Digital Commons Network^™

Clinical Features And Genomic Epidemiology Of Bloodstream Infections Due To Enterococcal Species Other Than Enterococcus Faecalis Or E Faecium In Patients With Cancer, Dierdre B Axell-House, Patrycja A Ashley, Stephanie L Egge, Truc T Tran, Claudia Pedroza, Meng Zhang, An Q Dinh, Shelby R Simar, Pranoti V Sahasrabhojane, William R Miller, Samuel A Shelburne, Blake M Hanson, Cesar A Arias

Faculty, Staff and Student Publications

BACKGROUND: Non–Enterococcus faecium, non–E. faecalis (NFF) enterococci are a heterogeneous group of clinically pathogenic enterococci that include species with intrinsic low-level vancomycin resistance. Patients with cancer are at increased risk for bacteremia with NFF enterococci, but their clinical and molecular epidemiology have not been extensively described.

METHODS: We conducted a retrospective review of all patients (n = 70) with NFF bacteremia from 2016 to 2022 at a major cancer center. The main outcomes assessed were 30-day mortality, microbiological failure (positive blood cultures for ≥4 days), and recurrence of bacteremia (positive blood cultureclearance). Whole-genome sequencing was performed on all …

Duration Of Androgen Deprivation Therapy With Postoperative Radiotherapy For Prostate Cancer: A Comparison Of Long-Course Versus Short-Course Androgen Deprivation Therapy In The Radicals-Hd Randomised Trial, Chris C Parker, Howard Kynaston, Adrian D Cook, Noel W Clarke, Charles N Catton, William R Cross, Peter M Petersen, Rajendra A Persad, Cheryl A Pugh, Fred Saad, John Logue, Heather Payne, Lorna C Bower, Chris Brawley, Mary Rauchenberger, Maroie Barkati, David M Bottomley, Klaus Brasso, Hans T Chung, Peter W M Chung, Ruth Conroy, Alison Falconer, Vicky Ford, Chee L Goh, Catherine M Heath, Nicholas D James, Charmaine Kim-Sing, Ravi Kodavatiganti, Shawn C Malone, Stephen L Morris, Abdenour Nabid, Aldrich D Ong, Rakesh Raman, Sree Rodda, Paula Wells, Jane Worlding, Wendy R Parulekar, Mahesh K B Parmar, Matthew R Sydes

Faculty, Staff and Student Publications

BACKGROUND: Previous evidence supports androgen deprivation therapy (ADT) with primary radiotherapy as initial treatment for intermediate-risk and high-risk localised prostate cancer. However, the use and optimal duration of ADT with postoperative radiotherapy after radical prostatectomy remains uncertain.

METHODS: RADICALS-HD was a randomised controlled trial of ADT duration within the RADICALS protocol. Here, we report on the comparison of short-course versus long-course ADT. Key eligibility criteria were indication for radiotherapy after previous radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to add 6 months of ADT …

Mash: Mediation Analysis Of Survival Outcome And High-Dimensional Omics Mediators With Application To Complex Diseases, Sunyi Chi, Christopher R Flowers, Ziyi Li, Xuelin Huang, Peng Wei

Faculty, Staff and Student Publications

Environmental exposures such as cigarette smoking influence health outcomes through intermediate molecular phenotypes, such as the methylome, transcriptome, and metabolome. Mediation analysis is a useful tool for investigating the role of potentially high-dimensional intermediate phenotypes in the relationship between environmental exposures and health outcomes. However, little work has been done on mediation analysis when the mediators are high-dimensional and the outcome is a survival endpoint, and none of it has provided a robust measure of total mediation effect. To this end, we propose an estimation procedure for Mediation Analysis of Survival outcome and High-dimensional omics mediators (MASH) based on sure …

International Consensus Guidelines For The Definition, Detection, And Interpretation Of Autophagy-Dependent Ferroptosis, Xin Chen, Andrey S Tsvetkov, Han-Ming Shen, Ciro Isidoro, Nicholas T Ktistakis, Andreas Linkermann, Werner J H Koopman, Hans-Uwe Simon, Lorenzo Galluzzi, Shouqing Luo, Daqian Xu, Wei Gu, Olivier Peulen, Qian Cai, David C Rubinsztein, Jen-Tsan Chi, Donna D Zhang, Changfeng Li, Shinya Toyokuni, Jinbao Liu, Jong-Lyel Roh, Enyong Dai, Gabor Juhasz, Wei Liu, Jianhua Zhang, Minghua Yang, Jiao Liu, Ling-Qiang Zhu, Weiping Zou, Mauro Piacentini, Wen-Xing Ding, Zhenyu Yue, Yangchun Xie, Morten Petersen, David A Gewirtz, Michael A Mandell, Charleen T Chu, Debasish Sinha, Eftekhar Eftekharpour, Boris Zhivotovsky, Sébastien Besteiro, Dmitry I Gabrilovich, Do-Hyung Kim, Valerian E Kagan, Hülya Bayir, Guang-Chao Chen, Scott Ayton, Jan D Lünemann, Masaaki Komatsu, Stefan Krautwald, Ben Loos, Eric H Baehrecke, Jiayi Wang, Jon D Lane, Junichi Sadoshima, Wan Seok Yang, Minghui Gao, Christian Münz, Michael Thumm, Martin Kampmann, Di Yu, Marta M Lipinski, Jace W Jones, Xuejun Jiang, Herbert J Zeh, Rui Kang, Daniel J Klionsky, Guido Kroemer, Daolin Tang

Faculty, Staff and Student Publications

Macroautophagy/autophagy is a complex degradation process with a dual role in cell death that is influenced by the cell types that are involved and the stressors they are exposed to. Ferroptosis is an iron-dependent oxidative form of cell death characterized by unrestricted lipid peroxidation in the context of heterogeneous and plastic mechanisms. Recent studies have shed light on the involvement of specific types of autophagy (e.g. ferritinophagy, lipophagy, and clockophagy) in initiating or executing ferroptotic cell death through the selective degradation of anti-injury proteins or organelles. Conversely, other forms of selective autophagy (e.g. reticulophagy and lysophagy) enhance the cellular defense …

The Combination Of Tumor Mutational Burden And T-Cell Receptor Repertoire Predicts The Response To Immunotherapy In Patients With Advanced Non-Small Cell Lung Cancer, Yalun Li, Liyan Ji, Yingqian Zhang, Jiexin Zhang, Alexandre Reuben, Hao Zeng, Qin Huang, Qi Wei, Sihan Tan, Xuefeng Xia, Weimin Li, Jianjun Zhang, Panwen Tian

Faculty, Staff and Student Publications

Tumor mutational burden (TMB) and T-cell receptor (TCR) might predict the response to immunotherapy in patients with non-small cell lung cancer (NSCLC). However, the predictive value of the combination of TMB and TCR was not clear. Targeted DNA and TCR sequencing were performed on tumor biopsy specimens. We combined TMB and TCR diversity into a TMB-and-TCR (TMR) score using logistic regression. In total, 38 patients with advanced NSCLC were divided into a discovery set (

Longitudinal Changes In The Carotid Arteries Of Head And Neck Cancer Patients Following Radiation Therapy: Results From A Prospective Serial Imaging Biomarker Characterization Study, Efstratios Koutroumpakis, Abdallah Sherif Radwan Mohamed, Peter Chaftari, David I Rosenthal, Dorothy Gujral, Christopher Nutting, Serageldin Kamel, Mohamed A Naser, Peter Kim, Roland Bassett, Clifton D Fuller, Elie Mouhayar, Md Anderson Head Neck Radiation Oncology Cardiovascular Working Group

Faculty, Staff and Student Publications

INTRODUCTION: We prospectively evaluated morphologic and functional changes in the carotid arteries of patients treated with unilateral neck radiation therapy (RT) for head and neck cancer.

METHODS: Bilateral carotid artery duplex studies were performed at 0, 3, 6, 12, 18 months and 2, 3, 4, and 5 years following RT. Intima media thickness (IMT); global and regional circumferential, as well as radial strain, arterial elasticity, stiffness, and distensibility were calculated.

RESULTS: Thirty-eight patients were included. A significant difference in the IMT from baseline between irradiated and unirradiated carotid arteries was detected at 18 months (median, 0.073 mm vs -0.003 mm; …

Prioritization Of Kidney Cell Types Highlights Myofibroblast Cells In Regulating Human Blood Pressure, Mahboube Ganji-Arjenaki, Zoha Kamali, International Consortium Of Blood Pressure; Soroush Sardari, Soroush Sardari, Martin De Borst, Harold Snieder, Ahmad Vaez

Faculty, Staff and Student Publications

INTRODUCTION: Blood pressure (BP) is a highly heritable trait with over 2000 underlying genomic loci identified to date. Although the kidney plays a key role, little is known about specific cell types involved in the genetic regulation of BP.

METHODS: Here, we applied stratified linkage disequilibrium score (LDSC) regression to connect BP genome-wide association studies (GWAS) results to specific cell types of the mature human kidney. We used the largest single-stage BP genome-wide analysis to date, including up to 1,028,980 adults of European ancestry, and single-cell transcriptomic data from 14 mature human kidneys, with mean age of 41 years.

RESULTS: …

A Phase I Study Of Tak-659 And Paclitaxel In Patients With Taxane-Refractory Advanced Solid Tumors, M A Gouda, J Shunyakova, A Naing, E Dumbrava, D S Hong, Y Yuan, P Yang, A Myers, Y Liang, J Peng, D Karp, A M Tsimberidou, J Rodon, T A Yap, S A Piha-Paul, F Meric-Bernstam, S Fu

Faculty, Staff and Student Publications

BACKGROUND: Paclitaxel resistance limits durability of response in patients with initial clinical benefit. Overexpression of spleen tyrosine kinase (SYK) has been proposed as a possible resistance mechanism. This phase I trial evaluated the safety and preliminary activity of the SYK inhibitor TAK-659 combined with paclitaxel in patients with advanced taxane-refractory solid tumors.

PATIENTS AND METHODS: Patients with advanced solid tumors and prior progression on taxane-based therapy received intravenous infusion of paclitaxel on days 1, 8, and 15 plus oral TAK-659 daily in 28-day cycles. The dose-escalation phase included six cohorts treated at different dose levels; the dose-expansion phase included patients …

Common Epilepsy Variants From The General Population Are Not Associated With Epilepsy Among Individuals With Tuberous Sclerosis Complex, Melissa A Richard, Philip J Lupo, Erik A Ehli, Mustafa Sahin, Darcy A Krueger, Joyce Y Wu, Elizabeth M Bebin, Kit Sing Au, Hope Northrup, Laura S Farach

Faculty, Staff and Student Publications

Common genetic variants identified in the general population have been found to increase phenotypic risks among individuals with certain genetic conditions. Up to 90% of individuals with tuberous sclerosis complex (TSC) are affected by some type of epilepsy, yet the common variants contributing to epilepsy risk in the general population have not been evaluated in the context of TSC-associated epilepsy. Such knowledge is important to help uncover the underlying pathogenesis of epilepsy in TSC which is not fully understood, and critical as uncontrolled epilepsy is a major problem in this population. To evaluate common genetic modifiers of epilepsy, our study …

Contemporary Analysis Of Reexcision And Conversion To Mastectomy Rates And Associated Healthcare Costs For Women Undergoing Breast-Conserving Surgery, Youngran Kim, Cecilia Ganduglia-Cazaban, Nina Tamirisa, Anthony Lucci, Trudy Millard Krause

Faculty, Staff and Student Publications

Purpose: This study was designed to provide a comprehensive and up-to-date understanding of population-level reoperation rates and incremental healthcare costs associated with reoperation for patients who underwent breast-conserving surgery (BCS).

Methods: This is a retrospective cohort study using Merative™ MarketScan® commercial insurance data and Medicare 5% fee-for-service claims data. The study included females aged 18-64 years in the commercial cohort and females aged 18 years and older in the Medicare cohort, who underwent initial BCS for breast cancer in 2017-2019. Reoperation rates within a year of the initial BCS and overall 1-year healthcare costs stratified by reoperation status were measured. …

Influence Of Parental Nativity And Perceived Neighborhood Environment On Physical Activity And Screen Time Of United States Youth, Natalia I Heredia, Ethan T Hunt, Kevin Lanza

Faculty, Staff and Student Publications

OBJECTIVE: This study assessed how parental nativity and perceived environment are associated with physical activity and screen time of U.S. children and adolescents.

METHODS: Data originated from the 2020-21 U.S. National Survey of Children's Health. We conducted multivariable Poisson regression to assess the cross-sectional association of parental nativity and perceived neighborhood environment variables on parental reports of youth meeting national physical activity and screen time guidelines. We tested interactions of parental nativity and neighborhood environment variables on both outcomes. Analyses were conducted using STATA v17 and p < 0.05 indicated statistical significance.

RESULTS: The sample of 24,928 children and 30,951 adolescents was 11.6 years of …

Deformable Motion Compensation In Interventional Cone-Beam Ct With A Context-Aware Learned Autofocus Metric, Heyuan Huang, Yixuan Liu, Jeffrey H Siewerdsen, Alexander Lu, Yicheng Hu, Wojciech Zbijewski, Mathias Unberath, Clifford R Weiss, Alejandro Sisniega

Faculty, Staff and Student Publications

Purpose: Interventional Cone-Beam CT (CBCT) offers 3D visualization of soft-tissue and vascular anatomy, enabling 3D guidance of abdominal interventions. However, its long acquisition time makes CBCT susceptible to patient motion. Image-based autofocus offers a suitable platform for compensation of deformable motion in CBCT, but it relies on handcrafted motion metrics based on first-order image properties and that lack awareness of the underlying anatomy. This work proposes a data-driven approach to motion quantification via a learned, context-aware, deformable metric, VIFDL , that quantifies the amount of motion degradation as well as the realism of the structural anatomical content in the image. …

Environmental Magnesium Ion Affects Global Gene Expression, Motility, Biofilm Formation And Virulence Of Vibrio Parahaemolyticus, Xue Li, Xiaobai Zhang, Miaomiao Zhang, Xi Luo, Tingting Zhang, Xianjin Liu, Renfei Lu, Yiquan Zhang

Faculty, Staff and Student Publications

No abstract provided.

Contemporary Analysis Of Reexcision And Conversion To Mastectomy Rates And Associated Healthcare Costs For Women Undergoing Breast-Conserving Surgery, Youngran Kim, Cecilia Ganduglia-Cazaban, Nina Tamirisa, Anthony Lucci, Trudy Millard Krause

Faculty, Staff and Student Publications

PURPOSE: This study was designed to provide a comprehensive and up-to-date understanding of population-level reoperation rates and incremental healthcare costs associated with reoperation for patients who underwent breast-conserving surgery (BCS).

METHODS: This is a retrospective cohort study using Merative™ MarketScan® commercial insurance data and Medicare 5% fee-for-service claims data. The study included females aged 18-64 years in the commercial cohort and females aged 18 years and older in the Medicare cohort, who underwent initial BCS for breast cancer in 2017-2019. Reoperation rates within a year of the initial BCS and overall 1-year healthcare costs stratified by reoperation status were measured. …

Fibroblast Subpopulations In Systemic Sclerosis: Functional Implications Of Individual Subpopulations And Correlations With Clinical Features, Honglin Zhu, Hui Luo, Brian Skaug, Tracy Tabib, Yi-Nan Li, Yongguang Tao, Alexandru-Emil Matei, Marka A Lyons, Georg Schett, Robert Lafyatis, Shervin Assassi, Jörg H W Distler

Faculty, Staff and Student Publications

Fibroblasts constitute a heterogeneous population of cells. In this study, we integrated single-cell RNA-sequencing and bulk RNA-sequencing data as well as clinical information to study the role of individual fibroblast populations in systemic sclerosis (SSc). SSc skin demonstrated an increased abundance of COMP+, COL11A1+, MYOC+, CCL19+, SFRP4/SFRP2+, and PRSS23/SFRP2+ fibroblasts signatures and decreased proportions of CXCL12+ and PI16+ fibroblast signatures in the Prospective Registry of Early Systemic Sclerosis and Genetics versus Environment in Scleroderma Outcome Study cohorts. Numerical differences were confirmed by multicolor immunofluorescence for selected fibroblast populations. COMP+, COL11A1+, SFRP4/SFRP2+, PRSS23/SFRP2+, and PI16+ fibroblasts were similarly altered between normal …

Associations Between Radiation Oncologist Demographic Factors And Segmentation Similarity Benchmarks: Insights From A Crowd-Sourced Challenge Using Bayesian Estimation, Kareem A Wahid, Onur Sahin, Suprateek Kundu, Diana Lin, Anthony Alanis, Salik Tehami, Serageldin Kamel, Simon Duke, Michael V Sherer, Mathis Rasmussen, Stine Korreman, David Fuentes, Michael Cislo, Benjamin E Nelms, John P Christodouleas, James D Murphy, Abdallah S R Mohamed, Renjie He, Mohammed A Naser, Erin F Gillespie, Clifton D Fuller

Faculty, Staff and Student Publications

PURPOSE: The quality of radiotherapy auto-segmentation training data, primarily derived from clinician observers, is of utmost importance. However, the factors influencing the quality of clinician-derived segmentations are poorly understood; our study aims to quantify these factors.

METHODS: Organ at risk (OAR) and tumor-related segmentations provided by radiation oncologists from the Contouring Collaborative for Consensus in Radiation Oncology data set were used. Segmentations were derived from five disease sites: breast, sarcoma, head and neck (H&N), gynecologic (GYN), and GI. Segmentation quality was determined on a structure-by-structure basis by comparing the observer segmentations with an expert-derived consensus, which served as a reference …

Trends In Fatal Opioid-Related Overdose In American Indian And Alaska Native Communities, 1999-2021, Cici Bauer, Ghada H Hassan, Ric Bayly, Jack Cordes, Dana Bernson, Cedric Woods, Xiaona Li, Wenjun Li, Leland K Ackerson, Marc R Larochelle, Thomas J Stopka

Faculty, Staff and Student Publications

INTRODUCTION: Opioid-related overdose mortality rates have increased sharply in the U.S. over the past two decades, and inequities across racial and ethnic groups have been documented. Opioid-related overdose trends among American Indian and Alaska Natives require further quantification and assessment.

METHODS: Observational, U.S. population-based registry data on opioid-related overdose mortality between 1999 and 2021 were extracted in 2023 using ICD-10 codes from the U.S. Centers for Disease Control and Prevention's Wide-Ranging Online Data for Epidemiologic Research multiple cause of death file by race, Hispanic ethnicity, sex, and age. Segmented time series analyses were conducted to estimate opioid-related overdose mortality growth …

Prevalence And Descriptive Epidemiology Of Choanal Atresia And Stenosis In Texas, 1999–2018, Renata H Benjamin, Lisa K Marengo, Angela E Scheuerle, A J Agopian, Laura E Mitchell

Faculty, Staff and Student Publications

Choanal atresia and stenosis are common causes of congenital nasal obstruction, but their epidemiology is poorly understood. Compared to bilateral choanal atresia/stenosis, unilateral choanal atresia/stenosis is generally diagnosed later and might be under-ascertained in birth defect registries. Data from the population-based Texas Birth Defects Registry and Texas vital records, 1999-2018, were used to assess the prevalence of choanal atresia/stenosis. Poisson regression models were used to evaluate associations with infant and maternal characteristics in two analytic groups: isolated choanal atresia/stenosis (n = 286) and isolated, bilateral choanal atresia/stenosis (n = 105). The overall prevalence of choanal atresia/stenosis was 0.92/10,000, and the …

Efficacy And Safety Of Tepotinib In Asian Patients With Advanced Nsclc With Met Exon 14 Skipping Enrolled In Vision, Terufumi Kato, James Chih-Hsin Yang, Myung-Ju Ahn, Hiroshi Sakai, Masahiro Morise, Yuh-Min Chen, Ji-Youn Han, Jin-Ji Yang, Jun Zhao, Te-Chun Hsia, Karin Berghoff, Rolf Bruns, Helene Vioix, Simone Lang, Andreas Johne, Xiuning Le, Paul K Paik

Faculty, Staff and Student Publications

BACKGROUND: Tepotinib, a MET inhibitor approved for the treatment of MET exon 14 (METex14) skipping NSCLC, demonstrated durable clinical activity in VISION (Cohort A + C; N = 313): objective response rate (ORR) 51.4% (95% CI: 45.8, 57.1); median duration of response (mDOR) 18.0 months (95% CI: 12.4, 46.4). We report outcomes in Asian patients from VISION (Cohort A + C) (cut-off: November 20, 2022).

METHODS: Patients with advanced METex14 skipping NSCLC, detected by liquid or tissue biopsy, received tepotinib 500 mg (450 mg active moiety) once daily.

PRIMARY ENDPOINT: objective response (RECIST 1.1) by independent review. Secondary endpoints included: …

Multi-Task Deep Neural Networks For Irregularly Sampled Multivariate Clinical Time Series, Yuxi Liu, Zhenhao Zhang, Shaowen Qin, Jiang Bian

Faculty, Staff and Student Publications

Multivariate clinical time series data, such as those contained in Electronic Health Records (EHR), often exhibit high levels of irregularity, notably, many missing values and varying time intervals. Existing methods usually construct deep neural network architectures that combine recurrent neural networks and time decay mechanisms to model variable correlations, impute missing values, and capture the impact of varying time intervals. The complete data matrices thus obtained from the imputation task are used for downstream risk prediction tasks. This study aims to achieve more desirable imputation and prediction accuracy by performing both tasks simultaneously. We present a new multi-task deep neural …

Life-Space Mobility, Transportation, And The Companionship Network Of Members Of A Hispanic Senior Center, Rebecca L Mauldin, Rupal Parekh, John P Connolly, Stephen P Mattingly, Aiman Mushtaq, Kayo Fujimoto

Faculty, Staff and Student Publications

Objectives: Companions (i.e., friends who spend time together) are important for the well-being of older adults. Senior centers in the United States are places for older adults to participate in group activities and form and maintain companionships. However, differences in mobility and transportation may affect the ability of older adults to leverage senior center activities into actual companionships.

Methods: This social network analysis was conducted to characterize the companionship network among members of a senior center in relation to their life-space mobility and transportation resources. An exponential random graph model was estimated to identify mobility- and transportation-related correlates of the …

Patient Location And Disparities In Access To Fertility Preservation For Women With Gynecologic Or Breast Cancer, Alexa Kanbergs, Kirsten Jorgensen, Nuria Agusti, David Viveros-Carreño, Chi-Fang Wu, Roni Nitecki, John A Harris, Terri Woodard, Ryan Ramphul, Jose Alejandro Rauh-Hain

Faculty, Staff and Student Publications

Objective: To assess the effect of geographic factors on fertility-sparing treatment or assisted reproductive technology (ART) utilization among women with gynecologic or breast cancers.

Methods: We conducted a cohort study of reproductive-aged patients (18-45 years) with early-stage cervical, endometrial, or ovarian cancer or stage I-III breast cancer diagnosed between January 2000 and December 2015 using linked data from the California Cancer Registry, the California Office of Statewide Health Planning and Development, and the Society for Assisted Reproductive Technology. Generalized linear mixed models were used to evaluate associations between distance from fertility and gynecologic oncology clinics, as well as California Healthy …

Correction: Contemporary Analysis Of Reexcision And Conversion To Mastectomy Rates And Associated Healthcare Costs For Women Undergoing Breast-Conserving Surgery, Youngran Kim, Cecilia Ganduglia-Cazaban, Nina Tamirisa, Anthony Lucci, Trudy Millard Krause

Faculty, Staff and Student Publications

Correction: Annals of Surgical Oncology 10.1245/s10434-024-14902-z

The article “Contemporary Analysis of Reexcision and Conversion to Mastectomy Rates and Associated Healthcare Costs for Women Undergoing Breast‑Conserving Surgery”, written by Kim et al. was originally published electronically on the publisher’s internet portal on February 6, 2024, without open access. With the authors‘ decision to opt for Open Choice the copyright of the article changed on March 14, 2024, to © The Author(s) 2024, and the article is forthwith distributed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long …

Time-To-Event Genome-Wide Association Study For Incident Cardiovascular Disease In People With Type 2 Diabetes, Soo Heon Kwak, Ryan B Hernandez-Cancela, Daniel A Dicorpo, David E Condon, Jordi Merino, Peitao Wu, Jennifer A Brody, Jie Yao, Xiuqing Guo, Fariba Ahmadizar, Mariah Meyer, Murat Sincan, Josep M Mercader, Sujin Lee, Jeffrey Haessler, Ha My T Vy, Zhaotong Lin, Nicole D Armstrong, Shaopeng Gu, Noah L Tsao, Leslie A Lange, Ningyuan Wang, Kerri L Wiggins, Stella Trompet, Simin Liu, Ruth J F Loos, Renae Judy, Philip H Schroeder, Natalie R Hasbani, Maxime M Bos, Alanna C Morrison, Rebecca D Jackson, Alexander P Reiner, Joann E Manson, Ninad S Chaudhary, Lynn K Carmichael, Yii-Der Ida Chen, Kent D Taylor, Mohsen Ghanbari, Joyce Van Meurs, Achilleas N Pitsillides, Bruce M Psaty, Raymond Noordam, Ron Do, Kyong Soo Park, J Wouter Jukema, Maryam Kavousi, Adolfo Correa, Stephen S Rich, Scott M Damrauer, Catherine Hajek, Nam H Cho, Marguerite R Irvin, James S Pankow, Girish N Nadkarni, Robert Sladek, Mark O Goodarzi, Jose C Florez, Daniel I Chasman, Susan R Heckbert, Charles Kooperberg, Josée Dupuis, Rajeev Malhotra, Paul S De Vries, Ching-Ti Liu, Jerome I Rotter, James B Meigs

Faculty, Staff and Student Publications

Objective: To identify genetic risk factors for incident cardiovascular disease (CVD) among people with type 2 diabetes (T2D).

Research design and methods: We conducted a multiancestry time-to-event genome-wide association study for incident CVD among people with T2D. We also tested 204 known coronary artery disease (CAD) variants for association with incident CVD.

Results: Among 49,230 participants with T2D, 8,956 had incident CVD events (event rate 18.2%). We identified three novel genetic loci for incident CVD: rs147138607 (near CACNA1E/ZNF648, hazard ratio [HR] 1.23, P = 3.6 × 10-9), rs77142250 (near HS3ST1, HR 1.89, P = 9.9 × 10-9), and rs335407 (near …

Lymphovenous Anastomosis For The External And Internal Types Of Head And Neck Lymphedema: A Case Series And Preliminary Clinical Results, Ying-Sheng Lin, Chia-Ju Liu, Chen-Han Chou

Faculty, Staff and Student Publications

BACKGROUND: Head and neck lymphedema (HNL), including external and internal types, could be a possible consequence for patients who have received neck dissection and radiotherapy for head and neck cancer. Initially, the common presentations are heaviness or tightness, followed by swelling in appearance, or difficulty speaking and swallowing in internal edema cases. Lymphovenous anastomosis (LVA) is an established approach to treat extremity lymphedema. We hereby present our preliminary experience in using LVA to treat HNL.

METHODS: Between March 2021 and January 2024, six patients with HNL were treated with LVA via a preauricular or submandibular incision of the obstructed side. …

Genome-Wide Interaction Study Of Dietary Intake Of Fibre, Fruits, And Vegetables With Risk Of Colorectal Cancer, Nikos Papadimitriou, Andre Kim, Eric S Kawaguchi, John Morrison, Virginia Diez-Obrero, Demetrius Albanes, Sonja I Berndt, Stéphane Bézieau, Stephanie A Bien, D Timothy Bishop, Emmanouil Bouras, Hermann Brenner, Daniel D Buchanan, Peter T Campbell, Robert Carreras-Torres, Andrew T Chan, Jenny Chang-Claude, David V Conti, Matthew A Devall, Niki Dimou, David A Drew, Stephen B Gruber, Tabitha A Harrison, Michael Hoffmeister, Jeroen R Huyghe, Amit D Joshi, Temitope O Keku, Anshul Kundaje, Sébastien Küry, Loic Le Marchand, Juan Pablo Lewinger, Li Li, Brigid M Lynch, Victor Moreno, Christina C Newton, Mireia Obón-Santacana, Jennifer Ose, Andrew J Pellatt, Anita R Peoples, Elizabeth A Platz, Conghui Qu, Gad Rennert, Edward Ruiz-Narvaez, Anna Shcherbina, Mariana C Stern, Yu-Ru Su, Duncan C Thomas, Claire E Thomas, Yu Tian, Konstantinos K Tsilidis, Cornelia M Ulrich, Caroline Y Um, Kala Visvanathan, Jun Wang, Emily White, Michael O Woods, Stephanie L Schmit, Finlay Macrae, John D Potter, John L Hopper, Ulrike Peters, Neil Murphy, Li Hsu, Marc J Gunter, W James Gauderman

Faculty, Staff and Student Publications

Background: Consumption of fibre, fruits and vegetables have been linked with lower colorectal cancer (CRC) risk. A genome-wide gene-environment (G × E) analysis was performed to test whether genetic variants modify these associations.

Methods: A pooled sample of 45 studies including up to 69,734 participants (cases: 29,896; controls: 39,838) of European ancestry were included. To identify G × E interactions, we used the traditional 1--degree-of-freedom (DF) G × E test and to improve power a 2-step procedure and a 3DF joint test that investigates the association between a genetic variant and dietary exposure, CRC risk and G × E interaction …

Risk-Benefit Trade-Offs And Precision Utilities In Phase I-Ii Clinical Trials, Pavlos Msaouel, Juhee Lee, Peter F Thall

Faculty, Staff and Student Publications

Background: Identifying optimal doses in early-phase clinical trials is critically important. Therapies administered at doses that are either unsafe or biologically ineffective are unlikely to be successful in subsequent clinical trials or to obtain regulatory approval. Identifying appropriate doses for new agents is a complex process that involves balancing the risks and benefits of outcomes such as biological efficacy, toxicity, and patient quality of life.

Purpose: While conventional phase I trials rely solely on toxicity to determine doses, phase I-II trials explicitly account for both efficacy and toxicity, which enables them to identify doses that provide the most favorable risk-benefit …

High Community-Level Social Vulnerability Is Associated With Worse Recurrence-Free Survival (Rfs) After Resection Of Extremity And Truncal Soft Tissue Sarcoma, Raymond S Traweek, Heather G Lyu, Russell G Witt, Rebecca A Snyder, Elise F Nassif, David D Krijgh, Jeffrey M Smith, Gordon S Tilney, Chun Feng, Yi-Ju Chiang, Keila E Torres, Margaret J Roubaud, Christopher P Scally, Kelly K Hunt, Emily Z Keung, Alexander F Mericli, Christina L Roland

Faculty, Staff and Student Publications

Background: Although social vulnerability has been associated with worse postoperative and oncologic outcomes in other cancer types, these effects have not been characterized in patients with soft tissue sarcoma. This study evaluated the association of social vulnerability and oncologic outcomes.

Methods: The authors conducted a single-institution cohort study of adult patients with primary and locally recurrent extremity or truncal soft tissue sarcoma undergoing resection between January 2016 and December 2021. The social vulnerability index (SVI) was measured on a low (SVI 1-39%, least vulnerable) to high (60-100%, most vulnerable) SVI scale. The association of SVI with overall survival (OS) and …

Omicsmic: A Comprehensive Benchmarking Platform For Robust Comparison Of Imputation Methods In Mass Spectrometry-Based Omics Data, Weiqiang Lin, Jiadong Ji, Kuan-Jui Su, Chuan Qiu, Qing Tian, Lan-Juan Zhao, Zhe Luo, Chong Wu, Hui Shen, Hongwen Deng

Faculty, Staff and Student Publications

Mass spectrometry is a powerful and widely used tool for generating proteomics, lipidomics and metabolomics profiles, which is pivotal for elucidating biological processes and identifying biomarkers. However, missing values in mass spectrometry-based omics data may pose a critical challenge for the comprehensive identification of biomarkers and elucidation of the biological processes underlying human complex disorders. To alleviate this issue, various imputation methods for mass spectrometry-based omics data have been developed. However, a comprehensive comparison of these imputation methods is still lacking, and researchers are frequently confronted with a multitude of options without a clear rationale for method selection. To address …

Fine-Grained Patient Similarity Measuring Using Contrastive Graph Similarity Networks, Yuxi Liu, Zhenhao Zhang, Shaowen Qin, Flora D Salim, Jiang Bian, Antonio Jimeno Yepes

Faculty, Staff and Student Publications

Predictive analytics using Electronic Health Records (EHRs) have become an active research area in recent years, especially with the development of deep learning techniques. A popular EHR data analysis paradigm in deep learning is patient representation learning, which aims to learn a condensed mathematical representation of individual patients. However, EHR data are often inherently irregular, i.e., data entries were captured at different times as well as with different contents due to the individualized needs of each patient. Most of the work focused on the provision of deep neural networks with attention mechanisms that generate complete patient representations that can be …