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  1. Article ; Online: The antibiotic resistance reservoir of the lung microbiome expands with age in a population of critically ill patients

    Victoria T. Chu / Alexandra Tsitsiklis / Eran Mick / Lilliam Ambroggio / Katrina L. Kalantar / Abigail Glascock / Christina M. Osborne / Brandie D. Wagner / Michael A. Matthay / Joseph L. DeRisi / Carolyn S. Calfee / Peter M. Mourani / Charles R. Langelier

    Nature Communications, Vol 15, Iss 1, Pp 1-

    2024  Volume 10

    Abstract: Abstract Antimicrobial resistant lower respiratory tract infections are an increasing public health threat and an important cause of global mortality. The lung microbiome can influence susceptibility of respiratory tract infections and represents an ... ...

    Abstract Abstract Antimicrobial resistant lower respiratory tract infections are an increasing public health threat and an important cause of global mortality. The lung microbiome can influence susceptibility of respiratory tract infections and represents an important reservoir for exchange of antimicrobial resistance genes. Studies of the gut microbiome have found an association between age and increasing antimicrobial resistance gene burden, however, corollary studies in the lung microbiome remain absent. We performed an observational study of children and adults with acute respiratory failure admitted to the intensive care unit. From tracheal aspirate RNA sequencing data, we evaluated age-related differences in detectable antimicrobial resistance gene expression in the lung microbiome. Using a multivariable logistic regression model, we find that detection of antimicrobial resistance gene expression was significantly higher in adults compared with children after adjusting for demographic and clinical characteristics. This association remained significant after additionally adjusting for lung bacterial microbiome characteristics, and when modeling age as a continuous variable. The proportion of adults expressing beta-lactam, aminoglycoside, and tetracycline antimicrobial resistance genes was higher compared to children. Together, these findings shape our understanding of the lung resistome in critically ill patients across the lifespan, which may have implications for clinical management and global public health.
    Keywords Science ; Q
    Subject code 610
    Language English
    Publishing date 2024-01-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Integrated host/microbe metagenomics enables accurate lower respiratory tract infection diagnosis in critically ill children

    Eran Mick / Alexandra Tsitsiklis / Jack Kamm / Katrina L. Kalantar / Saharai Caldera / Amy Lyden / Michelle Tan / Angela M. Detweiler / Norma Neff / Christina M. Osborne / Kayla M. Williamson / Victoria Soesanto / Matthew Leroue / Aline B. Maddux / Eric A.F. Simões / Todd C. Carpenter / Brandie D. Wagner / Joseph L. DeRisi / Lilliam Ambroggio /
    Peter M. Mourani / Charles R. Langelier

    The Journal of Clinical Investigation, Vol 133, Iss

    2023  Volume 7

    Abstract: BACKGROUND Lower respiratory tract infection (LRTI) is a leading cause of death in children worldwide. LRTI diagnosis is challenging because noninfectious respiratory illnesses appear clinically similar and because existing microbiologic tests are often ... ...

    Abstract BACKGROUND Lower respiratory tract infection (LRTI) is a leading cause of death in children worldwide. LRTI diagnosis is challenging because noninfectious respiratory illnesses appear clinically similar and because existing microbiologic tests are often falsely negative or detect incidentally carried microbes, resulting in antimicrobial overuse and adverse outcomes. Lower airway metagenomics has the potential to detect host and microbial signatures of LRTI. Whether it can be applied at scale and in a pediatric population to enable improved diagnosis and treatment remains unclear.METHODS We used tracheal aspirate RNA-Seq to profile host gene expression and respiratory microbiota in 261 children with acute respiratory failure. We developed a gene expression classifier for LRTI by training on patients with an established diagnosis of LRTI (n = 117) or of noninfectious respiratory failure (n = 50). We then developed a classifier that integrates the host LRTI probability, abundance of respiratory viruses, and dominance in the lung microbiome of bacteria/fungi considered pathogenic by a rules-based algorithm.RESULTS The host classifier achieved a median AUC of 0.967 by cross-validation, driven by activation markers of T cells, alveolar macrophages, and the interferon response. The integrated classifier achieved a median AUC of 0.986 and increased the confidence of patient classifications. When applied to patients with an uncertain diagnosis (n = 94), the integrated classifier indicated LRTI in 52% of cases and nominated likely causal pathogens in 98% of those.CONCLUSION Lower airway metagenomics enables accurate LRTI diagnosis and pathogen identification in a heterogeneous cohort of critically ill children through integration of host, pathogen, and microbiome features.FUNDING Support for this study was provided by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Heart, Lung, and Blood Institute (UG1HD083171, 1R01HL124103, UG1HD049983, UG01HD049934, UG1HD083170, ...
    Keywords Infectious disease ; Pulmonology ; Medicine ; R
    Subject code 610
    Language English
    Publishing date 2023-04-01T00:00:00Z
    Publisher American Society for Clinical Investigation
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Workshop-based learning and networking

    Celine Perier / Emmanuel Nasinghe / Isabelle Charles / Leoson Junior Ssetaba / Vida Ahyong / Derek Bangs / P. Robert Beatty / Nadine Czudnochowski / Amy Diallo / Eli Dugan / Jacqueline M. Fabius / Hildy Fong Baker / Jackson Gardner / Stephen Isaacs / Birungi Joanah / Katrina Kalantar / David Kateete / Matt Knight / Maria Krasilnikov /
    Nevan J. Krogan / Chaz Langelier / Eric Lee / Lucy M. Li / Daniel Licht / Katie Lien / Zilose Lyons / Gerald Mboowa / Ivan Mwebaza / Savannah Mwesigwa / Geraldine Nalwadda / Robert Nichols / Maria Elena Penaranda / Sarah Petnic / Maira Phelps / Stephen J. Popper / Michael Rape / Arthur Reingold / Richard Robbins / Oren S. Rosenberg / David F. Savage / Samuel Schildhauer / Matthew L. Settles / Ivan Sserwadda / Sarah Stanley / Cristina M. Tato / Alexandra Tsitsiklis / Erik Van Dis / Manu Vanaerschot / Joanna Vinden / Jeffery S. Cox

    Global Health Action, Vol 15, Iss

    a scalable model for research capacity strengthening in low- and middle-income countries

    2022  Volume 1

    Abstract: Science education and research have the potential to drive profound change in low- and middle-income countries (LMICs) through encouraging innovation, attracting industry, and creating job opportunities. However, in LMICs, research capacity is often ... ...

    Abstract Science education and research have the potential to drive profound change in low- and middle-income countries (LMICs) through encouraging innovation, attracting industry, and creating job opportunities. However, in LMICs, research capacity is often limited, and acquisition of funding and access to state-of-the-art technologies is challenging. The Alliance for Global Health and Science (the Alliance) was founded as a partnership between the University of California, Berkeley (USA) and Makerere University (Uganda), with the goal of strengthening Makerere University’s capacity for bioscience research. The flagship program of the Alliance partnership is the MU/UCB Biosciences Training Program, an in-country, hands-on workshop model that trains a large number of students from Makerere University in infectious disease and molecular biology research. This approach nucleates training of larger and more diverse groups of students, development of mentoring and bi-directional research partnerships, and support of the local economy. Here, we describe the project, its conception, implementation, challenges, and outcomes of bioscience research workshops. We aim to provide a blueprint for workshop implementation, and create a valuable resource for bioscience research capacity strengthening in LMICs.
    Keywords capacity strengthening ; africa ; uganda ; research ; infectious diseases ; Public aspects of medicine ; RA1-1270
    Subject code 380
    Language English
    Publishing date 2022-12-01T00:00:00Z
    Publisher Taylor & Francis Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Launching a saliva-based SARS-CoV-2 surveillance testing program on a university campus.

    Alexander J Ehrenberg / Erica A Moehle / Cara E Brook / Andrew H Doudna Cate / Lea B Witkowsky / Rohan Sachdeva / Ariana Hirsh / Kerrie Barry / Jennifer R Hamilton / Enrique Lin-Shiao / Shana McDevitt / Luis Valentin-Alvarado / Kaitlyn N Letourneau / Lauren Hunter / Amanda Keller / Kathleen Pestal / Phillip A Frankino / Andrew Murley / Divya Nandakumar /
    Elizabeth C Stahl / Connor A Tsuchida / Holly K Gildea / Andrew G Murdock / Megan L Hochstrasser / Elizabeth O'Brien / Alison Ciling / Alexandra Tsitsiklis / Kurtresha Worden / Claire Dugast-Darzacq / Stephanie G Hays / Colin C Barber / Riley McGarrigle / Emily K Lam / David C Ensminger / Lucie Bardet / Carolyn Sherry / Anna Harte / Guy Nicolette / Petros Giannikopoulos / Dirk Hockemeyer / Maya Petersen / Fyodor D Urnov / Bradley R Ringeisen / Mike Boots / Jennifer A Doudna / IGI SARS-CoV-2 Testing Consortium

    PLoS ONE, Vol 16, Iss 5, p e

    2021  Volume 0251296

    Abstract: Regular surveillance testing of asymptomatic individuals for SARS-CoV-2 has been center to SARS-CoV-2 outbreak prevention on college and university campuses. Here we describe the voluntary saliva testing program instituted at the University of California, ...

    Abstract Regular surveillance testing of asymptomatic individuals for SARS-CoV-2 has been center to SARS-CoV-2 outbreak prevention on college and university campuses. Here we describe the voluntary saliva testing program instituted at the University of California, Berkeley during an early period of the SARS-CoV-2 pandemic in 2020. The program was administered as a research study ahead of clinical implementation, enabling us to launch surveillance testing while continuing to optimize the assay. Results of both the testing protocol itself and the study participants' experience show how the program succeeded in providing routine, robust testing capable of contributing to outbreak prevention within a campus community and offer strategies for encouraging participation and a sense of civic responsibility.
    Keywords Medicine ; R ; Science ; Q
    Language English
    Publishing date 2021-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Lower respiratory tract infections in children requiring mechanical ventilation

    Alexandra Tsitsiklis, PhD / Christina M Osborne, MD / Jack Kamm, PhD / Kayla Williamson, MS / Katrina Kalantar, PhD / Gytis Dudas, PhD / Saharai Caldera, BA / Amy Lyden, BA / Michelle Tan, BS / Norma Neff, PhD / Victoria Soesanto, BS / J Kirk Harris, PhD / Lilliam Ambroggio, PhD / Aline B Maddux, MD / Todd C Carpenter, MD / Ron W Reeder, PhD / Chris Locandro, MS / Eric A F Simões, ProfMD / Matthew K Leroue, MD /
    Mark W Hall, ProfMD / Athena F Zuppa, ProfMD / Joseph Carcillo, ProfMD / Kathleen L Meert, ProfMD / Anil Sapru, ProfMD / Murray M Pollack, ProfMD / Patrick S McQuillen, ProfMD / Daniel A Notterman, ProfMD / J Michael Dean, ProfMD / Matt S Zinter, MD / Brandie D Wagner, PhD / Joseph L DeRisi, ProfPhD / Peter M Mourani, ProfMD / Charles R Langelier, MDPhD

    The Lancet Microbe, Vol 3, Iss 4, Pp e284-e

    a multicentre prospective surveillance study incorporating airway metagenomics

    2022  Volume 293

    Abstract: Summary: Background: Lower respiratory tract infections (LRTI) are a leading cause of critical illness and mortality in mechanically ventilated children; however, the pathogenic microbes frequently remain unknown. We combined traditional diagnostics with ...

    Abstract Summary: Background: Lower respiratory tract infections (LRTI) are a leading cause of critical illness and mortality in mechanically ventilated children; however, the pathogenic microbes frequently remain unknown. We combined traditional diagnostics with metagenomic next generation sequencing (mNGS) to evaluate the cause of LRTI in critically ill children. Methods: We conducted a prospective, multicentre cohort study of critically ill children aged 31 days to 17 years with respiratory failure requiring mechanical ventilation (>72 h) in the USA. By combining bacterial culture and upper respiratory viral PCR testing with mNGS of tracheal aspirate collected from all patients within 24 h of intubation, we determined the prevalence, age distribution, and seasonal variation of viral and bacterial respiratory pathogens detected by either method in children with or without LRTI. Findings: Between Feb 26, 2015, and Dec 31, 2017, of the 514 enrolled patients, 397 were eligible and included in the study (276 children with LRTI and 121 with no evidence of LRTI). A presumptive microbiological cause was identified in 255 (92%) children with LRTI, with respiratory syncytial virus (127 [46%]), Haemophilus influenzae (70 [25%]), and Moraxella catarrhalis (65 [24%]) being most prevalent. mNGS identified uncommon pathogens including Ureaplasma parvum and Bocavirus. Co-detection of viral and bacterial pathogens occurred in 144 (52%) patients. Incidental carriage of potentially pathogenic microbes occurred in 82 (68%) children without LRTI, with rhinovirus (30 [25%]) being most prevalent. Respiratory syncytial virus (p<0·0001), H influenzae (p=0·0006), and M catarrhalis (p=0·0002) were most common in children younger than 5 years. Viral and bacterial LRTI occurred predominantly during winter months. Interpretation: These findings demonstrate that respiratory syncytial virus, H influenzae, and M catarrhalis contribute disproportionately to severe paediatric LRTI, co-infections are common, and incidental carriage of potentially ...
    Keywords Medicine (General) ; R5-920 ; Microbiology ; QR1-502
    Subject code 610
    Language English
    Publishing date 2022-04-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Tracheal aspirate RNA sequencing identifies distinct immunological features of COVID-19 ARDS

    Aartik Sarma / Stephanie A. Christenson / Ashley Byrne / Eran Mick / Angela Oliveira Pisco / Catherine DeVoe / Thomas Deiss / Rajani Ghale / Beth Shoshana Zha / Alexandra Tsitsiklis / Alejandra Jauregui / Farzad Moazed / Angela M. Detweiler / Natasha Spottiswoode / Pratik Sinha / Norma Neff / Michelle Tan / Paula Hayakawa Serpa / Andrew Willmore /
    K. Mark Ansel / Jennifer G. Wilson / Aleksandra Leligdowicz / Emily R. Siegel / Marina Sirota / Joseph L. DeRisi / Michael A. Matthay / COMET Consortium / Carolyn M. Hendrickson / Kirsten N. Kangelaris / Matthew F. Krummel / Prescott G. Woodruff / David J. Erle / Carolyn S. Calfee / Charles R. Langelier

    Nature Communications, Vol 12, Iss 1, Pp 1-

    2021  Volume 10

    Abstract: Here, the authors perform transcriptional profiling on tracheal aspirates of adults requiring mechanical ventilation for SARS-CoV2-induced acute respiratory distress syndrome (ARDS) and identify a dysregulated host response predicted to predicted to be ... ...

    Abstract Here, the authors perform transcriptional profiling on tracheal aspirates of adults requiring mechanical ventilation for SARS-CoV2-induced acute respiratory distress syndrome (ARDS) and identify a dysregulated host response predicted to predicted to be potentially modulated by dexamethasone.
    Keywords Science ; Q
    Language English
    Publishing date 2021-08-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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