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Neurological Recovery After Ich Is Mediated By The Aryl Hydrocarbon Receptor-Bilirubin Interplay Through Improved Erythrophagocytosis, Xiurong Zhao, Shun-Ming Ting, Guanghua Sun, Jaroslaw Aronowski Feb 2026

Neurological Recovery After Ich Is Mediated By The Aryl Hydrocarbon Receptor-Bilirubin Interplay Through Improved Erythrophagocytosis, Xiurong Zhao, Shun-Ming Ting, Guanghua Sun, Jaroslaw Aronowski

Faculty, Staff and Student Publications

Hematoma clearance after ICH is a pro-hemostatic process aiming at repair/recovery and is achieved through microglia/macrophages (MMΦ)-mediated erythrophagocytosis. Upon the engulfment of masses of erythrocytes and toxic hemolysis products, hemoglobin and heme, phagocytes convert them to bilirubin (BrB). Bilirubin is essentially not soluble in water and when overproduced, it precipitates within the cell causing injury. Thus, keeping bilirubin soluble and at a low intracellular level is needed for proper function of MMΦ. Here, using cultured microglia (MG), we found that intracellular formation of BrB in microglia during erythrophagocytosis coincides with the activation of transcription factor AhR, and AhR target genes …


Cardiometabolic Parameter Change By Weight Regain On Tirzepatide Withdrawal In Adults With Obesity: A Post Hoc Analysis Of The Surmount-4 Trial, Deborah B Horn, Bruno Linetzky, Melanie J Davies, Luke J Laffin, Hui Wang, Madhumita A Murphy, Sarah Zimner-Rapuch, Eva Lau, Avigdor D Arad, Clare J Lee Feb 2026

Cardiometabolic Parameter Change By Weight Regain On Tirzepatide Withdrawal In Adults With Obesity: A Post Hoc Analysis Of The Surmount-4 Trial, Deborah B Horn, Bruno Linetzky, Melanie J Davies, Luke J Laffin, Hui Wang, Madhumita A Murphy, Sarah Zimner-Rapuch, Eva Lau, Avigdor D Arad, Clare J Lee

Faculty, Staff and Student Publications

Importance: In the SURMOUNT-4 trial, most adults with obesity who had tirzepatide withdrawn following a 36-week treatment regained weight. The association between the degree of weight regain and cardiometabolic parameters after tirzepatide withdrawal is unknown.

Objective: To assess changes in cardiometabolic parameters by degree of weight regain after withdrawal of tirzepatide.

Design, setting, and participants: This post hoc analysis of the SURMOUNT-4 trial included tirzepatide-treated participants with 10% or greater weight reduction at week 36 initially randomized to placebo. Data were collected from March 2021 to May 2023, and data were analyzed from February 2024 to March 2025.

Interventions: After …


Role Of Childhood Trauma In Interoception And Alexithymia In Schizophrenia, Samantha Narvaez, Krista Wisner, Alina Siatka, L Elliot Hong, Joshua Chiappelli Feb 2026

Role Of Childhood Trauma In Interoception And Alexithymia In Schizophrenia, Samantha Narvaez, Krista Wisner, Alina Siatka, L Elliot Hong, Joshua Chiappelli

Faculty, Staff and Student Publications

Childhood trauma (CT) is a notable risk factor for schizophrenia. Separately, CT has been associated with alexithymia, referring to difficulties in identifying and describing one's own feelings, as well as disturbed interoception, referring to difficulties sensing and responding to signals that originate from within the body. Both self-perception impairments have been observed in schizophrenia; however, the role of CT in these observations in schizophrenia is unclear. To address this gap, interoception was assessed using the Multidimensional Assessment of Interoceptive Awareness (MAIA), alexithymia was assessed using the Toronto Alexithymia Scale (TAS-20), and CT was measured using the Childhood Trauma Questionnaire (CTQ) …


Dopamine Agonist Therapy Induced Fatal Pneumocephalus In Giant Prolactinoma, Archana M H, Anurag Ranjan Lila, Manjiri Karlekar, Saba Samad Memon, Rohit Barnabas, Tushar Bandgar Feb 2026

Dopamine Agonist Therapy Induced Fatal Pneumocephalus In Giant Prolactinoma, Archana M H, Anurag Ranjan Lila, Manjiri Karlekar, Saba Samad Memon, Rohit Barnabas, Tushar Bandgar

Faculty, Staff and Student Publications

We report a man in the fifth decade of his life with an invasive giant prolactinoma (size: 7.3 cm; serum prolactin 56820 ng/mL [SI: 2470.4 nmol/L], reference range, 5-25 ng/mL [SI: 0.22-1.09 nmol/L]) who presented with hypogonadism and headache. Dopamine agonist (DA) cabergoline (0.25 mg twice weekly) was initiated, and serum prolactin levels reached 3941 ng/mL (SI: 171.3 nmol/L) after 2 doses. Two weeks later, he developed acute symptoms of headache, vomiting, and drowsiness associated with cerebrospinal fluid rhinorrhea. He presented to the casualty after 48 hours of the onset of these acute symptoms in an altered state. Neuroimaging demonstrated …


Cultural Influences On Camouflaging And Autistic Burnout: Examining The Experiences Of Latino Autistic Young Adults, Antonio F Pagán, Katherine A Loveland, Ron Acierno Feb 2026

Cultural Influences On Camouflaging And Autistic Burnout: Examining The Experiences Of Latino Autistic Young Adults, Antonio F Pagán, Katherine A Loveland, Ron Acierno

Faculty, Staff and Student Publications

The present study explored the relationship between camouflaging, autistic burnout, and cultural factors in Latino young adults with autism spectrum disorder (ASD). While autistic burnout and camouflaging have been widely studied in general ASD populations, limited research has focused on Latino individuals, who may experience unique pressures due to cultural values such as collectivism, familism, and traditional gender roles. Participants (N = 56) from the ¡Iniciando! la Adultez therapy program completed measures assessing burnout, camouflaging, acculturation, and cultural values. Results indicate that participants reported moderate to high levels of autistic burnout, with the highest levels observed in heightened self-awareness …


Bet Inhibitor-Based Combinations Targeting Novel Dependencies In Mecom-Rearranged (R) Aml, Christine E Birdwell, Warren Fiskus, Christopher P Mill, Tapan M Kadia, Naval Daver, Courtney D Dinardo, Koji Sasaki, John A Davis, Kaberi Das, Hanxi Hou, Antrix Jain, Anna Malovannaya, Lauren B Flores, Rasoul Pourebrahim, Selina Yuan, Xiaoping Su, Michele Ceribelli, Kapil N Bhalla Feb 2026

Bet Inhibitor-Based Combinations Targeting Novel Dependencies In Mecom-Rearranged (R) Aml, Christine E Birdwell, Warren Fiskus, Christopher P Mill, Tapan M Kadia, Naval Daver, Courtney D Dinardo, Koji Sasaki, John A Davis, Kaberi Das, Hanxi Hou, Antrix Jain, Anna Malovannaya, Lauren B Flores, Rasoul Pourebrahim, Selina Yuan, Xiaoping Su, Michele Ceribelli, Kapil N Bhalla

Faculty, Staff and Student Publications

MECOM rearrangement in AML involves either inv(3)(q21;q26.2) or t(3;3)(q21;q26.2), where the dislocated GATA2 enhancer drives overexpression of the transcriptional regulator EVI1, causes concomitant GATA2 repression, and promotes AML progression, aggressive phenotype and therapy refractoriness. Treatment with BET protein inhibitor (BETi) induces in vitro and in vivo efficacy in MECOM-r AML cells. Utilizing an unbiased, high-throughput drug screen, focused on mechanistically-annotated drugs, we identified BRD4, PIK3CA, mTOR, BCL-xL and XIAP as dependencies in the MECOM-r AML cells. Monotherapy with mivebresib (BETi), dactolisib (PI3K/mTORi) and LCL161 (IAPi) dose-dependently induced greater lethality in PD MECOM-r versus non-MECOM-r AML cells. RNA-Seq and/or mass spectrometry …


Cleavage And Polyadenylation Specificity Factor Subunit 5 Regulates Pulmonary Artery Smooth Muscle Expansion And Hypoxic Response, Scott D Collum, Lisha Zhu, Tingting W Mills, Rene Girard, Jamie Tran, Tinne C J Mertens, Cory Wilson, Nancy Wareing, Erik E Suarez, Howard J Huang, Rahat Hussain, Bindu Akkanti, Wenjin J Zheng, Hari K Yalamanchili, Bela Patel, Eric J Wagner, Sandeep Agarwal, Harry Karmouty-Quintana Feb 2026

Cleavage And Polyadenylation Specificity Factor Subunit 5 Regulates Pulmonary Artery Smooth Muscle Expansion And Hypoxic Response, Scott D Collum, Lisha Zhu, Tingting W Mills, Rene Girard, Jamie Tran, Tinne C J Mertens, Cory Wilson, Nancy Wareing, Erik E Suarez, Howard J Huang, Rahat Hussain, Bindu Akkanti, Wenjin J Zheng, Hari K Yalamanchili, Bela Patel, Eric J Wagner, Sandeep Agarwal, Harry Karmouty-Quintana

Faculty, Staff and Student Publications

Pulmonary hypertension (PH) is a fatal condition that affects individuals with systemic sclerosis (SSc), a multiorgan fibrotic disease with limited treatment options. A central feature of PH is vascular remodeling, defined by the narrowing of the arteriole lumen due to cell proliferation and extracellular matrix deposition. Herein, we identify a central mechanism that can regulate multiple transcripts important for vascular remodeling. The highlight of our study is the demonstration that reduced pulmonary artery smooth muscle (PASMC) Nudt21, which codes for the RNA binding protein Cleavage and Polyadenylation Specificity Factor Subunit 5 (CPSF5) The, known to regulate alternative polyadenylation, results …


Lessons Learned In A Data Linkage Project On Fatal Drowning, Rohit P Shenoi, Ned Levine, Elizabeth A Camp, Linh Nguyen, Sandra Mckay, Shaila Zaman Feb 2026

Lessons Learned In A Data Linkage Project On Fatal Drowning, Rohit P Shenoi, Ned Levine, Elizabeth A Camp, Linh Nguyen, Sandra Mckay, Shaila Zaman

Faculty, Staff and Student Publications

Background: Drowning is the leading cause of death in US children 1-4 years old. The epidemiology of drowning at a regional level is understudied because no single data source provides complete information on persons who drown. Probabilistic data linkage is a novel way of studying the epidemiology of drowning. This study aimed to document the lessons learned during the linkage process.

Methods: This was a cross-sectional study of persons of all ages who died from unintentional drowning in metropolitan Houston from 2016 to 2022. We describe the lessons learned during the project planning and execution phases which pertained to data …


Determinants Of Severe Financial Distress In U.S. Acute Care Hospitals: A National Longitudinal Study, James R Langabeer, Francine R Vega, Audrey Sarah Cohen, Tiffany Champagne-Langabeer, Andrea J Yatsco, Karima Lalani Jan 2026

Determinants Of Severe Financial Distress In U.S. Acute Care Hospitals: A National Longitudinal Study, James R Langabeer, Francine R Vega, Audrey Sarah Cohen, Tiffany Champagne-Langabeer, Andrea J Yatsco, Karima Lalani

Faculty, Staff and Student Publications

Background: Financial sustainability remains a central challenge for U.S. hospitals as rising operating costs, shifting federal reimbursement, and policy uncertainty intensify economic pressures. This study estimates the prevalence and recent changes in financial distress among U.S. short-term acute care hospitals.

Methods: We conducted a national longitudinal analysis of all U.S. short-term acute care hospitals from 2021 to 2023 using financial and operational data from Medicare cost reports linked with community-level data from the American Community Survey. Financial distress was measured using the Altman Z-score, with severe distress defined as Z ≤ 1.8. Logistic regression models were used to …


Supercharging-Enhanced Ndia-Ms Enables Global Profiling Of Drug-Induced Proteome Solubility Shifts, Yun Xiong, Huimin Zhang, Lin Tan, Bo Wei, John N Weinstein, Philip L Lorenzi Jan 2026

Supercharging-Enhanced Ndia-Ms Enables Global Profiling Of Drug-Induced Proteome Solubility Shifts, Yun Xiong, Huimin Zhang, Lin Tan, Bo Wei, John N Weinstein, Philip L Lorenzi

Faculty, Staff and Student Publications

Mass spectrometry (MS) is indispensable for high-throughput quantitation of protein expression. But protein function is regulated by factors beyond abundance alone. Here, we evaluate two supercharging reagents, dimethyl sulfoxide (DMSO) and m-nitrobenzyl alcohol (mNBA), in narrow-window data-independent acquisition (nDIA)-MS. DMSO markedly enhances MS signal and protein identification, whereas mNBA primarily increases peptide identifications. Optimizating nDIA-MS with 3% DMSO boosts signal intensity by up to 56%, enabling identification of ~9,600 proteins from 1 µg HeLa digest in 15 min. Using this methodology, we quantify solubility and abundance changes in 8,694 proteins across three cell lines following short-term treatment with the proteasome …


High-Throughput Proteomic Profiling To Evaluate Differentiation Syndrome With Menin Inhibition, Miriam B Garcia, Bofei Wang, Irtiza Sheikh, Georgina El Hajjar, David Mccall, Cesar Nunez, Amber Gibson, Philip L Lorenzi, Ghayas C Issa, Branko Cuglievan, Hussein A Abbas Jan 2026

High-Throughput Proteomic Profiling To Evaluate Differentiation Syndrome With Menin Inhibition, Miriam B Garcia, Bofei Wang, Irtiza Sheikh, Georgina El Hajjar, David Mccall, Cesar Nunez, Amber Gibson, Philip L Lorenzi, Ghayas C Issa, Branko Cuglievan, Hussein A Abbas

Faculty, Staff and Student Publications

High-throughput proteomic profiling provides a comprehensive analysis of systemic cancer effects and tumor microenvironment interactions. Characterizing soluble proteins driving inflammation in acute myeloid leukemia (AML) offers insight into inflammatory diseases like differentiation syndrome (DS) related to AML therapies like menin inhibitors. We present our application of NUcleic acid-Linked Immuno-Sandwich Assay (NULISA), a novel technology leveraging next-generation sequencing (NGS) for high-throughput, ultra-sensitive characterization of secreted inflammatory proteins in plasma or serum. Here we report its use to identify dynamic soluble protein changes during treatment and at the time of suspected DS in pediatric AML patients treated with the menin inhibitor revumenib …


Seipin Expression In Hepatocytes Impairs The Assembly Of Vldls And Exacerbates Steatohepatitis, Qianqian Dong, Yidan Ma, Xin Chen, Xiaowei Wang, Ziwei Liu, Chenxi Liang, Liwen Qiu, Jinye Tang, Jin Wu, Yang Liu, Xiaoqin Wu, Yaru Zhou, Mingming Gao, Hongyuan Yang Jan 2026

Seipin Expression In Hepatocytes Impairs The Assembly Of Vldls And Exacerbates Steatohepatitis, Qianqian Dong, Yidan Ma, Xin Chen, Xiaowei Wang, Ziwei Liu, Chenxi Liang, Liwen Qiu, Jinye Tang, Jin Wu, Yang Liu, Xiaoqin Wu, Yaru Zhou, Mingming Gao, Hongyuan Yang

Faculty, Staff and Student Publications

VLDLs are crucial for maintaining liver and whole-body lipid homeostasis. Limited knowledge exists regarding the lipidation process of VLDL. Endoplasmic reticulum (ER) luminal lipid droplets (LLDs) have been suggested to provide lipids for VLDL lipidation and maturation. Seipin, an integral membrane protein of the ER, plays key roles in the formation of cytoplasmic LDs (CLDs) and adipocyte differentiation. Surprisingly, seipin is hardly detectable in hepatocytes. Given the critical contribution of seipin in forming CLDs, we hypothesize that the absence of seipin in hepatocytes might ensure the proper formation of LLDs and the lipidation and assembly of VLDLs. To explore the …


Downregulation Of Slc40a1 Leads To Iron Accumulation In Fibrotic Lung Fibroblasts, Quanjin Dang, Chaoqun Huang, Yurong Liang, Akshaya Surendran, Dharanya Muthiah, Kishore Vaddadi, Sankha Hewawasam, Tingting W Mills, Lin Liu Jan 2026

Downregulation Of Slc40a1 Leads To Iron Accumulation In Fibrotic Lung Fibroblasts, Quanjin Dang, Chaoqun Huang, Yurong Liang, Akshaya Surendran, Dharanya Muthiah, Kishore Vaddadi, Sankha Hewawasam, Tingting W Mills, Lin Liu

Faculty, Staff and Student Publications

Iron is an essential nutrient for almost all organisms. However, excess iron generates reactive oxygen species and causes tissue injuries. Iron is implicated in idiopathic pulmonary fibrosis (IPF). In this study, we examined iron accumulation in fibrotic lung fibroblasts and the underlying mechanisms. We hypothesize that the downregulation of Solute Carrier Family 40 Member 1 (SLC40A1) results in iron accumulation in lung fibroblasts of IPF patients. Using a Prussian Blue iron staining, we found that iron accumulated in the fibrotic region of the lungs from IPF patients and bleomycin- and asbestos-induced lung fibrosis mice. Iron was partially co-localized with the …


An Application-Based Ontological Knowledge Base Of Medications To Support Health Literacy And Adherence For The Consumer Population: An Aging Population Use Case, Clifford Chen, Muhammad Amith, Kirk Roberts, Rebecca Mauldin, Renata Komalasari, Cui Tao Jan 2026

An Application-Based Ontological Knowledge Base Of Medications To Support Health Literacy And Adherence For The Consumer Population: An Aging Population Use Case, Clifford Chen, Muhammad Amith, Kirk Roberts, Rebecca Mauldin, Renata Komalasari, Cui Tao

Faculty, Staff and Student Publications

No abstract provided.


Comparative Outcomes Of Abdominal, Laparoscopic, And Vaginal Sacral Colpopexy: A National Analysis Of Apical Suspension Procedures (2014–2022), Smit Bharat Solanki, Apurva B Pancholy, Vishal Pancholy Jan 2026

Comparative Outcomes Of Abdominal, Laparoscopic, And Vaginal Sacral Colpopexy: A National Analysis Of Apical Suspension Procedures (2014–2022), Smit Bharat Solanki, Apurva B Pancholy, Vishal Pancholy

Faculty, Staff and Student Publications

Objective: Sacral colpopexy is a well-established procedure for apical suspension, but the relative outcomes of abdominal, laparoscopic, and vaginal approaches remain debated. This study compared perioperative outcomes across these surgical routes using a national database and evaluated trends in robotic assistance.

Materials and methods: We analyzed sacral colpopexy cases from the American College of Surgeons National Surgical Quality Improvement Program between 2014 and 2022. Patient demographics, complication rates, and surgical outcomes were compared among abdominal, laparoscopic, and vaginal procedures. Relative risks (RR) were adjusted for confounders. The utilization of robotic systems in laparoscopic procedures was examined.

Results: Among 61,524 cases, …


A Robust Convnext-Based Framework For Efficient, Generalizable, And Explainable Brain Tumor Classification On Mri, Kirti Pant, Pijush Kanti Dutta Pramanik, Zhongming Zhao Jan 2026

A Robust Convnext-Based Framework For Efficient, Generalizable, And Explainable Brain Tumor Classification On Mri, Kirti Pant, Pijush Kanti Dutta Pramanik, Zhongming Zhao

Faculty, Staff and Student Publications

Background: Accurate and dependable brain tumor classification from magnetic resonance imaging (MRI) is essential for clinical decision support, yet remains challenging due to inter-dataset variability, heterogeneous tumor appearances, and limited generalization of many deep learning models. Existing studies often rely on single-dataset evaluation, insufficient statistical validation, or lack interpretability, which restricts their clinical reliability and real-world deployment.

Methods: This study proposes a robust brain tumor classification framework based on the ConvNeXt Base architecture. The model is evaluated across three independent MRI datasets comprising four classes-glioma, meningioma, pituitary tumor, and no tumor. Performance is assessed using class-wise and aggregate metrics, including …


The Cortico-Cortical And Subcortical Circuits Of The Human Brain Language Centers Including The Dual Limbic And Language Functioning Fiber Tracts, Arash Kamali, Nithya P Narayana, Anastasia Loiko, Anusha Gandhi, Paul E Schulz, Nitin Tandon, Manish N Shah, Vinodh A Kumar, Larry A Kramer, Jay-Jiguang Zhu, Haris Sair, Roy F Riascos, Khader M Hasan Jan 2026

The Cortico-Cortical And Subcortical Circuits Of The Human Brain Language Centers Including The Dual Limbic And Language Functioning Fiber Tracts, Arash Kamali, Nithya P Narayana, Anastasia Loiko, Anusha Gandhi, Paul E Schulz, Nitin Tandon, Manish N Shah, Vinodh A Kumar, Larry A Kramer, Jay-Jiguang Zhu, Haris Sair, Roy F Riascos, Khader M Hasan

Faculty, Staff and Student Publications

Background/Objectives: In recent years, MRI-based diffusion-weighted tractography techniques have uncovered additional white matter pathways that have significant roles in language processing and production. In this review, we aim to outline the major language centers of the brain and major language pathways along with association tracts that serve dual roles in both the language and limbic systems. According to the current dual-stream model of language processing, the brain's language network is organized into a dorsal stream, responsible for mapping sound to articulation, and a ventral stream, which maps sound to meaning.

Materials and Methods: The literature cited in this …


Beyond Neurons: Impact Of Cannabidiol On Glial Cells In Ischemic Stroke, Victória Linden De Rezende, Khiany Mathias, Cinara Ludvig Gonçalves, Rafael Mariano De Bitencourt, Tatiana Barichello, Fabricia Petronilho Jan 2026

Beyond Neurons: Impact Of Cannabidiol On Glial Cells In Ischemic Stroke, Victória Linden De Rezende, Khiany Mathias, Cinara Ludvig Gonçalves, Rafael Mariano De Bitencourt, Tatiana Barichello, Fabricia Petronilho

Faculty, Staff and Student Publications

Ischemic stroke triggers a complex cascade of events involving inflammation, oxidative stress, and glial cell dysfunction, all of which contribute to neuronal damage and impaired recovery. Glial cells (e.g., astrocytes, microglia, and oligodendrocytes) play key roles in neuroinflammatory responses, making them attractive targets for therapeutic modulation. Cannabidiol, a non-psychoactive phytocannabinoid from Cannabis sativa, exhibits anti-inflammatory, antioxidant, and neuroprotective properties. Preclinical evidence indicates that cannabidiol attenuates glial reactivity, reduces pro-inflammatory signaling, mitigates oxidative stress, and preserves blood-brain and intestinal barrier integrity in stroke models. Moreover, cannabidiol modulates key molecular pathways (e.g., nuclear factor-κB, tumor necrosis factor, and calcium-related signaling), contributing to …


Targeting Interleukin-6 Trans-Signaling To Improve Post-Stroke Inflammation: A Precision Immunotherapy Perspective, Kate Mendoza, Dustin T Nguyen, Anjali Chauhan Jan 2026

Targeting Interleukin-6 Trans-Signaling To Improve Post-Stroke Inflammation: A Precision Immunotherapy Perspective, Kate Mendoza, Dustin T Nguyen, Anjali Chauhan

Faculty, Staff and Student Publications

No abstract provided.


Structures Of Invertebrate Pezo-1 Isoforms With A Compact Architecture And A Dispensable Pore-Distal N-Terminal Blade, Briar Bell, Angela M Jaramillo-Granada, Daniel J Orlin, Wei-Hsiang Weng, Haosheng Wen, Marcos Sotomayor, Alexander T Chesler, Matthew L Baker, Julio F Cordero-Morales, Valeria Vásquez Jan 2026

Structures Of Invertebrate Pezo-1 Isoforms With A Compact Architecture And A Dispensable Pore-Distal N-Terminal Blade, Briar Bell, Angela M Jaramillo-Granada, Daniel J Orlin, Wei-Hsiang Weng, Haosheng Wen, Marcos Sotomayor, Alexander T Chesler, Matthew L Baker, Julio F Cordero-Morales, Valeria Vásquez

Faculty, Staff and Student Publications

PIEZO channels are mechanosensitive ion channels conserved from plants to humans, yet structures exist for only a few mammalian orthologs. We define the structural and functional diversity of Caenorhabditis elegans PEZO-1, a single gene with extensive alternative splicing, by determining cryo-electron microscopy structures of three representative isoforms: G (full length), K (lacking the pore-distal N-terminal blade), and L (missing most of the blade). PEZO-1G displays mechanically evoked currents yet adopts a compact, semi-flattened conformation that significantly differs from the mammalian domes. The blades exhibit a three-step slope architecture stabilized by inter-blade latching among transmembrane helical units, yielding a circular, steering-wheel-like …


Structures Of Trpv1 Bound By Hyperthermia-Inducing Analgesics, Yu-Hao Gao, Yi-Zhe Huang, Zhao-Xing Li, Xiao-Ying Chen, Chang-Yan Shao, Han-Wen Li, Bin Liu, Fán Yang, Mei-Rong Chen, Mei-Ling Lu, Michael X Zhu, Fan Yang, Yi-Bei Xiao, Ye Yu Jan 2026

Structures Of Trpv1 Bound By Hyperthermia-Inducing Analgesics, Yu-Hao Gao, Yi-Zhe Huang, Zhao-Xing Li, Xiao-Ying Chen, Chang-Yan Shao, Han-Wen Li, Bin Liu, Fán Yang, Mei-Rong Chen, Mei-Ling Lu, Michael X Zhu, Fan Yang, Yi-Bei Xiao, Ye Yu

Faculty, Staff and Student Publications

TRPV1, a member of the transient receptor potential vanilloid subfamily, mediates nociception and thermoregulation. TRPV1-targeting analgesics frequently induce hyperthermia, underscoring the need for structural insights to guide the development of safer compounds. Here, we determined the structures of rat TRPV1 bound to the clinical candidate analgesics AMG517, AMG9810, and SB366791. AMG517 and AMG9810 are deeply situated within the S3-S4 interface of the vanilloid pocket, where they interact with residues from the S3-S6 helices, as well as the S4-S5 linker. These interactions induce local deformations in the TRP-box and lower S6 helix, accompanied by a modest rotation of the S1-S4 bundle, …


Differentiation In The Human Urothelia Is Defined By Distinct Alternative Polyadenylation, Ninh B Le, Surbhi Sona, Briana Santo, Yi Zhang, Rosie Ou, R Allen Schweickart, Veena Kochat, William I Padron, Kunal Rai, Shih-Han Lee, Joo Mi Yi, Oliver Wessely, Byron H Lee, Angela H Ting Jan 2026

Differentiation In The Human Urothelia Is Defined By Distinct Alternative Polyadenylation, Ninh B Le, Surbhi Sona, Briana Santo, Yi Zhang, Rosie Ou, R Allen Schweickart, Veena Kochat, William I Padron, Kunal Rai, Shih-Han Lee, Joo Mi Yi, Oliver Wessely, Byron H Lee, Angela H Ting

Faculty, Staff and Student Publications

Distinct epithelial cell states arise during differentiation, but mechanisms generating transcriptomic diversity among them remain poorly defined. The human ureter urothelium contains basal progenitor, intermediate cells, and terminally differentiated umbrella cells. Prior single-cell RNA sequencing revealed similar global gene expression profiles across these states, raising the question of how distinct identities emerge. Here, we show that alternative cleavage and polyadenylation (APA) introduces a major layer of transcriptomic diversity during urothelial differentiation, largely independent of changes in mRNA levels. Analysis of 13,544 urothelial cells identified hundreds of differentiation-associated APA events. Single-cell imaging revealed spatially specific APA patterns, and reporter assays demonstrated …


Differentiation In The Human Urothelia Is Defined By Distinct Alternative Polyadenylation, Ninh B Le, Surbhi Sona, Briana Santo, Yi Zhang, Rosie Ou, R Allen Schweickart, Veena Kochat, William I Padron, Kunal Rai, Shih-Han Lee, Joo Mi Yi, Oliver Wessely, Byron H Lee, Angela H Ting Jan 2026

Differentiation In The Human Urothelia Is Defined By Distinct Alternative Polyadenylation, Ninh B Le, Surbhi Sona, Briana Santo, Yi Zhang, Rosie Ou, R Allen Schweickart, Veena Kochat, William I Padron, Kunal Rai, Shih-Han Lee, Joo Mi Yi, Oliver Wessely, Byron H Lee, Angela H Ting

Faculty, Staff and Student Publications

Distinct epithelial cell states arise during differentiation, but mechanisms generating transcriptomic diversity among them remain poorly defined. The human ureter urothelium contains basal progenitor, intermediate cells, and terminally differentiated umbrella cells. Prior single-cell RNA sequencing revealed similar global gene expression profiles across these states, raising the question of how distinct identities emerge. Here, we show that alternative cleavage and polyadenylation (APA) introduces a major layer of transcriptomic diversity during urothelial differentiation, largely independent of changes in mRNA levels. Analysis of 13,544 urothelial cells identified hundreds of differentiation-associated APA events. Single-cell imaging revealed spatially specific APA patterns, and reporter assays demonstrated …


Payload Diversification Overcomes Resistance And Guides Sequential Antibody-Drug Conjugate Therapy In Breast Cancer, Dileep Reddy Rampa, Minji Seo, Nanae Ogata, Zhaoxuan Yang, Nithya Sridhar, Fujii Takeo, Chalothorn Wannaphut, Jennifer A Maynard, Kyoji Tsuchikama, George W Sledge, Naoto T Ueno, Jangsoon Lee Jan 2026

Payload Diversification Overcomes Resistance And Guides Sequential Antibody-Drug Conjugate Therapy In Breast Cancer, Dileep Reddy Rampa, Minji Seo, Nanae Ogata, Zhaoxuan Yang, Nithya Sridhar, Fujii Takeo, Chalothorn Wannaphut, Jennifer A Maynard, Kyoji Tsuchikama, George W Sledge, Naoto T Ueno, Jangsoon Lee

Faculty, Staff and Student Publications

Purpose: Antibody-drug conjugates (ADCs) have transformed the treatment of breast cancer. FDA-approved ADCs such as trastuzumab deruxtecan (T-DXd), sacituzumab govitecan (SG), and datopotamab deruxtecan (Dato-DXd) have demonstrated clinical benefit; however, drug resistance will almost inevitably emerge in the metastatic setting, and there is no established strategy for selecting subsequent ADCs after disease progression to the first exposure to the ADC. This study aimed to define mechanisms of acquired resistance and evaluate rational sequencing approaches.

Experimental design: We generated breast cancer cell lines resistant to T-DXd (TDXd-R) and SG (SG-R). We assessed antigen expression, internalization, and resistance pathways, including efflux transporter …


Cabozantinib And Thromboembolism In Patients With Cancer: A Systematic Review, Meta-Analysis, And Retrospective Study, Harish Eswaran, Rohan R Kasthuri, Pavan K Bendapudi, Alok A Khorana, Raj S Kasthuri, Nick Van Es, Steven P Grover Jan 2026

Cabozantinib And Thromboembolism In Patients With Cancer: A Systematic Review, Meta-Analysis, And Retrospective Study, Harish Eswaran, Rohan R Kasthuri, Pavan K Bendapudi, Alok A Khorana, Raj S Kasthuri, Nick Van Es, Steven P Grover

Faculty, Staff and Student Publications

Antiangiogenic agents, including vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs), represent an important class of treatments for a range of solid tumors. However, concerns have arisen over potential associations between antiangiogenic agents and thromboembolic events. We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) that compared a frequently used VEGFR TKI, cabozantinib, with placebo or usual care. The primary outcome was the risk of any thromboembolism. Secondary outcomes included the risk of venous thromboembolism (VTE), risk of arterial thromboembolism (ATE) and progression-free survival. 14 RCTs were included with a combined total of 4204 patients, …


Mechanistic Insights Into The Antimicrobial Effect Of Benzodioxane-Benzamides Against Escherichia Coli, Lorenzo Suigo, Alessia Lanzini, Valentina Straniero, William Margolin Jan 2026

Mechanistic Insights Into The Antimicrobial Effect Of Benzodioxane-Benzamides Against Escherichia Coli, Lorenzo Suigo, Alessia Lanzini, Valentina Straniero, William Margolin

Faculty, Staff and Student Publications

Background/Objectives: The bacterial cell division machinery is emerging as an attractive target for antimicrobial compounds. FtsZ, a highly conserved essential division protein, is the target for a number of small molecules such as benzamides. Recent studies show that benzodioxane-benzamides (BDOBs) are among the most potent inhibitors of FtsZ function in Gram-positive bacteria, although their ability to inhibit Gram-negative FtsZ, in particular Escherichia coli FtsZ, has been more controversial.

Methods: Here, we use genetic and cytological methods to demonstrate that FtsZ of efflux pump-disabled E. coli can be efficiently targeted by BDOBs.

Results: We show that engineered mutants …


Ai-Enabled Ecg Analysis Improves Diagnostic Accuracy And Reduces False Stemi Activations: A Multicenter U.S. Registry, Robert Herman, Bryn E Mumma, Jake D Hoyne, Benjamin L Cooper, Nils P Johnson, Timea Kisova, Anthony Demolder, Adam Rafajdus, Andrej Iring, Timotej Palus, Marta Belmonte, Emanuele Barbato, Suzanne J Baron, Robert Hatala, Stephen W Smith, H Pendell Meyers, Scott W Sharkey, Jozef Bartunek, Timothy D Henry Jan 2026

Ai-Enabled Ecg Analysis Improves Diagnostic Accuracy And Reduces False Stemi Activations: A Multicenter U.S. Registry, Robert Herman, Bryn E Mumma, Jake D Hoyne, Benjamin L Cooper, Nils P Johnson, Timea Kisova, Anthony Demolder, Adam Rafajdus, Andrej Iring, Timotej Palus, Marta Belmonte, Emanuele Barbato, Suzanne J Baron, Robert Hatala, Stephen W Smith, H Pendell Meyers, Scott W Sharkey, Jozef Bartunek, Timothy D Henry

Faculty, Staff and Student Publications

Background: Timely reperfusion is critical in reducing mortality in ST-segment elevation myocardial infarction (STEMI). Although electrocardiography-guided cardiac catheterization laboratory (CCL) activation on the basis of first medical contact recognition improves system-level response, diagnostic uncertainty, particularly in atypical presentations, contributes to false positive activations (FPAs) and reperfusion delays.

Objectives: The aim of this study was to evaluate the diagnostic performance and operational impact of artificial intelligence (AI)-based electrocardiographic (ECG) analysis in real-world STEMI triage across a multicenter U.S. registry.

Methods: A total of 1,032 patients with suspected STEMI who triggered emergent CCL activation at 3 geographically diverse percutaneous coronary intervention centers …


Multilevel Analysis Of The Food And Physical Activity Environment And Adult Obesity Across U.S. Counties And States, Ann Mary Abraham, Michael D Swartz, Alexandra E Van Den Berg, Stephen H Linder Jan 2026

Multilevel Analysis Of The Food And Physical Activity Environment And Adult Obesity Across U.S. Counties And States, Ann Mary Abraham, Michael D Swartz, Alexandra E Van Den Berg, Stephen H Linder

Faculty, Staff and Student Publications

Adult obesity rates have risen steadily across the United States over the past decade, with more than 40% of adults affected. Persistent geographic and demographic disparities exist in obesity prevalence across the nation. While prior research has examined individual or environmental associated factors of obesity, limited studies have addressed both physical activity and food environments across the nation using multilevel approaches. This cross-sectional ecological study (2014-2024) used a two-level random intercept model to assess the association between county- and state-level factors and adult obesity prevalence across over 3000 U.S. counties nested within 51 states. County-level associated factors included food insecurity, …


Clinical Workflow Of Spine Stereotactic Radiotherapy And Radiosurgery: Insights From A Single-Institution Physics Perspective, Dennis Mackin, Gizem Cifter, Yana Zlateva, Jihong Wang, Yao Ding, Muhammad Shafiq Ul Hassan, Zhiheng Wang, Parmeswaran Diagaradjane, Fada Guan, Travis C Salzillo, Shane Krafft, Jing Li, Martin C Tom, Amol J Ghia, Tina Marie Briere Jan 2026

Clinical Workflow Of Spine Stereotactic Radiotherapy And Radiosurgery: Insights From A Single-Institution Physics Perspective, Dennis Mackin, Gizem Cifter, Yana Zlateva, Jihong Wang, Yao Ding, Muhammad Shafiq Ul Hassan, Zhiheng Wang, Parmeswaran Diagaradjane, Fada Guan, Travis C Salzillo, Shane Krafft, Jing Li, Martin C Tom, Amol J Ghia, Tina Marie Briere

Faculty, Staff and Student Publications

Spine stereotactic radiotherapy and radiosurgery (SSRS) techniques, encompassing both fractionated stereotactic treatments and single-fraction radiosurgery, are widely used for the management of spinal metastases due to their ability to deliver highly conformal radiation while limiting dose to adjacent critical structures. Clinical outcomes following SSRS, including durable local control and acceptable toxicity, have been reported previously in multiple institutional series. In this manuscript, we describe the clinical workflow used to deliver SSRS at a high-volume academic center, with emphasis on the medical physics processes that support routine clinical practice. Key elements of the workflow include patient selection, treatment region-specific immobilization, CT …


Association Between The 2022 Aha/Acc/Hfsa Heart Failure Staging And Cardiovascular And Kidney Outcomes In Patients With Diabetes And Kidney Disease: A Post Hoc Analysis Of The Scored Randomized Controlled Trial, Ayodele Odutayo, Deepak L Bhatt, Vikas S Sridhar, Michael Szarek, Christopher P Cannon, Lawrence A Leiter, Darren K Mcguire, Julia B Lewis, Renato D Lopes, Benjamin M Scirica, Kausik K Ray, Michael J Davies, Phillip Banks, Manon Girard, Subodh Verma, Jacob A Udell, Bertram Pitt, Ph Gabriel Steg, David Z I Cherney Jan 2026

Association Between The 2022 Aha/Acc/Hfsa Heart Failure Staging And Cardiovascular And Kidney Outcomes In Patients With Diabetes And Kidney Disease: A Post Hoc Analysis Of The Scored Randomized Controlled Trial, Ayodele Odutayo, Deepak L Bhatt, Vikas S Sridhar, Michael Szarek, Christopher P Cannon, Lawrence A Leiter, Darren K Mcguire, Julia B Lewis, Renato D Lopes, Benjamin M Scirica, Kausik K Ray, Michael J Davies, Phillip Banks, Manon Girard, Subodh Verma, Jacob A Udell, Bertram Pitt, Ph Gabriel Steg, David Z I Cherney

Faculty, Staff and Student Publications

Background: The 2022 American Heart Association/American College of Cardiology/Heart Failure Society of America heart failure (HF) classification incorporates cardiac biomarkers to identify early risk of HF. The HF stages may also guide the prognosis and management of cardiovascular and kidney-related events.

Methods: SCORED (Effect of Sotagliflozin on Cardiovascular and Renal Events in Patients With Type 2 Diabetes and Moderate Renal Impairment Who Are at Cardiovascular Risk) was a randomized trial in diabetes with kidney disease comparing sotagliflozin versus placebo on cardiovascular death, HF hospitalizations, and urgent HF visits. SCORED participants were grouped by HF stage post hoc. Stage A: no …