Life Sciences Commons^™

Bariatric Surgery Impacts Immune Cell Metabolism And Function Dependent On Metabolic Status, Samantha N. Hart

University of Kentucky Doctoral Dissertations

Type 2 Diabetes (T2D), one of the top ten causes of death worldwide, is fueled by chronic inflammation. T2D is considered a metabolic disease, and there is a great push to target metabolic and associated inflammatory pathways to ameliorate the disease & its comorbidities i.e., obesity and cardiovascular disease. Thus far, clinical trials of anti-inflammatory drugs have had modest impacts on T2D and have not led to changes in clinical practice. This may in part be due to a gap in knowledge in the mechanism(s) driving obesity-associated chronic inflammation. I posit that metabolic abnormalities in immune cells in those with …

Chronic Alcohol Consumption Enhances The Differentiation Capacity Of Hematopoietic Stem And Progenitor Cells Into Osteoclast Precursors, Hami Hemati, Madison B. Blanton, Jude Koura, Rupak Khadka, Kathleen A. Grant, Ilhem Messaoudi

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Chronic alcohol consumption (CAC) is associated with an enhanced risk of bone fracture, reduced bone density, and osteoporosis. In a rhesus macaque model of voluntary ethanol consumption, CAC induces functional, transcriptomic, and epigenomic changes in hematopoietic stem and progenitor cells (HSPCs) and their resultant monocytes/macrophages, skewing them toward a hyper-inflammatory response. In the present study, those studies were extended to investigate alterations in osteoclast development, which, in postnatal life, differentiate from HSPCs and play a critical role in maintaining bone homeostasis. Spectral flow cytometry revealed a skewing of HSPCs toward granulocyte-monocyte progenitors in the CAC group, consistent with an increased …

Chronic Alcohol Consumption Reprograms Osteoclast Lineage Communications To Promote Osteoclastogenesis, Hami Hemati, Brianna M. Doratt, Ilhem Messaoudi

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Chronic alcohol consumption increases the risk of osteoporosis and fracture by disrupting bone remodeling, in part by enhancing osteoclastogenesis. However, the cellular mechanisms underlying this process remain incompletely defined. We analyzed scRNA-seq data from osteoclasts differentiated in vitro from bone marrow mononuclear cells obtained from macaques following 12 months of chronic ethanol or isocaloric control solution consumption. Module scoring, trajectory inference with generalized additive modeling (tradeSeq), and CellChat-based analyses of intercellular communication were applied to uncover ethanol-induced changes in metabolic reprogramming, lineage progression, and signaling network dynamics. Module scoring indicated metabolic reprogramming toward oxidative phosphorylation, with reduced glycolytic, migratory, and …

Alcohol Consumption Exacerbates High-Fat Diet- Mediated Disruptions In Myelopoiesis And Osteoclastogenesis In Mouse Models Of Metabolic Dysfunction-Associated Liver Diseases, Hami Hemati, Madison B. Blanton, Lauren Rutt, Nicholas Keiran, Rebecca Geron, Florence Lima, Rebecca L. Mccullough, Ilhem Messaoudi

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Objective: Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) and Metabolic Dysfunction-Associated Alcohol-related Liver Disease (MetALD) exhibit systemic immune abnormalities. Given that such immune dysregulation is closely linked to the skeletal complications frequently observed in MASLD and MetALD, we sought to comprehensively characterize the bone marrow hematopoietic compartment and its link to osteoclastogenesis.

Methods: We utilized bone marrow from mouse models of MASLD (high-fat diet, HFD) and MetALD (high-fat diet plus ethanol, HFD+EtOH), followed by flow cytometric analysis to phenotype hematopoietic stem and progenitor cells (HSPCs), as well as in vitro and in vivo assays to evaluate osteoclastogenesis.

Results: We found that …

Transcriptional Signatures Of Rapid Protection From Sudan Virus Infection By A Single Dose Of A Vesicular Stomatitis Virus-Based Vaccine, Brianna M. Doratt, Sheridan B. Wagner, Delphine C. Malherbe, Gregory T. Smith, Andrea Marzi, Ilhem Messaoudi

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Sudan virus (SUDV) has caused multiple outbreaks of human disease with case fatality rates ranging from 41 to 100%. We have previously shown that a single vaccination with a recombinant vesicular stomatitis virus-based vaccine expressing the SUDV-Gulu glycoprotein (VSV-SUDV) prevented clinical and fatal disease from lethal SUDV challenge in cynomolgus macaques. With the high probability of future outbreaks, it is critical to determine the molecular mechanisms of VSV-SUDV-mediated protection and the ability to impart rapid protection against SUDV infection. In this study, RNA from whole blood samples obtained from nine cynomolgus macaques that were challenged with SUDV-Gulu post-vaccination with either …

Characterizing Immune Perturbations In Peripheral Blood Following The East Palestine, Ohio Train Derailment, Sheridan B. Wagner, Hami Hemati, Siva Gandhapudi, Timothy J. Hilbert, Candace J. Brancato, Erin N. Haynes, Ilhem Messaoudi

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Background: The East Palestine, Ohio, train derailment on February 3rd, 2023, resulted in the exposure of residents and the surrounding area to numerous hazardous chemicals, which included known acute irritants and human carcinogens. Despite evacuation and cleanup, both residents and responders reported high occurrences of symptoms associated with exposure in the months following, such as eye, skin, and respiratory irritation, headaches, and fatigue. The long-term health consequences for residents remain uncertain.

Objective: To assess the potential for immune perturbations resulting from the exposure, we performed a broad investigation of circulating immune cells and mediators from residents of East Palestine, OH, …

Combinatorial Immunotherapy Drives Exhaustion In Tumor Antigen–Specific Cd8+ T Cells Within The Mouse Renal Tumor Microenvironment, Holly R. Stephens, Elizabeth Elkins, Jing Li, Zoey N. Swalley, Henry Nnaemeka Ogbonna, Pia Muri, Zachary Roberts, Francesca R. Dempsey, Md Akkas Ali, Md Hasanul Banna Siam, Richard Kirkman, Jianqing Zhang, Sunil Sudarshan, Daniel J. Tyrrell, Hubert M. Tse, Daniel L. Smith Jr, Lyse A. Norian

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Immunotherapies have greatly improved outcomes for patients with renal cell carcinoma (RCC), yet response rates remain suboptimal and the factors promoting therapy resistance versus sensitivity are incompletely understood. Currently, no preclinical model of orthotopic renal cancer exists that permits evaluation of tumor antigen–specific (TAS) CD8⁺ tumor-infiltrating lymphocytes (TILs). To address this deficiency, we developed a mouse renal cancer model that permits tracking of adoptively transferred TAS CD8⁺ T cells. Renca-LUC tumor cells were transduced to express tumor ERK (tERK), a model antigen expressing a one-amino-acid change from wild-type ERK, resulting in recognition by tERK/H-2K^d-specific DUC Thy1.1 …

Polyfluoroalkyl Substances And Altered Glucose Homeostasis In Adolescents Following Bariatric Surgery, Elizabeth Costello, Brittney O Baumert, Zhenjiang Li, Vishal Midya, Shudi Pan, Justin R Ryder, Thomas H Inge, Todd M Jenkins, Stephanie Sisley, Stavra A Xanthakos, Anita Courcoulas, Douglas I Walker, Nikos Stratakis, Damaskini Valvi, Scott M Bartell, Angela L Slitt, Rohit Kohli, Sarah Rock, Michele A La Merrill, Sandrah P Eckel, Max T Aung, Rob Mcconnell, David V Conti, Lida Chatzi

Children’s Nutrition Research Center Staff Publications

Objectives: Bariatric surgery is an effective treatment for severe obesity and associated metabolic comorbidities. Exposure to polyfluoroalkyl substance (PFAS) before bariatric surgery may attenuate improvements in glucose metabolism and explain some of the heterogeneity in post-surgery outcomes.

Design: This is an observational cohort study.

Methods: Adolescents (n = 186) enrolled in the Teen-Longitudinal Assessment of Bariatric Surgery study were included. Eight-PFAS congeners were measured in plasma before surgery. Linear and logistic regressions were used to examine cross-sectional associations between log2-transformed PFAS (ng/mL) and fasting glucose, insulin, hemoglobin A1c (HbA1c), and homeostatic model assessment for insulin resistance (HOMA-IR). Linear mixed …

Test-Retest Apparent Diffusion Coefficient Reproducibility In Head And Neck Cancer Using A 15-T Mr-Linac, Brigid A Mcdonald, Dina El-Habashy, Renjie He, Sam Mulder, Sarah Mirbahaeddin, Abdallah S R Mohamed, Sara Ahmed, Yao Ding, Jihong Wang, Stephen Y Lai, Alex Dresner, John Christodouleas, Clifton D Fuller

Faculty, Staff and Student Publications

Purpose

To evaluate the reproducibility of apparent diffusion coefficient (ADC) measurements in head and neck squamous cell carcinoma (HNSCC) using a 1.5-T MR-linac (MRI-guided linear accelerator) system.

Materials and Methods

In this retrospective study, conducted between February 2021 and January 2024, patients with HNSCC lesions underwent echo-planar imaging diffusion-weighted MRI on a 1.5-T MR-linac system at two time points before the start of radiation therapy. Mean and median ADC values and volumes were measured for each lesion. Absolute and percent reproducibility coefficients (RCs) were calculated. Linear regression analyses and F tests were performed to determine whether the lesion volume or …

Not Biological, But Built: Structural And Metabolic Pathways Driving Black Maternal Health Disparities In The United States, Alexandra I. Umegboh

CMC Senior Theses

Black infants in the United States are more than twice as likely to die before their first birthday than white infants, a disparity often attributed to genetics, behavior, or individual health choices. However, this idea is challenged by a key contradiction: African immigrant women consistently experience better birth outcomes than U.S.-born Black women despite being similarly racialized. This thesis investigates the origins of this reproductive advantage and the factors contributing to its decline over time. By drawing on epidemiological data, metabolic health research, and literature on African diasporic healing traditions, it argues that the “healthy immigrant effect” is not biological, …

Tick Lipocalin Triggers Mammalian Igfbp-3-Mediated Apoptosis In Macrophages And Keratinocytes, Krittika Nandy, P. P. Mahesh, Lichao Liu, Daniel E. Sonenshine, Hameeda Sultana, Girish Neelakanta

Biological Sciences Faculty Publications

Ticks secrete several molecules, including lipocalins, in their saliva during blood feeding on a vertebrate host. In this study, we provide novel evidence on the role of Ornithodoros turicata americanus tick lipocalin (Otlip) in modulating cytokine expression and in triggering apoptosis in mammalian macrophages and keratinocytes. The cytokine array analysis revealed significantly increased secretion of insulin-like growth factor-binding protein 3 (IGFBP3) from murine macrophage cell line upon treatment with recombinant Otlip protein (rGST-Otlip) when compared to the secretion noted from cells treated with a control protein (rGST). Similar observation with cytokine protein array analysis was noted when murine macrophages were …

Brain-Derived Extracellular Vesicles Potentially Mediate Crosstalk With Peripheral Organs In Neurodegenerative Diseases, Ramzi H. Hamdalla, Vibha B. Bhaskar, Changhai Tian

Toxicology and Cancer Biology Faculty Publications

Brain-Derived Extracellular vesicles (BDEVs) are emerging mediators of intra- and interorgan communication in neurodegenerative diseases (NDs) such as Alzheimer’s Disease (AD) and Parkinson’s Disease (PD). A growing body of evidence suggests that BDEVs play an important role in modulating intercellular communication within the central nervous system in the pathogenesis of many NDs. By transporting non-coding RNAs (e.g., miRNAs) and important pathological proteins, BDEVs also influence peripheral organs and contribute to the progression of disease in the central nervous system (CNS). This review extends the understanding of NDs beyond solely brain dysfunction and gives a novel framework for the progression of …

A Ubiquitous Organophosphate Flame Retardant Disrupts Energy And Glucose Homeostasis In Mice, Krystal M. Sewell, Kelly Oriakhi, Sara Y. Ngo Tenlep, Megan L. Weaver, Mansura Shahad Bawa, Se-Hyung Park, Shubh Saraswat, Xiaohua D. Zhang, Robert N. Helsley, Samir Softic, Cetewayo S. Rashid

Pharmacology and Nutritional Sciences Faculty Publications

Organophosphate flame retardants (OPFRs) are used in many consumer products, and their presence in our environment raises concerns about potential health dangers. In humans, exposure to OPFRs, such as tris(1,3-dichloro-2-propyl) phosphate (TDCPP) is associated with metabolic disorders such as obesity, hyperglycemia, and insulin resistance. Our current study seeks to determine how TDCPP exposure affects body composition, glucose homeostasis, and energy balance in a rodent model. C57Bl/6 J mice were divided into two weight-matched groups and fed purified low phytoestrogen diets containing either 0.1 % DMSO (control) or TDCPP 415 mg/kg resulting in an approximate exposure of 50 mg/kg/day. Both male …

Contribution Of Metabolism-Independent Glucose Sensing To Metabolic Homeostasis, Nadia Rashid, Kavaljit H. Chhabra

Pharmacology and Nutritional Sciences Faculty Publications

Glucose sensing and signaling are central to cellular metabolic machinery for the regulation of metabolic homeostasis. Glucose sensing has been almost always assumed to be coupled with glucose metabolism; however, recent findings have unraveled metabolism-independent sensing mechanisms. Here, we discuss whether glucose transporters (GLUTs) and sodium-glucose co-transporters (SGLTs) may also function as glucose sensors independent of their roles in transporting glucose. Moreover, we review the emerging roles of G protein-coupled receptors (GPCRs) in sensing glucose and, consequently, initiating its signaling pathways in a cell-specific manner. Altogether, this review offers insights into the newly identified glucose sensing mechanisms and highlights the …

Anatomical Atlas Of Kinase Responsiveness To Weight Gain: Adipose Depot Reprogramming In Diet-Induced Adiposity, Wang-Hsin Lee, Zachary A. Kipp, Sally N. Pauss, Genesee J. Martinez, Mei Xu, Terry D. Hinds, Jr.

Pharmacology and Nutritional Sciences Faculty Publications

Background/Objectives: Adipose tissue depots located at different anatomical sites exert differential functions in response to adiposity and glucose intolerance. These fat depots exhibit distinct metabolic signaling patterns that may influence pathological fat accumulation, thereby affecting the efficacy of anti-obesity interventions. Nonetheless, the mechanisms underpinning depot-specific signaling and pathway responsiveness remain insufficiently understood.

Methods: Kinase activity was characterized during the progression of adiposity across five adipose tissue depots in obese versus lean mice using the advanced PamGene kinome technology. Furthermore, kinase pathways in human preadipocytes and mouse 3T3-L1 preadipocytes were analyzed and compared with those in their differentiated, mature adipocytes. The …

An Ensemble Classifier For Ordinal Outcomes In High-Dimensional Genomics Data, Heranga K. Rathnasekara, Sinjini Sikdar

Mathematics & Statistics Faculty Publications

Analysis of genomics data for predicting disease outcomes is a fast-growing field in medical research. There often exist categorical, specifically, ordinal outcomes that need to be predicted based on genomic profiles. This has led to recent development of some high-dimensional ordinal classification methods that can address the large dimensionality of the genomic covariate set. These high-dimensional ordinal models tend to vary widely in their performance depending on the data they are applied to and the evaluation criteria used. In this article, we outline an ensemble ordinal classifier that integrates different ordinal modeling approaches through bootstrap-based model evaluation, multi-metric performance assessment, …

Bringing Awareness And Education To Rural Areas About The Role Occupational Therapy (Ot) Has In Infant Care, Makenzi Richwald

Occupational Therapy Doctorate Capstone Posters

This capstone project focused on education and advocacy. The aim of my capstone project was to provide education to parents of eastern Kentucky (KY) about what Occupational Therapy (OT) can address with infants aged 0-18 months. I saw a gap in knowledge in the eastern KY community about what OT could do for infants and wanted to address this. Through my research, consultation with my mentors, and collaboration with the occupational therapists at my site (BPT) I discerned 14 areas of development and/or common reasons of needed referral for OT services by this age group. These educational materials aimed to …

A Narrative Review Of The High-Carbohydrate Fueling Revolution (≥100 G/H) In The Professional Peloton, Patrick B. Wilson

Exercise Science Faculty Publications

High-carbohydrate fueling in cycling (defined as ≥ 100 g/h for this paper) has received significant media attention in recent years. Whether this practice improves performance, however, remains an unresolved issue in the scientific literature. The purpose of this narrative review is to provide an up-to-date analysis of the practice of high-carbohydrate fueling, with a specific focus on potential performance implications in professional cycling. Topics covered include historical carbohydrate intake guidelines, research directly comparing high-carbohydrate fueling with traditional fueling guidelines, theorized benefits of high-carbohydrate fueling specific to cycling, potential risks associated with high-carbohydrate fueling, and personalizing carbohydrate intakes. Among a small …

Granulomatous Cellular Signatures In Nontuberculous And Tuberculous Mycobacterial Infections, Brianna M. Doratt, Ethan G. Napier, Mahdi Eskandarian Boroujeni, Sarah Douglas, Michael H. Davies, Luiz Bermudez, Eliot Spindel, Erin F. Mccaffrey, Ilhem Messaoudi

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Mycobacterium tuberculosis (Mtb) and nontuberculous mycobacteria (NTM) are acid-fast bacilli that trigger granuloma formation, a hallmark immune response aimed at containing infection. While the biology of Mtb granulomas has been widely investigated, far less is known about granulomas caused by NTM infection, despite the increasing prevalence and clinical challenge of NTM cases worldwide. Because granulomas influence infection control, pathology, and treatment response, understanding their cellular organization and signaling is critical to improving therapeutic strategies. Therefore, we characterized granulomas formed following infection of rhesus macaques with Mycobacterium avium subsp. hominissuis (MAH) and compared them to granulomas from cynomolgus macaques infected with …

Glycoprotein-Specific Transcriptional Response Contributes To Differential Vaccine Protection Against Lethal Ebola Virus Infection, Sheridan B. Wagner, Delphine C. Malherbe, Ethan G. Napier, Andrea Marzi, Ilhem Messaoudi

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Since the West African Ebola virus (EBOV) epidemic in 2014-2016, recurrent outbreaks of the EBOV-Makona variant have been driven by recrudescence and human-to-human transmission emphasizing the need for effective vaccination strategies. A live-attenuated recombinant vesicular stomatitis virus (VSV)-based vaccine expressing the EBOV-Kikwit variant glycoprotein (VSV-Kik) received FDA approval in December 2019 and provides complete, rapid protection against EBOV-Makona as early as 7 days post-vaccination (DPV). During the 2018-2020 Ebola outbreak, the VSV-Kik vaccine, known as ERVEBO, was administered to lower-risk individuals at a 5-fold dose reduction of the standard 2 × 10 ⁷ PFU to provide broader population protection. Identification …

Expanding The Role Of Muscle Stem Cell Fusion In Muscle Under Hypertrophic Stimulus, Jensen Goh Zhong Sheng

Theses and Dissertations--Physiology

Muscle stem cells (MuSCs) are a unique stem cell population that can activate in response to both injury and growth stimuli. Studies on muscle regeneration have shown MuSC activation follows a uniform progression through proliferation, differentiation, and fusion. Therefore, to determine whether MuSC replication is a prerequisite for differentiation under hypertrophic stimulus, I used a lineage-tracking mouse model (Pax7^rtTA; TRE-H2B-GFP) to label MuSC nuclei and simultaneously tracked DNA synthesis via EdU incorporation. This dual-labeling approach allowed us to not only distinguish MuSC-derived nuclei but also demarcate which MuSC had proliferated prior to fusion. I then employed a mechanical …

Investigation Into The A/Ss Of Cervical Cancer And Its Effects On Tumor Control Probability In Radiation Therapy, Cameron Thayer-Freeman

Theses and Dissertations--Radiation Medicine

The standard of care for locally advanced cervical cancer is chemoradiation, consisting of conventional external beam therapy (EBT) followed by a boost of high dose rate (HDR) brachytherapy. These two radiation treatments will illicit different degrees of biological response depending on the tissue in question, and quantifying the overall effect the combined treatments will have require some form of biological modeling. The linear quadratic (LQ) model of cell survival is the most widely used radiobiological model in clinics across the nation.

It is quantified by the parameters a and ß, which model how radiation generates lethal damage in a population …

Hsp90 Inhibitor, At13387 Mitigates Chronic Lung Injury In Pre-Pubertal Mice: A Therapeutic Axis In Bronchopulmonary Dysplasia, Pavel A. Solopov, Christiana Dimitropoulou, John D. Catravas, Ruben M. L. Colunga Biancatelli

Bioelectrics Publications

Exposure to hydrochloric acid (HCl) can provoke severe chronic pulmonary injury. Children are particularly vulnerable due to their smaller airways, higher respiratory rate, and stronger inflammatory response; yet no countermeasures exist for HCl-induced chronic lung injury in the pediatric population. We have previously demonstrated the involvement of HSP90 during HCl-induced lung injury in pre-pubertal (p24) mice, who develop stronger persistent inflammation with higher NLRP3 inflammasome activation, but less pulmonary fibrosis compared to adults. Here, we tested the hypothesis that post-treatment with the second-generation HSP90 inhibitor AT13387 (Onalespib), administered subcutaneously beginning 24 h after HCl instillation, would prevent HCl-induced chronic lung …

Limosilactobacillus Reuteri Alleviates Proinflammatory T-Cell-Mediated Liver Injury And Transcriptomic Changes In Immunocompromised Mice, Ana Fadhel Alvarez, Zheng Yin, Beanna Okeugo, Alexander Banerjee, Meng Luo, Christopher M Taylor, Salomea Giorgberidze, Vaishali Harne, Rambabu Majji, Melissa N Munroe, Ji Ho Suh, Stephen T C Wong, Kang Ho Kim, Hari Krishna Yalamanchili, Suhair Al Salihi, Jon Marc Rhoads, Yuying Liu

Children’s Nutrition Research Center Staff Publications

Background: A deficiency of immunosuppressive regulatory T cells, as seen in scurfy (SF) mice or in IPEX syndrome in humans, can lead to multiorgan inflammation. Oral administration of the probiotic Limosilactobacillus reuteri Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH (DSM) 17938 prolongs survival and reduces Th1- and Th2-associated inflammation in SF mice. It remains unclear how DSM 17938-educated SF-CD4+ T cells modulate T-cell-liver communication.

Methods: To characterize CD4+ T cells from SF mice orally administered DSM 17938 (Prob-SF-CD4+ T cells) and to compare them with CD4+ T cells from SF mice (SF-CD4+ T cells), cells isolated from SF spleens were …

Kinase Signaling In Liver Disease Via Clinical-Trial-On-A-Pamchip: A Distinctive Methodology For Drug Mechanisms And Personalized Medicine, Zachary A. Kipp, Evelyn A. Bates, Genesee J. Martinez, Wang-Hsin Lee, Sally N. Pauss, Terry D. Hinds, Jr.

Pharmacology and Nutritional Sciences Faculty Publications

The utilization of extensive datasets, such as those generated by DNA or RNA sequencing, has become a central focus in drug discovery and personalized medicine (PerMed). Nonetheless, these datasets are constrained by the absence of protein-functionality testing, which affects physiological responses. In this study, we employed PamGene PamStation technology to quantify protein function by kinase activity across more than 500 signaling pathways from patients with hepatocellular carcinoma (HCC). Using proteins derived from nine patients and five human HCC cell lines for drug discovery and the clinical trial-on-a-chip approach, we developed comprehensive PerMed scores from the PamStation data to differentiate individual …

A Novel Tyrosine Kinase Axis In Innate Immune Signaling, Santanu Das, Pracheta Sengupta, Manoj Veleeparambil, Saurabh Chattopadhyay

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Tyrosine phosphorylation has emerged as a central regulatory mechanism in innate immunity. Building on our recent studies that Syk and EGFR sequentially phosphorylate TLR9 to fully activate it, we discuss how similar mechanisms operate across other Toll-like receptors and the cytosolic DNA sensor STING. Evidence from complementary systems reveals that receptor and nonreceptor tyrosine kinases, including Src-family kinases, Syk, BTK, and EGFR, form an integrated signaling network that triggers receptor activation, trafficking, and downstream gene expression. Scavenger receptors such as SR-A further drive this kinase cascade by coordinating viral recognition to TLR activation. These observations reveal a novel ‘tyrosine kinase …

Maternal Opioid Use Disorder And Hepatitis C Infection In Pregnancy Reshape The Peripheral Immune Landscape At Term, Brianna M. Doratt, Heather E. True, Sheridan B. Wagner, Delphine C. Malherbe, Zachary M. Reynolds, Cynthia Cockerham, John O'Brien, Ilhem Messaoudi

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Background: Pregnancy requires precisely timed immune adaptations to maintain foetal tolerance while enabling timely initiation of labour, a process often conceptualised as the ‘immune clock’ of pregnancy. Disruption of this immune clock contributes to adverse obstetric outcomes. While maternal opioid use disorder (OUD) is a recognised risk factor for poor maternal and neonatal health, its impact on maternal immune landscape at delivery remains poorly understood.

Methods: We analysed peripheral blood collected from pregnant individuals with and without OUD at time of admission for delivery before the onset of active labour. We employed multiparameter flow cytometry, cytokine profiling, and single-cell-RNA sequencing …

“Shaking The Ladder” Reveals How Analytic Choices Can Influence Associations In Nutrition Epidemiology: Beef Intake And Coronary Heart Disease As A Case Study, Colby J Vorland, Lauren E O'Connor, Beate Henschel, Cuiqiong Huo, James M Shikany, Carlos A Serrano, Robert Henschel, Stephanie L Dickinson, Keisuke Ejima, Aurelian Bidulescu, David B Allison, Andrew W Brown

Children’s Nutrition Research Center Staff Publications

Nutrition epidemiological models involve many analytic decisions, such as defining exposures, selecting which covariates to include, or configuring variables in different ways. We explored the impact of analytical decisions on conclusions in nutrition epidemiology using self-reported beef intake and incident coronary heart disease as a case study. We used REasons for Geographic and Racial Differences in Stroke (REGARDS) data, and selected covariates and their configurations from published literature to recapitulate common models used to assess associations between meat intake and health outcomes. Three model sets were designed: sets one and two used continuous and quintile-defined beef intakes, respectively, each with …

A Pragmatic Guide To Data Integration For Pediatric Researchers: The Nuts And Bolts Of Mixed Methods Analysis, Kathleen A Knafl, Janet A Deatrick, Veronica M Swallow, Yelena P Wu, Debbe Thompson

Children’s Nutrition Research Center Staff Publications

Objective: To provide pragmatic guidance on data analysis, integration, and reporting guidance for investigators new to mixed methods research.

Methods: Three core mixed methods designs (convergent, explanatory sequential, and exploratory sequential) are described. Key decision points related to data integration-specifying intent, data selection, data preparation, integration strategies, use of analysis software, reporting-are explained, including comparison of decision points across the different mixed methods designs.

Results: Recommendations for addressing key decisions during analysis are provided and supported with published examples from mixed methods studies focused on pediatric populations.

Conclusions: Integration of qualitative and quantitative data is the defining characteristic of mixed …

Sustainable Community-Wide Model To Enhance Cancer Data Usage And Utility, Emily S Boja, Mousumi Ghosh, Ying Huang, Tung-Shing Mamie Lih, Rawan Shraim, Gregory Wheeler, Diana Thomas, Rakesh Khanna, Stephanie Sandor, Jinghui Zhang, Sapna Oberoi, Nicolas J Llosa, Aditya Suru, Fernanda Silva Michels, Eric Durbin, Anna Fernandez, Lucy Han, James Galbraith, Yin Lu, Brian Furner, James H Tanis, Michael Watkins, David Higgins, Gavriel Matt, Xin Zhou, Yang Li, Marcin Cieslik, Jamie Estill, Michael Sierk, Yanling Sun, Weiping Ma, Joseph Flores-Toro, Freddie Pruitt, Subhashini Jagu, Elmer A Fernández, Daniela Orschanski, Stephanie J Spielman, Jaclyn Taroni, Trinh Nguyen, Brian Capaldo, Erin Beck, Tanja Davidsen, Johanna Goderre Jones, Minghong Ward, Anne Sturcke, Jennifer M Torres Del Valle, Sean Hanlon, Danielle Daee, Brandon Wright, Nathaniel Boyd, Heather Basehore, Liang Liu, Ying Hu, Daoud Meerzaman, Huiqing Li, Ying Wu, Gregory H Reaman, Erin Rudzinski, Jack F Shern, Brigitte Widemann, Warren Kibbe, Jaime Guidry Auvil

Children’s Nutrition Research Center Staff Publications

Despite vast investments in data collection, generation, and sharing from childhood cancer studies, for example, Gabriella Miller Kids First Research Program, Childhood Cancer Data Initiative, and other efforts, secondary use of data remains a challenge especially for rare diseases. The National Cancer Institute (NCI) Office of Data Sharing (ODS) aimed to promote FAIR (Findable, Accessible, Interoperable, Reusable) data sharing practices to enhance data utility, accelerate discovery, and foster interdisciplinary collaboration. NCI ODS launched its inaugural Data Jamboree focusing on childhood cancer alongside its third Annual Symposium in September 2025. Over 120 participants with diverse backgrounds coalesced into 23 multidisciplinary teams …