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Mucus dispersal by Dithiothreitol (DTT) reduces ciliary dyskinesia

2024· article· en· W4404096859 on OpenAlexaff
Anna Straatman-Iwanowska, Maria Khan, Neeta Kulkarni, Gwyneth Williams, Christopher O’Callaghan, Robert A. Hirst

Bibliographic record

Venuenot available
Typearticle
Languageen
FieldMedicine
TopicCystic Fibrosis Research Advances
Canadian institutionsInstitute of Infection and Immunity
Fundersnot available
KeywordsDithiothreitolPrimary ciliary dyskinesiaMucusBiological dispersalCell biologyChemistryBiologyMedicineInternal medicineBronchiectasisBiochemistryEcologyLung

Abstract

fetched live from OpenAlex

Primary Ciliary Dyskinesia (PCD) is predominantly an autosomal recessive disease that reduces normal cilia movement and impairs the mucociliary escalator leading to lung disease. Nasal brush biopsy samples often contain high levels of mucous that can interfere with ciliary beat frequency (CBF) and ciliary beat pattern (CBP). These secondary changes can hinder diagnostic testing for PCD using high-speed video analysis. To determine if DTT treatment reduced the effect of mucus overlying the respiratory epithelium on ciliary function (CBP and CBF). 5 Nasal brush biopsies from non-PCD subjects were taken and ciliated epithelium was resuspended in M199 with or without 10mM DTT. High speed video microscopy (HSVM) was used to determine the ciliary function and mucous. Samples that contained well-ciliated epithelium and mucous, that was unable to be cleared, were chosen for DTT treatment. DTT was added for 30 minutes and HSVM performed at 37°C. Movies were replayed in slow motion and CBF and CBP (% dyskinetic cilia) were determined. Total number of edges studied was 60, and the number of readings taken for evaluation of CBP and CBF was 246. DTT significantly (p<0.05) improved the CBP (dyskinetic cilia 84±8 cf 33±4%). CBF was not significantly (p>0.05) changed by DTT treatment (9.6±4 cf 10.6±0.6Hz). The effect of DTT treatment on cilia structure and epithelial histopathology will be presented. DTT is effective for mucous dispersal in ciliated biopsy samples, and in the samples studied, increased the proportion of cilia with a normal beat pattern. We are testing this approach on samples from PCD patients and healthy controls to see if it can improve our PCD diagnostic pathway for resolving mucous-induced dyskinesia.

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 score0.004
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 communication0.0000.000
Open science0.0000.000
Research integrity0.0000.001
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 head0.009
GPT teacher head0.318
Teacher spread0.309 · 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".

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Citations0
Published2024
Admission routes1
Has abstractyes

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