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Record W4311584845 · doi:10.1126/scitranslmed.abq6682

A B1a–natural IgG–neutrophil axis is impaired in viral- and steroid-associated aspergillosis

2022· article· en· W4311584845 on OpenAlexafffund
Nicole Sarden, Sarthak Sinha, Kyle Potts, Erwan Pernet, Carlos Hiroji Hiroki, Mortaza Fatehi Hassanabad, Angela Nguyen, Yuefei Lou, Raquel Farias, Brent W. Winston, Amy Bromley, Brendan D. Snarr, Amanda Z. Zucoloto, Graciela Andonegui, Daniel A. Muruve, Braedon McDonald, Donald C. Sheppard, Douglas J. Mahoney, Maziar Divangahi, Nicole L. Rosin, Jeff Biernaskie, Bryan G. Yipp

Bibliographic record

VenueScience Translational Medicine · 2022
Typearticle
Languageen
FieldMedicine
TopicAntifungal resistance and susceptibility
Canadian institutionsMcGill UniversityMcGill University Health CentreUniversity of Calgary
FundersCanadian Institutes of Health Research
KeywordsImmunologyAspergillus fumigatusAspergillosisContext (archaeology)AntibodyPneumoniaInnate immune systemAspergillusBiologyMedicineVirologyImmune systemMicrobiologyInternal medicine

Abstract

fetched live from OpenAlex

The lung naturally resists Aspergillus fumigatus ( Af ) in healthy individuals, but multiple conditions can disrupt this resistance, leading to lethal invasive infections. Core processes of natural resistance and its breakdown are undefined. We investigated three distinct conditions predisposing to lethal aspergillosis—severe SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection, influenza A viral pneumonia, and systemic corticosteroid use—in human patients and murine models. We found a conserved and essential coupling of innate B1a lymphocytes, Af -binding natural immunoglobulin G antibodies, and lung neutrophils. Failure of this axis concealed Af from neutrophils, allowing rapid fungal invasion and disease. Reconstituting the axis with immunoglobulin therapy reestablished resistance, thus representing a realistic pathway to repurpose currently available therapies. Together, we report a vital host resistance pathway that is responsible for protecting against life-threatening aspergillosis in the context of distinct susceptibilities.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.146
Threshold uncertainty score0.861

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.001
Science and technology studies0.0000.001
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.019
GPT teacher head0.294
Teacher spread0.275 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations52
Published2022
Admission routes2
Has abstractyes

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