Medical Sciences Commons^™

Multiparametric Mri To Predict Response To Irreversible Electroporation Plus Anti-Pd-1 Immunotherapy In Pancreatic Ductal Adenocarcinoma, Qizhen Cao, Mark D Pagel, Charles V Kingsley, Jingfei Ma, James P Long, Xiaoxia Wen, Seth T Gammon, Jorge Delacerda, Sanaz Javadi, Chun Li

Faculty, Staff and Student Publications

Purpose: To investigate contrast-enhanced T1-weighted MRI and diffusion-weighted magnetic resonance imaging (DWI) for early prediction of tumor response to combined irreversible electroporation (IRE) and anti-PD-1 immunotherapy.

Methods: Murine pancreatic ductal adenocarcinoma (PDAC) cells KRAS* were inoculated into the pancreas of C57BL/6 mice. IRE was performed when tumors became palpable. After IRE, mice received six intraperitoneal injections of anti-PD-1 over 2 weeks. T2-weighted MRI, T1-weighted MRI with macromolecular contrast agent poly(L-glutamic acid)-conjugated gadolinium (PG-Gd), and DWI were performed before and after IRE. Survival was analyzed using Kaplan-Meier curves. Mice surviving at least 100 days without recurrence after IRE were considered complete …

Identifying Sorafenib Benefit Among Patients With Hepatocellular Carcinoma: A Transcriptomic And Genomic Approach, Sun Young Yim, Hayeon Kim, Tae Hyung Kim, Sang-Hee Kang, Youngwoo Lee, Eunho Choi, Yang Jae Yoo, Seong Hee Kang, Young-Sun Lee, Young Kul Jung, Yeon Seok Seo, Hyung Joon Yim, Jong Eun Yeon, Kyung Suk Yang, Yitao Tang, Bowha Sohn, Yun Seong Jeong, Hyewon Park, Han Liang, Ju-Seog Lee, Ji Hoon Kim

Faculty, Staff and Student Publications

Background & aims: Sorafenib has been a cornerstone of hepatocellular carcinoma (HCC) therapy; however, its efficacy is limited, and identifying patients who will benefit from sorafenib is challenging. We aimed to identify predictive biomarkers of sorafenib benefit in patients with HCC.

Methods: Gene expression data from 33 HCC tumors treated with sorafenib were analyzed to construct a prediction model aimed at identifying patients with greater benefit from sorafenib treatment. The robustness of the predictor was validated using gene expression data from two phase III clinical trials, IMbrave150 and STORM.

Results: The analysis of transcriptome data revealed a 50-gene signature, the …

Axillary Management After Neoadjuvant Endocrine Therapy (Net), Laura Leonard, Min Yi, Emma Wingate, Puneet Singh, Abigail Caudle, Rosa F Hwang, Isabelle Bedrosian, Vicente Valero, Jennifer Litton, Nuhad Ibrahim, Kelly K Hunt

Faculty, Staff and Student Publications

BACKGROUND: In patients with hormone receptor-positive (HR

PATIENTS AND METHODS: We performed a retrospective review of patients with clinical stage I-III, HR

RESULTS: A total of 230 patients were included; 120 (52.2%) were clinically node-negative (cN0), while 110 (47.8%) were clinically node-positive (cN+). In the cN+ group, 7.3% (8/110) had a nodal pathologic complete response (pCR). In total, 76.4% (84/110) in the cN+ group underwent axillary lymph node dissection (ALND) as the initial axillary procedure, and 90.9% (100/110) underwent ALND overall. In total, 98.3% (118/120) with cN0 disease underwent sentinel lymph node dissection (SLND), and 28 (23.7%) had positive nodes. …

Unraveling The Nexus: Tumor Mutational Burden, Pd-L1 Expression, And Oncogenic Alterations In Non-Small Cell Lung Cancer Cytology Specimens, Min Dai, Francis Anthony San Lucas, Hector Alvarez, Leomar Ballester, Hui Chen, Keyur P Patel, Asif Rashid, Shun Rao, Mark J Routbort, Gloria Sura, Keith Sweeney, Gokce Toruner, Peng Wei, Richard Yang, Hyvan Dang, Rajyalakshmi Luthra, Sinchita Roy-Chowdhuri

Faculty, Staff and Student Publications

Background: PD-L1 expression and tumor mutational burden (TMB) are biomarkers for immune checkpoint inhibitor (ICI) therapy in non-small cell lung cancer (NSCLC); however, patients harboring oncogenic alterations have limited benefit from ICIs. The impact of oncogenic alterations on TMB and PD-L1 tumor proportion score in lung cytology specimens is poorly understood. Herein, the association between oncogenic alterations, TMB, and PD-L1 in NSCLC cytology specimens is explored.

Methods: Next-generation sequencing results from 312 NSCLC cytology specimens were retrospectively reviewed that interrogate 610 genes and select immuno-oncology signatures. TMB and PD-L1 immunohistochemical expression across oncogenic alterations were analyzed to explore associations.

Results: …

Gompertz Growth With A Shared Carrying Capacity Optimally Simulates Primary And Metastatic Tumor Growth Dynamics, Pirmin Schlicke, Preethi Korangath, Xiaoxi Pan, Caner Ercan, Kathleen Gabrielson, Lyndsey Werhane, Yinyin Yuan, Sébastien Benzekry, Robert Ivkov, Heiko Enderling

Faculty, Staff and Student Publications

Background: Cancer is a systemic disease with most deaths attributed to metastatic burden. Primary and metastatic tumors, albeit at different anatomic locations, are interconnected through multiple biological processes. Pre-clinical and clinical observations of growth acceleration of metastases after surgery, or abscopal effects outside the radiation field are widely reported, yet reliably triggering favorable and avoiding unfavorable systemic responses remains an unmet clinical need. Understanding local and systemic tumor interaction dynamics will help guide future treatments.

Methods: We analyze the data of multiple in vivo tumor models. We formalize the systemic interplay of tumors as mathematical differential equation and calibrate parameters …

Tumor Flare Reaction With Brentuximab-Vedotin In Mycosis Fungoides, Rishabh Lohray, Seda Purnak, Samruddhi Arkatkar, Madeleine Duvic, Victor Prieto, Carlos Torres-Cabala, Auris Huen

Faculty, Staff and Student Publications

No abstract provided.

Tfeb Degradation Is Regulated By An Ikk/Β-Trcp2 Phosphorylation-Ubiquitination Cascade, Yan Xiong, Jaiprakash Sharma, Meggie N Young, Wen Xiong, Ali Jazayeri, Karl F Poncha, Ma Xenia G Ilagan, Qing Wang, Bei Gao, Hui Zheng, Nicolas L Young, Marco Sardiello

Center on Aging Staff Publications

Transcription factor EB (TFEB) is a master regulator of lysosomal biogenesis and cellular clearance pathways. TFEB activity is tightly controlled by multiple post-translational mechanisms, but the exact molecular mechanism controlling its stability has remained elusive. Here, we identify the IκB kinase (IKK) complex as a key regulator of TFEB protein stability through a phosphorylation-ubiquitination cascade. A high-content kinase inhibitor screen reveals that IKK inhibition increases TFEB protein levels, and genetic ablation of IKK components increases TFEB stability, upregulates lysosomal genes, and enhances lysosomal biogenesis and degradative capacity. Mechanistically, we show that IKK phosphorylates TFEB on a cluster of serine residues …

Predicting Ventilation From Single Breathing Phase Non-Contrast Ct Using Swin Transformers, Yi-Kuan Liu, Hsu-Ting Kuo, Alaa Melek, Richard Castillo, Yevgeniy Vinogradskiy, Lili Zhao, Girish Nair, Edward Castillo

Department of Radiation Oncology Faculty Papers

BACKGROUND: Pulmonary ventilation imaging enables functional avoidance radiotherapy treatment plans by quantifying regional lung function. However, current clinical standards, such as 99𝑚Tc-based single-photon emission computed tomography (SPECT), rely on radioactive tracers, which can introduce imaging deposition artifacts. CT ventilation imaging (CTVI) methods based on both physical models and deep learning approaches currently require multiple CT images as input, such as the inhale/exhale phases of a 4DCT. While the theoretical foundation of physics-based CTVI is built on multi-phase information, the feasibility of single-phase deep learning CTV models has not been determined.

PURPOSE: While deep learning methods have predicted SPECT ventilation from …

Author Correction: Phenome-Wide Analysis Of Copy Number Variants In 470,727 Uk Biobank Genomes, Xueqing Zoe Zou, Fengyuan Hu, Haiyi Lou, Oliver S Burren, Xiaoyin Li, Karyn Megy, Eleanor Wheeler, Qiang Wu, Santosh S Atanur, Marcin Karpinski, Douglas Loesch, Zammy Fairhurst-Hunter, Sri V V Deevi, Erin Oerton, Sean Wen, Xiao Jiang, Cecilia Salvoro, Jonathan Mitchell, Abhishek Nag, Ben Hollis, Amanda O'Neill, Astrazeneca Genomics Initiative, Jen Harrow, Stewart Macarthur, Sebastian Wasilewski, Sean O'Dell, Lifeng Tian, Katherine R Smith, Guillermo Del Angel, Margarete Fabre, Ryan S Dhindsa, Quanli Wang, Slavé Petrovski, Keren Carss

Duncan NRI Faculty and Staff Publications

No abstract provided.

Dominant Clones Leverage Developmental Epigenomic States To Drive Ependymoma, Alisha S Kardian, Hua Sun, Siri Ippagunta, Nicholas Laboe, Srinidhi Varadharajan, Kwanha Yu, Hsiao-Chi Chen, Erik Emanus, Tuyu Zheng, Riley M Deneen, Jon P Connelly, Yong-Dong Wang, Jiangshan Zhan, Hengxi Liu, Kimberley Lowe, Taylor Bugbee, Rakesh Pathak, Amanda Bland, Sanya Mehta, Sophie Cochiolo, Amir Arabzade, Blake Holcomb, Kaitlin M Budd, Gabriele Kembuan, Tristen Wright, Emma Caesar, Maxwell Park, Amelia Hancock, David Gee, Joel Murdoch, Yi Xiao, Samuel K Mcbrayer, Thomas E Merchant, Jun Qi, Adam D Durbin, Lindsay A Schwarz, Li Wang, Andrew M Donson, Nicholas K Foreman, Sameer Agnihotri, Alfonso Lavado, Suzanne J Baker, David W Ellison, Hyun Kyoung Lee, Shondra M Pruett-Miller, Kelsey C Bertrand, Benjamin Deneen, Stephen C Mack

Faculty, Staff and Students Publications

ZFTA–RELA is the most recurrent genetic alteration seen in paediatric supratentorial ependymoma (EPN) and is sufficient to initiate tumours in mice1. Despite its oncogenic potential, ZFTA–RELA (ZR) is observed nearly exclusively in childhood EPN, with tumours located distinctly in the supratentorial brain of the central nervous system1. We proposed that specific chromatin modules accessible during brain development would render distinct cell lineage programs at direct risk of transformation by ZR. To test this hypothesis, we performed combined single-nucleus assay for transposase-accessible chromatin and RNA (snMultiome) sequencing of the developing mouse forebrain compared with ZR-driven mouse …

Phenome-Wide Analysis Of Copy Number Variants In 470,727 Uk Biobank Genomes, Xueqing Zoe Zou, Fengyuan Hu, Haiyi Lou, Oliver S Burren, Xiaoyin Li, Karyn Megy, Eleanor Wheeler, Qiang Wu, Santosh S Atanur, Marcin Karpinski, Douglas Loesch, Zammy Fairhurst-Hunter, Sri V V Deevi, Erin Oerton, Sean Wen, Xiao Jiang, Cecilia Salvoro, Jonathan Mitchell, Abhishek Nag, Ben Hollis, Amanda O'Neill, Jen Harrow, Stewart Macarthur, Sebastian Wasilewski, Sean O'Dell, Lifeng Tian, Katherine R Smith, Guillermo Del Angel, Margarete Fabre, Ryan S Dhindsa, Quanli Wang, Slavé Petrovski, Keren Carss

Duncan NRI Faculty and Staff Publications

Copy number variants (CNVs) are key drivers of human diversity and disease risk1. Here we evaluate the role of CNVs across a broad range of human phenotypes and diseases by analysing CNVs from 470,727 UK Biobank whole-genome sequences and conducting a variant- and gene-level phenome-wide association study (PheWAS) with 2,941 plasma protein abundance measurements, 13,336 binary clinical phenotypes and 1,911 quantitative traits. Proteomic analyses validated functional associations of CNVs with nearby genes (cis-protein quantitative trait loci; cis-pQTLs)—with deletions and duplications typically associated with reduced and increased protein levels, respectively—and uncovered previously unknown protein–protein interactions …

Waktu Pemulihan Saturasi Oksigen Pada Pasien Covid-19 Di Rsnd Semarang: Pengaruh Usia, Derajat Keparahan, Dan Komorbiditas, Hererapratita Aysha Hapsari, Yosef Purwoko, Edwin Basyar, Dwi Ngestiningsih

Jurnal Penyakit Dalam Indonesia

Introduction. COVID-19 may cause impaired oxygenation that affects the recovery process, making oxygen saturation an important parameter in clinical monitoring. Age, disease severity, and comorbidities are suspected to influence the duration of oxygen saturation recovery. This study aimed to analyze differences in oxygen saturation recovery time based on age, disease severity, and comorbidity status in hospitalized COVID-19 patients.

Methods. This was an observational analytic study with a retrospective cohort design using a survival analysis approach. The study was conducted at Diponegoro National Hospital (RSND) Semarang from October to November 2021 using medical records of hospitalized COVID-19 patients from …

(Giga)Time For The Era Of Ai: Virtual Multiplex Immunofluorescence From Routine H&E For Large Populations, Shao-Ping Yang, Dihua Yu

Faculty, Staff and Student Publications

No abstract provided.

Gene-Agnostic Therapeutic Strategies For Inherited Retinal Diseases: Neuroprotection And Immunomodulation, Lucas W. Rowe, S. Patricia Becerra, Robert E. Maclaren, Robert L. Avery, Charles C. Wykoff, Allen C. Ho, Carl D. Regillo, Dean Eliott, Andrew Osborne, Katie M. Binley, Thomas A. Ciulla

Wills Eye Hospital Papers

Background/Objectives: Inherited retinal diseases (IRDs) represent a genetically heterogeneous group of disorders caused by mutations in over 280 genes with more than 3100 identified variants. While gene-specific replacement therapies have achieved landmark success with voretigene neparvovec (Luxturna) for biallelic RPE65-associated retinal dystrophy, developing individual therapies for each genetic subtype remains impractical. This review examines gene-agnostic therapeutic approaches utilizing neuroprotection and immunomodulation that target common pathophysiological mechanisms shared across multiple IRD genotypes. Methods: We reviewed the literature on neuroprotective and immunomodulatory gene therapy strategies for IRDs, focusing on neurotrophic factors and complement system modulation. Results: Neuroprotective approaches delivering neurotrophic factors—including pigment …

Letter To The Editor: Evidence For A Two-Step Species-Level Pulmonary Nocardiosis Diagnostic Approach, John Halphen, Mohadese Ahmadzade, Babith Mankidy, Ashkan Berenji, Mohammad Ghasemi-Rad

Faculty, Staff and Students Publications

Pulmonary nocardiosis, a rare and diagnostically challenging infection, usually presents with heterogeneous radiographic findings, compounded by the low sensitivity of traditional confirmatory cultures. In their most recent work, Wang et al analyzed 102 patients with pulmonary nocardiosis to address these concerns, investigating species-characteristic imaging patterns, pathological associations, and the role of metagenomic next-generation sequencing (mNGS) in the diagnostic approach. High-resolution computed tomography (CT) in adult patients with pulmonary infections caused by Nocardia wallacei was demonstrated to have a sensitive (85.71%) and specific (83.34%) presentation of bronchopneumonia in relation to the five Nocardia species in the sample with CT data. The …

Influenza Infection Has Higher Risk Of Postoperative Complications Than Covid-19 In Shoulder Arthroplasty Patients, Jad J Lawand, Umar Ghilzai, Caleb Witsken, Dion Birhiray, Abdullah Ghali, Youssef M Khalafallah, Rohan G Reddy, Sameer R Khawaja, Adil Shahzad Ahmed

Faculty, Staff and Students Publications

INTRODUCTION: The COVID-19 pandemic has captured the attention of healthcare systems worldwide, and testing remains a mainstay of preoperative testing before all surgical procedures, including shoulder arthroplasty. Other viral illnesses, specifically influenza, while still having severe complications, are either overshadowed by testing for COVID-19 or not tested at all.

METHODS: A multi-institutional cohort study using the TriNetX network examined patients undergoing total or hemi shoulder arthroplasty from January 2020 to March 2024. Matched cohorts were created: one with influenza and one with COVID-19 infection, 14 days before surgery.

RESULTS: A total of 3233 and 18,209 patients were included in the …

An Atlas Of Genetic Effects On The Monocyte Methylome Across European And African Populations, Wanheng Zhang, Chuan Qiu, Xiao Zhang, Zichen Zhang, Kuan-Jui Su, Zhe Luo, Minghui Liu, Bingxin Zhao, Lang Wu, Qing Tian, Hui Shen, Chong Wu, Hong-Wen Deng

Faculty, Staff and Student Publications

No abstract provided.

Incidence Of High Volume Residual Gastric Content In Perioperative Patients Taking Glucagon-Like Peptide-1 Receptor Agonists, And Its Dependence On The Duration Of Preoperative Fasting And Drug Holding: A Prospective Observational Study, Marissa Huggins, Ion Hobai

Cumberland Medica

Background: Glucagon-like peptide-1 receptor agonists (GLP-1RAs), including semaglutide and dulaglutide, are increasingly prescribed for type 2 diabetes mellitus and obesity. These agents delay gastric emptying and have been associated with a higher incidence of unexpected full stomachs in procedural patients. To prevent pulmonary aspiration, current recommendations include extending preoperative fasting (e.g., 24 hours instead of the standard 8 hours) and/or withholding the GLP-1RA medication before surgery (≥1 drug half-lives). However, the efficacy of these strategies have remained unclear and are evaluated in this study.

Hypothesis: GLP-1RA use in surgical patients is associated with increased incidence and volume of residual gastric …

Mouse White Matter Matters: Cortical Origins And Spatial Organization Of Mouse White Matter Tracts, Sofia D Gordeev, Melissa Franch, Sarah R Heilbronner

Faculty, Staff and Students Publications

White matter—the fundamental structure underlying network connectivity—lies at the heart of the brain’s computational power. White matter is organized into fiber tracts, or bundles, in both human and nonhuman primate brains. These bundles consist of long-range axonal projections with a set of shared origin and termination points and exhibit a predictable organization. However, the organization of white matter in the mouse brain remains relatively unknown. This knowledge gap is surprising given the central role of mice in neuroscience, with mouse brains serving as the dominant model for transgenics, in vivo calcium imaging, and circuit manipulation. To address this gap, we …

3'Utr Mapping Reveals Alternative Polyadenylation In Right Ventricular Failure, Rahul Neupane, Kartiga Natarajan, Erik E Suarez, Henry J Pownall, Kai-Lieh Huang, Eric J Wagner, Ajay Kumar Verma, Rambabu Majji, Hari Krishna Yalamanchili, Ashrith Guha, Rajarajan A Thandavarayan

Children’s Nutrition Research Center Staff Publications

No abstract provided.

Proposed Standardized Nomenclature For Anomalous Aortic Origin Of A Coronary Artery: An International Multidisciplinary Initiative, Carlos M Mery, Meena Nathan, Christoph Gräni, Rajesh Krishnamurthy, Cristina Basso, Marshall L Jacobs, Julie A Brothers, Massimo A Padalino, Silvana Molossi

Faculty, Staff and Students Publications

Increasing use of advanced noninvasive imaging has provided great anatomic and morphologic details to characterize congenital coronary artery anomalies. Anomalous aortic origin of a coronary artery (AAOCA) is a subtype that may lead to myocardial ischemia with variable clinical manifestations across the lifespan. Management decision making in AAOCA is hindered by anatomic variants of differing physiologic consequences. Several systems of nomenclature have been used that lack uniformity in potentially high-risk morphologic features. The ICAAC (International Coronary Artery Anomalies Collaborative), a group of experts in coronary artery anomalies, proposes a standardized nomenclature to describe anatomy and morphologic features of AAOCA using …

Monitoring Relapse In Post-Transplant Acute Myeloid Leukemia Requires Integrated Assessment, With Flow Cytometry Showing The Highest Efficacy, Wei J Wang, Sa A Wang, Hong Fang, Qing Wei, Shimin Hu, Sanam Loghavi, Gheath Al-Atrash, Chenxuan Zang, Peng Wei, Jeffrey L Medeiros, Wei Wang

Faculty, Staff and Student Publications

No abstract provided.

Incidence Of Autoimmune Diseases In Children With Atopy Treated With Dupilumab, Stanislaw J Gabryszewski, Kathryn Hirabayashi, Morgan Botdorf, Mitchell Maltenfort, Christopher B Forrest, Theresa W Guilbert, Madeline Schutt, Hiroki Morizono, Gerardo Vazquez Garcia, Anna Cristina Garza-Mayers, Joseph Demetrius Hernandez, Sara Anvari, Suchitra Rao, Jonathan M Spergel

Faculty, Staff and Students Publications

Background: The type 2 inflammation-blocking agent dupilumab has gained traction as an effective treatment of multiple atopic diseases. New-onset autoimmune manifestations have been infrequently reported in dupilumab-treated atopic patients, primarily among adults. Autoimmune outcomes in atopic children on dupilumab are less clear.

Objective: We aimed to determine if dupilumab treatment of atopic children is associated with increased autoimmune or autoinflammatory disease diagnosis risk.

Methods: Using a multi-institutional electronic health record database composed of 10 PEDSnet academic health systems, we performed a retrospective cohort study of children aged 6-17 with atopy (ie, moderate-to-severe atopic dermatitis and/or persistent asthma, as defined by …

Genome-Wide Crispr Screen Identifies A Cytokine-Enhancer Circuit Driving Hif-2Α Activation In Renal Cancer, Jun Fang, Jeremy M Simon, Tao Wang, Yunpeng Gao, Xianju Bi, Lianxin Hu, Chengheng Liao, Cheng Zhang, Yayoi Adachi, Jin Zhou, Hongyi Liu, Qian Liang, James A Nathan, Ram Mani, James Brugarolas, Qing Zhang

Faculty, Staff and Student Publications

Resistance to HIF-2α inhibitors such as Belzutifan underscores the need to better understand how HIF-2α is transcriptionally regulated in clear cell renal cell carcinoma (ccRCC). Here, we uncover a cytokine-driven enhancer mechanism that sustains HIF-2α expression through the JAK1-STAT3 signaling pathway. Using a genome-wide CRISPR screen in VHL-deficient ccRCC cells, we identified SOCS3 as a key negative regulator of HIF-2α. Mechanistically, loss of SOCS3 activates JAK1-STAT3 signaling, leading to the recruitment of STAT3 to distal enhancers upstream of EPAS1 that physically loop to its promoter to drive HIF-2α transcription. This cytokine-enhancer circuit was recapitulated in ccRCC patient samples and functionally …

Fecal Carbohydrate-Degrading Bacteria Are Associated With Reduced Incidence Of Lower Gastrointestinal Gvhd, Christopher Fan, Tomo Hayase, Chia-Chi Chang, Israel K Glover, Ivonne I Flores, Lauren K Mcdaniel, Miriam R Ortega, Christopher A Sanchez, Rawan K El-Himri, Alexandria N Brown, Jennifer L Karmouch, Mohamed A Jamal, Saira S Ahmed, Taylor M Halsey, Yimei Jin, Wen-Bin Tsai, Rishika Prasad, Altai Enkhbayar, Aqsa Mohammed, Maren Schmiester, Ashish Damania, Nadim J Ajami, Jennifer A Wargo, Christine B Peterson, Gabriela Rondon, Taha Al-Juhaishi, Amin M Alousi, Jeffrey J Molldrem, Richard E Champlin, Elizabeth J Shpall, Eric Martens, Cesar A Arias, Robert R Jenq, Eiko Hayase

Faculty, Staff and Student Publications

Lower gastrointestinal graft-versus-host disease (LGI-GVHD) carries morbidity and mortality for patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT), with critical contributions from the intestinal microbiome. In a retrospective cohort of metagenomic sequencing of stool from patients with allo-HSCT (N = 90), we found that a reduction in specific Parabacteroides and Bacteroides species around the time of engraftment contributes to LGI-GVHD risk. Given the known diverse carbohydrate-degrading functionality of these bacteria, we investigated gene abundances for carbohydrate-active enzymes (CAZymes) and found that Parabacteroides merdae, P distasonis, and Bacteroides ovatus abundances were significantly correlated with CAZymes in patients who did not develop …

A Retrospective Analysis Of Taxane-Based Chemotherapy In Small Bowel Adenocarcinoma, Mir Lim, Nikhil Grandhi, Preksha Shah, Kanwal Raghav, Victoria Serpas, Maria Pia Morelli, Katrina Pedersen, Aparna Kalyan, Mohamed Salem, Ryan Huey, John Paul Shen, Huamin Wang, Hua Wang, Anjali Vinocha, Jane Thomas, Robert Wolff, Michael J Overman

Faculty, Staff and Student Publications

Background: Small bowel adenocarcinoma (SBA) is molecularly distinct from colorectal and gastric cancers, yet treatment typically parallels colorectal cancer. We evaluated the activity of taxane-based therapy in the largest SBA cohort to date.

Methods: We retrospectively reviewed SBA patients treated with taxane-based chemotherapy at MD Anderson Cancer Center from 1994-2024. Eligible patients had pathologic confirmation, received >1 treatment cycle, and had tumor response evaluation. Survival analyses were analyzed using Kaplan-Meier and Cox proportional hazard models.

Results: Seventy patients were identified. Median age was 57, and 59% were male. Primary sites were duodenum (44%), jejunum (34%), and Ileum (16%). Metastatic sites …

Plant-Based Dietary Patterns Are Associated With Slower Epigenetic Aging, Hyunju Kim, Christina A Castellani, Jiantao Ma, Alexis C Wood, Audrey Ting, Morgan E Grams, Bing Yu, Kelly Ruggles, James S Floyd, Dan E Arking, Casey M Rebholz

Faculty, Staff and Students Publications

Greater adherence to plant-based diets is associated with health benefits. Dietary intake can modify DNA methylation patterns, but it is unknown whether plant-based diets in a largely non-vegetarian population are associated with DNA methylation-based epigenetic aging measures. We examined the associations between 4 different types of plant-based diets indices (PDI) [overall PDI, provegetarian diet, healthy PDI, and unhealthy PDI] and epigenetic aging. We used data from the Atherosclerosis Risk in Communities (ARIC) Study (N=2,810) and National Health and Nutrition Examination Survey (NHANES, N=2,056). PDIs negatively scored higher intake of animal products and positively scored higher intake of all or selected …

Integration Of Cross-Species Multi-Omics With In Vivo Experimental Validation Identifies Parkinson’S Disease Therapeutic Targets And Novel Risk Factors Within Endolysosomal Pathway Subnetworks, Justin Moore, Leo Rao, Sara Garcia-Bellido, Fangfei Guo, Jorge Botas, Juan Botas

Duncan NRI Faculty and Staff Publications

Parkinson's disease (PD), the most common neurodegenerative movement disorder, imposes a growing healthcare and socioeconomic burden worldwide. A defining hallmark of PD is the accumulation of α-synuclein (αSyn) within intracellular inclusions such as Lewy bodies and Lewy neurites. Genomic studies have identified numerous PD risk factors within the endolysosomal pathway (ELP), an essential cellular system for protein and membrane recycling. Concordantly, recurrent transcriptomic and proteomic alterations in ELP components implicate broad ELP dysfunction as a causal contributor to PD and suggest that additional, uncharacterized ELP genes may cooperate in polygenic disease mechanisms. A promising but underexplored therapeutic concept is that …

Immunotherapy Of Tsa-1.C4 Or In Combination With Bnz Confers Protection Against Trypanosoma Cruzi Infection With A Distinct Cytokine Response, Landy Magaly Pech-Pisté, Victor Dzul-Huchim, Christian Florian Teh-Poot, Fabian Gusovsky, Kathryn Jones, Peter Hotez, Liliana Estefanía Villanueva-Lizama, Maria Elena Bottazzi, Jaime Ortega-Lopez, Julio Vladimir Cruz-Chan

Faculty, Staff and Students Publications

Chagas disease is a poverty-related neglected tropical disease caused by the protozoan Trypanosoma cruzi affecting approximately 6.3 million people, predominantly in the Americas. Approximately 30% of T. cruzi infections progress to chronic cardiomyopathy and 10% of these cases end in death from cardiac failure. The first-line drug Benznidazole (BNZ) require a prolonged treatment regimen and can be highly toxic. Here, we evaluate a therapeutic vaccine in T. cruzi-infected mice, based on the recombinant Trypomastigote Surface Antigen 1 (TSA-1.C4) protein and the emulsified adjuvant E6020, and in combination with a suboptimal dose of BNZ. We observed a reduced burden parasite in …

Evaluating Eight Smoking Metrics For Modelling Survival In Non-Small Cell Lung Cancer, Andrew Cl Lam, Yao Li, M Catherine Brown, Yangqing Deng, Katrina Hueniken, Natasha B Leighl, Frances A Shepherd, Kiera Murison, Zhichao Wang, Jui Kothari, Angela S Wenzlaff, Haoran Liu, Takashi Kohno, Angela Cecilia Pesatori, Curtis Harris, Hongxia Ma, Juncheng Dai, Matthew J Barnett, Ryan Diver, Leticia Ferro Leal, Guillermo Fernandez-Tardon, Mónica Pérez-Ríos, Michael Pa Davies, Bernd Holleczek, Paul Brennan, David Zaridze, Ivana Holcatova, Jolanta Lissowska, Beata Świątkowska, Dana Mates, Milan Savic, Hermann Brenner, Angeline S Andrew, Fiona Taylor, John K Field, Alberto Ruano-Ravina, Sanjay S Shete, Adonina Tardon, Ying Wang, Loic Le Marchand, Rui Manuel Reis, Matthew B Schabath, Marian L Neuhouser, Hongbing Shen, Maria Teresa Landi, Kouya Shiraishi, Jie Zhang, Ann G Schwartz, Ming S Tsao, David C Christiani, Ping Yang, Rayjean J Hung, Wei Xu, Geoffrey Liu

Faculty, Staff and Student Publications

Introduction: Smoking is a strong modifiable prognostic factor for lung cancer survival. We compared eight smoking metrics to determine which metric best models the relationship between smoking exposure with overall survival (OS) and lung cancer-specific survival (LCSS). These metrics included cigarettes-per-day, smoking duration, pack-years, square-root pack-years, logcig-years, the comprehensive smoking index, age-of-initiation, and years-since-quit.

Materials/methods: This retrospective, pooled analysis included 25 International Lung Cancer Consortium studies between June 1, 1983-December 31, 2019. The performance of smoking metrics for modelling OS was compared based on 1) strength and significance in adjusted Cox-proportional hazard models and 2) linearity based on the goodness-of-fit …