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Record W3215270358 · doi:10.1073/pnas.2111946118

BAP1 forms a trimer with HMGB1 and HDAC1 that modulates gene × environment interaction with asbestos

2021· article· en· W3215270358 on OpenAlexaff
Flavia Novelli, Angela Bononi, Qian Wang, Fang Bai, Simone Patergnani, Franz Kricek, Ellinor Haglund, Joelle Sacks Suarez, Mika Tanji, Ronghui Xu, Yasutaka Takanishi, Michael Minaai, Sandra Pastorino, Paul Morris, G Sakamoto, Harvey I. Pass, Haithem Barbour, Giovanni Gaudino, Carlotta Giorgi, Paolo Pinton, José N. Onuchic, Haining Yang, Michele Carbone

Bibliographic record

VenueProceedings of the National Academy of Sciences · 2021
Typearticle
Languageen
FieldMedicine
TopicOccupational and environmental lung diseases
Canadian institutionsUniversité de Montréal
FundersDivision of ChemistryNational Cancer InstituteUniversità degli Studi di FerraraNational Institute of Environmental Health SciencesFondazione Umberto VeronesiCenter for Theoretical Biological PhysicsGenentechNational Science FoundationAssociazione Italiana per la Ricerca sul CancroWelch FoundationUniversity of Hawaiʻi FoundationAndrew and Jaime Sullivan Family FoundationMinistero della SaluteU.S. Department of Defense
KeywordsAcetylationBAP1Cancer researchMesotheliomaHMGB1HDAC1ChemistryCarcinogenesisHistoneBiologyCell biologyHistone deacetylaseGeneBiochemistryImmunologyMedicineInflammationMelanomaPathology

Abstract

fetched live from OpenAlex

Significance Our findings explain mechanistically the observed gene × environment (G×E) interaction in mesotheliomas occurring in carriers of heterozygous germline BAP1 mutations ( BAP1 +/− ) exposed to asbestos. The increased amount of acetylated HMGB1 can be measured in the serum and may prove useful as a diagnostic/prognostic biomarker of mesothelioma in BAP1 +/− individuals. Inhibition of HMGB1 secretion in Bap1 +/− mutant mice exposed to asbestos significantly decreased the incidence of mesothelioma and prolonged the survival of those who developed mesothelioma. This strategy may be translated to carriers of germline BAP1 mutations with the aim of decreasing their incidence of mesothelioma.

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)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation 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 score0.058
Threshold uncertainty score0.169

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
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 integrity0.0000.000
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 head0.031
GPT teacher head0.274
Teacher spread0.243 · 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

Citations30
Published2021
Admission routes1
Has abstractyes

Explore more

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