Digital Commons Network^™

Fibroblast Growth Factor 15/19 Expression, Regulation, And Function: An Overview, Greg Guthrie, Caitlin Vonderohe, Douglas Burrin

Children’s Nutrition Research Center Staff Publications

Since the discovery of fibroblast growth factor (FGF)-19 over 20 years ago, our understanding of the peptide and its role in human biology has moved forward significantly. A member of a superfamily of paracrine growth factors regulating embryonic development, FGF19 is unique in that it is a dietary-responsive endocrine hormone linked with bile acid homeostasis, glucose and lipid metabolism, energy expenditure, and protein synthesis during the fed to fasted state. FGF19 achieves this through targeting multiple tissues and signaling pathways within those tissues. The diverse functional capabilities of FGF19 is due to the unique structural characteristics of the protein and …

Global Community Of Practice: A Means For Capacity And Community Strengthening For Health Professionals In Low- And Middle-Income Countries, Allison Silverstein, Amy Benson, Catriona Gates, Diane Nguyen

Faculty, Staff and Students Publications

BACKGROUND: Low- and middle-income countries face distinct challenges in providing health care services and training. The community of practice (CoP) has been described as a method of facilitating much-needed connections and conversations on this topic and has been adapted over time to include virtual CoPs. We describe the development and evaluation of a global Clinical Lead Forum (CLF) using a CoP framework to structure informal continuing professional development (CPD) and enhance the capacity of health care professionals in low- and middle-income countries.

METHODS: Baylor College of Medicine International Pediatric AIDS Initiative (BIPAI) and its network of affiliated, independent non-governmental organizations …

Relational Graph Convolutional Networks For Predicting Blood-Brain Barrier Penetration Of Drug Molecules, Yan Ding, Xiaoqian Jiang, Yejin Kim

Faculty, Staff and Student Publications

MOTIVATION: Evaluating the blood-brain barrier (BBB) permeability of drug molecules is a critical step in brain drug development. Traditional methods for the evaluation require complicated in vitro or in vivo testing. Alternatively, in silico predictions based on machine learning have proved to be a cost-efficient way to complement the in vitro and in vivo methods. However, the performance of the established models has been limited by their incapability of dealing with the interactions between drugs and proteins, which play an important role in the mechanism behind the BBB penetrating behaviors. To address this limitation, we employed the relational graph convolutional …

An Evidence-Based Lexical Pattern Approach For Quality Assurance Of Gene Ontology Relations, Rashmie Abeysinghe, Yuntao Yang, Mason Bartels, W Jim Zheng, Licong Cui

Faculty, Staff and Student Publications

Gene Ontology (GO) is widely used in the biological domain. It is the most comprehensive ontology providing formal representation of gene functions (GO concepts) and relations between them. However, unintentional quality defects (e.g. missing or erroneous relations) in GO may exist due to the large size of GO concepts and complexity of GO structures. Such quality defects would impact the results of GO-based analyses and applications. In this work, we introduce a novel evidence-based lexical pattern approach for quality assurance of GO relations. We leverage two layers of evidence to suggest potentially missing relations in GO as follows. We first …

Chronic Lymphocytic Leukemia Progression Diagnosis With Intrinsic Cellular Patterns Via Unsupervised Clustering, Pingjun Chen, Siba El Hussein, Fuyong Xing, Muhammad Aminu, Aparajith Kannapiran, John D Hazle, L Jeffrey Medeiros, Ignacio I Wistuba, David Jaffray, Joseph D Khoury, Jia Wu

Faculty, Staff and Student Publications

Identifying the progression of chronic lymphocytic leukemia (CLL) to accelerated CLL (aCLL) or transformation to diffuse large B-cell lymphoma (Richter transformation; RT) has significant clinical implications as it prompts a major change in patient management. However, the differentiation between these disease phases may be challenging in routine practice. Unsupervised learning has gained increased attention because of its substantial potential in data intrinsic pattern discovery. Here, we demonstrate that cellular feature engineering, identifying cellular phenotypes via unsupervised clustering, provides the most robust analytic performance in analyzing digitized pathology slides (accuracy = 0.925, AUC = 0.978) when compared to alternative approaches, such …

Targeting A Chemo-Induced Adaptive Signaling Circuit Confers Therapeutic Vulnerabilities In Pancreatic Cancer, Xu Feng, Mengfan Tang, Merve Dede, Dan Su, Guangsheng Pei, Dadi Jiang, Chao Wang, Zhen Chen, Mi Li, Litong Nie, Yun Xiong, Siting Li, Jeong-Min Park, Huimin Zhang, Min Huang, Klaudia Szymonowicz, Zhongming Zhao, Traver Hart, Junjie Chen

Faculty, Staff and Student Publications

Exploiting cancer vulnerabilities is critical for the discovery of anticancer drugs. However, tumor suppressors cannot be directly targeted because of their loss of function. To uncover specific vulnerabilities for cells with deficiency in any given tumor suppressor(s), we performed genome-scale CRISPR loss-of-function screens using a panel of isogenic knockout cells we generated for 12 common tumor suppressors. Here, we provide a comprehensive and comparative dataset for genetic interactions between the whole-genome protein-coding genes and a panel of tumor suppressor genes, which allows us to uncover known and new high-confidence synthetic lethal interactions. Mining this dataset, we uncover essential paralog gene …

Rapid Acceleration Of Kras-Mutant Pancreatic Carcinogenesis Via Remodeling Of Tumor Immune Microenvironment By Pparδ, Yi Liu, Yasunori Deguchi, Daoyan Wei, Fuyao Liu, Micheline J Moussalli, Eriko Deguchi, Donghui Li, Huamin Wang, Lovie Ann Valentin, Jennifer K Colby, Jing Wang, Xiaofeng Zheng, Haoqiang Ying, Mihai Gagea, Baoan Ji, Jiaqi Shi, James C Yao, Xiangsheng Zuo, Imad Shureiqi

Faculty, Staff and Student Publications

Pancreatic intraepithelial neoplasia (PanIN) is a precursor of pancreatic ductal adenocarcinoma (PDAC), which commonly occurs in the general populations with aging. Although most PanIN lesions (PanINs) harbor oncogenic KRAS mutations that initiate pancreatic tumorigenesis; PanINs rarely progress to PDAC. Critical factors that promote this progression, especially targetable ones, remain poorly defined. We show that peroxisome proliferator-activated receptor-delta (PPARδ), a lipid nuclear receptor, is upregulated in PanINs in humans and mice. Furthermore, PPARδ ligand activation by a high-fat diet or GW501516 (a highly selective, synthetic PPARδ ligand) in mutant KRASG12D (KRASmu) pancreatic epithelial cells strongly accelerates PanIN progression to PDAC. This …

Factors Associated With Covid-19 Death In The United States: Cohort Study, Uan-I Chen, Hua Xu, Trudy Millard Krause, Raymond Greenberg, Xiao Dong, Xiaoqian Jiang

Faculty, Staff and Student Publications

Background: Since the initial COVID-19 cases were identified in the United States in February 2020, the United States has experienced a high incidence of the disease. Understanding the risk factors for severe outcomes identifies the most vulnerable populations and helps in decision-making.

Objective: This study aims to assess the factors associated with COVID-19-related deaths from a large, national, individual-level data set.

Methods: A cohort study was conducted using data from the Optum de-identified COVID-19 electronic health record (EHR) data set; 1,271,033 adult participants were observed from February 1, 2020, to August 31, 2020, until their deaths due to COVID-19, deaths …

Factors Associated With Covid-19 Death In The United States: Cohort Study, Uan-I Chen, Hua Xu, Trudy Millard Krause, Raymond Greenberg, Xiao Dong, Xiaoqian Jiang

Faculty, Staff and Student Publications

BACKGROUND: Since the initial COVID-19 cases were identified in the United States in February 2020, the United States has experienced a high incidence of the disease. Understanding the risk factors for severe outcomes identifies the most vulnerable populations and helps in decision-making.

OBJECTIVE: This study aims to assess the factors associated with COVID-19-related deaths from a large, national, individual-level data set.

METHODS: A cohort study was conducted using data from the Optum de-identified COVID-19 electronic health record (EHR) data set; 1,271,033 adult participants were observed from February 1, 2020, to August 31, 2020, until their deaths due to COVID-19, deaths …

Treatment For Mild Chronic Hypertension During Pregnancy, Alan T Tita, Jeff M Szychowski, Kim Boggess, Lorraine Dugoff, Baha Sibai, Kirsten Lawrence, Brenna L Hughes, Joseph Bell, Kjersti Aagaard, Rodney K Edwards, Kelly Gibson, David M Haas, Lauren Plante, Torri Metz, Brian Casey, Sean Esplin, Sherri Longo, Matthew Hoffman, George R Saade, Kara K Hoppe, Janelle Foroutan, Methodius Tuuli, Michelle Y Owens, Hyagriv N Simhan, Heather Frey, Todd Rosen, Anna Palatnik, Susan Baker, Phyllis August, Uma M Reddy, Wendy Kinzler, Emily Su, Iris Krishna, Nicki Nguyen, Mary E Norton, Daniel Skupski, Yasser Y El-Sayed, Dotum Ogunyemi, Zorina S Galis, Lorie Harper, Namasivayam Ambalavanan, Nancy L Geller, Suzanne Oparil, Gary R Cutter, William W Andrews

Faculty, Staff and Students Publications

BACKGROUND: The benefits and safety of the treatment of mild chronic hypertension (blood pressure, <160/100 mm Hg) during pregnancy are uncertain. Data are needed on whether a strategy of targeting a blood pressure of less than 140/90 mm Hg reduces the incidence of adverse pregnancy outcomes without compromising fetal growth.

METHODS: In this open-label, multicenter, randomized trial, we assigned pregnant women with mild chronic hypertension and singleton fetuses at a gestational age of less than 23 weeks to receive antihypertensive medications recommended for use in pregnancy (active-treatment group) or to receive no such treatment unless severe hypertension (systolic pressure, ≥160 mm Hg; or diastolic pressure, ≥105 mm Hg) developed (control group). The primary outcome was a composite of preeclampsia with severe features, medically indicated preterm birth at less than 35 weeks' gestation, placental abruption, or fetal …

Prioritization Of Risk Genes In Multiple Sclerosis By A Refined Bayesian Framework Followed By Tissue-Specificity And Cell Type Feature Assessment, Andi Liu, Astrid M Manuel, Yulin Dai, Zhongming Zhao

Faculty, Staff and Student Publications

BACKGROUND: Multiple sclerosis (MS) is a debilitating immune-mediated disease of the central nervous system that affects over 2 million people worldwide, resulting in a heavy burden to families and entire communities. Understanding the genetic basis underlying MS could help decipher the pathogenesis and shed light on MS treatment. We refined a recently developed Bayesian framework, Integrative Risk Gene Selector (iRIGS), to prioritize risk genes associated with MS by integrating the summary statistics from the largest GWAS to date (n = 115,803), various genomic features, and gene-gene closeness.

RESULTS: We identified 163 MS-associated prioritized risk genes (MS-PRGenes) through the Bayesian framework. …

Lncrnas Uc145 And Prkg1-As1 Determine The Functional Output Of Dkk1 In Regulating The Wnt Signaling Pathway In Gastric Cancer, Jung-Ho Yoon, Hyojoo Byun, Cristina Ivan, George A Calin, Dahyun Jung, Sangkil Lee

Faculty, Staff and Student Publications

DKK1 inhibits the canonical Wnt signaling pathway that is known to be involved in various cancers. However, whether DKK1 acts as an oncogene or tumor suppressor gene remains controversial. Furthermore, the DKK1-regulating mechanism in gastric cancer has not yet been defined. The aim of this study was to explore whether the ultraconserved region UC.145 regulates epigenetic changes in DKK1 expression in gastric cancer. Microarray analysis revealed that UC.145 exhibited the highest binding affinity to EZH2, a histone methyltransferase. The effects of UC.145 inactivation were assessed in gastric cancer cell lines using siRNA. The results indicated that UC.145 triggers DKK1 methylation …

Immunogenomic Intertumor Heterogeneity Across Primary And Metastatic Sites In A Patient With Lung Adenocarcinoma, Runzhe Chen, Jun Li, Junya Fujimoto, Lingzhi Hong, Xin Hu, Kelly Quek, Ming Tang, Akash Mitra, Carmen Behrens, Chi-Wan Chow, Peixin Jiang, Latasha D Little, Curtis Gumbs, Xingzhi Song, Jianhua Zhang, Dongfeng Tan, John V Heymach, Ignacio Wistuba, P Andrew Futreal, Don L Gibbons, Lauren A Byers, Jianjun Zhang, Alexandre Reuben

Faculty, Staff and Student Publications

Background: Lung cancer is the leading cause of cancer death, partially owing to its extensive heterogeneity. The analysis of intertumor heterogeneity has been limited by an inability to concurrently obtain tissue from synchronous metastases unaltered by multiple prior lines of therapy.

Methods: In order to study the relationship between genomic, epigenomic and T cell repertoire heterogeneity in a rare autopsy case from a 32-year-old female never-smoker with left lung primary late-stage lung adenocarcinoma (LUAD), we did whole-exome sequencing (WES), DNA methylation and T cell receptor (TCR) sequencing to characterize the immunogenomic landscape of one primary and 19 synchronous metastatic tumors. …

The Technical Landscape For Patient-Centered Cds: Progress, Gaps, And Challenges, Prashila Dullabh, Krysta Heaney-Huls, David F Lobach, Lauren S Hovey, Shana F Sandberg, Priyanka J Desai, Edwin Lomotan, James Swiger, Michael I Harrison, Chris Dymek, Dean F Sittig, Aziz Boxwala

Faculty, Staff and Student Publications

Supporting healthcare decision-making that is patient-centered and evidence-based requires investments in the development of tools and techniques for dissemination of patient-centered outcomes research findings via methods such as clinical decision support (CDS). This article explores the technical landscape for patient-centered CDS (PC CDS) and the gaps in making PC CDS more shareable, standards-based, and publicly available, with the goal of improving patient care and clinical outcomes. This landscape assessment used: (1) a technical expert panel; (2) a literature review; and (3) interviews with 18 CDS stakeholders. We identified 7 salient technical considerations that span 5 phases of PC CDS development. …

Concerted Type I Interferon Signaling In Microglia And Neural Cells Promotes Memory Impairment Associated With Amyloid Β Plaques, Ethan R Roy, Gabriel Chiu, Sanming Li, Nicholas E Propson, Rupa Kanchi, Baiping Wang, Cristian Coarfa, Hui Zheng, Wei Cao

Faculty, Staff and Students Publications

The principal signals that drive memory and cognitive impairment in Alzheimer's disease (AD) remain elusive. Here, we revealed brain-wide cellular reactions to type I interferon (IFN-I), an innate immune cytokine aberrantly elicited by amyloid β plaques, and examined their role in cognition and neuropathology relevant to AD in a murine amyloidosis model. Using a fate-mapping reporter system to track cellular responses to IFN-I, we detected robust, Aβ-pathology-dependent IFN-I activation in microglia and other cell types. Long-term blockade of IFN-I receptor (IFNAR) rescued both memory and synaptic deficits and resulted in reduced microgliosis, inflammation, and neuritic pathology. Microglia-specific Ifnar1 deletion attenuated …

Asthma And Technology In Emerging African American Adults (The Athena Project): Protocol For A Trial Using The Multiphase Optimization Strategy Framework, Alan Baptist, Wanda Gibson-Scipio, April Idalski Carcone, Samiran Ghosh, Angela J Jacques-Tiura, Amy Hall, Karen Kolmodin Macdonell

Faculty, Staff and Student Publications

BACKGROUND: Asthma causes substantial morbidity and mortality in the United States, particularly among African American emerging adults (AAEAs; aged 18-30 years), but very few asthma programs have targeted this population. Interventions that provide education and address underlying motivation for managing asthma may be the most effective. However, intensive face-to-face interventions are often difficult to implement in this population.

OBJECTIVE: The purpose of this study is to develop an effective mobile asthma management intervention to improve control among AAEAs.

METHODS: We will assess the ability of multiple technologic components to assist and improve traditional asthma education. The first component is the …

Ezh2 Engages Tgfβ Signaling To Promote Breast Cancer Bone Metastasis Via Integrin Β1-Fak Activation, Lin Zhang, Jingkun Qu, Yutao Qi, Yimin Duan, Yu-Wen Huang, Zhifen Zhou, Ping Li, Jun Yao, Beibei Huang, Shuxing Zhang, Dihua Yu

Faculty, Staff and Student Publications

Bone metastases occur in 50-70% of patients with late-stage breast cancers and effective therapies are needed. The expression of enhancer of zeste homolog 2 (EZH2) is correlated with breast cancer metastasis, but its function in bone metastasis hasn't been well-explored. Here we report that EZH2 promotes osteolytic metastasis of breast cancer through regulating transforming growth factor beta (TGFβ) signaling. EZH2 induces cancer cell proliferation and osteoclast maturation, whereas EZH2 knockdown decreases bone metastasis incidence and outgrowth in vivo. Mechanistically, EZH2 transcriptionally increases ITGB1, which encodes for integrin β1. Integrin β1 activates focal adhesion kinase (FAK), which phosphorylates TGFβ receptor type …

Identification Of Biomarkers Of Response To Preoperative Talazoparib Monotherapy In Treatment Naïve Gbrca+ Breast Cancers, Xuan Liu, Zhongqi Ge, Fei Yang, Alejandro Contreras, Sanghoon Lee, Jason B White, Yiling Lu, Marilyne Labrie, Banu K Arun, Stacy L Moulder, Gordon B Mills, Helen Piwnica-Worms, Jennifer K Litton, Jeffrey T Chang

Faculty, Staff and Student Publications

Germline mutations in BRCA1 or BRCA2 exist in ~2-7% of breast cancer patients, which has led to the approval of PARP inhibitors in the advanced setting. We have previously reported a phase II neoadjuvant trial of single agent talazoparib for patients with germline BRCA pathogenic variants with a pathologic complete response (pCR) rate of 53%. As nearly half of the patients treated did not have pCR, better strategies are needed to overcome treatment resistance. To this end, we conducted multi-omic analysis of 13 treatment naïve breast cancer tumors from patients that went on to receive single-agent neoadjuvant talazoparib. We looked …

Evaluation Of Heat Inactivation Of Human Norovirus In Freshwater Clams Using Human Intestinal Enteroids, Tsuyoshi Hayashi, Yoko Yamaoka, Atsushi Ito, Takashi Kamaishi, Ryuichi Sugiyama, Mary K Estes, Masamichi Muramatsu, Kosuke Murakami

Faculty, Staff and Students Publications

Foodborne disease attributed to the consumption of shellfish contaminated with human norovirus (HuNoV) is one of many global health concerns. Our study aimed to determine the conditions of the heat-inactivation of HuNoV in freshwater clams (Corbicula japonica) using a recently developed HuNoV cultivation system employing stem-cell derived human intestinal enteroids (HIEs). We first measured the internal temperature of the clam tissue in a water bath during boiling at 90 °C and found that approximately 2 min are required for the tissue to reach 90 °C. Next, GII.4 HuNoV was spiked into the center of the clam tissue, followed …

Biliverdin Reductase Bridges Focal Adhesion Kinase To Src To Modulate Synaptic Signaling, Chirag Vasavda, Evan R Semenza, Jason Liew, Ruchita Kothari, Ryan S Dhindsa, Shruthi Shanmukha, Anthony Lin, Robert Tokhunts, Cristina Ricco, Adele M Snowman, Lauren Albacarys, Francesco Pastore, Cristian Ripoli, Claudio Grassi, Eugenio Barone, Michael D Kornberg, Xinzhong Dong, Bindu D Paul, Solomon H Snyder

Duncan NRI Faculty and Staff Publications

Synapses connect discrete neurons into vast networks that send, receive, and encode diverse forms of information. Synaptic function and plasticity—the neuronal process of adapting to diverse and variable inputs—depend on the dynamic nature of synaptic molecular components, which is mediated in part by cell adhesion signaling pathways. Here, we found that the enzyme biliverdin reductase (BVR) physically links together key focal adhesion signaling molecules at the synapse. BVR-null (BVR−/−) mice exhibited substantial deficits in learning and memory on neurocognitive tests, and hippocampal slices in which BVR was postsynaptically depleted showed deficits in electrophysiological responses to stimuli. …

Bi-Order Multimodal Integration Of Single-Cell Data, Jinzhuang Dou, Shaoheng Liang, Vakul Mohanty, Qi Miao, Yuefan Huang, Qingnan Liang, Xuesen Cheng, Sangbae Kim, Jongsu Choi, Yumei Li, Li Li, May Daher, Rafet Basar, Katayoun Rezvani, Rui Chen, Ken Chen

Faculty, Staff and Student Publications

Integration of single-cell multiomics profiles generated by different single-cell technologies from the same biological sample is still challenging. Previous approaches based on shared features have only provided approximate solutions. Here, we present a novel mathematical solution named bi-order canonical correlation analysis (bi-CCA), which extends the widely used CCA approach to iteratively align the rows and the columns between data matrices. Bi-CCA is generally applicable to combinations of any two single-cell modalities. Validations using co-assayed ground truth data and application to a CAR-NK study and a fetal muscle atlas demonstrate its capability in generating accurate multimodal co-embeddings and discovering cellular identity.

Central Nervous System Immune Interactome Is A Function Of Cancer Lineage, Tumor Microenvironment, And Stat3 Expression, Hinda Najem, Martina Ott, Cynthia Kassab, Arvind Rao, Ganesh Rao, Anantha Marisetty, Adam M Sonabend, Craig Horbinski, Roel Verhaak, Anand Shankar, Santhoshi N Krishnan, Frederick S Varn, Víctor A Arrieta, Pravesh Gupta, Sherise D Ferguson, Jason T Huse, Gregory N Fuller, James P Long, Daniel E Winkowski, Ben A Freiberg, Charles David James, Leonidas C Platanias, Maciej S Lesniak, Jared K Burks, Amy B Heimberger

Faculty, Staff and Student Publications

BACKGROUND

Immune cell profiling of primary and metastatic CNS tumors has been focused on the tumor, not the tumor microenvironment (TME), or has been analyzed via biopsies.

METHODS

En bloc resections of gliomas (n = 10) and lung metastases (n = 10) were analyzed via tissue segmentation and high-dimension Opal 7-color multiplex imaging. Single-cell RNA analyses were used to infer immune cell functionality.

RESULTS

Within gliomas, T cells were localized in the infiltrating edge and perivascular space of tumors, while residing mostly in the stroma of metastatic tumors. CD163⁺ macrophages were evident throughout the TME of metastatic …

Racial And Ethnic Differences In Genomic Profiling Of Early Onset Colorectal Cancer, David M Hein, Weiye Deng, Marylena Bleile, Syed Ali Kazmi, Brooke Rhead, Francisco M De La Vega, Amy L Jones, Radhika Kainthla, Wen Jiang, Brandi Cantarel, Nina N Sanford

Faculty, Staff and Student Publications

The incidence and mortality of early onset colorectal cancer (EOCRC) is rising; outcomes appear to differ by race and ethnicity. We aimed to assess differences in mutational landscape and gene expression of EOCRC by racial and ethnic groups (non-Hispanic Asian, non-Hispanic Black, non-Hispanic White, White Hispanic) using data from the American Association for Cancer Research Project GENIE (10.2) and University of Texas Southwestern, the latter enriched in Hispanic patients. All statistical tests were 2-sided. Of 1752 EOCRC patients, non-Hispanic Black patients had higher rates of KRAS mutations (60.9%; P = .001, q = 0.015), and non-Hispanic White and non-Hispanic Black …

Pattern Differentiation And Tuning Shift In Human Sensory Cortex Underlie Long-Term Threat Memory, Yuqi You, Lucas R Novak, Kevin J Clancy, Wen Li

Faculty, Staff and Student Publications

The amygdala-prefrontal-cortex circuit has long occupied the center of the threat system 1, but new evidence has rapidly amassed to implicate threat processing outside this canonical circuit 2-4. Through non-human research, the sensory cortex has emerged as a critical substrate for long-term threat memory 5-9, underpinned by sensory cortical pattern separation/completion 10,11 and tuning shift 12,13. In humans, research has begun to associate the human sensory cortex with long-term threat memory 14,15, but the lack of mechanistic insights obscures a direct linkage. Towards that end, …

Characterization Of Retinal Function And Structure In The Mptp Murine Model Of Parkinson's Diseasecharacterization Of Retinal Function And Structure In The Mptp Murine Model Of Parkinson’S Disease, Katie K N Tran, Vickie H Y Wong, Jeremiah K H Lim, Ali Shahandeh, Anh Hoang, David I Finkelstein, Bang V Bui, Christine T O Nguyen

Faculty, Staff and Student Publications

In addition to well characterized motor symptoms, visual disturbances are increasingly recognized as an early manifestation in Parkinson's disease (PD). A better understanding of the mechanisms underlying these changes would facilitate the development of vision tests which can be used as preclinical biomarkers to support the development of novel therapeutics for PD. This study aims to characterize the retinal phenotype of a mouse model of dopaminergic dysfunction and to examine whether these changes are reversible with levodopa treatment. We use a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD to characterize the neurotoxic effects of MPTP on in vivo retinal function (electroretinography, …

The Ep300/Tp53 Pathway, A Suppressor Of The Hippo And Canonical Wnt Pathways, Is Activated In Human Hearts With Arrhythmogenic Cardiomyopathy In The Absence Of Overt Heart Failure, Leila Rouhi, Siyang Fan, Sirisha M Cheedipudi, Aitana Braza-Boïls, Maria Sabater Molina, Yan Yao, Matthew J Robertson, Cristian Coarfa, Juan R Gimeno, Pilar Molina, Priyatansh Gurha, Esther Zorio, Ali J Marian

Faculty, Staff and Students Publications

AIMS: Arrhythmogenic cardiomyopathy (ACM) is a primary myocardial disease that typically manifests with cardiac arrhythmias, progressive heart failure, and sudden cardiac death (SCD). ACM is mainly caused by mutations in genes encoding desmosome proteins. Desmosomes are cell-cell adhesion structures and hubs for mechanosensing and mechanotransduction. The objective was to identify the dysregulated molecular and biological pathways in human ACM in the absence of overt heart failure.

METHODS AND RESULTS: Transcriptomes in the right ventricular endomyocardial biopsy samples from three independent individuals carrying truncating mutations in the DSP gene and five control samples were analysed by RNA-Seq (discovery group). These cases …

Perceptions Of Integrating Immersive Virtual Reality Simulation As A Teaching Methodology In A Hospital Setting, Ladonna Christy

Dissertations and Theses (Open Access)

Introduction As newly licensed nurses enter the workforce with limited experience and limited clinical reasoning skills, nursing educators must employ innovative strategies to teach graduate nurses how to identify and manage clinical deterioration – skills which are vital to saving lives and improving outcomes. Fully immersive Virtual Reality (VR), (also defined as Immersive VR) is one effective educational strategy available for hospital educators to use for preparing newly licensed nurses to recognize and manage clinical deterioration.

Objective The purpose of this study was to explore perceptions of hospital-based nurse educators, simulation specialists, and nursing leaders with respect to integrating immersive …

Postpartum Depression Screening In The Neonatal Intensive Care Unit: Maternal And Provider Perspectives, Candice Triulzi

Dissertations and Theses (Open Access)

Objective: Although mothers of preterm infants are at increased risk for postpartum depression (PPD), PPD screening conducted by neonatal providers in the Neonatal Intensive Care Unit (NICU) is currently not a standard of care. The purpose of this study was to explore maternal and provider perceptions of neonatal providers conducting PPD screening in the NICU.

Design: This study was conducted with a qualitative approach.

Setting: A 24-bed Level III NICU in Houston, TX acted as the study site.

Participants: Participants were purposively sampled (N=31) and included mothers of NICU infants (n=15) and NICU providers (n=16).

Methods: Semi-structured individual and paired …

Factors Associated With Advance Care Planning Engagement In Healthy Young Adults, Pablo J. Vasquez

Dissertations and Theses (Open Access)

Background: Advance care planning (ACP) is a process that supports individuals at any stage of health in understanding and sharing their personal values and goals pertaining current or future medical needs with their families and healthcare providers. Although ACP is applicable to adults of any age and any stage of the health continuum, it is widely associated with older or terminally ill populations, and the need for end-of-life (EOL) planning in healthy young adults is generally found unnecessary. The National Institutes of Health supports the expansion of ACP research in understudied populations. Investigating ACP in healthy young adults support such …

Burden Of Cardiovascular Risk Factors And Disease In Five Asian Groups In Catalonia: A Disaggregated, Population-Based Analysis Of 121 000 First-Generation Asian Immigrants, Priyanka Satish, Emili Vela, Usama Bilal, Montse Cleries, Alka M Kanaya, Namratha Kandula, Salim S Virani, Nadia Islam, Javier Valero-Elizondo, Tamer Yahya, Josep Comin-Colet, Khurram Nasir, Josepa Mauri, Miguel Cainzos-Achirica

Faculty, Staff and Students Publications

AIMS: To evaluate the burden of cardiovascular risk factors and disease (CVD) among five Asian groups living in Catalonia (Spain): Indian, Pakistani, Bangladeshi, Filipino, and Chinese.

METHODS AND RESULTS: Retrospective cohort study using the Catalan Health Surveillance System database including 42 488 Pakistanis, 40 745 Chinese, 21 705 Indians, 9544 Filipinos, and 6907 Bangladeshis; and 5.3 million native individuals ('locals'). We estimated the age-adjusted prevalence (as of 31 December 2019) and incidence (during 2019) of diabetes, hypertension, hyperlipidaemia, obesity, tobacco use, coronary heart disease (CHD), cerebrovascular disease, atrial fibrillation, and heart failure (HF). Bangladeshis had the highest prevalence of diabetes …