Digital Commons Network^™

Clinical Outcomes Following Stereotactic Mri-Guided Laser Ablation In Children With Tuberous Sclerosis Complex And Intractable Epilepsy, Chelsey Ortman, Rohini Coorg, Irfan Ali, Dave Clarke, Gloria Diaz-Medina, Kimberly Houck, Akshat Katyayan, Laura Masters, Deepankar Mohanty, Anuranjita Nayak, Michael Quach, Vijay M Ravindra, James J Riviello, Sonali Sen, Elaine Seto, Danielle Takacs, Cristina Trandafir, John T Freiling, Karen Evankovich, Yingchao Yuan, Kalman A Katlowitz, Daniel Curry, Howard L Weiner, Anne Anderson

Faculty, Staff and Students Publications

Objective: In children with tuberous sclerosis complex (TSC) and drug-resistant epilepsy (DRE), magnetic resonance imaging-guided stereotactic laser ablation (SLA) therapy offers less-invasive treatment compared to craniotomy and resection. Our study seeks to further expand on the long-term outcomes in patients with TSC-related DRE who have undergone SLA.

Methods: Patients with TSC and DRE treated with SLA, between July 1, 2016 and January 1, 2022, at our institution were identified retrospectively. Reduction in number of anti-seizure medications (ASMs), developmental improvement as reported by the patients' families, seizure frequency measured in surgically targeted seizure type and total seizures per day, and Engel …

Predominant Symptom In Gastroparesis: Relationships To Quality Of Life, Treatments, And Outcome, Henry P Parkman, Laura A Wilson, William L Hasler, Madhusudan Grover, Bruno P Chumpitazi, Helen Burton-Murray, Irene Sarosiek, Baha Moshiree, Geoffrey A Preidis, Robert J Shulman, Laura A Miriel, Dave Shade, Braden Kuo, Richard W Mccallum, Thomas L Abell, Pankaj J Pasricha

Faculty, Staff and Students Publications

Background: Patients with gastroparesis (Gp) can have a variety of symptoms. Apart from use of prokinetics, symptomatic therapies for the predominant symptom (PrS) are used.

Aims: (1) To classify Gp patients based on their PrS; (2) To determine differences in Gp symptoms, gastric emptying (GE), quality of life (QOL), treatments, and symptom improvement among Gp patients with different PrS.

Methods: Gp patients were enrolled in a multicenter registry and followed for 96-weeks. Patients recorded their PrS and completed questionnaires assessing symptoms and QOL at enrollment and at follow up visits.

Results: Of 1013 Gp patients (361 diabetic, 607 idiopathic, 45 …

Relationship Between Heart Rate Variability And Sleep Among Girls And Boys With Abdominal Pain-Related Disorders Of Gut-Brain Interaction, Kendra J Kamp, Robert L Burr, Camden E Matherne, Emily Simonds, Tasha Murphy, Margaret M Heitkemper, Rona L Levy, Robert J Shulman, Miranda A L Van Tilburg

Faculty, Staff and Students Publications

Background: Children with abdominal pain-related disorders of gut-brain interaction (AP-DGBI) often experience sleep disturbances which may be linked to the autonomic nervous system. Heart rate variability (HRV) is a non-invasive measure of autonomic nervous system activity. Our aim was to examine if HRV was associated with characteristics of disturbed sleep in children with AP-DGBI in order to elucidate the underlying physiological mechanisms of disturbed sleep.

Methods: This analysis used baseline data from a randomized control trial of 156 children ages 7-12 years with AP-DGBI. HRV was measured after dinner using a Polar monitor. Sleep disturbances were evaluated using the Children's …

Rural-Urban Differences In Use Of Mental Health Care For Serious Mental Illness At The Veterans Health Administration: A Retrospective Cohort Analysis, Alexandra B Caloudas, Amber B Amspoker, Ashley Smith, Liang Chen, Amy K Cuellar, Giselle Day, Alexandra Zingg, Julianna Hogan, Jan A Lindsay

Faculty, Staff and Students Publications

PURPOSE: Rural Veterans with serious mental illness (SMI) encounter significant barriers to accessing mental health care, related to SMI symptoms and rurality. A 2023 Government Accountability Office report found that rural Veterans used Veterans Health Administration (VHA) intensive mental health care for SMI less than urban Veterans relative to their population distributions. Our purpose was to deepen understanding of rural-urban differences in use of VHA mental health care among Veterans with SMI.

METHODS: Using VHA databases, we conducted a retrospective cohort analysis of 387,477 Veterans diagnosed with SMI, examining rurality as a predictor of intensive care for SMI and other …

Real-World Effectiveness Of Second-Line Therapies In Advanced Non-Small Cell Lung Cancer: Insights From Propensity-Weighted Comparative Analyses Of Longitudinal Ehr Data, Gary C N Hettinger, Qi Long, Ravi B Parikh

Faculty, Staff and Student Publications

Background: While substantial research has focused on first-line (1L) therapies for advanced-stage non-small cell lung cancer (aNSCLC), less is known about the effectiveness of second-line (2L) treatments following disease progression on 1L. The poor prognosis after 1L progression, limited guidance for 2L treatment, and constraints of clinical trials in addressing these questions underscore the need for real-world comparative effectiveness research.

Methods: We conducted a retrospective analysis to compare real-world overall survival (rwOS) associated with 2L treatments among patients with disease progression during 1L. Eligible patients were selected from Flatiron Health's nationwide electronic health record (EHR)-derived de-identified database. 1L and 2L …

Information Extraction From Clinical Notes: Are We Ready To Switch To Large Language Models?, Yan Hu, Xu Zuo, Yujia Zhou, Xueqing Peng, Jimin Huang, Vipina K Keloth, Vincent J Zhang, Ruey-Ling Weng, Cathy Shyr, Qingyu Chen, Xiaoqian Jiang, Kirk E Roberts, Hua Xu

Faculty, Staff and Student Publications

Objectives: To assess the performance, generalizability, and computational efficiency of instruction-tuned Large Language Model Meta AI (LLaMA)-2 and LLaMA-3 models compared to bidirectional encoder representations from transformers (BERT) for clinical information extraction (IE) tasks, specifically named entity recognition (NER) and relation extraction (RE).

Materials and methods: We developed a comprehensive annotated corpus of 1588 clinical notes from 4 data sources-UT Physicians (UTP) (1342 notes), Transcribed Medical Transcription Sample Reports and Examples (MTSamples) (146), Medical Information Mart for Intensive Care (MIMIC)-III (50), and Informatics for Integrating Biology and the Bedside (i2b2) (50), capturing 4 clinical entities (problems, tests, medications, other treatments) …

Urinary Cotinine Cut-Offs For Tobacco Smoke Exposure In Pregnancy And Associations With Child Intelligence Quotient: A Multi-Cohort Analysis, Yu Ni, Logan C Dearborn, Adam A Szpiro, Christine T Loftus, Qi Zhao, Nicole R Bush, Kaja Z Lewinn, Marnie F Hazlehurst, Thomas F Northrup, Penelope J E Quintana, Eunha Hoh, Georg Matt, Catherine J Karr

Faculty, Staff and Student Publications

Background: Prenatal exposure to tobacco smoke may impair neurodevelopment in children. However, accurately characterizing this exposure remains challenging.

Methods: We pursued two objectives in this large population study. First, in 1708 pregnant women from the Environmental Influences on Child Health Outcomes (ECHO) cohort, we constructed Receiver Operating Characteristic (ROC) curves to determine urinary cotinine cut-offs to classify firsthand (FHS), environmental (ETS), and no exposure, and further distinguished secondhand (SHS) from thirdhand smoke (THS) exposure within ETS. Second, among 1593 participants in three pregnancy cohorts nested in ECHO, we fit multivariable linear regressions to examine the association between the newly defined …

A Patient-Derived Organ-On-Chip Platform For Modeling The Tumor Microenvironment And Drug Responses In Pancreatic Cancer, Darbaz Adnan, Natan Roberto De Barros, Luca S Santovito, Xuhong Cheng, Kristi M Lawrence, Mariah K Barnett, Martine D Boetto, Neal Mehta, Ajaypal Singh, Lin Cheng, Xiangsheng Huang, Faraz Bishehsari

Faculty, Staff and Student Publications

Pancreatic ductal adenocarcinoma (PDAC) is a fatal malignancy. Current conventional chemotherapeutics are inadequate in controlling the disease; hence, there is an urgent need for precision medicine. Ex vivo models that replicate the tumor and its microenvironment can advance precision medicine in PDAC. Patient‐derived organoids (PDOs) offer a promising solution by retaining the functional features of the tumor, allowing for individualized study of cancer biology and drug response. However, PDOs fall short in replicating the tumor microenvironment (TME), which includes various stromal and immune cells influencing tumor growth and chemoresistance. We hypothesize that combining PDO technology with organ‐on‐a‐chip (OoC) systems can …

Influence Of Pullback Pressure Gradient On Residual Angina At One Year, Takuya Mizukami, Kazumasa Ikeda, Daniel Munhoz, Koshiro Sakai, Jeroen Sonck, Hitoshi Matsuo, Toshiro Shinke, Hirohiko Ando, Brian Ko, Simone Biscaglia, Fernando Rivero, Thomas Engstrøm, Antonio Maria Leone, Lokien X Van Nunen, William F Fearon, Evald Høj Christiansen, Stephane Fournier, Liyew Desta, Andy Yong, Julien Adjedj, Javier Escaned, Masafumi Nakayama, Ashkan Eftekhari, Frederik M Zimmermann, Tatyana Storozhenko, Frédéric Bouisset, Domenico Galante, Bruno R Da Costa, Gianluca Campo, Colin Berry, Damien Collison, Tetsuya Amano, Divaka Perera, Allen Jeremias, Ziad A Ali, Ethan Korngold, Eric Wyffels, Adriaan Wilgenhof, Nico Pijls, Bernard De Bruyne, Nils P Johnson, Carlos Collet

Faculty, Staff and Student Publications

Background: The pullback pressure gradient (PPG) is a novel physiological metric that quantifies coronary artery disease patterns as focal or diffuse on a scale from 0 to 1. This study assessed the relationship between PPG and residual angina at 1 year.

Methods: PPG Global is a prospective, investigator-initiated, single-arm, multicenter study that enrolled patients with at least 1 lesion with a fractional flow reserve ≤0.80 intended to be treated with percutaneous coronary intervention. After the PPG calculation, physicians could revise treatment assignment to medical therapy or coronary artery bypass graft surgery instead of percutaneous coronary intervention. Focal and diffuse disease …

High Accuracy Stool Biomarkers Of Precancerous Colorectal Cancer Identified Using A 2000-Plex Immunoproteomic Screen, Kamala Vanarsa, Jessica Castillo, Hao Li, Kala T Pham, Maria Akter, Sravya Gude, Kyung Hyun Lee, Claudia Pedroza, Robert Bresalier, Nicholas Chia, Chandra Mohan

Faculty, Staff and Student Publications

Given the morbidity and mortality associated with colorectal cancer (CRC), novel biomarkers are clearly warranted, especially for early detection. An antibody-based screen of 2000 proteins was utilized to identify stool proteins that were elevated in patients with CRC, compared with healthy controls (HCs). Thirty-seven lead candidates were selected for ELISA validation in three independent cohorts comprised of CRC patients, advanced adenoma patients, and HCs, drawn from two different ethnicities. Of the 2000 proteins interrogated, 116 were differentially expressed in CRC stool, with 45 being elevated at twofold or higher; 37 of these proteins were selected for ELISA validation in three …

[Factors Associated With Adhd Medication Adherence And Treatment Outcomes, Hali Temkin, Kerri L Daniel, Diana Martinez, Julia C Bennett, Paris A Nix, Linh Nguyen, Yen-Chi Le, Bruno Kluwe-Schiavon, Cesar A Soutullo

Faculty, Staff and Student Publications

Introduction: Attention-Deficit/Hyperactivity Disorder (ADHD) is a neurodevelopmental disorder that affects 5 to 8% of youth and 2.5 to 4% of adults. Pharmacological treatments are among the most effective when treating ADHD, yet adherence to medication is still sub-optimal. We reviewed the literature on clinical and socio demographic factors that may influence adherence and compared it to our clinical data.

Methods: We conducted a targeted literature review on factors associated with ADHD medication adherence. These factors were compared within our sample of patients aged 3-18 with ADHD at the Child and Adolescent Mood Disorders Program (ChAMP) at (UT Health) - Houston. …

Childhood Pulmonary Outcomes After Late Preterm Antenatal Corticosteroids, Cynthia Gyamfi-Bannerman, Rebecca G Clifton, Robert A Wise, Alan T N Tita, Jessica A De Voest, Sharon A Mcgrath-Morrow, Elizabeth C Matsui, Sean C Blackwell, Monica Longo, Sabine Z Bousleiman, Felecia Ortiz, Sankaran Krishnan, Dwight J Rouse, Torri D Metz, George R Saade, Maged M Costantine, Kent D Heyborne, John M Thorp, Kelly S Gibson, Geeta K Swamy, William A Grobman, Yasser Y El-Sayed, George A Macones, Eunice Kennedy Shriver National Institute Of Child Health And Human Development Maternal-Fetal Medicine Units Network And The National Heart, Lung, And Blood Institute

Faculty, Staff and Student Publications

Objective: To evaluate whether antenatal betamethasone affects childhood respiratory impairment.

Methods: This was a prospective follow-up study of children aged 6 years and older from parents in the ALPS (Antenatal Late Preterm Steroids) trial randomized to betamethasone or placebo from 34 0/7 to 36 6/7 weeks of gestation. Primary outcome composite included the following: 1) abnormal spirometry, forced expiratory volume in 1 second (FEV 1 ) below the lower limit of normal, FEV 1 /forced vital capacity (FVC) below the lower limit of normal, or FVC below the lower limit of normal, defined as below the 5th percentile by the …

Impact Of Mutational Landscape And Burden On Rbc Transfusion Response In Patients With Lower-Risk Myelodysplastic Syndromes (Lr-Mds) In The Commands Study, Rami S Komrokji, Sheida Hayati, Manuel Ugidos, Guillermo Garcia-Manero, Matteo Giovanni Della Porta, Amer M Zeidan, Valeria Santini, Uwe Platzbecker, Anita K Gandhi, Rajasekhar N V S Suragani

Faculty, Staff and Student Publications

The COMMANDS trial established luspatercept as a first‐line treatment for anemia in transfusion‐dependent lower‐risk (LR) myelodysplastic syndromes (MDS). Here we report red blood cell (RBC) transfusion response analysis based on somatic mutations profile and disease risk for patients treated with luspatercept or epoetin alfa in the COMMANDS trial. Of 350 evaluable patients, 238 (68.0%) had MDS with multiple lineage dysplasia and ring sideroblasts (RS) according to World Health Organization 2016 criteria, and 320 (91.4%) had somatic mutations in ≥ 1 gene (median, 2) with median variant allele frequencies (VAF) of 2%–59%. Mutation profiles were similar in the treatment groups. Luspatercept …

Perioperative And Follow-Up Tcar Outcomes Of A Single Institution, Shah-Jahan M Dodwad, Hanaa Dakour-Aridi, Gordon H Martin, Naveed U Saqib, Akiko Tanaka, Arash Keyhani, Kourosh Keyhani, S Keisin Wang

Faculty, Staff and Student Publications

Background: The ARIES-HM3 trial demonstrated the safety and effectiveness of aspirin elimination from the antithrombotic regimen after HeartMate 3 (HM3) left ventricular assist device (LVAD) implantation. We explored the interaction of atrial fibrillation, diabetes mellitus, and obesity (AF/DM/Ob) with aspirin elimination on hemocompatibility-related adverse events at 1-year postimplant.

Methods: This prospective, double-blind, placebo-controlled trial randomized patients with an HM3 LVAD implant to receive aspirin (100 mg/d) or placebo, in addition to a vitamin K antagonist. The primary endpoint was survival free of nonsurgical (>14 days postimplant) hemocompatibility-related adverse events, including stroke, pump thrombosis, bleeding, and arterial peripheral thromboembolism at …

Asymmetric Sacral Dysmorphism: Prevalence And Impact On Surgical Planning, Adeet Amin, Kathryn Barth, Colin Ward, Ryan Deangelis, Gregory Schimizzi, Connor Park, Milton L Routt, Stephen J Warner, Patrick Kellam, Mark R Adams, Jonathan G Eastman

Faculty, Staff and Student Publications

Objectives: To determine the prevalence and surgical relevance of asymmetry in patients with sacral dysmorphism.

Design: Retrospective review.

Setting: Level 1 academic trauma center.

Patient selection criteria: Included were patients between 16 and 85 years old with an operative pelvic ring injury (Orthopaedic Trauma Association/Arbeitsgemeinschaft für Osteosynthesefragen (OTA/AO) 61A-C) and a thin-cut pelvis computed tomography (≤2.0 mm) with 3D reformats. Sacral dysmorphism was defined by the inability to place a transiliac-transsacral screw in the upper sacral segment.

Outcome measures and comparisons: Asymmetry was assessed by evaluating side-to-side differences in neuroforaminal height, upper sacral segment pathway obliquity, and anterior-posterior pathway width. …

Evaluation Of Large Language Models As Decision Support Tools For Head And Neck Cancer Management: A Blinded Multidisciplinary Simulation Study, Sholem Hack, Ron J Karni, Antonino Maniaci, Christopher E Fundakowski, Luca Castellani, Fabiola Incandela, Remo Accorona, Miguel Mayo-Yanez, Martina Violati, Lorenzo Giannini, Niccolo' Mevio, Alberto Maria Saibene

Faculty, Staff and Student Publications

Background: The management of head and neck cancer relies on multidisciplinary expertise; however, access to tumor boards remains variable. Large language models (LLMs) may support guideline-based decision-making, although performance in complex oncologic scenarios is not well defined.

Methods: Fourteen synthetic cases based on real tumor board encounters were evaluated. Five blinded comparator arms produced recommendations: a human expert, Non-RAG-GPT-4, Non-RAG-GPT-5, RAG-GPT-4, and RAG-GPT-5. Eight head and neck oncologic surgeons scored each recommendation for appropriateness, clarity, specificity, and feasibility using 5-point Likert scales. Paired permutation testing and inter-rater reliability were assessed.

Results: LLM outputs showed close alignment with expert recommendations. RAG-based …

Disposition At Equipoise: A Qualitative Study Of Emergency Physicians' Decision-Making About Hospitalizing People With Dementia, Anita N Chary, Annika R Bhananker, Rebecca Franks, Jason Bowman, Adrian D Haimovich, Victoria Martell, Elizabeth M Schoenfeld, Cameron J Gettel, Shan W Liu, Kei Ouchi, Maura Kennedy, Aanand Naik, Manish N Shah

Faculty, Staff and Student Publications

Background: People with dementia are often hospitalized from the emergency department (ED) for conditions that could potentially be treated in the outpatient setting. In scenarios of clinical equipoise-where either admission or discharge may be appropriate-little is known about how emergency physicians make disposition decisions.

Methods: We conducted a qualitative study with attending emergency physicians at a single academic medical center. Interviews included open-ended questions about disposition decision-making in general as well as structured case scenarios using a think-aloud protocol. We used an inductive approach to code interview data and elucidate themes about the factors emergency physicians consider in disposition decisions …

Beyond Short Microhomologies: Mismatch-Compatible Pol Θ-Mediated Dna Damage Repair, Yuzhen Li, Richard D Wood

Faculty, Staff and Student Publications

DNA polymerase θ (Pol θ)-mediated end-joining (TMEJ), one of several pathways for repairing DNA double-strand breaks, is traditionally thought to initiate via anchoring at short, consecutive, and perfectly matched microhomologies (MHs). Emerging evidence indicates that Pol θ can utilize MHs containing mismatches both in vitro and in vivo. This revised definition of MH provides a mechanistic explanation for a broader spectrum of Pol θ-dependent repair outcomes. Here, we summarize recent findings on the revised definition of MHs utilized by Pol θ, assess the applicability of this concept across species, and compare TMEJ with other (micro)hom(e)ology-mediated repair pathways. We explore how …

Spatial Profiling Reveals Distinct Molecular And Immune Evolution Of Mouse Lung Adenocarcinoma Precancers With Or Without Carcinogen Exposure, Bo Zhu, Muhammad Aminu, Pingjun Chen, Jian-Rong Li, Chuanpeng Dong, Chenyang Li, Yanhua Tian, Shao-Wei Lu, Hong Chen, Chenxi Ma, Xin Hu, Jie Ye, Andrew Y Liu, Beibei Huang, Frank R Rojas, Parra Cuentas Edwin Roger, Ou Shi, Monique B Nilsson, Alissa Poteete, Khaja B Khan, Wei Lu, Luisa M Solis Soto, Junya Fujimoto, Cara Haymaker, Ignacio I Wistuba, Zhubo Wei, Linghua Wang, Don L Gibbons, Ken Chen, Alexandre Reuben, Jason M Schenkel, John V Heymach, Chao Cheng, Jia Wu, Jianjun Zhang

Faculty, Staff and Student Publications

Tumor evolution involves genetic, transcriptional, and phenotypic alterations that shape cancer cell behavior and interactions with the microenvironment. While single‐cell technologies have advanced our understanding of this process, spatial dynamics remain incompletely characterized. Here, whole‐exome sequencing (WES), imaging mass cytometry (IMC), and spatial transcriptomics (ST) were integrated to study molecular evolution and immune responses in two lung adenocarcinoma (LUAD) mouse models: a genetically engineered model (129S4/Sv‐KrasLSL‐G12D, termed 129S4 K) and a carcinogen‐induced precancer model (129S4 U). Compared to 129S4 K, 129S4 U tumors exhibited higher mutational, neoantigen but lower copy number variation (CNV) burdens at matched developmental timepoints, consistent with …

Clinicopathologic And Molecular Characteristics Of High-Grade Appendiceal Mucinous Neoplasms, Ashlee N Seldomridge, Michael G White, Christopher Scally, Richard E Royal, Mark Routbort, Jbryan Iorgulescu, Michael J Overman, Sun Mi Lee, Wai Chin Foo, Melissa W Taggart, Yun Song, Paul F Mansfield, Keith F Fournier, John Paul Shen, Beth A Helmink

Faculty, Staff and Student Publications

Background: Although 2016 consensus guidelines defined high-grade appendiceal mucinous neoplasms (HAMNs) as a distinct histologic entity, their clinical course and optimal management remain poorly characterized. Comparative data with low-grade appendiceal mucinous neoplasms (LAMNs) are limited. This study aims to detail the clinical management and outcomes of patients with HAMN and those with LAMN.

Methods: This retrospective cohort study was conducted at a large academic cancer center. An internal database was queried to identify patients with LAMN or HAMN who underwent appendectomy between 2016 and 2024. Kaplan-Meier survival analyses were used to assess the impact of primary tumor type and peritoneal …

Use Of A Cystatin C-Based Gfr Equation In A Population Pharmacokinetic Model Of Methotrexate Clearance In Adult Patients With Lymphoma., Zachary L. Taylor, Erin F. Barreto, Kristin C. Cole, Andrew D. Rule, Kianoush B. Kashani, Nelson Leung, Carrie A. Thompson, Thomas E. Witzig, Laura Ramsey, Jason N. Barreto

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: High-dose methotrexate (HDMTX) is a key treatment for lymphoma with central nervous system involvement. Whether incorporating cystatin C into glomerular filtration rate estimation improves methotrexate (MTX) clearance prediction remains unclear.

OBJECTIVES: We aimed to evaluate whether cystatin C-inclusive glomerular filtration rate equations improve MTX clearance prediction and to explore the relationship between MTX exposure and acute kidney injury (AKI) in adult patients with lymphoma receiving HDMTX.

METHODS: This was a prospective single-center study performed on 80 adult patients with lymphoma receiving HDMTX (1.5-8 g/m²) over a 4-h infusion. A population pharmacokinetic model was constructed using data from …

Shiny-Magec: A Bayesian R Shiny Application For Meta-Analysis Of Censored Adverse Events, Zihan Zhou, Zizhong Tian, Christine Peterson, Le Bao, Shouhao Zhou

Faculty, Staff and Student Publications

Accurate assessment of adverse event (AE) incidence is critical in clinical research for drug safety. While meta-analysis serves as an essential tool to comprehensively synthesize the evidence across multiple studies, incomplete AE reporting in clinical trials remains a persistent challenge. In particular, AEs occurring below study-specific reporting thresholds are often omitted from publications, leading to left-censored data. Failure to account for these censored AE counts can result in biased AE incidence estimates. We present an R Shiny application that implements a Bayesian meta-analysis model specifically designed to incorporate censored AE data into the estimation process. This interactive tool provides a …

Impact Of Cyp2d6 Metabolizer Status On Ondansetron Efficacy In Early Pregnancy Induced Nausea And Vomiting: A Case Control Study., Michelle Liu, Megan M. Shuey, Sabrina E. Holley, Darlene F. Fountain, James Jaworski, Carol Griffin, Jeewoo Kim, Melissa Stec, Sudeep D. Sunthankar, Henry H. Ong, Srushti Gangireddy, Wei-Qi Wei, Andrea Gaedigk, Digna R. Velez Edwards, Vivian K. Kawai

Manuscripts, Articles, Book Chapters and Other Papers

Real-world data investigating CYP2D6 on the efficacy of ondansetron for nausea and vomiting in pregnancy (NVP) is lacking. Evidence shows CYP2D6 ultrarapid metabolizers are at risk of ondansetron nonresponse due to increased metabolism. We conducted a retrospective cohort study of early pregnant patients on ondansetron for NVP. Genotype data for 11 CYP2D6 variants and copy number variations were translated into activity score (AS) and metabolizer status: poor (PM), intermediate (IM), normal (NM), and ultrarapid (UM) metabolizers. A total of 264 women met inclusion/exclusion criteria (99 cases and 165 controls). Multivariate regression analyses of metabolizer status and AS were adjusted for …

Linkage Disequilibrium Score Regression Identifies Genetic Correlations Between Hepatocellular Carcinoma And Clinically Relevant Traits, Younghun Han, Vikram R Shaw, Jinyoung Byun, Aaron P Thrift, Catherine Zhu, Donghui Li, Rikita I Hatia, Robin Kate Kelley, Sean P Cleary, Anna S Lok, Paige M Bracci, Jennifer B Permuth, Roxana Bucur, Jennifer Knox, Jian-Min Yuan, Amit G Singal, Prasun K Jalal, R Mark Ghobrial, Yuko Kono, Dimpy P Shah, Mindie H Nguyen, Neehar D Parikh, Richard Kim, Hui-Chen Wu, Hashem El-Serag, Ping Chang, Yun Shin Chun, Jian Gu, Chad Huff, Asif Rashid, Lu-Yu Hwang, Alison P Klein, Saira A Khaderi, Ahmed O Kaseb, Kathrine A Mcglynn, Lewis R Roberts, Manal M Hassan, Christopher I Amos

Faculty, Staff and Students Publications

Hepatocellular carcinoma (HCC) mortality is increasing globally, partly due to the growing prevalence of nonviral liver diseases. Genome-wide association studies (GWAS) have identified genetic variants associated with HCC development. Leveraging GWAS summary statistics and linkage disequilibrium score regression (LDSR), we investigated disease co-development with hepatitis C virus-negative (HCV-negative) HCC to provide unique insights into HCC etiology and prioritize relationships for further causal inquiry. We utilized the LDSR statistical framework to estimate the genetic correlation and heritability between HCV-negative HCC with 901 epidemiologic, behavioral, and clinical traits from the United Kingdom Biobank (UKBB). First, we set the threshold for observed scale …

The Role Of Top-Down Appetite Self-Regulation In The Development Of Healthy Eating Behaviors Among Children: A Narrative Review And Socialization Framework, David J Bridgett, Sheryl O Hughes, Matthew Broussard, Daniela Mccourt, Christina M Croce, Jennifer O Fisher

Faculty, Staff and Students Publications

Appetite self-regulation (ASR) among children is thought to have a fundamental role in shaping the development of healthy eating behaviors, dietary intake, and growth during childhood. Parallel to developmental frameworks for understanding "general" self-regulation among children, ASR has been described as involving children's use of "top-down" cognitive processes to moderate "bottom-up" biological drives around food approach and avoidance in the interest of achieving desired eating behaviors or outcomes. Whereas bottom-up ASR processes during early childhood are well characterized, particularly in the context of dysregulation and obesity risk, the role of top-down ASR processes in the development of healthy eating behaviors …

Classification Of Major Depressive Disorder Using Vertex-Wise Brain Sulcal Depth, Curvature, And Thickness With A Deep And A Shallow Learning Model, Roberto Goya-Maldonado, Tracy Erwin-Grabner, Ling-Li Zeng, Christopher R K Ching, Andre Aleman, Alyssa R Amod, Zeynep Basgoze, Francesco Benedetti, Bianca Besteher, Katharina Brosch, Robin Bülow, Romain Colle, Colm G Connolly, Emmanuelle Corruble, Baptiste Couvy-Duchesne, Kathryn Cullen, Udo Dannlowski, Christopher G Davey, Annemiek Dols, Jan Ernsting, Jennifer W Evans, Lukas Fisch, Paola Fuentes-Claramonte, Ali Saffet Gonul, Ian H Gotlib, Hans J Grabe, Nynke A Groenewold, Dominik Grotegerd, Tim Hahn, J Paul Hamilton, Laura K M Han, Ben J Harrison, Tiffany C Ho, Neda Jahanshad, Alec J Jamieson, Andriana Karuk, Tilo Kircher, Bonnie Klimes-Dougan, Sheri-Michelle Koopowitz, Thomas Lancaster, Ramona Leenings, Meng Li, David E J Linden, Frank P Macmaster, David M A Mehler, Susanne Meinert, Elisa Melloni, Bryon A Mueller, Benson Mwangi, Igor Nenadić, Amar Ojha, Yasumasa Okamoto, Mardien L Oudega, Brenda W J H Penninx, Sara Poletti, Edith Pomarol-Clotet, Maria J Portella, Joaquim Radua, Elena Rodríguez-Cano, Matthew D Sacchet, Raymond Salvador, Anouk Schrantee, Kang Sim, Jair C Soares, Aleix Solanes, Dan J Stein, Frederike Stein, Aleks Stolicyn, Sophia I Thomopoulos, Yara J Toenders, Aslihan Uyar-Demir, Eduard Vieta, Yolanda Vives-Gilabert, Henry Völzke, Martin Walter, Heather C Whalley, Sarah Whittle, Nils Winter, Katharina Wittfeld, Margaret J Wright, Mon-Ju Wu, Tony T Yang, Carlos Zarate, Dick J Veltman, Lianne Schmaal, Paul M Thompson, Enigma Major Depressive Disorder Working Group

Faculty, Staff and Student Publications

Major depressive disorder (MDD) is a complex psychiatric disorder that affects the lives of hundreds of millions of individuals around the globe. Even today, researchers debate if morphological alterations in the brain are linked to MDD, likely due to the heterogeneity of this disorder. The application of deep learning tools to neuroimaging data, capable of capturing complex non-linear patterns, has the potential to provide diagnostic and predictive biomarkers for MDD. However, previous attempts to demarcate MDD patients and healthy controls (HC) based on segmented cortical features via linear machine learning approaches have reported low accuracies. In this study, we used …

Frontotemporal Network Interactions Causally Support Rapid Concreteness Judgments During Reading, Elliot Murphy, Oscar Woolnough, Cale W Morse, Xavier Scherschligt, Nitin Tandon

Faculty, Staff and Student Publications

Neurobiological models of conceptual processing have been limited in spatiotemporal resolution, and uncertainty remains about the causal role of specific regions in concept representation. We utilized intracranial recordings in human neurosurgical patients with epilepsy (n = 19) during a concreteness judgement paradigm of single word reading. Concrete concepts showed greater high-frequency activation across a frontal and ventrotemporal network, while greater activation for abstract words was found in lateral posterior middle temporal cortex. Intercortical communications, measured by high-frequency partial direct coherence, revealed bidirectional frontal and ventral plus lateral temporal interactions. Words occupying the middle range of the concreteness scale (e.g., "profit") …

Quantifying Rate-Limiting Genetic Variation In Breast And Ovarian Tumourigenesis, Kathleen E Houlahan, Mahad Bihie, Yves Greatti, Julián Grandvallet Contreras, Daniel J Fulop, Gonzalo Lopez, Marc Williams, Hsin-Hsiung Huang, Peter Van Loo, Paul C Boutros, Kuan-Lin Huang

Faculty, Staff and Student Publications

Background: The number and type of genetic alterations required to initiate breast and ovarian cancer remain unclear. While germline BRCA1/2 carriers show markedly elevated cancer risk, it is uncertain whether point mutations or copy number alterations constitute the rate-limiting events of tumourigenesis.

Methods: We developed a statistical framework extending prior incidence-mutation models to estimate the minimal number and type of driver events required for cancer initiation. Somatic mutation and copy-number data from >3000 breast and ovarian cancers in TCGA and METABRIC were compared between germline BRCA1/2 carriers and non-carriers matched on subtypes. Results were validated through analyses of evolutionary timing …

Cd44v9 As A Therapeutic Target For Antibody-Drug Conjugate In Advanced Breast Cancer, Dileep R Reddy, Mckenna E Flynn, Yasuaki Anami, Zhaoxuan Yang, Jayden Aleman, Minji Seo, Kyoji Tsuchikama, Jennifer A Maynard, Naoto T Ueno, Jangsoon Lee

Faculty, Staff and Student Publications

Antibody-drug conjugates (ADCs) have revolutionized breast cancer therapy. HER2 is the only validated biomarker guiding ADC therapy in breast cancer. However, their clinical benefit remains confined to HER2- and TROP2-targeted therapies. Tumor heterogeneity and acquired resistance often limit durable responses, underscoring the need for novel, tumor-specific ADC targets. CD44 variant isoform 9 (CD44v9), a splice variant of the CD44 family, is largely absent in normal tissues but enriched in aggressive breast cancers, where it contributes to stemness, redox regulation, and therapy resistance. In this study, we developed a chimeric monoclonal antibody against CD44v9 (clone SUM24.1, IgG1) and conjugated it to …

Tuscan: Tumor Segmentation And Classification Analysis In Spatial Transcriptomics, Chenxuan Zang, Charles C Guo, Yaohong Wang, Peng Wei, Ziyi Li

Faculty, Staff and Student Publications

The identification of tumor cells is pivotal for understanding tumor heterogeneity and the tumor microenvironment. Recent advances in spatially resolved transcriptomics (SRT) have revolutionized the way that transcriptomic profiles are characterized and have enabled the simultaneous quantification of transcript locations in intact tissue samples. SRT is a promising alternative method to study gene expression patterns in spatial domains. Nevertheless, the precise detection of tumor regions within intact tissue remains a great challenge. A common strategy for identifying tumor cells is via tumor-specific marker gene expression signatures, which are highly dependent on marker accuracy. Another effective approach is through aneuploid copy …