastasis (LNM) is a critical prognostic factor for patients with oral squamous cell carcinoma (OSCC). Previous research has implicated the partial epithelial-to-mesenchymal transition of tumor cells and myofibroblastic cancer-associated fibroblasts (myCAFs) in the LNM process. However, the underlying molecular mechanisms remain poorly understood. Here, we conducted a comprehensive molecular analysis integrating original and publicly available OSCC data from bulk genome and transcriptome, single-cell transcriptome, and spatial transcriptome analyses. We found that myCAFs were quantitatively and functionally activated in LNM-positive samples and spatially colocalized with OSCC cells within the invasive tumor front (ITF), providing a niche that may facilitate …

Sex Disparities In Chlamydia And Gonorrhea Treatment In Us Adult Emergency Departments: A Systematic Review And Meta-Analysis, Rachel E Solnick, Rahi Patel, Ethan Chang, Carmen Vargas-Torres, Maaz Munawar, Carlin Pendell, Judith E Smith, Ethan Cowan, Keith E Kocher, Roland C Merchant

Faculty, Staff and Student Publications

BACKGROUND: Empiric antibiotic treatment for gonorrhea (GC) and chlamydia (CT) is common in U.S. emergency departments (EDs) due to the delayed availability of test results. Local studies have identified sex-based disparities in sexually transmitted infection (STI) care, with females potentially receiving less empiric treatment than males. This study evaluates how STI treatment aligns with laboratory-confirmed results to quantify potential overtreatment and undertreatment rates and investigates sex differences for these outcomes.

METHODS: We conducted a preregistered (PROSPERO #241429) systematic review and meta-analysis of studies published between January 2010 and January 2025 in U.S. EDs, excluding studies conducted exclusively in pediatric settings. …

Reliability And Spatial Consistency Of Mr Diffusion Tensor Imaging Measures Along The Cerebral Perivascular Space, Enchao Qiu, Joga Chaganti, Phillip Phan, M. Alizadeh, Devon Middleton, Kiran Talekar, Prabath Mondel, Scott H. Faro, Feroze Mohamed, Hsiangkuo Yuan

Department of Radiology Faculty Papers

BACKGROUND AND PURPOSE: Diffusion tensor imaging analysis along the perivascular space (DTI-ALPS) has emerged as a promising noninvasive method for evaluating water motion that may reflect glymphatic system function. However, the reliability of DTI-ALPS measurements across different region-of-interest (ROI) selection methods remains underinvestigated. This study aimed to assess the interrater reliability among three neuroradiologists in native space and compare DTI-ALPS indices derived from ROIs placed in subjects' native space versus standardized Montreal Neurological Institute (MNI) space.

METHODS: DTI-ALPS indices from 16 healthy subjects were calculated from both left and right hemispheres using two ROI placement approaches: (1) native space ROIs …

Risk Of Major Depression In Partners Of People With Alzheimer's Disease: A National Cohort Study, Casey Crump, Jingkai Wei, Barbara G Vickrey, Alexis C Edwards, Paul E Schulz, Weiva Sieh, Jan Sundquist, Kristina Sundquist

Faculty, Staff and Student Publications

Background: Alzheimer's disease (AD) may cause significant psychosocial distress not only in the patient but also their partner. However, long-term risks of major depression in partners of AD patients are largely unknown.

Methods: A national cohort study was conducted of all 145 289 partners of people diagnosed with all-cause dementia, including 57 113 partners of people diagnosed with AD, in Sweden during 1998-2017, and 1 300 561 population-based controls. Cox regression was used to compute hazard ratios (HRs) for subsequent risk of major depression identified from nationwide outpatient and inpatient diagnoses through 2018, adjusting for sociodemographic factors and prior mental …

Hiv-1 Controllers Possess A Unique Cd8+ T Cell Activation Phenotype And Loss Of Control Is Associated With Increased Expression Of Exhaustion Markers, Amber D. Jones, Zachary Capriotti, Erin Santos, Angel Lin, Rachel Van Duyne, Stephen Smith, Zachary Klase

Kimmel Cancer Center Papers, Presentations, and Grand Rounds

BACKGROUND: HIV-1 controllers are a rare population of individuals that exhibit spontaneous control of HIV-1 infection without antiretroviral therapy. Understanding the mechanisms by which HIV-1 controllers maintain and eventually lose this ability would be highly valuable in HIV-1 cure or vaccine research. Previous work revealed the ability of CD8+ T cells isolated from HIV-1 controllers to suppress HIV-1 replication in matched CD4+ T cells and PBMCs ex vivo and suggested the loss of control may be tied to CD8+ T cell exhaustion.

RESULTS: We explored whether CD8+ T cell exhaustion plays a role in the maintenance and loss of control …

A Protective Role Of Src-1 Against Aging Associated Cognitive Decline, Hesong Liu, Yongjie Yang, Jonathan C Bean, Yang He, Hailan Liu, Rambabu Majji, Chen Liang, Nan Zhang, Meng Yu, Longlong Tu, Qingzhuo Liu, Yue Deng, Kristine M Conde, Na Yin, Mengjie Wang, Yongxiang Li, Junying Han, Sanika Vattakuzhiyil Jossy, Megan Elyse Burt, Hari Krishna Yalamanchili, Chunmei Wang

Duncan NRI Faculty and Staff Publications

Introduction: Research indicates a strong correlation between obesity and the risk of dementia, both are linked to steroid receptor coactivator-1 (SRC-1), a transcriptional coactivator.

Methods: We used RNA sequencing analysis (RNA-Seq) to investigate the transcriptome of SRC-1-KO mice, and identified S100 calcium-binding protein A6 (S100A6), an AD associated gene, as one target of SRC-1. We tested cognitive behaviors in SRC-1-KO mice and mice with a humanized SRC-1 mutation (SRC-1L1376P), and performed promoter luciferase assays on S100A6.

Results: Loss of SRC-1 caused alterations in gene signatures that are commonly associated with neurodegenerative diseases, including AD, and diminished the neural plasticity of …

Heterozygous Variants In Plcg1 Affect Hearing, Vision, Cardiac, And Immune Function, Mengqi Ma, Yiming Zheng, Mingxi Deng, Shenzhao Lu, Xueyang Pan, Xi Luo, Michelle Etoundi, David Li-Kroeger, Kim C Worley, Lindsay C Burrage, Lauren S Blieden, Aimee Allworth, Wei-Liang Chen, Giuseppe Merla, Barbara Mandriani, Catherine E Otten, Pierre Blanc, Jill A Rosenfeld, Debdeep Dutta, Shinya Yamamoto, Michael F Wangler, Ian A Glass, Jingheng Chen, Elizabeth Blue, Paolo Prontera, Jeremie Rosain, Sandrine Marlin, Seema R Lalani, Hugo J Bellen, Undiagnosed Diseases Network

Duncan NRI Faculty and Staff Publications

Phospholipase C isozymes (PLCs) hydrolyze phosphatidylinositol 4,5-bisphosphate (PIP₂) into inositol 1,4,5-trisphosphate (IP₃) and diacylglycerol (DAG), important signaling molecules involved in many cellular processes including Ca²⁺ release from the endoplasmic reticulum (ER). PLCG1 encodes the PLCγ1 isozyme that is broadly expressed. Hyperactive somatic mutations of PLCG1 are observed in multiple cancers, but only one germline variant has been reported. Here, we describe seven individuals with heterozygous missense variants in PLCG1 [p.(Asp1019Gly), p.(His380Arg), p.(Asp1165Gly), and p.(Leu597Phe)] who present with hearing impairment (5/7), ocular pathology (4/7), cardiac septal defects (3/6), and various immunological issues (5/7). To model these …

Multiplex Imaging Mass Cytometry Reveals Prognostic Immunosuppressive Subpopulations And Macrophage-Driven Metastasis In Osteosarcoma, Benjamin B Gyau, Junyan Wang, Weiguo Wu, Brooks Scull, Angela M Major, Weidong Jin, Justin M M Cates, John Hicks, Tsz-Kwong Man

Faculty, Staff and Students Publications

Osteosarcoma is a type of bone cancer that mostly affects kids and teens. The biggest danger is when the cancer spreads to the lungs, and current treatments do not work well for those cases. Immunotherapy, which helps the body’s immune system fight cancer, has worked for other cancers but is limited for osteosarcoma because we do not fully understand the environment around the tumor. Our research looked at various cells around the tumor to study why patients have worse outcomes. We found that certain cells, called M2 macrophages (M2) and myeloid-derived suppressor cells (MDSC), which weaken the immune system, are …

High-Speed Voltage Imaging Of Action Potentials In Molecular Layer Interneurons Reveals Sensory-Driven Synchrony That Augments Movement, Spencer T Brown, Meghana R Holla, Michelle A Land, Shuyuan Yang, Alex J Mcdonald, François St-Pierre, Indira M Raman

Faculty, Staff and Students Publications

Testing whether the synchrony of action potential firing is a cerebellar coding mechanism requires simultaneous recording, with high temporal fidelity, from populations of identified neurons. Here, we used targeted one-photon voltage imaging at 2–4 kHz to record action potentials from groups of ~10–300 molecular layer interneurons (MLIs) expressing a positively tuned, genetically encoded voltage indicator, FORCE1f or pAce. In awake resting mice, crus I MLIs fired brief (~1-ms) spikes at 20–60 spikes/s. Sensory stimuli of air puffs to the whiskers evoked short-latency (< 10 ms) increases in spiking probability. In most trials, >50% of MLIs fired synchronously with 4-ms temporal precision. The magnitude of puff-evoked whisks correlated tightly with …

Outcomes Of Brexucabtagene Autoleucel In Patients With Relapsed/Refractory Acute Lymphoblastic Leukemia With Cns Involvement, Ibrahim N Muhsen, Gregory W Roloff, Rawan Faramand, Tamer Othman, Yannis Valtis, Noam E Kopmar, Simone E Dekker, Matthew Connor, Santiago Mercadal, Timothy E O'Connor, Kaitlyn C Dykes, Mohamed Ahmed, Nikeshan Jeyakumar, Amy Zhang, Katharine Miller, Katherine C Sutherland, Caitlin Guzowski, Vishal K Gupta, Navneet Majhail, Minoo Battiwalla, Melhem M Solh, Shahbaz A Malik, John Mathews, Caspian H Oliai, Paul Shaughnessy, Luke Mountjoy, Catherine J Lee, Aaron C Logan, Stephanie B Tsai, Jessica T Leonard, Marc Schwartz, Joshua P Sasine, Muthu Kumaran, Noelle Frey, Jae H Park, Divya Koura, Ryan D Cassaday, Bijal D Shah, Ibrahim Aldoss, Lori S Muffly, Laquisa C Hill

Faculty, Staff and Students Publications

Patients with relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL) with central nervous system (CNS) involvement (CNS B-ALL) have poor outcomes and were frequently excluded from CD19-targeting chimeric antigen receptor (CAR) T-cell clinical trials. The efficacy and safety of brexucabtagene autoleucel (brexu-cel) in adults with R/R B-ALL was established by the ZUMA-3 trial, which excluded patients with advanced or symptomatic CNS involvement. In this retrospective multicenter analysis, we investigated the safety and efficacy of brexu-cel in patients with CNS B-ALL using data from the ROCCA (Real-World Outcomes Collaborative for CAR T in ALL) consortium. Of 189 patients who received infusion, 31 …

30-Day And 1-Year Outcomes From The Optimize Pro Tavr Evolut Fx Addendum Study., Hemal Gada, Ramzi F Khalil, Stanley J Chetcuti, G Michael Deeb, Kendra J Grubb, Adam B Greenbaum, David Lorenz, Robert D Jumper, Ibrahim Sultan, Dustin Kliner, Paul Mahoney, Deepak R Talreja, Mustafa I Ahmed, Joshua D Rovin, Lang Lin, Paul Sorajja, Douglas G W Fraser, Suneet Mittal, Tamim Nazif, Josep Rodes-Cabau, Amit N Vora, Kathleen Ertelt, Amanda C Tenhoff, Yu Jung Yeh, Steven J Yakubov

Heart and Vascular Articles

BACKGROUND: Primary results from the Optimize PRO study demonstrated that transcatheter aortic valve replacement (TAVR) with the cusp overlap technique (COT) resulted in low 30-day permanent pacemaker implantation (PPI) rates and no moderate or greater aortic regurgitation (AR).

OBJECTIVES: The aim of this study was to evaluate outcomes after Evolut FX implantation using the COT and postprocedural computed tomography (CT).

METHODS: The Optimize PRO FX Addendum study is a postmarket, prospective, multicenter, nonrandomized study. Patients with severe aortic stenosis underwent TAVR with the Evolut FX using the COT protocol. Postprocedurally, COT adherence was evaluated to identify key steps, and CT-assessed …

Placental Polycyclic Aromatic Hydrocarbon (Pah) Levels Are Associated With Spontaneous Preterm Birth, Gwendolynn Hummel, Sohini Banerjee, Vasanta Putluri, Inaara Malick, Grace Johnson, Abu Hena Mostafa Kamal, Chandra Shekar R Ambati, Nagireddy Putluri, Lori Showalter, Cynthia D Shope, Joseph Hagan, Kjersti M Aagaard, Bhagavatula Moorthy, Melissa A Suter

Faculty, Staff and Students Publications

While the cause of preterm birth (PTB) (i.e., delivery before 37 weeks of gestation) is likely multifactorial, ambient exposure to environmental chemicals has been postulated to play a role in its etiology. Our prior studies of exposure to polycyclic aromatic hydrocarbons (PAHs) in pregnancy have shown an increased level of placental PAH-induced bulky DNA adducts with increasing levels of PAH exposures. In this investigation, we hypothesized that higher levels of placental PAHs would be associated with an increased risk of PTB. Using gas chromatography and mass spectrometry (GC-MS/MS), we measured levels of benzo(a)pyrene (BaP), benzo(b)fluoranthene (BbF) and dibenz(a,h)anthracene (DBA) from …

Targeting Sting To Disrupt Macrophage-Mediated Adhesion In Encapsulating Peritoneal Sclerosis, Juan Sun, Yuxiang Sun, Dandan Guo, Huolin Ye, Qiang Huang, Hu Zhou, Canming Li, Mei Liao, Yujia You, Hongli Shang, Pan Zhou, Dongxuan Wu, Janusz Witowski, Zhaoyong Hu, Hui Peng

Faculty, Staff and Students Publications

Encapsulating peritoneal sclerosis (EPS) is a life-threatening fibrotic condition characterized by severe abdominal adhesions, chronic inflammation, and significant morbidity. The lack of effective treatments for EPS stems from a limited understanding of its underlying mechanisms. In this study, we developed a modified mouse model of PD-induced EPS and investigated the role of the STING signaling pathway in disease progression. Our findings reveal that STING activation in peritoneal mesothelial cells significantly increases the secretion of the macrophage chemokine CCL2, leading to enhanced macrophage infiltration and the formation of pathological adhesions. Notably, pharmacological inhibition of STING using the inhibitor H151 effectively reduced …

Racial And Socioeconomic Disparities In Long Term Survival After Surgery And Radiation For Spinal Cord Hemangioblastoma, Abdul Karim Ghaith, Xinlan Yang, Joshua Weinberg, Shaan Bhandarkar, Taha Khalilullah, Abdel-Hameed Al-Mistarehi, Khaled Zaitoun, Meghana Bhimreddy, Arjun K. Menta, Antony A. Fuleihan, Kamel Chebaro, Jawad Khalifeh, Andrew Grossbach, Nicholas Theodore, Daniel Lubelski

Department of Medicine Faculty Papers

Spinal cord hemangioblastomas are rare, benign, intradural tumors that, despite their nonmalignant histopathology, can lead to substantial neurological morbidity. While disparities in outcomes based on race and socioeconomic status have been well-documented in other spinal tumor populations, their role in spinal cord hemangioblastoma remains poorly understood. In this study, we utilize the National Cancer Database (NCDB) to evaluate the influence of race, socioeconomic factors, and healthcare access on survival outcomes in patients with spinal cord hemangioblastoma. Additionally, we explore the utility of machine learning-based survival models to improve individualized risk prediction and to identify key clinical and sociodemographic determinants of …

Organizational Climate And Decision Aid Sustainability In Lupus Care: Mixed Methods Study, Aizhan Karabukayeva, Larry R Hearld, Nathan W Carroll, Reena Kelly, Jasvinder A Singh

Faculty, Staff and Students Publications

Background: Digital decision aids (DAs) are increasingly used in health care to support shared decision-making and promote patient engagement. In the context of systemic lupus erythematosus (SLE), a complex autoimmune disease characterized by diverse symptoms and uncertain prognoses, DAs offer guidance to patients in navigating treatment risks and benefits. Although numerous studies have examined the initial implementation of evidence-based tools, there is limited evidence on the organizational factors that influence their long-term sustainability in clinical practice. This gap is particularly salient for digital interventions, where integration into routine workflows and ongoing use require alignment with clinic readiness and culture. This …

Prefrontal Cortex Astrocytes Modulate Distinct Neuronal Populations To Control Anxiety-Like Behavior, Eunyoung Kim, Hairuo Du, Yanqi Tan, Brandon L Brown, Yaowen Chang, Blanca Díaz-Castro, Jonathan V Sweedler, Xinzhu Yu

Faculty, Staff and Student Publications

Accumulating evidence has supported diverse regulatory functions of astrocytes in different neural circuits as well as various aspects of complex behaviors. However, little is known about how astrocytes regulate different neuronal subpopulations that are linked to specific behavioral aspects within a single brain region. Here, we show that astrocytes in the medial prefrontal cortex (mPFC) encode anxiogenic environmental cues in freely behaving mice. Silencing mPFC astrocyte Ca

Germline Structural Variations Involving The Pediatric Brain Tumor Transcriptome Include Disease-Relevant And Ancestry-Related Genes, Fengju Chen, Yiqun Zhang, Luis F Paulin, Fritz J Sedlazeck, Chad J Creighton

Faculty, Staff and Students Publications

Background: Germline Structural Variants (SVs) represent an important source of genetic diversity, in large part due to their influence on gene transcription. It is necessary to systematically catalog germline SVs and their associated impacted genes across different cohorts and tissue and cellular contexts, including pediatric brain or Central Nervous System (CNS) tumors.

Methods: We combined RNA with whole genome sequencing across 1430 pediatric brain or CNS tumor patients from the Children's Brain Tumor Network. We set out to systematically identify genes for which the proximity of germline SVs was recurrently and significantly associated with differential expression in the tumor sample …

Dissatisfaction And Residual Symptoms In Younger And Older Adult Patients After Total Knee Arthroplasty, Nicholas Pohl, Parker Brush, Adrian Santana, Sebastian Fras, Eleanor Jenkins, Arjun Saxena

Department of Orthopaedic Surgery Faculty Papers

INTRODUCTION: Total knee arthroplasty (TKA) is an increasingly used treatment option for younger patients with osteoarthritis. Previous research has found only 66% patients < 60 years who underwent TKA postoperatively reported that their knees felt normal. However, the prior studies did not compare underlying causes for dissatisfaction based on age. This study compared the satisfaction and residual symptom rates between patients ages < 60 and ≥60 years and identified specific reasons for their dissatisfaction between the age groups.

METHODS: Patients who underwent unilateral TKA for osteoarthritis from 2014 to 2016 were electronically sent a 15-question survey pertaining to surgery satisfaction. Following patient identification and survey completion, patient demographics, medical history, surgical time, and length of stay were collected through manual review of medical records. Patients who completed surveys were grouped by age (< 60 years or ≥60 years) for analysis.

RESULTS: In total, 1189 ≥ 60-year-old patients and 388 < 60-year-old patients were included. Most patients in both cohorts reported satisfaction with overall knee function (< 60: 68.6%; ≥60: 71.8%; P = 0.175). Fewer < 60-year patients reported normal knee function (66.5% vs. 75.2%; P < 0.001). The most common residual symptom in both cohorts was continued pain.

CONCLUSION: Patients younger than 60 years reported less satisfaction with performing normal activities …

Proteogenomic Characterization Unveils Biomarkers Associated With Chemoresistance In Muscle-Invasive Bladder Cancer, Matthew V Holt, Yongchao Dou, Meggie N Young, Alexander B Saltzman, Meenakshi Anurag, Jonathan T Lei, Antrix Jain, Mei Leng, Beom-Jun Kim, Lacey E Dobrolecki, Stefanie F Faucher, Sara Savage, Chenwei Wang, Zhiao Shi, Hugo Villanueva, Karoline Kremers, Kyle D Drinnon, Patricia D Castro, Michael M Ittmann, Mehak Mehboob Khatani, Sung Han Kim, Matthew J Ellis, Bing Zhang, Anna Malovannaya, Seth P Lerner

Faculty, Staff and Students Publications

To explore potential chemoresistance mechanisms and identify therapeutic opportunities in muscle-invasive bladder cancer (MIBC), we conduct comprehensive proteogenomic characterization of 46 pre- and 14 post-treatment MIBC tumors incorporating genomics, transcriptomics, proteomics, and phosphoproteomics. Multi-omics clustering not only recapitulated established molecular subtypes but also revealed subtypes associated with chemotherapy sensitivity. Protein isoform level analysis identifies protein abundance of a short isoform of ATAD1 and RAF family proteins as biomarkers of chemosensitivity. Integration of proteomic and phosphoproteomic data reveals Wnt signaling via GSK3B-S9 phosphorylation and the JAK/STAT pathway as potential targets to overcome chemoresistance. Correlations between PD-L1 and TROP-2/NECTIN-4 indicate an additive …

Revisiting The Effect Of Udenafil On Exercise Performance In Patients With Fontan Circulation: Results Of A Post Hoc Analysis Of The Fuel Trial., David J. Goldberg, Victor Zak, Chenwei Hu, Adam M. Lubert, Rahul H. Rathod, Daniel J. Penny, Robert Whitehill, Kurt R. Schumacher, Salil Ginde, Michelle Ploutz, Gi Beom Kim, Todd T. Nowlen, Michael V. Dimaria, Benjamin P. Frischhertz, Jonathan B. Wagner, Kimberly E. Mchugh, Brian W. Mccrindle, Mark J. Cartoski, Jon Detterich, Anji T. Yetman, Anitha S. John, Marc E. Richmond, Matthew Files, R Mark Payne, Andrew S. Mackie, Christopher K. Davis, William B. Orr, Ruchira Garg, Kevin D. Hill, Jennifer S. Yauck, Michael G. Mcbride, James Yeager, Gail D. Pearson, Stephen M. Paridon, Bryan H. Goldstein

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: In the FUEL (Fontan Udenafil Exercise Longitudinal) trial, a positive treatment effect was identified for outcomes at the ventilatory anaerobic threshold but not for the primary outcome, oxygen consumption (Vo₂ in participants with near-normal baseline exercise performance.

METHODS: Participants were divided into subgroups by baseline predicted peak Vo₂ (< 80% versus ≥80%). Treatment effect was evaluated in those with a baseline peak Vo2 < 80% predicted and linear regression was performed to examine the interaction between subgroup and response to therapy for the primary and secondary outcomes.

RESULTS: Of the 379 participants with paired exercise data, 302 (80%) had a baseline peak Vo₂ < 80% predicted. In this subgroup, the primary outcome of peak Vo₂ improved significantly after 6 months of udenafil treatment, when compared with placebo (0.23±4.17 mL/kg per min versus -0.90±3.74 mL/kg per min; P=0.021). Secondary outcome measures, including Vo₂ at …

Dna Methylation Signatures Of Cardiovascular Health Provide Insights Into Diseases, Madeleine Carbonneau, Yi Li, Yishu Qu, Yinan Zheng, Alexis C Wood, Mengyao Wang, Chunyu Liu, Tianxiao Huan, Roby Joehanes, Xiuqing Guo, Jie Yao, Kent D Taylor, Russell P Tracy, Peter Durda, Yongmei Liu, W Craig Johnson, Wendy S Post, Tom Blackwell, Jerome I Rotter, Stephen S Rich, Susan Redline, Myriam Fornage, Jun Wang, Hongyan Ning, Lifang Hou, Donald Lloyd-Jones, Kendra Ferrier, Yuan-I Min, April P Carson, Laura M Raffield, Alexander Teumer, Hans J Grabe, Henry Völzke, Matthias Nauck, Marcus Dörr, Arce Domingo-Relloso, Amanda Fretts, Maria Tellez-Plaza, Shelley A Cole, Ana Navas-Acien, Meng Wang, Joanne M Murabito, Nancy L Heard-Costa, Brenton Prescott, Vanessa Xanthakis, Dariush Mozaffarian, Daniel Levy, Jiantao Ma

Faculty, Staff and Students Publications

Background: The association of overall cardiovascular health (CVH) with changes in DNA methylation (DNAm) has not been well characterized.

Methods: We calculated the American Heart Association's Life's Essential 8 score to reflect CVH in 5 cohorts with diverse backgrounds (mean age 54 years, 55% women, and enrollment year ranging from 1989 to 2012). Epigenome-wide association studies (EWAS) for Life's Essential 8 score were conducted, followed by bioinformatic analyses. DNAm loci significantly associated with Life's Essential 8 score were used to calculate a CVH DNAm score. We examined the association of the CVH DNAm score with incident cardiovascular disease (CVD), cardiovascular …

Trpc4 Regulates Limbic Behavior And Neuronal Development By Stabilizing Dendrite Branches Through Actomyosin-Driven Integrin Activation, Jaepyo Jeon, Travis I Moore, Insuk So, Marc Freichel, Veit Flockerzi, Lutz Birnbaumer, Michael X Zhu

Faculty, Staff and Student Publications

Transient Receptor Potential Canonical 4 (TRPC4) channels have been implicated in multiple neurological functions, including anxiety and sociability. TRPC4 variants were also found in patients with autism. However, the contributions of TRPC4 to neurodevelopment remain undefined. Here, we show that neurobehavioral deficits appear early in young TRPC4 knockout (Trpc4^−/−) mice immediately after weaning, manifesting as alterations in multiple, limbic-related behaviors, such as nesting, marble burying, burrowing, self-grooming, and social interactions. Hippocampal neurons of Trpc4−/− mice exhibit reduced dendritic arborization both in vivo and in vitro. Mechanistically, we found that TRPC4 expression in dendrites surged at the …

Extended Survival With Pancreatic Carcinosarcoma: A Case Report And Literature Review, Tian Xiao, Claire Browne, Morgan Black, Celia Marginean, Elena Tsvetkova

Faculty, Staff and Students Publications

Pancreatic carcinosarcoma is a rare and aggressive malignancy that can mimic pancreatic adenocarcinomas in presentation but often has different disease biology and different responses to conventional treatment for pancreatic adenocarcinoma. Case reports have documented a 5-year overall survival of approximately 13% only if the disease is caught at an earlier stage and is amenable to multi-modality treatment, including surgery, chemotherapy, and radiation. In the advanced stage, treatments do not often provide benefit, and patients may decline rapidly. There are currently no studies demonstrating survival benefits with chemotherapy in patients with metastatic carcinosarcoma, owing to both the rarity and the often …

High-Grade Glioma With Pleomorphic And Pseudopapillary Features: A Single-Institution Series Of Three Cases, Eric A Goethe, Rasha Alfattal, Subhiksha Srinivasan, Pushan Dasgupta, Vinay Puduvalli, Shiao-Pei Weathers, Leomar Y Ballester, Jeffrey S Weinberg, Sujit Prabhu, Sherise D Ferguson, Maria A Gubbiotti

Faculty, Staff and Students Publications

Introduction: Modern molecular diagnostic techniques such as DNA methylation profiling are leading to the reclassification of several central nervous system malignancies and discovery of novel diagnostic entities, such as high-grade glioma with pleomorphic and pseudopapillary features (HPAP).

Methods: We performed a retrospective chart review of all patients with HPAP confirmed with methylation profiling at a single institution between 2023 and 2025. Demographic, radiographic, surgical, and outcome data were collected.

Results: Three patients were identified: two females and one male with a mean age of 49.7 years (range 25-62). No patients had a prior cancer history. One patient had an incidentally …

Kdm2b Variants In The Cxxc Domain Impair Its Dna-Binding Ability And Cause A Distinct Neurodevelopmental Syndrome, Amber S E Van Oirsouw, Michael A Hadders, Martijn Koetsier, Edith D J Peters, Nurit Assia Batzir, Tahsin Stefan Barakat, Diana Baralle, Adelyn Beil, Marie-Noëlle Bonnet-Dupeyron, Philip M Boone, Arjan Bouman, Deanna Alexis Carere, Benjamin Cogne, Leslie Dunnington, Laura S Farach, Casie A Genetti, Bertrand Isidor, Louis Januel, Aakash Joshi, Nayana Lahiri, Kristen N Lee, Idit Maya, Meriel Mcentagart, Hope Northrup, Mathilde Pujalte, Kate Richardson, Susan Walker, Bobby P C Koeleman, Mariëlle Alders, Richard H Van Jaarsveld, Renske Oegema

Faculty, Staff and Student Publications

Rare variants affecting the epigenetic regulator KDM2B cause a recently delineated neurodevelopmental disorder. Interestingly, we previously identified both a general KDM2B-associated episignature and a subsignature specific to variants in the DNA-binding CxxC domain. In light of the existence of a distinct subsignature, we set out to determine if KDM2B CxxC variants are associated with a unique phenotype and disease mechanism. We recruited individuals with heterozygous CxxC variants and assessed the variants' effect on protein expression and DNA-binding ability. We analyzed clinical data from 19 individuals, including ten previously undescribed individuals with seven novel CxxC variants. The core phenotype of the …

Outcomes Of Patients With Newly Diagnosed Acute Myeloid Leukemia With Flt3-Tyrosine Kinase Domain Mutations: Prognostic Implications Of Npm1 Co-Mutation, Sankalp Arora, Wei-Ying Jen, Musa Yilmaz, Indraneel Deshmukh, Jayastu Senapati, Sanam Loghavi, Ghayas C Issa, Nicholas J Short, Tapan M Kadia, Courtney D Dinardo, Gautam Borthakur, Joseph Jabbour, Naveen Pemmaraju, Michael Andreeff, Koichi Takahashi, Kapil Bhalla, Uday Popat, Elizabeth J Shpall, Betul Oran, Hussein A Abbas, Guillermo Garcia-Manero, Farhad Ravandi, Hagop Kantarjian, Naval Daver

Faculty, Staff and Student Publications

Background: The prognostic impact of Fms-like tyrosine kinase 3 (FLT3)-tyrosine kinase domain (TKD) mutation in patients with acute myeloid leukemia (AML) is not well defined. The authors described outcomes of one of the largest cohorts of patients with FLT3-TKD mutated (FLT3-TKDmut) AML to date.

Methods: This retrospective study included patients with newly diagnosed AML who received frontline treatment at The University of Texas MD Anderson Cancer Center from January 2012 to March 2024 divided into two cohorts: FLT3-TKDmut AML and nucleophosmin-mutated (NPM1mut)/FLT3-TKD wild-type (FLT3-TKDwt) AML. Patients with FLT3 internal tandem duplication mutations were excluded.

Results: In total, 2922 patients were …