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Record W3179667220 · doi:10.1038/s41698-021-00178-z

TCERG1L allelic variation is associated with cisplatin-induced hearing loss in childhood cancer, a PanCareLIFE study

2021· article· en· W3179667220 on OpenAlexafffund
Annelot J. M. Meijer, Franciscus A. Diepstraten, Thorsten Langer, Linda Broer, Ivan K. Domingo, Eva Clemens, André G. Uitterlinden, Andrica C. H. de Vries, Martine van Grotel, Wilbert P. Vermeij, Rutger A. Ozinga, Harald Binder, Julianne Byrne, Eline van Dulmen‐den Broeder, Maria Luisa Garrè, Desiree Grabow, Peter Kaatsch, Melanie Kaiser, Line Kenborg, Jeanette Falck Winther, Catherine Rechnitzer, Henrik Hasle, Tomáš Kepák, Kateřina Kepáková, Wim J. E. Tissing, Anne-Lotte van der Kooi, Leontien C.M. Kremer, Jarmila Kruseová, Saskia M.F. Pluijm, Claudia E. Kuehni, Helena J. H. van der Pal, Ross Parfitt, Claudia Spix, Amélie Tillmanns, Dirk Deuster, Peter Matulat, Gabriele Calaminus, Alex E. Hoetink, Susanne Elsner, Judith Gebauer, Riccardo Haupt, Herwig Lackner, Claudia Blattmann, Sebastian Neggers, Shahrad R. Rassekh, Galen E.B. Wright, Beth Brooks, A. Paul Nagtegaal, Britt I. Drögemöller, Colin J.D. Ross, Amit P. Bhavsar, Antoinette Gertrud am Zehnhoff-Dinnesen, Bruce Carleton, Oliver Zolk, Marry M. van den Heuvel‐Eibrink

Bibliographic record

Venuenpj Precision Oncology · 2021
Typearticle
Languageen
FieldNeuroscience
TopicHearing, Cochlea, Tinnitus, Genetics
Canadian institutionsBC Children's HospitalUniversity of British ColumbiaUniversity of Alberta
FundersCanadian Institutes of Health ResearchMedizinische Universität GrazHospital for Sick ChildrenUniversität UlmUniversitair Medisch Centrum GroningenIWK Health CentreUniversity of AlbertaAmsterdam University Medical CentersErasmus Medisch CentrumChildren's Hospital FoundationUniversitätsmedizin der Johannes Gutenberg-Universität MainzKarl-Franzens-Universität GrazStollery Children’s Hospital FoundationCanada Research ChairsChildren's Health Research InstituteWestfälische Wilhelms-Universität MünsterUniversität zu LübeckWomen and Children's Health Research InstituteUniversiteit van AmsterdamBC Children's HospitalUniversity of BernEuropean CommissionLondon Health Sciences Centre
KeywordsOtotoxicityCisplatinHearing lossGenome-wide association studyAlleleCancerOncologyGenetic variationPhenotypeCohortBiologyGenetic predispositionToxicityGeneticsMedicineCancer researchInternal medicineGeneSingle-nucleotide polymorphismGenotypeChemotherapyAudiology

Abstract

fetched live from OpenAlex

Abstract In children with cancer, the heterogeneity in ototoxicity occurrence after similar treatment suggests a role for genetic susceptibility. Using a genome-wide association study (GWAS) approach, we identified a genetic variant in TCERG1L (rs893507) to be associated with hearing loss in 390 non-cranial irradiated, cisplatin-treated children with cancer. These results were replicated in two independent, similarly treated cohorts (n = 192 and 188, respectively) (combined cohort: P = 5.3 × 10−10, OR 3.11, 95% CI 2.2–4.5). Modulating TCERG1L expression in cultured human cells revealed significantly altered cellular responses to cisplatin-induced cytokine secretion and toxicity. These results contribute to insights into the genetic and pathophysiological basis of cisplatin-induced ototoxicity.

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)0.001
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 score0.008
Threshold uncertainty score0.017

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0020.000

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 head0.074
GPT teacher head0.357
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 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

Citations22
Published2021
Admission routes2
Has abstractyes

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