Digital Commons Network^™

A Pocket Manual For Human Papillomavirus Vaccines, Natalie A Voss, J Brooks Jackson, Mary B Rysavy

Faculty, Staff and Student Publications

Human papillomavirus (HPV) is the most common sexually transmitted infection worldwide and is responsible for the majority of cervical, anal, and vaginal cancers. The first prophylactic HPV vaccine was introduced in the United States in 2006. Extensive evidence demonstrates the HPV vaccine is highly efficacious and effective, particularly when administered prior to HPV exposure. Despite strong safety data and proven cost-effectiveness, HPV vaccine uptake in the United States and globally remains suboptimal. Barriers to vaccination include limited knowledge, safety concerns, and logistical challenges. Current advancements focus on single-dose vaccine regimens, development of therapeutic vaccines, and higher-valent formulations. Expanding HPV vaccine …

Associations Of Moderate-To-Vigorous Physical Activity Timing With Type 2 Diabetes Incidence In Uk Biobank And Prevalent Glycemic Measures In Nhanes, Qiuyu Feng, Gali Albalak, Linjun Ao, Qian Xiao, Heming Wang, Jeroen H P M Van Der Velde, Jessica C Kiefte-De Jong, Martin K Rutter, Charles E Matthews, Joshua R Freeman, Ko Willems Van Dijk, Diana Van Heemst, Raymond Noordam

Faculty, Staff and Student Publications

Objective: We assessed the association between timing of moderate-to-vigorous physical activity (MVPA) with incident type 2 diabetes (T2D) and glycemic measures.

Research design and methods: Regression models were used to assess associations between accelerometer-derived MVPA timing and incident T2D in UK Biobank (UKB) (n = 84,528, prospective), prevalent diabetes, and glycemic measures in the National Health and Nutrition Examination Survey (NHANES) (n = 6,998, cross-sectional).

Results: In UKB, with early morning (0500-0959) MVPA as reference and before adjustment for total MVPA, "variable-timing" MVPA was associated with the lowest incident T2D risk; while after adjustment, afternoon-evening MVPA (1500-2400) showed the lowest …

Barriers To Occupational And Physical Therapy Utilization For Children With Cancer, Maria C Swartz, Shiming Zhang, Donna Kelly, Clark R Andersen, Keri Schadler, Alakh P Rajan, Eduardo Gonzalez Villarreal, Stephanie J Wells, Amy Heaton, Karen Moody

Faculty, Staff and Student Publications

Introduction: Occupational and physical therapy (OT/PT) referrals and utilization barriers for childhood cancer patients have not been adequately examined. The current study investigated factors influencing referrals to and utilization of OT/PT services among children with cancer at an NIH-designated cancer center.

Methods: This retrospective cohort study included pediatric cancer patients (up to 18.99 years) presenting to the center over a 33.5-month period. Variables that could influence referrals to OT/PT were extracted from the electronic medical record (EMR) including OT and PT referrals (inpatient and outpatient), OT and PT consult completion, age at diagnosis, cancer type, sex, race/ethnicity, insurance, cancer treatment, …

Physical Activity In Osteosarcoma Patients During And Post Therapy: A Single Site Prospective Observational Study, Elysia R Cohen, Clark Andersen, Karen Moody, Maria C Swartz, Michael C Robertson, Alakh Rajan, Theresa Honey, Sandra Lugo, Grace Waterman, Keri Schadler

Faculty, Staff and Student Publications

PURPOSE: Osteosarcoma is the most common primary bone tumor in childhood and adolescence. Many patients face long-term impairments in their mobility and function after treatment, leading to a decrease in their quality of life. Exercise has been shown to improve functional recovery and improve quality of life in patients with cancer, though data specific to children with osteosarcoma are sparse. Exercise has also been shown to be feasible in patients undergoing chemotherapy, with numerous potential benefits to health and quality of life. To design the most effective exercise interventions for children and adolescents with osteosarcoma, we must first understand the …

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 …

Optimizing Feasibility And Acceptability Of An Online Expressive Writing Intervention For Survivors Of Adolescent And Young Adult Cancer: A Pilot Randomized Trial Of Iterative Modifications And Outcomes, Eunju Choi, Yusi Aveva Xu, Celia Cy Wong-Meli, Michael E Roth, Yisheng Li, Qian Lu

Faculty, Staff and Student Publications

Objective: To evaluate the feasibility of an online expressive writing (EW) intervention for survivors of adolescent and young adult (AYA) cancer and determine whether iterative, theory-driven modifications can enhance response, adherence, and completion rates.

Methods: In this randomized pilot trial, survivors of AYA cancer were recruited through a hospital-based AYA oncology clinic and an online community. Forty participants were randomly assigned to the EW intervention or control group. To improve on lower-than-expected adherence and completion rates in a previous cohort, the protocol was iteratively revised using the Framework for Reporting Adaptations and Modifications to Evidence-based Implementation Strategies (FRAME-IS). Modifications included …

Establishing Proof-Of-Concept For The Feasibility And Implementation Of A Point-Of-Sale Firearm Safety Counseling Program: A Qualitative Case Study, Amanda Koong, Mike Henson-Garcia, Lauren Malthaner, Katelyn Jetelina, Belinda Hernandez, Sandra Mckay

Faculty, Staff and Student Publications

Safe firearm storage is critical for injury prevention, yet there is limited evidence surrounding effective interventions to promote storage behaviors among owners. One potential avenue for intervention is at the point-of-sale, a concept well-proven in the nutrition promotion and tobacco cessation space. This study explored firearm retailer attitudes toward a firearm storage intervention delivered at the point of sale. Seventeen in-depth interviews were conducted with firearm retailers from a suburban gun shop in Fort Bend, USA. This semi-structured interview assessed firearm retailer perceptions of the proposed point-of-sale intervention. Interviews were transcribed and independently coded to identify themes that emerged from …

Expectant Management Vs Medication For Patent Ductus Arteriosus In Preterm Infants: The Pda Randomized Clinical Trial, Matthew M Laughon, Sonia M Thomas, Kristi L Watterberg, Kathleen A Kennedy, Martin Keszler, Namisavayam Ambalavanan, Alexis S Davis, Jonathan L Slaughter, Ronnie Guillet, Tarah T Colaizy, C Michael Cotten, Megan A Dhawan, Carl L Bose, Jennifer Talbert, Sarah Smucny, William E Benitz, Matthew A Rysavy, Robin K Ohls, Mariana C Baserga, Sara B Demauro, Mambarambath Jaleel, Wesley M Jackson, Waldemar A Carlo, Karen M Puopolo, Anna Maria Hibbs, Anup Katheria, Pablo J Sánchez, Carl T D'Angio, Ravi M Patel, Beth Ann Johnson, Valerie Y Chock, Abhay J Bhatt, Stephanie L Merhar, Ryan Moore, Abbot R Laptook, Sarvin Ghavam, Janell Fuller, Shilpa Vyas-Read, Stephen D Kicklighter, Baiba Steinbrekera, Kathryn Anderson, Praveen K Chandrasekharan, Myra H Wyckoff, Cassandra Montoya, Abhik Das, Barbara Do, Samantha Chang, Rosemary D Higgins, Michele C Walsh

Faculty, Staff and Student Publications

Importance: The management of patent ductus arteriosus (PDA) in preterm infants is controversial.

Objective: To determine whether expectant management compared with active treatment of a protocol-defined PDA in preterm infants decreases the incidence of death or bronchopulmonary dysplasia (BPD).

Design, setting, and participants: A randomized clinical trial including infants born at 22 to 28 weeks' gestation and diagnosed with a protocol-defined PDA between the age of 48 hours and 21 days at screening. The trial was conducted from December 2018 to December 2024 at 33 hospitals within the National Institute of Child Health and Human Development Neonatal Research Network. The …

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 …

Tumor-Immune-Neural Circuit Disrupts Energy Homeostasis In Cancer Cachexia, Xiuhui Shi, Alex X Arreola, Zhijun Zhou, Jingxuan Yang, Mingyang Liu, Yang Cai, Yu Ren, Hao Yuan, Qun Chen, Xinjie Chen, Xinyu Yang, Yimei Meng, Jingyi Wang, Wenyi Luo, Michael C Rudolph, Rohan Varshney, Kar-Ming Fung, Chao Xu, Wei R Chen, Michael S Bronze, Lei Zheng, Yi-Ping Li, Courtney W Houchen, Yuqing Zhang, Min Li

Faculty, Staff and Student Publications

Cancer-induced cachexia and anorexia are debilitating complications across many cancers, yet effective treatments remain limited due to a poor understanding of the underlying mechanisms. Here, we identify an uncharacterized tumor-immune-neural circuit driving these syndromes, centered on growth and differentiation factor 15 (GDF15). Using genetically engineered mouse models, we find that loss of GDF15 protects against appetite loss, muscle wasting, and fat loss in pancreatic, lung, and skin cancers. Single-cell RNA sequencing reveals macrophages as a major source of GDF15, induced by tumor-derived colony-stimulating factor 1 (CSF1). GDF15 acts via the central nervous system to enhance β-adrenergic signaling in the tumor …

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

Faculty, Staff and Student Publications

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

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

Faculty, Staff and Student Publications

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

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

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

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 …

Transcriptomics And Metabolomics Analysis Reveal Cell Subpopulations Of Trophoblast Cells Associated With Preeclampsia, Xiaojun Zhu, Ying Jiang, Lilin Wang, Peiyue Jiang, Zixing Zhong, Hetong Li, Caihong Zheng, Lujiao Chen, Juan Wei, Xishi Lin, Peng Ding, Zehua Dong, Xiaosheng Wang, Qiong Luo

Faculty, Staff and Student Publications

Placental abnormalities are central to preeclampsia (PE), yet the cellular and molecular mechanisms underlying this dysfunction remain unclear. We applied a multi-layered, integrative approach to investigate placental tissue from patients with PE and matched controls. Single-cell RNA sequencing (scRNA-seq; GSE173193) and bulk RNA sequencing (bulk RNA-seq; GSE203507) datasets were obtained from the Gene Expression Omnibus. The scRNA-seq dataset included two PE and two control samples, whereas the bulk RNA-seq dataset focused on eight early-onset PE and five uncomplicated term births. Trophoblast subpopulations were identified via scRNA-seq, and pseudotime analysis was used to trace differentiation trajectories. Differential expression and pathway enrichment …

Examination Of Traffic Safety In Neighborhoods Associated With Active Commuting To School In Austin, Texas, Kathryn G Burford, Deborah Salvo, Harold W Kohl, Leigh Ann Ganzar, Cici X Bauer, Eugen Resendiz, Yuzi Zhang, Deanna M Hoelscher

Faculty, Staff and Student Publications

Background: Only 10% of US children participate in active commuting (walking and bicycling) to school (ACS). Parental concerns related to traffic are a primary barrier to ACS, yet no studies have assessed these concerns together with neighborhood traffic safety-related features. This study examined the associations between traffic safety-related features in neighborhoods and ACS among school-age children in Austin, Texas.

Methods: This cross-sectional analysis utilized pre-COVID-19 baseline data (2019-2020) of parent-child dyads enrolled in the Safe TRavel Environment Evaluation in Texas Schools study. ACS, traffic safety-related features in the neighborhood (sidewalk availability, safe road crossings, traffic safety, traffic speed, and safety …

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 …

Circulating Fatty Acid Binding Protein 4 (Fabp-4) Concentrations And Mortality In Individuals With Colorectal Cancer In The European Prospective Investigation Into Cancer And Nutrition Study, Thu Thi Pham, Katharina Nimptsch, Krasimira Aleksandrova, Mazda Jenab, Veronika Fedirko, Anja Olsen, Anne Tjønneland, Claire Cadeau, Gianluca Severi, Matthias B Schulze, Renée Turzanski Fortner, Verena Katzke, Claudia Agnoli, Carlotta Sacerdote, Rosario Tumino, Simona Signoriello, Camino Trobajo-Sanmartín, Jesús-Humberto Gómez, María-Dolores Chirlaque, Maria-Jose Sánchez, Marta Crous-Bou, Anne May, Alicia Heath, Dagfinn Aune, Elisabete Weiderpass, Tobias Pischon

Faculty, Staff and Student Publications

Human fatty acid binding protein‐4 (FABP‐4), a protein elevated in obesity that promotes colon cancer cell invasiveness and metastasis, may be associated with higher mortality in individuals with colorectal cancer (CRC) and may serve as a mediator of the obesity–mortality association in these individuals. We used a causal diagram to inform covariate selection and applied Cox proportional hazards models to estimate hazard ratios (HRs) for CRC‐specific, non‐CRC‐specific, and all‐cause mortality by FABP‐4 levels measured in baseline blood samples from 1371 incident CRC cases from the European Prospective Investigation into Cancer and Nutrition cohort. Competing risk analyses were adapted for CRC …

Hypoglossal Neuropathy In The Pathogenesis Of Fibrosis-Related Late-Radiation Associated Dysphagia: A Correlative Analysis Utilizing Electromyography To Explore The Frequency Of Clinical And Subclinical Neuropathy In A Pilot Dysphagia Trial, Holly Mcmillan, Christine Okoro, Sheila Buoy, Karin Woodman, Nicolaas Anderson, Clifton Fuller, Stephen Y Lai, Katherine Hutcheson

Faculty, Staff and Student Publications

Background: Late radiation-associated dysphagia (late-RAD) commonly presents in patients with signs of hypoglossal neuropathy, with hallmark clinical features including lingual atrophy, deviation, and fasciculation. Gold-standard electromyography (EMG) has not been used to explore the frequency of hypoglossal neuropathy in patients with late-RAD.

Methods: Exploratory post hoc secondary analysis of MANTLE trial (NCT03612531) was completed. The presence of cranial nerve XII (CN XII) neuropathy was classified by (1) features of clinical assessment as well as (2) intramuscular genioglossus EMG pre-MANTLE intervention in disease-free HNC survivors ≥ 2 years post-radiotherapy (RT) with grade ≥ 2 fibrosis and dysphagia.

Results: All …

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 …

Modern Home Cooking Practices, The Role Of New Media, And Implications For Culinary Medicine: A Qualitative Study Among Mothers With Low Income, Margaret Raber, Maria Vazquez, Syeda Khan, Sahiti Myneni, Debbe Thompson

Faculty, Staff and Student Publications

Culinary medicine offers a practical, experiential approach to nutrition education, but in-person programs are resources intensive. Digital interventions may offer a scalable, acceptable approach to culinary medicine in populations that are at increased risk for poor diet, such as parents with low income. The purpose of this study was to examine modern home cooking behavior and the role of new media from the perspective of parents with low income and identify implications for culinary medicine research. Twenty parents from 6- to 11-year-old children that qualify for free/reduced school lunch programs completed a survey and interview examining online cooking information seeking …

Cardiometabolic Indicators Of Cognitive Impairment In The Cameron County Hispanic Cohort, Fadi I Musfee, Seema Agarwal, Vahed Maroufy, Chelsea Liu, Joseph B Mccormick, Susan Fisher-Hoch, Sean I Savitz

Faculty, Staff and Student Publications

Background

Objective

Methods

Antenatal Prediction Of Early Cord Clamping Among Infants Born Extremely Preterm, Anup C Katheria, Rebecca A Dorner, William A Grobman, Matthew A Rysavy, Jenny Koo, Myra H Wyckoff, Grecio Sandoval, Sara B Demauro, Abhik Das, Henry C Lee, Michael Cotten, Laura Calvo, Shampa Saha

Faculty, Staff and Student Publications

Objective: To identify prenatal risk factors associated with early cord clamping (ECC) in infants born extremely preterm (22-28 weeks) and to use these factors to predict which infants have the highest risk of ECC.

Study design: Stepwise logistic regression and classification and regression tree analysis were performed to identify variables most associated with ECC and to build a parsimonious model to identify infants born preterm who are at the highest risk of ECC.

Results: There were 12 622 infants eligible for analysis (ECC, n = 8465 vs deferred cord clamping [DCC], n = 4157). In the classification and regression tree …

The Origin Of Hepatocellular Carcinoma Depends On Metabolic Zonation, Jason Guo, Roger Liang, Andrew Chung, Zhijie Li, Boyuan Li, Eric Chen, Lin Li, Jingjing Wang, Meng-Hsiung Hsieh, Ivy Xiangyi Fang, Benjamin Kroger, Yunguan Wang, Min Zhu, Xiongzhao Ren, Greg Mannino, Yuemeng Jia, Yonglong Wei, Stephen Moore, Daniel J Siegwart, Stephen S Chung, Zixi Wang, Tripti Sharma, Suman Komjeti, Yi Han, Purva Gopal, Guanghua Xiao, Tao Wang, Hao Zhu

Faculty, Staff and Student Publications

The origin of cancer is poorly understood because premalignant cells are rarely followed in their native environments. Although the spatial compartmentalization of metabolic functions is critical for proper liver function, it is unknown whether cancers arise from some zones but not others and whether there are metabolic determinants of cancer risk. Zone-specific, mosaic introduction of Ctnnb1 (catenin beta 1) and Arid2 (AT-rich interaction domain 2) mutations, commonly co-mutated genes in hepatocellular carcinoma (HCC), in mouse models showed that position and metabolic context determine clone fates. Ctnnb1/Arid2-driven cancers were much more likely to arise in zone 3. The …

Differentiation In The Human Urothelia Is Defined By Distinct Alternative Polyadenylation, Ninh B Le, Surbhi Sona, Briana Santo, Yi Zhang, Rosie Ou, R Allen Schweickart, Veena Kochat, William I Padron, Kunal Rai, Shih-Han Lee, Joo Mi Yi, Oliver Wessely, Byron H Lee, Angela H Ting

Faculty, Staff and Student Publications

Distinct epithelial cell states arise during differentiation, but mechanisms generating transcriptomic diversity among them remain poorly defined. The human ureter urothelium contains basal progenitor, intermediate cells, and terminally differentiated umbrella cells. Prior single-cell RNA sequencing revealed similar global gene expression profiles across these states, raising the question of how distinct identities emerge. Here, we show that alternative cleavage and polyadenylation (APA) introduces a major layer of transcriptomic diversity during urothelial differentiation, largely independent of changes in mRNA levels. Analysis of 13,544 urothelial cells identified hundreds of differentiation-associated APA events. Single-cell imaging revealed spatially specific APA patterns, and reporter assays demonstrated …

Differentiation In The Human Urothelia Is Defined By Distinct Alternative Polyadenylation, Ninh B Le, Surbhi Sona, Briana Santo, Yi Zhang, Rosie Ou, R Allen Schweickart, Veena Kochat, William I Padron, Kunal Rai, Shih-Han Lee, Joo Mi Yi, Oliver Wessely, Byron H Lee, Angela H Ting

Faculty, Staff and Student Publications

Distinct epithelial cell states arise during differentiation, but mechanisms generating transcriptomic diversity among them remain poorly defined. The human ureter urothelium contains basal progenitor, intermediate cells, and terminally differentiated umbrella cells. Prior single-cell RNA sequencing revealed similar global gene expression profiles across these states, raising the question of how distinct identities emerge. Here, we show that alternative cleavage and polyadenylation (APA) introduces a major layer of transcriptomic diversity during urothelial differentiation, largely independent of changes in mRNA levels. Analysis of 13,544 urothelial cells identified hundreds of differentiation-associated APA events. Single-cell imaging revealed spatially specific APA patterns, and reporter assays demonstrated …

Multilevel Analysis Of The Food And Physical Activity Environment And Adult Obesity Across U.S. Counties And States, Ann Mary Abraham, Michael D Swartz, Alexandra E Van Den Berg, Stephen H Linder

Faculty, Staff and Student Publications

Adult obesity rates have risen steadily across the United States over the past decade, with more than 40% of adults affected. Persistent geographic and demographic disparities exist in obesity prevalence across the nation. While prior research has examined individual or environmental associated factors of obesity, limited studies have addressed both physical activity and food environments across the nation using multilevel approaches. This cross-sectional ecological study (2014-2024) used a two-level random intercept model to assess the association between county- and state-level factors and adult obesity prevalence across over 3000 U.S. counties nested within 51 states. County-level associated factors included food insecurity, …

Metabolome Contribution To Sex Differences In The Link Between Alcohol Consumption And Type 2 Diabetes: A Prospective Analysis In The Hispanic Community Health Study/Study Of Latinos (Hchs/Sol), Brian Wang, Kai Luo, Wenyan Ma, Yanbo Zhang, Christina Cordero, Amber Pirzada, Martha Daviglus, Krista M Perreira, Bing Yu, Eric Boerwinkle, Robert C Kaplan, Qibin Qi

Faculty, Staff and Student Publications

Background: Light-to-moderate alcohol consumption has been linked to improved insulin resistance and lower type 2 diabetes (T2D) risk predominantly in females but not males. Potential mechanisms underlying this sex difference remain unclear.

Objective: This study evaluated associations of sex-specific alcohol-associated metabolomic signatures (AMSs) with insulin resistance and T2D risk in US Hispanic/Latino adults.

Methods: We analyzed serum metabolome data in the HCHS/SOL, a prospective, multicenter, community-based study of Hispanics/Latinos, aged 18 to 74 years old, enrolled from four U.S. metropolitan areas between 2008 and 2011. Sex-specific AMSs were developed using Elastic Net to identify serum metabolites uniquely associated with alcohol …

Proton Versus Photon Radiotherapy For Patients With Oropharyngeal Cancer In The Usa: A Multicentre, Randomised, Open-Label, Non-Inferiority Phase 3 Trial, Steven J Frank, Paul M Busse, J Jack Lee, David I Rosenthal, Mike Hernandez, David M Swanson, Adam S Garden, G Brandon Gunn, Samir H Patel, James W Snider, Daniel J Ma, Jason K Molitoris, Nancy Y Lee, Upendra Parvathaneni, Mark W Mcdonald, Noah S Kalman, Alexander Lin, Nasiruddin Mohammed, Christina Henson, Christian Hyde, Gopal K Bajaj, Sanford R Katz, Roi Dagan, William H Morrison, Jay P Reddy, C David Fuller, Shalin J Shah, Jack Phan, Gregory M Chronowski, Lauren Mayo, Erich M Sturgis, Renata Ferrarotto, Xiaorong R Zhu, Xiaodong Zhang, Li Wang, Katherine A Hutcheson, Adel K El-Naggar, Amy C Moreno, Anna Lee, Michael T Spiotto, Neil D Gross, Stephen Y Lai, Jay J Liao, Jonathan Paly, Zhongxing Liao, Robert L Foote

Faculty, Staff and Student Publications

Background: Radiotherapy is an integral component of treatment for oropharyngeal cancer. Toxicity from the current state-of-the-art photon radiotherapy, intensity-modulated radiation therapy (IMRT), has prompted the search for alternative, less toxic therapies. One such alternative that might de-intensify treatment is proton therapy. In this trial, we aimed to directly compare IMRT with intensity-modulated proton therapy (IMPT), both concurrent with systemic therapy, hypothesising comparable disease control and survival and lower toxicity.

Methods: This randomised, multicentre, open-label, non-inferiority, phase 3 trial was conducted in 21 sites (cancer centres or universities) in the USA. Patients (aged ≥18 years) with stage III or stage IV …