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Increased Prevalence Of Clostridioides Difficile Infection Among Pediatric Oncology Patients: Risk Factors For Infection And Complications, Brianna R Murphy, Natalie J Dailey Garnes, Hyunsoo Hwang, Christine B Peterson, Kevin W Garey, Pablo Okhuysen Feb 2024

Increased Prevalence Of Clostridioides Difficile Infection Among Pediatric Oncology Patients: Risk Factors For Infection And Complications, Brianna R Murphy, Natalie J Dailey Garnes, Hyunsoo Hwang, Christine B Peterson, Kevin W Garey, Pablo Okhuysen

Faculty, Staff and Student Publications

Background: Pediatric oncology patients, who are typically immunosuppressed, exposed to medications associated with increased Clostridioides difficile infection (CDI) risk and hospitalized, are expected to be at substantial risk for infection and complications. Although certain C. difficile ribotypes have been associated with more severe infection in adults, such an association has not been described in children.

Methods: To characterize CDI epidemiology, including risk factors and complications among pediatric oncology patients, we retrospectively reviewed charts of patients 1-18 years old treated at a designated cancer center during 2000-2017. We used fluorescence-based polymerase chain reaction to identify ribotypes causing disease at our institution. …


Phase 1/2 Trial Of Avelumab Combined With Utomilumab (4–1bb Agonist), Pf-04518600 (Ox40 Agonist), Or Radiotherapy In Patients With Advanced Gynecologic Malignancies, Anne Knisely, Jibran Ahmed, Bettzy Stephen, Sarina A Piha-Paul, Daniel Karp, Abdulrazzak Zarifa, Siqing Fu, David Sanghyun Hong, Jordi Rodon Ahnert, Timothy A Yap, Apostolia M Tsimberidou, Anas Alshawa, Ecaterina E Dumbrava, Yali Yang, Juhee Song, Funda Meric-Bernstam, Amir A Jazaeri, Aung Naing Feb 2024

Phase 1/2 Trial Of Avelumab Combined With Utomilumab (4–1bb Agonist), Pf-04518600 (Ox40 Agonist), Or Radiotherapy In Patients With Advanced Gynecologic Malignancies, Anne Knisely, Jibran Ahmed, Bettzy Stephen, Sarina A Piha-Paul, Daniel Karp, Abdulrazzak Zarifa, Siqing Fu, David Sanghyun Hong, Jordi Rodon Ahnert, Timothy A Yap, Apostolia M Tsimberidou, Anas Alshawa, Ecaterina E Dumbrava, Yali Yang, Juhee Song, Funda Meric-Bernstam, Amir A Jazaeri, Aung Naing

Faculty, Staff and Student Publications

Background: Immune checkpoint blockade has shown mixed results in advanced/recurrent gynecologic malignancies. Efficacy may be improved through costimulation with OX40 and 4-1BB agonists. The authors sought to evaluate the safety and efficacy of avelumab combined with utomilumab (a 4-1BB agonist), PF-04518600 (an OX40 agonist), and radiotherapy in patients with recurrent gynecologic malignancies.

Methods: The primary end point in this six-arm, phase 1/2 trial was safety of the combination regimens. Secondary end points included the objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumors and immune-related Response Evaluation Criteria in Solid Tumors, the disease control rate (DCR), the …


Mediators Of Necroptosis: From Cell Death To Metabolic Regulation, Xiaoqin Wu, Laura E Nagy, Jérémie Gautheron Feb 2024

Mediators Of Necroptosis: From Cell Death To Metabolic Regulation, Xiaoqin Wu, Laura E Nagy, Jérémie Gautheron

Faculty, Staff and Student Publications

Necroptosis, a programmed cell death mechanism distinct from apoptosis, has garnered attention for its role in various pathological conditions. While initially recognized for its involvement in cell death, recent research has revealed that key necroptotic mediators, including receptor-interacting protein kinases (RIPKs) and mixed lineage kinase domain-like protein (MLKL), possess additional functions that go beyond inducing cell demise. These functions encompass influencing critical aspects of metabolic regulation, such as energy metabolism, glucose homeostasis, and lipid metabolism. Dysregulated necroptosis has been implicated in metabolic diseases, including obesity, diabetes, metabolic dysfunction-associated steatotic liver disease (MASLD) and alcohol-associated liver disease (ALD), contributing to chronic …


Locoregional Therapies In Immunologically "Cold" Tumors: Opportunities And Clinical Trial Design Considerations, Pavlos Msaouel, Rahul A Sheth Feb 2024

Locoregional Therapies In Immunologically "Cold" Tumors: Opportunities And Clinical Trial Design Considerations, Pavlos Msaouel, Rahul A Sheth

Faculty, Staff and Student Publications

Immunotherapy has revolutionized cancer management, but many tumors, particularly immunologically "cold" tumors, remain resistant to the therapy. The combination of conventional systemic immunotherapies and locoregional interventional radiology approaches is being explored to transform these cold tumors into immunologically active "hot" ones. The present article uses the example of chromophobe renal cell carcinoma (ChRCC), a renal cell carcinoma subtype resistant to current systemic immunotherapies, to address practical and conceptual challenges that have prevented the activation of clinical trials specifically designed for this malignancy to date. The practical framework discussed herein can help overcome logistic and funding limitations and facilitate the development …


Epidemiology And Preventability Of Hospital-Onset Bacteremia And Fungemia In 2 Hospitals In India, Sumanth Gandra, Dorothy Sinclair, Dustin Stwalley, Jacaranda Van Rheenen, David K Warren, Et Al. Feb 2024

Epidemiology And Preventability Of Hospital-Onset Bacteremia And Fungemia In 2 Hospitals In India, Sumanth Gandra, Dorothy Sinclair, Dustin Stwalley, Jacaranda Van Rheenen, David K Warren, Et Al.

2020-Current year OA Pubs

OBJECTIVE: Studies evaluating the incidence, source, and preventability of hospital-onset bacteremia and fungemia (HOB), defined as any positive blood culture obtained after 3 calendar days of hospital admission, are lacking in low- and middle-income countries (LMICs).

DESIGN, SETTING, AND PARTICIPANTS: All consecutive blood cultures performed for 6 months during 2020-2021 in 2 hospitals in India were reviewed to assess HOB and National Healthcare Safety Network (NHSN) reportable central-line-associated bloodstream infection (CLABSI) events. Medical records of a convenience sample of 300 consecutive HOB events were retrospectively reviewed to determine source and preventability. Univariate and multivariable logistic regression analyses were performed to …


Correlates Of Risk For Disinhibited Behaviors In The Million Veteran Program Cohort, Peter B Barr, Tim B Bigdeli, Jacquelyn L Meyers, Roseann E Peterson, Sandra Sanchez-Roige, Travis T Mallard, Danielle M Dick, K Paige Harden, Anna Wilkinson, David P Graham, David A Nielsen, Alan C Swann, Rachele K Lipsky, Thomas R Kosten, Mihaela Aslan, Philip D Harvey, Nathan A Kimbrel, Jean C Beckham Feb 2024

Correlates Of Risk For Disinhibited Behaviors In The Million Veteran Program Cohort, Peter B Barr, Tim B Bigdeli, Jacquelyn L Meyers, Roseann E Peterson, Sandra Sanchez-Roige, Travis T Mallard, Danielle M Dick, K Paige Harden, Anna Wilkinson, David P Graham, David A Nielsen, Alan C Swann, Rachele K Lipsky, Thomas R Kosten, Mihaela Aslan, Philip D Harvey, Nathan A Kimbrel, Jean C Beckham

Faculty, Staff and Students Publications

Importance: Many psychiatric outcomes share a common etiologic pathway reflecting behavioral disinhibition, generally referred to as externalizing (EXT) disorders. Recent genome-wide association studies (GWASs) have demonstrated the overlap between EXT disorders and important aspects of veterans' health, such as suicide-related behaviors and substance use disorders (SUDs).

Objective: To explore correlates of risk for EXT disorders within the Veterans Health Administration (VA) Million Veteran Program (MVP).

Design, setting, and participants: A series of phenome-wide association studies (PheWASs) of polygenic risk scores (PGSs) for EXT disorders was conducted using electronic health records. First, ancestry-specific PheWASs of EXT PGSs were conducted in the …


Herpes Zoster And Risk Of Incident Parkinson's Disease In Us Veterans: A Matched Cohort Study, Louis Tunnicliffe, Rimona S Weil, Judith Breuer, Maria C Rodriguez-Barradas, Liam Smeeth, Christopher T Rentsch, Charlotte Warren-Gash Feb 2024

Herpes Zoster And Risk Of Incident Parkinson's Disease In Us Veterans: A Matched Cohort Study, Louis Tunnicliffe, Rimona S Weil, Judith Breuer, Maria C Rodriguez-Barradas, Liam Smeeth, Christopher T Rentsch, Charlotte Warren-Gash

Faculty, Staff and Students Publications

Background: Although some systemic infections are associated with Parkinson's disease (PD), the relationship between herpes zoster (HZ) and PD is unclear.

Objective: The objective is to investigate whether HZ is associated with incident PD risk in a matched cohort study using data from the US Department of Veterans Affairs.

Methods: We compared the risk of PD between individuals with incident HZ matched to up to five individuals without a history of HZ using Cox proportional hazards regression. In sensitivity analyses, we excluded early outcomes.

Results: Among 198,099 individuals with HZ and 976,660 matched individuals without HZ (median age 67.0 years …


Zika Virus Co-Opts Microrna Networks To Persist In Placental Niches Detected By Spatial Transcriptomics, Enrico R Barrozo, Maxim D Seferovic, Mark P Hamilton, David N Moorshead, Michael D Jochum, Trang Do, Derek S O'Neil, Melissa A Suter, Kjersti M Aagaard Feb 2024

Zika Virus Co-Opts Microrna Networks To Persist In Placental Niches Detected By Spatial Transcriptomics, Enrico R Barrozo, Maxim D Seferovic, Mark P Hamilton, David N Moorshead, Michael D Jochum, Trang Do, Derek S O'Neil, Melissa A Suter, Kjersti M Aagaard

Faculty, Staff and Students Publications

BACKGROUND: Zika virus congenital infection evades double-stranded RNA detection and may persist in the placenta for the duration of pregnancy without accompanying overt histopathologic inflammation. Understanding how viruses can persist and replicate in the placenta without causing overt cellular or tissue damage is fundamental to deciphering mechanisms of maternal-fetal vertical transmission.

OBJECTIVE: Placenta-specific microRNAs are believed to be a tenet of viral resistance at the maternal-fetal interface. We aimed to test the hypothesis that the Zika virus functionally disrupts placental microRNAs, enabling viral persistence and fetal pathogenesis.

STUDY DESIGN: To test this hypothesis, we used orthogonal approaches in human and …


Circadian Immunity From Bench To Bedside: A Practical Guide, Huram Mok, Elaine Ostendorf, Alex Ganninger, Avi J. Adler, Guy Hazan, Jeffrey A. Haspel Feb 2024

Circadian Immunity From Bench To Bedside: A Practical Guide, Huram Mok, Elaine Ostendorf, Alex Ganninger, Avi J. Adler, Guy Hazan, Jeffrey A. Haspel

2020-Current year OA Pubs

The immune system is built to counteract unpredictable threats, yet it relies on predictable cycles of activity to function properly. Daily rhythms in immune function are an expanding area of study, and many originate from a genetically based timekeeping mechanism known as the circadian clock. The challenge is how to harness these biological rhythms to improve medical interventions. Here, we review recent literature documenting how circadian clocks organize fundamental innate and adaptive immune activities, the immunologic consequences of circadian rhythm and sleep disruption, and persisting knowledge gaps in the field. We then consider the evidence linking circadian rhythms to vaccination, …


Distribution Of P2y And P2x Purinergic Receptor Expression Within The Intestine, Kristen A Engevik, Francesca J Scribano, J Thomas Gebert, Jacob L Perry, Sue E Crawford, Joseph M Hyser Feb 2024

Distribution Of P2y And P2x Purinergic Receptor Expression Within The Intestine, Kristen A Engevik, Francesca J Scribano, J Thomas Gebert, Jacob L Perry, Sue E Crawford, Joseph M Hyser

Faculty, Staff and Students Publications

Nucleotides are potent extracellular signaling molecules during homeostasis, infection, and injury due to their ability to activate purinergic receptors. The nucleotide ATP activates P2X receptors (P2RXs), whereas the nucleotides ADP, ATP, UTP, and UDP-glucose selectively activate different P2Y receptors (P2RYs). Several studies have established crucial roles for P2 receptors during intestinal inflammatory and infectious diseases, yet the most extensive characterization of purinergic signaling has focused on immune cells and the central and enteric nervous systems. As epithelial cells serve as the first barrier against irritants and infection, we hypothesized that the gut epithelium may express multiple purinergic receptors that respond …


Proteome Analysis For Inflammation Related To Acute And Convalescent Infection, Tara K Sigdel, Swastika Sur, Patrick Boada, Suzanne M Mcdermott, Cecilia S Lindestam Arlehamn, Kristy O Murray, Linda K Bockenstedt, Maggie Kerwin, Elaine F Reed, Eva Harris, Ken Stuart, Bjoern Peters, Ana Sesma, Ruth R Montgomery, Minnie M Sarwal Feb 2024

Proteome Analysis For Inflammation Related To Acute And Convalescent Infection, Tara K Sigdel, Swastika Sur, Patrick Boada, Suzanne M Mcdermott, Cecilia S Lindestam Arlehamn, Kristy O Murray, Linda K Bockenstedt, Maggie Kerwin, Elaine F Reed, Eva Harris, Ken Stuart, Bjoern Peters, Ana Sesma, Ruth R Montgomery, Minnie M Sarwal

Faculty, Staff and Students Publications

Infectious diseases are a significant burden in global healthcare. Pathogens engage with different host defense mechanisms. However, it is currently unknown if there are disease-specific immune signatures and/or if different pathogens elicit common immune-associated molecular entities to common therapeutic interventions. We studied patients enrolled through the Human Immunology Project Consortium (HIPC), which focuses on immune responses to various infections. Blood samples were collected and analyzed from patients during infection and follow-up time points at the convalescent stage. The study included samples from patients with Lyme disease (LD), tuberculosis (TB), malaria (MLA), dengue virus (DENV), and West Nile virus (WNV), as …


Evolving Concepts In Helicobacter Pylori Management, Steven F Moss, Shailja C Shah, Mimi C Tan, Hashem B El-Serag Feb 2024

Evolving Concepts In Helicobacter Pylori Management, Steven F Moss, Shailja C Shah, Mimi C Tan, Hashem B El-Serag

Faculty, Staff and Students Publications

Helicobacter pylori is the most common chronic bacterial infection worldwide and the most significant risk factor for gastric cancer, which remains a leading cause of cancer-related death globally. H pylori and gastric cancer continue to disproportionately impact racial and ethnic minority and immigrant groups in the United States. The approach to H pylori case-finding thus far has relied on opportunistic testing based on symptoms or high-risk indicators, such as racial or ethnic background and family history. However, this approach misses a substantial proportion of individuals infected with H pylori who remain at risk for gastric cancer because most infections remain …


Risk Factors For Childhood Brain Tumours: A Systematic Review And Meta-Analysis Of Observational Studies From 1976 To 2022, Felix M Onyije, Roya Dolatkhah, Ann Olsson, Liacine Bouaoun, Isabelle Deltour, Friederike Erdmann, Audrey Bonaventure, Michael E Scheurer, Jacqueline Clavel, Joachim Schüz Feb 2024

Risk Factors For Childhood Brain Tumours: A Systematic Review And Meta-Analysis Of Observational Studies From 1976 To 2022, Felix M Onyije, Roya Dolatkhah, Ann Olsson, Liacine Bouaoun, Isabelle Deltour, Friederike Erdmann, Audrey Bonaventure, Michael E Scheurer, Jacqueline Clavel, Joachim Schüz

Center for Medical Ethics and Health Policy Staff Publications

BACKGROUND: Childhood brain tumours (CBTs) are the leading cause of cancer death in children under the age of 20 years globally. Though the aetiology of CBT remains poorly understood, it is thought to be multifactorial. We aimed to synthesize potential risk factors for CBT to inform primary prevention.

METHODS: We conducted a systematic review and meta-analysis of epidemiological studies indexed in the PubMed, Web of Science, and Embase databases from the start of those resources through 27 July 2023. We included data from case-control or cohort studies that reported effect estimates for each risk factor around the time of conception, …


Safety, Immunogenicity, And Mechanism Of A Rotavirus Mrna-Lnp Vaccine In Mice, Chenxing Lu, Yan Li, Rong Chen, Xiaoqing Hu, Qingmei Leng, Xiaopeng Song, Xiaochen Lin, Jun Ye, Jinlan Wang, Jinmei Li, Lida Yao, Xianqiong Tang, Xiangjun Kuang, Guangming Zhang, Maosheng Sun, Yan Zhou, Hongjun Li Jan 2024

Safety, Immunogenicity, And Mechanism Of A Rotavirus Mrna-Lnp Vaccine In Mice, Chenxing Lu, Yan Li, Rong Chen, Xiaoqing Hu, Qingmei Leng, Xiaopeng Song, Xiaochen Lin, Jun Ye, Jinlan Wang, Jinmei Li, Lida Yao, Xianqiong Tang, Xiangjun Kuang, Guangming Zhang, Maosheng Sun, Yan Zhou, Hongjun Li

Faculty, Staff and Student Publications

Rotaviruses (RVs) are a major cause of diarrhea in young children worldwide. The currently available and licensed vaccines contain live attenuated RVs. Optimization of live attenuated RV vaccines or developing non-replicating RV (e.g., mRNA) vaccines is crucial for reducing the morbidity and mortality from RV infections. Herein, a nucleoside-modified mRNA vaccine encapsulated in lipid nanoparticles (LNP) and encoding the VP7 protein from the G1 type of RV was developed. The 5' untranslated region of an isolated human RV was utilized for the mRNA vaccine. After undergoing quality inspection, the VP7-mRNA vaccine was injected by subcutaneous or intramuscular routes into mice. …


Enhancing Antibody Responses By Multivalent Antigen Display On Thymus-Independent Dna Origami Scaffolds, Eike-Christian Wamhoff, James Brett Case, Shilpa Sanapala, Michael S Diamond, Et Al. Jan 2024

Enhancing Antibody Responses By Multivalent Antigen Display On Thymus-Independent Dna Origami Scaffolds, Eike-Christian Wamhoff, James Brett Case, Shilpa Sanapala, Michael S Diamond, Et Al.

2020-Current year OA Pubs

Protein-based virus-like particles (P-VLPs) are commonly used to spatially organize antigens and enhance humoral immunity through multivalent antigen display. However, P-VLPs are thymus-dependent antigens that are themselves immunogenic and can induce B cell responses that may neutralize the platform. Here, we investigate thymus-independent DNA origami as an alternative material for multivalent antigen display using the receptor binding domain (RBD) of the SARS-CoV-2 spike protein, the primary target of neutralizing antibody responses. Sequential immunization of mice with DNA-based VLPs (DNA-VLPs) elicits protective neutralizing antibodies to SARS-CoV-2 in a manner that depends on the valency of the antigen displayed and on T …


Complement Receptor 1 Is The Human Erythrocyte Receptor For Plasmodium Vivax Erythrocyte Binding Protein, Seong-Kyun Lee, Cécile Crosnier, Paola Carolina Valenzuela-Leon, Brian L P Dizon, John P Atkinson, Jianbing Mu, Gavin J Wright, Eric Calvo, Karthigayan Gunalan, Louis H Miller Jan 2024

Complement Receptor 1 Is The Human Erythrocyte Receptor For Plasmodium Vivax Erythrocyte Binding Protein, Seong-Kyun Lee, Cécile Crosnier, Paola Carolina Valenzuela-Leon, Brian L P Dizon, John P Atkinson, Jianbing Mu, Gavin J Wright, Eric Calvo, Karthigayan Gunalan, Louis H Miller

2020-Current year OA Pubs

The discovery that Africans were resistant to infection by


Invasive Group A Streptococcus In Infants Less Than 1-Year Of Age From 2012 To 2022: A Single-Center Experience, Taylor Nack, Jesus G Vallejo, James Dunn, Anthony R Flores, J Chase Mcneil Jan 2024

Invasive Group A Streptococcus In Infants Less Than 1-Year Of Age From 2012 To 2022: A Single-Center Experience, Taylor Nack, Jesus G Vallejo, James Dunn, Anthony R Flores, J Chase Mcneil

Faculty, Staff and Students Publications

The incidence of invasive Group A Streptococcus (iGAS) has varied throughout the COVID-19 pandemic. We reviewed iGAS infections in infants ≤1 year from 2012 to 2022. Twenty-five percent of cases occurred in the last quarter of 2022. Pneumonia (21.8%) was the most common presentation. Twenty-one patients (65.6%) were successfully transitioned to oral antibiotics.


Prevention And Potential Treatment Strategies For Respiratory Syncytial Virus, Bo-Wen Sun, Peng-Peng Zhang, Zong-Hao Wang, Xia Yao, Meng-Lan He, Rui-Ting Bai, Hao Che, Jing Lin, Tian Xie, Zi Hui, Xiang-Yang Ye, Li-Wei Wang Jan 2024

Prevention And Potential Treatment Strategies For Respiratory Syncytial Virus, Bo-Wen Sun, Peng-Peng Zhang, Zong-Hao Wang, Xia Yao, Meng-Lan He, Rui-Ting Bai, Hao Che, Jing Lin, Tian Xie, Zi Hui, Xiang-Yang Ye, Li-Wei Wang

Faculty, Staff and Student Publications

Respiratory syncytial virus (RSV) is a significant viral pathogen that causes respiratory infections in infants, the elderly, and immunocompromised individuals. RSV-related illnesses impose a substantial economic burden worldwide annually. The molecular structure, function, and in vivo interaction mechanisms of RSV have received more comprehensive attention in recent times, and significant progress has been made in developing inhibitors targeting various stages of the RSV replication cycle. These include fusion inhibitors, RSV polymerase inhibitors, and nucleoprotein inhibitors, as well as FDA-approved RSV prophylactic drugs palivizumab and nirsevimab. The research community is hopeful that these developments might provide easier access to knowledge and …


The Durability Of Antibody Responses Of Two Doses Of High-Dose Relative To Two Doses Of Standard-Dose Inactivated Influenza Vaccine In Pediatric Hematopoietic Cell Transplant Recipients: A Multi-Center Randomized Controlled Trial., Jennifer E. Schuster, Lubna Hamdan, Daniel E. Dulek, Carrie L. Kitko, Einas Batarseh, Zaid Haddadin, Laura S. Stewart, Anna Stahl, Molly Potter, Herdi Rahman, Spyros A. Kalams, Claire E. Bocchini, Elizabeth A. Moulton, Susan E. Coffin, Monica I. Ardura, Rachel L. Wattier, Gabriela Maron, Michael Grimley, Grant Paulsen, Christopher J. Harrison, Jason L. Freedman, Paul A. Carpenter, Janet A. Englund, Flor M. Munoz, Lara Danziger-Isakov, Andrew J. Spieker, Natasha B. Halasa, Pediatric Hct Flu Study Jan 2024

The Durability Of Antibody Responses Of Two Doses Of High-Dose Relative To Two Doses Of Standard-Dose Inactivated Influenza Vaccine In Pediatric Hematopoietic Cell Transplant Recipients: A Multi-Center Randomized Controlled Trial., Jennifer E. Schuster, Lubna Hamdan, Daniel E. Dulek, Carrie L. Kitko, Einas Batarseh, Zaid Haddadin, Laura S. Stewart, Anna Stahl, Molly Potter, Herdi Rahman, Spyros A. Kalams, Claire E. Bocchini, Elizabeth A. Moulton, Susan E. Coffin, Monica I. Ardura, Rachel L. Wattier, Gabriela Maron, Michael Grimley, Grant Paulsen, Christopher J. Harrison, Jason L. Freedman, Paul A. Carpenter, Janet A. Englund, Flor M. Munoz, Lara Danziger-Isakov, Andrew J. Spieker, Natasha B. Halasa, Pediatric Hct Flu Study

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Our previous study established a 2-dose regimen of high-dose trivalent influenza vaccine (HD-TIV) to be immunogenically superior compared to a 2-dose regimen of standard-dose quadrivalent influenza vaccine (SD-QIV) in pediatric allogeneic hematopoietic cell transplant (HCT) recipients. However, the durability of immunogenicity and the role of time post-HCT at immunization as an effect modifier are unknown.

METHODS: This phase II, multi-center, double-blinded, randomized controlled trial compared HD-TIV to SD-QIV in children 3-17 years old who were 3-35 months post-allogeneic HCT, with each formulation administered twice, 28-42 days apart. Hemagglutination inhibition (HAI) titers were measured at baseline, 28-42 days following each …


Virology-The Path Forward, Angela L Rasmussen, Gigi K Gronvall, Anice C Lowen, Felicia Goodrum, James Alwine, Kristian G Andersen, Simon J Anthony, Joel Baines, Arinjay Banerjee, Andrew J Broadbent, Christopher B Brooke, Samuel K Campos, Patrizia Caposio, Arturo Casadevall, Gary C Chan, Anna R Cliffe, Donna Collins-Mcmillen, Nancy Connell, Blossom Damania, Matthew D Daugherty, Kari Debbink, Terence S Dermody, Daniel Dimaio, W Paul Duprex, Michael Emerman, Denise A Galloway, Robert F Garry, Stephen A Goldstein, Alexander L Greninger, Amy L Hartman, Brenda G Hogue, Stacy M Horner, Peter J Hotez, Jae U Jung, Jeremy P Kamil, Stephanie M Karst, Lou Laimins, Seema S Lakdawala, Igor Landais, Michael Letko, Brett Lindenbach, Shan-Lu Liu, Micah Luftig, Grant Mcfadden, Andrew Mehle, Juliet Morrison, Anne Moscona, Elke Mühlberger, Joshua Munger, Karl Münger, Eain Murphy, Christopher J Neufeldt, Janko Z Nikolich, Christine M O'Connor, Andrew Pekosz, Sallie R Permar, Julie K Pfeiffer, Saskia V Popescu, John G Purdy, Vincent R Racaniello, Charles M Rice, Jonathan A Runstadler, Martin J Sapp, Rona S Scott, Gregory A Smith, Erin M Sorrell, Emily Speranza, Daniel Streblow, Scott A Tibbetts, Zsolt Toth, Koenraad Van Doorslaer, Susan R Weiss, Elizabeth A White, Timothy M White, Christiane E Wobus, Michael Worobey, Satoko Yamaoka, Andrew Yurochko Jan 2024

Virology-The Path Forward, Angela L Rasmussen, Gigi K Gronvall, Anice C Lowen, Felicia Goodrum, James Alwine, Kristian G Andersen, Simon J Anthony, Joel Baines, Arinjay Banerjee, Andrew J Broadbent, Christopher B Brooke, Samuel K Campos, Patrizia Caposio, Arturo Casadevall, Gary C Chan, Anna R Cliffe, Donna Collins-Mcmillen, Nancy Connell, Blossom Damania, Matthew D Daugherty, Kari Debbink, Terence S Dermody, Daniel Dimaio, W Paul Duprex, Michael Emerman, Denise A Galloway, Robert F Garry, Stephen A Goldstein, Alexander L Greninger, Amy L Hartman, Brenda G Hogue, Stacy M Horner, Peter J Hotez, Jae U Jung, Jeremy P Kamil, Stephanie M Karst, Lou Laimins, Seema S Lakdawala, Igor Landais, Michael Letko, Brett Lindenbach, Shan-Lu Liu, Micah Luftig, Grant Mcfadden, Andrew Mehle, Juliet Morrison, Anne Moscona, Elke Mühlberger, Joshua Munger, Karl Münger, Eain Murphy, Christopher J Neufeldt, Janko Z Nikolich, Christine M O'Connor, Andrew Pekosz, Sallie R Permar, Julie K Pfeiffer, Saskia V Popescu, John G Purdy, Vincent R Racaniello, Charles M Rice, Jonathan A Runstadler, Martin J Sapp, Rona S Scott, Gregory A Smith, Erin M Sorrell, Emily Speranza, Daniel Streblow, Scott A Tibbetts, Zsolt Toth, Koenraad Van Doorslaer, Susan R Weiss, Elizabeth A White, Timothy M White, Christiane E Wobus, Michael Worobey, Satoko Yamaoka, Andrew Yurochko

Faculty, Staff and Students Publications

In the United States (US), biosafety and biosecurity oversight of research on viruses is being reappraised. Safety in virology research is paramount and oversight frameworks should be reviewed periodically. Changes should be made with care, however, to avoid impeding science that is essential for rapidly reducing and responding to pandemic threats as well as addressing more common challenges caused by infectious diseases. Decades of research uniquely positioned the US to be able to respond to the COVID-19 crisis with astounding speed, delivering life-saving vaccines within a year of identifying the virus. We should embolden and empower this strength, which is …


Targeting Efferocytosis In Inflammaging, Ivan K H Poon, Kodi S Ravichandran Jan 2024

Targeting Efferocytosis In Inflammaging, Ivan K H Poon, Kodi S Ravichandran

2020-Current year OA Pubs

Rapid removal of apoptotic cells by phagocytes, a process known as efferocytosis, is key for the maintenance of tissue homeostasis, the resolution of inflammation, and tissue repair. However, impaired efferocytosis can result in the accumulation of apoptotic cells, subsequently triggering sterile inflammation through the release of endogenous factors such as DNA and nuclear proteins from membrane permeabilized dying cells. Here, we review the molecular basis of the three key phases of efferocytosis, that is, the detection, uptake, and degradation of apoptotic materials by phagocytes. We also discuss how defects in efferocytosis due to the alteration of phagocytes and dying cells …


Drug Preparation, Injection-Related Infections, And Harm Reduction Practices Among A National Sample Of Individuals Entering Treatment For Opioid Use Disorder, Laura R Marks, Michael J Durkin, Kelly Ayres, Matthew Ellis Jan 2024

Drug Preparation, Injection-Related Infections, And Harm Reduction Practices Among A National Sample Of Individuals Entering Treatment For Opioid Use Disorder, Laura R Marks, Michael J Durkin, Kelly Ayres, Matthew Ellis

2020-Current year OA Pubs

BACKGROUND: The rise in injection drug use in the USA has led to an increase in injection site infections. We performed a national survey of people who use drugs to evaluate common drug use preparation, harm reduction practices, and experiences with injection site infections.

METHODS: A survey was disseminated to members of the Survey of Key Informants' Patients Program from 2021 to 2022 and distributed to patients 18 years or older newly entering one of 68 substance use disorder treatment programs across the USA with a primary diagnosis of an opioid use disorder. Participants were surveyed about practices when preparing …


Syphilis Complicating Pregnancy And Congenital Syphilis, Irene A Stafford, Kimberly A Workowski, Laura H Bachmann Jan 2024

Syphilis Complicating Pregnancy And Congenital Syphilis, Irene A Stafford, Kimberly A Workowski, Laura H Bachmann

Faculty, Staff and Student Publications

No abstract provided.


Comparison Of Three Rapid Diagnostic Tests For Bloodstream Infections Using Benefit-Risk Evaluation Framework (Bed-Frame), Richard D Smith, Min Zhan, Shanshan Zhang, Surbhi Leekha, Anthony Harris, Yohei Doi, Scott Evans, J Kristie Johnson, Robert K Ernst Jan 2024

Comparison Of Three Rapid Diagnostic Tests For Bloodstream Infections Using Benefit-Risk Evaluation Framework (Bed-Frame), Richard D Smith, Min Zhan, Shanshan Zhang, Surbhi Leekha, Anthony Harris, Yohei Doi, Scott Evans, J Kristie Johnson, Robert K Ernst

Faculty, Staff and Student Publications

Rapid diagnostic tests (RDTs) for bloodstream infections have the potential to reduce time to appropriate antimicrobial therapy and improve patient outcomes. Previously, an in-house, lipid-based, matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) method, Fast Lipid Analysis Technique (FLAT MS), has shown promise as a rapid pathogen identification method. In this study, FLAT MS for direct from blood culture identification was evaluated and compared to FDA-cleared identification methods using the Benefit-risk Evaluation Framework (BED-FRAME) analysis. FLAT MS was evaluated and compared to Bruker Sepsityper and bioMérieux BioFire FilmArray BCID2 using results from a previous study. For this study, 301 …


The Respiratory Enzyme Complex Rnf Is Vital For Metabolic Adaptation And Virulence In Fusobacterium Nucleatum, Timmie A Britton, Chenggang Wu, Yi-Wei Chen, Dana Franklin, Yimin Chen, Martha I Camacho, Truc T Luong, Asis Das, Hung Ton-That Jan 2024

The Respiratory Enzyme Complex Rnf Is Vital For Metabolic Adaptation And Virulence In Fusobacterium Nucleatum, Timmie A Britton, Chenggang Wu, Yi-Wei Chen, Dana Franklin, Yimin Chen, Martha I Camacho, Truc T Luong, Asis Das, Hung Ton-That

Faculty, Staff and Student Publications

The Gram-negative oral pathobiont Fusobacterium nucleatum can traverse to extra-oral sites such as placenta and colon, promoting adverse pregnancy outcomes and colorectal cancer, respectively. How this anaerobe sustains many metabolically changing environments enabling its virulence potential remains unclear. Informed by our genome-wide transposon mutagenesis, we report here that the highly conserved Rhodobacter nitrogen-fixation (Rnf) complex, encoded by the rnfCDGEAB gene cluster, is key to fusobacterial metabolic adaptation and virulence. Genetic disruption of the Rnf complex via non-polar, in-frame deletion of rnfC (ΔrnfC) abrogates polymicrobial interaction (or coaggregation) associated with adhesin RadD and biofilm formation. The defect in coaggregation …


In-Patient Evolution Of A High-Persister Escherichia Coli Strain With Reduced In Vivo Antibiotic Susceptibility, Joshua B Parsons, Ashelyn E Sidders, Amanda Z Velez, Blake M Hanson, Michelle Angeles-Solano, Felicia Ruffin, Sarah E Rowe, Cesar A Arias, Vance G Fowler, Joshua T Thaden, Brian P Conlon Jan 2024

In-Patient Evolution Of A High-Persister Escherichia Coli Strain With Reduced In Vivo Antibiotic Susceptibility, Joshua B Parsons, Ashelyn E Sidders, Amanda Z Velez, Blake M Hanson, Michelle Angeles-Solano, Felicia Ruffin, Sarah E Rowe, Cesar A Arias, Vance G Fowler, Joshua T Thaden, Brian P Conlon

Faculty, Staff and Student Publications

Gram-negative bacterial bloodstream infections (GNB-BSI) are common and frequently lethal. Despite appropriate antibiotic treatment, relapse of GNB-BSI with the same bacterial strain is common and associated with poor clinical outcomes and high healthcare costs. The role of persister cells, which are sub-populations of bacteria that survive for prolonged periods in the presence of bactericidal antibiotics, in relapse of GNB-BSI is unclear. Using a cohort of patients with relapsed GNB-BSI, we aimed to determine how the pathogen evolves within the patient between the initial and subsequent episodes of GNB-BSI and how these changes impact persistence. Using


Knowledge, Attitudes, And Subjective Norms Associated With Covid-19 Vaccination Among Pregnant Women In Kenya: An Online Cross-Sectional Pilot Study Using Whatsapp, Sylvia Ayieko, Walter Jaoko, Rose Okoyo Opiyo, Elkanah Omenge Orang'o, Sarah E Messiah, Kimberly Baker, Christine Markham Jan 2024

Knowledge, Attitudes, And Subjective Norms Associated With Covid-19 Vaccination Among Pregnant Women In Kenya: An Online Cross-Sectional Pilot Study Using Whatsapp, Sylvia Ayieko, Walter Jaoko, Rose Okoyo Opiyo, Elkanah Omenge Orang'o, Sarah E Messiah, Kimberly Baker, Christine Markham

Faculty, Staff and Student Publications

COVID-19 vaccination during pregnancy has been recommended, but the perceptions related to uptake remain unexplored. This pilot study aimed to explore how perceptions influence COVID-19 vaccine uptake among a sample of 115 pregnant women in Kenya, recruited via WhatsApp. Data were collected using an adapted online questionnaire between May and October 2022. Logistic analyses assessed the relationship between COVID-19 vaccination uptake and the Theory of Reasoned Action (TRA) constructs: attitudes and subjective norms. COVID-19 vaccination coverage was 73%, with vaccine hesitancy estimated at 41.4% among the unvaccinated group. Most participants had completed college education and had good knowledge of COVID-19 …


The Pan-Microbiome Profiling System Taxa4meta Identifies Clinical Dysbiotic Features And Classifies Diarrheal Disease, Qinglong Wu, Shyam Badu, Sik Yu So, Todd J Treangen, Tor C Savidge Jan 2024

The Pan-Microbiome Profiling System Taxa4meta Identifies Clinical Dysbiotic Features And Classifies Diarrheal Disease, Qinglong Wu, Shyam Badu, Sik Yu So, Todd J Treangen, Tor C Savidge

Faculty, Staff and Students Publications

Targeted metagenomic sequencing is an emerging strategy to survey disease-specific microbiome biomarkers for clinical diagnosis and prognosis. However, this approach often yields inconsistent or conflicting results owing to inadequate study power and sequencing bias. We introduce Taxa4Meta, a bioinformatics pipeline explicitly designed to compensate for technical and demographic bias. We designed and validated Taxa4Meta for accurate taxonomic profiling of 16S rRNA amplicon data acquired from different sequencing strategies. Taxa4Meta offers significant potential in identifying clinical dysbiotic features that can reliably predict human disease, validated comprehensively via reanalysis of individual patient 16S data sets. We leveraged the power of Taxa4Meta's pan-microbiome …


Gut Microbiome And Antibiotic Resistance Effects During Travelers' Diarrhea Treatment And Prevention, Kevin S Blake, Drew J Schwartz, Srinand Paruthiyil, Bin Wang, Jie Ning, Harris Whiteson, Gautam Dantas, Et Al. Jan 2024

Gut Microbiome And Antibiotic Resistance Effects During Travelers' Diarrhea Treatment And Prevention, Kevin S Blake, Drew J Schwartz, Srinand Paruthiyil, Bin Wang, Jie Ning, Harris Whiteson, Gautam Dantas, Et Al.

2020-Current year OA Pubs

The travelers' gut microbiome is potentially assaulted by acute and chronic perturbations (e.g., diarrhea, antibiotic use, and different environments). Prior studies of the impact of travel and travelers' diarrhea (TD) on the microbiome have not directly compared antibiotic regimens, and studies of different antibiotic regimens have not considered travelers' microbiomes. This gap is important to be addressed as the use of antibiotics to treat or prevent TD-even in moderate to severe cases or in regions with high infectious disease burden-is controversial based on the concerns for unintended consequences to the gut microbiome and antimicrobial resistance (AMR) emergence. Our study addresses …


Portable Air Purifiers To Mitigate The Harms Of Wildfire Smoke For People With Asthma, Tianshi David Wu Jan 2024

Portable Air Purifiers To Mitigate The Harms Of Wildfire Smoke For People With Asthma, Tianshi David Wu

Faculty, Staff and Students Publications

No abstract provided.