Digital Commons Network^™

Genetic Newborn Screening For Retinoblastoma: A Belgian Initiative Baby Detect, Daniel A Rodriguez, Alex Song, Anshul Bhatnagar, Christina Y Weng

Faculty, Staff and Students Publications

Baby Detect Project, started in September 2022, aimed to create a newborn screening test using targeted next-generation sequencing for all early-onset, treatable, and serious conditions. The elaborated gene panel covers 405 genes, associated with 165 genetic conditions, and includes RB1, linked to retinoblastoma, the only oncological disease tested for. Germline RB1 mutations concern around 50% of all retinoblastoma cases and 100% of the most severe, bilateral cases. Ninety percent of them occur de novo, which delays the diagnosis by about a year with subsequent loss of vision and sometimes the eye itself. Detecting children with germline RB1 mutation at …

Predictive Equation Derived From 6,497 Doubly Labelled Water Measurements Enables The Detection Of Erroneous Self-Reported Energy Intake, Rania Bajunaid, Chaoqun Niu, Catherine Hambly, Zongfang Liu, Yosuke Yamada, Heliodoro Aleman-Mateo, Liam J Anderson, Lenore Arab, Issad Baddou, Linda Bandini, Kweku Bedu-Addo, Ellen E Blaak, Carlijn V C Bouten, Soren Brage, Maciej S Buchowski, Nancy F Butte, Stefan G J A Camps, Regina Casper, Graeme L Close, Jamie A Cooper, Richard Cooper, Sai Krupa Das, Peter S W Davies, Prasangi Dabare, Lara R Dugas, Simon Eaton, Ulf Ekelund, Sonja Entringer, Terrence Forrester, Barry W Fudge, Melanie Gillingham, Annelies H Goris, Michael Gurven, Asmaa El Hamdouchi, Hinke H Haisma, Daniel Hoffman, Marije B Hoos, Sumei Hu, Noorjehan Joonas, Annemiek M Joosen, Peter Katzmarzyk, Misaka Kimura, William E Kraus, Wantanee Kriengsinyos, Rebecca Kuriyan, Robert F Kushner, Estelle V Lambert, Pulani Lanerolle, Christel L Larsson, William R Leonard, Nader Lessan, Marie Löf, Corby K Martin, Eric Matsiko, Anine C Medin, James C Morehen, James P Morton, Aviva Must, Marian L Neuhouser, Theresa A Nicklas, Christine D Nyström, Robert M Ojiambo, Kirsi H Pietiläinen, Yannis P Pitsiladis, Jacob Plange-Rhule, Guy Plasqui, Ross L Prentice, Susan B Racette, David A Raichlen, Eric Ravussin, Leanne M Redman, John J Reilly, Rebecca Reynolds, Susan B Roberts, Dulani Samaranayakem, Luis B Sardinha, Analiza M Silva, Anders M Sjödin, Marina Stamatiou, Eric Stice, Samuel S Urlacher, Ludo M Van Etten, Edgar G A H Van Mil, George Wilson, Jack A Yanovski, Tsukasa Yoshida, Xueying Zhang, Alexia J Murphy-Alford, Srishti Sinha, Cornelia U Loechl, Amy H Luke, Herman Pontzer, Jennifer Rood, Hiroyuki Sagayama, Dale A Schoeller, Klaas R Westerterp, William W Wong, John R Speakman

Faculty, Staff and Students Publications

Nutritional epidemiology aims to link dietary exposures to chronic disease, but the instruments for evaluating dietary intake are inaccurate. One way to identify unreliable data and the sources of errors is to compare estimated intakes with the total energy expenditure (TEE). In this study, we used the International Atomic Energy Agency Doubly Labeled Water Database to derive a predictive equation for TEE using 6,497 measures of TEE in individuals aged 4 to 96 years. The resultant regression equation predicts expected TEE from easily acquired variables, such as body weight, age and sex, with 95% predictive limits that can be used …

Cervical Cancer Prevention Behaviors In Young Black Women, Angela J Johnson, Monica J Johnson, Juinell B Williams, Emma Muscari, Laura Palmo, Michelle Ruiz, Brianna Bush, Lisa C Campbell

Faculty, Staff and Students Publications

Background: In the United States, Black women have the second highest incidence of cervical cancer (CC) due to high incidence of human papillomavirus (HPV), slow HPV clearance rates, and low receipt of preventive pap smears and vaccines.

Objective: A Black Feminist Thought framework was used to examine how the media portrayal of Black women, racial identity, and familial factors impact CC prevention behaviors among young Black women.

Design: Black women enrolled at a large southeastern university consented and participated in an online mixed-methods survey examining facilitators and barriers to CC prevention behaviors. Quantitative items were analyzed via descriptive statistics, and …

From Trials To Practice: Implementing A Clinical Intervention In Community Settings, Elizabeth M Vaughan, Xiaoying Yu, Victor J Cardenas, Craig A Johnston, Salim S Virani, Ashok Balasubramanyam, Christie M Ballantyne, Aanand D Naik

Faculty, Staff and Students Publications

Introduction/objectives: Diabetes increases the risk of complications, especially for vulnerable populations. Our previous randomized clinical trial (RCT), TIME (Telehealth-supported, Integrated Community Health Workers (CHWs), Medication access, group visit Education), showed the efficacy of CHW-led diabetes care. This study aimed to gather data on transitioning TIME from clinical trials to practical implementation.

Methods: We conducted a 12-month RCT at a nonprofit community clinic using the Consolidated Framework for Implementation Research (CFIR). Participants, Hispanic adults without insurance and with type 2 diabetes (N = 58; 29/arm), were randomized to TIME (intervention) or usual care (control). The intervention included monthly group visits and …

Nutcracker Syndrome (A Delphi Consensus), Floor Heilijgers, Suresh Vedantham, Et Al.

2020-Current year OA Pubs

BACKGROUND: Nutcracker syndrome (NCS) describes the symptomatic compression of the left renal vein between the aorta and superior mesenteric artery. Whereas asymptomatic compression is a common radiological finding, patients with NCS can report a range of symptoms. There are no specific diagnostic criteria and interventions include a range of open surgical and endovascular procedures. Therefore, we wished to develop an international consensus document covering aspects of diagnosis, management, and follow-up for patients with NCS.

METHODS: A three-stage modified Delphi consensus was performed. A steering committee developed 37 statements covering 3 categories for patients with NCS: diagnosis, management, and follow-up. These …

Vagus Nerve Stimulation In Treatment-Resistant Depression: A One-Year, Randomized, Sham-Controlled Trial, Charles R Conway, Christopher L Kriedt, Et Al.

2020-Current year OA Pubs

BACKGROUND: Few treatments are available for individuals with marked treatment-resistant depression (TRD).

OBJECTIVE: Evaluate the safety and effectiveness of FDA-approved adjunctive vagus nerve stimulation (VNS) in patients with marked TRD.

METHODS: This 12-month, multicenter, double-blind, sham-controlled trial included 493 adults with marked treatment-resistant major depression who were randomized to active or no-stimulation sham VNS for 12 months. The primary outcome was percent time in response across months 3-12, with response defined as a ≥50 % change from baseline on the Montgomery-Åsberg Depression Rating Scale (MADRS). Several secondary endpoints were evaluated.

RESULTS: Overall, 88.4 % of participants completed the trial. Percent …

Sars-Cov-2 Genomic Surveillance Using Self-Collected Saliva Specimens During Occupational Testing Programs, Andy T. Schnaubelt, David Brett-Major, Janet Williamson, Bailey Barcal, Julie Carstens, Ashley Peer, Michael R. Wiley, M. Jana Broadhurst

Journal Articles: Epidemiology

Continually emerging SARS-CoV-2 variants pose challenges to clinical and public health interventions, necessitating sustainable approaches to real-time variant monitoring. This case study describes an innovative SARS-CoV-2 screening and surveillance program that demonstrates the utility of sequencing-based variant monitoring using self-collected saliva specimens. We conducted saliva-based SARS-CoV-2 screening in occupational settings in Omaha, Nebraska from December 2021 through November 2022. 8,372 saliva specimens collected from 1,480 participants were tested for SARS-CoV-2 RNA by extraction-free PCR, with 334 positive samples referred for whole-genome sequencing analysis. Program utilization, quality metrics, and sequencing outputs were compared across sites. Specimen quality was high across program …

Understanding The Pathogenesis Of Uveitis In Ebola Virus Disease Survivors: An Observational Cohort And Cross-Sectional Study Protocol For Clinical, Molecular Virologic And Immunologic Characterisation, Caleb D. Hartley, Susanne Linderman, Tolulope Fashina, Laura Ward, Carolyn Drews-Botsch, Catherine Pratt, Sanjana Kuthyar, Alcides Filho Fernandes, Ye Huang, Charlene Choo, Nam Nguyen, Jessica Carag, Jill Morgan, Colleen S. Kraft, Angela L. Hewlett, David Brett-Major, John S. Schieffelin, Robert F. Garry, Donald Grant, Grant A. Justin, Christopher D. Conrady, Justine R. Smith, Brent R. Hayek, Shiama Balendra, Nisha Acharya, Thuy Doan, Anais Legand, Pierre Formenty, Xiankun Zeng, Ibrahim Conteh, Matthew Jusu Vandy, Lloyd Harrison-Williams, Jalikatu Mustapha, Zikan Koroma, Michael R. Wiley, Ian Crozier, Jean-Claude Mwanza, Jessica G. Shantha, Rafi Ahmed, Steven Yeh, Smile And Evict-Vr Investigator Study Groups

Journal Articles: Epidemiology

INTRODUCTION: The 2013-2016 Western African outbreak of the Ebola virus disease (EVD), the largest recorded outbreak since the discovery of Ebola virus (EBOV) in 1976, destabilised local health systems and left thousands of survivors at risk for postacute sequelae, including vision-threatening uveitis. In an EVD survivor with severe panuveitis, the detection of persistent EBOV in the aqueous humour, long after clearance of acute viremia, focused clinical and research attention on the host-EBOV interaction in the unique terrain of ocular immune privilege. Despite the recognition that uveitis is common and consequential in EVD survivors, our understanding of pathogenesis is extremely limited, …

Rethinking Immune Check Point Inhibitors Use In Liver Transplantation: Implications And Resistance, Vivian Ortiz, Emilien Loeuillard

2020-Current year OA Pubs

Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy, including the two most common liver tumors, hepatocellular carcinoma and cholangiocarcinoma, but their use in the peri-transplantation period is controversial. ICI therapy aims to heighten cytotoxic T lymphocytes response against tumors. However, tumor recurrence is common owing to tumor immune response escape involving ablation of CTL response by interfering with antigen presentation, triggering CLT apoptosis and inducing epigenetic changes that promote ICI therapy resistance. ICI can also affect tissue resident memory T cell population, impact tolerance in the post-transplant period, and induce acute inflammation risking graft survival post-transplant. Their interaction with immunosuppression …

Maintenance Therapy With A P2y12 Receptor Inhibitor After Cangrelor In Patients With Acute Coronary Syndrome The Electra-Sirio 2 Investigators’ Viewpoint, Jacek Kubica, Piotr Adamski, Robert Gajda, Aldona Kubica, Małgorzata Ostrowska, Gavino Casu, Diana A Gorog, Paul A Gurbel, Tomasz Hajdukiewicz, Miłosz Jaguszewski, Young-Hoon Jeong, Agata Kosobucka-Ozdoba, Zuzana Motovska, Piotr Niezgoda, Maciej Piasecki, Przemysław Podhajski, Paolo Raggi, Uzeyir Rahimov, Jolanta M Siller-Matula, Grzegorz Skonieczny, Łukasz Szarpak, Paweł Szymański, Udaya Tantry, Eliano P Navarese

Faculty, Staff and Students Publications

According to the ESC guidelines, cangrelor may be considered in P2Y12-inhibitor-naïve acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI). The aim of this review is to summarize available evidence on the optimal maintenance therapy with P2Y12 receptor inhibitor after cangrelor. Transitioning from cangrelor to a thienopyridine, but not ticagrelor, can be associated with a drug-drug interaction (DDI); therefore, a ticagrelor loading dose (LD) can be given any time before, during, or at the end of a cangrelor infusion, while a LD of clopidogrel or prasugrel should be administered at the time the infusion of cangrelor ends or within …

Monoallelic Expression Can Govern Penetrance Of Inborn Errors Of Immunity, O'Jay Stewart, Conor Gruber, Haley E Randolph, Roosheel Patel, Meredith Ramba, Enrica Calzoni, Lei Haley Huang, Jay Levy, Sofija Buta, Angelica Lee, Christos Sazeides, Zoe Prue, David P Hoytema Van Konijnenburg, Ivan K Chinn, Luis A Pedroza, James R Lupski, Erica G Schmitt, Megan A Cooper, Anne Puel, Xiao Peng, Stéphanie Boisson-Dupuis, Jacinta Bustamante, Satoshi Okada, Marta Martin-Fernandez, Jordan S Orange, Jean-Laurent Casanova, Joshua D Milner, Dusan Bogunovic

Faculty, Staff and Students Publications

Inborn errors of immunity (IEIs) are genetic disorders that underlie susceptibility to infection, autoimmunity, autoinflammation, allergy and/or malignancy1. Incomplete penetrance is common among IEIs despite their monogenic basis2. Here we investigate the contribution of autosomal random monoallelic expression (aRMAE), a somatic commitment to the expression of one allele3,4, to phenotypic variability observed in families with IEIs. Using a clonal primary T cell system to assess aRMAE status of genes in healthy individuals, we find that 4.30% of IEI genes and 5.20% of all genes undergo aRMAE. Perturbing H3K27me3 and DNA methylation alters …

Nanoparticle Contrast Agents For Photon-Counting Computed Tomography: Recent Developments And Future Opportunities, Laxman Devkota, Rohan Bhavane, Cristian T Badea, Eric A Tanifum, Ananth V Annapragada, Ketan B Ghaghada

Faculty, Staff and Students Publications

The clinical availability of photon-counting computed tomography (PCCT) has ushered in a new era of CT imaging. Spectral imaging coupled with superior contrast resolution, and ultrahigh spatial resolution (200 μm) offered by PCCT has the potential to revolutionize value-driven imaging. The potential of multicolor PCCT has generated excitement, and renewed interest, in novel contrast agent development for comprehensive disease interrogation, prediction and monitoring of treatment outcomes. Nanoparticles provide a versatile and powerful platform for the development of next generation contrast agents for spectral PCCT. In this article, we review recent developments and use of nanoparticle contrast agents for PCCT. We …

Mutations In Retinal Cyclic Nucleotide-Gated Channels Identified In Familial Cases Of Inherited Retinal Dystrophies From Pakistan, Zainab Akhtar, Kiran Afshan, Yumei Li, Sumaira Altaf, Aleesha Asghar, Ume Sughra, Wajid Ali Khan, Haiba Kaul, Rui Chen, Sabika Firasat

Faculty, Staff and Students Publications

Purpose: Cyclic nucleotide-gated (CNG) channels are ligand-gated ion channels that transduce light signals into electrical signals in the retinal photoreceptors. Pathogenic variants in CNG channel genes are reported to cause inherited retinal dystrophies (IRDs). The current study used targeted panel sequencing to describe the mutational spectrum of CNG channel genes in familial cases of IRDs from eight consanguineous Pakistani families.

Methods: The current study included consanguineous Pakistani families with at least two affected members. DNA was extracted from whole blood samples by the phenol-chloroform method. Two affected members from each family were initially analyzed using targeted panel sequencing of 344 …

Eradication Rates Of Empiric Helicobacter Pylori Treatment Regimens By Race/Ethnicity In A Predominantly Immigrant Us Population, Min J Kim, Isiah Gonzalez, Nia M Choi, David Y Graham, Hashem B El-Serag, Mimi C Tan

Faculty, Staff and Students Publications

Background: Helicobacter pylori infections are mostly treated empirically (without antibiotic susceptibility testing). Determining eradication rates of different treatment regimens can inform antibiotic resistance. Our aim was to examine eradication rates of empiric H. pylori treatments based on treatment regimen, race/ethnicity and previous treatment status in a multiethnic U.S.

Materials and methods: This was a retrospective cross-sectional study of patients with a positive H. pylori test from 7/2021 to 4/2022 at Harris Health (Houston, Texas) who had received treatment and eradication testing within 1 year. We compared eradication rates based on treatment regimen, race/ethnicity, and prior treatment and examined other possible …

Interval Advanced Adenomas And Neoplasia In Patients With Negative Colonoscopy Following Positive Stool-Based Colorectal Cancer Screening Test, Kyle S Liu, Rollin George, Caleb Shin, Jia Q Xiong, Taher Jamali, Yan Liu, Priya Roy, Sonia Singh, Samuel Ma, Hashem B El-Serag, Mimi C Tan

Faculty, Staff and Students Publications

BACKGROUND/AIMS: Fecal occult blood test (FOBT) and fecal immunohistochemical test (FIT) are used for colorectal cancer (CRC) screening. However, when no adenomas are found following a positive FOBT/FIT, the future risk of advanced adenomas or colorectal cancer (CRC) is unclear. We determined the incidence and determinants of advanced adenomas or CRC after a negative index colonoscopy following a positive FOBT/FIT.

METHODS: We identified patients in the Harris Health System (Houston, Texas) who underwent a colonoscopy following a positive FOBT/FIT from 01/2010 to 01/2013. We compared the incidence rates of advanced adenomas (≥ 1 cm, villous histopathology, or high-grade dysplasia) or …

Resilience Of The Gut Microbiome To Short Proton Pump Inhibitor Therapy With Or Without High-Dosage L Reuteri In H Pylori-Infected Adults, Stefano Bibbò, Gustav Ahlström, Giovanni Mario Pes, David Y Graham, Lars Engstrand, Elettra Merola, Maria Pina Dore

Faculty, Staff and Students Publications

Background: Helicobacter pylori eradication therapy typically consists of a combination of antibiotics and an antisecretory drug. Probiotics may be added to reduce side effects and possibly improve outcomes.

Materials and methods: We conducted a double-blind, randomized trial of pantoprazole plus either Lactobacillus reuteri (Gastrus) (high dose) or a matching placebo to assess the impact on the gut microbiota of H. pylori-positive adults. Fecal samples were collected at baseline and after one and 2 months for shotgun metagenomic sequencing.

Results: A total of 26 patients were recruited and completed therapy. L. reuteri was only detected in the group that received supplemental …

Deletions In The Cdkl5 5′ Untranslated Region Lead To Cdkl5 Deficiency Disorder, Isabel Haviland, Ralph D Hector, Lindsay C Swanson, Aubrie Soucy Verran, Emma Sherrill, Zoë Frazier, Annemarie M Denny, Jenna Lucash, Bo Zhang, Holly A Dubbs, Eric D Marsh, Judith L Weisenberg, Helen Leonard, Milena Crippa, Francesca Cogliati, Silvia Russo, Bernhard Suter, Rajsekar Rajaraman, Alan K Percy, John M Schreiber, Scott Demarest, Timothy A Benke, Maya Chopra, Timothy W Yu, Heather E Olson

Faculty, Staff and Students Publications

Pathogenic variants in the cyclin-dependent kinase-like 5 (CDKL5) gene are associated with CDKL5 deficiency disorder (CDD), a severe X-linked developmental and epileptic encephalopathy. Deletions affecting the 5' untranslated region (UTR) of CDKL5, which involve the noncoding exon 1 and/or alternatively spliced first exons (exons 1a-e), are uncommonly reported. We describe genetic and phenotypic characteristics for 15 individuals with CDKL5 partial gene deletions affecting the 5' UTR. All individuals presented characteristic features of CDD, including medically refractory infantile-onset epilepsy, global developmental delay, and visual impairment. We performed RNA sequencing on fibroblast samples from three individuals with small deletions involving exons 1 …

Evaluation Of Methotrexate Pharmacogenomic Variation To Predict Acute Neurotoxicity In Children With Acute Lymphoblastic Leukemia, Rachel D Harris, Olga A Taylor, M Monica Gramatges, Amy E Hughes, Mark Zobeck, Sandi Pruitt, M Brooke Bernhardt, Ashley Chavana, Van Huynh, Kathleen Ludwig, Laura Klesse, Kenneth Heym, Timothy Griffin, Rodrigo Erana, Juan Carlos Bernini, Ashley Choi, Yuu Ohno, Melissa A Richard, Alanna C Morrison, Han Chen, Bing Yu, Philip J Lupo, Karen Rabin, Michael E Scheurer, Austin L Brown

Faculty, Staff and Students Publications

BACKGROUND: Methotrexate is an important component of curative therapy in childhood acute lymphoblastic leukemia (ALL), but the role of genetic variation influencing methotrexate clearance and transport in toxicity susceptibility in children with ALL is not well established. Therefore, we evaluated the association between suspected methotrexate pharmacogenomic variants and methotrexate-related neurotoxicity.

METHODS: This study included children (aged 2-20 years) diagnosed with ALL (2005-2019) at six treatment centers in the southwest United States. Clinical information was abstracted from medical records. Suspected neurotoxic events occurring within 21 days of intravenous and/or intrathecal methotrexate delivered between the end of induction and start of maintenance …

The Reprogramming Factor Klf4 In Normal And Malignant Blood Cells, H Daniel Lacorazza

Faculty, Staff and Students Publications

The Krüppel-like factor 4 (KLF4) is an evolutionarily conserved zinc finger transcription factor that regulates cellular processes in stem cells, epithelial cells, and immune blood cells by controlling gene expression through genetic, epigenetic, and chromatin remodeling. The landmark 2006 publication identified KLF4 as one of the factors involved in reprogramming differentiated cells into pluripotent stem cells, sparking increased interest in KLF4 research a decade after its discovery, particularly in the fields of stem cell research, epithelial cell biology, endothelial cell function, and tumorigenesis. Over the years, KLF4 has emerged as a key transcription factor in modulating innate and adaptive immunity, …

A Pipeline For Rapid, High-Throughput Imaging And Quantitative Analysis Of Human Intestinal Organoids, Faith M Sawyer, Fabio Stossi, Erika Nachman, Robert A Britton, Michael J Bolt, Michael A Mancini, Mary K Estes, Sarah E Blutt

Faculty, Staff and Students Publications

Human intestinal organoids (HIOs) are a model system for studying human intestinal epithelium. Utilizing HIOs for high-throughput studies remains inefficient, as analyzing their cellular composition and responses to varying experimental conditions requires extensive time and labor. We describe a 96-well plate-based automated pipeline for rapidly imaging and quantifying fluorescent labeling in HIOs using a high-throughput confocal microscope and image analysis software. The pipeline was leveraged to quantify varying levels of cell proliferation among donor HIO lines in response to microbial products. Cytoplasmic fluorescence via antibody labeling was also quantified with the pipeline, enabling measurement of the prevalence of specific cell …

Urinary Ammonium: A Potential Novel Biomarker For Diarrhea Severity In Patients With Ulcerative Colitis, Jared A Sninsky, L Parker Gregg, Mahbubur Rahman, Adith Ram, Jason K Hou

Faculty, Staff and Students Publications

No abstract provided.

Efficacy And Safety Of Dostarlimab In Combination With Chemotherapy In Patients With Dmmr/Msi-H Primary Advanced Or Recurrent Endometrial Cancer In A Phase 3, Randomized, Placebo-Controlled Trial (Engot-En6-Nsgo/Gog-3031/Ruby), Matthew A Powell, Carolyn Mccourt, Et Al.

2020-Current year OA Pubs

OBJECTIVES: Part 1 of the RUBY trial (NCT03981796) demonstrated improved survival in patients with primary advanced or recurrent endometrial cancer (EC) treated with dostarlimab plus carboplatin-paclitaxel versus placebo plus carboplatin-paclitaxel. Here, we examine additional efficacy and safety data from patients with mismatch repair deficient/microsatellite instability-high (dMMR/MSI-H) EC in the RUBY trial.

METHODS: Patients were randomized 1:1 to dostarlimab 500 mg or placebo plus carboplatin-paclitaxel every 3 weeks for 6 cycles followed by dostarlimab or placebo every 6 weeks for up to 3 years. In the dMMR/MSI-H population of RUBY Part 1, analysis of progression-free survival by investigator assessment compared with …

Exploring Factors Contributing To Patient Decision-Making In The Care Journey To Elective Hernia Care In Kenya, Helen W. Li, Jesse Kiprono Too, Sarah Nyanchama Nyariki, Charles Nathan Nessle, Sara Malone, Rachel Matsumoto, Teddy Ashibende Aurah, Jeffrey A. Blatnik, Joanna Hunter-Squires, Ivan Seno Saruni

2020-Current year OA Pubs

BACKGROUND: Capacity for elective general surgical care is an important reflection of a health system's ability to meet a population's surgical needs and is currently known to be inadequate in many low- and middle-income countries. Patient agency is a key, understudied factor which shapes how and when patients ultimately decide to engage with formal care. Understanding factors which influence patient care seeking activity can have important implications for how current and future health systems may be utilized. This study aims to explore how patients approach the navigation and triage of their elective hernia condition within the Kenyan surgical care system. …

The Role Of Complement In Normal Pregnancy And Preeclampsia, Richard M Burwick, Anuja Java, Jean F Regal

2020-Current year OA Pubs

Preeclampsia affects 3-4% of pregnancies with adverse effects for both mother and child. Minimal therapeutic options are available, and biomarkers are urgently needed to identify those at greatest risk early in the pregnancy. Both the innate and adaptive immune systems are well regulated during normal pregnancy including the complement system. A functioning complement system with some degree of complement activation participates in proper placental development, ensuring a healthy pregnancy and assisting with host defense. However, aberrant complement activation can lead to adverse pregnancy outcomes such as preeclampsia. An overview of the complement system will be presented, along with review of …

Mapping Of Rorγt+ Dendritic Cells In Human Tissues Establishes Their Preferential Niche In Adult Lymph Nodes, Silvia Lonardi, Shitong Wu, Alina Ulezko Antonova, Yizhou A Liu, Marina Cella, Marco Colonna, William Vermi, Et Al.

2020-Current year OA Pubs

BACKGROUND: The retinoic-acid-receptor-related orphan receptor gamma t (RORγt) isoform is required for the development of lymphoid organs, T-helper 17 cells (Th17), and innate lymphoid cells (ILC3s). Recent data in mouse and human have revealed non-T, non-ILC3 cell populations with antigen presenting features that express RORγt. This study maps the presence of RORγt cells with dendritic cell (DC) features in human adult and fetal lymphoid tissues.

METHODS: By combining multicolor flow cytometry, RNAseq of peripheral blood cells, analysis of lymph node scRNAseq datasets, and microscopic analysis on human tissue sections and single-cell suspensions, this study maps the presence of RORγt cells …

Th9 Cells Provide Protective Tb Immunity, Mei Xia, Azra Blazevic, Huan Ning, Christopher S Eickhoff, Chad E Storer, Richard D Head, Jianguo Liu, Jessica Jarvela, David Stoeckel, Erin Rakey, Jan Tennant, Daniel L Miller, Kathleen R Holloway, Richard F Silver, Daniel F Hoft

2020-Current year OA Pubs

INTRODUCTION: CD4+ Th9 cells have been associated with inflammatory and allergic diseases. IL-9/Th9 can function as both positive and negative immune regulators, but their protective effects against

METHODS: To study TB-specific Th9 protective effects, we generated Th9 cells from ESAT6-specific TCR transgenic mice and healthy human donors.

RESULTS: Both murine and human Th9 cells significantly inhibited intracellular mycobacterial growth. In both

DISCUSSION: Th9 cells can provide important protection against Mtb infection, and should be targeted with future TB vaccine strategies. Furthermore, Th9 cells appear to utilize a novel protective mechanism independent from Th1-mediated protective responses.

An Exploratory Graphical Analysis Of The Montgomery-Åsberg Depression Rating Scale Pre- And Post-Treatment Using Pooled Antidepressant Trial Secondary Data, David Byrne, Arunangshu Ghoshal, Fiona Boland, Susan Brannick, Robert M Carney, Pim Cuijpers, Alexandra L Dima, Kenneth E Freedland, Suzanne Guerin, David Hevey, Bishember Kathuria, Vincent Mcdarby, Emma Wallace, Frank Doyle

2020-Current year OA Pubs

BACKGROUND: The 10-item Montgomery-Åsberg Depression Rating Scale (MADRS) is a commonly used measure of depression in antidepressant clinical trials. Numerous studies have adopted classical test theory perspectives to assess the psychometric properties of this scale, finding generally positive results. However, its network configural structure and stability is unexplored across different time-points and treatment groups.

AIMS: To assess the network structure and stability of the MADRS in clinical settings pre- and post-treatment, and to determine a configurally invariant and stable model across time-points and treatment groups (placebo and intervention).

METHOD: Individual participant data for 6440 participants from 14 clinical trials of …

Cervical Cancer In Women With Hiv: A Call To Action For Equitable Prevention In Low- And Middle-Income Countries, Jonathan Klutse, Yeena Abla Tay, Dzidzor Aku Attoh, Emmanuel Frimpong Gyekye, Charlotte Borteley Bortey, Esenam Dzifa Buatsi, Charlayne Cherylyn Oppong, Helena Lamptey, Collins Stephen Ahorlu, George Boateng Kyei, Evelyn Yayra Bonney

2020-Current year OA Pubs

Cervical cancer is preventable; however, it remains the leading cause of death in low- and middle-income countries (LMICs). Women with HIV (WWHs) have a sixfold higher risk of developing and dying from cervical cancer than women without HIV. Cervical cancer can be prevented by vaccination against high-risk human papillomaviruses (hrHPVs) and by screening for and treating precancer cervical lesions. While these preventive measures are routinely available to WWHs in developed countries, they are lacking in most LMICs, where the burden of HIV and cervical cancer is the highest. To prevent cervical cancer deaths among WWHs in LMICs, it is imperative …

Viral Kinetics Among Persons Living With Hiv (Plwh) On Dolutegravir-Based Antiretroviral Regimen: A Retrospective And Prospective Analysis From Selected Hiv Clinics In Ghana, Samuel Badu Nyarko, Joel Adu Twum, Aikins Sarpong Obeng, Helena Dede Djangba, Oksana Ryabinina, Foster Kyei, George Boateng Kyei, Nicholas Ekow Thomford

2020-Current year OA Pubs

BACKGROUND: Dolutegravir (DTG)-based antiretroviral therapy has demonstrated superior efficacy, tolerability, and durability when compared to other HIV treatment regimens. However, monitoring viral kinetics is critical for determining treatment efficacy and making sound judgments. The purpose of this study was to assess viral kinetics in people living with HIV (PLWH) on DTG-based ART and identify characteristics related to virologic response in the Cape Coast Metropolis, Ghana.

METHODS: Among people living with HIV (PLWH) attending HIV clinics between January 2020 and December 2023, a prospective and retrospective analysis of viral kinetics and clinical data were carried out. Data on viral loads, clinical …

Molecular Regulation And Therapeutic Targeting Of Vldl Production In Cardiometabolic Disease, Kendall H Burks, Nathan O Stitziel, Nicholas O Davidson

2020-Current year OA Pubs

There exists a complex relationship between steatotic liver disease (SLD) and atherosclerotic cardiovascular disease (CVD). CVD is a leading cause of morbidity and mortality among individuals with SLD, particularly those with metabolic dysfunction-associated SLD (MASLD), a significant proportion of whom also exhibit features of insulin resistance. Recent evidence supports an expanded role of very low-density lipoprotein (VLDL) in the pathogenesis of CVD in patients, both with and without associated metabolic dysfunction. VLDL represents the major vehicle for exporting neutral lipid from hepatocytes, with each particle containing one molecule of apolipoproteinB100 (APOB100). VLDL production becomes dysregulated under conditions characteristic of MASLD …