Diseases Commons^™

Risk Of Variceal Hemorrhage And Pretransplant Mortality In Children With Biliary Atresia, Lee M Bass, Wen Ye, Kieran Hawthorne, Daniel H Leung, Karen F Murray, Jean P Molleston, Rene Romero, Saul Karpen, Philip Rosenthal, Kathleen M Loomes, Kasper S Wang, Robert H Squires, Alexander Miethke, Vicky L Ng, Simon Horslen, M Kyle Jensen, Ronald J Sokol, John C Magee, Benjamin L Shneider, Children

Faculty, Staff and Students Publications

BACKGROUND AND AIMS: The natural history of gastroesophageal variceal hemorrhage (VH) in biliary atresia (BA) is not well characterized. We analyzed risk factors, incidence, and outcomes of VH in a longitudinal multicenter study.

APPROACH AND RESULTS: Participants enrolled in either an incident (Prospective Database of Infants with Cholestasis [PROBE]) or prevalent (Biliary Atresia Study of Infants and Children [BASIC]) cohort of BA were included. Variceal hemorrhage (VH) was defined based on gastrointestinal bleeding in the presence of varices accompanied by endoscopic or nontransplant surgical intervention. Cumulative incidence of VH and transplant-free survival was compared based on features of portal hypertension …

Outcomes For Endoscopic Submucosal Dissection Of Pathologically Staged T1b Esophageal Cancer: A Multicenter Study, Abel Joseph, Peter V Draganov, Fauze Maluf-Filho, Hiroyuki Aihara, Norio Fukami, Neil R Sharma, Amitabh Chak, Dennis Yang, Salmaan Jawaid, John Dumot, Omar Alaber, Tiffany Chua, Rituraj Singh, Lady Katherine Mejia-Perez, Ruishen Lyu, Xuefeng Zhang, Suneel Kamath, Sunguk Jang, Sudish Murthy, John Vargo, Amit Bhatt

Faculty, Staff and Students Publications

BACKGROUND AND AIMS: The outcomes of endoscopic submucosal dissection (ESD) for T1b esophageal cancer (EC) and its recurrence rates remain unclear in the West. Using a multicenter cohort, we evaluated technical outcomes and recurrence rates of ESD in the treatment of pathologically staged T1b EC.

METHODS: We included patients who underwent ESD of T1b EC at 7 academic tertiary referral centers in the United States (n = 6) and Brazil (n = 1). We analyzed demographic, procedural, and histopathologic characteristics and follow-up data. Time-to-event analysis was performed to evaluate recurrence rates.

RESULTS: Sixty-six patients with pathologically staged T1b EC after …

Sex Differences In Physical Activity Among Individuals With Type 2 Diabetes Across The Life Span: A Systematic Review And Meta-Analysis, Mary O Whipple, Ana J Pinto, Layla A Abushamat, Audrey Bergouignan, Kristina Chapman, Amy G Huebschmann, Kevin S Masters, Kristen J Nadeau, Rebecca L Scalzo, Irene E Schauer, Deirdre Rafferty, Jane E B Reusch, Judith G Regensteiner

Faculty, Staff and Students Publications

BACKGROUND: Physical activity (PA) is a cornerstone of type 2 diabetes mellitus (T2DM) treatment. Sex differences in PA behavior or barriers/facilitators to PA among individuals with T2DM are unclear.

PURPOSE: To summarize the evidence related to sex differences in participation in PA and barriers/facilitators to PA among individuals with T2DM across the life span.

DATA SOURCES: Systematic searches (CRD42021254246) were conducted with Ovid MEDLINE, Embase, Web of Science, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Allied and Complementary Medicine Database (AMED), APA PsychInfo, and SPORTDiscus.

STUDY SELECTION: We included studies with assessment of PA, sedentary behaviors (SB), or …

Dietary Fat Composition Shapes Bile Acid Metabolism And Severity Of Liver Injury In A Pig Model Of Pediatric Nafld, Rodrigo Manjarín, Kayla Dillard, Morgan Coffin, Gabriella V Hernandez, Victoria A Smith, Trista Noland-Lidell, Tanvi R Gehani, Hayden J Smart, Kevin Wheeler, Kimberly A Sprayberry, Mark S Edwards, Rob K Fanter, Hunter Glanz, Chad Immoos, Tasha M Santiago-Rodriguez, Jason M Blank, Douglas G Burrin, Brian D Piccolo, Mohammed Abo-Ismail, Michael R La Frano, Magdalena Maj

Faculty, Staff and Students Publications

The objective of this study was to investigate the effect of dietary fatty acid (FA) composition on bile acid (BA) metabolism in a pig model of NAFLD, by using a multiomics approach combined with histology and serum biochemistry. Thirty 20-day-old Iberian pigs pair-housed in pens were randomly assigned to receive 1 of 3 hypercaloric diets for 10 wk: 1) lard-enriched (LAR; n = 5 pens), 2) olive oil-enriched (OLI; n = 5), and 3) coconut oil-enriched (COC; n = 5). Animals were euthanized on week 10 after blood sampling, and liver, colon, and distal ileum (DI) were …

Quality Of Life, Illness Perceptions, And Parental Lived Experiences In Tango2-Related Metabolic Encephalopathy And Arrhythmias, Chaya N Murali, Seema R Lalani, Mahshid S Azamian, Christina Y Miyake, Hadley Stevens Smith

Faculty, Staff and Students Publications

TANGO2 disorder is a rare genetic disease with multi-system effects that causes episodic crises. Quality of life and psychosocial effects of this rare disease have not previously been studied. To examine health-related quality of life (HRQoL), illness perceptions, and lived experience, we surveyed 16 children and 31 parents of children with TANGO2 disorder identified via a disease-specific social media group and research foundation email distribution list. We assessed HRQoL by parent proxy-report and child self-report using the Pediatric Quality of Life Inventory (PedsQL™). Parental perceptions of their child's condition were assessed using the revised illness perceptions questionnaire adapted for TANGO2 …

Precision Diabetes: Lessons Learned From Maturity-Onset Diabetes Of The Young (Mody), Mustafa Tosur, Louis H Philipson

Faculty, Staff and Students Publications

Maturity-onset of diabetes of the young (MODY) are monogenic forms of diabetes characterized by early onset diabetes with autosomal dominant inheritance. Since its first description about six decades ago, there have been significant advancements in our understanding of MODY from clinical presentations to molecular diagnostics and therapeutic responses. The prevalence of MODY is estimated as at least 1.1-6.5% of the pediatric diabetes population with a high degree of geographic variability that might arise from several factors in the criteria used to ascertain cases. GCK-MODY, HNF1A-MODY, and HNF4A-MODY account for >90% of MODY cases. While some MODY forms do not require …

Extracellular Vesicles In Β Cell Biology: Role Of Lipids In Vesicle Biogenesis, Cargo, And Intercellular Signaling, Rebecca S Aguirre, Abhishek Kulkarni, Matthew W Becker, Xiaoyong Lei, Soumyadeep Sarkar, Sasanka Ramanadham, Edward A Phelps, Ernesto S Nakayasu, Emily K Sims, Raghavendra G Mirmira

Faculty, Staff and Students Publications

BACKGROUND: Type 1 diabetes (T1D) is a complex autoimmune disorder whose pathogenesis involves an intricate interplay between β cells of the pancreatic islet, other islet cells, and cells of the immune system. Direct intercellular communication within the islet occurs via cell surface proteins and indirect intercellular communication has traditionally been seen as occurring via secreted proteins (e.g., endocrine hormones and cytokines). However, recent literature suggests that extracellular vesicles (EVs) secreted by β cells constitute an additional and biologically important mechanism for transmitting signals to within the islet.

SCOPE OF REVIEW: This review summarizes the general mechanisms of EV formation, with …

Risk Score Using Demographic And Clinical Risk Factors Predicts Gastric Intestinal Metaplasia Risk In A Us Population, Mimi C Tan, Quynh Ho, Theresa H Nguyen, Yan Liu, Hashem B El-Serag, Aaron P Thrift

Faculty, Staff and Students Publications

BACKGROUND/AIMS: Screening for gastric intestinal metaplasia (GIM) may lead to early gastric cancer detection. We developed and validated a pre-endoscopy risk prediction model for detection of GIM based on patient-level risk factors in a U.S.

METHODS: We used data from 423 GIM cases and 1796 controls from a cross-sectional study among primary care and endoscopy clinic patients at the Houston VA. We developed the model using backwards stepwise regression and assessed discrimination using area under the receiver operating characteristic (AUROC). The model was internally validated using cross-validation and bootstrapping. The final expanded model was compared to a model including H. …

Virtual Global Health In Graduate Medical Education: A Systematic Review, Lisa Umphrey, Nora Lenhard, Suet Kam Lam, Nathaniel E Hayward, Shaina Hecht, Priya Agrawal, Amy Chambliss, Jessica Evert, Heather Haq, Stephanie M Lauden, George Paasi, Mary Schleicher, Megan Song Mchenry

Faculty, Staff and Students Publications

OBJECTIVES: To synthesize recent virtual global health education activities for graduate medical trainees, document gaps in the literature, suggest future study, and inform best practice recommendations for global health educators.

METHODS: We systematically reviewed articles published on virtual global health education activities from 2012-2021 by searching MEDLINE, EMBASE, Cochrane Library, ERIC, Scopus, Web of Science, and ProQuest Dissertations & Theses A&I. We performed bibliography review and search of conference and organization websites. We included articles about primarily virtual activities targeting for health professional trainees. We collected and qualitatively analyzed descriptive data about activity type, evaluation, audience, and drivers or barriers. …

Endophenotype Effect Sizes Support Variant Pathogenicity In Monogenic Disease Susceptibility Genes, Jennifer L Halford, Valerie N Morrill, Seung Hoan Choi, Sean J Jurgens, Giorgio Melloni, Nicholas A Marston, Lu-Chen Weng, Victor Nauffal, Amelia W Hall, Sophia Gunn, Christina A Austin-Tse, James P Pirruccello, Shaan Khurshid, Heidi L Rehm, Emelia J Benjamin, Eric Boerwinkle, Jennifer A Brody, Adolfo Correa, Brandon K Fornwalt, Namrata Gupta, Christopher M Haggerty, Stephanie Harris, Susan R Heckbert, Charles C Hong, Charles Kooperberg, Henry J Lin, Ruth J F Loos, Braxton D Mitchell, Alanna C Morrison, Wendy Post, Bruce M Psaty, Susan Redline, Kenneth M Rice, Stephen S Rich, Jerome I Rotter, Peter F Schnatz, Elsayed Z Soliman, Nona Sotoodehnia, Eugene K Wong, Nhlbi Trans-Omics For Precision Medicine (Topmed) Consortium, Marc S Sabatine, Christian T Ruff, Kathryn L Lunetta, Patrick T Ellinor, Steven A Lubitz

Faculty, Staff and Student Publications

Accurate and efficient classification of variant pathogenicity is critical for research and clinical care. Using data from three large studies, we demonstrate that population-based associations between rare variants and quantitative endophenotypes for three monogenic diseases (low-density-lipoprotein cholesterol for familial hypercholesterolemia, electrocardiographic QTc interval for long QT syndrome, and glycosylated hemoglobin for maturity-onset diabetes of the young) provide evidence for variant pathogenicity. Effect sizes are associated with pathogenic ClinVar assertions (P < 0.001 for each trait) and discriminate pathogenic from non-pathogenic variants (area under the curve 0.82-0.84 across endophenotypes). An effect size threshold of ≥ 0.5 times the endophenotype standard deviation nominates up to 35% of rare variants of uncertain significance or not in ClinVar in disease susceptibility genes with pathogenic potential. We propose that variant associations with quantitative endophenotypes for monogenic diseases can provide evidence supporting pathogenicity.

Comparative Risks Of Initial Aortic Events Associated With Genetic Thoracic Aortic Disease, Ellen S Regalado, Shaine A Morris, Alan C Braverman, Ellen M Hostetler, Julie De Backer, Ruosha Li, Reed E Pyeritz, Anji T Yetman, Elena Cervi, Sherene Shalhub, Richmond Jeremy, Scott Lemaire, Maral Ouzounian, Arturo Evangelista, Catherine Boileau, Guillaume Jondeau, Dianna M Milewicz

Faculty, Staff and Student Publications

BACKGROUND: Pathogenic variants in 11 genes predispose individuals to heritable thoracic aortic disease (HTAD), but limited data are available to stratify the risk for aortic events associated with these genes.

OBJECTIVES: This study sought to compare the risk of first aortic event, specifically thoracic aortic aneurysm surgery or an aortic dissection, among 7 HTAD genes and variant types within each gene.

METHODS: A retrospective cohort of probands and relatives with rare variants in 7 genes for HTAD (n = 1,028) was assessed for the risk of first aortic events based on the gene altered, pathogenic variant type, sex, proband status, …

Association Between Fall History And Gait, Balance, Physical Activity, Depression, Fear Of Falling, And Motor Capacity: A 6-Month Follow-Up Study, Catherine Park, Md Moin Uddin Atique, Ramkinker Mishra, Bijan Najafi

Center on Aging Staff Publications

Maintaining function in older adults is key to the quality of life and longevity. This study examined the potential impact of falls on accelerating further deterioration over time in gait, balance, physical activity, depression, fear of falling, and motor capacity in older adults. 163 ambulatory older adults (age = 76.5 ± 7.7 years) participated and were followed for 6 months. They were classified into fallers or non-fallers based on a history of falling within the past year. At baseline and 6 months, all participants were objectively assessed for gait, balance, and physical activity using wearable sensors. Additional assessments included psychosocial …

Rna Binding Protein Rbm46 Regulates Mitotic-To-Meiotic Transition In Spermatogenesis, Baomei Qian, Yang Li, Ruoyu Yan, Shenglin Han, Zhiwen Bu, Jie Gong, Bangjin Zheng, Zihan Yuan, Sen Ren, Qing He, Jinwen Zhang, Chen Xu, Ruilin Wang, Zheng Sun, Mingyan Lin, Jian Zhou, Lan Ye

Faculty, Staff and Students Publications

Meiosis entry during spermatogenesis requires reprogramming from mitotic to meiotic gene expression profiles. Transcriptional regulation has been extensively studied in meiosis entry, but gain of function for master transcription factors is insufficient to down-regulate mitotic genes. RNA helicase YTHDC2 and its partner MEIOC emerge as essential posttranscriptional regulators of meiotic entry. However, it is unclear what governs the RNA binding specificity of YTHDC2/MEIOC. Here, we identified RNA binding protein RBM46 as a component of the YTHDC2/MEIOC complex. Testis-specific Rbm46 knockout in mice causes infertility with defective mitotic-to-meiotic transition, phenocopying global Ythdc2 or Meioc knockout. RBM46 binds to 3′ UTR of …

Genome-Wide Interaction Analysis Identified Low-Frequency Variants With Sex Disparity In Lung Cancer Risk, Yafang Li, Xiangjun Xiao, Jianrong Li, Jinyoung Byun, Chao Cheng, Yohan Bossé, James Mckay, Demetrios Albanes, Stephen Lam, Adonina Tardon, Chu Chen, Stig E Bojesen, Maria T Landi, Mattias Johansson, Angela Risch, Heike Bickeböller, H-Erich Wichmann, David C Christiani, Gad Rennert, Susanne Arnold, Gary Goodman, John K Field, Michael P A Davies, Sanjay S Shete, Loic Le Marchand, Olle Melander, Hans Brunnström, Geoffrey Liu, Rayjean J Hung, Angeline S Andrew, Lambertus A Kiemeney, Hongbing Shen, Ryan Sun, Shan Zienolddiny, Kjell Grankvist, Mikael Johansson, Neil Caporaso, Dawn M Teare, Yun-Chul Hong, Philip Lazarus, Matthew B Schabath, Melinda C Aldrich, Ann G Schwartz, Ivan Gorlov, Kristen Purrington, Ping Yang, Yanhong Liu, Younghun Han, Joan E Bailey-Wilson, Susan M Pinney, Diptasri Mandal, James C Willey, Colette Gaba, Paul Brennan, Christopher I Amos, Integral-Ilcco Lung Cancer Consortium

Faculty, Staff and Students Publications

Differences by sex in lung cancer incidence and mortality have been reported which cannot be fully explained by sex differences in smoking behavior, implying existence of genetic and molecular basis for sex disparity in lung cancer development. However, the information about sex dimorphism in lung cancer risk is quite limited despite the great success in lung cancer association studies. By adopting a stringent two-stage analysis strategy, we performed a genome-wide gene-sex interaction analysis using genotypes from a lung cancer cohort including ~ 47 000 individuals with European ancestry. Three low-frequency variants (minor allele frequency < 0.05), rs17662871 [odds ratio (OR) = 0.71, P = 4.29×10-8); rs79942605 (OR = 2.17, P = 2.81×10-8) and rs208908 (OR = 0.70, P = 4.54×10-8) were identified with different risk effect of lung cancer between men and women. Further expression quantitative trait loci and functional annotation analysis suggested rs208908 affects lung cancer risk through differential regulation of Coxsackie virus and adenovirus receptor gene expression in lung tissues between men and women. Our study is one of the first studies to provide novel insights about the genetic and molecular basis for sex disparity in lung cancer development.

Adiposity, Insulin Resistance, Cardiorespiratory Fitness, And Bone Health In Hispanic Children, Reem S Shawar, Maurice Puyau, Roman Shypailo, Salma Musaad, Nancy F Butte, Fida Bacha

Faculty, Staff and Students Publications

CONTEXT: Childhood obesity disproportionately affects Hispanic youth. The skeletal system appears to be a target organ of the adverse effects of obesity. Yet, the relationship between adiposity and bone health in youth and the modulating factors are not well understood.

OBJECTIVE: This work aims to examine the relationship between adiposity, insulin resistance (IR), cardiorespiratory fitness (CRF), and bone mass in Hispanic youth.

METHODS: A total of 951 Hispanic youth (50% male), aged 4 to 19 years, participated in this cross-sectional design study from the Viva La Familia Study at Children's Nutrition Research Center. Bone mineral content (BMC) and density (BMD), …

A Case Series Of Children With Acute Hepatitis And Human Adenovirus Infection, L Helena Gutierrez Sanchez, Henry Shiau, Julia M Baker, Stephanie Saaybi, Markus Buchfellner, William Britt, Veronica Sanchez, Jennifer L Potter, L Amanda Ingram, David Kelly, Xiaoyan Lu, Stephanie Ayers-Millsap, Wesley G Willeford, Negar Rassaei, Julu Bhatnagar, Hannah Bullock, Sarah Reagan-Steiner, Ali Martin, Michael E Rogers, Anna M Banc-Husu, Sanjiv Harpavat, Daniel H Leung, Elizabeth A Moulton, Daryl M Lamson, Kirsten St George, Aron J Hall, Umesh Parashar, Adam Macneil, Jacqueline E Tate, Hannah L Kirking

Faculty, Staff and Students Publications

BACKGROUND: Human adenoviruses typically cause self-limited respiratory, gastrointestinal, and conjunctival infections in healthy children. In late 2021 and early 2022, several previously healthy children were identified with acute hepatitis and human adenovirus viremia.

METHODS: We used International Classification of Diseases, 10th Revision, codes to identify all children (<18 years of age) with hepatitis who were admitted to Children’s of Alabama hospital between October 1, 2021, and February 28, 2022; those with acute hepatitis who also tested positive for human adenovirus by whole-blood quantitative polymerase chain reaction (PCR) were included in our case series. Demographic, clinical, laboratory, and treatment data were obtained from medical records. Residual blood specimens were sent for diagnostic confirmation and human adenovirus typing.

RESULTS: A total of 15 children were identified with acute hepatitis - 6 (40%) who had hepatitis with an identified cause and 9 (60%) who had hepatitis without a known cause. Eight (89%) of the patients with hepatitis of unknown cause tested positive for human adenovirus. These 8 patients plus 1 …

The Prostate Cancer Androgen Receptor Cistrome In African American Men Associates With Upregulation Of Lipid Metabolism And Immune Response, Jacob E Berchuck, Elio Adib, Sarah Abou Alaiwi, Amit K Dash, Jin Na Shin, Dallin Lowder, Collin Mccoll, Patricia Castro, Ryan Carelli, Elisa Benedetti, Jenny Deng, Matthew Robertson, Sylvan C Baca, Connor Bell, Heather M Mcclure, Talal El Zarif, Matthew P Davidsohn, Gitanjali Lakshminarayanan, Kinza Rizwan, Darlene G Skapura, Sandra L Grimm, Christel M Davis, Erik A Ehli, Kaitlin M Kelleher, Ji-Heui Seo, Nicholas Mitsiades, Cristian Coarfa, Mark M Pomerantz, Massimo Loda, Michael Ittmann, Matthew L Freedman, Salma Kaochar

Faculty, Staff and Students Publications

African-American (AA) men are more likely to be diagnosed with and die from prostate cancer than European American (EA) men. Despite the central role of the androgen receptor (AR) transcription factor in prostate cancer, little is known about the contribution of epigenetics to observed racial disparities. We performed AR chromatin immunoprecipitation sequencing on primary prostate tumors from AA and EA men, finding that sites with greater AR binding intensity in AA relative to EA prostate cancer are enriched for lipid metabolism and immune response genes. Integration with transcriptomic and metabolomic data demonstrated coinciding upregulation of lipid metabolism gene expression and …

Gray And White Matter Abnormality In Patients With T2dm-Related Cognitive Dysfunction: A Systemic Review And Meta-Analysis, Teng Ma, Ze-Yang Li, Ying Yu, Bo Hu, Yu Han, Min-Hua Ni, Yu-Xiang Huang, Hao-Han Chen, Wen Wang, Lin-Feng Yan, Guang-Bin Cui

Faculty, Staff and Student Publications

Aims/hypothesis

Brain structure abnormality in patients with type 2 diabetes mellitus (T2DM)-related cognitive dysfunction (T2DM-CD) has been reported for decades in magnetic resonance imaging (MRI) studies. However, the reliable results were still unclear. This study aimed to make a systemic review and meta-analysis to find the significant and consistent gray matter (GM) and white matter (WM) alterations in patients with T2DM-CD by comparing with the healthy controls (HCs).

Methods

Published studies were systemically searched from PubMed, MEDLINE, Cochrane Library and Web of Science databases updated to November 14, 2021. Studies reporting abnormal GM or WM between patients with T2DM-CD and …

Genetic Variants In Cyp2b6 And Hsd17b12 Associated With Risk Of Squamous Cell Carcinoma Of The Head And Neck, Hongliang Liu, Guojun Li, Erich M Sturgis, Sanjay Shete, Kristina R Dahlstrom, Mulong Du, Christopher I Amos, David C Christiani, Philip Lazarus, Qingyi Wei

Faculty, Staff and Students Publications

Polycyclic aromatic hydrocarbons (PAH) and tobacco-specific nitrosamines (TSNA) metabolism-related genes play an important role in the development of cancers. We assessed the associations of genetic variants in genes involved in the metabolism of PAHs and TSNA with risk of squamous cell carcinoma of the head and neck (SCCHN) in European populations using two published genome-wide association study datasets. In the single-locus analysis, we identified two SNPs (rs145533669 and rs35246205) in CYP2B6 to be associated with risk of SCCHN (P = 1.57 × 10

Targeting Hyaluronic Acid Synthase-3 (Has3) For The Treatment Of Advanced Renal Cell Carcinoma, Xiaohan Xu, Kyle L Poulsen, Lijuan Wu, Shan Liu, Tatsunori Miyata, Qiaoling Song, Qingda Wei, Chenyang Zhao, Chunhua Lin, Jinbo Yang

Faculty, Staff and Student Publications

Non-alcohol-associated fatty liver/steatohepatitis (NAFL/NASH) has become the leading cause of liver disease worldwide. NASH, an advanced form of NAFL, can be progressive and more susceptible to developing cirrhosis and hepatocellular carcinoma. Currently, lifestyle interventions are the most essential and effective strategies for preventing and controlling NAFL without the development of fibrosis. While there are still limited appropriate drugs specifically to treat NAFL/NASH, growing progress is being seen in elucidating the pathogenesis and identifying therapeutic targets. In this review, we discussed recent developments in etiology and prospective therapeutic targets, as well as pharmacological candidates in pre/clinical trials and patents, with a …

Muscle And Adipose Tissue Segmentations At The Third Cervical Vertebral Level In Patients With Head And Neck Cancer, Kareem A Wahid, Brennan Olson, Rishab Jain, Aaron J Grossberg, Dina El-Habashy, Cem Dede, Vivian Salama, Moamen Abobakr, Abdallah S R Mohamed, Renjie He, Joel Jaskari, Jaakko Sahlsten, Kimmo Kaski, Clifton D Fuller, Mohamed A Naser

Faculty, Staff and Student Publications

The accurate determination of sarcopenia is critical for disease management in patients with head and neck cancer (HNC). Quantitative determination of sarcopenia is currently dependent on manually-generated segmentations of skeletal muscle derived from computed tomography (CT) cross-sectional imaging. This has prompted the increasing utilization of machine learning models for automated sarcopenia determination. However, extant datasets currently do not provide the necessary manually-generated skeletal muscle segmentations at the C3 vertebral level needed for building these models. In this data descriptor, a set of 394 HNC patients were selected from The Cancer Imaging Archive, and their skeletal muscle and adipose tissue was …

Association Between Social Vulnerability Index And Cardiovascular Disease: A Behavioral Risk Factor Surveillance System Study, Vardhmaan Jain, Mahmoud Al Rifai, Safi U Khan, Ankur Kalra, Fatima Rodriguez, Zainab Samad, Yashashwi Pokharel, Arunima Misra, Laurence S Sperling, Jamal S Rana, Waqas Ullah, Ankit Medhekar, Salim S Virani

Faculty, Staff and Students Publications

Background Social and environmental factors play an important role in the rising health care burden of cardiovascular disease. The Centers for Disease Control and Prevention developed the Social Vulnerability Index (SVI) from US census data as a tool for public health officials to identify communities in need of support in the setting of a hazardous event. SVI (ranging from a least vulnerable score of 0 to a most vulnerable score of 1) ranks communities on 15 social factors including unemployment, minoritized groups status, and disability, and groups them under 4 broad themes: socioeconomic status, housing and transportation, minoritized groups, and …

3’Utr Shortening Of Has2 Promotes Hyaluronan Hyper-Synthesis And Bioenergetic Dysfunction In Pulmonary Hypertension, Victor Tseng, Scott D Collum, Ayed Allawzi, Kathryn Crotty, Samantha Yeligar, Aaron Trammell, M Ryan Smith, Bum-Yong Kang, Roy L Sutliff, Jennifer L Ingram, Soma S S K Jyothula, Rajarajan A Thandavarayan, Howard J Huang, Eva S Nozik, Eric J Wagner, C Michael Hart, Harry Karmouty-Quintana

Faculty, Staff and Student Publications

Pulmonary hypertension (PH) comprises a diverse group of disorders that share a common pathway of pulmonary vascular remodeling leading to right ventricular failure. Development of anti-remodeling strategies is an emerging frontier in PH therapeutics that requires a greater understanding of the interactions between vascular wall cells and their extracellular matrices. The ubiquitous matrix glycan, hyaluronan (HA), is markedly elevated in lungs from patients and experimental models with PH. Herein, we identified HA synthase-2 (HAS2) in the pulmonary artery smooth muscle cell (PASMC) layer as a predominant locus of HA dysregulation. HA upregulation involves depletion of NUDT21, a master regulator of …

Placental Pathology In Spontaneous And Iatrogenic Preterm Birth: Different Entities With Unique Pathologic Features, Lucy T Brink, Drucilla J Roberts, Colleen A Wright, Daan G Nel, Pawel T Schubert, Theonia K Boyd, David R Hall, Hein Odendaal

Faculty, Staff and Student Publications

INTRODUCTION: Placental pathology is an important contributor to the understanding of preterm birth and reveals major differences between spontaneous preterm birth (SPTB) and iatrogenic preterm birth (IPTB). The aim of this study was to investigate these relationships.

METHODS: Research midwives collected placentas from 1101 women with singleton pregnancies who were enrolled in the Safe Passage Study. Trained pathology technologists prepared and processed placenta specimens for macroscopic and microscopic examination by designated pathologists. Statistical analyses were done with STATISTICA version 13.

RESULTS: In SPTB we found more cases of accelerated villous maturation; however, the other features of maternal vascular malperfusion (MVM) …

International Prevalence And Mechanisms Of Sars-Cov-2 In Childhood Arterial Ischemic Stroke During The Covid-19 Pandemic, Lauren A Beslow, Shannon C Agner, Jonathan D Santoro, Dipak Ram, Jenny L Wilson, Dana Harrar, Brian Appavu, Stuart M Fraser, Thomas Rossor, Marcela D Torres, Manoëlle Kossorotoff, Yenny C Zuñiga Zambrano, Marta Hernández-Chávez, Sahar M A Hassanein, Dimitrios Zafeiriou, Michael M Dowling, Ilona Kopyta, Nicholas V Stence, Timothy J Bernard, Nomazulu Dlamini

Faculty, Staff and Student Publications

BACKGROUND: Data from the early pandemic revealed that 0.62% of children hospitalized with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had an acute arterial ischemic stroke (AIS). In a larger cohort from June 2020 to December 2020, we sought to determine whether our initial point estimate was stable as the pandemic continued and to understand radiographic and laboratory data that may clarify mechanisms of pediatric AIS in the setting of SARS-CoV-2.

METHODS: We surveyed international sites with pediatric stroke expertise to determine numbers of hospitalized SARS-CoV-2 patients <18 >years, numbers of incident AIS cases among children (29 days to <18 >years), frequency …

Advances In Head And Neck Cancer Pain, Y Ye, D D Jensen, C T Viet, H L Pan, W M Campana, M Amit, M D Boada

Faculty, Staff and Student Publications

Head and neck cancer (HNC) affects over 890,000 people annually worldwide and has a mortality rate of 50%. Aside from poor survival, HNC pain impairs eating, drinking, and talking in patients, severely reducing quality of life. Different pain phenotype in patients (allodynia, hyperalgesia, and spontaneous pain) results from a combination of anatomical, histopathological, and molecular differences between cancers. Poor pathologic features (e.g., perineural invasion, lymph node metastasis) are associated with increased pain. The use of syngeneic/immunocompetent animal models, as well as a new mouse model of perineural invasion, provides novel insights into the pathobiology of HNC pain. Glial and immune …

The Geriatric Nutritional Risk Index As A Predictor Of Complications In Geriatric Trauma Patients: Author Reply In Response To: “The Admission Serum Level Of Albumin Cannot Thoroughly Represent The Nutritional Status Of Trauma Patients”, Heather R Kregel, Patrick B Murphy, Mina Attia, David E Meyer, Rachel S Morris, Ezenwa C Onyema, Sasha D Adams, Charles E Wade, John A Harvin, Lillian S Kao, Thaddeus J Puzio

Faculty, Staff and Student Publications

BACKGROUND: Malnutrition is associated with increased morbidity and mortality after trauma. The Geriatric Nutritional Risk Index (GNRI) is a validated scoring system used to predict the risk of complications related to malnutrition in nontrauma patients. We hypothesized that GNRI is predictive of worse outcomes in geriatric trauma patients.

METHODS: This was a single-center retrospective study of trauma patients 65 years or older admitted in 2019. Geriatric Nutritional Risk Index was calculated based on admission albumin level and ratio of actual body weight to ideal body weight. Groups were defined as major risk (GNRI98). The primary outcome was mortality. Secondary outcomes …

Tp53-Altered Chronic Lymphocytic Leukemia Treated With Firstline Bruton’S Tyrosine Kinase Inhibitor-Based Therapy: A Retrospective Analysis, Hua-Jay J Cherng, Raamis Khwaja, Rashmi Kanagal-Shamanna, Guilin Tang, Jan Burger, Philip Thompson, Alessandra Ferrajoli, Zeev Estrov, Koji Sasaki, Deepa Sampath, Xuemei Wang, Hagop Kantarjian, Michael Keating, William G Wierda, Nitin Jain

Faculty, Staff and Student Publications

Long-term follow up of prospective studies has shown that continuous Bruton's tyrosine kinase inhibitor (BTKi) therapy leads to durable remissions in previously untreated patients with TP53-altered chronic lymphocytic leukemia (CLL); however, it is unknown how variant allele frequency (VAF) of TP53 mutation (TP53-m) or percentage of cells with deletion of chromosome 17p [del(17p)] influences efficacy of firstline BTKi. We performed a retrospective analysis of 130 patients with CLL with baseline del(17p) and/or TP53-m treated with BTKi with or without the BCL2 inhibitor venetoclax (VEN) and with or without CD20 antibody in the firstline setting. A total of 104/130 (80%) patients …

A Large-Scale Genome-Wide Gene-Gene Interaction Study Of Lung Cancer Susceptibility In Europeans With A Trans-Ethnic Validation In Asians, Ruyang Zhang, Sipeng Shen, Yongyue Wei, Ying Zhu, Yi Li, Jiajin Chen, Jinxing Guan, Zoucheng Pan, Yuzhuo Wang, Meng Zhu, Junxing Xie, Xiangjun Xiao, Dakai Zhu, Yafang Li, Demetrios Albanes, Maria Teresa Landi, Neil E Caporaso, Stephen Lam, Adonina Tardon, Chu Chen, Stig E Bojesen, Mattias Johansson, Angela Risch, Heike Bickeböller, H-Erich Wichmann, Gadi Rennert, Susanne Arnold, Paul Brennan, James D Mckay, John K Field, Sanjay S Shete, Loic Le Marchand, Geoffrey Liu, Angeline S Andrew, Lambertus A Kiemeney, Shan Zienolddiny-Narui, Annelie Behndig, Mikael Johansson, Angela Cox, Philip Lazarus, Matthew B Schabath, Melinda C Aldrich, Juncheng Dai, Hongxia Ma, Yang Zhao, Zhibin Hu, Rayjean J Hung, Christopher I Amos, Hongbing Shen, Feng Chen, David C Christiani

Faculty, Staff and Students Publications

INTRODUCTION: Although genome-wide association studies have been conducted to investigate genetic variation of lung tumorigenesis, little is known about gene-gene (G × G) interactions that may influence the risk of non-small cell lung cancer (NSCLC).

METHODS: Leveraging a total of 445,221 European-descent participants from the International Lung Cancer Consortium OncoArray project, Transdisciplinary Research in Cancer of the Lung and UK Biobank, we performed a large-scale genome-wide G × G interaction study on European NSCLC risk by a series of analyses. First, we used BiForce to evaluate and rank more than 58 billion G × G interactions from 340,958 single-nucleotide polymorphisms …

Immune Phenotype Of The Cd4+ T Cells In The Aged Lymphoid Organs And Lacrimal Glands, Claudia M Trujillo-Vargas, Kelsey E Mauk, Humberto Hernandez, Rodrigo G De Souza, Zhiyuan Yu, Jeremias G Galletti, Jana Dietrich, Friedrich Paulsen, Cintia S De Paiva

Faculty, Staff and Students Publications

Aging is associated with a massive infiltration of T lymphocytes in the lacrimal gland. Here, we aimed to characterize the immune phenotype of aged CD4+ T cells in this tissue as compared with lymphoid organs. To perform this, we sorted regulatory T cells (Tregs, CD4+CD25+GITR+) and non-Tregs (CD4+CD25negGITRneg) in lymphoid organs from female C57BL/6J mice and subjected these cells to an immunology NanoString® panel. These results were confirmed by flow cytometry, live imaging, and tissue immunostaining in the lacrimal gland. Importantly, effector T helper 1 (Th1) genes were highly upregulated on aged Tregs, including the master regulator Tbx21. Among …