Digital Commons Network^™

Associations Of Steps Per Day And Step Intensity With The Risk Of Diabetes: The Hispanic Community Health Study / Study Of Latinos (Hchs/Sol)., Carmen C. Cuthbertson, Christopher C. Moore, Daniela Sotres-Alvarez, Gerardo Heiss, Carmen R. Isasi, Yasmin Mossavar-Rahmani, Jordan A. Carlson, Linda C. Gallo, Maria M. Llabre, Olga L. Garcia-Bedoya, David Goldsztajn Farelo, Kelly R. Evenson

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Higher levels of moderate-to-vigorous physical activity have been associated with a lower risk of diabetes, but less is known about how daily step counts (steps/day) are associated with diabetes risk. Therefore, we examined the association of steps/day and step intensity with incident diabetes.

METHODS: We included 6634 adults from the population-based prospective cohort Hispanic Community Health Study/Study of Latinos (HCHS/SOL) (2008-2017). Cox proportional hazard models that accounted for complex survey design and sampling weights were used to estimate the association of baseline accelerometer-assessed steps/day and step intensity with 6-year risk of incident diabetes as hazard ratios (HR) and 95% …

Classification Of Human Chronic Inflammatory Skin Disease Based On Single-Cell Immune Profiling, Yale Liu, Hao Wang, Mark Taylor, Christopher Cook, Alejandra Martínez-Berdeja, Jeffrey P North, Paymann Harirchian, Ashley A Hailer, Zijun Zhao, Ruby Ghadially, Roberto R Ricardo-Gonzalez, Roy C Grekin, Theodora M Mauro, Esther Kim, Jaehyuk Choi, Elizabeth Purdom, Raymond J Cho, Jeffrey B Cheng

Staff and Researcher Publications

Inflammatory conditions represent the largest class of chronic skin disease, but the molecular dysregulation underlying many individual cases remains unclear. Single-cell RNA sequencing (scRNA-seq) has increased precision in dissecting the complex mixture of immune and stromal cell perturbations in inflammatory skin disease states. We single-cell-profiled CD45+ immune cell transcriptomes from skin samples of 31 patients (7 atopic dermatitis, 8 psoriasis vulgaris, 2 lichen planus (LP), 1 bullous pemphigoid (BP), 6 clinical/histopathologically indeterminate rashes, and 7 healthy controls). Our data revealed active proliferative expansion of the Treg and Trm components and universal T cell exhaustion in human rashes, with a relative …

Convection Enhanced Delivery Of The Oncolytic Adenovirus Delta24-Rgd In Patients With Recurrent Gbm: A Phase I Clinical Trial Including Correlative Studies, Erik H P Van Putten, Anne Kleijn, Victor W Van Beusechem, David Noske, Cor H J Lamers, Anna L De Goede, Sander Idema, Daphna Hoefnagel, Jenneke J Kloezeman, Juan Fueyo, Frederick F Lang, Charlotte E Teunissen, René M Vernhout, Cathy Bakker, Winald Gerritsen, David T Curiel, Arnold Vulto, Martine L M Lamfers, Clemens M F Dirven

Faculty, Staff and Student Publications

Purpose: Testing safety of Delta24-RGD (DNX-2401), an oncolytic adenovirus, locally delivered by convection enhanced delivery (CED) in tumor and surrounding brain of patients with recurrent glioblastoma.

Patients and methods: Dose-escalation phase I study with 3+3 cohorts, dosing 107 to 1 × 1011 viral particles (vp) in 20 patients. Besides clinical parameters, adverse events, and radiologic findings, blood, cerebrospinal fluid (CSF), brain interstitial fluid, and excreta were sampled over time and analyzed for presence of immune response, viral replication, distribution, and shedding.

Results: Of 20 enrolled patients, 19 received the oncolytic adenovirus Delta24-RGD, which was found to be safe and feasible. …

Convection Enhanced Delivery Of The Oncolytic Adenovirus Delta24-Rgd In Patients With Recurrent Gbm: A Phase I Clinical Trial Including Correlative Studies, Erik H P Van Putten, David T Curiel, Et Al

Open Access Publications

PURPOSE: Testing safety of Delta24-RGD (DNX-2401), an oncolytic adenovirus, locally delivered by convection enhanced delivery (CED) in tumor and surrounding brain of patients with recurrent glioblastoma.

PATIENTS AND METHODS: Dose-escalation phase I study with 3+3 cohorts, dosing 107 to 1 × 1011 viral particles (vp) in 20 patients. Besides clinical parameters, adverse events, and radiologic findings, blood, cerebrospinal fluid (CSF), brain interstitial fluid, and excreta were sampled over time and analyzed for presence of immune response, viral replication, distribution, and shedding.

RESULTS: Of 20 enrolled patients, 19 received the oncolytic adenovirus Delta24-RGD, which was found to be safe and feasible. …

Targeting Non-Coding Rnas To Overcome Cancer Therapy Resistance, Baoqing Chen, Mihnea P Dragomir, Chen Yang, Qiaoqiao Li, David Horst, George A Calin

Faculty, Staff and Student Publications

It is now well known that non-coding RNAs (ncRNAs), rather than protein-coding transcripts, are the preponderant RNA transcripts. NcRNAs, particularly microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), are widely appreciated as pervasive regulators of multiple cancer hallmarks such as proliferation, apoptosis, invasion, metastasis, and genomic instability. Despite recent discoveries in cancer therapy, resistance to chemotherapy, radiotherapy, targeted therapy, and immunotherapy continue to be a major setback. Recent studies have shown that ncRNAs also play a major role in resistance to different cancer therapies by rewiring essential signaling pathways. In this review, we present the intricate mechanisms through …

Identification Of Small Regions Of Overlap From Copy Number Variable Regions In Patients With Hypospadias, Carter H Scott, Ina E Amarillo

Open Access Publications

Hypospadias is a common form of congenital atypical sex development that is often associated with other congenital comorbidities. Many genes have been associated with the condition, most commonly single sequence variations. Further investigations of recurrent and overlapping copy number variations (CNVs) have resulted in the identification of genes and chromosome regions associated with various conditions, including differences of sex development (DSD). In this retrospective study, we investigated the DECIPHER database, as well as an internal institutional database, to identify small recurrent CNVs among individuals with isolated and syndromic hypospadias. We further investigated these overlapping recurrent CNVs to identify 75 smallest …

Distinct Molecular And Immune Hallmarks Of Inflammatory Arthritis Induced By Immune Checkpoint Inhibitors For Cancer Therapy, Sang T Kim, Yanshuo Chu, Mercy Misoi, Maria E Suarez-Almazor, Jean H Tayar, Huifang Lu, Maryam Buni, Jordan Kramer, Emma Rodriguez, Zulekha Hussain, Sattva S Neelapu, Jennifer Wang, Amishi Y Shah, Nizar M Tannir, Matthew T Campbell, Don L Gibbons, Tina Cascone, Charles Lu, George R Blumenschein, Mehmet Altan, Bora Lim, Vincente Valero, Monica E Loghin, Janet Tu, Shannon N Westin, Aung Naing, Guillermo Garcia-Manero, Noha Abdel-Wahab, Hussein A Tawbi, Patrick Hwu, Isabella C Glitza Oliva, Michael A Davies, Sapna P Patel, Jun Zou, Andrew Futreal, Adi Diab, Linghua Wang, Roza Nurieva

Faculty, Staff and Student Publications

Immune checkpoint inhibitors are associated with immune-related adverse events (irAEs), including arthritis (arthritis-irAE). Management of arthritis-irAE is challenging because immunomodulatory therapy for arthritis should not impede antitumor immunity. Understanding of the mechanisms of arthritis-irAE is critical to overcome this challenge, but the pathophysiology remains unknown. Here, we comprehensively analyze peripheral blood and/or synovial fluid samples from 20 patients with arthritis-irAE, and unmask a prominent Th1-CD8

Cngpld: Case-Control Copy-Number Analysis Using Gaussian Process Latent Difference, David J H Shih, Ruoxing Li, Peter Müller, W Jim Zheng, Kim-Anh Do, Shiaw-Yih Lin, Scott L Carter

Faculty, Staff and Student Publications

MOTIVATION: Cross-sectional analyses of primary cancer genomes have identified regions of recurrent somatic copy-number alteration, many of which result from positive selection during cancer formation and contain driver genes. However, no effective approach exists for identifying genomic loci under significantly different degrees of selection in cancers of different subtypes, anatomic sites or disease stages.

RESULTS: CNGPLD is a new tool for performing case-control somatic copy-number analysis that facilitates the discovery of differentially amplified or deleted copy-number aberrations in a case group of cancer compared with a control group of cancer. This tool uses a Gaussian process statistical framework in order …

Human Pancreatic Microenvironment Promotes Β-Cell Differentiation Via Non-Canonical Wnt5a/Jnk And Bmp Signaling, Jolanta Chmielowiec, Wojciech J Szlachcic, Diane Yang, Marissa A Scavuzzo, Katrina Wamble, Alejandro Sarrion-Perdigones, Omaima M Sabek, Koen J T Venken, Malgorzata Borowiak

Faculty, Staff and Students Publications

In vitro derivation of pancreatic β-cells from human pluripotent stem cells holds promise as diabetes treatment. Despite recent progress, efforts to generate physiologically competent β-cells are still hindered by incomplete understanding of the microenvironment's role in β-cell development and maturation. Here, we analyze the human mesenchymal and endothelial primary cells from weeks 9-20 fetal pancreas and identify a time point-specific microenvironment that permits β-cell differentiation. Further, we uncover unique factors that guide in vitro development of endocrine progenitors, with WNT5A markedly improving human β-cell differentiation. WNT5A initially acts through the non-canonical (JNK/c-JUN) WNT signaling and cooperates with Gremlin1 to inhibit …

Selective Hypermethylation Is Evident In Small Intestine Samples From Infants With Necrotizing Enterocolitis, Misty Good, Tianjiao Chu, Patricia Shaw, Lila S Nolan, Joseph Wrobleski, Carlos Castro, Qingqing Gong, Olivia Dewitt, David N Finegold, David Peters

2020-Current year OA Pubs

OBJECTIVE: Necrotizing enterocolitis (NEC) is the most common and lethal gastrointestinal disease affecting preterm infants. NEC develops suddenly and is characterized by gut barrier destruction, an inflammatory response, intestinal necrosis and multi-system organ failure. There is currently no method for early NEC detection, and the pathogenesis of NEC remains unclear.

DESIGN: To further understand the molecular mechanisms that support NEC, we used solution phase hybridization and next-generation DNA sequencing of bisulfite converted DNA to perform targeted genome-wide analysis of DNA methylation at high read depth.

RESULTS: We found that ileal samples from surgical NEC infants (n = 5) exist in …

An Imaging Biomarker Of Tumor-Infiltrating Lymphocytes To Risk-Stratify Patients With Hpv-Associated Oropharyngeal Cancer, Germán Corredor, Wade Thorstad, Et Al.

2020-Current year OA Pubs

BACKGROUND: Human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) has excellent control rates compared to nonvirally associated OPSCC. Multiple trials are actively testing whether de-escalation of treatment intensity for these patients can maintain oncologic equipoise while reducing treatment-related toxicity. We have developed OP-TIL, a biomarker that characterizes the spatial interplay between tumor-infiltrating lymphocytes (TILs) and surrounding cells in histology images. Herein, we sought to test whether OP-TIL can segregate stage I HPV-associated OPSCC patients into low-risk and high-risk groups and aid in patient selection for de-escalation clinical trials.

METHODS: Association between OP-TIL and patient outcome was explored on whole slide …

Role Of Drosophila In Human Disease Research 2.0, Masamitsu Yamaguchi, Shinya Yamamoto

Duncan NRI Faculty and Staff Publications

The fruit fly Drosophila melanogaster is a highly tractable animal model to study various human diseases [1]. Many biological pathways are highly conserved between humans and flies, and nearly 85% of human disease-causing genes have homologs in Drosophila. Drosophila has a relatively short life span and produces a large number of progenies, allowing researchers to perform rapid experiments that can easily be reproduced, allowing reliable statistical analyses of biological data. In addition, there are fewer ethical concerns when using Drosophila for biomedical research compared to mammalian models. Importantly, sophisticated genetic experiments can be designed to answer complicated …

An Imaging Biomarker Of Tumor-Infiltrating Lymphocytes To Risk-Stratify Patients With Hpv-Associated Oropharyngeal Cancer, Germán Corredor, Paula Toro, Can Koyuncu, Cheng Lu, Christina Buzzy, Kaustav Bera, Pingfu Fu, Mitra Mehrad, Kim A Ely, Mojgan Mokhtari, Kailin Yang, Deborah Chute, David J Adelstein, Lester D R Thompson, Justin A Bishop, Farhoud Faraji, Wade Thorstad, Patricia Castro, Vlad Sandulache, Shlomo A Koyfman, James S Lewis, Anant Madabhushi

Faculty, Staff and Students Publications

BACKGROUND: Human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) has excellent control rates compared to nonvirally associated OPSCC. Multiple trials are actively testing whether de-escalation of treatment intensity for these patients can maintain oncologic equipoise while reducing treatment-related toxicity. We have developed OP-TIL, a biomarker that characterizes the spatial interplay between tumor-infiltrating lymphocytes (TILs) and surrounding cells in histology images. Herein, we sought to test whether OP-TIL can segregate stage I HPV-associated OPSCC patients into low-risk and high-risk groups and aid in patient selection for de-escalation clinical trials.

METHODS: Association between OP-TIL and patient outcome was explored on whole slide …

Racial Disparities In Prostate Cancer: A Complex Interplay Between Socioeconomic Inequities And Genomics, Dallin Lowder, Kinza Rizwan, Collin Mccoll, Alyssa Paparella, Michael Ittmann, Nicholas Mitsiades, Salma Kaochar

Faculty, Staff and Students Publications

The largest US cancer health disparity exists in prostate cancer, with Black men having more than a two-fold increased risk of dying from prostate cancer compared to all other races. This disparity is a result of a complex network of factors including socioeconomic status (SES), environmental exposures, and genetics/biology. Inequity in the US healthcare system has emerged as a major driver of disparity in prostate cancer outcomes and has raised concerns that the actual incidence rates may be higher than current estimates. However, emerging studies argue that equalizing healthcare access will not fully eliminate racial health disparities and highlight the …

The Efficacy Of Low-Dose Aspirin In Pregnancy Among Women In Malaria-Endemic Countries, Melissa Bauserman, Sequoia I Leuba, Jennifer Hemingway-Foday, Tracy L Nolen, Janet Moore, Elizabeth M Mcclure, Adrien Lokangaka, Antoinette Tsehfu, Jackie Patterson, Edward A Liechty, Fabian Esamai, Waldemar A Carlo, Elwyn Chomba, Robert L Goldenberg, Sarah Saleem, Saleem Jessani, Marion Koso-Thomas, Matthew Hoffman, Richard Derman, Steven R Meshnick, Carl L Bose

Department of Medicine Faculty Papers

Background: Low dose aspirin (LDA) is an effective strategy to reduce preterm birth. However, LDA might have differential effects globally, based on the etiology of preterm birth. In some regions, malaria in pregnancy could be an important modifier of LDA on birth outcomes and anemia.

Methods: This is a sub-study of the ASPIRIN trial, a multi-national, randomized, placebo controlled trial evaluating LDA effect on preterm birth. We enrolled a convenience sample of women in the ASPIRIN trial from the Democratic Republic of Congo (DRC), Kenya and Zambia. We used quantitative polymerase chain reaction to detect malaria. We calculated crude prevalence …

Meta-Analysis Of Genome-Wide Association Studies Identifies Ancestry-Specific Associations Underlying Circulating Total Tau Levels, Chloé Sarnowski, Mohsen Ghanbari, Joshua C Bis, Mark Logue, Myriam Fornage, Aniket Mishra, Shahzad Ahmad, Alexa S Beiser, Eric Boerwinkle, Vincent Bouteloup, Vincent Chouraki, L Adrienne Cupples, Vincent Damotte, Charles S Decarli, Anita L Destefano, Luc Djoussé, Alison E Fohner, Carol E Franz, Tiffany F Kautz, Jean-Charles Lambert, Michael J Lyons, Thomas H Mosley, Kenneth J Mukamal, Matthew P Pase, Eliana C Portilla Fernandez, Robert A Rissman, Claudia L Satizabal, Ramachandran S Vasan, Amber Yaqub, Stephanie Debette, Carole Dufouil, Lenore J Launer, William S Kremen, William T Longstreth, M Arfan Ikram, Sudha Seshadri

Faculty, Staff and Student Publications

Circulating total-tau levels can be used as an endophenotype to identify genetic risk factors for tauopathies and related neurological disorders. Here, we confirmed and better characterized the association of the 17q21 MAPT locus with circulating total-tau in 14,721 European participants and identified three novel loci in 953 African American participants (4q31, 5p13, and 6q25) at P < 5 × 10-8. We additionally detected 14 novel loci at P < 5 × 10-7, specific to either Europeans or African Americans. Using whole-exome sequence data in 2,279 European participants, we identified ten genes associated with circulating total-tau when aggregating rare variants. Our genetic study sheds light on genes reported to be associated with neurological diseases including stroke, Alzheimer's, and Parkinson's (F5, MAP1B, and BCAS3), with Alzheimer's pathological hallmarks (ADAMTS12, IL15, and FHIT), or with an important function in the brain (PARD3, ELFN2, UBASH3B, SLIT3, and NSD3), and suggests that the genetic architecture of circulating total-tau may differ according to ancestry.

Exploiting 4–1bb Immune Checkpoint To Enhance The Efficacy Of Oncolytic Virotherapy For Diffuse Intrinsic Pontine Gliomas, Virginia Laspidea, Montserrat Puigdelloses, Sara Labiano, Lucía Marrodán, Marc Garcia-Moure, Marta Zalacain, Marisol Gonzalez-Huarriz, Naiara Martínez-Vélez, Iker Ausejo-Mauleon, Daniel De La Nava, Guillermo Herrador-Cañete, Javier Marco-Sanz, Elisabeth Guruceaga, Carlos E De Andrea, María Villalba, Oren Becher, Massimo Squatrito, Verónica Matía, Jaime Gállego Pérez-Larraya, Ana Patiño-García, Sumit Gupta, Candelaria Gomez-Manzano, Juan Fueyo, Marta M Alonso

Faculty, Staff and Student Publications

Diffuse intrinsic pontine gliomas (DIPGs) are aggressive pediatric brain tumors, and patient survival has not changed despite many therapeutic efforts, emphasizing the urgent need for effective treatments. Here, we evaluated the anti-DIPG effect of the oncolytic adenovirus Delta-24-ACT, which was engineered to express the costimulatory ligand 4-1BBL to potentiate the antitumor immune response of the virus. Delta-24-ACT induced the expression of functional 4-1BBL on the membranes of infected DIPG cells, which enhanced the costimulation of CD8+ T lymphocytes. In vivo, Delta-24-ACT treatment of murine DIPG orthotopic tumors significantly improved the survival of treated mice, leading to long-term survivors that developed …

In-Depth Analysis Of Sars-Cov-2-Specific T Cells Reveals Diverse Differentiation Hierarchies In Vaccinated Individuals, Li Li, Muharrem Muftuoglu, Shaoheng Liang, Mahesh Basyal, Jiangxing Lv, Mehmet Emin Akdogan, Ken Chen, Michael Andreeff, Christopher R Flowers, Simrit Parmar

Faculty, Staff and Student Publications

SARS-CoV-2 vaccines pose as the most effective approach for mitigating the COVID-19 pandemic. High-degree efficacy of SARS-CoV-2 vaccines in clinical trials indicates that vaccination invariably induces an adaptive immune response. However, the emergence of breakthrough infections in vaccinated individuals suggests that the breadth and magnitude of vaccine-induced adaptive immune response may vary. We assessed vaccine-induced SARS-CoV-2 T cell response in 21 vaccinated individuals and found that SARS-CoV-2-specific T cells, which were mainly CD4+ T cells, were invariably detected in all individuals but the response was varied. We then investigated differentiation states and cytokine profiles to identify immune features associated with …

Recurrent De Novo Missense Variants Across Multiple Histone H4 Genes Underlie A Neurodevelopmental Syndrome., Federico Tessadori, Karen Duran, Karen Knapp, Matthias Fellner, Deciphering Developmental Disorders Study, Sarah Smithson, Ana Beleza Meireles, Mariet W. Elting, Quinten Waisfisz, Anne O'Donnell-Luria, Catherine Nowak, Jessica Douglas, Anne Ronan, Theresa Brunet, Urania Kotzaeridou, Shayna Svihovec, Margarita S. Saenz, Isabelle Thiffault, Florencia Del Viso, Patrick Devine, Shannon Rego, Jessica Tenney, Arie Van Haeringen, Claudia A L Ruivenkamp, Saskia Koene, Stephen P. Robertson, Charulata Deshpande, Rolph Pfundt, Nienke Verbeek, Jiddeke M. Van De Kamp, Janneke M M Weiss, Anna Ruiz, Elisabeth Gabau, Ehud Banne, Alexander Pepler, Armand Bottani, Sacha Laurent, Michel Guipponi, Emilia Bijlsma, Ange-Line Bruel, Arthur Sorlin, Mary Willis, Zoe Powis, Thomas Smol, Catherine Vincent-Delorme, Diana Baralle, Estelle Colin, Nicole Revencu, Eduardo Calpena, Andrew O M Wilkie, Maya Chopra, Valerie Cormier-Daire, Boris Keren, Alexandra Afenjar, Marcello Niceta, Alessandra Terracciano, Nicola Specchio, Marco Tartaglia, Marlene Rio, Giulia Barcia, Sophie Rondeau, Cindy Colson, Jeroen Bakkers, Peter D. Mace, Louise S. Bicknell, Gijs Van Haaften

Manuscripts, Articles, Book Chapters and Other Papers

Chromatin is essentially an array of nucleosomes, each of which consists of the DNA double-stranded fiber wrapped around a histone octamer. This organization supports cellular processes such as DNA replication, DNA transcription, and DNA repair in all eukaryotes. Human histone H4 is encoded by fourteen canonical histone H4 genes, all differing at the nucleotide level but encoding an invariant protein. Here, we present a cohort of 29 subjects with de novo missense variants in six H4 genes (H4C3, H4C4, H4C5, H4C6, H4C9, and H4C11) identified by whole-exome sequencing and matchmaking. All individuals present with neurodevelopmental features of intellectual disability and …

Repurposing Probenecid For The Treatment Of Heart Failure (Re-Prosper-Hf): A Study Protocol For A Randomized Placebo-Controlled Clinical Trial, Jack Rubinstein, Nathan Robbins, Karen Evans, Gabrielle Foster, Kevin Mcconeghy, Toluwalope Onadeko, Julie Bunke, Melanie Parent, Xi Luo, Jacob Joseph, Wen-Chih Wu

Faculty, Staff and Student Publications

BACKGROUND: Improving contractility in heart failure with reduced ejection fraction (HFrEF) has resurfaced as a potential treatment goal. Inotropic therapy is now better understood through its underlying mechanism as opposed to the observed effect of increasing contractility. Calcitropes are a subgroup of inotropes that largely depend on the stimulation of adenylyl cyclase to transform ATP into cyclic adenosine monophosphate (cAMP). At least two clinically relevant calcitropes-istaroxime and probenecid-improve contractility through an increase in systolic intracellular calcium without activating cAMP production. Probenecid, which has been safely used clinically for decades in non-cardiac conditions, has recently been identified as an agonist of …

Hsp90-Cdc37 Functions As A Chaperone For The Oncogenic Fgfr3-Tacc3 Fusion, Tao Li, Farideh Mehraein-Ghomi, M Elizabeth Forbes, Sanjeev V Namjoshi, E Ashley Ballard, Qianqian Song, Ping-Chieh Chou, Xuya Wang, Brittany C Parker Kerrigan, Frederick F Lang, Glenn Lesser, Waldemar Debinski, Xuejun Yang, Wei Zhang

Faculty, Staff and Student Publications

The FGFR3-TACC3 (F3-T3) fusion gene was discovered as an oncogenic molecule in glioblastoma and bladder cancers, and has subsequently been found in many cancer types. Notably, F3-T3 was found to be highly expressed in both untreated and matched recurrence glioblastoma under the concurrent radiotherapy and temozolomide (TMZ) treatment, suggesting that targeting F3-T3 is a valid strategy for treatment. Here, we show that the F3-T3 protein is a client of heat shock protein 90 (HSP90), forming a ternary complex with the cell division cycle 37 (CDC37). Deprivation of HSP90 or CDC37 disrupts the formation of the ternary complex, which destabilizes glycosylated …

Left Ventricular Hypertrophy And Biomarkers Of Cardiac Damage And Stress In Aortic Stenosis, Elliot J Stein, Nishath Quader, Alan Zajarias, Anna Vatterott, Et Al

2020-Current year OA Pubs

Background Left ventricular hypertrophy (LVH) is associated with increased mortality risk and rehospitalization after transcatheter aortic valve replacement among those with severe aortic stenosis. Whether cardiac troponin (cTnT) and NT-proBNP (N-terminal pro-B-type natriuretic peptide) risk stratify patients with aortic stenosis and without LVH is unknown. Methods and Results In a multicenter prospective registry of 923 patients with severe aortic stenosis undergoing transcatheter aortic valve replacement, we included 674 with core-laboratory-measured LV mass index, cTnT, and NT-proBNP. LVH was defined by sex-specific guideline cut-offs and elevated biomarker levels were based on age and sex cut-offs. Adjusted Cox proportional hazards models evaluated …

Perceptions Of Weight Status And Energy Balance Behaviors Among Patients With Non-Alcoholic Fatty Liver Disease, Natalia I Heredia, Ruchi Gaba, Yan Liu, Shilpa Jain, Manasi Rungta, Manav Rungta, Hashem B El-Serag, Fasiha Kanwal, Aaron P Thrift, Maya Balakrishnan

Faculty, Staff and Students Publications

Weight loss through behavioral modification is central to treating non-alcoholic fatty liver disease (NAFLD). To achieve this, patients need to accurately self-perceive their health behaviors. We aimed to identify predictors of concordance between self-perception and objective measures of body weight, physical activity (PA) and dietary behaviors. We used data from the Harris County NAFLD Cohort, an ongoing prospective study in a regional safety-net healthcare system. Patients completed self-administered baseline questionnaires on demographics, diet, PA, and self-perceptions. We assessed concordance between actual and self-perceived body weight and energy-balance behaviors. Multivariable logistic regression identified predictors of concordance. Patients (n = 458; average …

Harmonizing Model Organism Data In The Alliance Of Genome Resources., Alliance Of Genome Resources Consortium, Anna V. Anagnostopoulos, Susan M. Bello, Judith A. Blake, Olin Blodgett, Carol J. Bult, Karen R. Christie, Mary E. Dolan, Paul Hale, James A. Kadin, Monica S. Mcandrews, Howie Motenko, David R. Shaw, Constance M. Smith, Cynthia L. Smith, Monika Tomczuk, Laurens G. Wilming

Faculty Research 2022

The Alliance of Genome Resources (the Alliance) is a combined effort of 7 knowledgebase projects: Saccharomyces Genome Database, WormBase, FlyBase, Mouse Genome Database, the Zebrafish Information Network, Rat Genome Database, and the Gene Ontology Resource. The Alliance seeks to provide several benefits: better service to the various communities served by these projects; a harmonized view of data for all biomedical researchers, bioinformaticians, clinicians, and students; and a more sustainable infrastructure. The Alliance has harmonized cross-organism data to provide useful comparative views of gene function, gene expression, and human disease relevance. The basis of the comparative views is shared calls of …

Prep Patient Attitudes, Beliefs And Perceived Barriers Surrounding Hpv Vaccination: A Qualitative Study Of Semistructured Interviews With Prep Patients In Primary Care Clinics In Kansas And Missouri., Zoe C Sullivan-Blum, Margaret Brophy, Ryan Didde, Radha Nagireddy, Hannah Swagerty, Sumiko Weir, Kevin J. Sykes, Craig Dietz, Marcus Alt, Megha Ramaswamy, Paul Rotert

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVES: Men who have sex with men who use pre-exposure prophylaxis (PrEP) have not traditionally been targets for human papillomavirus (HPV) vaccine programmes, despite their high risk for HPV-related cancers and HPV vaccine being approved by the U.S. Food and Drug Administration (FDA) for people up to age 45. The objective of this study was to assess attitudes and barriers towards HPV vaccine for adult PrEP users in the primary care context.

METHODS: Semistructured phone interviews of 16 primary care patients taking PrEP in the Kansas City metropolitan area were conducted, with interviews assessing HPV vaccination status, and attitudes, beliefs …

Methylation Quantitative Trait Loci Are Largely Consistent Across Disease States In Crohn’S Disease, Suresh Venkateswaran, Hari K Somineni, Varun Kilaru, Seyma Katrinli, Jarod Prince, David T Okou, Jeffrey S Hyams, Lee A Denson, Richard Kellermayer, Greg Gibson, David J Cutler, Alicia K Smith, Subra Kugathasan, Karen N Conneely

Faculty, Staff and Students Publications

Recently, we identified 1,189 CpG sites whose DNA methylation level in blood associated with Crohn's disease. Here, we examined associations between DNA methylation and genetic variants to identify methylation quantitative trait loci across disease states in (1) 402 blood samples from 164 newly diagnosed pediatric Crohn's disease patients taken at 2 time points (diagnosis and follow-up), and 74 non-inflammatory bowel disease controls, (2) 780 blood samples from a non-Crohn's disease adult population, and (3) 40 ileal biopsies (17 Crohn's disease cases and 23 non-inflammatory bowel disease controls) from group (1). Genome-wide DNAm profiling and genotyping were performed using the Illumina …

Auriculocondylar Syndrome 2 Results From The Dominant-Negative Action Of Plcb4 Variants., Stanley M Kanai, Caleb Heffner, Timothy C Cox, Michael L Cunningham, Francisco A Perez, Aaron M Bauer, Philip Reigan, Cristan Carter, Stephen A Murray, David E Clouthier

Faculty Research 2022

Auriculocondylar syndrome 2 (ARCND2) is a rare autosomal dominant craniofacial malformation syndrome linked to multiple genetic variants in the coding sequence of phospholipase C β4 (PLCB4). PLCB4 is a direct signaling effector of the endothelin receptor type A (EDNRA)-Gq/11 pathway, which establishes the identity of neural crest cells (NCCs) that form lower jaw and middle ear structures. However, the functional consequences of PLCB4 variants on EDNRA signaling is not known. Here, we show, using multiple signaling reporter assays, that known PLCB4 variants resulting from missense mutations exert a dominant-negative interference over EDNRA signaling. In addition, using CRISPR/Cas9, we find that …

Utility Of The Milan System For Reporting Salivary Gland Cytology, With Focus On The Incidence And Histologic Correlates Of Atypia Of Undetermined Significance (Aus) And Salivary Gland Neoplasm Of Uncertain Malignant Potential (Sump): A 3-Year Institutional Experience, Christopher M Cormier, Shweta Agarwal

Pathology Research and Scholarship

BACKGROUND: Fine-needle aspiration (FNA) is the preferred diagnostic test for salivary gland lesions. The purpose of the Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) is to standardize salivary gland cytology reporting and guide treatment decisions. The objective of the current study was to evaluate the utility and performance of the MSRSGC, with a focus on the cytomorphology of lesions diagnosed as atypia of undetermined significance (AUS) and salivary gland neoplasm of uncertain malignant potential (SUMP).

METHODS: In total, 123 salivary gland FNAs were included in the study. FNA diagnoses for all cases were reviewed and recategorized, as applicable, according …

Femur Morphology In Healthy Infants And Young Children, Nathan P. Brown, Angela Thompson, Karen Bertocci, Natalie L. Adolphi, Lauren Dvorscak, Mary Clyde Pierce, Gina Bertocci

Pathology Research and Scholarship

The objective of this study was to characterize femur morphology in healthy infants and young children. Anterior-posterior (AP) radiographs of the femur from children age 0-3 years with no history of bone disease were obtained from two children's hospitals and one medical examiner's office. Femur morphological measures (bone length, minimum diaphysis diameter, growth plate width, and femur radius of curvature) and sectional structural measures were determined. Measures were described and compared based on subject age and mass. Relationships between measures and age and mass were evaluated. The 169 AP femur radiographs were obtained from 99 children (59.6% males, median age …

Is Breast Conservation Superior To Mastectomy In Early Stage Triple Negative Breast Cancer?, Omran Saifi, Mohamad A. Chahrour, Zhuo Li, Jawad Hoballah, Joseph Panoff, Laura A. Vallow, Youssef H. Zeidan

Surgery Articles

PURPOSE: Compare overall survival (OS) and breast cancer-specific survival (BCSS) outcomes of breast conservative therapy (BCT) and mastectomy in a large cohort of patients with early-stage triple negative breast cancer (TNBC), using a propensity score-based matching approach.

METHODS: Surveillance, Epidemiology, and End Results (SEER) database was used to study the role of RT in early stage TNBC. Primary end points were OS and BCSS. Cox proportional hazard regression models and Kaplan-Meier plots were used to generate the desired outcomes. Propensity score matching was done to minimize bias.

RESULTS: 12,761 patients with T1-2N0M0 TNBC as their first malignancy were retrieved. Of …