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Record W2883740762 · doi:10.1164/rccm.201802-0338le

Ataluren, a New Therapeutic for Alpha-1 Antitrypsin–Deficient Individuals with Nonsense Mutations

2018· letter· en· W2883740762 on OpenAlexaff
Emer P. Reeves, Ciara A. O’Dwyer, Danielle M. Dunlea, Mark R. Wormald, Padraig Hawkins, Mohammed Alfares, Darrell N. Kotton, Steven M. Rowe, Andrew A. Wilson, Noel G. McElvaney

Bibliographic record

VenueAmerican Journal of Respiratory and Critical Care Medicine · 2018
Typeletter
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicProtease and Inhibitor Mechanisms
Canadian institutionsSickKids FoundationHospital for Sick ChildrenUniversity of TorontoSt. Michael's Hospital
FundersNational Center for Advancing Translational SciencesNational Institute of Diabetes and Digestive and Kidney DiseasesNational Heart, Lung, and Blood InstituteRoyal College of Surgeons in IrelandMedical Research Charities GroupSchool of Medicine, Boston UniversityNational Institutes of HealthAlpha-1 Foundation
KeywordsMedicineNonsenseNonsense mutationAlpha (finance)Alpha 1-antitrypsin deficiencyGeneticsMutationInternal medicineGeneSurgeryMissense mutation

Abstract

fetched live from OpenAlex

Figure 1).This injurious inflation pattern is known to cause overstretch and tidal recruitment in dependent, atelectatic lung, and thereby worsen dependent lung injury (7-9).Reverse triggering increased dependent lung stretch equivalent to that applied by VT of up to 15 ml/kg during muscle paralysis, despite a constant VT (Figure 2).Second, the magnitude of negative swing in Pes during reverse triggering is proportional to the local lung stretch in dependent lung, reflecting greater propensity to injury.Monitoring Pes or electrical activity of diaphragm could contribute in two ways.Each of these modalities increases the recognition of reverse triggering, and they quantify the magnitude of inspiratory muscle force during reverse triggering.Although reverse triggering associated with breath stacking is readily detected, in the absence of breath stacking it is likely to be unnoticed by clinicians relying on standard waveforms (e.g., airway pressure and flow).In addition, it will be underestimated when VT is controlled (4).Reverse triggering occurs in deeply sedated patients, a scenario in which clinicians consider the risk for asynchrony to be minimal (4), in contrast to easily detected vigorous effort, which is widely recognized to be harmful (2, 10).Thus, sedation may reduce harm from vigorous effort but increase the incidence of subtle and unsuspected reverse triggering.Finally, estimation of inspiratory muscle force during reverse triggering may be important to decrease dependent lung stretch and potentially lessen injury.It is uncertain whether the inflation pattern associated with reverse triggering is also observed with other ventilator modes.In conclusion, during reverse triggering, injurious inflation occurred in dependent lung despite the constant overall VT, and dependent lung stretch was proportional to the negative deflection in Pes.Early recognition of reverse triggering may be beneficial.

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: Not applicable · Consensus signal: none
GenreCandidate signal: Commentary · Consensus signal: none
Teacher disagreement score0.007
Threshold uncertainty score0.023

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 studies0.0000.000
Scholarly communication0.0000.000
Open science0.0010.000
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0070.003

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 head0.020
GPT teacher head0.307
Teacher spread0.287 · 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 designNot applicable
Domainnot available
GenreCommentary

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

Citations8
Published2018
Admission routes1
Has abstractyes

Explore more

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