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Record W3193600692 · doi:10.1101/2021.08.13.456228

A diabetic <i>milieu</i> increases cellular susceptibility to SARS-CoV-2 infections in engineered human kidney organoids and diabetic patients

2021· preprint· en· W3193600692 on OpenAlexaff
Elena Garreta, Patricia Prado, Megan L. Stanifer, Vanessa Monteil, Carmen Hurtado del Pozo, Asier Ullate‐Agote, Amaia Vilas‐Zornoza, Juan P. Romero, Gustav Jonsson, Roger Oria, Alexandra Leopoldi, Astrid Hagelkrüys, Daniel Moya‐Rull, Federico Gonzãlez, Andrés Marco, Carolina Tarantino, Pere Domingo‐Pedrol, Omar Hasan Ali, Pedro Ventura‐Aguiar, Josep M. Campistol, Felipe Prósper, Alì Mirazimi, Steeve Boulant, Josef Penninger, Núria Montserrat

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2021
Typepreprint
Languageen
FieldMedicine
TopicCOVID-19 Clinical Research Studies
Canadian institutionsUniversity of British Columbia
Fundersnot available
KeywordsOrganoidDiabetic nephropathyKidneyAngiotensin-converting enzyme 2Diabetes mellitusDownregulation and upregulationCoronavirus disease 2019 (COVID-19)MedicineSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2)BiologyInternal medicineEndocrinologyImmunologyCancer researchDiseaseCell biologyGeneGeneticsInfectious disease (medical specialty)

Abstract

fetched live from OpenAlex

Summary SARS-CoV-2 infections lead to a high risk of hospitalization and mortality in diabetic patients. Why diabetic individuals are more prone to develop severe COVID-19 remains unclear. Here, we established a novel human kidney organoid model that mimics early hallmarks of diabetic nephropathy. High oscillatory glucose exposure resulted in metabolic changes, expansion of extracellular membrane components, gene expression changes determined by scRNAseq, and marked upregulation of angiotensin-converting enzyme 2 (ACE2). Upon SARS-CoV-2 infection, hyperglycemic conditions lead to markedly higher viral loads in kidney organoids compared to normoglycemia. Genetic deletion of ACE2, but not of the candidate receptor BSG/CD147, in kidney organoids demonstrated the essential role of ACE2 in SARS-CoV-2 infections and completely prevented SARS-CoV-2 infection in the diabetogenic microenvironment. These data introduce a novel organoid model for diabetic kidney disease and show that diabetic-induced ACE2 licenses the diabetic kidney to enhanced SARS-CoV-2 replication.

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 machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.002
Threshold uncertainty score0.007

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0010.000
Open science0.0000.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0020.000

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 head0.020
GPT teacher head0.298
Teacher spread0.278 · 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 source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
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

Citations2
Published2021
Admission routes1
Has abstractyes

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