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Pain Prevalence And Pain Management At The End Of Life: Regional And Urban-Rural Differences From A National-Representative Survey Of Chinese Older Adults, Yaolin Pei, Xiang Qi, Zexi Zhou, Yifan Lou, Jing Wang, Yang Li, Bei Wu

Faculty, Staff and Student Publications

Background: Effective pain management is essential for improving quality of life at the end of life. However, challenges persist globally, particularly in China, where palliative care remains underdeveloped. This study investigates pain prevalence and the associations between pain severity, place of death, and the quality of pain management among older adults in China, with a focus on regional and urban-rural disparities.

Methods: We used data from the 2014, 2016, 2018, and 2020 waves of the China Longitudinal Aging Social Survey. The final sample included 1,525 older adults who died during the study period. We conducted OLS regression analyses to examine …

Zingiber Officinale-Mediated Zinc Oxide Nanoparticles: Antimicrobial Activity Against Multidrug-Resistant Bacteria, Maureen Bakor Tabe, Ovgu Isbilen, Jennifer N Walker, Ender Cinar

Faculty, Staff and Student Publications

Background: The fight against infectious diseases has transformed over the past century with the emergence of multidrug-resistant bacteria, where pathogens that exhibit resistance to multiple antibiotic classes leading to significant challenges to modern medicine. Zingiber officinale is well-documented to exhibit diverse biological activities, including strong antioxidant, antimicrobial, and anti-neuroinflammatory effects. Zinc oxide nanoparticles can be synthesized cost-effectively and are widely utilized in biomedical applications, including their use as anticancer agents and drug-delivery systems, as well as for their intrinsic antibacterial and anti-inflammatory properties. In this study, we aimed to take a combinatorial approach to investigate the antimicrobial effects of Z. …

Evidence-Based Team Intervention To Reduce Diagnostic Errors In Anaemia And Ckd Diagnoses In Primary Care: Protocol For A Stepped-Wedge Cluster Rct, Zhanna Novikov, Nikhilesh Mehra, Xiao Li, Rebecca Wells, Madelene Ottosen, Kevin Hwang, Elenir B C Avritscher, Charles Green, Kyung Hyun Lee, Xochitl Oguin, Mariesa Janecka, Mary Espinoza, Bolanle Adebowale, Alejandro Araya, Amer Wahed, Eric Thomas

Faculty, Staff and Student Publications

Introduction: Diagnostic errors in primary care are common, particularly in the interpretation and follow-up of abnormal haemoglobin (Hgb) and estimated glomerular filtration rate (eGFR) results. These errors frequently result in missed or delayed diagnoses of serious conditions such as anaemia and chronic kidney disease. This protocol describes a stepped-wedge cluster randomised controlled trial designed to evaluate a novel, evidence-based, team-based intervention aimed at improving diagnostic safety and efficiency.

Methods and analysis: The study will be conducted across 12 University of Texas Physicians (UTPs) primary care clinics in Houston, Texas, USA. Adult patients (≥18 years) with newly identified abnormal Hgb or …

Phase I Study Of Bevacizumab And Temsirolimus Combination Therapy In Advanced Malignancies: Safety, Efficacy, And Ovarian Cancer Expansion, Sarina A Piha-Paul, Chieh Tseng, Emily Thompson, R Jason Stafford, Hung Le, Lei Kang, Siqing Fu, Apostolia Tsimberidou, George Blumenschein, Jordi Rodon Ahnert, John M Slopis, David Hong, Aung Naing, Funda Meric-Bernstam, Chaan S Ng, Shannon Westin, Anil K Sood

Faculty, Staff and Student Publications

Background: Bevacizumab and temsirolimus target angiogenic and mTOR pathways in cancer progression.

Methods: This phase I study enrolled 48 heavily pretreated patients with advanced solid tumors, including an ovarian cancer expansion cohort. Patients received bevacizumab biweekly plus temsirolimus weekly in a 3 + 3 design to assess safety, maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs). Exploratory analyses included tumor genomic profiling and dynamic contrast-enhanced MRI (DCE-MRI).

Results: Patients had a median age of 59 and median four prior therapies. Common tumor types were ovarian (27%) and head and neck (15%). Treatment-related adverse events occurred in 93.8%, with 31.3% ≥grade …

Recommendations From The Blue Ribbon Panel On Fluoroscopy Safety, Dustin A Gress, M Mahesh, Kevin W Dickey, John F Angle, D Duane Baldwin, Stephen Balter, Wayne Batchelor, Lisa Bruedigan, Christopher Davis, Deirdre Elder, R Paul Guillerman, Maged N Guirguis, David Hardwick, Carrie M Hayes, Jeremy J Heit, A Kyle Jones, Melissa Kirkwood, Andrew Kuhls-Gilcrist, Bonnie Martin-Harris, William W Mayo-Smith, Sarah E Mckenney, Richard Miguel, Donald L Miller, Eric Monroe, Kristi Moore, Thomas L Morgan, Kari J Nelson, Kathryn Petrovic, Shellie Pike, Carlos A Pino, Travis Prowant, Jonathan W Revels, Vinil Shah, Andrew Y Wang, David B Weiss, Darcy J Wolfman, Kevin A Wunderle, Jessica Zarzour, Michael E Zychowicz, Alan H Matsumoto

Faculty, Staff and Student Publications

There are many challenges associated with the safe use of fluoroscopy. These challenges include but are not limited to highly variable regulatory requirements, scope of practice concerns, inconsistent education and training, and lack of staff empowerment. Challenges are further compounded by the increasing use of fluoroscopy across a wide range of medical specialties. To facilitate consensus on how to address the issues, the ACR convened the multidisciplinary Blue Ribbon Panel on Fluoroscopy Safety (BRP-FS), with 32 organizations represented. The goal of the BRP-FS is to establish multi- and interspecialty consensus standards for the safe use of fluoroscopy in health care, …

Comparative Analysis Of Ctdna Monitoring Strategies In Advanced Nsclc With Met Exon 14 Skipping Mutations Treated With Ensartinib, Mo Zhou, Yin Zhu, Xuqi Sun, Ying Han, Rui Jin, Panwen Tian, Jun Zhao, Yang Jin, Zhiyuan Guo, Yongchang Zhang, Yiran Meng, Fei Liu, Wen Li, Xiuning Le, Haifeng Shen, Yang Xia

Faculty, Staff and Student Publications

Mesenchymal-epithelial transition exon 14 skipping mutations (METex14) define a targetable molecular subset of non-small cell lung cancer (NSCLC), but optimal circulating tumor DNA (ctDNA) biomarkers to guide MET tyrosine kinase inhibitor therapy remain undefined. Within the EMBRACE trial of ensartinib, we conducted a prospective biomarker analysis with plasma collected at baseline (V0) and 4 weeks after treatment initiation (V1). ctDNA was profiled using a hybrid-capture next-generation sequencing panel covering 229 cancer-related genes, and mutations were classified into three monitoring paradigms: MET-specific alterations, canonical alterations (tier I/II), and pan-alterations (any variant in any gene on the panel). Baseline ctDNA positivity rates …

Transient Protein Structure Guides Surface Diffusion Pathways For Electron Transport In Membrane Supercomplexes, Chun Kit Chan, Jonathan Nguyen, Corey F Hryc, Chitrak Gupta, Kevin Redding, William Dowhan, Matthew L Baker, Alberto Perez, Eugenia Mileykovskaya, Abhishek Singharoy

Faculty, Staff and Student Publications

The exact biological role of mitochondrial supercomplexes remains debated, particularly their role in guiding redox proteins across membranes during energy conversion. We integrate multiscale modeling and single particle cryo-electron microscopy (cryo-EM) to examine electron transfer in mitochondrial supercomplexes composed of complexes III and IV (CIII and CIV). Using bioinformatic and entropy-based methods, we generated structural ensembles capturing conformations of CIII's disordered QCR6 hinge within the yeast CIII2CIV2 supercomplex. Molecular and Brownian Dynamics simulations reveal that these negatively charged hinge states electrostatically couple with redox proteins, promoting their binding and directional diffusion across the membrane on millisecond timescales. Rather than hindering …

The Setd2 L1609p Mutation Found In Leukemia Disrupts Methyltransferase Activity And Reduces Histone H3k36 Trimethylation, Christina Michail, Jérémy Berthelet, Ariel E Mechaly, Linh-Chi Bui, Haopeng Yang, Duo Cai, Amira Al Mahi, Aowei Xie, Valeria Bisio, Valentina Sirri, Jean-Marie Dupret, Fabien Guidez, Ximing Xu, Nicolas Joly, Leslie Regad, Mireille Viguier, Frédérique Deshayes, Nicolas Dulphy, Michael R Green, Ahmed Haouz, Fernando Rodrigues Lima

Faculty, Staff and Student Publications

SETD2 is the primary methyltransferase responsible for generating H3K36me3, an epigenetic mark that is essential for transcriptional regulation and chromatin integrity. SETD2 mutations are frequently observed in various cancers and tend to cluster within its catalytic SET domain. Despite the clinical relevance of SETD2 missense mutations in cancer, their biochemical and structural consequences remain insufficiently characterized. Here, we present the enzymatic and structural characterization of the SETD2 L1609P mutant enzyme identified in leukemia. The L1609 residue is located in the SET domain within a conserved hydrophobic pocket that is involved in substrate H3K36 recognition. Interestingly, site-directed mutagenesis of residues within …

A Case Of Dislocation And Successful Reduction Of A Right Anterior Shoulder Inside A Space Suit: Considerations For Future Protocols, Samuel Beger, Curtis Lowery, Nicolas Heft, Amran Asadi, Brandon Trapp, Jaime Mateus, Alejandro Garbino

Faculty, Staff and Student Publications

Shoulder dislocations are prevalent on Earth and pose unique challenges in spaceflight and spaceflight training, particularly during extravehicular activities (EVAs). This case report describes a 50-year-old male who experienced an anterior shoulder dislocation while performing an emergency egress exercise in a SpaceX EVA suit. The report describes the medical thought process, the operational constraints, and the reduction techniques employed to achieve a successful shoulder reduction without fully removing or damaging the suit. NASA estimates a high likelihood of shoulder injuries during long-duration lunar missions, emphasizing the importance of suit designs and rescue protocols. Quick and effective medical intervention is crucial, …

Multiparent Recombinant Inbred Lines Crossed To A Tester Provide Novel Insights Into Sources Of Cis And Trans Regulation Of Gene Expression, Fabio Marroni, Alison M Morse, Adalena V Nanni, Nadja Nolte, Patricka Williams-Simon, Luis G León-Novelo, Rita M Graze, Paul Schmidt, Elizabeth King, Lauren M Mcintyre

Faculty, Staff and Student Publications

To understand the relative importance of cis and trans effects on regulation, we crossed multi-parent recombinant-inbred lines (RILs) to a common tester and measured allele-specific gene expression in the offspring. Testing the difference of allelic imbalance between two RIL × Tester crosses is a test of cis or trans, depending on the RIL alleles compared. The study design also enables to separation of two sources of trans variation, genetic and environmental, detected via interactions with cis effects. We demonstrate the effectiveness of this approach in a long-read RNA-seq experiment in female abdominal tissue at two time points in Drosophila melanogaster. …

Ubiquitination Of Oncogenic Mutant P53 Via Attenuation Of Ribosome Biogenesis Machinery Effectively Inhibits Pancreatic Tumor Growth, Mudassier Ahmad, Sahir Sultan Alvi, Haider Ahsan, Carlos Perez, Andrew Massey, Vivek K Kashyap, Neeraj Chauhan, Emmanuel Anning, Manish K Tripathi, Dae J Kim, Nirakar Sahoo, Tamer Oraby, Murali M Yallapu, Mohammad Moshahid Khan, Manu M Sebastian, Subhash C Chauhan, Bilal B Hafeez

Faculty, Staff and Student Publications

Dysregulated ribosome biogenesis and p53 mutations are known to play oncogenic roles in various cancers, including pancreatic cancer. In this study, we demonstrated the therapeutic potential of BMH-21, a pharmacologic inhibitor of RNA polymerase I, against pancreatic cancer by uncovering a novel molecular mechanism involving RPA194-mediated ubiquitination of mutant p53 without affecting the ubiquitination of wild-type p53. Our key findings are that (i) BMH-21 selectively induces apoptosis and cell growth inhibition of pancreatic cancer cells with no effect on normal human pancreatic ductal epithelial cells; (ii) BMH-21 degrades RPA194; (iii) BMH-21 inhibits recruitment of both RPA194 and RPA135 on rDNA …

Early Postnatal Polymerase Chain Reaction Testing In The Identification Of Perinatal Transmission Of Hepatitis C Virus, Mona Prasad, Grecio J Sandoval, George R Saade, Brenna L Hughes, Rebecca G Clifton, Uma M Reddy, Anna Bartholomew, Ashley Salazar, Edward K Chien, Alan T N Tita, John M Thorp, Torri D Metz, Ronald J Wapner, Vishakha Sabharwal, Hyagriv N Simhan, Geeta K Swamy, Kent D Heyborne, Baha M Sibai, William A Grobman, Yasser Y El-Sayed, Brian M Casey, Samuel Parry, George A Macones

Faculty, Staff and Student Publications

In this study, a single hepatitis C virus (HCV) RNA at 2-6 months was sensitive and specific (86.7% and 95% confidence interval [CI], 62.1%-96.3% and 100% and 95% CI, 98.8%-100%, respectively) in identifying perinatal transmission of HCV. No cases of perinatal infection requiring treatment were missed.

Gain Of Function Notch4 Variants Disrupt Angiogenesis In Systemic Sclerosis, Urvashi Kaundal, Pei-Suen Tsou, Mousumi Sahu, Mengqi Huang, Steven E Boyden, Curtis M Woodford, Daniel Shriner, Emilee Stenson, Sarah Ayla Safran, Yuechen Zhou, Taylor A Talley, Kaavya Gudapati, Xuetao Zhang, Yosuke Kunishita, Janet Wang, Ami A Shah, Maureen D Mayes, Ayo P Doumatey, Amy R Bentley, Robyn Domsic, Thomas A Medsger, Paula S Ramos, Richard M Silver, Virginia Steen, John Varga, Vivien Hsu, Lesley Ann Saketkoo, Elena Schiopu, Jessica K Gordon, Lindsey A Criswell, Heather Gladue, Chris Derk, Elana J Bernstein, S Louis Bridges, Victoria Shanmugam, Lorinda Chung, Suzanne Kafaja, Reem Jan, Marcin Trojanowski, Avram Goldberg, Benjamin D Korman, James Mullikin, James W Thomas, Stefania Dell'orso, Davide Randazzo, Adebowale Adeyemo, Elaine F Remmers, Pamela L Schwartzberg, Ivona Aksentijevich, Charles Rotimi, Fredrick M Wigley, Rong A Wang, Francesco Boin, Dinesh Khanna, Robert Lafyatis, Daniel L Kastner, Pravitt Gourh

Faculty, Staff and Student Publications

Objectives: Vasculopathy and fibrosis are central to the pathogenesis of systemic sclerosis (SSc) and their genetic underpinnings are largely unknown. Here, we sought to examine the aetiology of severe vascular phenotypes and poorer outcomes in African American (AA) patients with SSc.

Methods: The study focuses on AA patients with SSc who have more severe vascular phenotypes and poorer outcomes and combines genetics, single-cell RNA sequencing, functional assays, and a mouse model to explore the role of NOTCH4 in SSc vasculopathy and the potential for NOTCH4-directed therapies.

Results: Gene-based testing identified NOTCH4 association at an exome-wide significance with SSc (P = …

The Next Layer: Augmenting Foundation Models With Structure-Preserving And Attention-Guided Learning For Local Patches To Global Context Awareness In Computational Pathology, Muhammad Waqas, Rukhmini Bandyopadhyay, Eman Showkatian, Amgad Muneer, Anas Zafar, Frank R Alvarez, Maricel Corredor Marin, Wentao Li, David Jaffray, Cara Haymaker, John V Heymach, Natalie Vokes, Luisa M Solis Soto, Jianjun Zhang, Jia Wu

Faculty, Staff and Student Publications

Foundation models have emerged as powerful feature extractors in computational pathology. However, they typically omit mechanisms for leveraging the global spatial structure of tissues and the local contextual relationships among diagnostically relevant regions-key elements for understanding the tumor microenvironment. Multiple instance learning (MIL) remains an essential next step following the foundation model, designing a framework to aggregate patch-level features into slide-level predictions. We present EAGLE-Net, a structure-preserving, attention-guided MIL architecture designed to augment prediction and interpretability. EAGLE-Net integrates multi-scale absolute spatial encoding to capture global tissue architecture, a top-K neighborhood-aware loss to focus attention on local microenvironments, and background suppression …

Tumor Radiosensitization With Gold Nanoparticles: Evolving Strategies To Improve Tumoral Gold Uptake And Catalyze Future Clinical Translation, Prapannajeet Biswal, Geraldine V Vijay, Gabrielle Krouse, Phuoc Minh Quan Mai, Bhoomika Muruvekere Lakshmisha, Sanaz Keshavarz Shahbaz, Mahdieh Yousefi Taba, Aria Sabbagh, Lydia Wt Cheung, Yuri Mackeyev, Khadijeh Koushki, Sunil Krishnan

Faculty, Staff and Student Publications

Radiation therapy is integral to the treatment regimens of over 50% of cancer patients. However, it is not biologically targeted to just the tumor, leading to adverse effects in peritumoral normal tissue. Selective uptake of gold nanoparticles (AuNPs) by tumors realizes tumor-specific radiosensitization via increased secondary electron release from high atomic number gold atoms. Here, we review AuNP-mediated radiosensitization and outline strategies to optimize tumor-targeted AuNP delivery. Modifying the physicochemical characteristics of AuNPs, including size, shape, charge, and surface chemistry, can increase their ability to evade the reticuloendothelial system (RES) and penetrate the dense tumor stromal architecture, thereby promoting tumor …

Repurposing Of The Macrolide Antibiotic Clarithromycin For The Prevention Of Lung Cancer, Shanshan Deng, Tabish Hussain, Thais F Bartelli, Manu M Sebastian, Melody Zarghooni, Walter V Velasco, Brandon Somerville, Linda Phan, Michelle I Savage, Yurong Song, John L Clifford, Humam Kadara, Florencia Mcallister, Powel H Brown, Seyed Javad Moghaddam, C Marcelo Aldaz

Faculty, Staff and Student Publications

Drug repurposing is the process of reusing existing pharmaceuticals for novel clinical purposes, which offers advantages such as streamlined clinical trial access and reduced drug development costs. Clarithromycin (CAM), a member of the macrolide antibiotics family, is a promising candidate for repurposing in cancer therapy due to its known preclinical and clinical immunomodulatory and anticancer properties. In the current study, we investigated whether CAM could be repurposed as a preventive treatment for KRAS-mutant lung cancer, a subtype of lung adenocarcinoma that is strongly associated with heavy smoking. CCSPCre; LSL-KrasG12D mice at an early stage of tumor development were treated with …

Exploring Sex Differences In Stroke Outcomes: A Comprehensive Analysis From The Span 1 Trial, Anjali Chauhan, Eunyoung Angela Lee, Rakesh B Patel, Mariia Kumskova, Enrique C Leira, Anil Chauhan, Yanrong Shi, Suyi Cao, Raymond C Koehler, Krishnan M Dhandapani, Mohammad Badruzzaman Khan, Pradip K Kamat, Ali Arbab, David C Hess, Alison L Herman, Ligia Boisserand, Lauren H Sansing, Andreia Morais, Xuyan Jin, Sanem Aykan, Takahiko Imai, Cenk Ayata, Karisma A Nagarkatti, Jessica Lamb, Márcio A Diniz, Patrick D Lyden, Jaroslaw Aronowski, Louise D Mccullough

Faculty, Staff and Student Publications

Background: Stroke is a sexually dimorphic disease, with different risk factors, incidence, outcomes, and treatment responses in men and women. While sex differences have been documented in preclinical studies, these findings often come from single-site studies with small sample sizes and require validation across diverse research settings.

Methods: We used data from the SPAN (Stroke Preclinical Assessment Network), a randomized, placebo-controlled, blinded, multilaboratory trial, to determine if sex differences in neurological outcomes are present in preclinical stroke models. We analyzed data from 665 stroke animals treated with saline, including young mice, diet-induced obese mice, aging mice, young rats, and spontaneously …

Nci-Designated Cancer Centers' Policies And Practices With Regard To Alcohol And Cancer: A Call To Lead, Ernest T Hawk, Stephanie L Martch, Meghan Si, Sanjay Shete

Faculty, Staff and Student Publications

Background: Alcohol, a known carcinogen since 1988, increases risk of cancers of the mouth, pharynx, larynx, esophagus, liver, breast, and colorectum. More than one half of US adults consume alcohol whereas about two thirds are unsure whether or unaware that alcohol intake is linked to cancer risk.

Methods: Our objective was to survey awareness, beliefs, intentions, policies, practices, and goals/perceived responsibilities related to establishing/promoting actions to reduce alcohol-related cancer risks from leaders of 72 NCI-Designated Cancer Centers.

Results: Sixty-one percent responded. Forty-three percent either believed in or were uncertain about alcohol's purported health benefits. Nevertheless, 86% considered it part of …

Suvorexant For Alcohol Use Disorder And Post-Traumatic Stress Disorder: Study Protocol For A Phase Ii Randomized Clinical Trial, Lara A Ray, Steven J Nieto, Karen Miotto, Larissa Mooney, Richard Lebeau, Jin H Yoon, Joy M Schmitz, Ron Acierno, Nathaniel W Bailey, Jessica Jenkins, Jessica Vincent, Tracy Nolen, Shawn Hirsch, Alexis Williams, Scott D Lane

Faculty, Staff and Student Publications

Background: Alcohol use disorder (AUD) represents a highly prevalent, costly, and often untreated condition in the United States. Post-traumatic stress disorder (PTSD) represents a common comorbidity with AUD which worsens outcomes and decreases functional outcomes. Suvorexant (SUV) shows clear promise as a novel therapeutic candidate to treat AUD and PTSD.

Methods: This study features a promising compound (i.e., suvorexant), the application of a well-established human laboratory paradigm (i.e., alcohol cue reactivity), and a novel early efficacy laboratory model (i.e., practice quit attempt) to provide a cost/time-efficient evaluation of safety and initial efficacy of suvorexant for AUD with comorbid PTSD. Additionally, …

Proceedings From The Inaugural Conference On The Science Of Cancer Health Equity For Sexual And Gender Minority (Sgm) Communities, Charles S Kamen, Milena E Insalaco, Richard Brown, Chasity Burrows Walters, Shine Chang, Viktor Clark, Jason Domogauer, Lauren V Ghazal, Kelly Haviland, Forrest Hosea, Nelson Sanchez, Matthew B Schabath, Zul Surani, Gwendolyn P Quinn

Faculty, Staff and Student Publications

Purpose: Sexual and gender minority people (SGM) experience multiple cancer-related disparities, including higher rates of cancer risk factors, lower rates of cancer screening, higher lifetime risk of cancer, and unmet needs throughout cancer survivorship. Although many national organizations, including the National Cancer Institute (NCI) and the American Cancer Society (ACS), have emphasized the need for more cancer research among SGM communities, currently no consensus exists about the highest research priorities, promising research models, or mechanisms to support collaboration between geographically dispersed scientific teams.

Methods: To address this gap, we convened a three-day conference to focus on the "Science of Cancer …

Anxiety Or Depression Trends By Disability Status And Demographic Intersections In Us Adults, 2019-2023, David Adzrago, Kayo Fujimoto, J Michael Wilkerson, Typhanye V Dyer, Faustine Williams

Faculty, Staff and Student Publications

Importance: Mental health problems, particularly anxiety and depression, remain among the leading causes of disease burden in the US. However, trends in anxiety and depression across disability status and demographics remain understudied.

Objective: To examine trends in anxiety and depression prevalence among US adults from 2019 to 2023 by disability status and demographic characteristics.

Design, setting, and participants: This cross-sectional study used national population-based data from the National Health Interview Surveys from 2019 to 2023. Data were collected from household probability samples of noninstitutionalized US civilian adults aged at least 18 years. Data analyses were performed from December 6, 2024, …

The Impact Of Vascular Management On Postoperative Complications In Patients Undergoing Surgery For Retroperitoneal Leiomyosarcoma, Neha Malik, Seokhun Kim, Christopher P Scally, Emily Z Keung, Heather Lillemoe, Keila E Torres, Kelly K Hunt, Sophia Khan, Christina L Roland, Heather G Lyu

Faculty, Staff and Student Publications

Background: Retroperitoneal leiomyosarcomas are aggressive malignancies. Complete surgical resection with negative margins is crucial to decrease the risk of recurrence but can be risky due to vascular involvement. The aim of our study was to evaluate the different approaches to IVC and renal vein management and their impact on postoperative complications.

Methods: We performed a retrospective review of patients who underwent surgery for retroperitoneal leiomyosarcoma with IVC and/or renal vein involvement at our institution from 2016 to 2024. Patients were stratified by intraoperative vascular management, including ligation only versus varying forms of vascular reconstruction. Postoperative complications, including bleeding, transfusions, the …

Cd8+ T Cells In The Tumor Microenvironment Modulate The Response To Endocrine Therapy In Breast Cancer, Fabiana Napolitano, Yunguan Wang, Dhivya R Sudhan, Paula I Gonzalez-Ericsson, Luigi Formisano, Nisha Unni, Shahbano Shakeel, James Z Zhu, Khushi Ahuja, Lei Guo, María Rosario Chica-Parrado, Yuki Matsunaga, Pamela Luna, Chang-Ching A Lin, Yasuaki Uemoto, Kyung-Min Lee, Hongli Ma, Nathaniel J Evans, Alberto Servetto, Saurabh Mendiratta, Spencer D Barnes, Roberto Bianco, Yisheng V Fang, Lin Xu, Jeon Lee, Tao Wang, Justin M Balko, Gordon B Mills, Marilyne Labrie, Ariella B Hanker, Carlos L Arteaga

Faculty, Staff and Student Publications

The role of the tumor immune microenvironment (TIME) in modulating responses to antiestrogen therapy in hormone receptor-positive (HR+) breast cancers remains unclear. We analyzed pre- and on-treatment biopsies from patients with HR+ breast cancer treated with letrozole to induce estrogen deprivation (ED). Stromal tumor-infiltrating lymphocytes, assessed by H&E staining, and immune-related gene sets, including IFN-γ signaling genes, measured by RNA-Seq, were increased in ED-resistant tumors. Cyclic immunofluorescence and spatial transcriptomics revealed an abundance of CD8+ T cells and enhanced antigen processing and immune gene signatures in ED-resistant tumors. In this group, the expression of CXCL9, CXCL10, and CXCL11 - chemokine …

Women's Preferences For Home-Based Self-Sampling Or Clinic-Based Testing For Cervical Cancer Screening, Joël Fokom Domgue, Monalisa Chandra, Olajumoke Oladoyin, Manali Desai, Robert Yu, Sanjay Shete

Faculty, Staff and Student Publications

Importance: While home-based self-sampling for cervical cancer screening is an evidence-based strategy proven to increase screening access and uptake, it is not currently recommended in the US despite recent Food and Drug Administration approval of the first at-home self-sampling device. Little nationally representative research has examined preference for and drivers of home-based self-sampling over clinic-based testing (the standard of care).

Objective: To assess women's perspectives about, reasons for considering, and factors associated with preferring at-home self-sampling for cervical cancer screening.

Design, setting, and participants: This population-based cross-sectional study used data from the 2024 Health Interview National Trends Survey (HINTS 7), …

Dispersion-Enhanced Nitrogen-Centered Photocatalysis Of The Direct Hydrogen Atom Transfer, Jiasong Zhang, Kaitong Zhuang, Ramon Trevino, Babu Raj Dhungana, Huiying Sun, Shuyu Yin, Yuting Li, Jacob A Sanchez, Xiaoyu Xia, Ramy Elerian, Yao Sun, Seth O Fremin, Chao Huang, Min He, Maosheng Cheng, Oleg V Larionov, Shengfei Jin

Faculty, Staff and Student Publications

The development of structurally distinct and modular photocatalysts for direct hydrogen atom transfer (HAT) has emerged as a key frontier in radical-mediated C-H functionalization of strong carbon-hydrogen bonds. Despite the largely untapped potential across the fields of organic synthesis, medicinal chemistry, and materials science, few classes of direct HAT photocatalysts are currently known, and the approaches to enhancing their photocatalytic activity remain underdeveloped. We report herein the development of nitrogen-centered direct HAT photocatalysts based on the acridine framework, which leverage a C9-ortho-biaryl substituent for enhancing the photocatalytic activity through stabilizing dispersion interactions with the substrate as the key steering effect. …

Osimertinib Activates A Tgf-Β2-Dependent Secretory Program That Drives Lung Adenocarcinoma Progression, Madhurima Ghosh, Chao Wu, Abhishek Kumar, Monique Nilsson, John V Heymach, Weina Zhao, Jiang Yu, Xin Liu, Na Ding, Shike Wang, Guan-Yu Xiao, Angelo Chen, Kate Grimley, William K Russell, Chad J Creighton, Xiaochao Tan, Jonathan M Kurie

Faculty, Staff and Student Publications

EGFR-mutant lung adenocarcinomas (LUADs) that are vulnerable to the EGFR antagonist osimertinib (Osi) eventually relapse, owing in part to the emergence of drug-tolerant persister (DTP) cells that arise through epigenetic mechanisms. Intratumoral DTP cells can herald a worse clinical outcome, but the way in which DTP cells influence LUAD progression remains unclear. Osi-resistant (OR) cells exhibit typical DTP cell features, including a propensity to undergo senescence and epithelial-mesenchymal transition (EMT), which can activate heightened secretory states. Therefore, we postulated that OR cells influence LUAD progression through paracrine mechanisms. To test this hypothesis, we utilized congenic pairs of EGFR-mutant LUAD cell …

Hootation: A Gui And Api Library For Ontology Validation And Verbalization., Muhammad Amith, Xubing Hao, Warren Manuel, Manqi Li, Shun Rao, Kirk Roberts, Hua Xu, Yang Gong, Frank Manion, Cui Tao, Licong Cui

Faculty, Staff and Student Publications

Ontology verbalization refers to the process of translating formal axioms into natural language expressions. The primary objective is to facilitate the review and validation of ontology content by subject matter experts without requiring extensive technical expertise. While previous approaches based on templates or controlled grammar have been effective, they often face limitations in scalability, fluency, and adaptability. To address these issues, we developed Hootation, an open-source software system that supports ontology verbalization through both a graphical user interface and an API library. The tool implements rule-based translation of OWL2 axioms and further incorporates optional Large Language Model (LLM) components for …

Comparing The Effectiveness Of A Medication Knowledge Base Product As Designed With Real-World Hospital Implementations Using The Leapfrog Group’S Computerized Physician Order Entry (Cpoe/Ehr) Evaluation Tool, Zoe Co, Howard R Strasberg, Bruce R Hanway, Dean F Sittig, David C Classen

Faculty, Staff and Student Publications

Objectives: We sought to compare and analyze the performance of a medication knowledge base (MKB) vendor's (Medi-Span) fully enabled, factory settings product to operational implementations in hospitals using the Leapfrog Group's Computerized Physician Order Entry (CPOE)/electronic health record (EHR) Evaluation Tool.

Materials and methods: We randomly selected a hospital that used the MKB vendor's product to complete the Leapfrog CPOE/EHR Evaluation Tool in 2018 and used this version of the tool to assess the MKB vendor's fully enabled product. Next, we retrospectively evaluated all hospitals, regardless of EHR vendor, that used the MKB vendor's product in the tool from 2017 …

Prism-Xqtl: Pleiotropic Relationships Integrated With System-Level Multiomic Qtl Analysis For Causal Genes And Molecular Mediators In Alzheimer’S Disease, Nitesh Enduru, Zhongming Zhao

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Introduction: Most Alzheimer's disease (AD) risk variants identified by genome-wide association studies (GWAS) reside in noncoding regions, complicating causal interpretation.

Methods: We developed PRISM-xQTL (Pleiotropic Relationships Integrated with System-level Multiomic QTL), integrating pleiotropy, co-localization, Mendelian randomization, and mediation analyses across multiomic quantitative trait loci (QTLs; expression QTL [eQTL], methylation QTL [meQTL], splicing QTL [sQTL], proteomic [pQTL], single-cell [sc-eQTL]). Seventy pleiotropic single-nucleotide polymorphisms (SNPs) shared between AD and 11 immune disorders were analyzed. AlphaGenome assessed functional regulation, and The Alzheimer's Cell Atlas (TACA) database was used for drug-target relevance of FCER1G.

Results: Across 54 Genotype-Tissue Expression (GTEx) tissues, 410 SNP-gene-tissue co-localizations …

Inferring High-Fat Dietary Patterns From Electronic Health Record Data Using Machine Learning, Ya-Yun Yeh, Hsin-Yueh Lin, Jingchuan Guo, Ramon C Sun, Sizun Jiang, Jiang Bian, Hao Dai

Faculty, Staff and Student Publications

Objectives: Electronic health records (EHRs) rarely capture dietary detail, limiting diet-disease research. We aimed to develop machine learning (ML) computable phenotypes to identify high-fat diet (HFD) using variables typically available in EHRs.

Materials and methods: We used National Health and Nutrition Examination Survey (NHANES) 1999-2020 data, where 24-h dietary recall served as ground truth. Dietary fat intake was summarized into a score (0-30) based on percent energy from fat, carbohydrate, and protein; lower scores indicated HFD. We defined HFD at cutoffs of 10, 15, and 20, and trained ML models (Extreme Gradient Boosting, logistic regression, random forest) using EHR-compatible variables …