Health Services Research Commons^™

Impact Of Sanitation System Types On Residential And Environmental Presence Of Human Waste And Parasites In Alabama, Brandon Hunter, Catherine Coleman Flowers, Rojelio Mejia, Marc Arnold Deshusses

Faculty, Staff and Students Publications

Lowndes County is a predominantly Black rural county in Alabama, in the United States, which has a historical and current legacy of racial discrimination, creating inequitable infrastructure access and adverse health impacts. Over 80% rely on on-site sanitation infrastructure and most are failing. A community assessment of exposure to untreated sewage was conducted using samples from residential drinking water, surface swabs, and soil combined with environmental water and soil samples using culture-based and quantitative polymerase chain reaction (qPCR) methods. Testing varied slightly across samples, due to difficulty of access or availability. Of 43 households, 68% and 55% of houses had …

Rapid High-Sensitivity Detection Of Antibodies To Trypanosoma Cruzi With A Recombinant Tc24 Antigen-Based Magneto-Immunoassay: A Pilot Study, Kavya L Singampalli, Bin Zhan, Rojelio Mejia, Peter B Lillehoj

Faculty, Staff and Students Publications

The diagnosis of chronic Chagas disease is challenging due to the wide genetic diversity of Trypanosoma cruzi, the causative agent of Chagas disease, and low levels of parasitemia, resulting in low sensitivity and accuracy with existing diagnostics. We report a magneto-immunoassay that employs dually labeled magnetic beads incorporating a recombinant Tc24 antigen, which is homologous across multiple discrete typing units of T cruzi. In this pilot study, 102 serum samples from 7 endemic countries were tested by this magneto-immunoassay, revealing its ability to distinguish Chagas-positive from Chagas-negative cases more accurately and faster than a standard Tc24-based immunoassay.

Global Diversity Of Soil-Transmitted Helminths Reveals Population-Biased Genetic Variation That Impacts Diagnostic Targets, Marina Papaiakovou, Andrea Waeschenbach, Olumide Ajibola, Sitara Sr Ajjampur, Roy M Anderson, Robin Bailey, Jade Benjamin-Chung, Maria Cambra-Pellejà, Nicolas R Caro, David Chaima, Rubén O Cimino, Piet Cools, Anélsio Cossa, Julia Dunn, Sean Galagan, Javier Gandasegui, Berta Grau-Pujol, Emma L Houlder, Moudachirou Ibikounlé, Timothy P Jenkins, Khumbo Kalua, Eyrun F Kjetland, Alejandro J Krolewiecki, Bruno Levecke, Adrian Jf Luty, Andrew S Macdonald, Inácio Mandomando, Malathi Manuel, Maria Martínez-Valladares, Rojelio Mejia, Zeleke Mekonnen, Augusto Messa, Harriet Mpairwe, Osvaldo Muchisse, Jose Muñoz, Pauline Mwinzi, Valdemiro Novela, Maurice R Odiere, Charfudin Sacoor, Judd L Walson, Steven A Williams, Stefan Witek-Mcmanus, D Timothy J Littlewood, Cinzia Cantacessi, Stephen R Doyle

Faculty, Staff and Students Publications

Soil-transmitted helminths (STHs) are intestinal parasites that affect over a billion people worldwide. STH control relies on microscopy-based diagnostics to monitor parasite prevalence and enable post-treatment surveillance; however, molecular diagnostics are rapidly being developed due to increased sensitivity, particularly in low-STH-prevalence settings. The genetic diversity of helminths and its potential impact on molecular diagnostics remain unclear. Using low-coverage genome sequencing, we assess the genetics of STHs within worm, faecal, and purified egg samples from 27 countries, identifying differences in the genetic connectivity and diversity of STH-positive samples across regions and cryptic diversity between closely related human- and pig-infective species. We …

Single-Cell Profiling Of Bone Metastasis Ecosystems From Multiple Cancer Types Reveals Convergent And Divergent Mechanisms Of Bone Colonization, Fengshuo Liu, Yunfeng Ding, Zhan Xu, Xiaoxin Hao, Tianhong Pan, George Miles, Siyue Wang, Yi-Hsuan Wu, Jun Liu, Igor L Bado, Weijie Zhang, Ling Wu, Yang Gao, Liqun Yu, David G Edwards, Hilda L Chan, Sergio Aguirre, Michael Warren Dieffenbach, Elina Chen, Yichao Shen, Dane Hoffman, Luis Becerra Dominguez, Charlotte Helena Rivas, Xiang Chen, Hai Wang, Zbigniew Gugala, Robert L Satcher, Xiang H-F Zhang

Faculty, Staff and Students Publications

Bone is a common site for metastasis of solid cancers. The diversity of histological and molecular characteristics of bone metastases (BMs) remains poorly studied. Here, we performed single-cell RNA sequencing on 42 BMs from eight cancer types, identifying three distinct ecosystem archetypes, each characterized by an enrichment of specific immune cells: macrophages/osteoclasts, regulatory/exhausted T cells, or monocytes. We validated these archetypes by immunostaining on tissue sections and bioinformatic analysis of bulk RNA sequencing/microarray data from 158 BMs across more than 10 cancer types. Interestingly, we found only a modest correlation between the BM archetypes and the tissues of origin; BMs …

High-Affinity Cd16a Polymorphism Associated With Reduced Risk Ofsevere Covid-19, Anita E Qualls, Tasha Tsao, Irene Lui, Shion A Lim, Yapeng Su, Ernie Chen, Dylan Duchen, Holden T Maecker, Seunghee Kim-Schulze, Ruth R Montgomery, Florian Krammer, Charles R Langelier, Ofer Levy, Lindsey R Baden, Esther Melamed, Lauren Ir Ehrlich, Grace A Mccomsey, Rafick P Sekaly, Charles B Cairns, Elias K Haddad, Albert C Shaw, David A Hafler, David B Corry, Farrah Kheradmand, Mark A Atkinson, Scott C Brakenridge, Nelson I Agudelo Higuita, Jordan P Metcalf, Catherine L Hough, William B Messer, Bali Pulendran, Kari C Nadeau, Mark M Davis, Ana Fernandez-Sesma, Viviana Simon, Monica Kraft, Christian Bime, Carolyn S Calfee, David J Erle, Joanna Schaenmann, Al Ozonoff, Bjoern Peters, Steven H Kleinstein, Alison D Augustine, Joann Diray-Arce, Patrice M Becker, Nadine Rouphael, Impacc Network, Jason D Goldman, Daniel R Calabrese, James R Heath, James A Wells, Elaine F Reed, Lewis L Lanier, Harry Pickering, Oscar A Aguilar

Faculty, Staff and Students Publications

CD16A is an activating Fc receptor on NK cells that mediates antibody-dependent cellular cytotoxicity (ADCC), a key mechanism in antiviral immunity. However, the role of NK cell-mediated ADCC in SARS-CoV-2 infection remains unclear, particularly whether it limits viral spread and disease severity or contributes to the immunopathogenesis of COVID-19. We hypothesized that the high-affinity CD16AV176 polymorphism influences these outcomes. Using an in vitro reporter system, we demonstrated that CD16AV176 is a more potent and sensitive activator than the common CD16AF176 allele. To assess its clinical relevance, we analyzed 1,027 patients hospitalized with COVID-19 from the Immunophenotyping Assessment in a COVID-19 …

Pan-Cancer, Multi-Omic Correlates Of Survival Transcending Tumor Lineage Across 11,019 Patients Reveal Targets And Pathways, Yiqun Zhang, Fengju Chen, Chad J Creighton

Faculty, Staff and Students Publications

Molecular correlates of cancer patient overall survival (OS) can provide new insights. Here, we systematically cataloged pan-cancer, multi-omic correlates of OS transcending tumor lineage across 11,019 patients, involving multiple cancer types while correcting for cancer-type-intrinsic OS differences. Significant fractions of genes with mRNA associated with OS in pan-cancer analyses showed concordant associations at the levels of DNA copy number alteration or methylation. Pan-cancer gene signatures of T-cell and macrophage tumor infiltrates were associated with better and worse OS, respectively. Pathways implicated by molecular OS associations included metabolism, PI3K/Akt, Wnt, and TGF-beta receptor. Significant fractions of worse OS-associated genes were essential …

Assessment Of Functioning Using The Whodas 20 Among People With Myasthenia Gravis-Associated Disability: A Nationwide Follow-Up Study, Jia-Pei Hong, Chih-Hong Lee, Chien Tai Hong, Lung Chan, Chen-Chih Chung, Prangthip Charoenpong, Hou-Chang Chiu, Tsan-Hon Liou

Faculty, Staff and Students Publications

Background: Advancements in treatment have increased the life expectancy of patients with Myasthenia Gravis (MG), yet the understanding of functional changes in these individuals remains limited. In our study, we explored the functional abilities of individuals with MG using the World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0).

Methods: This observational study analyzed data from 286 patients with MG, acquired from the Data Bank of Persons with Disabilities (TDPD) in Taiwan between July 11, 2012, and December 31, 2021. Participants were diagnosed with MG after the acute phase. The functional disability outcome was assessed using the WHODAS 2.0. Due …

Figo Position Statement: Gamete Donations, Laurie Henry, Aris Antsaklis, Dov Feldberg, Jaideep Malhotra, Suchitra Pandit, Carlos Salazar, Alex Vidaeff, Rafal Zadykowicz, M Louise Hull, Nikhil Purandare

Faculty, Staff and Students Publications

Gamete donation has become a crucial part of Assisted Reproductive Technologies (ARTs), providing hope to individuals, including those who may have no other option for parenthood. This process comes with a wide range of ethical, medical, and legal challenges that need to be carefully addressed to protect the well-being and rights of all parties involved: donors, recipients, and offspring. Navigating these complexities requires strict ethical standards, robust regulatory frameworks, and international collaboration. By standardizing these, the field of gamete donation can continue to develop while ensuring that all parties are well informed and safeguarded. This paper explores the ethical concerns …

Microbial Biosensor For Sensing And Treatment Of Intestinal Inflammation, Duolong Zhu, Jeffrey Galley, Jason Pizzini, Elena Musteata, Martin V Douglas, Walter J Chazin, Eric P Skaar, Jeffrey J Tabor, Robert A Britton

Faculty, Staff and Students Publications

Synthetic biology has enabled the development of biosensors to detect intestinal inflammation, yet few target the clinically validated biomarker of intestinal inflammation calprotectin with both diagnostic and therapeutic capabilities. Here, an optimized calprotectin biosensor is presented that leverages a zinc uptake regulator (Zur) controlled promoter coupled with a memory circuit to detect and record intestinal inflammation in vivo. The level of biosensor activation strongly correlates with calprotectin levels in the colon of two independent mouse models of colitis. Coupling of the biosensor with the production of the anti-inflammatory cytokine IL10 allowed for the resolution of chemically induced colitis, demonstrating the …

Unfolding The Mystery Of Autoimmunity: The Environmental Determinants Of Diabetes In The Young (Teddy) Study, Marian Rewers, Daniel Agardh, Suzanne Bennett Johnson, Ezio Bonifacio, Helena Elding Larsson, Patricia Gesualdo, William Hagopian, Michael J Haller, Heikki Hyöty, Randi Johnson, Richard Mcindoe, Eoin Mckinney, Jessica Melin, Åke Lernmark, Richard E Lloyd, Kristian F Lynch, Jill M Norris, Stephen S Rich, Roswith Roth, Desmond Schatz, Jorma Toppari, Eric Triplett, Kendra Vehik, Suvi M Virtanen, Anette-G Ziegler, Beena Akolkar, Jeffrey P Krischer, Teddy Study Group

Faculty, Staff and Students Publications

In 2025, the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at the National Institutes of Health celebrates 75 years of leadership in diabetes research. The NIDDK serves people of the U.S. affected by or at risk for many chronic diseases, including diabetes and other endocrine, metabolic, and digestive disorders, by funding innovative research to develop better treatment and prevention and a cure for these conditions. Autoimmunity that leads to type 1 diabetes or celiac disease or thyroid autoimmunity affects 1 in 20 children and adolescents in the U.S. While treatments are available, prevention of these common autoimmune …

Anemia In Inflammatory Bowel Disease: Practice Patterns And Clinical Outcomes In A Large National Veterans Cohort, Jared A Sninsky, Carolyn Brooks, Shubhada Sansgiry, Richa Shukla, Stalin Subramanian, Jason K Hou

Faculty, Staff and Students Publications

Background: Anemia is a common complication of inflammatory bowel disease (IBD), impacting patient quality of life and clinical outcomes. This study examines anemia management practices and clinical outcomes in a national cohort of veterans with IBD.

Methods: A retrospective cohort study of 89 687 veterans with IBD from 2000 to 2017 was conducted using Veterans Health Administration data. We assessed anemia screening, iron store assessments, and iron therapy. Primary outcomes included anemia resolution within 12 months. Secondary outcomes included IBD-related hospitalizations, steroid use, and surgery within five years. Multivariate logistic regression models assessed associations between patient characteristics and clinical outcomes. …

Dichotomous Roles Of Acbd3 In Nsclc Growth And Metastasis, Xiaochao Tan, Chao Wu, Priyam Banerjee, Shike Wang, Derrick L Cardin, Yuting Xu, Chad J Creighton, William K Russell

Faculty, Staff and Students Publications

Lung cancer continues to be the leading cause of cancer-related deaths globally. Unraveling the regulators behind lung cancer growth and its metastatic spread, along with understanding the underlying mechanisms, is crucial for developing novel and effective therapeutic strategies. While much research has focused on identifying potential oncogenes or tumor suppressors, the roles of certain genes can vary depending on the context and may even exhibit contradictory effects. In this study, we demonstrate that acyl-CoA binding domain containing 3 (ACBD3), a Golgi resident protein, promotes primary lung cancer growth by recruiting phosphatidylinositol (PI)-4-kinase IIIβ (PI4KB) to the Golgi, thereby enhancing oncogenic …

Cytokine Release Syndrome And Neurotoxicity Following Cd19 Car-T In B-Cell Lymphoma, Roni Shouval, Christopher Strouse, Soyoung Kim, Temitope Oloyede, Sairah Ahmed, Farrukh T Awan, Danny Luan, Veronika Bachanova, Talha Badar, Merav Bar, Pere Barba, Amer M Beitinjaneh, Amanda Cashen, Bhagirathbhai Dholaria, Mahmoud Elsawy, Siddhartha Ganguly, Praveen Ramakrishnan Geethakumari, Uri Greenbaum, Hamza Hashmi, Laquisa C Hill, Michael D Jain, Tania Jain, Partow Kebriaei, Adam S Kittai, Frederick L Locke, Premal D Lulla, Elena Mead, Joseph P Mcguirk, Alberto Mussetti, Taiga Nishihori, Amanda L Olson, Martina Pennisi, Miguel-Angel Perales, Peter A Riedell, Wael Saber, Abu-Sayeef Mirza, Margarida Magalhaes-Silverman, Elizabeth J Shpall, Mohamed Sorror, Kitsada Wudhikarn, Cameron J Turtle, Amy Moskop, Marcelo C Pasquini

Faculty, Staff and Students Publications

Chimeric antigen receptor T cell (CAR-T) therapy is an effective treatment for relapsed-refractory large B-cell lymphoma (LBCL). However, toxicities, particularly cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), remain significant concerns. Analyze temporal trends, risk factors, and associations between these toxicities and their severity. In this registry study by the Center for International Blood and Marrow Transplant Research, we studied CRS and ICANS in 1916 LBCL patients treated with commercial CAR-T therapies (axicabtagene ciloleucel 74.9%, tisagenlecleucel 25.1%) between 2018 and 2020. Outcomes include development of CRS/ICANS, timing and severity according to ASTC grading, overall survival (OS). Risk …

Performance Of Stool Xpert Mtb/Rif Ultra For Detection Of Mycobacterium Tuberculosis Among Adults Living With Hiv: A Multicentre, Prospective Diagnostic Study, George W Kasule, Sabine Hermans, Sozinho Acacio, Alexander Kay, Joachim Kikoyo Nsubuga, Carlos Fernández-Escobar, Nosisa Shiba, Lucia Carratalá-Castro, Derrick Semugenze, Patricia Mwachan, Shilzia Munguambe, Joanna Ehrlich, Elisa Lopez-Varela, Andrew R Dinardo, Frank Cobelens, Christoph Lange, Moses Joloba, Anna M Mandalakas, Willy Ssengooba, Alberto L García-Basteiro

Faculty, Staff and Students Publications

Background: When people living with HIV develop pulmonary tuberculosis, it often manifests without detectable acid-fast bacilli on sputum microscopy. We aimed to assess the diagnostic accuracy of stool Xpert MTB/RIF Ultra (hereafter, Ultra) for Mycobacterium tuberculosis detection among adults with HIV.

Methods: This multicentre, prospective diagnostic accuracy study was done in outpatient and inpatient health centres in Eswatini, Mozambique, and Uganda. We enrolled adults aged 15 years and older with HIV with presumptive tuberculosis. We evaluated the diagnostic accuracy of stool Ultra using the simple one-step processing method against a composite microbiological reference standard (CMRS) including three WHO-recommended tuberculosis diagnostic …

Complete Genomic Characterization Of Global Pathogens Respiratory Syntical Virus And Human Norovirus Using Probe Based Capture Enrichment, Sravya V Bhamidipati, Anil Surathu, Hsu Chao, Daniel P Agustinho, Qin Xiang, Kavya Kottapalli, Abirami Santhanam, Zeineen Momin, Kimberly Walker, Vipin K Menon, George Weissenberger, Nathanael Emerick, Faria Mahjabeen, Qingchang Meng, Jianhong Hu, Richard Sucgang, David Henke, Fritz J Sedlazeck, Ziad M Khan, Ginger A Metcalf, Vasanthi Avadhanula, Pedro A Piedra, Sasirekha Ramani, Robert L Atmar, Mary K Estes, Joseph F Petrosino, Richard A Gibbs, Donna M Muzny, Sara Cregeen Javornik, Harsha Doddapaneni

Faculty, Staff and Students Publications

Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infections in children worldwide, while human noroviruses (HuNoV) are a leading cause of epidemic and sporadic acute gastroenteritis. Generating full-length genome sequences for these viruses is crucial for understanding viral diversity and tracking emerging variants. However, obtaining high-quality sequencing data is often challenging due to viral strain variability, quality, and low titers. Here, we present a set of comprehensive oligonucleotide probe sets designed from 1,570 RSV and 1,376 HuNoV isolate sequences in GenBank. Using these probe sets and a capture enrichment sequencing workflow, 85 RSV positive nasal swab …

Military Inhalational Exposures Outside The Theater Of Conflict And Chronic Respiratory Symptoms, Reza Hosseini, Eric Garshick, Martin D Slade, Andrew Timmons, Anna M Korpak, Nicholas L Smith, Karen S Nakayama, Coleen P Baird, Paul Ciminera, Farrah Kheradmand, Vincent S Fan, Jaime E Hart, Petros Koutrakis, Ware Glenn Kuschner, Octavian C Ioachimescu, Michael Jerrett, Philippe R Montgrain, Susan P Proctor, Christine H Wendt, Cherry Wongtrakool, Emily S Wan, Paul D Blanc, Carrie A Redlich

Faculty, Staff and Students Publications

Importance: Deployment to Afghanistan and Southwest Asia has been associated with adverse respiratory health outcomes. However, the impact of inhalational exposures (eg, vapor, dust, gas, fumes), which are known correlates of reduced lung function and future chronic lung disease, during military service time outside this deployment period has not been assessed.

Objective: To assess military inhalational exposures during nonwartime routine activities and their associations with chronic respiratory symptoms.

Design, setting, and participants: This cross-sectional study used data from the US Department of Veterans Affairs Service and Health Among Deployed Veterans study. US veterans who served between October 7, 2001, and …

Inhibition Of The Gsk3Β/Nav16 Complex Suppresses Early-Stage Alzheimer’S Hyperexcitability, Timothy John Baumgartner, Manuel Silva-Pérez, Zahra Haghighijoo, Nolan Michael Dvorak, Aditya Kumar Singh, Nana Aboadwe Goode, Jully Singh, Berenice Gutierrez Grebenkova, Mate Marosi, Jessica Di Re, Leandra Koff, Wissarut Wijitrmektong, Manu Bala, Hanyue Liao, Marijn Lijffijt, Adam Thomas Szafran, Michael James Bolt, Michael A Mancini, Gregory D Cuny, Diana Shu-Lian Chow, Agenor Limon, Jeannie Chin, Fernanda Laezza

Faculty, Staff and Students Publications

Introduction: Network hyperexcitability (NH) is observed in patients with early-stage Alzheimer's disease (AD), emerging decades before cognitive decline. A key molecular determinant of NH is voltage-gated Na+ channel 1.6 (Nav1.6), which mediates action potential firing in CA1 hippocampal neurons. Ameliorating NH through inhibition of the glycogen-synthase kinase 3β (GSK3β/Nav1.6 complex may provide immediate benefits to cognition and memory and slow AD progression.

Methods: Hight-throughput virtual screening and multiple in vitro biological assays were utilized to identify compound 1063. Patch-clamp electrophysiology and electroencephalogram recordings were utilized to functionally assess 1063 in models of AD neuropathology.

Results: Building on previous studies identifying …

Decoding Metastatic Microenvironments Through Single-Cell Omics Reveals New Insights Into Niche Dynamics And Tumor Evolution, Fengshuo Liu, Xiang H-F Zhang

Faculty, Staff and Students Publications

Metastasis is the predominant cause of cancer mortality, primarily driven by complex tumor-host interactions within specialized metastatic niches. Recent advances in single-cell technologies have provided unprecedented insights into metastatic niche formation, evolution and function, including how primary tumors precondition distant organs for metastases and how disseminated tumor cells dynamically interact with host cells to modulate their environments. Integrated single-cell studies across multiple cancer types have also revealed divergent and convergent metastatic adaptation strategies. These findings collectively highlight metastasis as a dynamic, cooperative process shaped by intricate tumor-host interactions, and provide a foundation for novel therapeutic strategies targeting components of the …

Association Of Statin Use On Survival Outcomes Of Patients With Early-Stage Her2-Positive Breast Cancer In The Aphinity Trial, Christian Maurer, Elisa Agostinetto, Lieveke Ameye, Matteo Lambertini, Samuel Martel, Noam Ponde, Mariana Brandão, Francesca Poggio, Arlindo Ferreira, Rachel Schiff, Carmine De Angelis, Richard D Gelber, Susan Dent, Christoph Thomssen, Martine Piccart, Evandro De Azambuja

Faculty, Staff and Students Publications

Purpose: There is evidence that statins might improve the outcome of patients with breast cancer. The role of statins in patients with early HER2-positive breast cancer is unknown. Therefore, we explored the association between statin use and survival outcomes in early HER2-positive breast cancer patients in the phase III APHINITY trial (adjuvant pertuzumab/trastuzumab).

Methods: All patients (intent-to-treat population, n = 4804) were included (6.2 years median follow-up database). The primary objective was to investigate the association of statin use on invasive disease-free survival (IDFS), distant relapse-free interval (DRFI), and overall survival (OS). Patients who received statins at baseline, or started …

High Prevalence Of Strongyloides Stercoralis In People Living With Hiv: A Critical Health Challenge In The Peruvian Amazon Basin, Silvia Otero-Rodriguez, Martin Casapia-Morales, Viviana Pinedo-Cancino, Seyer Mego-Campos, Victoria-Ysabel Villacorta-Pezo, Jorge Parráguez-De-La-Cruz, Eva H Clark, Esperanza Merino, Jose-Manuel Ramos-Rincon

Faculty, Staff and Students Publications

Introduction: Strongyloidiasis is an important but underdiagnosed soil-transmitted helminthiasis, particularly in tropical areas and some vulnerable groups.

Objectives: To assess the parasitological prevalence, seroprevalence and sociodemographic factors of Strongyloides stercoralis infection in patients living with human immunodeficiency virus (PLWH) in an endemic area.

Materials and methods: We performed a cross-sectional study of strongyloidiasis in 537 PLWH in two hospitals in Iquitos, Peru, from 20 Oct 2023 to 20 May 2024. We tested patient sera using Strongyloides IgG enzyme-linked immunosorbent assay (ELISA) and stool via the modified Baermann technique and/or charcoal fecal culture as highly sensitive parasitological techniques. We used multivariable …

Self-Powered Rapid Antigen-Specific T-Cell Response Assay For Mycobacterium Tuberculosis Infections, Bo Ning, Sutapa Chandra, Yongchun Pan, Riti Sharan, Ngan Ha, Sanjay Singh, Alexandra Portillo Varela, Lin Li, Qingli Wu, Alexander Kay, Gugu P Maphalala, Clement Adu-Gyamfi, Santiago Carrero Longlax, Anna M Mandalakas, Smriti Mehra, Christopher J Lyon, Edward A Graviss, Andrew R Dinardo, Tony Hu

Faculty, Staff and Students Publications

Interferon-gamma release assays (IGRAs) that evaluate an individual’s T-cell activation response to Mycobacterium tuberculosis (M.tb)-specific peptides serve an important role in diagnosing tuberculosis (TB). However, there are substantial challenges to the use of IGRAs in resource-limited settings. Further, IGRA diagnostic performance can also be compromised in anergic individuals. Here we describe a microfluidic chip-based antigen-specific T-cell response assay (ASTRA) that automates the detection of M.tb-specific T-cell activation responses to facilitate screening for latent M.tb infection and TB. We observe that ASTRA demonstrates high specificity for M.tb infection in independent patient cohorts. Compared with IGRA, ASTRA shows greater …

Btp2 Restricts Tulane Virus And Human Norovirus Replication Independent Of Store-Operated Calcium Entry, Francesca J Scribano, J Thomas Gebert, Kristen A Engevik, Nicole M Hayes, Jorge Villanueva, Son Pham, Soni Kaundal, Janam J Dave, B V Venkataram Prasad, Mary K Estes, Sasirekha Ramani, Joseph M Hyser

Faculty, Staff and Students Publications

Human norovirus is the leading cause of viral gastroenteritis across all age groups. While there is a need for human norovirus antivirals, therapeutic development has been hindered by a lack of cell culture systems and animal models of infection. Surrogate viruses, such as Tulane virus (TV), have provided tractable systems to screen potential antiviral compounds. Our previous work demonstrated that TV encodes a viral ion channel, which dysregulates cytosolic calcium signaling. We set out to investigate whether host pathways triggered by viral ion channel activity, including store-operated calcium entry (SOCE), play a role in virus replication. Using pharmacologic inhibitors and …

Regulation Of Myogenesis By Mechanomir-200c/Foxo3 Axis, Junaith S Mohamed, Aladin M Boriek

Faculty, Staff and Students Publications

Cyclic mechanical stretch has been shown to inhibit myoblast differentiation while promoting proliferation. However, the underlying molecular mechanisms are not well understood. Here, we report that mechanical stretch inhibits the differentiation of mouse primary myoblasts by promoting the cell cycle program and by inhibiting the expression of the myogenic regulator MyoD. Stretch alters the miRNA expression profile as evidenced by miRNA microarray analysis. We identified miR-200c as one of the highly downregulated mechanosensitive miRNAs (mechanomiRs) whose expression level was increased during differentiation. This suggests that mechanomiRs-200c is a myogenic miRNA. Overexpression of mechanomiR-200c revoked the effect of stretch on myoblast …

Impact Of Sociodemographic Determinants On Enrollment Into Contemporary Lymphoma Clinical Trials: A Systematic Review, Jun Yang Jiang, Ang Li, Alexis Romero, Christopher R Flowers, Chijioke Nze

Faculty, Staff and Students Publications

While the incidence and survival associated with lymphoma have improved in recent years, outcome disparities related to sociodemographic factors such as age, sex, race, ethnicity, socioeconomic status (SES), and other social determinants of health (SDOH) remain prevalent in the modern era. Clinical trials are crucial for further improving outcomes, yet not all sociodemographic groups are equally represented in contemporary lymphoma trials. We conducted a systematic review of the literature evaluating the impact of SDOH on enrollment into clinical trials in the United States and identified 21 relevant studies. We confirmed that Black and Hispanic individuals are underrepresented in lymphoma clinical …

Career Impact Of The National Interprofessional Fellowship In Patient Safety: An Alumni Evaluation, Bradley V Watts, Kathleen Carluzzo, Blake F Webb, Kelley Arredondo

Faculty, Staff and Students Publications

Background: There has been a proliferation of health professions training programmes focused on quality and patient safety, but little information regarding the outcomes of these programmes. The purpose of this study was to examine the impact of an interprofessional quality and patient safety curriculum on career outcomes of interprofessional healthcare learners for the Veterans Affairs Patient Safety Fellowship.

Method: We conducted a survey-based assessment of 117 alumni of the Interprofessional Fellowship in Patient Safety assessing their satisfaction with the training program and career impacts.

Results: 84 of 117 alumni were located and participated in the assessment. Fellows entered the training …

Phage-Induced Protection Against Lethal Bacterial Reinfection, Yikun Xing, Haroldo J Hernandez Santos, Ling Qiu, Samantha R Ritter, Jacob J Zulk, Rachel Lahowetz, Kathryn A Patras, Austen L Terwilliger, Anthony W Maresso

Faculty, Staff and Students Publications

Bacteriophages, or phages, are viruses that target and infect bacteria. Due to a worldwide rise in antimicrobial resistance (AMR), phages have been proposed as a promising alternative to antibiotics for the treatment of resistant bacterial infections. Up to this point in history, phage use in preclinical animal studies, clinical trials, and emergency-use compassionate care cases has centered around the original observation from 1915 showing phage as lytic agent, and thus a treatment that kills bacteria. Here, we describe an activity associated with phage therapy that extends beyond lytic activity that results in long-term protection against reinfection. This activity is potent, …

Adipocyte/Tumor Cell Crosstalk Via Igf-1/Txnip Axis Promotes Malignancy And Endocrine Resistance In Breast Cancer, Amanda Caruso, Felice Maria Accattatis, Cinzia Giordano, Luca Gelsomino, Piercarlo Del Console, Maria Francesca Fiorita, Balazs Gyorffy, Laura Bianchi, Alfonso Carleo, Rossana De Salvo, Bruno M Simões, Robert B Clarke, Lorenzo Memeo, Cristina Colarossi, Eleonora Aiello, Francesco Conforti, Suzanne A W Fuqua, Matilde Todaro, Giorgio Stassi, Catia Morelli, Diego Sisci, Daniela Bonofiglio, Stefania Catalano, Sebastiano Andò, Ines Barone

Faculty, Staff and Students Publications

Background: Despite significant improvements in the outcome of Estrogen Receptor (ER) α-positive breast cancer (BC) following the use of endocrine therapies, resistance remains a major challenge. Clinical studies proved that obesity, in addition to promote BC progression, is associated with a reduced efficacy to these treatments, but mechanisms remain unclear.

Methods: We used co-culture systems followed by validation through an ‘ex vivo’ model of human mammary obese (Ob) adipocytes and obese endocrine-resistant metastatic Patient-Derived Organoids (PDOs). Transcriptomics with MixOmics-MINT and MetaCore Functional Tools along with lentiviral and pharmacological approaches provide insights into mechanisms. Clinical relevance was investigated using public datasets, …

Aged Regulatory T Cells Fail To Control Autoimmune Lacrimal Gland Pathogenic Cd4+ T Cells, Kaitlin K Scholand, Laura Schaefer, Gowthaman Govindarajan, Zhiyuan Yu, Jeremias G Galletti, Cintia S De Paiva

Faculty, Staff and Students Publications

CD25KO mice are a model of Sjögren disease. CD25KO mice have severe inflammation and infiltrating lymphocytes to the lacrimal glands (LG). Whether the pathogenicity of CD25KO CD4+ T cells can be controlled in vivo by Tregs is unknown. Eight-week-old B6 and CD25KO mice LGs were submitted for RNA bulk sequencing. A total of 3481 genes were differentially expressed in CD25KO LG compared to B6. Tear washing analysis identified CD25KO mice had elevated protein levels of TNF, IFN-γ, and CCL5 and decreased protein levels of IL-12p40 and VEGF-A. Co-adoptive transfer of CD25KO CD4+ T cells with either young or aged B6 …

Dietary Interventions To Support And Improve Sleep Disturbances And Insomnia Disorder In Menopause: From Bench To Bedside, Rosie H Musgrave, Sara Nowakowski, Tamlyn J Watermeyer, Emily J Arentson-Lantz, Greg J Elder

Faculty, Staff and Students Publications

Sleep is essential for maintaining physical and psychological health, and also cognitive health (referred to as 'brain health'). However, the transition to menopause has a direct impact upon sleep. Sleep disturbances are reported by approximately 40%-60% of menopausal women, and insomnia disorder is also prevalent. Diet-based interventions could potentially be used to improve subjective sleep quality in this population, and although there are several promising interventions which have been used in other groups that could be trialled, the evidence base is currently lacking. One particularly promising area for future research is that these interventions might be used alongside, or instead …

Performance Of Stool-Based Molecular Tests And Processing Methods For Paediatric Tuberculosis Diagnosis: A Systematic Review And Meta-Analysis, Lucía Carratalà-Castro, Shilzia Munguambe, Belén Saavedra-Cervera, Petra De Haas, Alexander Kay, Olivier Marcy, Pamela Nabeta, Willy Ssengooba, Elisabetta Ghimenton-Walters, Sozinho Acácio, Maryline Bonnet, Joanna Ehrlich, Andrew R Dinardo, Anca Vasiliu, Christoph Lange, Sabine Hermans, Anna M Mandalakas, Elisa López-Varela, Alberto L García-Basteiro

Faculty, Staff and Students Publications

Background: There has been a global pursuit to improve the diagnosis of tuberculosis in young children by applying diagnostic methods on accessible biospecimens such as stool. We aimed to conduct a systematic review on the accuracy of stool-based molecular tests for tuberculosis diagnosis in children and to assess the impact of the available pre-processing methods and other design characteristics.

Methods: In this systematic review and meta-analysis, we evaluated studies in children younger than 16 years with presumptive tuberculosis that were published in English, Spanish, French, and Portuguese from Jan 1, 2000, to May 3, 2024, in MEDLINE, Embase, and Embase …