Digital Commons Network^™

Survey Of Nationwide Public Perceptions Regarding Acceptance Of Wastewater Used For Community Health Monitoring In The United States., A. Scott Lajoie, Rochelle H. Holm, Lauren B. Anderson, Heather D. Ness, Ted Smith

Faculty and Staff Scholarship

To assess the levels of infection across communities during the coronavirus disease 2019 pandemic, researchers have measured severe acute respiratory syndrome coronavirus 2 RNA in feces dissolved in sewer water. This activity is colloquially known as sewer monitoring and is referred to as wastewater-based epidemiology in academic settings. Although global ethical principles have been described, sewer monitoring is unregulated for health privacy protection when used for public health surveillance in the United States. This study used Qualtrics XM, a national research panel provider, to recruit participants to answer an online survey. Respondents (N = 3,083) answered questions about their knowledge, …

Spatially Resolved Transcriptomics Of High-Grade Serous Ovarian Carcinoma, Elaine Stur, Sara Corvigno, Mingchu Xu, Ken Chen, Yukun Tan, Sanghoon Lee, Jinsong Liu, Emily Ricco, Daniel Kraushaar, Patricia Castro, Jianhua Zhang, Anil K Sood

Faculty, Staff and Students Publications

Bulk and single-cell RNA sequencing do not provide full characterization of tissue spatial diversity in cancer samples, and currently available in situ techniques (multiplex immunohistochemistry and imaging mass cytometry) allow for only limited analysis of a small number of targets. The current study represents the first comprehensive approach to spatial transcriptomics of high-grade serous ovarian carcinoma using intact tumor tissue. We selected a small cohort of patients with highly annotated high-grade serous ovarian carcinoma, categorized them by response to neoadjuvant chemotherapy (poor or excellent), and analyzed pre-treatment tumor tissue specimens. Our study uncovered extensive differences in tumor composition between the …

Skp2 Stabilizes Mcl-1 And Confers Radioresistance In Colorectal Cancer, Xinfang Yu, Li Zhou, Wenbin Liu, Lijun Liu, Feng Gao, Wei Li, Haidan Liu

Faculty, Staff and Students Publications

Overexpression of Skp2 plays a critical role in tumorigenesis and correlates with poor prognosis in human malignancies. Thus, Skp2 has been proposed as an attractive target for anti-tumor interventions. The expression of Skp2 in human colorectal cancer (CRC) and the role of Skp2 in tumorigenic properties and irradiation sensitivities of CRC cells were examined by anchorage-dependent and -independent growth assays, immunoblot, flow cytometry, immunohistochemical staining, ubiquitination analysis, co-immunoprecipitation assay, CRISPR-Cas9-based gene knockout, and xenograft experiments. Skp2 is highly expressed in CRC patient tissues. Blocking Skp2 expression reduces the tumorigenic properties of CRC cells in vitro and in vivo. Depletion of …

The Therapeutic Effect Of Exogenous Melatonin On Depressive Symptoms: A Systematic Review And Meta-Analysis, Cancan Li, Dandan Ma, Min Li, Tao Wei, Xuan Zhao, Yuanyuan Heng, Delong Ma, Enoch Odame Anto, Yanbo Zhang, Mingyun Niu, Wangxin Zhang

Research outputs 2022 to 2026

Background: Depression-related mortality and morbidity pose growing public health burdens worldwide. Although the therapeutic effect of exogenous melatonin on depression has been investigated, findings remain inconsistent. We conducted this systematic review and meta-analysis to clarify the effectiveness of melatonin in the treatment of depression, including primary and secondary depression symptoms. Methods: We searched the online databases of PubMed, EMBASE, and the Cochrane Library for original studies published up to May 2021. We used STATA 14.0 software to synthesize the results of included studies. To evaluate the effectiveness of melatonin, we calculated the standardized mean differences (SMDs) and 95% confidence intervals …

Monitoring Sars-Cov-2 In Wastewater During New York City's Second Wave Of Covid-19: Sewershed-Level Trends And Relationships To Publicly Available Clinical Testing Data, Catherine Hoar, Francoise Chauvin, Alexander Clare, Hope Mcgibbon, Esmeraldo Castro, Samantha Patinella, Dimitrios Katehis, John J. Dennehy, Monica Trujillo, Davida S. Smyth, Andrea I. Silverman

Publications and Research

New York City's wastewater monitoring program tracked trends in sewershed-level SARS-CoV-2 loads starting in the fall of 2020, just before the start of the city's second wave of the COVID-19 outbreak. During a five-month study period, from November 8, 2020 to April 11, 2021, viral loads in influent wastewater from each of New York City's 14 wastewater treatment plants were measured and compared to new laboratory-confirmed COVID-19 cases for the populations in each corresponding sewershed, estimated from publicly available clinical testing data. We found significant positive correlations between viral loads in wastewater and new COVID-19 cases. The strength of the …

The Effect Of Task And Environment Constraints On Aquatic Locomotor Behavior: Qualitative Data Analysis, Ernani Xavier Filho, Edison J. Manoel

International Journal of Aquatic Research and Education

Many constraints (environmental, organismic, and task) act on all patterns of motor coordination, although their effects on swimming is less well understood. To this end, we carried out the current study with fifty-six participants, ages ranging from six to twelve years. The experimental tasks were created from the original task in which changes in task speed and environmental context were manipulated. Four aspects in the results were notable: a) a main trend was one of performance with the same developmental status among the tasks; b) when behaviour changed, this occurred due to environmental constraints, leading to more rudimentary patterns of …

Trends In Scientific Output On The Lesbian, Gay, Bisexual, And Transgender (Lgbt) Community Research: A Bibliometric Analysis Of The Literature, David An, Kavita Batra

School of Medicine Faculty Research

Introduction: Lesbian, Gay, Bisexual, and Transgender (LGBT) represent a diverse group with special needs due to the unusual developmental experiences and social inequalities. This paper aims to explore and outline a future research direction in LGBT issues through tracing our historical understanding of this population from an aspect of scientific research. Methods: LGBT-related peer-reviewed documents were retrieved from the PubMed database and the study period was set from the inception to 2021. Python-based methods were then performed to analyze the publication metadata and extract the most prominent research topics based on the abstract contents. Key points covered in the study …

American Heart Association's Life's Simple 7: Lifestyle Recommendations, Polygenic Risk, And Lifetime Risk Of Coronary Heart Disease, Natalie R Hasbani, Symen Ligthart, Michael R Brown, Adam S Heath, Allison Bebo, Kellan E Ashley, Eric Boerwinkle, Alanna C Morrison, Aaron R Folsom, David Aguilar, Paul S De Vries

Faculty, Staff and Students Publications

BACKGROUND: Understanding the effect of lifestyle and genetic risk on the lifetime risk of coronary heart disease (CHD) is important to improving public health initiatives. Our objective was to quantify remaining lifetime risk and years free of CHD according to polygenic risk and the American Heart Association's Life's Simple 7 (LS7) guidelines in a population-based cohort study.

METHODS: Our analysis included data from participants of the ARIC (Atherosclerosis Risk in Communities) study: 8372 White and 2314 Black participants; 45 years of age and older; and free of CHD at baseline examination. A polygenic risk score (PRS) comprised more than 6 …

Creation Of An Influenza A Virus Neuraminidase Consensus Vaccine In An Adenoviral Vector, Leigh Jahnke

Honors Program: Senior Projects (Public)

In the last decade, the estimated annual burden of the flu includes 12,000-52,000 deaths, 140,000-710,000 hospitalizations, and 9 million – 41 million illnesses (Centers for Disease Control and Prevention: Disease burden of the flu). Influenza A virus can mutate and infect a variety of different hosts, which results in frequent antigenic changes and even pandemics. This has led to increased attention on the creation of a universal Influenza A vaccine containing broader immunogenic coverage than current vaccines. Our research involved detailing the steps of the cloning process utilizing a consensus neuraminidase antigen. We utilized the pAdEasy Adenoviral Vector …

Triglyceride-Rich Lipoproteins, Apolipoprotein C-Iii, Angiopoietin-Like Protein 3, And Cardiovascular Events In Older Adults: Atherosclerosis Risk In Communities (Aric) Study, Aliza Hussain, Caroline Sun, Elizabeth Selvin, Vijay Nambi, Josef Coresh, Xiaoming Jia, Christie M Ballantyne, Ron C Hoogeveen

Faculty, Staff and Students Publications

AIMS: Despite statin and antihypertensive therapies, older Americans have high atherosclerotic cardiovascular disease (ASCVD) risk. Novel measures of triglyceride-rich lipoproteins, low-density lipoprotein triglycerides (LDL-TG), and remnant-like particle cholesterol (RLP-C), are associated with ASCVD in middle-aged adults. Polymorphisms in genes encoding angiopoietin-related protein 3 (ANGPTL3) and apolipoprotein C-III (apoC-III), two proteins involved in triglyceride catabolism, are associated with increased risk for hypertriglyceridaemia and ASCVD and are potential therapeutic targets. We examined associations of LDL-TG, RLP-C, apoC-III, and ANGPTL3 levels with ASCVD events in older adults in the Atherosclerosis Risk in Communities (ARIC) study.

METHODS AND RESULTS: In 6359 participants (mean age …

Antibacterial And Anti-Hiv-1 Gp120 Activities Of Selected Medicinal Plants, Rose J. Masalu, Cyprian B. Mpinda

Journal of Humanities and Social Sciences

Medicinal plants play an important role in traditional medicine and drug development research because of their numerous bioactivities. However, some concerns have risen on the inefficiencies of such products due to improper use of medicinal plant products, notably when mixed with other traditional remedies. This study evaluates the antibacterial and anti-human immunodeficiency virus 1 glycoprotein 120/CD4 (anti-HIV-1 GP120/CD4) activities of medicinal plants species Sapium ellipticum, Pseudospondias microcarpa, and Capparis erythrocarpos; and their respective combinations effects. Results revealed that aqueous and ethyl acetate extracts of S. ellipticum and P. microcarpa had antimicrobial activities against S. aureus (ATCC 25923), E. coli (ATCC …

Determinants Of Covid-19 Vaccinations Among A State-Wide Year-Long Surveillance Initiative In A Conservative Southern State, Lídia Gual-Gonzalez, Maggie S.J. Mccarter, Kyndall Dye-Braumuller, Stella Self, Connor H. Ross, Chloe Rodriguez-Ramos, Virginie G. Daguise, Melissa Nolan Ph.D., Mph

Faculty Publications

By the end of 2021, the COVID-19 pandemic resulted in over 54 million cases and more than 800,000 deaths in the United States, and over 350 million cases and more than 5 million deaths worldwide. The uniqueness and gravity of this pandemic have been reflected in the public health guidelines poorly received by a growing subset of the United States population. These poorly received guidelines, including vaccine receipt, are a highly complex psychosocial issue, and have impacted the successful prevention of disease spread. Given the intricate nature of this important barrier, any single statistical analysis methodologically fails to address all …

Elucidating Mechanisms Of Genetic Cross-Disease Associations At The Procr Vascular Disease Locus, David Stacey, Lingyan Chen, Paulina J Stanczyk, Joanna M M Howson, Amy M Mason, Stephen Burgess, Stephen Macdonald, Jonathan Langdown, Harriett Mckinney, Kate Downes, Neda Farahi, James E Peters, Saonli Basu, James S Pankow, Weihong Tang, Nathan Pankratz, Maria Sabater-Lleal, Paul S De Vries, Nicholas L Smith, Amy D Gelinas, Daniel J Schneider, Nebojsa Janjic, Nilesh J Samani, Shu Ye, Charlotte Summers, Edwin R Chilvers, John Danesh, Dirk S Paul

Faculty, Staff and Student Publications

Many individual genetic risk loci have been associated with multiple common human diseases. However, the molecular basis of this pleiotropy often remains unclear. We present an integrative approach to reveal the molecular mechanism underlying the PROCR locus, associated with lower coronary artery disease (CAD) risk but higher venous thromboembolism (VTE) risk. We identify PROCR-p.Ser219Gly as the likely causal variant at the locus and protein C as a causal factor. Using genetic analyses, human recall-by-genotype and in vitro experimentation, we demonstrate that PROCR-219Gly increases plasma levels of (activated) protein C through endothelial protein C receptor (EPCR) ectodomain shedding in endothelial cells, …

Applying Transformative Evaluation To Assess Service Provided To African Americans Through The Snap-Ed Program, Matthew Greene

LSU Doctoral Dissertations

Obesity and food insecurity are disproportionately experienced by African Americans compared to white Americans. African Americans encounter multiple barriers to healthful eating in their food environment, in part due to structural racism. Four studies were undertaken to understand how SNAP-Ed may best address the needs of African Americans and whether the program is serving African Americans in Louisiana equitably. In the first study, a scoping review was conducted to describe nutrition interventions addressing structural racism experienced by African Americans and compare them to the Getting to Equity in Obesity Prevention Framework. Nearly all included studies focused on PSE change interventions …

Intergenerational Risk And Resilience Pathways From Discrimination And Acculturative Stress To Infant Mental Health, Sabrina R. Liu, Curt A. Sandman, Elyssia Poggi Davis, Laura M. Glynn

Psychology Faculty Articles and Research

Preconception and prenatal stress impact fetal and infant development, and women of color are disproportionately exposed to sociocultural stressors like discrimination and acculturative stress. However, few studies examine links between mothers’ exposure to these stressors and offspring mental health, or possible mitigating factors. Using linear regression, we tested associations between prenatally assessed maternal acculturative stress and discrimination on infant negative emotionality among 113 Latinx/Hispanic, Asian American, Black, and Multiethnic mothers and their children. Additionally, we tested interactions between stressors and potential pre- and postnatal resilience-promoting factors: community cohesion, social support, communalism, and parenting self-efficacy. Discrimination and acculturative stress were related …

Structural And Computational Studies Of The Sars-Cov-2 Spike Protein Binding Mechanisms With Nanobodies: From Structure And Dynamics To Avidity-Driven Nanobody Engineering, Gennady M. Verkhivker

Mathematics, Physics, and Computer Science Faculty Articles and Research

Nanobodies provide important advantages over traditional antibodies, including their smaller size and robust biochemical properties such as high thermal stability, high solubility, and the ability to be bioengineered into novel multivalent, multi-specific, and high-affinity molecules, making them a class of emerging powerful therapies against SARS-CoV-2. Recent research efforts on the design, protein engineering, and structure-functional characterization of nanobodies and their binding with SARS-CoV-2 S proteins reflected a growing realization that nanobody combinations can exploit distinct binding epitopes and leverage the intrinsic plasticity of the conformational landscape for the SARS-CoV-2 S protein to produce efficient neutralizing and mutation resistant characteristics. Structural …

Effective Lifeguard Scanning: A Review, Stephen J. Langendorfer Ph.D., Francesco (Frank) A. Pia Ph.D., Angela K. Beale-Tawfeeq Ph.D.

International Journal of Aquatic Research and Education

The purpose of this scientific review was to address the question of what evidence-based visual surveillance/scanning skills exist in the peer-reviewed scholarly literature. It is well known that lifeguards spend a majority of their on-duty time surveying bathers and swimmers in the water. Lifeguards need to quickly distinguish among swimmers in distress and drowning persons from other bathers in order to rapidly come to their aid to prevent drowning. To be able to accomplish this task, Signal Detection Theory reveals that lifeguards need specific and extensive training in identifying the behavioral patterns associated with drowning persons and swimmers in distress. …

Covid-19 In Cns And Pns: Basic And Clinical Focus On The Mechanisms Of Infection And New Tools For The Therapeutic Approach, Jorge Matias-Guiu, Jordi A. Matias-Guiu, Carmen Garrido, Genaro Pimienta, Patricio F. Reyes, Abdul Mannan Baig, Ulises Gomez-Pinedo

Department of Biological & Biomedical Sciences

No abstract provided.

Civic Engagement As A Pathway To Meaningful Medical Student Engagement On The Social Determinants Of Health, Alexander Reardon, Jennie Deblanc, Alister Martin

Journal of Health Disparities Research and Practice

The social determinants of health have gained increasing prominence in medical education, but medical students and professionals alike are under-prepared to address those determinants. There is a growing body of evidence that voting and other forms of civic engagement affect the health of patients and communities. Registering patients in healthcare settings offers students and professionals an opportunity to impact their patients’ health beyond the clinical encounter. Medical students are particularly well suited to this work for a variety of reasons, including increasingly positive attitudes toward this kind of advocacy, increasing diversity in the medical student body, and lighter clinical and …

The Importance Of Health Literacy: A Student-Led Workshop On Lay Communication, Sarah Jean Kamp, Jafra D. Thomas

Kinesiology and Public Health

The purpose of this experiential senior project workshop was to advance the knowledge and practice of health communication by (a) delivering a training workshop to Cal Poly undergraduate students and (b) by exploring the relationship between health literacy and effective communication through completion of a rapid review of the literature. The reviewed literature served the purpose of helping the student further design the workshop to elicit a foundational understanding of the elements of effective communication of health information as well as the history and evolution of health literacy as a concept. The workshop revised and delivered by the student was …

Impacts Of Climate Change And Heat Stress On Farmworkers' Health: A Scoping Review, Moussa El Khayat, Dana A. Halwani, Layal Hneiny, Ibrahim Alameddine, Mustapha A. Haidar, Rima R. Habib

Faculty Publications

Due to the continuous rise of global temperatures and heatwaves worldwide as a result of climate change, concerns for the health and safety of working populations have increased. Workers in the food production chain, particularly farmworkers, are especially vulnerable to heat stress due to the strenuous nature of their work, which is performed primarily outdoors under poor working conditions. At the cross-section of climate change and farmworkers' health, a scoping review was undertaken to summarize the existing knowledge regarding the health impacts associated with climate change and heat stress, guide future research toward better understanding current and future climate change …

Interactions Of Agricultural Pesticide Use Near Home During Pregnancy And Adverse Childhood Experiences On Adolescent Neurobehavioral Development In The Chamacos Study, Carly Hyland

Public and Population Health Faculty Publications and Presentations

Background: Studies have documented independent adverse associations between prenatal and early-life exposure to environmental chemicals and social adversity with child neurodevelopment; however, few have considered these exposures jointly. The objective of this analysis is to examine whether associations of pesticide mixtures and adolescent neurobehavioral development are modified by early-life adversity in the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) cohort.

Methods: We used linear mixed effects Bayesian Hierarchical Models (BHM) to examine the joint effect of applications of 11 agricultural pesticides within 1 km of maternal homes during pregnancy and youth-reported Adverse Childhood Experiences (ACEs) …

Sexual Coercion, Unintended Pregnancy, And Poor Reproductive Health Among Adolescent Girls (Aged 13 - 19) In Mexico, Arun Kumar Acharya, Maria Luisa Martinez

Dignity: A Journal of Analysis of Exploitation and Violence

In Mexico, nearly 23,000 adolescents between the ages of 12-17 years suffer sexual coercion every year. This group also has a high birth rate of 77/1,000 adolescents, which indicates that one in every five pregnant women is an adolescent. This study describes the sexual coercion of victims and their views regarding the experience based on data collected from 37 Mexican girls between the age of 13 to 19, selected purposively using the snowball method in Monterrey city, Mexico. Results indicate that sexual coercion among adolescents is a serious problem, where 70% of adolescents experienced vaginal sexual coercion, nearly 22% experienced …

Riding The Wave: Reactive Vector-Borne Disease Policy Renders The United States Vulnerable To Outbreaks And Insecticide Resistance, Kyndall C. Dye-Braumuller, Jennifer R. Gordon, Kaci Mccoy, Danielle Johnson, Rhoel Dinglasan, Melissa Nolan Ph.D., Mph

Faculty Publications

Funding for vector-borne disease surveillance, management, and research is cyclical and reactive in the United States. The subsequent effects have yielded gross inequities nationally that unintentionally support recurrent outbreaks. This policy forum is comprised of four primary subsections that collectively identify specific areas for improvement and offer innovative solutions to address national inadequacies in vector borne disease policy and infrastructure.

Travel Ban Effects On Sars-Cov-2 Transmission Lineages In The Uae As Inferred By Genomic Epidemiology, Andreas Henschel, Samuel F. Feng, Rifat A. Hamoudi, Gihan Daw Elbait, Ernesto Damiani, Fathimathuz Waasia, Guan K. Tay, Bassam H. Mahboub, Maimunah Hemayet Uddin, Juan Acuna, Eman Alefishat, Rabih Halwani, Herbert F. Jelinek, Farah Mustafa, Nawal Alkaabi, Habiba S. Alsafar

Research outputs 2022 to 2026

Global and local whole genome sequencing of SARS-CoV-2 enables the tracing of domestic and international transmissions. We sequenced Viral RNA from 37 sampled Covid-19 patients with RT-PCR-confirmed infections across the UAE and developed time-resolved phylogenies with 69 local and 3,894 global genome sequences. Furthermore, we investigated specific clades associated with the UAE cohort and, their global diversity, introduction events and inferred domestic and international virus transmissions between January and June 2020. The study comprehensively characterized the genomic aspects of the virus and its spread within the UAE and identified that the prevalence shift of the D614G mutation was due to …

Clinical Outcomes And Bacterial Characteristics Of Carbapenem-Resistant Klebsiella Pneumoniae Complex Among Patients From Different Global Regions (Crackle-2): A Prospective, Multicentre, Cohort Study, Minggui Wang, Michelle Earley, Liang Chen, Blake M Hanson, Yunsong Yu, Zhengyin Liu, Soraya Salcedo, Eric Cober, Lanjuan Li, Souha S Kanj, Hainv Gao, Jose M Munita, Karen Ordoñez, Greg Weston, Michael J Satlin, Sandra L Valderrama-Beltrán, Kalisvar Marimuthu, Martin E Stryjewski, Lauren Komarow, Courtney Luterbach, Steve H Marshall, Susan D Rudin, Claudia Manca, David L Paterson, Jinnethe Reyes, Maria V Villegas, Scott Evans, Carol Hill, Rebekka Arias, Keri Baum, Bettina C Fries, Yohei Doi, Robin Patel, Barry N Kreiswirth, Robert A Bonomo, Henry F Chambers, Vance G Fowler, Cesar A Arias, David Van Duin, Multi-Drug Resistant Organism Network Investigators

Faculty, Staff and Student Publications

BACKGROUND: Carbapenem-resistant Klebsiella pneumoniae (CRKP) is a global threat. We therefore analysed the bacterial characteristics of CRKP infections and the clinical outcomes of patients with CRKP infections across different countries.

METHODS: In this prospective, multicentre, cohort study (CRACKLE-2), hospitalised patients with cultures positive for CRKP were recruited from 71 hospitals in Argentina, Australia, Chile, China, Colombia, Lebanon, Singapore, and the USA. The first culture positive for CRKP was included for each unique patient. Clinical data on post-hospitalisation death and readmission were collected from health records, and whole genome sequencing was done on all isolates. The primary outcome was a desirability …

Type 2 Diabetes Partitioned Polygenic Scores Associate With Disease Outcomes In 454,193 Individuals Across 13 Cohorts, Daniel Dicorpo, Jessica Leclair, Joanne B Cole, Chloé Sarnowski, Fariba Ahmadizar, Lawrence F Bielak, Anneke Blokstra, Erwin P Bottinger, Layal Chaker, Yii-Der I Chen, Ye Chen, Paul S De Vries, Tariq Faquih, Mohsen Ghanbari, Valborg Gudmundsdottir, Xiuqing Guo, Natalie R Hasbani, Dorina Ibi, M Arfan Ikram, Maryam Kavousi, Hampton L Leonard, Aaron Leong, Josep M Mercader, Alanna C Morrison, Girish N Nadkarni, Mike A Nalls, Raymond Noordam, Michael Preuss, Jennifer A Smith, Stella Trompet, Petra Vissink, Jie Yao, Wei Zhao, Eric Boerwinkle, Mark O Goodarzi, Vilmundur Gudnason, J Wouter Jukema, Sharon L R Kardia, Ruth J F Loos, Ching-Ti Liu, Alisa K Manning, Dennis Mook-Kanamori, James S Pankow, H Susan J Picavet, Naveed Sattar, Eleanor M Simonsick, W M Monique Verschuren, Ko Willems Van Dijk, Jose C Florez, Jerome I Rotter, James B Meigs, Josée Dupuis, Miriam S Udler

Faculty, Staff and Student Publications

OBJECTIVE: Type 2 diabetes (T2D) has heterogeneous patient clinical characteristics and outcomes. In previous work, we investigated the genetic basis of this heterogeneity by clustering 94 T2D genetic loci using their associations with 47 diabetes-related traits and identified five clusters, termed β-cell, proinsulin, obesity, lipodystrophy, and liver/lipid. The relationship between these clusters and individual-level metabolic disease outcomes has not been assessed.

RESEARCH DESIGN AND METHODS: Here we constructed individual-level partitioned polygenic scores (pPS) for these five clusters in 12 studies from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium and the UK Biobank (n = 454,193) …

Elucidating The Clinical Spectrum And Molecular Basis Of Hyal2 Deficiency, James Fasham, Siying Lin, Promita Ghosh, Francesca Clementina Radio, Emily G Farrow, Isabelle Thiffault, Jennifer Kussman, Dihong Zhou, Rick Hemming, Kenneth Zahka, Barry A Chioza, Lettie E Rawlins, Olivia K Wenger, Adam C Gunning, Simone Pizzi, Roberta Onesimo, Giuseppe Zampino, Emily Barker, Natasha Osawa, Megan Christine Rodriguez, Teresa M Neuhann, Elaine H Zackai, Beth Keena, Jenina Capasso, Alex V Levin, Elizabeth Bhoj, Dong Li, Hakon Hakonarson, Ingrid M Wentzensen, Adam Jackson, Kate E Chandler, Zeynep H Coban-Akdemir, Jennifer E Posey, Siddharth Banka, James R Lupski, Sarah E Sheppard, Marco Tartaglia, Barbara Triggs-Raine, Andrew H Crosby, Emma L Baple

Faculty, Staff and Student Publications

PURPOSE: We previously defined biallelic HYAL2 variants causing a novel disorder in 2 families, involving orofacial clefting, facial dysmorphism, congenital heart disease, and ocular abnormalities, with Hyal2 knockout mice displaying similar phenotypes. In this study, we better define the phenotype and pathologic disease mechanism.

METHODS: Clinical and genomic investigations were undertaken alongside molecular studies, including immunoblotting and immunofluorescence analyses of variant/wild-type human HYAL2 expressed in mouse fibroblasts, and in silico modeling of putative pathogenic variants.

RESULTS: Ten newly identified individuals with this condition were investigated, and they were associated with 9 novel pathogenic variants. Clinical studies defined genotype-phenotype correlations and …

Determinant Of Repeat Revascularization Within 5 Years Of Percutaneous Coronary Lntervention At A Tertiary Care Hospital, Karachi: A Matched Case-Control Study, Komal Valliani, Azmina Artani, Iqbal Azam, Javed Tai, M. Masood Kadir

Community Health Sciences

Objective: To determine factors associated with repeat revascularization among adults aged 25 years and above within 5 years of first Percutaneous Coronary Intervention (PCI) at a tertiary care hospital.
Methods: A matched case-control study was conducted through a hospital records review. A total of 90 cases with repeat revascularization and 180 controls without repeat revascularization were included. Data was analyzed using Multiple Conditional Logistic Regression.
Results: The mean age was similar in cases and controls (60.05 ± 10.01 vs 62.20 ± 10.43 years) and sex (male: 77.8% vs. 76.1%). History of being an ever-smoker (40% vs. 25%), overweight (36.3% vs. …

Tissue-Targeted Crispr-Cas9-Mediated Genome Editing Of Multiple Homeologs In F0 Generation Xenopus Laevis Embryos, Mark E Corkins, Bridget D Delay, Rachel K Miller

Faculty, Staff and Student Publications

Xenopus laevis frogs are a powerful developmental model that enables studies combining classical embryology and molecular manipulation. Because of the large embryo size, ease of microinjection, and ability to target tissues through established fate maps, X. laevis have become the predominant amphibian research model. Given that their allotetraploid genome has complicated the generation of gene knockouts, strategies need to be established for efficient mutagenesis of multiple homeologs to evaluate gene function. Here we describe a protocol to utilize CRISPR-Cas9-mediated genome editing to target either single alleles or multiple alloalleles in F0 X. laevis embryos. A single guide (sg) RNA is …