Digital Commons Network^™

The Chasm In Percutaneous Coronary Intervention And In-Hospital Mortality Rates Among Acute Myocardial Infarction Patients In Rural And Urban Hospitals In China: A Mediation Analysis, Miao Cai, Echu Liu, Peng Bai, Nan Zhang, Siyu Wang, Wei Li, Hualiang Lin, Xiaojun Lin

2020-Current year OA Pubs

No abstract provided.

Public Policy (Not The Coronavirus) Should Shape What Endemic Means, Ronald U. Mendoza, Kenneth Hartigan-Go, Alex B. Brillantes, Karl Ev Ruiz, Ivyrose S. Baysic, Sheena A. Valenzuela

Ateneo School of Government Publications

Endemicity is not only a biological and health event but has several inter-dependencies cross-cutting with the management of the economy, including governance and policies. Within the context of the discourse on inequity, what does endemicity mean for poor and low-income families, where policies on social inclusion and social welfare need to be re-calibrated?

Does The Novel Coronavirus Use The Ocular Surface As An Entrance Into The Body Or As An Infection Site?, Remzi Karadag, Alp Kayiran, Christopher J Rapuano

Wills Eye Hospital Papers

This study attempts to review whether the coronavirus disease-2019 (COVID-19) is transmitted through the ocular surface and examine the symptoms and signs of ocular disease. Considering that COVID-19 is transmitted by airborne droplets and close contact with infected individuals, we will also review the conditions to which eye clinics and ophthalmologists should pay attention to prevent the transmission of the disease. Although some researchers have argued that COVID-19 transmission cannot occur through the ocular surface, most of them are of the opinion that the ocular surface is a potential pathway of transmission. Until date, ocular signs and symptoms have been …

Temporal Cohort Logic, Guo-Qiang Zhang, Xiaojin Li, Yan Huang, Licong Cui

Faculty, Staff and Student Publications

We introduce a new logic, called Temporal Cohort Logic (TCL), for cohort specification and discovery in clinical and population health research. TCL is created to fill a conceptual gap in formalizing temporal reasoning in biomedicine, in a similar role that temporal logics play for computer science and its applications. We provide formal syntax and semantics for TCL and illustrate the various logical constructs using examples related to human health. Relationships and distinctions with existing temporal logical frameworks are discussed. Applications in electronic health record (EHR) and in neurophysiological data resource are provided. Our approach differs from existing temporal logics, in …

Racial And Socioeconomic Disparities In Patients With Meningioma: A Retrospective Cohort Study, Hudin N Jackson, Caroline C Hadley, A Basit Khan, Ron Gadot, James C Bayley, Arya Shetty, Jacob Mandel, Ali Jalali, K Kelly Gallagher, Alex D Sweeney, Arif O Harmanci, Akdes S Harmanci, Tiemo Klisch, Shankar P Gopinath, Ganesh Rao, Daniel Yoshor, Akash J Patel

Faculty, Staff and Student Publications

BACKGROUND: Meningiomas are the most common intracranial neoplasms. Although genomic analysis has helped elucidate differences in survival, there is evidence that racial disparities may influence outcomes. African Americans have a higher incidence of meningiomas and poorer survival outcomes. The etiology of these disparities remains unclear, but may include a combination of pathophysiology and other factors.

OBJECTIVE: To determine factors that contribute to different clinical outcomes in racial populations.

METHODS: We retrospectively reviewed 305 patients who underwent resection for meningiomas at a single tertiary care facility. We used descriptive statistics and univariate, multivariable, and Kaplan-Meier analyses to study clinical, radiographical, and …

Facilitating Federated Genomic Data Analysis By Identifying Record Correlations While Ensuring Privacy, Leonard Dervishi, Xinyue Wang, Wentao Li, Anisa Halimi, Jaideep Vaidya, Xiaoqian Jiang, Erman Ayday

Faculty, Staff and Student Publications

With the reduction of sequencing costs and the pervasiveness of computing devices, genomic data collection is continually growing. However, data collection is highly fragmented and the data is still siloed across different repositories. Analyzing all of this data would be transformative for genomics research. However, the data is sensitive, and therefore cannot be easily centralized. Furthermore, there may be correlations in the data, which if not detected, can impact the analysis. In this paper, we take the first step towards identifying correlated records across multiple data repositories in a privacy-preserving manner. The proposed framework, based on random shuffling, synthetic record …

Caries Risk Documentation And Prevention: Emeasures For Dental Electronic Health Records, Suhasini Bangar, Ana Neumann, Joel M White, Alfa Yansane, Todd R Johnson, Gregory W Olson, Shwetha V Kumar, Krishna K Kookal, Aram Kim, Enihomo Obadan-Udoh, Elizabeth Mertz, Kristen Simmons, Joanna Mullins, Ryan Brandon, Muhammad F Walji, Elsbeth Kalenderian

Faculty, Staff and Student Publications

BACKGROUND: Longitudinal patient level data available in the electronic health record (EHR) allows for the development, implementation, and validations of dental quality measures (eMeasures).

OBJECTIVE: We report the feasibility and validity of implementing two eMeasures. The eMeasures determined the proportion of patients receiving a caries risk assessment (eCRA) and corresponding appropriate risk-based preventative treatments for patients at elevated risk of caries (appropriateness of care [eAoC]) in two academic institutions and one accountable care organization, in the 2019 reporting year.

METHODS: Both eMeasures define the numerator and denominator beginning at the patient level, populations' specifications, and validated the automated queries. For …

Metabolic Imaging Using Hyperpolarization For Assessment Of Premalignancy, Shivanand Pudakalakatti, Priyank Raj, Travis C Salzillo, José S Enriquez, Dontrey Bourgeois, Prasanta Dutta, Mark Titus, Shayan Shams, Priya Bhosale, Michael Kim, Florencia Mcallister, Pratip K Bhattacharya

Faculty, Staff and Student Publications

There is an unmet need for noninvasive surrogate markers that can help identify premalignant lesions across different tumor types. Here we describe the methodology and technical details of protocols employed for in vivo

Automated Identification Of Missing Is-A Relations In The Human Phenotype Ontology, Maryamsadat Mohtashamian, Ran Hu, Rashmie Abeysinghe, Xubing Hao, Hua Xu, Licong Cui

Faculty, Staff and Student Publications

Auditing the Human Phenotype Ontology (HPO) is necessary to provide accurate terminology for its use in clinical research. We investigate an approach leveraging the lexical features of concepts in HPO to identify missing IS-A relations among HPO concepts. We first model the names of HPO concepts as sets of words in lower case. Then, we generate two types of concept-pairs which have at least a single common word: (1) Linked concept-pairs generated from concept-pairs having an IS-A relation; (2) Unlinked concept-pairs generated from concept-pairs without an IS- A relation. Concept-pairs generate Derived Term Pairs (DTPs) emphasizing unique lexical information of …

Health Workers On The Political Frontlines, Gideon Lasco

Development Studies Faculty Publications

No abstract provided.

Implementing Nih Behavior Change Consortium Treatment Fidelity Recommendations In A Multi-Site Randomized Controlled Trial Of An Active Music Engagement Intervention For Young Children With Cancer And Parents., Jessica A. Maclean, Kristin Stegenga, Amanda K. Henley, Sheri L. Robb

Manuscripts, Articles, Book Chapters and Other Papers

Treatment fidelity is the use of methodological strategies to monitor and enhance reliability and validity of behavioral intervention trials. Despite availability of guidelines and checklists, treatment fidelity remains underreported, hindering evaluation, interpretation, and cross-study comparisons. Treatment fidelity is particularly important for music interventions given the inherent complexity of musical stimuli and flexibility required for tailored delivery. The purpose of this paper is to define and describe treatment fidelity strategies for our trial of a music-based play intervention for young children with cancer and parents grounded in the NIH Behavior Change Consortium Treatment Fidelity Recommendations. We report strategies for all 5 …

Depletion And Enrichment Of Phytosterols In Soybean Oil Lipid Emulsions Directly Associate With Serum Markers Of Cholestasis In Preterm Parenteral Nutrition-Fed Pigs, Greg Guthrie, Barbara Stoll, Shaji Chacko, Mahmoud Mohammad, Candace Style, Mariatu Verla, Oluyinka Olutoye, Deborah Schady, Charlotte Lauridsen, Nick Tataryn, Douglas Burrin

Children’s Nutrition Research Center Staff Publications

Background: Clinical reports show a positive correlation between phytosterol concentrations and severity of cholestatic liver disease markers in infants during long-term administration of parenteral lipid emulsions. Establishing a causal link between phytosterols and cholestasis has been complicated by confounding factors of lipid emulsion load, fatty acid composition, and vitamin E in many of these studies. The goal of this study is to determine whether altering the phytosterol concentration within a common soybean oil-based emulsion will alter the onset and severity of cholestasis in parenterally fed preterm piglets.

Methods: Preterm piglets were administered, for 21 days, either enteral nutrition (ENT) or …

Maternal Feeding Styles And Child Appetitive Traits: Direction Of Effects In Hispanic Families With Low Incomes, Maria A Papaioannou, Nilda Micheli, Thomas G Power, Teresia M O'Connor, Jennifer Orlet Fisher, Sheryl O Hughes

Children’s Nutrition Research Center Staff Publications

Feeding styles of parents have been associated with dietary quality/intake and weight outcomes; however, much of the research to date has been cross sectional and the direction of influence unclear. This prospective longitudinal study evaluated the direction of effects between feeding styles and child appetitive traits over time in a sample of 129 Hispanic parent/child dyads that participated in a larger study. Data analyzed for the current study were collected when the children were 4-5 years old and again at ages 7-9 years. Parents (all mothers) reported on their feeding styles and children's appetitive traits using well-established questionnaires. Cross-lagged panel …

Associations Of Prenatal Phthalate Exposure With Neurobehavioral Outcomes In 45- And 75-Month-Old Infants, Jenna L N Sprowles, Kelsey L C Dzwilewski, Francheska M Merced-Nieves, Salma M A Musaad, Susan L Schantz, Sarah D Geiger

Children’s Nutrition Research Center Staff Publications

Phthalates are ubiquitous endocrine-disrupting chemicals, and research indicates that prenatal exposure to some phthalates may affect neurodevelopment. In a prospective birth cohort study, five first-morning urine samples collected across pregnancy were pooled and the following phthalate biomarkers assessed: sum of di-(2-ethylhexyl) phthalate metabolites (ΣDEHP), sum of diisononyl phthalate metabolites (ΣDINP), sum of dibutyl phthalate metabolites (ΣDBP), sum of anti-androgenic metabolites (ΣAA), monoethyl phthalate (MEP), and sum of all phthalate metabolites (ΣAll). The Ages & Stages Questionnaires® (ASQ), a standardized parent-reported, age-adapted screening tool, measured communication, personal-social, problem solving, and motor domains in infants at 4.5 and 7.5 months (n = …

Tissue-Specific Mechanisms Of Bile Acid Homeostasis And Activation Of Fxr-Fgf19 Signaling In Preterm And Term Neonatal Pigs, Caitlin Vonderohe, Greg Guthrie, Barbara Stoll, Shaji Chacko, Harry Dawson, Douglas G Burrin

Children’s Nutrition Research Center Staff Publications

The tissue-specific molecular mechanisms involved in perinatal liver and intestinal farnesoid X receptor (FXR)-fibroblast growth factor 19 (FGF19) signaling are poorly defined. Our aim was to establish how gestational age and feeding status affect bile acid synthesis pathway, bile acid pool size, ileal response to bile acid stimulation, genes involved in bile acid-FXR-FGF19 signaling and plasma FGF19 in neonatal pigs. Term (n = 23) and preterm (n = 33) pigs were born via cesarean section at 100% and 90% gestation, respectively. Plasma FGF19, hepatic bile acid and oxysterol profiles, and FXR target gene expression were assessed in pigs …

Investigation Of Urinary Metabolomics In A Phase I Hookworm Vaccine Trial In Gabon, Madeleine Eunice Betouke Ongwe, Yoanne D Mouwenda, Koen A Stam, Peter G Kremsner, Bertrand Lell, David Diemert, Jeff Bethony, Maria E Bottazzi, Peter J Hotez, Remko V Leeuwen, Martin P Grobusch, Ayola A Adegnika, Oleg A Mayboroda, Maria Yazdanbakhsh

Center for Medical Ethics and Health Policy Staff Publications

Metabolomics provides a powerful tool to study physiological changes in response to various perturbations such as vaccination. We explored whether metabolomic changes could be seen after vaccination in a phase I trial where Gabonese adults living either in rural or semi-urban areas received the subunit hookworm vaccine candidates (Na-GST-1 and Na-APR-1 (M74) adjuvanted with Alhydrogel plus GLA-AF (n = 24) or the hepatitis B vaccine (n = 8) as control. Urine samples were collected and assayed using targeted 1H NMR spectroscopy. At baseline, a set of metabolites significantly distinguished rural from semi-urban individuals. The pre- and post-vaccination comparisons indicated significant …

Application Of Artificial Intelligence And Machine Learning For Hiv Prevention Interventions, Yang Xiang, Jingcheng Du, Kayo Fujimoto, Fang Li, John Schneider, Cui Tao

Faculty, Staff and Student Publications

In 2019, the US Government announced its goal to end the HIV epidemic within 10 years, mirroring the initiatives set forth by UNAIDS. Public health prevention interventions are a crucial part of this ambitious goal. However, numerous challenges to this goal exist, including improving HIV awareness, increasing early HIV infection detection, ensuring rapid treatment, optimising resource distribution, and providing efficient prevention services for vulnerable populations. Artificial intelligence has had a pivotal role in revolutionising health care and has shown great potential in developing effective HIV prevention intervention strategies. Although artificial intelligence has been used in a few HIV prevention intervention …

The Neighborhood Environment And Hispanic/Latino Health, Natalia I Heredia, Tianlin Xu, Minjae Lee, Lorna H Mcneill, Belinda M Reininger

Faculty, Staff and Student Publications

PURPOSE: Hispanic/Latino adults on the Texas-Mexico border have high rates of chronic disease. Neighborhoods can influence health, though there is a limited research on neighborhood environment and health in Hispanics/Latinos. The purpose of this study was to assess the relation of neighborhood environment with health variables in Hispanic/Latino adults, including physical activity [PA], depression, anxiety, and lab-assessed conditions (type 2 diabetes, metabolic syndrome, and chronic inflammation).

METHODS: Participants were randomly-selected from a Hispanic/Latino cohort on the Texas-Mexico border. Neighborhood environment, self-reported PA, anxiety, and depression were assessed through questionnaires. Laboratory values determined Type 2 diabetes, metabolic syndrome, and C-reactive protein …

Guideline For Feedback Of Individual Genetic Research Findings For Genomics Research In Africa, Alice Matimba, Stuart Ali, Katherine Littler, Ebony Madden, Patricia Marshall, Sheryl Mccurdy, Victoria Nembaware, Laura Rodriguez, Janet Seeley, Paulina Tindana, Aminu Yakubu, Jantina De Vries, H3africa Ethics And Community Engagement Working Group

Faculty, Staff and Student Publications

As human genomics research in Africa continues to generate large amounts of data, ethical issues arise regarding how actionable genetic information is shared with research participants. The Human Heredity and Health in Africa Consortium (H3Africa) Ethics and Community Engagement Working group acknowledged the need for such guidance, identified key issues and principles relevant to genomics research in Africa and developed a practical guideline for consideration of feeding back individual genetic results of health importance in African research projects. This included a decision flowchart, providing a logical framework to assist in decision-making and planning for human genomics research projects. Although presented …

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 …

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 …

Racial Disparities In Treatments And Mortality Among A Large Population-Based Cohort Of Older Men And Women With Colorectal Cancer, Xianglin L Du, Lulu Song

Faculty, Staff and Student Publications

BACKGROUND: There were racial disparities in treatment and mortality among patients with colorectal cancer, but few studies incorporated information on hypertension and diabetes and their treatment status.

PATIENTS AND METHODS: The study identified 101,250 patients from Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database in the United States who were diagnosed with colorectal cancer at age ≥65 years between 2007 and 2015 with follow-up to December 2016.

RESULTS: There were substantial racial and ethnic disparities in the prevalence of hypertension and diabetes in patients with colorectal cancer, in receiving chemotherapy and radiation therapy, and in receiving antihypertensive and antidiabetic treatment. …

Incidence Rate Of Psychiatric Disorders In 2020: The Pivotal Role Played By Sars-Cov-2 Infection, Antonio L Teixeira, Regina M Hansen, Joseph S Wozny, Caroline M Schaefer, Rodrigo Machado-Vieira, Lokesh Shahani, Scott D Lane, Jair C Soares, Trudy M Krause

Faculty, Staff and Student Publications

IMPORTANCE: The Coronavirus Disease (COVID-19) pandemic has significantly impacted mental health outcomes. While the frequency of anxiety and depressive symptoms has increased in the whole population, the relationship between COVID-19 and new psychiatric diagnoses remains unclear.

OBJECTIVE: to compare the population incidence rate of emergence of de novo psychiatric disorders in 2020 compared to the previous years, and to compare the incidence rate of new psychiatric disorder diagnoses between people with vs without COVID-19.

DESIGN, SETTING, AND PARTICIPANTS: This study utilized administrative claims data from the Clinformatics® Data Mart database, licensed from Optum®. The study is a cross-sectional analysis that …

Covid-19 Vaccination In Palestine/Israel: Citizenship, Capitalism, And The Logic Of Elimination, Nicolas Howard, Emily Schneider

Sociology & Criminal Justice Faculty Publications

Despite Israel’s responsibility under international law to combat the spread of contagious diseases and epidemics in its occupied territories, Israeli officials have refused to distribute COVID-19 vaccines to Palestinians in the West Bank and Gaza Strip. Through a critical discourse analysis of Israeli officials’ statements regarding Israel’s COVID-19 vaccination campaign, this paper explores how Israel evades this responsibility while presenting itself as committed to public health and human rights. We find that Israeli officials strategically present Palestinians as an autonomous nation when discussing COVID-19 vaccinations, despite Israel’s ongoing attempts to prevent the creation of a Palestinian state. Relatedly, Israel justifies …

Loss Of Mmr And Tgfbr2 Increases The Susceptibility To Microbiota-Dependent Inflammation-Associated Colon Cancer, Elena Tosti, Ana S Almeida, Tam T T Tran, Mariel Barbachan E Silva, Pilib Ó Broin, Robert Dubin, Ken Chen, Amanda P Beck, Andrew S Mclellan, Eduardo Vilar, Aaron Golden, Paul W O'Toole, Winfried Edelmann

Faculty, Staff and Student Publications

Background and aims: Mutations in DNA mismatch repair (MMR) genes are causative in Lynch syndrome and a significant proportion of sporadic colorectal cancers (CRCs). MMR-deficient (dMMR) CRCs display increased mutation rates, with mutations frequently accumulating at short repetitive DNA sequences throughout the genome (microsatellite instability). The TGFBR2 gene is one of the most frequently mutated genes in dMMR CRCs. Therefore, we generated an animal model to study how the loss of both TGFBR2 signaling impacts dMMR-driven intestinal tumorigenesis in vivo and explore the impact of the gut microbiota.

Methods: We generated VCMsh2/Tgfbr2 mice in which Msh2loxP and Tgfbr2loxP alleles are …

A Phase I, Open-Label, Dose-Escalation Study Of The Ox40 Agonist Ivuxolimab In Patients With Locally Advanced Or Metastatic Cancers, Adi Diab, Omid Hamid, John A Thompson, Willeke Ros, Ferry A L M Eskens, Toshihiko Doi, Siwen Hu-Lieskovan, Samuel J Klempner, Bishu Ganguly, Catherine Fleener, Xiao Wang, Tenshang Joh, Ken Liao, Shahram Salek-Ardakani, Carrie Turich Taylor, Jeffrey Chou, Anthony B El-Khoueiry

Faculty, Staff and Student Publications

PURPOSE: Stimulation of effector T cells is an appealing immunotherapeutic approach in oncology. OX40 (CD134) is a costimulatory receptor expressed on activated CD4

PATIENTS AND METHODS: Adult patients (

RESULTS: The most common all-causality adverse events were fatigue (46.2%), nausea (28.8%), and decreased appetite (25.0%). Of 31 treatment-related adverse events, 30 (96.8%) were grade ≤2. No dose-limiting toxicities occurred. Ivuxolimab exposure increased in a dose-proportionate manner from 0.3 to 10 mg/kg. Full peripheral blood target engagement occurred at ≥0.3 mg/kg. Three (5.8%) patients achieved a partial response, and disease control was achieved in 56% of patients. Increased CD4

CONCLUSIONS: Ivuxolimab …

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

Understanding Contributors To Racial And Ethnic Inequities In Covid-19 Incidence And Mortality Rates, Karen E. Joynt Maddox, Mat Reidhead, Joshua Grotzinger, Timothy Mcbride, Aaloke Mody, Elna Nagasako, Will Ross, Joseph T. Steensma, Abigail R. Barker

Open Access Publications

BACKGROUND: Racial inequities in Coronavirus 2019 (COVID-19) have been reported over the course of the pandemic, with Black, Hispanic/Latinx, and Native American individuals suffering higher case rates and more fatalities than their White counterparts.

METHODS: We used a unique statewide dataset of confirmed COVID-19 cases across Missouri, linked with historical statewide hospital data. We examined differences by race and ethnicity in raw population-based case and mortality rates. We used patient-level regression analyses to calculate the odds of mortality based on race and ethnicity, controlling for comorbidities and other risk factors.

RESULTS: As of September 10, 2020 there were 73,635 confirmed …

Advances And Gaps In Sars-Cov-2 Infection Models, César Muñoz-Fontela, Michael S. Diamond, Et Al

Open Access Publications

The global response to Coronavirus Disease 2019 (COVID-19) is now facing new challenges such as vaccine inequity and the emergence of SARS-CoV-2 variants of concern (VOCs). Preclinical models of disease, in particular animal models, are essential to investigate VOC pathogenesis, vaccine correlates of protection and postexposure therapies. Here, we provide an update from the World Health Organization (WHO) COVID-19 modeling expert group (WHO-COM) assembled by WHO, regarding advances in preclinical models. In particular, we discuss how animal model research is playing a key role to evaluate VOC virulence, transmission and immune escape, and how animal models are being refined to …

A Test Of The Pioneer Factor Hypothesis Using Ectopic Liver Gene Activation, Jeffrey L. Hansen, Kaiser J. Loell, Barak A. Cohen

Open Access Publications

The pioneer factor hypothesis (PFH) states that pioneer factors (PFs) are a subclass of transcription factors (TFs) that bind to and open inaccessible sites and then recruit non-pioneer factors (non-PFs) that activate batteries of silent genes. The PFH predicts that ectopic gene activation requires the sequential activity of qualitatively different TFs. We tested the PFH by expressing the endodermal PF FOXA1 and non-PF HNF4A in K562 lymphoblast cells. While co-expression of FOXA1 and HNF4A activated a burst of endoderm-specific gene expression, we found no evidence for a functional distinction between these two TFs. When expressed independently, both TFs bound and …