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Multi-Omics Insights Into The Biological Mechanisms Underlying Statistical Gene-By-Lifestyle Interactions With Smoking And Alcohol Consumption, Timothy D Majarian, Amy R Bentley, Vincent Laville, Michael R Brown, Daniel I Chasman, Paul S De Vries, Mary F Feitosa, Nora Franceschini, W James Gauderman, Casey Marchek, Daniel Levy, Alanna C Morrison, Michael Province, Dabeeru C Rao, Karen Schwander, Yun Ju Sung, Charles N Rotimi, Hugues Aschard, C Charles Gu, Alisa K Manning, Charge Gene-Lifestyle Interactions Working Group Jan 2022

Multi-Omics Insights Into The Biological Mechanisms Underlying Statistical Gene-By-Lifestyle Interactions With Smoking And Alcohol Consumption, Timothy D Majarian, Amy R Bentley, Vincent Laville, Michael R Brown, Daniel I Chasman, Paul S De Vries, Mary F Feitosa, Nora Franceschini, W James Gauderman, Casey Marchek, Daniel Levy, Alanna C Morrison, Michael Province, Dabeeru C Rao, Karen Schwander, Yun Ju Sung, Charles N Rotimi, Hugues Aschard, C Charles Gu, Alisa K Manning, Charge Gene-Lifestyle Interactions Working Group

Faculty, Staff and Student Publications

Though both genetic and lifestyle factors are known to influence cardiometabolic outcomes, less attention has been given to whether lifestyle exposures can alter the association between a genetic variant and these outcomes. The Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium's Gene-Lifestyle Interactions Working Group has recently published investigations of genome-wide gene-environment interactions in large multi-ancestry meta-analyses with a focus on cigarette smoking and alcohol consumption as lifestyle factors and blood pressure and serum lipids as outcomes. Further description of the biological mechanisms underlying these statistical interactions would represent a significant advance in our understanding of gene-environment …


Integrated Molecular And Affiliation Network Analysis: Core-Periphery Social Clustering Is Associated With Hiv Transmission Patterns, Kayo Fujimoto, Dimitrios Paraskevis, Jacky C Kuo, Camden J Hallmark, Jing Zhao, Andre Hochi, Lisa M Kuhns, Lu-Yu Hwang, Angelos Hatzakis, John A Schneider Jan 2022

Integrated Molecular And Affiliation Network Analysis: Core-Periphery Social Clustering Is Associated With Hiv Transmission Patterns, Kayo Fujimoto, Dimitrios Paraskevis, Jacky C Kuo, Camden J Hallmark, Jing Zhao, Andre Hochi, Lisa M Kuhns, Lu-Yu Hwang, Angelos Hatzakis, John A Schneider

Faculty, Staff and Student Publications

This study investigates the two-mode core-periphery structures of venue affiliation networks of younger Black men who have sex with men (YBMSM). We examined the association between these structures and HIV phylogenetic clusters, defined as members who share highly similar HIV strains that are regarded as a proxy for sexual affiliation networks. Using data from 114 YBMSM who are living with HIV in two large U.S. cities, we found that HIV phylogenetic clustering patterns were associated with social clustering patterns whose members share affiliation with core venues that overlap with those of YBMSM. Distinct HIV transmission patterns were found in each …


Practice Change In Community Health Centers: A Qualitative Study Of Leadership Attributes, Jennifer H Tektiridis, Natalia I Heredia, Robert O Morgan, Osama I Mikhail, Betsy C Risendal, Michelle C Kegler, Maria E Fernandez Jan 2022

Practice Change In Community Health Centers: A Qualitative Study Of Leadership Attributes, Jennifer H Tektiridis, Natalia I Heredia, Robert O Morgan, Osama I Mikhail, Betsy C Risendal, Michelle C Kegler, Maria E Fernandez

Faculty, Staff and Student Publications

INTRODUCTION: This paper explores leadership attributes important for practice change in community health centers (CHCs) and assesses attributes' fit with the Full-Range Leadership Theory (FRLT).

METHODS: We conducted four focus groups and 15 in-depth interviews with 48 CHC leaders from several U.S. states using a modified appreciative inquiry approach. Thematic analysis was used to review transcripts for leadership concepts and code with

RESULTS: CHC leaders most often noted attributes associated with transformational leadership as essential for practice change. Important attributes included emphasizing a collective sense of mission and a compelling, achievable vision; expressing enthusiasm about what needs to be done; …


Severity Of Child Autistic Symptoms And Parenting Stress In Mothers Of Children With Autism Spectrum Disorder In Japan And Usa: Cross-Cultural Differences, Noriko Porter, Katherine A Loveland, Sepideh Saroukhani, Yana Posey, Kana Morimoto, Mohammad H Rahbar Jan 2022

Severity Of Child Autistic Symptoms And Parenting Stress In Mothers Of Children With Autism Spectrum Disorder In Japan And Usa: Cross-Cultural Differences, Noriko Porter, Katherine A Loveland, Sepideh Saroukhani, Yana Posey, Kana Morimoto, Mohammad H Rahbar

Faculty, Staff and Student Publications

The purpose of this study was to compare the relationship between parenting stress and autistic symptom severity in the U.S. and Japan. Fifty-two U.S. and 51 Japanese mothers of children aged 2-12 with autism completed measures of parenting stress and child characteristics, including the parenting stress index (PSI), the social communication questionnaire (SCQ), and social responsiveness scale-2 (SRS-2). There was a nonlinear relationship between the child's autistic symptom severity and parenting stress in both countries. We also found some cultural differences: in the parent domain, the relationships between children's SCQ scores and PSI scores differed significantly between the U.S. and …


Evaluation Of The Kitchen Microbiome And Food Safety Behaviors Of Predominantly Low-Income Families, Christina K Carstens, Joelle K Salazar, Shreela V Sharma, Wenyaw Chan, Charles Darkoh Jan 2022

Evaluation Of The Kitchen Microbiome And Food Safety Behaviors Of Predominantly Low-Income Families, Christina K Carstens, Joelle K Salazar, Shreela V Sharma, Wenyaw Chan, Charles Darkoh

Faculty, Staff and Student Publications

Bacterial pathogens in the domestic environment present a risk to residents, particularly among susceptible populations. However, the impact of consumer demographic characteristics and food handling methods on kitchen microbiomes is not fully understood. The domestic kitchen bacterial communities of ten predominantly low-income families in Houston, TX, were assessed in conjunction with a cross-sectional food safety survey to evaluate differences in household and surface-specific microbiomes and bacterial foodborne pathogen presence. Three kitchen surfaces within each household, including the sink drain, the refrigerator handle, and the counter, were environmentally sampled and metataxonomically evaluated via targeted 16S rRNA sequencing. Disposable dish sponges were …


Feasibility And Acceptability Of Technology-Supported Sexual Health Education Among Adolescents Receiving Inpatient Psychiatric Care, Allison E Olmsted, Christine M Markham, Ross Shegog, Ana M Ugueto, Erica L Johnson, Melissa F Peskin, Susan T Emery, Kimberley A Baker, Elizabeth W Newlin Jan 2022

Feasibility And Acceptability Of Technology-Supported Sexual Health Education Among Adolescents Receiving Inpatient Psychiatric Care, Allison E Olmsted, Christine M Markham, Ross Shegog, Ana M Ugueto, Erica L Johnson, Melissa F Peskin, Susan T Emery, Kimberley A Baker, Elizabeth W Newlin

Faculty, Staff and Student Publications

Mental illness in adolescence is associated with high-risk sexual behaviors including multiple sex partners, infrequent or inconsistent condom use, and nonuse of contraception. Inpatient psychiatric care represents a promising setting to provide sexual health education. This pilot study investigates the feasibility and acceptability of online sexual health education in this group by assessing usability and impact on short-term psychosocial outcomes. We administered online modules on healthy relationships, pregnancy prevention, condom use, and sexually transmitted infection (STI) prevention to youth. We evaluated outcomes using a single group, pre/post-intervention design. One quality improvement session assessed staff acceptability of the programming. Participants included …


"Don't Know Where To Go For Help": Safety And Economic Needs Among Violence Survivors During The Covid-19 Pandemic, Leila Wood, Elizabeth Baumler, Rachel Voth Schrag, Shannon Guillot-Wright, Dixie Hairston, Jeff Temple, Elizabeth Torres Jan 2022

"Don't Know Where To Go For Help": Safety And Economic Needs Among Violence Survivors During The Covid-19 Pandemic, Leila Wood, Elizabeth Baumler, Rachel Voth Schrag, Shannon Guillot-Wright, Dixie Hairston, Jeff Temple, Elizabeth Torres

Faculty, Staff and Student Publications

The COVID-19 pandemic and related quarantine has created additional problems for survivors of interpersonal violence. The purpose of this study is to gain a preliminary understanding of the health, safety, and economic impacts of the COVID-19 pandemic on people that are experiencing or have previously experienced violence, stalking, threats, and/or abuse. An online survey, open from April to June 2020, was taken by people with safety concerns from interpersonal violence. Participants were recruited from IPV and sexual assault-focused agencies, state coalitions, and social media. Quantitative data were summarized using descriptive methods in SPSS and coding methods from thematic and content …


Pathway Lasso: Pathway Estimation And Selection With High-Dimensional Mediators, Yi Zhao, Xi Luo Jan 2022

Pathway Lasso: Pathway Estimation And Selection With High-Dimensional Mediators, Yi Zhao, Xi Luo

Faculty, Staff and Student Publications

In many scientific studies, it becomes increasingly important to delineate the pathways through a large number of mediators, such as genetic and brain mediators. Structural equation modeling (SEM) is a popular technique to estimate the pathway effects, commonly expressed as the product of coefficients. However, it becomes unstable and computationally challenging to fit such models with high-dimensional mediators. This paper proposes a sparse mediation model using a regularized SEM approach, where sparsity means that a small number of mediators have a nonzero mediation effect between a treatment and an outcome. To address the model selection challenge, we innovate by introducing …


In Utero Exposure To 17Α-Hydroxyprogesterone Caproate And Risk Of Cancer In Offspring, Caitlin C Murphy, Piera M Cirillo, Nickilou Y Krigbaum, Barbara A Cohn Jan 2022

In Utero Exposure To 17Α-Hydroxyprogesterone Caproate And Risk Of Cancer In Offspring, Caitlin C Murphy, Piera M Cirillo, Nickilou Y Krigbaum, Barbara A Cohn

Faculty, Staff and Student Publications

BACKGROUND: 17α-hydroxyprogesterone caproate is a synthetic progestogen initially approved in the 1950s to treat gynecologic and obstetrical conditions. Despite continued concerns about safety and short-term efficacy regarding the use of 17α-hydroxyprogesterone caproate for the prevention of preterm birth in pregnant women, little is known about the long-term effects of 17α-hydroxyprogesterone caproate on the health of the offsprings.

OBJECTIVE: To examine the association between in utero exposure to 17α-hydroxyprogesterone caproate and the risk of cancer in the offspring.

STUDY DESIGN: The Child Health and Development Studies was a population-based cohort of >18,000 mother-child dyads receiving prenatal care in the Kaiser Foundation …


Using Implementation Mapping To Develop Implementation Strategies For The Delivery Of A Cancer Prevention And Control Phone Navigation Program: A Collaboration With 2-1-1, Lynn N Ibekwe, Timothy J Walker, Ebun Ebunlomo, Katharine Ball Ricks, Sapna Prasad, Lara S Savas, Maria E Fernandez Jan 2022

Using Implementation Mapping To Develop Implementation Strategies For The Delivery Of A Cancer Prevention And Control Phone Navigation Program: A Collaboration With 2-1-1, Lynn N Ibekwe, Timothy J Walker, Ebun Ebunlomo, Katharine Ball Ricks, Sapna Prasad, Lara S Savas, Maria E Fernandez

Faculty, Staff and Student Publications

Cancer prevention and control (CPC) behaviors, such as cancer screening, human papillomavirus vaccination, and smoking cessation, are critical public health issues. Evidence-based interventions have been identified to improve the uptake of CPC behaviors; however, they are often inconsistently implemented, affecting their reach and effectiveness. Patient navigation is an evidence-based approach to increasing CPC behaviors. Nevertheless, there are few navigation programs that use systematically developed implementation strategies to facilitate adoption, implementation, and maintenance, which affects uptake and outcomes. This article describes the development of a multifaceted implementation strategy designed to facilitate delivery of a CPC phone navigation program to increase breast, …


Incidence, Etiology, Sociodemographic And Clinical Characterization Of Acute Respiratory Failure In Pediatric Patients At A High-Altitude City: A Multicenter Cohort Study, Sarha M Vargas Muñoz, Sara De Vivero Haddad, Aldo M Beltran, Carolina Bonilla Gonzalez, Melisa Naranjo Vanegas, Sergio Moreno-Lopez, Paola Rueda-Guevara, Pedro Barrera, Juan Gabriel Piñeros, Luz Marina Mejía, María Lucia Mesa, Sonia Restrepo-Gualteros, Olga Lucía Baquero Castañeda, Andrea Ramírez Varela Jan 2022

Incidence, Etiology, Sociodemographic And Clinical Characterization Of Acute Respiratory Failure In Pediatric Patients At A High-Altitude City: A Multicenter Cohort Study, Sarha M Vargas Muñoz, Sara De Vivero Haddad, Aldo M Beltran, Carolina Bonilla Gonzalez, Melisa Naranjo Vanegas, Sergio Moreno-Lopez, Paola Rueda-Guevara, Pedro Barrera, Juan Gabriel Piñeros, Luz Marina Mejía, María Lucia Mesa, Sonia Restrepo-Gualteros, Olga Lucía Baquero Castañeda, Andrea Ramírez Varela

Faculty, Staff and Student Publications

BACKGROUND: Acute respiratory failure is a life-threatening medical condition, associated with a variety of conditions and risk factors, including acute respiratory diseases which are a frequent cause of pediatric morbidity and mortality worldwide. In Colombia, the literature related to ARF is scarce.

OBJECTIVE: To determine the incidence, causes, and sociodemographic and clinical characteristics of ARF in three hospitals in Bogota, a high-altitude city located in Colombia, during the COVID-19 pandemic.

METHODS: A multicenter prospective cohort study called the FARA cohort was developed between April 2020 - December 2021. Patients older than one month and younger than 18 years with respiratory …


Anti-Grp-R Monoclonal Antibody Antitumor Therapy Against Neuroblastoma, Jingbo Qiao, Junquan Liu, Jillian C Jacobson, Rachael A Clark, Sora Lee, Li Liu, Zhiqiang An, Ningyan Zhang, Dai H Chung Jan 2022

Anti-Grp-R Monoclonal Antibody Antitumor Therapy Against Neuroblastoma, Jingbo Qiao, Junquan Liu, Jillian C Jacobson, Rachael A Clark, Sora Lee, Li Liu, Zhiqiang An, Ningyan Zhang, Dai H Chung

Faculty, Staff and Student Publications

Standard treatment for patients with high-risk neuroblastoma remains multimodal therapy including chemoradiation, surgical resection, and autologous stem cell rescue. Immunotherapy has demonstrated success in treating many types of cancers; however, its use in pediatric solid tumors has been limited by low tumor mutation burdens. Gastrin-releasing peptide receptor (GRP-R) is overexpressed in numerous malignancies, including poorly-differentiated neuroblastoma. Monoclonal antibodies (mAbs) to GRP-R have yet to be developed but could serve as a potential novel immunotherapy. This preclinical study aims to evaluate the efficacy of a novel GRP-R mAb immunotherapy against neuroblastoma. We established four candidate anti-GRP-R mAbs by screening a single-chain …


Phenotype-Genotype Analysis Of Caucasian Patients With High Risk Of Osteoarthritis, Yanfei Wang, Jacqueline Chyr, Pora Kim, Weiling Zhao, Xiaobo Zhou Jan 2022

Phenotype-Genotype Analysis Of Caucasian Patients With High Risk Of Osteoarthritis, Yanfei Wang, Jacqueline Chyr, Pora Kim, Weiling Zhao, Xiaobo Zhou

Faculty, Staff and Student Publications

Background: Osteoarthritis (OA) is a common cause of disability and pain around the world. Epidemiologic studies of family history have revealed evidence of genetic influence on OA. Although many efforts have been devoted to exploring genetic biomarkers, the mechanism behind this complex disease remains unclear. The identified genetic risk variants only explain a small proportion of the disease phenotype. Traditional genome-wide association study (GWAS) focuses on radiographic evidence of OA and excludes sex chromosome information in the analysis. However, gender differences in OA are multifactorial, with a higher frequency in women, indicating that the chromosome X plays an essential role …


Predictors Of E-Cigarette Initiation And Use Among Middle School Youth In A Low-Income Predominantly Hispanic Community, M Yvonne Gaddy, Denise Vasquez, Louis D Brown Jan 2022

Predictors Of E-Cigarette Initiation And Use Among Middle School Youth In A Low-Income Predominantly Hispanic Community, M Yvonne Gaddy, Denise Vasquez, Louis D Brown

Faculty, Staff and Student Publications

Introduction: E-cigarette use among middle and high school youth increased from 2. 5 million in 2014 to 9.2 million in 2019, becoming the most common tobacco product used among youth. Hispanic youth, the largest ethnic minority in the United States, have higher rates of tobacco use, including e-cigarettes, than non-Hispanics. Identifying factors that put youth at risk for future e-cigarette use is vital to focusing prevention efforts. Informed by social cognitive theory, this study identifies predictors of e-cigarette uptake among e-cigarette naïve youth in a predominantly low-income Hispanic community.

Methods: 1,249 students (6-8th grades) from two middle schools in El …


Blood Metabolites Predicting Mild Cognitive Impairment In The Study Of Latinos-Investigation Of Neurocognitive Aging (Hchs/So), Shan He, Einat Granot-Hershkovitz, Ying Zhang, Jan Bressler, Wassim Tarraf, Bing Yu, Tianyi Huang, Donglin Zeng, Sylvia Wassertheil-Smoller, Melissa Lamar, Martha Daviglus, Maria J Marquine, Jianwen Cai, Thomas Mosley, Robert Kaplan, Eric Boerwinkle, Myriam Fornage, Charles Decarli, Bruce Kristal, Hector M Gonzalez, Tamar Sofer Jan 2022

Blood Metabolites Predicting Mild Cognitive Impairment In The Study Of Latinos-Investigation Of Neurocognitive Aging (Hchs/So), Shan He, Einat Granot-Hershkovitz, Ying Zhang, Jan Bressler, Wassim Tarraf, Bing Yu, Tianyi Huang, Donglin Zeng, Sylvia Wassertheil-Smoller, Melissa Lamar, Martha Daviglus, Maria J Marquine, Jianwen Cai, Thomas Mosley, Robert Kaplan, Eric Boerwinkle, Myriam Fornage, Charles Decarli, Bruce Kristal, Hector M Gonzalez, Tamar Sofer

Faculty, Staff and Student Publications

INTRODUCTION: Blood metabolomics-based biomarkers may be useful to predict measures of neurocognitive aging.

METHODS: We tested the association between 707 blood metabolites measured in 1451 participants from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), with mild cognitive impairment (MCI) and global cognitive change assessed 7 years later. We further used Lasso penalized regression to construct a metabolomics risk score (MRS) that predicts MCI, potentially identifying a different set of metabolites than those discovered in individual-metabolite analysis.

RESULTS: We identified 20 metabolites predicting prevalent MCI and/or global cognitive change. Six of them were novel and 14 were previously reported as …


Recent Advances On Dna Base Flipping: A General Mechanism For Writing, Reading, And Erasing Dna Modifications, Ren Ren, John R Horton, Samuel Hong, Xiaodong Cheng Jan 2022

Recent Advances On Dna Base Flipping: A General Mechanism For Writing, Reading, And Erasing Dna Modifications, Ren Ren, John R Horton, Samuel Hong, Xiaodong Cheng

Faculty, Staff and Student Publications

The modification of DNA bases is a classic hallmark of epigenetics. Four forms of modified cytosine-5-methylcytosine, 5-hydroxymethylcytosine, 5-formylcytosine, and 5-carboxylcytosine-have been discovered in eukaryotic DNA. In addition to cytosine carbon-5 modifications, cytosine and adenine methylated in the exocyclic amine-N4-methylcytosine and N6-methyladenine-are other modified DNA bases discovered even earlier. Each modified base can be considered a distinct epigenetic signal with broader biological implications beyond simple chemical changes. Since 1994, several crystal structures of proteins and enzymes involved in writing, reading, and erasing modified bases have become available. Here, we present a structural synopsis of writers, readers, and erasers of the modified …


Cell-Directed Aptamer Therapeutic Targeting For Cancers Including Those Within The Central Nervous System, Jun Wei, Renduo Song, Aria Sabbagh, Anantha Marisetty, Neal Shukla, Dexing Fang, Hinda Najem, Martina Ott, James Long, Lijie Zhai, Maciej S Lesniak, Charles David James, Leonidas Platanias, Michael Curran, Amy B Heimberger Jan 2022

Cell-Directed Aptamer Therapeutic Targeting For Cancers Including Those Within The Central Nervous System, Jun Wei, Renduo Song, Aria Sabbagh, Anantha Marisetty, Neal Shukla, Dexing Fang, Hinda Najem, Martina Ott, James Long, Lijie Zhai, Maciej S Lesniak, Charles David James, Leonidas Platanias, Michael Curran, Amy B Heimberger

Faculty, Staff and Student Publications

Osteopontin (OPN) is produced by tumor cells as well as by myeloid cells and is enriched in the tumor microenvironment (TME) of many cancers. Given the roles of OPN in tumor progression and immune suppression, we hypothesized that targeting OPN with aptamers that have high affinity and specificity could be a promising therapeutic strategy. Bi-specific aptamers targeting ligands for cellular internalization were conjugated to siRNAs to suppress OPN were created, and therapeutic leads were selected based on target engagement and


An Autoencoder-Based Deep Learning Method For Genotype Imputation, Meng Song, Jonathan Greenbaum, Joseph Luttrell, Weihua Zhou, Chong Wu, Zhe Luo, Chuan Qiu, Lan Juan Zhao, Kuan-Jui Su, Qing Tian, Hui Shen, Huixiao Hong, Ping Gong, Xinghua Shi, Hong-Wen Deng, Chaoyang Zhang Jan 2022

An Autoencoder-Based Deep Learning Method For Genotype Imputation, Meng Song, Jonathan Greenbaum, Joseph Luttrell, Weihua Zhou, Chong Wu, Zhe Luo, Chuan Qiu, Lan Juan Zhao, Kuan-Jui Su, Qing Tian, Hui Shen, Huixiao Hong, Ping Gong, Xinghua Shi, Hong-Wen Deng, Chaoyang Zhang

Faculty, Staff and Student Publications

Genotype imputation has a wide range of applications in genome-wide association study (GWAS), including increasing the statistical power of association tests, discovering trait-associated loci in meta-analyses, and prioritizing causal variants with fine-mapping. In recent years, deep learning (DL) based methods, such as sparse convolutional denoising autoencoder (SCDA), have been developed for genotype imputation. However, it remains a challenging task to optimize the learning process in DL-based methods to achieve high imputation accuracy. To address this challenge, we have developed a convolutional autoencoder (AE) model for genotype imputation and implemented a customized training loop by modifying the training process with a …


Highlights From The 7th Oncological Pathology Conference 'Pathological Anatomy In The Context Of The National Cancer Law: An Overview Of The Latin American Experience', 15, 22 And 23 July 2022, Trujillo, Peru, Caddie Laberiano-Fernández, Joan Moreno Luján, Bruno De Carvalho Dornelas, Magali Franco Benites, Patricia Gutiérrez Quispe, Valeria Aguilar Vásquez, Andric Guerrero Espinoza, Elsa Guerra Guerra, Gabriela Gil-Arroyo Álvarez, Juan Astigueta-Pérez, Maria Teresa Garcia De Dávila, Sandro Casavilca Zambrano, Tatiana Vidaurre Rojas, Alejandro Mariños, Emmanuel S González, Rossana Lazcano, Ricardo R Lastra, Isabel Alvarado-Cabrero, Henry Guerra Miller, Ricardo H Bardales, Milagros Abad-Licham Jan 2022

Highlights From The 7th Oncological Pathology Conference 'Pathological Anatomy In The Context Of The National Cancer Law: An Overview Of The Latin American Experience', 15, 22 And 23 July 2022, Trujillo, Peru, Caddie Laberiano-Fernández, Joan Moreno Luján, Bruno De Carvalho Dornelas, Magali Franco Benites, Patricia Gutiérrez Quispe, Valeria Aguilar Vásquez, Andric Guerrero Espinoza, Elsa Guerra Guerra, Gabriela Gil-Arroyo Álvarez, Juan Astigueta-Pérez, Maria Teresa Garcia De Dávila, Sandro Casavilca Zambrano, Tatiana Vidaurre Rojas, Alejandro Mariños, Emmanuel S González, Rossana Lazcano, Ricardo R Lastra, Isabel Alvarado-Cabrero, Henry Guerra Miller, Ricardo H Bardales, Milagros Abad-Licham

Faculty, Staff and Student Publications

The seventh session of the Oncological Pathology Conference (JoPaO) entitled 'Pathological Anatomy in the context of the National Cancer Law: An overview of the Latin American experience', was held virtually on July 15, 22 and 23. Peru was the headquarters for this event, where 17 national and international professors of high academic standing participated. They interacted in a multidisciplinary context through talks with national panellists and the general public. The recent promulgation of the 'National Cancer Law' fosters the development of discussion forums to analyse the national realities and uphold continuous learning about experiences in other Latin American countries with …


Serglycin Is Involved In Tgf-Β Induced Epithelial-Mesenchymal Transition And Is Highly Expressed By Immune Cells In Breast Cancer Tissue, Marta Tellez-Gabriel, Xavier Tekpli, Trine M Reine, Beate Hegge, Stephanie R Nielsen, Meng Chen, Line Moi, Lisa Svartdal Normann, Lill-Tove R Busund, George A Calin, Gunhild M Mælandsmo, Maria Perander, Achilleas D Theocharis, Svein O Kolset, Erik Knutsen Jan 2022

Serglycin Is Involved In Tgf-Β Induced Epithelial-Mesenchymal Transition And Is Highly Expressed By Immune Cells In Breast Cancer Tissue, Marta Tellez-Gabriel, Xavier Tekpli, Trine M Reine, Beate Hegge, Stephanie R Nielsen, Meng Chen, Line Moi, Lisa Svartdal Normann, Lill-Tove R Busund, George A Calin, Gunhild M Mælandsmo, Maria Perander, Achilleas D Theocharis, Svein O Kolset, Erik Knutsen

Faculty, Staff and Student Publications

Serglycin is a proteoglycan highly expressed by immune cells, in which its functions are linked to storage, secretion, transport, and protection of chemokines, proteases, histamine, growth factors, and other bioactive molecules. In recent years, it has been demonstrated that serglycin is also expressed by several other cell types, such as endothelial cells, muscle cells, and multiple types of cancer cells. Here, we show that serglycin expression is upregulated in transforming growth factor beta (TGF-β) induced epithelial-mesenchymal transition (EMT). Functional studies provide evidence that serglycin plays an important role in the regulation of the transition between the epithelial and mesenchymal phenotypes, …


Pathogenic Tau Accelerates Aging-Associated Activation Of Transposable Elements In The Mouse Central Nervous System, Paulino Ramirez, Gabrielle Zuniga, Wenyan Sun, Adrian Beckmann, Elizabeth Ochoa, Sarah L Devos, Bradley Hyman, Gabriel Chiu, Ethan R Roy, Wei Cao, Miranda Orr, Virginie Buggia-Prevot, William J Ray, Bess Frost Jan 2022

Pathogenic Tau Accelerates Aging-Associated Activation Of Transposable Elements In The Mouse Central Nervous System, Paulino Ramirez, Gabrielle Zuniga, Wenyan Sun, Adrian Beckmann, Elizabeth Ochoa, Sarah L Devos, Bradley Hyman, Gabriel Chiu, Ethan R Roy, Wei Cao, Miranda Orr, Virginie Buggia-Prevot, William J Ray, Bess Frost

Faculty, Staff and Student Publications

Transposable elements comprise almost half of the mammalian genome. A growing body of evidence suggests that transposable element dysregulation accompanies brain aging and neurodegenerative disorders, and that transposable element activation is neurotoxic. Recent studies have identified links between pathogenic forms of tau, a protein that accumulates in Alzheimer's disease and related "tauopathies," and transposable element-induced neurotoxicity. Starting with transcriptomic analyses, we find that age- and tau-induced transposable element activation occurs in the mouse brain. Among transposable elements that are activated at the RNA level in the context of brain aging and tauopathy, we find that the endogenous retrovirus (ERV) class …


Transcriptomic-Assisted Immune And Neoantigen Profiling In Premalignancy, Kyle Chang, Florencia Mcallister, Eduardo Vilar Jan 2022

Transcriptomic-Assisted Immune And Neoantigen Profiling In Premalignancy, Kyle Chang, Florencia Mcallister, Eduardo Vilar

Faculty, Staff and Student Publications

Immune-based cancer therapies such as checkpoint inhibitors (CPI) and vaccines have been increasingly studied across different cancer types. Response to such therapies depends on a number of factors such as mutational burden, neoantigen load, presence of tumor infiltrating lymphocytes, among others. Next-generation sequencing (NGS) technologies are particularly attractive to interrogate the immune response compared to traditional assays such as qRT-PCR and immunohistochemistry (IHC) because they enable the discovery of neoantigens and simultaneous profiling of immune infiltration using gene expression on a large scale. Current approaches in immune profiling utilizes whole-exome sequencing (WES) for human leukocyte allele (HLA) typing and neoantigen …


Electroacupuncture Ameliorates Inflammatory Response Induced By Retinal Ischemia-Reperfusion Injury And Protects The Retina Through The Dor-Bdnf/Trkb Pathway, Runjie Guo, Yongjie Zhang, Yue Geng, Ping Chen, Tiantian Fu, Yong Xia, Ren Zhang, Yuan Zhu, Jingling Jin, Nange Jin, Hong Xu, Xuesong Tian Jan 2022

Electroacupuncture Ameliorates Inflammatory Response Induced By Retinal Ischemia-Reperfusion Injury And Protects The Retina Through The Dor-Bdnf/Trkb Pathway, Runjie Guo, Yongjie Zhang, Yue Geng, Ping Chen, Tiantian Fu, Yong Xia, Ren Zhang, Yuan Zhu, Jingling Jin, Nange Jin, Hong Xu, Xuesong Tian

Faculty, Staff and Student Publications

Objectives: Retinal ischemia-reperfusion injury (RIRI) is the common pathological basis of many ophthalmic diseases in the later stages, and inflammation is the primary damage mechanism of RIRI. Our study aimed to assess whether electroacupuncture (EA) has a protective effect against RIRI and to elucidate its related mechanisms.

Methods: A high-intraocular pressure (HIOP) model was used to simulate RIRI in Wistar rats. EA was applied to the EA1 group [Jingming (BL1) + Shuigou (GV26)] and the EA2 group [Jingming (BL1) + Hegu (LI4)] respectively for 30 min starting immediately after the onset of reperfusion and repeated (30 min/time) at 12 h …


Exploiting Induced Vulnerability To Overcome Parpi Resistance And Clonal Heterogeneity In Brca Mutant Triple-Negative Inflammatory Breast Cancer, David J H Shih, Mei-Kuang Chen, Jun Yin, Daniel J Mcgrail, Hui Dai, Rongbin Wei, Jing Zhang, Wenjin Jim Zheng, Kim-Anh Do, Liuqing Yang, Mien-Chie Hung, Shiaw-Yih Lin Jan 2022

Exploiting Induced Vulnerability To Overcome Parpi Resistance And Clonal Heterogeneity In Brca Mutant Triple-Negative Inflammatory Breast Cancer, David J H Shih, Mei-Kuang Chen, Jun Yin, Daniel J Mcgrail, Hui Dai, Rongbin Wei, Jing Zhang, Wenjin Jim Zheng, Kim-Anh Do, Liuqing Yang, Mien-Chie Hung, Shiaw-Yih Lin

Faculty, Staff and Student Publications

Acquired resistance and clonal heterogeneity are critical challenges in cancer treatment, and the lack of effective computational tools hampers the discovery of new treatments to overcome resistance. Using high-throughput transcriptomic databases of compound perturbation profiles, we have developed a bioinformatic strategy for identifying candidate drugs to overcome resistance with combinatorial therapy. We devised this strategy during an investigation into the acquired resistance against PARP inhibitors (PARPi) in a triple-negative inflammatory breast cancer cell line. In this study, we derived multiple PARPi-resistant clones and characterized their transcriptomic adaptations compared to the parental clone. The transcriptomes of the resistant clones showed substantial …


The Current Status And Shortcomings Of Stereotactic Radiosurgery, Hunter Mehrens, Trang Nguyen, Sharbacha Edward, Shannon Hartzell, Mallory Glenn, Daniela Branco, Nadia Hernandez, Paola Alvarez, Andrea Molineu, Paige Taylor, Stephen Kry Jan 2022

The Current Status And Shortcomings Of Stereotactic Radiosurgery, Hunter Mehrens, Trang Nguyen, Sharbacha Edward, Shannon Hartzell, Mallory Glenn, Daniela Branco, Nadia Hernandez, Paola Alvarez, Andrea Molineu, Paige Taylor, Stephen Kry

Faculty, Staff and Student Publications

Background: Stereotactic radiosurgery (SRS) is a common treatment for intracranial lesions. This work explores the state of SRS treatment delivery to characterize current treatment accuracy based on treatment parameters.

Methods: NCI clinical trials involving SRS rely on an end-to-end treatment delivery on a patient surrogate (credentialing phantom) from the Imaging and Radiation Oncology Core (IROC) to test their treatment accuracy. The results of 1072 SRS phantom irradiations between 2012 and 2020 were retrospectively analyzed. Univariate analysis and random forest models were used to associate irradiation conditions with phantom performance. The following categories were evaluated in terms of how they predicted …


High-Resolution Metabolomics Of Exposure To Tobacco Smoke During Pregnancy And Adverse Birth Outcomes In The Atlanta African American Maternal-Child Cohort, Youran Tan, Dana Boyd Barr, P Barry Ryan, Veronika Fedirko, Jeremy A Sarnat, Audrey J Gaskins, Che-Jung Chang, Ziyin Tang, Carmen J Marsit, Elizabeth J Corwin, Dean P Jones, Anne L Dunlop, Donghai Liang Jan 2022

High-Resolution Metabolomics Of Exposure To Tobacco Smoke During Pregnancy And Adverse Birth Outcomes In The Atlanta African American Maternal-Child Cohort, Youran Tan, Dana Boyd Barr, P Barry Ryan, Veronika Fedirko, Jeremy A Sarnat, Audrey J Gaskins, Che-Jung Chang, Ziyin Tang, Carmen J Marsit, Elizabeth J Corwin, Dean P Jones, Anne L Dunlop, Donghai Liang

Faculty, Staff and Student Publications

Exposure to tobacco smoke during pregnancy has been associated with a series of adverse reproductive outcomes; however, the underlying molecular mechanisms are not well-established. We conducted an untargeted metabolome-wide association study to identify the metabolic perturbations and molecular mechanisms underlying the association between cotinine, a widely used biomarker of tobacco exposure, and adverse birth outcomes. We collected early and late pregnancy urine samples for cotinine measurement and serum samples for high-resolution metabolomics (HRM) profiling from 105 pregnant women from the Atlanta African American Maternal-Child cohort (2014-2016). Maternal metabolome perturbations mediating prenatal tobacco smoke exposure and adverse birth outcomes were assessed …


Progression Free Survival Prediction For Head And Neck Cancer Using Deep Learning Based On Clinical And Pet/Ct Imaging Data, Mohamed A Naser, Kareem A Wahid, Abdallah S R Mohamed, Moamen Abobakr Abdelaal, Renjie He, Cem Dede, Lisanne V Van Dijk, Clifton D Fuller Jan 2022

Progression Free Survival Prediction For Head And Neck Cancer Using Deep Learning Based On Clinical And Pet/Ct Imaging Data, Mohamed A Naser, Kareem A Wahid, Abdallah S R Mohamed, Moamen Abobakr Abdelaal, Renjie He, Cem Dede, Lisanne V Van Dijk, Clifton D Fuller

Faculty, Staff and Student Publications

Determining progression-free survival (PFS) for head and neck squamous cell carcinoma (HNSCC) patients is a challenging but pertinent task that could help stratify patients for improved overall outcomes. PET/CT images provide a rich source of anatomical and metabolic data for potential clinical biomarkers that would inform treatment decisions and could help improve PFS. In this study, we participate in the 2021 HECKTOR Challenge to predict PFS in a large dataset of HNSCC PET/CT images using deep learning approaches. We develop a series of deep learning models based on the DenseNet architecture using a negative log-likelihood loss function that utilizes PET/CT …


Deep-Learning-Based Generation Of Synthetic 6-Minute Mri From 2-Minute Mri For Use In Head And Neck Cancer Radiotherapy, Kareem A Wahid, Jiaofeng Xu, Dina El-Habashy, Yomna Khamis, Moamen Abobakr, Brigid Mcdonald, Nicolette O' Connell, Daniel Thill, Sara Ahmed, Christina Setareh Sharafi, Kathryn Preston, Travis C Salzillo, Abdallah S R Mohamed, Renjie He, Nathan Cho, John Christodouleas, Clifton D Fuller, Mohamed A Naser Jan 2022

Deep-Learning-Based Generation Of Synthetic 6-Minute Mri From 2-Minute Mri For Use In Head And Neck Cancer Radiotherapy, Kareem A Wahid, Jiaofeng Xu, Dina El-Habashy, Yomna Khamis, Moamen Abobakr, Brigid Mcdonald, Nicolette O' Connell, Daniel Thill, Sara Ahmed, Christina Setareh Sharafi, Kathryn Preston, Travis C Salzillo, Abdallah S R Mohamed, Renjie He, Nathan Cho, John Christodouleas, Clifton D Fuller, Mohamed A Naser

Faculty, Staff and Student Publications

Background: Quick magnetic resonance imaging (MRI) scans with low contrast-to-noise ratio are typically acquired for daily MRI-guided radiotherapy setup. However, for patients with head and neck (HN) cancer, these images are often insufficient for discriminating target volumes and organs at risk (OARs). In this study, we investigated a deep learning (DL) approach to generate high-quality synthetic images from low-quality images.

Methods: We used 108 unique HN image sets of paired 2-minute T2-weighted scans (2mMRI) and 6-minute T2-weighted scans (6mMRI). 90 image sets (~20,000 slices) were used to train a 2-dimensional generative adversarial DL model that utilized 2mMRI as input and …


Head And Neck Cancer Primary Tumor Auto Segmentation Using Model Ensembling Of Deep Learning In Pet/Ct Images, Mohamed A Naser, Kareem A Wahid, Lisanne V Van Dijk, Renjie He, Moamen Abobakr Abdelaal, Cem Dede, Abdallah S R Mohamed, Clifton D Fuller Jan 2022

Head And Neck Cancer Primary Tumor Auto Segmentation Using Model Ensembling Of Deep Learning In Pet/Ct Images, Mohamed A Naser, Kareem A Wahid, Lisanne V Van Dijk, Renjie He, Moamen Abobakr Abdelaal, Cem Dede, Abdallah S R Mohamed, Clifton D Fuller

Faculty, Staff and Student Publications

Auto-segmentation of primary tumors in oropharyngeal cancer using PET/CT images is an unmet need that has the potential to improve radiation oncology workflows. In this study, we develop a series of deep learning models based on a 3D Residual Unet (ResUnet) architecture that can segment oropharyngeal tumors with high performance as demonstrated through internal and external validation of large-scale datasets (training size = 224 patients, testing size = 101 patients) as part of the 2021 HECKTOR Challenge. Specifically, we leverage ResUNet models with either 256 or 512 bottleneck layer channels that demonstrate internal validation (10-fold cross-validation) mean Dice similarity coefficient …


Clinical Characteristics And Outcomes Of Castleman Disease: A Multicenter Consortium Study Of 428 Patients With 15-Year Follow-Up, Wanying Liu, Qingqing Cai, Tiantian Yu, Paolo Strati, Frederick B Hagemeister, Qiongli Zhai, Mingzhi Zhang, Ling Li, Xiaosheng Fang, Jianyong Li, Ruifang Sun, Shanxiang Zhang, Hanjin Yang, Zhaoming Wang, Wenbian Qian, Noriko Iwaki, Yasuharu Sato, Eric Oksenhendler, Zijun Y Xu-Monette, Ken H Young, Li Yu Jan 2022

Clinical Characteristics And Outcomes Of Castleman Disease: A Multicenter Consortium Study Of 428 Patients With 15-Year Follow-Up, Wanying Liu, Qingqing Cai, Tiantian Yu, Paolo Strati, Frederick B Hagemeister, Qiongli Zhai, Mingzhi Zhang, Ling Li, Xiaosheng Fang, Jianyong Li, Ruifang Sun, Shanxiang Zhang, Hanjin Yang, Zhaoming Wang, Wenbian Qian, Noriko Iwaki, Yasuharu Sato, Eric Oksenhendler, Zijun Y Xu-Monette, Ken H Young, Li Yu

Faculty, Staff and Student Publications

Castleman disease (CD) has been reported as a group of poorly understood lymphoproliferative disorders, including unicentric CD (UCD) and idiopathic multicentric CD (iMCD) which are human immunodeficiency virus (HIV) negative and human herpes virus 8 (HHV-8) negative. The clinical and independent prognostic factors of CD remain poorly elucidated. We retrospectively collected the clinical information of 428 patients with HIV and HHV-8 negative CD from 12 large medical centers with 15-year follow-up. We analyzed the clinicopathologic features of 428 patients (248 with UCD and 180 with iMCD) with a median age of 41 years. The histology subtypes were hyaline-vascular (HV) histopathology …