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Record W3124312347 · doi:10.1038/s41436-020-01073-x

Cystic fibrosis–related diabetes onset can be predicted using biomarkers measured at birth

2021· article· en· W3124312347 on OpenAlexafffundabout
Yu-Chung Lin, Katherine Keenan, Jiafen Gong, Naim Panjwani, Julie Avolio, Lin Fan, Damien Adam, P. K. M. Barrett, Stéphanie Bégin, Yves Berthiaume, Lara Bilodeau, Candice Bjornson, Janna Brusky, Caroline Burgess, Mark Chilvers, Raquel Consunji‐Araneta, Guillaume Côté-Maurais, Andrea Dale, Christine Donnelly, Lori Fairservice, Katie Griffin, Natalie Henderson, Angela Hillaby, Daniel Hughes, Shaikh Iqbal, Jennifer Itterman, Mary Jackson, Emma Karlsen, Lorna Kosteniuk, Lynda Lazosky, Winnie M. Leung, Valérie Lévesque, Émilie Maillé, Dimas Mateos‐Corral, Vanessa McMahon, Mays Merjaneh, Nancy Morrison, Michael D. Parkins, Jennifer Pike, April Price, Bradley S. Quon, Joe Reisman, C. Smith, Mary Jane Smith, Nathalie Vadeboncoeur, Danny Veniott, Terry Viczko, Pearce Wilcox, Richard van Wylick, Garry R. Cutting, Elizabeth Tullis, Félix Ratjen, Johanna M. Rommens, Lei Sun, Melinda Solomon, Anne L. Stephenson, Emmanuelle Brochiero, Scott M. Blackman, Harriet Corvol, Lisa J. Strug

Bibliographic record

VenueGenetics in Medicine · 2021
Typearticle
Languageen
FieldMedicine
TopicCystic Fibrosis Research Advances
Canadian institutionsSickKids FoundationSt Mary's Hospital CentreJaneway Children's Health and Rehabilitation CentreFoothills Medical CentreUniversity of Alberta HospitalAlberta Hospital EdmontonKingston Health Sciences CentreSt. Michael's HospitalSt. Paul's HospitalIzaak Walton Killam Health CentreAlberta Children's HospitalInstitut universitaire de cardiologie et de pneumologie de QuébecChildren's Hospital of Eastern OntarioChildren's Hospital of Western OntarioQueen Elizabeth II Health Sciences CentreBC Children's HospitalUniversité LavalHospital for Sick ChildrenUniversité de MontréalChildren's Hospital of WinnipegPublic Health OntarioRoyal University HospitalUniversity of Toronto
FundersCanadian Institutes of Health Research
KeywordsCystic fibrosisCystic fibrosis-related diabetesCystic fibrosis transmembrane conductance regulatorMedicineDiabetes mellitusInternal medicineGenome-wide association studyBioinformaticsGeneEndocrinologyGenotypeType 2 diabetesBiologyGeneticsImpaired glucose toleranceSingle-nucleotide polymorphism

Abstract

fetched live from OpenAlex

PURPOSE: Cystic fibrosis (CF), caused by pathogenic variants in the CF transmembrane conductance regulator (CFTR), affects multiple organs including the exocrine pancreas, which is a causal contributor to cystic fibrosis-related diabetes (CFRD). Untreated CFRD causes increased CF-related mortality whereas early detection can improve outcomes. METHODS: Using genetic and easily accessible clinical measures available at birth, we constructed a CFRD prediction model using the Canadian CF Gene Modifier Study (CGS; n = 1,958) and validated it in the French CF Gene Modifier Study (FGMS; n = 1,003). We investigated genetic variants shown to associate with CF disease severity across multiple organs in genome-wide association studies. RESULTS: The strongest predictors included sex, CFTR severity score, and several genetic variants including one annotated to PRSS1, which encodes cationic trypsinogen. The final model defined in the CGS shows excellent agreement when validated on the FGMS, and the risk classifier shows slightly better performance at predicting CFRD risk later in life in both studies. CONCLUSION: We demonstrated clinical utility by comparing CFRD prevalence rates between the top 10% of individuals with the highest risk and the bottom 10% with the lowest risk. A web-based application was developed to provide practitioners with patient-specific CFRD risk to guide CFRD monitoring and treatment.

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)0.005
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow), Insufficient payload (model declined to judge)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.545
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.005
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.002
Science and technology studies0.0000.001
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
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 head0.032
GPT teacher head0.315
Teacher spread0.283 · 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.

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".

Quick stats

Citations30
Published2021
Admission routes3
Has abstractyes

Explore more

Same venueGenetics in MedicineSame topicCystic Fibrosis Research AdvancesFrench-language works237,207