Digital Commons Network^™

2022 American College Of Rheumatology Guideline For Vaccinations In Patients With Rheumatic And Musculoskeletal Diseases, Anne R Bass, Eliza Chakravarty, Elie A Akl, Clifton O Bingham, Leonard Calabrese, Laura C Cappelli, Sindhu R Johnson, Lisa F Imundo, Kevin L Winthrop, Reuben J Arasaratnam, Lindsey R Baden, Roberta Berard, S Louis Bridges, Jonathan T L Cheah, Jeffrey R Curtis, Polly J Ferguson, Ida Hakkarinen, Karen B Onel, Grayson Schultz, Vidya Sivaraman, Benjamin J Smith, Jeffrey A Sparks, Tiphanie P Vogel, Eleanor Anderson Williams, Cassandra Calabrese, Joanne S Cunha, Joann Fontanarosa, Miriah C Gillispie-Taylor, Elena Gkrouzman, Priyanka Iyer, Kimberly S Lakin, Alexandra Legge, Mindy S Lo, Megan M Lockwood, Rebecca E Sadun, Namrata Singh, Nancy Sullivan, Herman Tam, Marat Turgunbaev, Amy S Turner, James Reston

Faculty, Staff and Students Publications

Objective: To provide evidence-based recommendations on the use of vaccinations in children and adults with rheumatic and musculoskeletal diseases (RMDs).

Methods: This guideline follows American College of Rheumatology (ACR) policy guiding management of conflicts of interest and disclosures and the ACR guideline development process, which includes the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. It also adheres to the Appraisal of Guidelines for Research and Evaluation (AGREE) criteria. A core leadership team consisting of adult and pediatric rheumatologists and a guideline methodologist drafted clinical population, intervention, comparator, outcomes (PICO) questions. A review team performed a systematic literature review …

2022 American College Of Rheumatology Guideline For Vaccinations In Patients With Rheumatic And Musculoskeletal Diseases, Anne R Bass, Eliza Chakravarty, Elie A Akl, Clifton O Bingham, Leonard Calabrese, Laura C Cappelli, Sindhu R Johnson, Lisa F Imundo, Kevin L Winthrop, Reuben J Arasaratnam, Lindsey R Baden, Roberta Berard, S Louis Bridges, Jonathan T L Cheah, Jeffrey R Curtis, Polly J Ferguson, Ida Hakkarinen, Karen B Onel, Grayson Schultz, Vidya Sivaraman, Benjamin J Smith, Jeffrey A Sparks, Tiphanie P Vogel, Eleanor Anderson Williams, Cassandra Calabrese, Joanne S Cunha, Joann Fontanarosa, Miriah C Gillispie-Taylor, Elena Gkrouzman, Priyanka Iyer, Kimberly S Lakin, Alexandra Legge, Mindy S Lo, Megan M Lockwood, Rebecca E Sadun, Namrata Singh, Nancy Sullivan, Herman Tam, Marat Turgunbaev, Amy S Turner, James Reston

Faculty, Staff and Students Publications

OBJECTIVE: To provide evidence-based recommendations on the use of vaccinations in children and adults with rheumatic and musculoskeletal diseases (RMDs).

METHODS: This guideline follows American College of Rheumatology (ACR) policy guiding management of conflicts of interest and disclosures and the ACR guideline development process, which includes the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. It also adheres to the Appraisal of Guidelines for Research and Evaluation (AGREE) criteria. A core leadership team consisting of adult and pediatric rheumatologists and a guideline methodologist drafted clinical population, intervention, comparator, outcomes (PICO) questions. A review team performed a systematic literature review …

Determinants And Mechanisms Of The Low Fusogenicity And High Dependence On Endosomal Entry Of Omicron Subvariants, Panke Qu, John P Evans, Chaitanya Kurhade, Cong Zeng, Yi-Min Zheng, Kai Xu, Pei-Yong Shi, Xuping Xie, Shan-Lu Liu

Faculty, Staff and Student Publications

The rapid spread and strong immune evasion of the SARS-CoV-2 Omicron subvariants has raised serious concerns for the global COVID-19 pandemic. These new variants exhibit generally reduced fusogenicity and increased endosomal entry pathway utilization compared to the ancestral D614G variant, the underlying mechanisms of which remain elusive. Here, we show that the C-terminal S1 mutations of the BA.1.1 subvariant, H655Y and T547K, critically govern the low fusogenicity of Omicron. Notably, H655Y also dictates the enhanced endosome entry pathway utilization. Mechanistically, T547K and H655Y likely stabilize the spike trimer conformation as suggested by increased molecular interactions in structural modeling and enhanced …

Association Of IsvSa3 With Multidrug Resistance In Salmonella Enterica Isolates From Cattle (Bos Taurus), Gentry L. Lewis, Robert J. Fenton, Etsuko Moriyama, John Dustin Loy, Rodney A. Moxley

School of Veterinary and Biomedical Sciences: Faculty Publications

Salmonella enterica is, globally, an important cause of human illness with beef being a significant attributable source. In the human patient, systemic Salmonella infection requires antibiotic therapy, and when strains are multidrug resistant (MDR), no effective treatment may be available. MDR in bacteria is often associated with the presence of mobile genetic elements (MGE) that mediate horizontal spread of antimicrobial resistance (AMR) genes. In this study, we sought to determine the potential relationship of MDR in bovine Salmonella isolates with MGE. The present study involved 111 bovine Salmonella isolates obtained collectively from specimens derived from healthy cattle or their environments …

Developing Consensus On Clinical Outcomes For Children With Mild Pneumonia: A Delphi Study, Todd A Florin, Joy Melnikow, Melissa Gosdin, Ryan Ciuffetelli, Jillian Benedetti, Dustin Ballard, Marianne Gausche-Hill, Matthew P Kronman, Lisa A Martin, Rakesh D Mistry, Mark I Neuman, Debra L Palazzi, Sameer J Patel, Wesley H Self, Samir S Shah, Sonal N Shah, Susan Sirota, Andrea T Cruz, Richard Ruddy, Jeffrey S Gerber, Nathan Kuppermann

Faculty, Staff and Students Publications

BACKGROUND: The absence of consensus for outcomes in pediatric antibiotic trials is a major barrier to research harmonization and clinical translation. We sought to develop expert consensus on study outcomes for clinical trials of children with mild community-acquired pneumonia (CAP).

METHODS: Applying the Delphi method, a multispecialty expert panel ranked the importance of various components of clinical response and treatment failure outcomes in children with mild CAP for use in research. During Round 1, panelists suggested additional outcomes in open-ended responses that were added to subsequent rounds of consensus building. For Rounds 2 and 3, panelists were provided their own …

Impact Of Penicillin Allergy Labels On Children Treated For Outpatient Respiratory Infections, Torsten Joerger, Margaret G Taylor, Yun Li, Debra L Palazzi, Jeffrey S Gerber

Faculty, Staff and Students Publications

BACKGROUND: Penicillin allergy is the most common antibiotic allergy, yet most children labeled as allergic tolerate penicillin. The impact of inaccurate penicillin allergy labels (PALs) on pediatric outpatients is unknown. The objective of this study was to compare outcomes between children with and without a PAL after treatment for outpatient respiratory tract infections (RTI).

METHODS: A retrospective, longitudinal birth cohort study was performed in children who received care in 90 pediatric primary care practices in Philadelphia and Houston metropolitan areas. Prescribing and clinical outcomes of children with a PAL at the time of an RTI were compared to non-allergic children, …

From Tuberculosis Bedside To Bench: Ube2b Splicing As A Potential Biomarker And Its Regulatory Mechanism, Mengyuan Lyu, Jian Zhou, Yanbing Zhou, Weelic Chong, Wei Xu, Hongli Lai, Lu Niu, Yang Hai, Xiaojun Yao, Sheng Gong, Qinglan Wang, Yi Chen, Yili Wang, Liyu Chen, Ganzi People's Hospital, Jiongjiong Zeng, Chengdi Wang, Binwu Ying

Student Papers, Posters & Projects

Alternative splicing (AS) is an important approach for pathogens and hosts to remodel transcriptome. However, tuberculosis (TB)-related AS has not been sufficiently explored. Here we presented the first landscape of TB-related AS by long-read sequencing, and screened four AS events (S100A8-intron1-retention intron, RPS20-exon1-alternaitve promoter, KIF13B-exon4-skipping exon (SE) and UBE2B-exon7-SE) as potential biomarkers in an in-house cohort-1. The validations in an in-house cohort-2 (2274 samples) and public datasets (1557 samples) indicated that the latter three AS events are potential promising biomarkers for TB diagnosis, but not for TB progression and prognosis. The excellent performance of classifiers further underscored the diagnostic value …

Addressing Barriers In Fair Data Practices For Biomedical Data, Laura D Hughes, Ginger Tsueng, Jack Digiovanna, Thomas D Horvath, Luke V Rasmussen, Tor C Savidge, Thomas Stoeger, Serdar Turkarslan, Qinglong Wu, Chunlei Wu, Andrew I Su, Lars Pache, Niaid Systems Biology Data Dissemination Working Group

Faculty, Staff and Students Publications

No abstract provided.

Developing A Standardized But Extendable Framework To Increase The Findability Of Infectious Disease Datasets, Ginger Tsueng, Marco A Alvarado Cano, José Bento, Candice Czech, Mengjia Kang, Lars Pache, Luke V Rasmussen, Tor C Savidge, Justin Starren, Qinglong Wu, Jiwen Xin, Michael R Yeaman, Xinghua Zhou, Andrew I Su, Chunlei Wu, Liliana Brown, Reed S Shabman, Laura D Hughes

Faculty, Staff and Students Publications

Biomedical datasets are increasing in size, stored in many repositories, and face challenges in FAIRness (findability, accessibility, interoperability, reusability). As a Consortium of infectious disease researchers from 15 Centers, we aim to adopt open science practices to promote transparency, encourage reproducibility, and accelerate research advances through data reuse. To improve FAIRness of our datasets and computational tools, we evaluated metadata standards across established biomedical data repositories. The vast majority do not adhere to a single standard, such as Schema.org, which is widely-adopted by generalist repositories. Consequently, datasets in these repositories are not findable in aggregation projects like Google Dataset Search. …

The Impact Of Procalcitonin In Assessing Outcomes In Pediatrics Severe Trauma Cases: A Three-Year Experience From A Tertiary Hospital, Waleed H. Albuali

BioMedicine

Background Although procalcitonin levels are raised in patients with systemic inflammation, its usage in pediatric patients, particularly those in the intensive care unit who are most susceptible to sepsis. Methods It is a retrospective research study that included pediatric patients aged more than two weeks who were brought to the King Fahd Hospital of the University's PICU owing to serious trauma or post-acute postoperative occurrences from January 2017 to December 2019. At 24 hours after admission, data such as age, gender, comorbidities, trauma severity as measured by the Injury Severity Score, and PRISM III score were collected. Results Following a …

Beyond Mental Stress-Induced Myocardial Ischemia Following The Covid-19 Vaccine, Chih-Cheng Lai, Po-Ren Hsueh

BioMedicine

No abstract provided.

A Cryptic Oxidoreductase Safeguards Oxidative Protein Folding In Corynebacterium Diphtheriae, Melissa E Reardon-Robinson, Minh Tan Nguyen, Belkys C Sanchez, Jerzy Osipiuk, Christian Rückert, Chungyu Chang, Bo Chen, Rahul Nagvekar, Andrzej Joachimiak, Andreas Tauch, Asis Das, Hung Ton-That

Faculty, Staff and Student Publications

In many gram-positive Actinobacteria, including Actinomyces oris and Corynebacterium matruchotii, the conserved thiol-disulfide oxidoreductase MdbA that catalyzes oxidative folding of exported proteins is essential for bacterial viability by an unidentified mechanism. Intriguingly, in Corynebacterium diphtheriae, the deletion of mdbA blocks cell growth only at 37 °C but not at 30 °C, suggesting the presence of alternative oxidoreductase enzyme(s). By isolating spontaneous thermotolerant revertants of the mdbA mutant at 37 °C, we obtained genetic suppressors, all mapped to a single T-to-G mutation within the promoter region of tsdA, causing its elevated expression. Strikingly, increased expression of tsdA—via …

The Immunomodulating Effects Of Delta-9 Tetrahydrocannabinol (Thc) And Cannabidiol (Cbd) In The Context Of Infection, Rose D. Goodman, Kate Rouse, Victor Jimenez

Annual Research Symposium

No abstract provided.

Sulforaphane Pre-Treatment Improves Cytoprotection Against Opportunistic Pathogens, Caleb Harrop, Nathan Clark

Annual Research Symposium

No abstract provided.

Sulopenem For The Treatment Of Complicated And Uncomplicated Bacterial Urinary Tract Infection (Uti), Aiyi Chen, Thanh-Liem Vu, Daniel J. Yang, Landon Olsen

Annual Research Symposium

No abstract provided.

Oral Sulopenem And Tebipenem For Complicated Urinary Tract Infection And Pyelonephritis In Patients With Extended-Spectrum Beta-Lactamase (Esbl)-Producing Gram Negative, Susceptible Bacteria, Daniel J. Yang, Thanh-Liem Vu, Landon Olsen, Aiyi Chen, H Stephen Lee

Annual Research Symposium

ESBL-producing gram negative Enterobacteria is becoming more prevalent, and carbapenems play a key role in combating against ESBL for complicated urinary tract infections (cUTI). However, carbapenems are only available intravenously in the U.S. FDA is currently reviewing the newly developed oral carbapenems (sulopenem and tebipenem) and have requested additional clinical trial information before granting approval for cUTI. Currently available phase 3 clinical trials for tebipenem and sulopenem are reviewed.

New Year, New Variant Or A Subvariant Of Old Omicron?, Parker Grossman, Manas Mandal

Annual Research Symposium

No abstract provided.

Comparison Of Two Diagnostic Assays For The Detection Of Serum Neutralizing Antibody To Porcine Epidemic Diarrhea Virus, Justin Brown, Korakrit Poonsuk, Ting-Yu Cheng, Chris Rademacher, Erin Kalkwarf, Liying Tian, Lauren A. Mckeen, Chong Wang, Luis Gimenez-Lirola, David Baum, Locke A. Karriker

School of Veterinary and Biomedical Sciences: Faculty Publications

Lactogenic immunity is important for the protection of piglets against many pathogens including porcine epidemic diarrhea virus. Circulating neutralizing antibodies levels in sow sera may help determine if a detectable immune response could confer protection to piglets. Neutralizing antibodies can be detected through various diagnostic assays. This study evaluated the diagnostic characteristics of two neutralizing antibody assays for porcine epidemic diarrhea virus neutralizing antibodies in serum of challenged gilts. Four treatment groups, control, non-vaccinated, vaccinated prior to challenge, and vaccinated following challenge, were comprised of 20 gilts. Serum sample were collected from each gilt prior to and following challenge with …

Decision-Making Under Risk And Theory Of Mind In Adolescent Offenders In Provisional Deprivation Of Liberty, Rubens José Loureiro, Flavio Takemi Kataoka, Thiago Wendt Viola, Gisele Iesbich Vargas, Breno Sanvicente-Vieira, Rodrigo Grassi-Oliveira, Bruno Kluwe-Schiavon

Faculty, Staff and Student Publications

INTRODUCTION: Delinquent behaviors are risky behaviors that increase during puberty and reach their highest peak in late adolescence. It has been proposed that poor decision-making and theory of mind (ToM) are key cognitive processes implicated with delinquency during adolescence, affecting evaluation of risks and impairing appreciation of social norms. Nevertheless, it is not yet clear whether adolescent offenders who are subjected to provisional deprivation of liberty due to conflict with the law (adolescents in conflict with the law [ACL]) might, in fact, present a specific profile with regard to these cognitive processes.

OBJECTIVES: To assess deliberative decision-making and ToM among …

Comparison Of Two Diagnostic Assays For The Detection Of Serum Neutralizing Antibody To Porcine Epidemic Diarrhea Virus, Justin Brown, Korakrit Poonsuk, Ting-Yu Cheng, Chris Rademacher, Erin Kalkwarf, Liying Tian, Lauren A. Mckeen, Chong Wang, Luis Gimenez-Lirola, Gimenez-Lirola Baum, Locke A. Karriker

Nebraska Center for Virology: Faculty Publications

Lactogenic immunity is important for the protection of piglets against many pathogens including porcine epidemic diarrhea virus. Circulating neutralizing antibodies levels in sow sera may help determine if a detectable immune response could confer protection to piglets. Neutralizing antibodies can be detected through various diagnostic assays. This study evaluated the diagnostic characteristics of two neutralizing antibody assays for porcine epidemic diarrhea virus neutralizing antibodies in serum of challenged gilts. Four treatment groups, control, non-vaccinated, vaccinated prior to challenge, and vaccinated following challenge, were comprised of 20 gilts. Serum sample were collected from each gilt prior to and following challenge with …

The Coronavirus Disease 2019 Pandemic Unmasked The Challenges Faced By Early-Stage Faculty In Infectious Diseases: A Call To Action, Erin M Scherer, Martin Backer, Karen Carvajal, Lara Danziger-Isakov, Sharon Frey, Leigh M Howard, Felicia Scaggs Huang, Angelica C Kottkamp, Tara Reid, Maria C Rodriguez-Barradas, Helen C Stankiewicz Karita, Zheyi Teoh, Anna Wald, Jennifer Whitaker, Zanthia Wiley, Igho Ofotokun, Kathryn M Edwards, Infectious Diseases Clinical Research Consortium (Idcrc) Mentorship Program Writing Group

Faculty, Staff and Students Publications

The coronavirus disease 2019 (COVID-19) pandemic and associated increase in family care responsibilities resulted in unsustainable personal and professional workloads for infectious diseases (ID) faculty on the front lines. This was especially true for early-stage faculty (ESF), many of whom had caregiving responsibilities. In addition, female faculty, underrepresented in medicine and science faculty and particularly ESF, experienced marked declines in research productivity, which significantly impacts career trajectories. When combined with staffing shortages due to an aging workforce and suboptimal recruitment and retention in ID, these work-life imbalances have brought the field to an inflection point. We propose actionable recommendations and …

Improved Survival After Liver Transplantation For Patients With Human Immunodeficiency Virus (Hiv) And Hiv/Hepatitis C Virus Coinfection In The Integrase Strand Transfer Inhibitor And Direct-Acting Antiviral Eras, Jake Sheraj Jacob, Anjiya Shaikh, Karthik Goli, Nicole E Rich, Jihane N Benhammou, Aijaz Ahmed, Donghee Kim, Abbas Rana, John A Goss, Susanna Naggie, Tzu-Hao Lee, Fasiha Kanwal, George Cholankeril

Faculty, Staff and Students Publications

BACKGROUND: People with human immunodeficiency virus (HIV) with and without hepatitis C virus (HCV) coinfection had poor outcomes after liver transplant (LT). Integrase strand transfer inhibitors (INSTIs) and direct-acting antivirals (DAAs) have changed the treatment landscape for HIV and HCV, respectively, but their impact on LT outcomes remains unclear.

METHODS: This retrospective analysis of adults with HIV monoinfection (n = 246) and HIV/HCV coinfection (n = 286) who received LT compared mortality in patients with HIV who received LT before versus after approval of INSTIs and in patients with HIV/HCV coinfection who received LT before versus after approval of DAAs. …

Cd5 Expression By Dendritic Cells Directs T Cell Immunity And Sustains Immunotherapy Responses, Mingyu He, Kate Roussak, Feiyang Ma, Nicholas Borcherding, Vince Garin, Mike White, Charles Schutt, Trine I Jensen, Yun Zhao, Courtney A Iberg, Kairav Shah, Himanshi Bhatia, Daniel Korenfeld, Sabrina Dinkel, Judah Gray, Alina Ulezko Antonova, Stephen Ferris, David Donermeyer, Cecilia Lindestam Arlehamn, Matthew M Gubin, Jingqin Luo, Laurent Gorvel, Matteo Pellegrini, Alessandro Sette, Thomas Tung, Rasmus Bak, Robert L Modlin, Ryan C Fields, Robert D Schreiber, Paul M Allen, Eynav Klechevsky

Faculty, Staff and Student Publications

The induction of proinflammatory T cells by dendritic cell (DC) subtypes is critical for antitumor responses and effective immune checkpoint blockade (ICB) therapy. Here, we show that human CD1c+CD5+ DCs are reduced in melanoma-affected lymph nodes, with CD5 expression on DCs correlating with patient survival. Activating CD5 on DCs enhanced T cell priming and improved survival after ICB therapy. CD5+ DC numbers increased during ICB therapy, and low interleukin-6 (IL-6) concentrations promoted their de novo differentiation. Mechanistically, CD5 expression by DCs was required to generate optimally protective CD5hi T helper and CD8+ T cells; further, deletion of CD5 from T …

Batf2 Promotes Hsc Myeloid Differentiation By Amplifying Ifn Response Mediators During Chronic Infection, Duy T Le, Marcus A Florez, Pawel Kus, Brandon T Tran, Bailee Kain, Yingmin Zhu, Kurt Christensen, Antrix Jain, Anna Malovannaya, Katherine Y King

Faculty, Staff and Students Publications

Basic leucine zipper ATF-like transcription factor 2 (BATF2), an interferon-activated immune response regulator, is a key factor responsible for myeloid differentiation and depletion of HSC during chronic infection. To delineate the mechanism of BATF2 function in HSCs, we assessed Batf2 KO mice during chronic infection and found that they produced less pro-inflammatory cytokines, less immune cell recruitment to the spleen, and impaired myeloid differentiation with better preservation of HSC capacity compared to WT. Co-IP analysis revealed that BATF2 forms a complex with JUN to amplify pro-inflammatory signaling pathways including CCL5 during infection. Blockade of CCL5 receptors phenocopied Batf2 KO differentiation …

Was Kaposi’S Sarcoma-Associated Herpesvirus Introduced Into China Via The Ancient Silk Road? An Evolutionary Perspective, Zhenqiu Liu, Qiwen Fang, Jialu Zuo, Veenu Minhas, Charles Wood, Na He, Tiejun Zhang

Nebraska Center for Virology: Faculty Publications

Kaposi’s sarcoma-associated herpesvirus (KSHV) has become widely dispersed worldwide since it was first reported in 1994, but the seroprevalence of KSHV varies geographically. KSHV is relatively ubiquitous in Mediterranean areas and the Xinjiang Uygur Autonomous Region, China. The origin of KSHV has long been puzzling. In the present study, we collected and analysed 154 KSHV ORF-K1 sequences obtained from samples originating from Xinjiang, Italy, Greece, Iran and southern Siberia using Bayesian evolutionary analysis in BEAST to test the hypothesis that KSHV was introduced into Xinjiang via the ancient Silk Road. According to the phylogenetic analysis, 72 sequences were subtype A …

Estimated Impact Of Low Isolate Numbers On The Reliability Of Cumulative Antibiogram Data, Christian Tran, John Hargy, Bryan Hess, Matthew Pettengill

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Antibiograms are cumulative reports of antimicrobial susceptibility results that are used to guide the selection of empirical antibiotic therapy. Although Clinical and Laboratory Standards Institute (CLSI) guidelines recommend including only organisms that have at least 30 isolates in an antibiogram, previous studies demonstrated that adherence to this recommendation is highly variable. This paper aims to model the impact of small sample sizes on expected levels of error in cumulative antibiograms by comparing percent susceptibility results for random samples to those of the larger, entire data set. The results demonstrate relatively high error rates when utilizing low numbers of isolates in …

Staphylococcus Aureus Breast Implant Infection Isolates Display Recalcitrance To Antibiotic Pocket Irrigants, Jesus M Duran Ramirez, Jana Gomez, Blake M Hanson, Taha Isa, Terence M Myckatyn, Jennifer N Walker

Faculty, Staff and Student Publications

Breast implant-associated infections (BIAIs) are the primary complication following placement of breast prostheses in breast cancer reconstruction. Given the prevalence of breast cancer, reconstructive failure due to infection results in significant patient distress and health care expenditures. Thus, effective BIAI prevention strategies are urgently needed. This study tests the efficacy of one infection prevention strategy: the use of a triple antibiotic pocket irrigant (TAPI) against Staphylococcus aureus, the most common cause of BIAIs. TAPI, which consists of 50,000 U bacitracin, 1 g cefazolin, and 80 mg gentamicin diluted in 500 mL of saline, is used to irrigate the breast implant …

Ambient Oxygen Levels Regulate Intestinal Dysbiosis And Gvhd Severity After Allogeneic Stem Cell Transplantation, Keisuke Seike, Anders Kiledal, Hideaki Fujiwara, Israel Henig, Marina Burgos Da Silva, Marcel R M Van Den Brink, Robert Hein, Matthew Hoostal, Chen Liu, Katherine Oravecz-Wilson, Emma Lauder, Lu Li, Yaping Sun, Thomas M Schmidt, Yatrik M Shah, Robert R Jenq, Gregory Dick, Pavan Reddy

Faculty, Staff and Student Publications

The severity of T cell-mediated gastrointestinal (GI) diseases such as graft-versus-host disease (GVHD) and inflammatory bowel diseases correlates with a decrease in the diversity of the host gut microbiome composition characterized by loss of obligate anaerobic commensals. The mechanisms underpinning these changes in the microbial structure remain unknown. Here, we show in multiple specific pathogen-free (SPF), gnotobiotic, and germ-free murine models of GI GVHD that the initiation of the intestinal damage by the pathogenic T cells altered ambient oxygen levels in the GI tract and caused dysbiosis. The change in oxygen levels contributed to the severity of intestinal pathology in …

Optimizing Dna Extraction From Pediatric Stool For Diagnosis Of Tuberculosis And Use In Next-Generation Sequencing Applications, Tara E Ness, Lennard Meiwes, Alexander Kay, Rojelio Mejia, Christoph Lange, Maha Farhat, Anna Mandalakas, Andrew Dinardo

Faculty, Staff and Students Publications

The WHO has endorsed the use of stool samples for diagnosis of tuberculosis (TB) in children, and targeted next-generation sequencing (tNGS) of stool has been shown to support diagnosis and provide information about drug susceptibility (DS). Optimizing extraction of DNA from stool for sequencing is critical to ensure high diagnostic sensitivity and accurate DS information. Human stool samples were spiked with various concentrations of Mycobacterium bovis bacillus Calmette-Guérin (BCG), and DNA was extracted from the samples using four different DNA extraction kits. Each sample was subjected to quantitative PCR for identifying Mycobacterium tuberculosis complex bacteria and underwent further analysis to …

Cell-Membrane-Coated Nanoparticles For Targeted Drug Delivery To The Brain For The Treatment Of Neurological Diseases, Jianzhuang Li, Yanhao Wei, Chunlin Zhang, Rentang Bi, Yanmei Qiu, Yanan Li, Bo Hu

Faculty, Staff and Student Publications

Neurological diseases (NDs) are a significant cause of disability and death in the global population. However, effective treatments still need to be improved for most NDs. In recent years, cell-membrane-coated nanoparticles (CMCNPs) as drug-targeting delivery systems have become a research hotspot. Such a membrane-derived, nano drug-delivery system not only contributes to avoiding immune clearance but also endows nanoparticles (NPs) with various cellular and functional mimicries. This review article first provides an overview of the function and mechanism of single/hybrid cell-membrane-derived NPs. Then, we highlight the application and safety of CMCNPs in NDs. Finally, we discuss the challenges and opportunities in …