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Record W4312143473 · doi:10.1016/j.bbadis.2022.166635

Organoids as a model to study intestinal and liver dysfunction in severe malnutrition

2022· article· en· W4312143473 on OpenAlexafffund
José M. Horcas‐Nieto, Christian J. Versloot, Miriam Langelaar‐Makkinje, Albert Gerding, Tjasso Blokzijl, Mirjam H. Koster, Mirjam Baanstra, Ingrid A. Martini, Robert P. Coppes, Céline Bourdon, Sven C.D. van IJzendoorn, Peter Kim, Robert Bandsma, Barbara M. Bakker

Bibliographic record

VenueBiochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · 2022
Typearticle
Languageen
FieldMedicine
TopicDiet and metabolism studies
Canadian institutionsUniversity of TorontoHospital for Sick Children
FundersH2020 Marie Skłodowska-Curie ActionsHorizon 2020Canadian Institutes of Health ResearchEuropean CommissionStichting De Cock-Hadders
KeywordsOrganoidMalnutritionBiologyPeroxisomeSteatosisPathophysiologyInternal medicineMedicineBioinformaticsEndocrinologyCell biology

Abstract

fetched live from OpenAlex

Hospitalized children with severe malnutrition face high mortality rates and often suffer from hepatic and intestinal dysfunction, with negative impacts on their survival. New treatments cannot be developed without understanding the underlying pathophysiology. We have established and characterized translational organoid models of severe malnutrition of the liver and the intestine. In these models, amino acid starvation recapitulates the expected organ-specific functional changes (e.g., hepatic steatosis, barrier dysfunction) accompanied by reduced mitochondrial and peroxisomal proteins, and altered intestinal tight junction proteins. Re-supplementation of amino acids or pharmacological interventions with rapamycin or fenofibrate lead to partial recovery. Restoration of protein levels aligned with signs of improved peroxisomal function in both organoids, and increased mitochondrial proteins and tight junction protein claudin-3 in intestinal organoids. We present two organoid models as novel tools to gain mechanistic insights and to act as a testing platform for potential treatments for intestinal and hepatic dysfunction in severe malnutrition.

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 score0.006

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0010.000
Science and technology studies0.0000.001
Scholarly communication0.0010.001
Open science0.0000.001
Research integrity0.0010.002
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 head0.013
GPT teacher head0.260
Teacher spread0.247 · 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

Citations17
Published2022
Admission routes2
Has abstractyes

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