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Record W4405182603 · doi:10.1136/jmg-2024-110251

Aortic and arterial manifestations and clinical features in <i>TGFB3</i>-related heritable thoracic aortic disease: results from the Montalcino Aortic Consortium

2024· article· en· W4405182603 on OpenAlexafffund
M. Lim, Dongchuan Guo, Walter Velasco Torrez, Andrew Lai, Jonathan Schweber, Nikita Garg, Julie Fleischer, Cathérine Boileau, Julie De Backer, Artur Evangelista, Guillaume Jondeau, Carine Le Goff, Olivier Milleron, Laura Muiño Mosquera, Shaine A. Morris, Maral Ouzounian, Elena Cervi, Julien Marcadier, Anthony Caffarelli, Sherene Shalhub, Reed E. Pyeritz, Angela Yetman, Dianna M. Milewicz, Alan C. Braverman

Bibliographic record

VenueJournal of Medical Genetics · 2024
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicConnective tissue disorders research
Canadian institutionsAlberta Children's HospitalUniversity of TorontoHospital for Sick Children
FundersTemerty Family Foundation
KeywordsMedicineAortic dissectionBicuspid aortic valveCardiologyInternal medicineAortic aneurysmThoracic aortic aneurysmInterquartile rangeCohortAortaSurgery

Abstract

fetched live from OpenAlex

Background Pathogenic variants in TGFB3 may lead to a syndromic genetic aortopathy. Heritable thoracic aortic disease (HTAD) and arterial events may occur in TGFB3 -related disease but there are limited outcomes data on vascular events in this condition. Methods Clinical data, phenotypical features and aortic outcomes in individuals with pathogenic/likely pathogenic (P/LP) TGFB3 variants enrolled in the Montalcino Aortic Consortium registry were reviewed. Results 34 individuals (56% male, median age 42 years, IQR 17–49, range 3–74 years) with P/LP TGFB3 variants were studied. Craniofacial, cutaneous and musculoskeletal features seen in Loeys-Dietz syndrome were variably present. Extra-aortic cardiovascular features included arterial tortuosity (25%), extra-aortic arterial aneurysms (6%) and mitral valve prolapse (21%). Aortic dilation (Z-Score&gt;2) was present in 10 individuals (29%) and aortic dissection occurred in 2 (6%). Type A aortic dissection occurred in two patients (aged between 55 years and 60 years), and one of these patients experienced a type B aortic dissection 6 years later. Seven adults (median age 62 years, range 32–69 years) with aortic root dilation (41–49 mm) are being followed. No patients have undergone prophylactic aortic surgery. Twenty-five per cent of children have aortic dilation. Sixty-eight per cent of the entire cohort remains free of aortic disease. No deaths have occurred. Conclusions TGFB3 -related HTAD is characterised by late-onset and less penetrant thoracic aortic and arterial disease compared with other transforming growth factor β HTAD. Based on our data, a larger aortic size threshold for prophylactic aortic surgery is appropriate in patients with TGFB3 -related HTAD compared with HTAD due to TGFBR1 or TGFBR2 variants.

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)0.001
metaresearch head score (Gemma)0.003
Version: codex-gemma-dda1882f352aValidation 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 score0.627
Threshold uncertainty score0.432

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.003
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)0.0000.000

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 head0.020
GPT teacher head0.372
Teacher spread0.352 · 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

Citations9
Published2024
Admission routes2
Has abstractyes

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