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Functional interaction between mutations in the granulocyte colony‐stimulating factor receptor in severe congenital neutropenia

2008· article· en· W1992778934 on OpenAlexaff
Alister C. Ward, Judith Gits, Fidel Majeed, Andrew A.G. Aprikyan, Rowena S. Lewis, Lynda A. O’Sullivan, Melvin H. Freedman, Sarah Shigdar, Ivo P. Touw, David C. Dale, Yigal Dror

Bibliographic record

VenueBritish Journal of Haematology · 2008
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicBlood disorders and treatments
Canadian institutionsSickKids FoundationHospital for Sick ChildrenUniversity of Toronto
FundersNational Institutes of HealthNational Cancer InstituteKWF KankerbestrijdingDeakin University
KeywordsCongenital NeutropeniaNeutrophil extracellular trapsGranulocyte colony-stimulating factorNeutropeniaMutationGranulocyteGranulocyte colony-stimulating factor receptorNeutrophil elastaseElastaseExtracellularImmunologyCancer researchBiologyMedicineInternal medicineGeneticsGeneChemotherapyBiochemistryInflammationEnzyme

Abstract

fetched live from OpenAlex

Most severe congenital neutropenia (SCN) cases possess constitutive neutrophil elastase mutations; a smaller cohort has acquired mutations truncating the granulocyte colony-stimulating factor receptor (G-CSF-R). We have described a case with constitutive extracellular G-CSF-R mutation hyporesponsive to ligand. Here we report two independent acquired G-CSF-R truncation mutations and a novel constitutive neutrophil elastase mutation in this patient. Co-expression of a truncated receptor chain restored STAT5 signalling responses of the extracellular G-CSF-R mutant, while constitutively-active STAT5 enhanced its proliferative capacity. These data add to our knowledge of SCN and further highlight the importance of STAT5 in mediating proliferative responses to G-CSF.

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: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.091
Threshold uncertainty score0.329

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 head0.023
GPT teacher head0.262
Teacher spread0.239 · 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

Citations14
Published2008
Admission routes1
Has abstractyes

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