Digital Commons Network^™

Point-Of-Care Hrhpv Mrna Detection With Reverse Transcription Recombinase Polymerase Amplification On A Portable Fluorimeter From Provider-Collected Cervical Samples In Maputo, Mozambique, Emilie Newsham Novak, Cannon J Hansen, Zoha Wazir, Ariel Ma, Jennifer Carns, Hira Atif, Jane R Montealegre, Michael E Scheurer, Cesaltina Lorenzoni, Daniel G Rosen, Mila P Salcedo, Kathleen M Schmeler, Rebecca R Richards-Kortum

Faculty, Staff and Students Publications

Background: Cervical cancer is the most common cancer in women in Mozambique, where limited screening infrastructure contributes to high disease burden. While testing for high-risk human papillomavirus (hrHPV) DNA can identify women at risk for cervical cancer, its limited specificity may lead to overtreatment in screen-and-treat programs, straining resources. We performed a pilot study to evaluate preliminary feasibility of a novel, accessible test to detect hrHPV mRNA, a more specific biomarker for cervical cancer risk, from 22 women who previously screened positive for visual inspection with acetic acid at Maputo Central Hospital in Mozambique.

Methods: Cervicovaginal samples were analyzed for …

Evaluating The Reproducibility And Verifiability Of Nutrition Research: A Case Study Of Studies Assessing The Relationship Between Potatoes And Colorectal Cancer, Yasaman Jamshidi-Naeini, Colby J Vorland, Pranav Kapoor, Bailey Ortyl, Jocelyn Mineo, Luke Still, Korlu Sorsor, Shelby Rodney, Xander Tooze, Brent Flickinger, Beate Henschel, Stephanie L Dickinson, David B Allison

Faculty, Staff and Students Publications

The credibility of nutritional research is dependent on the rigor with which studies are conducted and the ability for independent assessment to be performed. Despite the importance of these, more work is needed in the field of nutrition to buttress the trustworthiness of nutrition research. To develop and apply a process for evaluating the rigor, reproducibility, and verifiability of nutritional research, using the relationship between potato consumption and Colorectal Cancer (CRC) as a case study. We updated existing systematic reviews to include studies on potatoes and CRC, assessing their design, execution, and reporting quality. We attempted to reproduce and verify …

Self-Perceived Burden And Mental Health Outcomes In Adults With Osteogenesis Imperfecta, Emily R Strouphauer, Camille Villar, Ryan J Mccarty, Danqi Li, Gianna M Colombo, Brendan Lee, Chaya N Murali, Dianne Nguyen, Sarah Sadek, Marie-Eve Robinson, Jocelyn Gomez, Michelle Fynan, V Reid Sutton, Andrew D Wiese, Eric A Storch

Faculty, Staff and Students Publications

Osteogenesis Imperfecta (OI) is a rare disorder causing bone fragility, pain, and functional impairment that causes substantial psychosocial burden. This study examined how self-perceived burden (SPB), or distress from feelings of dependence on caregivers, relates to depression, anxiety, and suicidality in adults with OI. A total of 208 adults (M age = 42.9, predominately White and female) with OI were recruited to complete a cross-sectional survey assessing SPB, psychological symptoms, health, and sociodemographics. Results indicated that SPB was significantly higher among younger individuals, those not living with a partner, those living with adult family members, lower-income groups, and individuals …

Microglial Swell1 Deficiency Drives Male-Specific Seizure Vulnerability But Paradoxical Neuroprotection Through Impaired Phagocytosis, Abhijeet S Barath, Aastha Dheer, Laura Montier, Mekenzie M Peshoff, Emily Dale, Flavia Goche, Thanh Thanh Le Nguyen, Mastura Akter, Fangfang Qi, Dimitrios Kleidonas, Lauren Harris, Sarah A Jewanee, Anthony D Umpierre, Dale B Bosco, Koichiro Haruwaka, Rajan Sah, Long-Jun Wu, Rongzhuo Hua, Tejaswani Datla

The Brown Foundation: Institute of Molecular Medicine

The discovery of genes encoding the volume-regulated anion channel (VRAC) has enabled detailed exploration of its cell type-specific roles in the brain. LRRC8A (SWELL1) is the essential VRAC subunit. We observed seizure-induced, subunit-specific changes in microglial VRAC expression and investigated its function using conditional KO (cKO) of LRRC8A in microglia. SWELL1 cKO mice exhibited a male-specific increase in kainate-induced seizure severity, yet showed paradoxical neuroprotection against seizure-associated neuronal loss. Mechanistically, SWELL1 deletion led to a cell-autonomous reduction in microglial density and decreased release of VRAC-permeable neuroactive metabolites, including taurine, GABA, and glutamate in culture. Additionally, impaired phagocytic kinetics and reduced …

Toolkit For Multistate Disease Progression Simulation And Treatment Decision-Making Aid, Can Xie, Ruosha Li, Wael Saber, Jorge E Cortes, Nicholas J Short, Xuelin Huang

Faculty, Staff and Student Publications

Background: The optimal timing of a treatment within therapy lines can maximize its benefit while minimizing risks and side effects. Because patients differ in clinical and biological characteristics, personalized treatment planning can support physicians' decision-making. However, multistate disease progression complicates the comparison of treatment strategies, motivating the development of a user-friendly web tool for multistate disease progression simulation and treatment decision support. Microsimulation is a natural approach for comparing prespecified treatment-timing strategies, where it generates disease trajectories for a large number of virtual patients matched to an individual patient's observed data. In our framework, microsimulation is performed using a multistate …

A Multilevel Analysis Of Hiv Care Outcomes Across Age, Race, And Housing Among United States Women Veterans, Giselle Day, Amber B Amspoker, Alan Z Sheinfil, Liang Chen, Emmanuel Guajardo, Maria E Fernandez, Cici Bauer, Irene Tamí-Maury, Jan Lindsay

Faculty, Staff and Students Publications

Background: Women veterans with HIV represent a growing, diverse population within the Veterans Health Administration (VHA). This study examined HIV care continuum outcomes among women veterans using a multilevel intersectional approach.

Methods: We conducted a retrospective analysis of 1154 women veterans with HIV in VHA care in fiscal year 2022, with outcomes assessed in fiscal year 2023. We applied Multilevel Analysis of Individual Heterogeneity and Discriminatory Accuracy (MAIHDA) to evaluate how combinations of social positions (age, race/ethnicity, housing status) were associated with HIV outcomes.

Results: MAIHDA models showed that younger age (< 45 years) and being unhoused were consistently associated with lower odds of care engagement and viral suppression than midlife (45-64) and older (65+) housed women veterans. Additionally, predicted probability analyses revealed distinct clustering patterns. Younger non-Hispanic White women consistently ranked among the lowest performing strata across all outcomes, while midlife and older Hispanic and non-Hispanic Black women veterans clustered among the highest. Variance Partition Coefficients from null models were modest (1.8-3.0%). Fully adjusted models showed no remaining between-stratum variance, suggesting that the included social positions explained the observed differences in our dataset.

Conclusions: These findings highlight disparities in HIV care …

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 …

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 …

Conformational Cycling Of The Wntless Transporter Drives Trafficking And Secretion Of Wnt Morphogens, Yunhui Ge, Taciani De Almeida Magalhaes, Hongjiang Wu, Dick J H Van Den Boomen, Thu Uyen Nguyen, Tongyi Dou, Gaya P Yadav, Sukyeong Lee, Zhao Wang, Andrew Lemoff, Xuemei Luo, Sumitha S Menon, Min Zhang, Jin Wang, Zhicheng Jin, Jiansen Jiang, Adrian Salic, Pengxiang Huang

Faculty, Staff and Students Publications

Wnt proteins are lipid-modified morphogens fundamental in development and disease. During Wnt biogenesis, the G-protein-coupled receptor (GPCR)-like transporter Wntless (WLS) escorts lipidated Wnts from the endoplasmic reticulum to the plasma membrane, then transfers them to extracellular carriers, forming active and soluble morphogen-carrier complexes. To dissect the mechanisms involved, we solve cryo-EM structures of Wnt-bound WLS and unliganded WLS, and perform structure-guided functional experiments. Wnts engage WLS via three conserved hairpins, which are all required for Wnt trafficking to the cell surface and carrier-mediated secretion. Wnt release from cells is driven by dramatic conformational changes in the WLS transmembrane domain, reminiscent …

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. …

Fibulin-4 Expressed In Metastatic Breast Cancer Is A Target Of Peptide-Based Imaging Probes And Experimental Therapeutics, Alexes C Daquinag, Sukhen C Ghosh, Solmaz Aghaamiri, Stephen M Farmer, Sheng Zhang, Servando Hernandez Vargas, Ashwin K Ramesh, Zhiqiang An, Ali Azhdarinia, Mikhail G Kolonin

The Brown Foundation: Institute of Molecular Medicine

There is a lack of approaches to detect and kill metastatic cells. As an agent for metastasis targeting, a cyclic peptide BLMP6 has been previously characterized. As a step toward translation, we designed AZDye555-labeled BLMP6 and demonstrated its homing to metastases of human MDA-MB-231 cells in mice. We show that 68Ga-radiolabeled BLMP6 can be used for the detection of MDA-MB-231 metastases. We designed a peptide-drug conjugate consisting of monomethyl auristatin E (MMAE) and BLMP6. We show that MMAE-BLMP6 kills MDA-MB-231 cells in cell culture and in vivo. In mouse models of lung metastases, treatment with MMAE-BLMP6 suppressed metastasis growth …

Qeith: Quantifies Tumor Ecosystem Heterogeneity To Predict Cancer Progression And Treatment Benefit, Qiqi Liu, Jiangti Luo, Jiawei Wang, Bangqi Zhao, Xiaosheng Wang, Linjun You

Faculty, Staff and Student Publications

Intratumor heterogeneity (ITH) is a fundamental driver of therapeutic failure and disease progression. However, the complexity of the tumor ecosystem is a critical yet underexplored aspect, making its precise quantification essential for fully deciphering ITH and its clinical implications. To address this, we developed Quantifying Ecosystem Intratumor Heterogeneity (QeITH), a computational framework that applies Shannon entropy to quantify ecosystem heterogeneity by measuring the diversity and distributional entropy of cellular compositions and functional states across single-cell, bulk, and spatial transcriptomics. At the single-cell resolution, QeITH identifies elevated ITH as intrinsic markers of malignant transformation, yet enhanced sensitivity to therapy. Pan-cancer bulk …

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

Faculty, Staff and Students Publications

No abstract provided.

Oral Cancer Numerical Index (Ocni): Development And Validation Of A Cytology-Based Risk Assessment For Oral Lesions, Michael P Mcrae, Nadarajah Vigneswaran, Alexander Ross Kerr, Spencer W Redding, Martin H Thornhill, Craig Murdoch, Paul M Speight, Rachelle Wolk, Kritika S Rajsri, Pooja Gaikwad, Nancy Ruel, Nicolaos J Christodoulides, John T Mcdevitt

Faculty, Staff and Student Publications

Background/Objectives: Oral potentially malignant disorders (OPMDs) require accurate risk stratification to identify patients at the highest risk for severe oral epithelial dysplasia (OED) or oral squamous cell carcinoma (OSCC). We developed and internally validated the oral cancer numerical index (OCNI), a quantitative risk score derived from clinical features and deep learning-based brush cytology measurements.

Methods: This retrospective model development and internal validation study was conducted using data from the multicenter Grand Opportunity study. Prospectively recruited subjects with OPMD with complete data were divided at the subject level into a training set (n = 384) and a holdout test set …

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 …

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.

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, …

Virtual Lunch And Learn: Enhancing Research Communication With Visual Tools, Sonya Fogg

TMC Library Newsletter (2015-)

Virtual Lunch and Learn: Enhancing Research Communication with Visual Tools on June 26, 2026 at noon.

Understand the role of visual communication in medical research. Distinguish between data visualizations, infographics, and visual abstracts. Identify best practices and some resources and tools for creating effective visuals.

Register to attend this virtual session!

Resource Highlight: Accessdermatologydxrx, Joanne Romano

TMC Library Newsletter (2015-)

Try AccessDermatologyDxRx! It is your go-to Access collection in dermatology featuring core texts, review questions, cases, videos, 3D modules, and more, including: Fitzpatrick’s Dermatology Flashcards, Weinberg’s Color Atlas of Pediatric Dermatology and Taylor and Kelly’s Dermatology for Skin of Color.  Try it today!

Upcoming Holidays, Katie Prentice

TMC Library Newsletter (2015-)

No abstract provided.

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 …

Hp1bp3 Loss Links Chromatin Reorganization To Metabolic Vulnerability In Glioma, Brittney Lozzi, Taylor A Gatesman, Pushan Dasgupta, Debosmita Sardar, Yeunjung Ko, Chenyu Mao, Hsiao-Chi Chen, Rachel N Curry, Dongjoo Choi, Carrie A Mohila, Melissa L Bondy, Ganesh Rao, Marco Gallo, Sameer Agnihotri, Benjamin Deneen

Duncan NRI Faculty and Staff Publications

High-grade gliomas (HGGs) are aggressive brain tumors with poor prognosis, driven in part by metabolic and epigenetic adaptations. Methionine metabolism supports HGG growth by supplying S-adenosylmethionine for methylation reactions, yet how nutrient availability influences chromatin organization in HGG remains incompletely understood. Using an immunocompetent mouse model of HGG, we found that dietary methionine restriction reduced tumor proliferation, extended survival, and induced partial nuclear inversion. We identified Hp1bp3 as a key regulator of tumor growth that functions by interacting with nuclear tethering proteins to mediate chromatin reorganization. Loss of Hp1bp3 results in the upregulation of histone demethylases leading to selective depletion …

Development And Validation Of A Harmonized Memory Score For Multicenter Alzheimer’S Disease And Related Dementia Research, Mark Sanderson-Cimino, Alden L Gross, Leslie S Gaynor, Emily W Paolillo, Rowan Saloner, Marilyn S Albert, Liana G Apostolova, Brooke Boersema, Adam L Boxer, Bradley F Boeve, Kaitlin B Casaletto, Hilary W Heuer, Leah K Forsberg, Savannah R Hallgarth, Valentina E Diaz, Lindsay R Clark, Ani Eloyan, Sarah Tomaszewski Farias, Pauline Maillard, Mitzi M Gonzales, Dustin B Hammers, Renaud La Joie, Yann Cobigo, Amy Wolf, Benjamin M Hampstead, Dawn Mechanic-Hamilton, Bruce L Miller, Gil D Rabinovici, John M Ringman, Lina M D'Orazio, Howie J Rosen, Sephira G Ryman, Jillian L Prestopnik, David P Salmon, Glenn E Smith, Charles Decarli, Kumar B Rajan, Lee-Way Jin, Jason D Hinman, David K Johnson, Danielle J Harvey, Myriam Fornage, Maria C Carrillo, Bradford C Dickerson, Joel H Kramer, Adam M Staffaroni, , Leads Consortium, And Diverse Vascular Contributions To Cognitive Impairment And Dementia (Diverse Vcid) Study Investigators

Faculty, Staff and Student Publications

Introduction: List-learning tasks (LLTs) are important for characterizing memory in Alzheimer's disease and related dementias. However, as the Uniform Data Set Neuropsychological Battery (UDS-NB) historically did not require a specific LLT, centers have administered different LLTs. The newest UDS version (v4.0) requires one of two LLTs. To support harmonized UDS memory research, we developed a memory composite incorporating UDS memory tests and multiple LLTs.

Methods: Item-banking confirmatory factor analysis was applied to develop a memory composite in a diagnostically heterogeneous sample (n = 8716) that completed the UDS-NB and one of five LLTs. Construct validity was evaluated through associations with …

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 …

Glycosphingolipids Regulate Phosphatidylserine Transport Machinery That Operates At Er-Pm Contact Sites, Ritchel Gannaban, Sher Ali, Wei Chen, Melanie Nguyen, Li Lai, Travis I Moore, Yubin Zhou, John F Hancock, Junchen Liu

The Brown Foundation: Institute of Molecular Medicine

Plasma membrane (PM) localization of KRAS requires specific glycosphingolipids in the outer leaflet and phosphatidylserine (PS) in the inner leaflet. PM PS content is controlled by lipid transport proteins ORP5 and ORP8, which operate at ER-PM membrane contact sites (MCSs). Using high-resolution imaging, we now show that GSLs, including GM3 and SM4, are required to maintain ORP5 and ORP8 localization to MCSs. Genetic deletion or pharmacologic inhibition of enzymes required for the biosynthesis of GM3 or SM4 displaces PI4-kinase Type IIIα (PI4KIIIα) and its adaptor EFR3A from the PM, thereby reducing PM phosphatidylinositol 4-phosphate (PI4P) content. PM interactions of ORP5 …