Public Health Commons^™

Sox2 Regulates Foregut Squamous Epithelial Homeostasis And Is Lost During Barrett’S Esophagus Development, Ramon U Jin, Yuanwei Xu, T Mamie Lih, Yang-Zhe Huang, Toni M Nittolo, Blake E Sells, Olivia M Dres, Jean S Wang, Qing K Li, Hui Zhang, Jason C Mills

Faculty, Staff and Students Publications

Esophageal adenocarcinoma is increasingly prevalent and is thought to arise from Barrett's esophagus (BE), a metaplastic condition in which chronic acid and bile reflux transforms the esophageal squamous epithelium into a gastric-intestinal glandular mucosa. The molecular determinants driving this metaplasia are poorly understood. We developed a human BE organoid biobank that recapitulates BE's molecular heterogeneity. Bulk and single-cell transcriptomics, supported by patient tissue analysis, revealed that BE differentiation reflects a balance between SOX2 (foregut/esophageal) and CDX2 (hindgut/intestinal) transcription factors. Using squamous-specific inducible Sox2-KO (Krt5CreER/+ Sox2Δ/Δ ROSA26tdTomato/+) mice, we observed increased basal proliferation, reduced squamous differentiation, and expanded metaplastic glands at …

Hot Spring Associated Infectious Diseases In The Great Basin And Southwest, Matthew Bentz

UNLV Theses, Dissertations, Professional Papers, and Capstones

Like all bodies of freshwater, natural hot springs can harbor pathogenic microorganisms that carry the threat of infectious disease. The unique chemistry, increased temperature, and popularity for bathing may alter the risk profile of hot springs compared to other natural bodies of water. Despite this risk, the role of hot springs as a reservoir for infectious diseases remains understudied, particularly within the context of regional public health. Nevada and the Great Basin/Southwest have increasingly promoted hot springs for the purposes of tourism, and they share a strong link to the cultural heritage of the region. The unknown risk profile and …

Analyzing Food Access: An Investigation Of Food Insecurity Amongst Latinos In Rural Nebraska, Natalia Santos

Theses & Dissertations

Background: Food insecurity is a public health issue in the United States, with disproportionately higher rates among Latino/Hispanic households. Rural communities face unique geographical, socioeconomic, and systemic barriers that often exacerbate food access disparities. Despite the growing Latino population in rural areas, particularly in Midwestern states like Nebraska, there remains a critical gap in comprehensive research that integrates both objective and subjective understandings of their food environments. Understanding these multifaceted influences is crucial for developing effective, culturally sensitive interventions.

Problem Statement: This dissertation aims to answer the central question: How does food access and food insecurity manifest amongst Latinos in …

Co-Targeting Bcl-Xl With Mcl-1 Induces Lethal Mitochondrial Dysfunction In Diffuse Mesothelioma, Yuan Xu, Cristian G Medina, Deborah R Surman, Lacey E Dobrolecki, Monica Vilchis, Maheshwari Ramineni, Susan G Hilsenbeck, Yanming Li, Naren Li, Siqi Wu, Jaylon C Aggison, Xi Chen, Yi Zhu, Ying H Shen, R Taylor Ripley

Faculty, Staff and Students Publications

Diffuse mesothelioma (DM) is a rare but highly aggressive and treatment resistant neoplasm with low survival rates. Effective therapeutic strategies are limited, and resistance to treatment is a major obstacle. Myeloid Cell Leukemia (MCL)-1 and B-cell leukemia (BCL)-xL are anti-apoptotic B-cell lymphoma 2 (Bcl-2) family proteins that block cell-intrinsic apoptosis through interactions on the mitochondrial outer membrane which contribute to therapeutic resistance.

We investigated whether B-cell homology domain (BH)-3 profiles were consistent between intra-patient fresh tumor sample, patient-derived cells (PDC), and patient-derived xenografts (PDX) by BH3 profiling; we observed striking consistency which enabled cross model comparisons. Next, we co-targeted BCL-xl …

Enumerating Escherichia Coli (E. Coli) Concentrations And Evaluating Optical Brighteners As A Potential Indicator Of Human Wastewater Contamination In La Nana Bayou, Banita Creek, And Their Tributaries, Nacogdoches, Texas, Swastika Acharya, Matthew Mcbroom, Yuhui Weng, Yanli Zhang

Electronic Theses and Dissertations

La Nana Bayou was added to the Texas 303(d) list in 2000 after it failed to meet water quality standards set by the Texas Commission on Environmental Quality (TCEQ) for primary contact recreation due to elevated Escherichia coli (E. coli) levels. E. coli is a bacterial species commonly found in the intestines of humans and warm-blooded animals. It serves as an indicator of fecal contamination in freshwater, though its presence alone cannot identify the contamination source. Optical brighteners (OBs), chemicals found in laundry detergents, cleaning agents, toilet papers, and clothing, are unique to human wastewater. This study aimed …

Three Things We Can Do Now To Reduce The Risk Of Avian Influenza Spillovers, Kenneth B Yeh, William P Bahnfleth, Elaine Bradford, Carol Cardona, Kristen K Coleman, Peter J Hudson, Bernadeta Dadonaite, Rebecca J Hutchins, Anthony Maresso, C Raina Macintyre, Matthew Scotch

Faculty, Staff and Students Publications

No abstract provided.

Increased Fungal Burden In The Gastrointestinal Tract Of Brain-Dead Organ Donors, Erika J Nachman, Colleen K Ardis, A Kyle B Ardis, Javier Nieto, Madeline M Bresson, Clare M Robertson, Maggie N Seale, Nora M Villafuerte, Zhe Lyu, Eva C Preisner, Heather A Danhof, Sara C Di Rienzi, Yolanda T Becker, Robert A Britton

Faculty, Staff and Students Publications

Approximately 3% of organ transplant recipients will be diagnosed with an invasive fungal infection (IFI), with 10%-47% being fatal. The source of IFI is typically not known, but Candida spp. cause the majority of IFI cases. We obtained intestines from two types of organ donors, brain-dead (BD) (n = 7) and donation after circulatory death (DCD) (n = 5), to sample microbes from the mucosal surface and the lumen. BD donors were parenterally fed and treated with corticosteroids in the days before procurement, whereas DCD donors were enterally fed and not given corticosteroids. We found fungi present in …

Demographic Characteristics And Selected Personality Traits Of Women In Competitive Bodybuilding, Chloe A. Zeeuw

Master's Theses

This study investigated demographic characteristics and measures of personality (dimensions of performance perfectionism and five-factor model characteristics) in women in competitive bodybuilding between 18-25 years old. A total of 24 women completed an online survey which included a demographic questionnaire, the Five Factor Model Rating Form (FFMRF), and the Performance Perfectionism Scale for Sport (PPSS) inventories. Descriptive results for the FFMRF were Openness (18.17±3.12), Conscientiousness (25.58±3.33), Extraversion (19.96±3.46), Agreeableness (19.88±4.58), and Neuroticism (15.67±4.94), and for the PPS-S were Self-oriented performance perfectionism (20.96±3.53), Socially prescribed performance perfectionism (13.96±4.26), and Other-oriented performance perfectionism (10.54±4.23). Pearson’s correlation coefficients and Shapiro-Wilk tests revealed that …

Advanced Interactions Of Directed Energy With Retinal Pigment Epithelial Cells And Their Photochemical And Photothermal Responses, Jin B. Ha

Theses & Dissertations

Excess optical radiation can injure the retina through either rapid heat deposition (photothermal damage) or cumulative photo‑oxidative stress (photochemical damage), yet current laser‑safety limits treat these mechanisms as independent. To test that assumption, this dissertation integrated systematic wavelength, duration and temperature‑controlled laser exposures with live/dead fluorescence imaging in a melanin‑loaded hTERT‑RPE1 monolayer model. First, concurrent 447 nm (blue) and 2 µm (infra‑red) beams delivered for 200 s demonstrated a strong thermal–photochemical synergy: each beam alone was sub‑threshold (≤25 % lethality) but together produced 100 % RPE death without exceeding 50 °C, proving that modest heating markedly lowers the photon dose …

The Inside Scoop: Elucidating The Three-Way Relationship Between Schistosoma Mansoni, The Gut, And Vaccines, Mariam A. Mhanna

Biomedical Sciences Theses & Dissertations

Schistosomiasis is a neglected tropical disease that affects over 250 million people worldwide. This blood fluke infection burdens communities and areas with limited to no access to clean fresh water. When a host is exposed to cercariae, the infectious agent, in a body of water, it matures in the host’s circulation into adult female and male worms. Copulated adult worms migrate to the mesentery, in the case of Schistosoma mansoni, and produce eggs that can cross the intestinal barrier and get excreted in the feces to continue the lifecycle. The effects of S. mansoni infection on the host …

Low-Dose Metformin Requires Brain Rap1 For Its Antidiabetic Action, Hsiao-Yun Lin, Weisheng Lu, Yanlin He, Yukiko Fu, Kentaro Kaneko, Peimeng Huang, Ana B De La Puente-Gomez, Chunmei Wang, Yongjie Yang, Feng Li, Yong Xu, Makoto Fukuda

Faculty, Staff and Students Publications

Metformin is the most commonly prescribed antidiabetes drug, yet its precise mechanism of action remains controversial. Previous studies have suggested that metformin acts peripherally by reducing hepatic glucose output and altering gut functions. Here, we report a neural mechanism via the small guanosine triphosphatase Ras-related protein 1 (Rap1). Mice with forebrain-specific Rap1 knockout exhibited resistance to the antidiabetic effects of low-dose metformin while remaining sensitive to other antidiabetic agents. Centrally administered metformin inhibited brain Rap1 and reduced hyperglycemia. Conversely, forced activation of brain Rap1 increased glycemia and abolished the glycemic effect of metformin. Metformin activated a specific subset of neurons …

Nerve-To-Cancer Transfer Of Mitochondria During Cancer Metastasis, Gregory Hoover, Shila Gilbert, Olivia Curley, Clémence Obellianne, Mike T Lin, William Hixson, Terry W Pierce, Joel F Andrews, Mikhail F Alexeyev, Yi Ding, Ping Bu, Fariba Behbod, Daniel Medina, Jeffrey T Chang, Gustavo Ayala, Simon Grelet

Faculty, Staff and Students Publications

The nervous system has a pivotal role in cancer biology, and pathological investigations have linked intratumoural nerve density to metastasis1. However, the precise impact of cancer-associated neurons and the communication channels at the nerve–cancer interface remain poorly understood. Previous cancer denervation models in rodents and humans have highlighted robust cancer dependency on nerves, but the underlying mechanisms that drive nerve-mediated cancer aggressivity remain unknown2,3. Here we show that cancer-associated neurons enhance cancer metabolic plasticity by transferring mitochondria to cancer cells. Breast cancer denervation and nerve–cancer coculture models confirmed that neurons significantly improve tumour energetics. …

Single-Cell Transcriptomics Reveals Biomarker Heterogeneity Linked To Cdk4/6 Inhibitor Resistance In Breast Cancer Cell Lines, Ilenia Migliaccio, Martina Bonechi, Dario Romagnoli, Giulia Boccalini, Francesca Galardi, Cristina Guarducci, Agostina Nardone, Rachel Schiff, Laura Biganzoli, Luca Malorni, Matteo Benelli

Faculty, Staff and Students Publications

Cyclin dependent kinases 4 and 6 inhibitors have brought great improvements in the treatment of luminal breast cancer, but resistance is a major clinical hurdle. Multiple biomarkers of resistance have been proposed, but none is currently utilized in clinical practice. By performing single-cell RNA sequencing of seven palbociclib-naïve luminal breast cancer cell lines and palbociclib-resistant derivatives, we show that established biomarkers and pathways related to CDK4/6i resistance present marked intra- and inter- cell-line heterogeneity. Transcriptional features of resistance could be already observed in naïve cells correlating with levels of sensitivity (IC50) to palbociclib. Resistant derivatives showed transcriptional clusters that significantly …

Assessment Of Covid-19 Risks Related To Behaviour And Body Resistance In The Remote Area: Case Study In Jeneponto, Basri Basri, Andi Tilka Muftiah Ridjal, Lukman Setiawan, Renaldi M

Journal of Environmental Science and Sustainable Development

COVID-19 has posed significant global health threats, with responses varying across populations due to differences in risk perception, behaviour, and biological vulnerability. In Indonesia, most research has focused on urban settings, with limited attention paid to rural or remote communities. This study assesses COVID-19- risks related—specifically behavioural and immunity-related-factors—in the remote area of both Bontoramba Subdistrict, Jeneponto Regency. A cross-sectional study was conducted using cluster random sampling across eight villages, with 183 participants selected from a total of 12,242 households. Data were collected between November to December 2020 using a validated structured questionnaire, administered both online and face-to-face interviews. The …

Resilience Mediates The Association Between Discrimination And Psychological Distress Among Rural, Black Women In South Carolina: A Structural Equation Model, Camryn Garrett, Abhisheak Aggrawal, Huiyi Xia, Cheuk Chi Tam, Bankole Olatosi Ph.D., Sarah Wilcox Phd, Xiaoming Li Ph.D., Shan Qiao Ph.D.

Faculty Publications

Introduction

The marginalization of intersecting racial, gender, and rural identities compounds the structural vulnerabilities (e.g., discrimination, stigma, health disparities) experienced by Black women in South Carolina’s rural areas. Discriminatory experiences can deteriorate mental health; however, resilience can potentially reduce the ill effects of discrimination by decreasing associated psychological distress. This study examines the mediating role of resilience in the association between discrimination and psychological distress among rural, Black women in South Carolina in the post-pandemic era.

Methods

Black women (n = 300, mean age = 48.6) living in rural South Carolina were recruited from January to February 2024 using …

Phosphoglycerate Mutase Regulates Treg Differentiation Through Control Of Serine Synthesis And One-Carbon Metabolism, Wesley H Godfrey, Judy J Lee, Shruthi Shanmukha, Kaho Cho, Xiaojing Deng, Chandra Shekar R Ambati, Vasanta Putluri, Abu Hena Mostafa Kamal, Paul M Kim, Nagireddy Putluri, Michael D Kornberg

Faculty, Staff and Students Publications

The differentiation and suppressive functions of regulatory CD4 T cells (Tregs) are supported by a broad array of metabolic changes, providing potential therapeutic targets for immune modulation. In this study, we focused on the regulatory role of glycolytic enzymes in Tregs and identified phosphoglycerate mutase (PGAM) as being differentially overexpressed in Tregs and associated with a highly suppressive phenotype. Pharmacologic or genetic inhibition of PGAM reduced Treg differentiation and suppressive function while reciprocally inducing markers of a pro-inflammatory, T helper 17 (Th17)-like state. The regulatory role of PGAM was dependent on the contribution of 3-phosphoglycerate (3 PG), the PGAM substrate, …

Dietary Lipids Induce Ppard And Bcl6 To Repress Macrophage Il-23 Induction After Intestinal Injury And Lps Exposure, Ashleigh M Gil, Daniel F Zegarra-Ruiz, Wan-Jung Wu, Kendra Norwood, Adrien Assie, Buck S Samuel, Angela M Major, Gretchen E Diehl, Andrea A Hill Mcalester

Faculty, Staff and Students Publications

Unresolved tissue damage is a common feature of Inflammatory Bowel Disease (IBD) that facilitates disease progression. Here, we showed that high animal fat diets (HFD), an environmental risk factor associated with IBD pathogenesis, suppress intestinal macrophage production of critical tissue repair responses after damage. This includes reduced IL-23 production, which drives downstream production of IL-22, which is needed for barrier repair. Indicating that dietary lipids interfere with responses to microbial molecules needed to induce barrier protective functions, we found oleic acid could directly suppress macrophage Il23a induction after lipopolysaccharide (LPS) treatment. Deleting the lipid transporter CD36 on macrophages restored the …

Perception Of Quality Of Life, Brain Regions, And Cognitive Performance In Hispanic Adults: A Canonical Correlation Approach, Juan C. Lopez-Alvarenga, Jesus D. Melgarejo, Jesus Rivera-Sanchez, Lorena Velazquez-Alvarez, Rosa V. Pirela, John Blangero, Jose E. Cavazos, Michael C. Mahaney, Joseph D. Terwilliger, Gladys E. Maestre

School of Medicine Publications

The quality of life (QoL) perception has been studied in neurological diseases; however, there is limited information linking brain morphological characteristics, QoL, and cognition. Human behavior and perception are associated with specific brain areas that interact through diffuse electrochemical networking. We used magnetic resonance imaging (MRI) to analyze the brain region volume (BRV) correlation with the scores of Rand’s 36-item Short Form Survey (SF-36) and cognitive domains (memory and dementia status). We analyzed data from 420 adult participants in the Maracaibo Aging Study (MAS). Principal component analysis with oblimin axis rotation was used to gather redundant information from brain parcels …

Evaluation Of Physical, Mental, And Mechanical Aspects Of An Extreme Military Training Event: A Continuous Monitoring Approach, Tirthankar Chatterjee, Debojyoti Bhattacharyya, Roshani Meena

Journal of Human Performance in Extreme Environments

Soldiers receive extensive training at extremes of environments and simulated terrains to improve their battle efficiency. A study was designed to evaluate the actual cost of a military physical efficiency test consisting of several physically engaging activities to quantify physiological, mechanical, and subjective demands. Sixteen Indian soldiers participated in a military training session consisting of events such as a 5-km run, 4-m vertical rope climbing, a 2.75-m jump, a 60-m dash, and a 9-m horizontal rope climbing with 6.5 kg of equipment in a hot dry environment. Their physiological status was monitored continuously. National Aeronautics and Space Administration Task Load …

Mouse Metastable Epialleles Are Extremely Rare, Chathura J Gunasekara, Uditha Maduranga, Taylor Zhang, Jonathan N Wells, Maria S Baker, Eleonora Laritsky, Yumei Li, Cristian Coarfa, Yi Zhu, Robert A Waterland

Faculty, Staff and Students Publications

Metastable epialleles (MEs) are genomic loci at which epigenetic marks are established stochastically during early embryonic development and maintained during subsequent differentiation and throughout life, leading to stable epigenetic and phenotypic variation among genetically identical individuals. Although MEs were first described in mice over 20 years ago, the extent of epigenetic metastability in the mouse genome remains unknown. We present the first unbiased genome-wide screen for MEs in mice. Using deep whole-genome bisulfite sequencing across tissues derived from the three embryonic germ layers in isogenic C57BL/6J mice, we identified only 29 MEs, precisely localizing them and documenting their rarity. Consistent …

A Cancer Education Needs Assessment: Informing Middle-Aged Female Patients About The Relationships Between Obesity And Women’S Health Concerns In The Reproductive System, Breast, And Endometrial Health, Batul Mirza

MUSC Theses and Dissertations

Obesity significantly impacts women’s health, particularly among middle-aged women, by increasing the risk of hormone-sensitive cancers such as breast, endometrial, and reproductive system cancers. This study examines the educational needs of this demographic group regarding obesity-related cancer risks and explores effective intervention strategies. Obesity-induced mechanisms – hormonal imbalances, chronic inflammation, and insulin resistance – drive cancer susceptibility, emphasizing the need for targeted health education. The study employs a qualitative design, which includes interviews with subject matter experts (SMEs) and surveys of middle-aged women. The goal is to assess awareness, perceived barriers, and preferred learning methods. Findings suggest that with many …

Predicting Sleep And Sleep Stage In Children Using Actigraphy And Heartrate Via A Long Short-Term Memory Deep Learning Algorithm: A Performance Evaluation, Robert Weaver Med, Phd, James White, Olivia Finnegan, Hongpeng Yang, Zifei Zhong, Keagan Kiely, Catherine Jones, Yan Tong, Srihari Nelakuditi, Rahul Ghosal, David E. Brown, Russell R. Pate Ph.D., Gregory J. Welk, Massimiliano De Zambotti, Yuan Wang, Sarah Burkart, Elizabeth L. Adams Phd, Bridget Armstrong, Michael Beets Med, Mph, Phd

Faculty Publications

Children's ambulatory sleep is commonly measured via actigraphy. However, traditional actigraphy measured sleep (e.g., Sadeh algorithm) struggles to predict wake (i.e., specificity, values typically < 70) and cannot predict sleep stages. Long short-term memory (LSTM) is a machine learning algorithm that may address these deficiencies. This study evaluated the agreement of LSTM sleep estimates from actigraphy and heartrate (HR) data with polysomnography (PSG). Children (N = 238, 5–12 years,52.8% male, 50% Black 31.9% White) participated in an overnight laboratory polysomnography. Participants were referred be-cause of suspected sleep disruptions. Children wore an ActiGraph GT9X accelerometer and two of three consumer wearables(i.e., Apple Watch Series 7, Fitbit Sense, Garmin Vivoactive 4) on their non-dominant wrist during the polysomnogram. LSTM estimated sleep versus wake and sleep stage (wake, not-REM, REM) using raw actigraphy and HR data for each 30-s epoch. Logistic regression and random forest were also estimated as a benchmark for performance with which to compare the LSTM results. A 10-fold cross-validation technique was employed, and confusion matrices were constructed. Sensitivity and specificity were calculated to assess the agreement between research-grade and consumer wearables with the criterion polysomnography. For sleep versus wake classification, LSTM outperformed logistic regression and random forest with accuracy ranging from 94.1to 95.1, sensitivity ranging from 94.9 to 95.9 across different devices, and specificity ranging from 84.5 to 89.6. The addition of HR improved the prediction of sleep stages but not binary sleep versus wake. LSTM is promising for predicting sleep and sleep staging from actigraphy data, and HR may improve sleep stage prediction.

Altered Patterning Of Neural Activity In A Neuropathology, Clarissa Hoffman, Jingheng Cheng, Rodrigo Morales, Daoyun Ji, Yuri Dabaghian

Faculty, Staff and Students Publications

The dynamics of neural circuits and their role in mediating cellular and organismal phenomena remain poorly understood, despite numerous efforts to dissect these processes through precise instantaneous measurements or longer-time averages and approximations. We use an alternative approach: we investigate these dynamics at the system's mesoscale by analyzing spike trains and waveforms. These extended activity patterns carry robust, tractable information, are highly responsive to physiological specifics, and enable detailed tracking of circuit behavior. In particular, this methodology allows for characterizing the functionality of tau-pathology-afflicted hippocampal circuits and identifying circuit-level abnormalities that are missed by through traditional analyses. In healthy mice, …

Sensory Neuron-Expressed Fgf13 Controls Nociceptive Signaling In Diabetic Neuropathy Models, Aditya K Singh, Matteo Bernabucci, Nolan M Dvorak, Zahra Haghighijoo, Jessica Di Re, Nana A Goode, Feni K Kadakia, Laura A Maile, Olumarotimi O Folorunso, Paul A Wadsworth, Cynthia M Tapia, Pingyuan Wang, Jigong Wang, Haiying Chen, Yu Xue, Jully Singh, Kali Hankerd, Isaac J Gamez, Makenna Kager, Vincent Truong, Patrick Walsh, Stephanie I Shiers, Nishka Kuttanna, Hanyue Liao, Margherita Marchi, Erika Salvi, Ilaria D'Amato, Daniela D'Amico, Parsa Arman, Catharina G Faber, Rayaz A Malik, Marina De Tommaso, Dan Ziegler, Krishna Rajarathnam, Thomas A Green, Peter M Grace, Matthew R Sapio, Michael J Iadarola, Gregory D Cuny, Diana S Chow, Giuseppe Lauria Pinter, Steve Davidson, Dustin P Green, Jun-Ho La, Jin Mo Chung, Jia Zhou, Theodore J Price, Elizabeth Salisbury, Subo Yuan, Fernanda Laezza

Faculty, Staff and Student Publications

Nociception involves complex signaling, yet intrinsic mechanisms bidirectionally regulating this process remain unexplored. Here, we show that the fibroblast growth factor 13 (FGF13)/Nav1.7 protein-protein interaction (PPI) complex bidirectionally modulates nociception, and that the FGF13/Nav1.7 ratio is upregulated in type 2 diabetic neuropathy (T2DN). PW164, an FGF13/Nav1.7 channel C-terminal tail domain (CTD) PPI interface inhibitor, which reduces complex assembly, selectively suppressed Na+ currents sensitized by capsaicin-induced activation of TRPV1 channels in human induced pluripotent stem cell-derived (hIPSC-derived) sensory neurons and inhibited mechanical and thermal hyperalgesia in mice. FGF13 silencing mimics PW164 activity in culture and in vivo. Conversely, ZL192, an FGF13 …

Exogenous Arginine Differentially Regulates Inflammatory Cytokine And Inducible Nitric Oxide Synthase Expression In Macrophages, Kelsey Stayer, Saliha Pathan, Aalekhya Biswas, Huiqiao Li, Yi Zhu, Fong Wilson Lam, Juan Marini, Sundararajah Thevananther

Faculty, Staff and Students Publications

Immune dysfunction and late mortality from multiorgan failure are hallmarks of severe sepsis. Arginine, a semi-essential amino acid important for protein synthesis, immune response, and circulatory regulation, is deficient in sepsis. However, arginine supplementation in sepsis remains controversial due to the potential to upregulate inducible nitric oxide synthase (iNOS)-mediated excessive nitric oxide (NO) generation in macrophages, leading to vasodilation and hemodynamic catastrophe. Citrulline supplementation has been considered an alternative to replenishing arginine via de novo synthesis, orchestrated by argininosuccinate synthase 1 (ASS1) and argininosuccinate lyase (ASL). However, the functional relevance of the ASS1-ASL pathway in macrophages after endotoxin stimulation is …

Oral Dosing Of The Nucleoside Analog Obeldesivir Is Efficacious Against Rsv Infection In African Green Monkeys, Jared Pitts, J Lizbeth Reyes Zamora, Savrina Manhas, Thomas Aeschbacher, Josolyn Chan, Vincent Cutillas, Varsha Nair, Nicholas C Riola, Arya Vijjapurapu, Meghan S Vermillion, Stacey Eng, Christopher Richards, Dong Han, Jason K Perry, Subhra Chaudhuri, Szu-Wen Liu, Clarissa Martinez, Nadine Peinovich, Kai-Hui Sun, Arthur Cai, Ross Martin, Jasmine Moshiri, Charlotte Hedskog, Darius Babusis, Dustin S Siegel, Rao Kalla, Vasanthi Avadhanula, Pedro A Piedra, Kim Stobbelaar, Peter L Delputte, Caleb Marceau, Roberto Mateo, Evguenia Maiorova, Hongmei Mo, Raju Subramanian, Richard L Mackman, Tomas Cihlar, Simon P Fletcher, John P Bilello

Faculty, Staff and Students Publications

Respiratory syncytial virus (RSV) is a significant cause of morbidity and mortality in high-risk populations. Although prophylactic options are available, there are no effective oral therapeutics for RSV infection. Obeldesivir (ODV) is an orally bioavailable prodrug of the nucleoside analog GS-441524, which is converted intracellularly to its active nucleoside triphosphate and inhibits the RSV RNA polymerase. Here we report the potent antiviral activity of ODV against geographically and temporally diverse RSV A and B clinical isolates (EC50: 0.20–0.66 μM). Resistance selection studies with ODV and GS-441524 against RSV identify a single amino acid substitution, I777L, in the L polymerase with …

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 …

Sex-Specific Effects Of Early-Life Unpredictability On Hippocampal And Amygdala Responses To Novelty In Adolescents, Elysia Poggi Davis, Bianca T. Leonard, Robert J. Jirsaraie, David B. Keator, Steven L. Small, Curt A. Sandman, Victoria B. Risbrough, Hal S. Stern, Laura M. Glynn, Michael A. Yassa, Tallie Z. Baram, Jerod M. Rasmussen

Psychology Faculty Articles and Research

Background

Unpredictable childhood experiences are an understudied form of early-life adversity that impact neurodevelopment. The neurobiological processes by which exposure to early-life unpredictability impact development and vulnerability to psychopathology remain poorly understood. In the current study, we investigated the sex-specific consequences of early-life unpredictability on the limbic network, focusing on the hippocampus and the amygdala.

Methods

Participants included 150 youths (54% female). Early-life unpredictability was assessed using the Questionnaire of Unpredictability in Childhood (QUIC). Participants engaged in 1 or more task–functional magnetic resonance imaging scans between the ages of 8 and 17 (223 total observations) measuring blood oxygen level–dependent (BOLD) …

Alfred Russel Wallace Notes 37. What About Wallace On Vaccination . . . ?, Charles H. Smith

Faculty/Staff Personal Papers

Best known for his natural history studies on evolution and biogeography, Alfred Russel Wallace (1823−1913) had a significant second career as a social critic. One of his most controversial stances was his position on (smallpox) vaccination. Anti-vaxxers of the present frequently bring up his name as a resource for their side, but the situation is not so easily reducible to that.

Common Sources, Perceived Communication Efficacy And Sufficiency Of Cervical Cancer Information, Education And Communication Materials For Women With Hiv/Aids In Rural Kenya, Scholastic Musakali Adeli, Elkanah Orang'o, Violet Naanyu, Ann Mwangi, Peter Itsura, Barry Rosen, Patrick Loehrer

Obstetrics and Gynaecology, East Africa

Introduction: Cervical cancer is the greatest cause of cancer-related death among women in Sub-Saharan Africa, with particularly high incidence and mortality rates in rural regions. In Kenya, Women with HIV/AIDS (WLHA) are at a greater risk of developing cervical cancer though screening rate remains low. Information, education and communication (IEC) materials play a crucial role in raising awareness, promoting screening, and supporting early detection and treatment; however, little is known about the accessibility, content, and perceived effectiveness of these materials from the perspective of WLHA.

Methods: The objective of this study was to determine the common sources, perceived communication efficacy …