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Record W2046189491 · doi:10.1038/srep08717

Anthracycline-containing chemotherapy causes long-term impairment of mitochondrial respiration and increased reactive oxygen species release in skeletal muscle

2015· article· en· W2046189491 on OpenAlexafffund
Gilles Gouspillou, Celena Scheede‐Bergdahl, Sally Spendiff, Madhusudanarao Vuda, Brian Meehan, Heather Mlynarski, Élodie Archer-Lahlou, Nicolas Sgarioto, Fennigje M. Purves-Smith, Yana Konokhova, Janusz Rak, Stéphanie Chevalier, Tanja Taivassalo, Russell T. Hepple, R. Thomas Jagoe

Bibliographic record

VenueScientific Reports · 2015
Typearticle
Languageen
FieldMedicine
TopicChildhood Cancer Survivors' Quality of Life
Canadian institutionsMcGill UniversityMcGill University Health CentreMontreal Children's HospitalJewish General HospitalUniversité du Québec à Montréal
FundersCanadian Institutes of Health ResearchMcGill UniversitySchweizerischer Nationalfonds zur Förderung der Wissenschaftlichen ForschungMcGill University Health CentreNational Science Foundation
KeywordsSkeletal muscleMitochondrionMitochondrial biogenesisReactive oxygen speciesMitophagyBiologyEndocrinologyInternal medicineMitochondrial DNAAnthracyclineMedicineCell biologyApoptosisBiochemistryCancerAutophagyGene

Abstract

fetched live from OpenAlex

Anticancer treatments for childhood acute lymphoblastic leukaemia (ALL) are highly effective but are now implicated in causing impaired muscle function in long-term survivors. However, no comprehensive assessment of skeletal muscle mitochondrial functions in long-term survivors has been performed and the presence of persistent chemotherapy-induced skeletal muscle mitochondrial dysfunction remains a strong possibility. Non-tumour-bearing mice were treated with two drugs that have been used frequently in ALL treatment (doxorubicin and dexamethasone) for up to 4 cycles at 3-week intervals and euthanized 3 months after the 4th cycle. Treated animals had impaired growth and lower muscle mass as well as reduced mitochondrial respiration and increased reactive oxygen species production per unit oxygen consumption. Mitochondrial DNA content and protein levels of key mitochondrial membrane proteins and markers of mitochondrial biogenesis were unchanged, but protein levels of Parkin were reduced. This suggests a novel pattern of chemotherapy-induced mitochondrial dysfunction in skeletal muscle that persists because of an acquired defect in mitophagy signaling. The results could explain the observed functional impairments in adult survivors of childhood ALL and may also be relevant to long-term survivors of other cancers treated with similar regimes.

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: Observational · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.001
Threshold uncertainty score0.003

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 communication0.0000.000
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 head0.036
GPT teacher head0.318
Teacher spread0.282 · 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 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

Citations75
Published2015
Admission routes2
Has abstractyes

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