Evidence map›Paper›PMID 32275904›Full record

ArticleThe American journal of pathology2020

Quantification of Viral and Host Biomarkers in the Liver of Rhesus Macaques: A Longitudinal Study of Zaire Ebolavirus Strain Kikwit (EBOV/Kik).

Alexandra Greenberg, Bertrand R Huber, David X Liu, James P Logue, Amanda M W Hischak, Randy J Hart, Maureen Abbott, Nejra Isic, Yohei M Hisada, Nigel Mackman and 4 more

Open access · hybridAbstract read
In one paragraph

Article in The American journal of pathology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
0.4field-weighted citation impact, top 24% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

18 citing papers in PubMed, 24 citations in OpenAlex.

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  17. IBEX: A versatile multiplex optical imaging approach for deep phenotyping and spatial analysis of cells in complex tissues.Proceedings of the National Academy of Sciences of the United States of America · 2020
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors at 3 institutions in 1 country.

Alexandra GreenbergGraduate Medical Sciences, Boston University School of Medicine, Boston, Massachusetts.
Bertrand R HuberDepartment of Neurology, Boston University School of Medicine, Boston, Massachusetts.
David X LiuIntegrated Research Facility, National Institute for Allergy and Infectious Diseases (NIAID), Frederick, Maryland.
James P LogueIntegrated Research Facility, National Institute for Allergy and Infectious Diseases (NIAID), Frederick, Maryland.
Amanda M W HischakIntegrated Research Facility, National Institute for Allergy and Infectious Diseases (NIAID), Frederick, Maryland.
Randy J HartIntegrated Research Facility, National Institute for Allergy and Infectious Diseases (NIAID), Frederick, Maryland.
Maureen AbbottIntegrated Research Facility, National Institute for Allergy and Infectious Diseases (NIAID), Frederick, Maryland.
Nejra IsicIntegrated Research Facility, National Institute for Allergy and Infectious Diseases (NIAID), Frederick, Maryland.
Yohei M HisadaDivision of Hematology and Oncology, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
Nigel MackmanDivision of Hematology and Oncology, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
Richard S BennettIntegrated Research Facility, National Institute for Allergy and Infectious Diseases (NIAID), Frederick, Maryland.
Lisa E HensleyIntegrated Research Facility, National Institute for Allergy and Infectious Diseases (NIAID), Frederick, Maryland.
John H ConnorDepartment of Medicine, Boston University School of Medicine, Boston, Massachusetts.
Nicholas A CrosslandDepartment of Pathology and Laboratory Medicine, Boston University School of Medicine, Boston, Massachusetts. Electronic address: ncrossla@bu.edu.
National Institute of Allergy and Infectious Diseases · USBoston University · USUniversity of North Carolina at Chapel Hill · US

Funding

Regulatory Compliance CoreUC7AI095321 · NIAID · BOSTON UNIVERSITY MEDICAL CAMPUS · PI Ronald O'Brien · 2014 to 2026
$159.3M
NIAID NIH HHS HHSN272200700016INIAID NIH HHS UC7 AI095321
6 · The paper itself

Abstract

Zaire ebolavirus (EBOV) causes Ebola virus disease (EVD), which carries a fatality rate between 25% and 90% in humans. Liver pathology is a hallmark of terminal EVD; however, little is known about temporal disease progression. We used multiplexed fluorescent immunohistochemistry and in situ hybridization in combination with whole slide imaging and image analysis (IA) to quantitatively characterize temporospatial signatures of viral and host factors as related to EBOV pathogenesis. Eighteen rhesus monkeys euthanized between 3 and 8 days post-infection, and 3 uninfected controls were enrolled in this study. Compared with semiquantitative histomorphologic ordinal scoring, quantitative IA detected subtle and progressive features of early and terminal EVD that was not feasible with routine approaches. Sinusoidal macrophages were the earliest cells to respond to infection, expressing proinflammatory cytokine interleukin 6 (IL6) mRNA, which was subsequently also observed in fibrovascular compartments. The mRNA of interferon-stimulated gene-15 (ISG-15), also known as ISG15 ubiquitin like modifier (ISG15), was observed early, with a progressive and ubiquitous hybridization signature involving mesenchymal and epithelial compartments. ISG-15 mRNA was prominent near infected cells, but not in infected cells, supporting the hypothesis that bystander cells produce a robust interferon gene response. This study contributes to our current understanding of early EVD progression and illustrates the value that digital pathology and quantitative IA serve in infectious disease research.

Indexed as

AnimalsBiomarkersEbolavirusFemaleHemorrhagic Fever, EbolaHost-Pathogen InteractionsLiverLongitudinal StudiesMacaca mulattaMaleBiomarkers

Identifiers

PMID32275904
PMCPMC7322367
OpenAlexW3015861730

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.