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Record W4283072735 · doi:10.1186/s13023-022-02359-w

Clinical and genetic profile of patients enrolled in the Transthyretin Amyloidosis Outcomes Survey (THAOS): 14-year update

2022· article· en· W4283072735 on OpenAlexaff
Angela Dispenzieri, Teresa Coelho, Isabel Conceição, Márcia Waddington‐Cruz, Jonas Wixner, Arnt V. Kristen, Claudio Rapezzi, Violaine Planté‐Bordeneuve, Juan González‐Moreno, Mathew S. Maurer, Martha Grogan, Doug Chapman, Leslie Amass, Pablo García Pavía, Ivaylo Tarnev, José González‐Costello, Maria Alejandra Gonzalez Duarte Briseno, Hartmut Schmidt, Brian Drachman, Fábio Barroso, Taro Yamashita, Olivier Lairez, Yoshiki Sekijima, Giuseppe Vita, Eun‐Seok Jeon, Mazen Hanna, David Slosky, Marco Luigetti, Samantha LoRusso, Francisco Muñoz Beamud, David Adams, H. Moelgaard, Rayomand Press, Calogero Lino Cirami, Hans Nienhuis, Josep Maria Campistol Plana, Jocelyn Inamo, Daniel Jacoby, Michele Emdin, Dianna Quan, Scott L. Hummel, Ronald Witteles, Amir Dori, Sanjiv J. Shah, Daniel J. Lenihan, Olga Azevedo, Srinivas Murali, Saša Živković, Soon-Chai Low, José Nativi-Nicolau, Nowell M. Fine, José Tallaj, Carsten Tschöepe, Roberto Fernández‐Torrón, Michael Polydefkis, Giampaolo Merlini, Sorina Bădeliță, Stephen S. Gottlieb, James M. Tauras, Edileide Barros Correia, Hector Ventura, Burkhard Gess, Felix Darstein, Jeeyoung Oh, Tessa Marburger, Johan Van Cleemput, Valeria Salutto, Yeşim Parman, Chi‐Chao Chao, Nitasha Sarswat, Christopher R. Mueller, D. Eric Steidley, Jeffrey Ralph, Alberta L. Warner, William Cotts, James E. Hoffman, Marcelo Rugiero, Sonoko Misawa, J.L. Muñoz Blanco, Lucía Galán Dávila, Menachem Sadeh, Jin Luo, Theodoros Kyriakides, Annabel Wang, Horacio Kaufmann

Bibliographic record

VenueOrphanet Journal of Rare Diseases · 2022
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicAmyloidosis: Diagnosis, Treatment, Outcomes
Canadian institutionsFoothills Medical CentreUniversity of Alberta
FundersPfizer
KeywordsTransthyretinAmyloidosisHuman geneticsMedicineGenetic testingInternal medicinePediatricsBioinformaticsGeneticsBiologyGene

Abstract

fetched live from OpenAlex

BACKGROUND: Transthyretin amyloidosis (ATTR amyloidosis) is a rare, life-threatening disease caused by the accumulation of variant or wild-type (ATTRwt amyloidosis) transthyretin amyloid fibrils in the heart, peripheral nerves, and other tissues and organs. METHODS: Established in 2007, the Transthyretin Amyloidosis Outcomes Survey (THAOS) is the largest ongoing, global, longitudinal observational study of patients with ATTR amyloidosis, including both inherited and wild-type disease, and asymptomatic carriers of pathogenic TTR mutations. This descriptive analysis examines baseline characteristics of symptomatic patients and asymptomatic gene carriers enrolled in THAOS since its inception in 2007 (data cutoff: August 1, 2021). RESULTS: This analysis included 3779 symptomatic patients and 1830 asymptomatic gene carriers. Symptomatic patients were predominantly male (71.4%) and had a mean (standard deviation [SD]) age of symptom onset of 56.3 (17.8) years. Val30Met was the most common genotype in symptomatic patients in South America (80.9%), Europe (55.4%), and Asia (50.5%), and more patients had early- versus late-onset disease in these regions. The majority of symptomatic patients in North America (58.8%) had ATTRwt amyloidosis. The overall distribution of phenotypes in symptomatic patients was predominantly cardiac (40.7%), predominantly neurologic (40.1%), mixed (16.6%), and no phenotype (2.5%). In asymptomatic gene carriers, mean (SD) age at enrollment was 42.4 (15.7) years, 42.4% were male, and 73.2% carried the Val30Met mutation. CONCLUSIONS: This 14-year global overview of THAOS in over 5000 patients represents the largest analysis of ATTR amyloidosis to date and highlights the genotypic and phenotypic heterogeneity of the disease. CLINICALTRIALS: gov Identifier: NCT00628745.

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)0.001
metaresearch head score (Gemma)0.003
Version: metacan-v3-hybrid-931329e0061cValidation 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 score0.006
Threshold uncertainty score0.013

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.003
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0030.004
Science and technology studies0.0000.000
Scholarly communication0.0010.001
Open science0.0010.000
Research integrity0.0010.000
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 head0.013
GPT teacher head0.280
Teacher spread0.267 · 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 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

Citations89
Published2022
Admission routes1
Has abstractyes

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