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Record W4403267451 · doi:10.1016/j.isci.2024.111108

Preclinical validation of human recombinant glutamate-oxaloacetate transaminase for the treatment of acute ischemic stroke

2024· article· en· W4403267451 on OpenAlexafffund
María Pérez‐Mato, Antonio Dopico‐López, Yunus Akkoç, Sonia López-Amoedo, Clara Correa‐Paz, María Candamo-Lourido, Ramón Iglesias‐Rey, Esteban López‐Arias, Ana Bugallo-Casal, Andrés da Silva‐Candal, Susana B. Bravo, María del Pilar Chantada‐Vázquez, Susana Arias, María Santamaría-Cadavid, Ana Estany‐Gestal, Ahlem Zaghmi, Marc A. Gauthier, María Gutiérrez‐Fernández, Abraham Martín, Jordi Llop, Cristina Rodríguez, Ángeles Almeida, Martina Migliavacca, Ester Polo, Beatriz Pelaz, Devrim Gözüaçık, Naouale El Yamani, Tanima SenGupta, Elise Rundén‐Pran, José Vivancos, Mar Castellanos, Exuperio Díez‐Tejedor, Tomás Sobrino, Aharon Rabinkov, David Mirelman, José Castillo, Francisco Campos

Bibliographic record

VenueiScience · 2024
Typearticle
Languageen
FieldNeuroscience
TopicNeurological Disease Mechanisms and Treatments
Canadian institutionsInstitut National de la Recherche Scientifique
FundersAgencia Estatal de InvestigaciónInstituto de Salud Carlos IIIEuropean Research CouncilFonds de Recherche du Québec - SantéInstitut national de la recherche scientifiqueXunta de GaliciaConsellería de Economía, Emprego e Industria, Xunta de GaliciaMinisterio de Ciencia e InnovaciónFundación Mutua MadrileñaEuropean Regional Development FundEuropean CommissionFederación Española de Enfermedades RarasEuroNanoMed III
KeywordsTransaminaseGlutamate receptorRecombinant DNAStroke (engine)MedicineCitrate synthaseAspartate transaminaseBiochemistryPharmacologyChemistryInternal medicineNeuroscienceBiologyEnzymeAlkaline phosphatase

Abstract

fetched live from OpenAlex

The blood enzyme glutamate-oxaloacetate transaminase (GOT) has been postulated as an effective therapeutic to protect the brain during stroke. To demonstrate its potential clinical utility, a new human recombinant form of GOT (rGOT) was produced for medical use. We tested the pharmacokinetics and evaluated the protective efficacy of rGOT in rodent and non-human primate models that reflected clinical stroke conditions. We found that continuous intravenous administration of rGOT within the first 8 h after ischemic onset significantly reduced the infarct size in both severe (30%) and mild lesions (48%). Cerebrospinal fluid and proteomics analysis, in combination with positron emission tomography imaging, indicated that rGOT can reach the brain and induce cytoprotective autophagy and induce local protection by alleviating neuronal apoptosis. Our results suggest that rGOT can be safely used immediately in patients suspected of having a stroke. This study requires further validation in clinical stroke populations.

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)0.000
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: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.016
Threshold uncertainty score0.275

Codex and Gemma teacher scores by category

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)0.0000.000

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 head0.083
GPT teacher head0.356
Teacher spread0.274 · 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 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

Citations6
Published2024
Admission routes2
Has abstractyes

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