HB patients GENOMIC STUDY TRANSCRIPTOMIC STUDY METHYLATION STUDY CytoScan HD ®-array RNA-sequencing/ ddPCR HTA ®-array/ RT-qPCR 850K (EPIC)-array/ QUAlu Dysregulation of global RNA & BLCAP editing Overexpression of 14q32 DLK1-DIO3 genes 16 + VIM-gene signature (C1/C2/C2B) 2 epigenomic HB subtypes (Epi-CA & Epi-CB) CLINICAL PARAMETERS: prognostic marker identification Poor prognostic factors:-4q,-18, 17q11.2 AI (NF1) CHKA new therapeutic target Molecular risk stratification MRS1 MRS2 MRS3 Strong 14q32 Epi-CB Time Survival Highlights Hepatoblastoma (HB) involves global dysregulation of RNA editing, including in the tumor suppressor BLCAP. Overexpression of a 300 kb region within the 14q32 DLK1/DIO3 locus is a new hallmark of HB. We identified 2 epigenomic HB subtypes-Epi-CA and Epi-CB-with distinct degrees of DNA hypomethylation and CpG island hypermethylation. The molecular risk stratification of HB, based on the 14q32-signature and epigenomic subtypes, is associated with patient outcomes. The enzyme CHKA could be a novel therapeutic target for patients with HB.

Two versions of the “reliability ensemble averaging” (REA and REA Xu) method and an unweighted mean were used to generate multi‐model ensembles of 14 general circulation models (GCMs) from the Coupled Model Intercomparison Project Phase 5 (CMIP5) for a baseline (1971–2000) period and future scenarios (RCP4.5 and RCP8.5) for the 21st century. To test the consistency of the REA ensembles at different scales, one ensemble was area‐averaged at regional scale and two were obtained at 50‐km gridpoints. Climatic metrics of temperature and precipitation during the baseline period served to evaluate the performance of the GCMs and the ensembles in the North American monsoon (NAM) and the mid‐summer drought (MSD) regions. The metrics of the three REA ensembles are very similar among them in each region and show a better performance than the unweighted multi‐model ensemble (U‐MME). The majority of the GCMs overestimate winter precipitation in the NAM and fail to retract the end of the monsoon in autumn; REA ensembles reduce this overestimation. All ensembles capture well the MSD's double peak of rainfall, but underestimate summer precipitation. According to all ensembles, temperature increases of 1.5–2 °C in the two regions may be reached between 2035 and 2055 relative to the baseline, and by 2070–2099 temperature (precipitation) in Mexico may increase (decrease) between 2° C (5%) and 5.8 °C (10%) in the RCP4.5 and RCP8.5 scenarios, respectively. Annual changes of precipitation show a north (positive) and south of 35°N (negative) pattern. The largest impacts are expected during summer with a possible decrease of ~13% (up to −1.5 mm/day), especially in southern Mexico, Central America, and the Caribbean, while autumn precipitation may slightly increase. Future projections from the REA Xu (by gridpoint) ensemble show spatial patterns similar to the U‐MME, but with more regional detail, which could be an added value for regional climate impact studies.

The registry provides data about the prevalence of hemoglobinopathies in Spain and will permit future cohort studies and the possibility of comparison with other registries.

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