Digital Commons Network^™

Long Trimer-Immunization Interval And Appropriate Adjuvant Reduce Immune Responses To The Soluble Hiv-1-Envelope Trimer Base, Hongying Duan, Angela R Corrigan, Cheng Cheng, Andrea Biju, Christopher A Gonelli, Adam S Olia, I-Ting Teng, Kai Xu, Sijy O'Dell, Sandeep Narpala, Mike Castro, Leonid Serebryannyy, Jennifer Wang, Danealle K Parchment, Edward K Sarfo, Jelle Van Schooten, John-Paul Todd, Shuishu Wang, Darcy R Harris, Hui Geng, Alexander J Jafari, Vrc Production Program, Ruth A Woodward, Nicole A Doria-Rose, Kathryn E Foulds, Adrian B Mcdermott, Marit J Van Gils, Richard A Koup, Theodore C Pierson, Peter D Kwong, John R Mascola

Faculty, Staff and Student Publications

Soluble 'SOSIP'-stabilized HIV-1 envelope glycoprotein (Env) trimers elicit dominant antibody responses targeting their glycan-free base regions, potentially diminishing neutralizing responses. Previously, using a nonhuman primate model, we demonstrated that priming with fusion peptide (FP)-carrier conjugate immunogens followed by boosting with Env trimers reduced the anti-base response. Further, we demonstrated that longer immunization intervals further reduced anti-base responses and increased neutralization breadth. Here, we demonstrate that long trimer-boosting intervals, but not long FP immunization intervals, reduce the anti-base response. Additionally, we identify that FP priming before trimer immunization enhances antibody avidity to the Env trimer. We also establish that adjuvants Matrix …

Setting Research Priorities For Global Pandemic Preparedness: An International Consensus And Comparison With Chatgpt’S Output, Peige Song, Davies Adeloye, Chulwoo Park, For Full Author List, See Comments Below

Faculty Research, Scholarly, and Creative Activity

Background

In this priority-setting exercise, we sought to identify leading research priorities needed for strengthening future pandemic preparedness and response across countries.

Methods

The International Society of Global Health (ISoGH) used the Child Health and Nutrition Research Initiative (CHNRI) method to identify research priorities for future pandemic preparedness. Eighty experts in global health, translational and clinical research identified 163 research ideas, of which 42 experts then scored based on five pre-defined criteria. We calculated intermediate criterion-specific scores and overall research priority scores from the mean of individual scores for each research idea. We used a bootstrap (n = 1000) to …

Generalizable Pipeline For Constructing Hiv Risk Prediction Models Across Electronic Health Record Systems, Sarah B May, Thomas P Giordano, Assaf Gottlieb

Faculty, Staff and Student Publications

OBJECTIVE: The HIV epidemic remains a significant public health issue in the United States. HIV risk prediction models could be beneficial for reducing HIV transmission by helping clinicians identify patients at high risk for infection and refer them for testing. This would facilitate initiation on treatment for those unaware of their status and pre-exposure prophylaxis for those uninfected but at high risk. Existing HIV risk prediction algorithms rely on manual construction of features and are limited in their application across diverse electronic health record systems. Furthermore, the accuracy of these models in predicting HIV in females has thus far been …

Targeting Cyp51 In The Treatment Of Acanthamoeba Keratitis, Ashkan Hassani, Vineet Sadarangani, Brad Haubrich

Annual Research Symposium

Acanthamoeba castellanii causes a rare but serious ocular infection called Acanthamoeba keratitis. Risk factors for infection include contact with contaminated water and poor hygiene of contact lenses. The first-line treatment is comprised of a months-long schedule of antibiotics. However, in cases where pharmacological interventions fail to address the infection, surgery may be necessary, with the continued risk of potential vision loss. Consequently, new treatments are needed, whether new pharmacological agents or new combination therapies with current agents. As an aerobic parasite, Acanthamoeba synthesizes ergosterol as a cell membrane insert, and ergosterol biosynthesis inhibitors (EBIs), common in antifungal pharmaceuticals, could potentially …

Diabetes And Covid-19 Outcomes: An Analysis Of Freeman Health System Patients, Timothy Wiant, Logan Schmidt, Saibhavana Srikakolapu, Nova Beyersdorfer, Mariam Akhtar, Kerry Johnson, Greg Stahl, Darrin S. Goade, Robert Arnce

Faculty and Staff Publications

Background: As COVID-19 continues to affect millions of people around the world, it has become vital to understand how comorbidities such as diabetes affect the health outcomes of these patients. While earlier studies have focused on major metropolitan areas, rural settings have been comparatively understudied. The goal of this study is to understand the effect on mortality that these two diseases have in the inpatient setting of a rural population.

Methods: The electronic medical records of all adult patients admitted to Freeman Health System, Joplin, Missouri, United States, between April 1, 2020, and December 31, 2021, were reviewed for the …

The Lived Experiences Of Urhobo Women From The Niger Delta Region Of Nigeria During The Menopausal Transition, Omemiyere Sheila Uwayzor

Walden Dissertations and Doctoral Studies

This qualitative phenomenological study offered an in-depth exploration of the menopausal experiences of seven Urhobo women, ages 45–65 years old, representing diverse occupational backgrounds and communities from the Niger Delta region of Nigeria, who shed light on the multifaceted dimensions of menopausal experiences. Grounded in the Meleis transitions theory, the research presented thematic insights from semi-structured interviews, capturing the participants’ physiological, emotional, cultural, and healthcare-related experiences. Interviews were conducted with seven Urhobo women aged between 45 and 65 years old. These menopausal women responded to the research question regarding their lived experiences of Urhobo women during the menopausal transition. Using …

Guideline Concordance For Timely Chest Imaging After New Presentations Of Dyspnoea Or Haemoptysis In Primary Care: A Retrospective Cohort Study, Minjoung Monica Koo, Luke T A Mounce, Meena Rafiq, Matthew E J Callister, Hardeep Singh, Gary A Abel, Georgios Lyratzopoulos

Faculty, Staff and Students Publications

Background: Guidelines recommend urgent chest X-ray for newly presenting dyspnoea or haemoptysis but there is little evidence about their implementation.

Methods: We analysed linked primary care and hospital imaging data for patients aged 30+ years newly presenting with dyspnoea or haemoptysis in primary care during April 2012 to March 2017. We examined guideline-concordant management, defined as General Practitioner-ordered chest X-ray/CT carried out within 2 weeks of symptomatic presentation, and variation by sociodemographic characteristic and relevant medical history using logistic regression. Additionally, among patients diagnosed with cancer we described time to diagnosis, diagnostic route and stage at diagnosis by guideline-concordant status. …

Teaching And Learning In Stem With Computation, Modeling, And Simulation Practices, Alejandra J. Magana

Purdue University Press Books

Computation, modeling, and simulation practices are commonplace in the STEM workplace, yet formal training embedded in disciplinary practices is not as standard in the undergraduate classroom. Teaching and Learning in STEM With Computation, Modeling, and Simulation Practices: A Guide for Practitioners and Researchers gives instructors a handbook to ensure their curriculum bridges the gap between the classroom and workplace by equipping students with computational skills and preparing them for a rewarding career in STEM. Grounded in theory and supported by fifteen years of education research at the undergraduate level, this book provides instructional, pedagogical, and assessment guidance for integrating modeling …

Structural Insights Into The Molecular Mechanism Of High-Level Ceftazidime-Avibactam Resistance Conferred By Cmy-185, Akito Kawai, William C Shropshire, Masahiro Suzuki, Jovan Borjan, Samuel L Aitken, William C Bachman, Christi L Mcelheny, Micah M Bhatti, Ryan K Shields, Samuel A Shelburne, Yohei Doi

Faculty, Staff and Student Publications

β-Lactamases can accumulate stepwise mutations that increase their resistance profiles to the latest β-lactam agents. CMY-185 is a CMY-2-like β-lactamase and was identified in an Escherichia coli clinical strain isolated from a patient who underwent treatment with ceftazidime-avibactam. CMY-185, possessing four amino acid substitutions of A114E, Q120K, V211S, and N346Y relative to CMY-2, confers high-level ceftazidime-avibactam resistance, and accumulation of the substitutions incrementally enhances the level of resistance to this agent. However, the functional role of each substitution and their interplay in enabling ceftazidime-avibactam resistance remains unknown. Through biochemical and structural analysis, we present the molecular basis for the enhanced …

Yersiniabactin Is A Quorum-Sensing Autoinducer And Siderophore In Uropathogenic Escherichia Coli, James R Heffernan, John A Wildenthal, Hung Tran, George L Katumba, William H Mccoy, Jeffrey P Henderson

2020-Current year OA Pubs

Siderophores are secreted ferric ion chelators used to obtain iron in nutrient-limited environmental niches, including human hosts. While all

Drug Resistance Assessed In A Phase 3 Clinical Trial Of Maribavir Therapy For Refractory Or Resistant Cytomegalovirus Infection In Transplant Recipients, Sunwen Chou, Sophie Alain, Carlos Cervera, Roy F Chemaly, Camille N Kotton, Jens Lundgren, Genovefa A Papanicolaou, Marcus R Pereira, Jingyang J Wu, Rose Ann Murray, Neil E Buss, Martha Fournier

Faculty, Staff and Student Publications

Background: This drug resistance analysis of a randomized trial includes 234 patients receiving maribavir and 116 receiving investigator-assigned standard therapy (IAT), where 56% and 24%, respectively, cleared cytomegalovirus DNA at week 8 (treatment responders).

Methods: Baseline and posttreatment plasma samples were tested for mutations conferring drug resistance in viral genes UL97, UL54, and UL27.

Results: At baseline, genotypic testing revealed resistance to ganciclovir, foscarnet, or cidofovir in 56% of patients receiving maribavir and 68% receiving IAT, including 9 newly phenotyped mutations. Among them, 63% (maribavir) and 21% (IAT) were treatment responders. Detected baseline maribavir resistance mutations were UL27 L193F (n …

Sugar-Binding And Split Domain Combinations In Repeats-In-Toxin Adhesins From Vibrio Cholerae And Aeromonas Veronii Mediate Cell-Surface Recognition And Hemolytic Activities, Mustafa Sherik, Robert Eves, Shuaiqi Guo, Cameron J Lloyd, Karl E Klose, Peter L Davies

Faculty, Staff and Student Publications

Many pathogenic Gram-negative bacteria use repeats-in-toxin adhesins for colonization and biofilm formation. In the cholera agent Vibrio cholerae, flagellar-regulated hemagglutinin A (FrhA) enables these functions. Using bioinformatic analysis, a sugar-binding domain was identified in FrhA adjacent to a domain of unknown function. AlphaFold2 indicated the boundaries of both domains to be slightly shorter than previously predicted and assisted in the recognition of the unknown domain as a split immunoglobulin-like fold that can assist in projecting the sugar-binding domain toward its target. The AlphaFold2-predicted structure is in excellent agreement with the molecular envelope obtained from small-angle X-ray scattering analysis of …

Sars-Cov-2 Versus Other Duty-Related Deaths Among United States Law Enforcement Officers, Jessica Lizeth Alvitres

Walden Dissertations and Doctoral Studies

In 2020, more than half of United States law enforcement officer deaths were attributed to COVID-19, spurring the need for further investigation into the impact of the SARS-CoV-2 pandemic on this category of frontline essential workers. The purpose of this quantitative secondary data analysis study was to investigate the existence of associations between U.S. law enforcement officer deaths (SARS-CoV-2, non-SARS-CoV-2, or other duty-related) and the geographic region, as well as year of death while controlling for the officer rank, age, and sex. Based on the conceptual framework for evaluating mortality and morbidity following large-scale disasters from the National Academies of …

Microsporidiosis: Reviewing Clinical Presentation And Treatment Strategies, Julienne Zhou, Belinda Liu, Megan Dearmond, David Banach, Brad Haubrich

Annual Research Symposium

Microsporidiosis is an opportunistic infection caused by obligate intracellular pathogens within the taxon Microsporidia. Infection is zoonotic and has been associated with patients experiencing immunodeficiency, though incidence is increasing among other populations. Most commonly, the disease is gastrointestinal, typically by Enterocytozoon bieneusi and less commonly by Encephalitozoon intestinalis. Symptoms present with diarrhea and vomiting, and severe cases can lead to wasting and mortality. While the incorporation of anti-retroviral therapy for HIV patients has significantly decreased mortality in a subset of the vulnerable populations, treatment for microsporidiosis is still not standardized or well explored. Resistance to first-line treatment albendazole is increasing, …

Pharmacognosy And Trichomoniasis: A Scoping Review Protocol, Claire Hartwell, Melanie Arslanian, Brad Haubrich

Annual Research Symposium

Trichomoniasis, also called “trich”, is the most common non-viral sexually transmitted infection (STI). Its etiological agent is the protozoan parasite Trichomonas vaginalis, against which first-line antiparasitics usually work. However, resistance is on the rise. Trich has traditionally been considered a nuisance infection, with many (particularly AMAB patients) being asymptomatic. But research in recent years has begun to unravel correlations of trichomonal infections with a myriad of comorbitidies, including infertility, cancers, the pathogenesis of AIDS, and pelvic inflammatory disease (PID). Between the rise of drug resistance and the incidence of these comorbidities, new treatments are needed. In this work, we are …

Investigating Optimal Laboratory Growth Conditions Of Gracilibacillus Halotolerans In Media Supplemented With Salt, Isaac Young

Annual Research Symposium

As interest continues to grow in the field of persister cells and their morphology, there arises an ever-evolving desire to further understand specific strains of bacteria that exemplify the qualities of seemingly anomalous survival regardless of anti-bacterial treatment. In the case of the Gracilibacillus halotolerans, a halotolerant extremophile extracted from the Great Salt Lake with known persistent characteristics, uncovering its optimal growth conditions was essential for future investigations. Identifying the optimal salinity for the growth of G. halotolerans will allow us to standardize our growth methods, uncover several mechanisms of saline tolerance, and add to future investigations of persistence with …

A General Computational Design Strategy For Stabilizing Viral Class I Fusion Proteins, Karen J Gonzalez, Jiachen Huang, Miria F Criado, Avik Banerjee, Stephen M Tompkins, Jarrod J Mousa, Eva-Maria Strauch

2020-Current year OA Pubs

Many pathogenic viruses rely on class I fusion proteins to fuse their viral membrane with the host cell membrane. To drive the fusion process, class I fusion proteins undergo an irreversible conformational change from a metastable prefusion state to an energetically more stable postfusion state. Mounting evidence underscores that antibodies targeting the prefusion conformation are the most potent, making it a compelling vaccine candidate. Here, we establish a computational design protocol that stabilizes the prefusion state while destabilizing the postfusion conformation. With this protocol, we stabilize the fusion proteins of the RSV, hMPV, and SARS-CoV-2 viruses, testing fewer than a …

Forage Plant Secondary Metabolites At The Intersection Of Animal Health, Productivity, And Sustainability, Michael D. Flythe

IGC Proceedings (1977-2023)

The nutritive value of forages and other feeds have long been studied. However, the roles of secondary metabolites produced by forage-plants and their endophytes are an emerging field. Historically, the term secondary metabolite was used for compounds that were less abundant in plant tissue than the primary metabolites, such as fiber, sugars, and protein. It has become clear that secondary metabolites play important roles in the ecology of forage plants, and that both the detrimental and beneficial impacts of secondary metabolites to forage-animals should not be underestimated. This thematic session will consider fescue toxicosis, a detrimental outcome of ergot alkaloids …

Probiotic Limosilactobacillus Reuteri Dsm 17938 Changes Foxp3 Deficiency-Induced Dyslipidemia And Chronic Hepatitis In Mice, Erini Nessim Kostandy, Ji Ho Suh, Xiangjun Tian, Beanna Okeugo, Erin Rubin, Sara Shirai, Meng Luo, Christopher M. Taylor, Kang Ho Kim, J. Marc Rhoads, Yuying Liu

School of Medicine Faculty Publications

The probiotic Limosilactobacillus reuteri DSM 17938 produces anti-inflammatory effects in scurfy (SF) mice, a model characterized by immune dysregulation, polyendocrinopathy, enteropathy, and X-linked inheritance (called IPEX syndrome in humans), caused by regulatory T cell (Treg) deficiency and is due to a Foxp3 gene mutation. Considering the pivotal role of lipids in autoimmune inflammatory processes, we investigated alterations in the relative abundance of lipid profiles in SF mice (± treatment with DSM 17938) compared to normal WT mice. We also examined the correlation between plasma lipids and gut microbiota and circulating inflammatory markers. We noted a significant upregulation of plasma lipids …

“To Be Straight Or Closeted:” Lesbian, Gay, And Bisexual College Women In Greek Life In The Context Of The Lgb Experience In The United States, Olivia Morreale

Sociology Between the Gaps: Forgotten and Neglected Topics

No abstract provided.

Probiotic Limosilactobacillus Reuteri Dsm 17938 Changes Foxp3 Deficiency-Induced Dyslipidemia And Chronic Hepatitis In Mice, Erini Nessim Kostandy, Ji Ho Suh, Xiangjun Tian, Beanna Okeugo, Erin Rubin, Sara Shirai, Meng Luo, Christopher M Taylor, Kang Ho Kim, J Marc Rhoads, Yuying Liu

Faculty, Staff and Student Publications

The probiotic Limosilactobacillus reuteri DSM 17938 produces anti-inflammatory effects in scurfy (SF) mice, a model characterized by immune dysregulation, polyendocrinopathy, enteropathy, and X-linked inheritance (called IPEX syndrome in humans), caused by regulatory T cell (Treg) deficiency and is due to a Foxp3 gene mutation. Considering the pivotal role of lipids in autoimmune inflammatory processes, we investigated alterations in the relative abundance of lipid profiles in SF mice (± treatment with DSM 17938) compared to normal WT mice. We also examined the correlation between plasma lipids and gut microbiota and circulating inflammatory markers. We noted a significant upregulation of plasma lipids …

Probiotic Limosilactobacillus Reuteri Dsm 17938 Changes Foxp3 Deficiency-Induced Dyslipidemia And Chronic Hepatitis In Mice, Erini Nessim Kostandy, Ji Ho Suh, Xiangjun Tian, Beanna Okeugo, Erin Rubin, Sara Shirai, Meng Luo, Christopher M Taylor, Kang Ho Kim, J Marc Rhoads, Yuying Liu

Faculty, Staff and Student Publications

The probiotic Limosilactobacillus reuteri DSM 17938 produces anti-inflammatory effects in scurfy (SF) mice, a model characterized by immune dysregulation, polyendocrinopathy, enteropathy, and X-linked inheritance (called IPEX syndrome in humans), caused by regulatory T cell (Treg) deficiency and is due to a Foxp3 gene mutation. Considering the pivotal role of lipids in autoimmune inflammatory processes, we investigated alterations in the relative abundance of lipid profiles in SF mice (± treatment with DSM 17938) compared to normal WT mice. We also examined the correlation between plasma lipids and gut microbiota and circulating inflammatory markers. We noted a significant upregulation of plasma lipids …

A Case Report Of Pseudomonas Infection In A Patient With Nasal Septum Perforation, Cocaine Use Disorder, And A Perinuclear Anti-Neutrophil Cytoplasmic Antibody (P-Anca)-Positive Assay, Ian Brandon, Lorena Del Pilar Bonilla

All Publications

Nasal septum perforation (NSP) occurs secondary to many underlying etiologies, including facial trauma, drug use, malignancy, infection, or autoimmune disease. We present the case of a 39-year-old female with a past medical history of cocaine use disorder who presented with symptoms concerning facial cellulitis unresponsive to antibiotic therapy. Physical exam and subsequent imaging revealed the presence of NSP. The patient underwent a full workup exploring potential etiologies of NSP in the setting of cocaine use disorder, with lab results indicating Pseudomonas aeruginosa and Pseudomonas putida cellulitis as well as a positive perinuclear anti-neutrophil cytoplasmic antibody (p-ANCA) assay. This case highlights …

The Effect Of Breastfeeding Practices Of Undernourished Mothers In Rural Sierra Leone On Infant Growth And Mortality, Aminata Shamit Koroma, Kevin B Stephenson, Per O Iversen, Mark J Manary, David Taylor Hendrixson

2020-Current year OA Pubs

Breastfeeding provides optimal infant nutrition; however, <50% of infants are exclusively breastfed (EBF) for 6 months. We aimed to describe breastfeeding practices and their effects on growth and mortality among a high-risk mother-infant cohort in rural Sierra Leone. This was a secondary analysis of data from a randomized nutrition intervention trial among undernourished pregnant women. The study's primary outcomes were infant weight and length gains at 6 weeks of age. We included 1270 singleton infants in the analysis, with 1092 (85.6%) having 24-week outcome data. At 6 weeks, 88% were EBF, but the rate of EBF decreased to 17% at 24 weeks. The EBF infants at 6 weeks had improved length (difference of 0.9 mm/week; 95% CI 0.4 to 1.3;

Vaccination And The Defence Of Democracy – Authors’ Reply, Richard M Carpiano, Timothy Callahan, Jad A Elharake, Peter Hotez

Faculty, Staff and Students Publications

No abstract provided.

Dim111.1 Scholarly Perspectives On Design: Essay Example, Sae University College

Exemplars

Example of the DIM111 essay format

Design, Synthesis, X-Ray Crystallography, And Biological Activities Of Covalent, Non-Peptidic Inhibitors Of Sars-Cov-2 Main Protease, Md Ashraf-Uz-Zaman, Teck Khiang Chua, Xin Li, Yuan Yao, Bala Krishna Moku, Chandra Bhushan Mishra, Vasanthi Avadhanula, Pedro A Piedra, Yongcheng Song

Faculty, Staff and Students Publications

Highly contagious SARS-CoV-2 coronavirus has infected billions of people worldwide with flu-like symptoms since its emergence in 2019. It has caused deaths of several million people. The viral main protease (Mpro) is essential for SARS-CoV-2 replication and therefore a drug target. Several series of covalent inhibitors of Mpro were designed and synthesized. Structure-activity relationship studies show that 1) several chloroacetamide- and epoxide-based compounds targeting Cys145 are potent inhibitors with IC50 values as low as 0.49 μM, and 2) Cys44 of Mpro is not nucleophilic for covalent inhibitor design. High resolution X-ray studies revealed the protein-inhibitor interactions and mechanisms of inhibition. …

Aves Introducidas En El Parque Nacional Henri Pittier, Venezuela / Introduced Birds To The Henri Pittier National Park, Venezuela, Alberto Fernández-Badillo

Revista Venezolana de Ornitología

In order to assemble the historical information about the introduced birds reported in the Henri Pittier National Park and its areas of infl uence, an exhaustive literature review was performed based on 50 years of data. The work also reports on the current status of the species involved (established, not established), as well as their relative abundance and the potential threat to ecosystem and agriculture. A total of eight introduced bird species have been recorded in the Henri Pittier National Park. Most species were found still in their introduction stage, except for the Cattle Egret Bubulcus ibis and the Rock …

Prebiotic Proanthocyanidins Inhibit Bile Reflux–Induced Esophageal Adenocarcinoma Through Reshaping The Gut Microbiome And Esophageal Metabolome, Katherine M. Weh, Connor L. Howard, Yun Zhang, Bridget A. Tripp, Jennifer Clarke, Amy B. Howell, Joel H. Rubenstein, Julian A. Abrams, Maria Westerhoff, Laura A. Kresty

Department of Statistics: Faculty Publications

The gut and local esophageal microbiome progressively shift from healthy commensal bacteria to inflammation-linked pathogenic bacteria in patients with gastroesophageal reflux disease, Barrett’s esophagus, and esophageal adenocarcinoma (EAC). However, mechanisms by which microbial communities and metabolites contribute to reflux-driven EAC remain incompletely understood and challenging to target. Herein, we utilized a rat reflux-induced EAC model to investigate targeting the gut microbiome–esophageal metabolome axis with cranberry proanthocyanidins (C-PAC) to inhibit EAC progression. Sprague-Dawley rats, with or without reflux induction, received water or C-PAC ad libitum (700 μg/rat/day) for 25 or 40 weeks. C-PAC exerted prebiotic activity abrogating reflux-induced dysbiosis and mitigating …

Correction To: Should We Use Rifampicin In Periprosthetic Joint Infections Caused By Staphylococci When The Implant Has Been Exchanged? A Multicenter Observational Cohort Study, Tobias Siegfried Kramer, Alex Soriano, Sarah Tedeschi, Antonia Chen, Pierre Tattevin, Eric Senneville, Joan Gomez-Junyent, Victoria Birlutiu, Sabine Petersdorf, Vicens Diaz De Brito, Ignacio Sancho Gonzalez, Katherine Belden, Marjan Wouthuyzen-Bakker

Division of Infectious Diseases and Environmental Medicine Faculty Papers

No abstract provided.