Digital Commons Network^™

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 …

Pretreatment Risk Model For Radiation-Induced Lymphopenia Is Associated With Adjuvant Durvalumab Efficacy In Patients With Unresectable Stage Iii Nsclc, Peter S N Van Rossum, Pim J J Damen, Francesco Cortiula, Brian P Hobbs, Lorenzo De Marchi, Radhe Mohan, Max Peters, Famke L Schneiders, Dirk De Ruysscher, Robin Wijsman, Joost J C Verhoeff, Ting Xu, Zhongxing Liao, Steven H Lin

Faculty, Staff and Student Publications

Introduction: Severe radiation-induced lymphopenia (RIL) during concurrent chemoradiotherapy (CCRT) for NSCLC has been associated with poorer outcomes and reduced immunotherapy efficacy. Because RIL often develops late during CCRT, identifying patients at risk before treatment may be clinically relevant. This study aimed to develop and validate a nomogram based on pretreatment predictors for severe RIL, and secondarily to explore associations between predicted RIL risk and adjuvant durvalumab-associated survival.

Methods: A retrospective development cohort of consecutive patients with NSCLC treated with CCRT (2010-2019) was established, along with an independent external validation cohort from other institutions. A multivariable logistic regression model was developed …

Winner's Curse Free Robust Mendelian Randomization With Summary Data, Zhongming Xie, Wanheng Zhang, Jingshen Wang, Chong Wu

Faculty, Staff and Student Publications

In the past decade, the increased availability of genome-wide association studies summary data has popularized Mendelian Randomization (MR) for conducting causal inference. MR analyses, incorporating genetic variants as instrumental variables, are known for their robustness against reverse causation bias and unmeasured confounders. Nevertheless, classical MR analyses using summary data may still produce biased causal effect estimates due to the winner’s curse and pleiotropy issues. To address these two issues and establish valid causal conclusions, we propose a unified robust Mendelian Randomization framework with summary data, which systematically removes the winner’s curse and screens out invalid genetic instruments with pleiotropic effects. …

Innovative Approaches For Lung Cancer Screening And Interception, Jianjun Zhang, Matthew D Park, Tej Pandya, Elaine Shum, Jia Wu, Simon Heeke, Ramin Salehi-Rad, Thomas U Marron, Zhubo Wei, Hui Li, Torsten G Blum, John V Heymach, Steven M Dubinett, Pan-Chyr Yang, Charles Swanton, Miriam Merad

Faculty, Staff and Student Publications

Lung cancer remains the leading cause of cancer-related deaths worldwide, partly because many patients are diagnosed at late stages, highlighting the urgent need for effective early detection and intervention strategies. Low-dose computed tomography (LDCT)-based screening reduces lung cancer mortality in high-risk populations defined by age and smoking history; however, the uptake of LDCT remains low among eligible individuals. Compounding this issue, modelling studies estimate that nearly half of lung cancers occur in individuals who do not meet eligibility criteria for LDCT-based lung cancer screening under current guidelines. Moreover, LDCT-based screening has inherent limitations, including a high rate of false-positive results …

Airway Secretory Cells Contain Both A Perinuclear Golgi Ribbon And Dispersed Golgi Satellites, Oanh N Hoang, Colin E Chan, Joshua M Brenner, Denisse Leza-Rincon, Ana M Jaramillo, Brendan Dolan, Adam W Aziz, Rodolfo A Cardenas, Gerardo J Cardenas, Eduardo D Galvez, Joshua B Hales, Emilia S Nunez-Pena, Boxuan Yang, Reid T Powell, Leoncio Vergara, Harry Karmouty-Quintana, Jesper M Magnusson, Gunnar C Hansson, Roberto Adachi, John D Dickinson, Christopher M Evans, Justin A Courson, Alan R Burns, Michael J Tuvim, Burton F Dickey

Faculty, Staff and Student Publications

Rationale: Finely tuned production and secretion of the polymeric mucins MUC5AC and MUCB are required for lung health, but knowledge of many details between their translation and their packaging into secretory granules is lacking.

Objective: To analyze the structure and function of the Golgi apparatus, a key site of mucin glycosylation, folding, polymerization and packaging, in airway epithelial secretory cells.

Methods: Lung tissue was obtained from mice stimulated or not with IL-13 to upregulate mucin production, and from normal human lungs. Golgi elements in mouse and human tissue were imaged by high-resolution immunofluorescence microscopy and electron microscopy. Tissue from mice …

Adipocyte-Specific Deletion Of Sine Oculis Homeobox Homolog 1 Inhibits Lipolysis And Reduces Skin Fibrosis, Nancy Wareing, Tingting W Mills, Scott Collum, Minghua Wu, Lucy Revercomb, René Girard, Hui Liu, Alexes Daquinag, Mikhail Kolonin, Marka Lyons, Brian Skaug, Weizhen Bi, Meer A Ali, Haniyeh Koochak, Anthony R Flores, Yuntao Yang, W Jim Zheng, William R Swindell, Shervin Assassi, Harry Karmouty-Quintana

Faculty, Staff and Student Publications

Dermal fibrosis is a cardinal feature of systemic sclerosis (SSc) for which there are limited Systemic sclerosis (SSc) is characterized by dermal fibrosis accompanied by loss of dermal white adipose tissue (DWAT), yet the mechanisms linking adipocyte depletion to fibroblast activation remain unclear. Here we identify the transcription factor SIX1 as a central regulator coupling adipogenic repression with profibrotic signaling. SIX1 expression was increased in skin biopsies from two independent SSc cohorts and localized to fibroblast and perivascular stromal cells. In mice, ubiquitous or adipocyte-specific deletion of Six1 preserved DWAT, reduced collagen accumulation, and selectively decreased pro-fibrotic mediators. In cultured …

Cml-Like Biology Is A Unifying Feature Of Myeloid/Lymphoid Neoplasms With Tyrosine Kinase Fusions In Lymphoid Blast Phase Comment On: Multilineage Involvement In Abl-Class Fusion-Positive Pediatric B-Cell Acute Lymphoblastic Leukemia: Cml-Like Biology, Wei J Wang, Shimin Hu

Faculty, Staff and Student Publications

No abstract provided.

Sting-Induced Blood-Brain Barrier Opening Combined With Radiotherapy Potentiates Antitumor Response In A High-Grade Glioma Model, Shashwat Tripathi, Hinda Najem, Lisa Hurley, Ruochen Du, Crismita Dmello, Heba Ali, Kathleen Mccortney, Karl J Habashy, Peng Zhang, Craig M Horbinski, Lara Leoni, Ryan J Avery, Rimas V Lukas, Timothy L Sita, David R Raleigh, Sean Sachdev, Roger Stupp, Maciej S Lesniak, David M Ashley, Daniele Procissi, Michael A Curran, Irina Balyasnikova, Amy B Heimberger

Faculty, Staff and Student Publications

Radiation therapy (RT) is the standard of care for glioblastoma but is not curative. Triggering the cGAS/stimulator of interferon genes (STING) pathway with potent agonists, such as 8803, exerts activity across high-grade glioma preclinical models. To determine if the combination of 8803 with RT warrants consideration in the up-front treatment setting and to clarify the underlying mechanisms of therapeutic activity, C57BL/6J mice harboring intracerebral CT-2A or QPP8v gliomas were treated with RT, intratumoral 8803, or both. The treatment with the combination resulted in 80% long-term survival in the CT-2A model but not in the radiation-resistant QPP8v model. This therapeutic effect …

Clinical, Genetic, And Familial Features Of Pot1 Tumor Predisposition Syndrome, Courtney D Dinardo, Jennifer Croden, Hiam M Abdel-Salam, Tapan Kadia, Matteo Molica, Alexandre Bazinet, Prithviraj Bose, Abhishek Maiti, Fadi Haddad, Jan Burger, Hagop Kantarjian, William Wierda, Nitin Jain, Alessandra Ferrajoli

Faculty, Staff and Student Publications

Background: Protection of telomere 1 (POT1) tumor predisposition syndrome (POT1-TPD) is a hereditary leukemia syndrome that is identified in ∼5% of patients with chronic lymphocytic leukemia (CLL) and is characterized by a predisposition to other cancers, including gliomas, melanomas, and angiosarcomas. This study reports clinical and genetic characteristics of a large cohort of individuals with POT1-TPD.

Materials and methods: Individuals with pathogenic/likely pathogenic germline POT1 variants referred to the Hereditary Hematologic Malignancy Clinic at The University of Texas MD Anderson Cancer Center were included. Individuals with variants of uncertain significance were included if found to have telomeres >90th percentile of …

Common Serum Biomarkers And Combination Ratios In The Diagnosis Of Periprosthetic Joint Infection Following Total Hip Arthroplasty, Jason M Dayan, Don H Le, Anzar Sarfraz, Theodor Di Pauli Von Treuheim, Farouk Khury, Sallie Yassin, Vinay K Aggarwal, Ran Schwarzkopf, Alan J Dayan

Faculty, Staff and Student Publications

Accurate preoperative diagnosis of periprosthetic joint infection (PJI) is difficult, complicating distinction between septic and aseptic failures. This study assessed the value of common serum biomarkers and three calculated ratios-albumin-globulin ratio (AGR), C-reactive protein-albumin ratio (CAR), and C-reactive protein-AGR ratio (CAGR)-in diagnosing PJI after primary total hip arthroplasty (THA). We retrospectively reviewed patients undergoing revision THA for PJI or aseptic failure from 2011 to 2021 at a single institution. Inclusion required reported serum white blood cell count (WBC), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), albumin (Alb), and total protein (TP). Diagnostic performance was evaluated using areas under the curve …

Targeting Oxalate Production By Combining Enzyme Inhibition And Proteolysis Activation: A Novel Therapeutic Approach For Primary Hyperoxaluria Type 1, Fabio Arias, Sumati Rohilla, Yudibeth Sixto-López, Koral S E Richard, Sandeep Das, Sumit K Anand, Pilar Maria Luque-Navarro, Guillermo Bañuelos-Sanchez, Juan Luis Pacheco-García, Reethika Gade, M Peyton Mckinney, Dhananjay Kumar, Jemiah Maxie, W Rylan Corr, Nilesh Pandey, Harpreet Kaur, Jibin Ding, Lin Tan, Elisha Scott, Hyung Nam, Eyal Gottlieb, A Wayne Orr, Nirav Dhanesha, Arif Yurdagul, Angel L Pey, Francisco Franco-Montalbán, José A Gómez Vidal, Oren Rom, Mónica Díaz-Gavilán

Faculty, Staff and Student Publications

Primary hyperoxaluria type 1 (PH1) is a rare genetic disorder caused by hepatic oxalate overproduction due to alanine-glyoxylate aminotransferase (AGXT) deficiency. Therapeutic strategies targeting glycolate oxidase (GO) and lactate dehydrogenase A (LDHA), key enzymes in glyoxylate metabolism, have shown promise in reducing oxalate burden. However, recently approved siRNA therapies remain limited by high cost, unfavorable pharmacokinetics, and limited global accessibility. We report the development of compound 2, a dual GO/LDHA inhibitor (K i = 390 and 40 nM, respectively) that also promotes hydrophobic tag-mediated autophagic degradation of LDHA. Its efficacy was evaluated in Agxt –/– mice, both in primary …

Correction: The Hsp90-Myc-Cdk9 Network Drives Therapeutic Resistance In Mantle Cell Lymphoma, Fangfang Yan, Vivian Jiang, Alexa Jordan, Yuxuan Che, Yang Liu, Qingsong Cai, Yu Xue, Yijing Li, Joseph Mcintosh, Zhihong Chen, Jovanny Vargas, Lei Nie, Yixin Yao, Heng-Huan Lee, Wei Wang, Johnnelson R Bigcal, Maria Badillo, Jitendra Meena, Christopher Flowers, Jia Zhou, Zhongming Zhao, Lukas M Simon, Michael Wang

Faculty, Staff and Student Publications

No abstract provided.

High-Throughput Multi-Organ Proteomics Workflow For Drug Efficacy And Toxicity Analysis, Yun Xiong, Lin Tan, Wai-Kin Chan, Dandan Zhu, Huimin Zhang, Eric S Yin, Sri Ramya Donepudi, Jibin Ding, Bo Wei, Bao Tran, Sara Martinez, Iqbal Mahmud, Faiza Hanif Waghu, Hamish I Stewart, Daniel J Hermanson, Rehan Akbani, John N Weinstein, Junjie Chen, Philip L Lorenzi

Faculty, Staff and Student Publications

Rapid and comprehensive analysis of complex proteomes across large sample sets is vital for unlocking the potential of systems biology. We present a high-throughput mass spectrometry (MS) proteomics method that integrates narrow-window data-independent acquisition (nDIA) with short-gradient micro-flow chromatography, enabling profiling of >240 samples per day. This optimized MS approach identifies 6,201 and 7,466 human proteins with 1- and 2-min gradients, respectively. As a practical application, we analyzed 507 samples composed of 13 different tissues from mice treated with the enzyme-drug L-asparaginase (ASNase) or its glutaminase-free Q59L mutant, generating a quantitative profile of 11,472 proteins following drug treatment. The MS …

Genome And Transcriptome-Wide Analyses Identify Multiple Candidate Genes And A Significant Polygenic Contribution In Bicuspid Aortic Valve, Sébastien Thériault, Jacob A Holdcraft, Dinara Sharipova, Adèle Faucherre, Radoslaw M Debiec, Gina M Peloso, Baravan Al-Kassou, Sary Aranki, Elena Ashikhmina Swan, Andrea Ballotta, Michele Bellino, Hanna M Björck, Anne Sophie Boureau, Peter S Braund, François Corriveau, François Dagenais, Lasse Folkersen, Amalia Forte, Michael D Francke, Alessandro Frigiola, Svetlana Gorbatov, Dongchuan Guo, Karam M Habchi, Mahyar Heydarpour, Eric M Isselbacher, Chris Jopling, Fabien Laporte, Solena Le Scouarnec, Zhonglin Li, Peter Lichtner, Carlo Maj, Hasanga D Manikpurage, Christopher P Nelson, Thy B Nguyen, Russell A Norris, Chin Siang Ong, Philippe Pibarot, Tanmoy Roychowdhury, Berardo Sarubbi, Floriane Simonet, Thoralf Sundt, Ida Surakka, Idit Tessler, Cristen J Willer, Susanne Wittmann, Bo Yang, Igor Berezovets, Stefanie A Doppler, Martina Dreßen, Katharina Knoll, Thomas Puehler, Heribert Schunkert, Jean-François Avierinos, Malenka M Bissell, Aidan P Bolger, Yohan Bossé, Eduardo Bossone, María Brion, Rodolfo Citro, Carlo De Vincentiis, G Michael Deeb, Alessandro Della Corte, Christian Dina, Ronen Durst, Stephan Ensminger, Per Eriksson, Arturo Evangelista, Anders Franco-Cereceda, Dan Gilon, Betti Giusti, Simon L Hetherington, Gordon S Huggins, Markus Krane, Thierry Le Tourneau, Giuseppe Limongelli, Patrick Mathieu, David Messika-Zeitoun, Hector I Michelena, Dianna Milewicz, Jochen D Muehlschlegel, David R Murdock, Georg Nickenig, Stefano Nistri, Markus M Nöthen, Francesca Pluchinotta, Siddharth K Prakash, Nilesh J Samani, Jean-Jacques Schott, Tom R Webb, Stéphane Zaffran, Salim Abdelilah-Seyfried, Kim Eagle, Johannes Schumacher, Teresa Trenkwalder, Simon Body

Faculty, Staff and Student Publications

Background: Bicuspid aortic valve (BAV) is a frequent congenital heart defect with a high heritability. Despite this, only a limited number of genes have been associated with the disease, and the molecular mechanisms remain unexplained in most cases. This study aimed to further understand the genetic architecture of BAV.

Methods: A genome-wide association study meta-analysis including 9631 cases among 65 677 participants was performed. Genes were prioritized using transcriptomic analyses based on RNA sequencing in relevant tissues, including human fetal and adult aortic valves. The impact of the knockdown or knockout of 4 candidate genes on cardiac development was verified …

Identification Of A Cytokine Biomarker For Prognostic Modeling Of Breast Cancer-Related Lymphedema, Alison J Wu, Neil Lin, Jie Su, Cherie Lin, Madison-Shira Hossack, Wei Shi, Farnoosh Abbas-Aghababazadeh, Wei Xu, Benjamin Haibe-Kains, Simona F Shaitelman, Melissa B Aldrich, Fei-Fei Liu, Jennifer Y Y Kwan

Faculty, Staff and Student Publications

Lymphedema is a chronic complication of breast cancer treatment, and early intervention is crucial to reduce morbidity. This study evaluated the role of blood-based cytokine biomarkers in the prognostication of breast cancer-related lymphedema (BCRL) to improve risk prediction. A secondary analysis of inflammatory biomarkers for BCRL was performed using a previously published cohort of 147 breast cancer patients who had undergone serum cytokine profiling during their treatment at the Princess Margaret Cancer Centre from 2010-2014. Prognostic cytokine variables for lymphedema were selected by regression analysis and independence from known clinical risk factors. Regression-based modeling was employed to integrate prognostic variables …

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 …

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 …

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 …

The Long-Term Effectiveness Of The Anti-Obesity Medication Phentermine (Leap) Trial: Rationale, Design, And Baseline Characteristics, Caroline Blackwell Young, Emily Rives, Kimberly A Gudzune, Byron C Jaeger, Courtney G Simmons, Brian N White, Stephanie A Hooker, Deborah B Horn, Deborah R Young, Jennifer Vesely, Amanda Velazquez, Catherine Price, Shelly D Cook, Katy Martin-Fernandez, Galina Inzhakova, Nicholas M Pajewski, Jamy D Ard, Kristina H Lewis

Faculty, Staff and Student Publications

Background: Current clinical practice guidelines support the long-term use of pharmacotherapy for obesity treatment. Historically, phentermine has been one of the most prescribed obesity medications (OMs), however, its long-term efficacy and safety have never been evaluated in a randomized trial as its market approval predates such requirements. Here we describe the design, rationale, and baseline characteristics for a 24-month, double-blind, randomized controlled trial evaluating the efficacy, cardiovascular risk, and safety of phentermine in adults with overweight or obesity.

Methods: This multicenter trial will compare outcomes among participants randomized to phentermine 24 mg daily versus placebo for 24 months. All participants …

Scper: A Rigorous Computational Approach To Determine Cellular Subtypes In Tumors Aligned With Cancer Phenotypes From Total Rna Sequencing, Bingrui Li, Xiaobo Zhou, Raghu Kalluri

Faculty, Staff and Student Publications

Single-cell RNA sequencing (scRNA-seq) is a powerful technique for understanding cellular diversity, but processing large patient cohorts to identify phenotype-associated cell populations remains challenging. Here, scPER (Estimating cell Proportions using single-cell RNA-seq Reference), a rigorous approach combining adversarial autoencoder and extreme gradient boosting to estimate tumor microenvironment cell compositions and identify phenotype-associated subclusters for bulk RNA-seq samples. Integrating scRNA-seq datasets from diverse studies, scPER constructed comprehensive reference panels and disentangled confounders from true signals. scPER achieved superior accuracy in cellular proportion estimation compared to CIBERSORTx, BayesPrism, Scaden, MuSiC, SCDC, DeSide and ReCIDE. It showed high accuracy in predicting metastatic melanoma …

Genetic Architecture Of N-Terminal Pro-B-Type Natriuretic Peptide In A Multiancestry Study Population, Naman S Shetty, Akhil Pampana, Mokshad Gaonkar, Amrita Nayak, Harshvir S Bal, Nirav Patel, Nehal Vekariya, J Gustav Smith, Alanna C Morrison, Bing Yu, Bruce M Psaty, Eric Boerwinkle, James S Floyd, Jerome I Rotter, Kent D Taylor, Leslie A Lange, Marguerite R Irvin, Mary Cushman, Stephen S Rich, Ramachandran S Vasan, Thomas J Wang, Xiuqing Guo, Peng Li, Garima Arora, Pankaj Arora

Faculty, Staff and Student Publications

Background: NPs (natriuretic peptides) are bioactive hormones crucial for regulating blood pressure, glucose homeostasis, and lipid metabolism. Despite the high heritability of circulating NP levels, the genetic determinants of NP regulation, particularly across ancestries and sexes, remain poorly understood. The objective of the current study was to identify genetic variants associated with NT-proBNP (N-terminal pro-B-type NP) levels in a multiancestry study population.

Methods: Whole genome sequencing and array-based data from 81 213 individuals without heart failure were analyzed from the Trans-Omics for Precision Medicine cohorts, UK Biobank, All of Us Research Program, and REGARDS (Reasons for Geographic and Racial Differences …

Volumetric Buccal Bone Alterations At Immediate Implant Sites With Or Without Soft Tissue Augmentation: A 6-Month Assessment, Mary Jung, Duong Tran, Chi-Ching Chang, Sung K Kim, Yosuke Tsukiboshi, Seiko Min, Srinivas Ayilavarapu, Chun-Teh Lee

Faculty, Staff and Student Publications

Background: This study is part of a randomized controlled trial investigating the impact of soft tissue augmentation (STA) using subepithelial connective tissue graft (SCTG) (immediate implant with subepithelial connective tissue graft [ICT] group) or acellular dermal matrix (ADM) (immediate implant with acellular dermal matrix [IAD] group) versus no STA (control) on the clinical outcomes following immediate implant placement (IIP). This study aimed to investigate volumetric buccal bone dimensional changes at immediate implant sites 6 months after the surgery.

Methods: Forty-five patients requiring extraction of a maxillary anterior tooth or premolar and randomly assigned to one of the three groups were …

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 …

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 …

Fireproof: Intricacies Of Microglial Biology, Wei Cao

Faculty, Staff and Student Publications

No abstract provided.

A Step-By-Step Guide To Performing Cancer Metabolism Research Using Custom-Made Media, Sophie Seifert, Francisco Yanqui-Rivera, Tim Kühn, Lena Elise Høyland, Toman Borteçen, Bella Agranovich, Lara Elea Eckhardt, Martin Herdt, Alessa Henneberg, Verena Panitz, Faisal Hayat, Marie Migaud, Gernot Poschet, Ifat Abramovich, Eyal Gottlieb, Jeroen Krijgsveld, Mathias Ziegler, Mirja Tamara Prentzell, Christiane A Opitz

Faculty, Staff and Student Publications

The preparation of custom-made media offers precise control over nutrient composition, enabling detailed studies of cellular metabolism. We demonstrate how self-made media formulations enable diverse assay designs and readouts to assess cancer metabolism. Self-made media can be used in Seahorse assays to measure mitochondrial respiration under defined conditions. In nutrient deprivation experiments, amino acid or vitamin removal can uncover how cancer cells adapt to metabolic stress. Using labeled amino acids enables analysis of nascent protein synthesis and translational regulation, while stable-isotope tracing reveals metabolic fluxes through key pathways. This guide presents a suite of metabolic assays using custom-made media, covering …

Acta2 Pathogenic Variants Activating Heat Shock Factor 1 And Increasing Cholesterol Biosynthesis In Smooth Muscle Cells Predispose To Early Onset Atherosclerosis, Maura L Boerio, Abhijnan Chattopadhyay, Xue-Yan Duan, Aamuktha Karla, Ernesto Calderon Martinez, Amelie Pinard, Andrew K Morse, Darshan Reddy, Sree Dharma, Walter Velasco-Torrez, Julien Marcadier, Siddharth K Prakash, Sherene Shalhub, Julie De Backer, Richmond Jeremy, Shaine A Morris, Anji T Yetman, Alan C Braverman, Dianna M Milewicz

Faculty, Staff and Student Publications

Background: ACTA2 pathogenic variants predispose to thoracic aortic disease, and a subset of variants lead to early onset atherosclerotic cardiovascular disease (ASCVD). The molecular pathway linking misfolded SMA (α-smooth muscle actin) monomers to augmented atherosclerosis-associated smooth muscle cell phenotypic modulation can be modeled in vitro by stably expressing the ACTA2 p.R149C variant in Acta2-/- smooth muscle cells.

Methods: The Montalcino Aortic Consortium patient registry was used to identify cases with ACTA2 pathogenic/likely pathogenic missense variants. These patients were surveyed, and medical records were reviewed, to identify cases with early onset ASCVD. The variants for these cases, as well as …

The American College Of Radiology Diagnostic Fluoroscopy Dose Index Registry Pilot: Dosimetric Performance And Benchmarking Challenges, Steve D Mann, Donald L Miller, Grant Fong, Allen R Goode, Emily L Marshall, Thomas Nishino, Pavlina Boxx, Liqiang Ren, Celalettin Topbas, Alan H Schoenfeld, Vivek Singh, Jie Zhang

Faculty, Staff and Student Publications

Background: The ACR Diagnostic Fluoroscopy Dose Index Registry (DIR-Fluoro) is expanding to include diagnostic fluoroscopy. Variations in dose reference points and overhead radiography events may introduce unique challenges for benchmarking.

Purpose: To survey the technological status and dosimetric performance of fluoroscopes participating in the DIR-Fluoro pilot project, focusing on longitudinal stability and variability of fluoroscopic dose reporting accuracy across multiple institutions and vendors.

Methods: Sixty-six fluoroscopic systems from nine institutions (24 facilities) were surveyed for facility type, fluoroscope type, image receptor type, age, dose reporting capabilities, and other key features. Of these, 56 were evaluable. Semi-annual measurements assessed reference air …

Convolutional Neural Networks For Automatic Tuber Segmentation And Quantification Of Tuber Burden In Tuberous Sclerosis Complex, Iván Sánchez Fernández, Matheus D Soldatelli, Gillian N Miller, Catharina F Gout, Ellen C Broekhuizen, Iris C J Den Hertog, Daan A Pijs, Errol Apostolopoulos, Prabhjot Kaur, Abdelhakim Ouaalam, Martina E Bebin, Hope Northrup, Darcy A Krueger, Joyce Y Wu, Alexander L Cohen, Mustafa Sahin, Davood Karimi, Simon K Warfield, Jurriaan M Peters

Faculty, Staff and Student Publications

Objective: This study was undertaken to develop a fully automated algorithm for tuber segmentation and quantification of tuber volume that performs similarly to the gold standard human neuroradiologist.

Methods: We used brain magnetic resonance imaging (MRI) from patients with tuberous sclerosis complex (TSC) to train and validate a convolutional neural network (CNN), which was evaluated on segmentation with the Dice-Sørensen similarity coefficient (DSSC) and on tuber burden quantification with Spearman correlation coefficient against a neuroradiologist's gold standard in the test set.

Results: We collected 263 MRIs from 196 patients (57% males) with median (25th percentile-75th percentile) age of 4.3 (3.0-10.1) …

Presenilin L166p Mutation, A Model Of Familial Alzheimer's Disease, Leads To Early Onset Bone Loss, Vidyani Suryadevara, Connor J Krehbial, Anuradha K Valiya, Melinda Vang, Julian Balanta-Melo, Pierre P Eleniste, Sumana Posritong, Jung Min Hong, Katie Chester, Gabriel M Pagnotti, Teresita Bellido, Monte S Willis, Angela Bruzzaniti

Faculty, Staff and Student Publications

Accelerated bone loss has been reported in the early stages of Alzheimer's disease (AD) as indicated by reduced bone mineral density and increased fracture risk in these patients, compared to healthy individuals. In the present study, we investigated bone loss in mouse models of familial Alzheimer's disease harboring the Presenilin 1 (L166P) knock-in mutation (PSEN1 KI), with or without the human amyloid precursor protein transgene (hAPP Tg+) known to induce brain amyloid pathology by 6 months. Female and not male 12-month PSEN1/hAPP Tg+ mice exhibited reduced whole-body bone mineral density and bone mineral content, compared to sex-matched controls. Consistent with …