BUSCADOR RECOLECTA

[EN] It contains a collection of .csv files by country and a netCDF file. Last one need specific data analyse software. [ES] Contiene una colección de archivos .csv por país y un archivo netCDF. Este último necesita software de análisis de datos específico., [EN] This database includes the representative Standardized Precipitation Evapotranspiration Index (SPEI) series for the different countries of the world from 1901 at the time scales from 1 to 48 months. The data is based on the average precipitation and reference evapotranspiration series from the Climatic Research Unit (last version) for the different world countries., [ES] Esta base de datos incluye la serie representativa del Índice Estandarizado de Precipitación y Evapotranspiración (SPEI) para los diferentes países del mundo desde 1901 en las escalas de tiempo de 1 a 48 meses. Los datos se basan en las series de precipitación media y evapotranspiración de referencia de la Unidad de Investigación Climática (última versión) para los diferentes países del mundo., Peer reviewed

S2 Fig. EDEM-1 and EDEM-2 are required for CPL-1* degradation (A) Fluorescence intensities of WT animals carrying the CPL-1* transgene treated with indicated concentrations of kifunensine. Values in scatter gram represent mean fluorescence/µm2 x 1000 in arbitrary units (AU). The red bars indicate the average ±SEM. ****P<0.0001; one way ANOVA with Dunnett post test. (B) Immunoblot analysis of CPL-1* degradation in edem-1 and edem-2 mutants carrying the rescuing EDEM-1::mCherry and EDEM-2::mCherry transgenes, respectively. Total protein lysates derived from edem-1 and edem-2 mutants carrying the CPL-1* and rescuing transgenes were separated by SDS-PAGE and immunoblotted with anti-GFP polyclonal antisera. Tubulin was used as loading control. (C) Histogram showing the densitometry values of the bands presented in (B) normalized to the value of WT condition (n=3 ± SEM, one way ANOVA with Fisher test), *P<0.05; **P<0.01)., Peer reviewed

S3 Fig. EDEM depletion mitigates ER stress. (A) Representative confocal images of WT(EV) control or indicated RNAi depleted young adults carrying the Phsp-4::GFP transgene under non ER-stress conditions (upper panel), treatment with 5 μg/ml tunicamycin for 12h (middle panel), and heat shock, and 5 μM thapsigargin treatment (lower panel). TM-tunicamycin, HS-heat shock, TG-thapsigargin. The worms were outlined for better visualization. Images were obtained using the same confocal settings. Exposure adjustments were uniformly applied. Scale bar: 50 μm. (B) Quantitative RT-PCR measurements of Phsp-4::mRNA levels in indicated strains under non stress and treatment with 5 μg/ml tunicamycin (n = 3 independent experiments). (C) Quantitative RT-PCR measurements of Phsp-4::mRNA levels in indicated strains under non stress and heat stress treatment (n = 3 independent experiments). In (B) and (C) quantifications were normalized relative to WT non stress conditions. ****P<0.0001, ns, not significant. Quantifications were normalized relative to WT non stress conditions. (D) Representative confocal images of WT control and edem-2 mutants carrying the PC12C8.1::GFP transgene under non ER-stress conditions. The left panels show fluorescence images and the right panels DIC images., Peer reviewed

S4 Fig. edem response to thapsigargin. (A) Quantitative RT-PCR measurements of edem mRNA levels in WT young animals under non stress (NS) and treatment with 5 μM thapsigargin (TG), (n = 3 independent experiments). (B) Percentage of eggs that developed into L4 larvae after 3 days on 10 μM thapsigargin. Each strain was scored in three independent experiments in triplicates. (C) Quantification of WT (EV) or RNAi-treated day one adults carrying Phsp-4::GFP transgene, treated or not with 5 μM thapsigargin. The worms were kept on RNAi plates for one generation before exposure to ER stress treatments. Values represent mean fluorescence/µm2 x 1000. The red bars indicate the average ±SEM. (D) Analysis of xbp-1 spliced/unspliced ratio from young adults of indicated strains. Total RNA was isolated, reverse transcribed and used for PCR analysis of xbp-1 splicing forms., Peer reviewed

S1 Table. Strains used in this study., Peer reviewed

S2 Table. Primers used in this study., Peer reviewed

Additional file 9: Movie S5. Oscillations in D. Melanogaster basal follicle cells. Experimental conditions. Time-lapse movie of the D. Melanogaster basal follicle cells stained with Lifeact-GFP in conditions of over-expression of the two subunits of the integrin molecule., Ministerio de Ciencia, Innovación y Universidades, Peer reviewed

S3 Table. Raw numerical data of all the figures., Peer reviewed

Table S1. Treatment allocation based on the molecular profile. Table S2. Median PFS and OS and parameters for exponential extrapolation. Table S3. Dosage and estimated monthly costs of the treatments included in the analysis. References only cited in the supplementary material., To assess the cost-effectiveness of using next-generation sequencing (NGS) compared to sequential single-testing (SST) for molecular diagnostic and treatment of patients with advanced non-small cell lung cancer (NSCLC) from a Spanish single-center perspective, the Hospital Universitario Virgen del Rocio (HUVR). A decision-tree model was developed to assess the alterations detection alterations and diagnostic cost in patients with advanced NSCLC, comparing NGS versus SST. Model inputs such as testing, positivity rates, or treatment allocation were obtained from the literature and the clinical practice of HUVR experts through consultation. Several sensitivity analyses were performed to test the robustness of the model. Using NGS for molecular diagnosis of a 100-patients hypothetical cohort, 30 more alterations could be detected and 3 more patients could be enrolled in clinical-trials than using SST. On the other hand, diagnostic costs were increased up to €20,072 using NGS instead of SST. Using NGS time-to-results would be reduced from 16.7 to 9 days. The implementation of NGS at HUVR for the diagnostic of patients with advanced NSCLC provides significant clinical benefits compared to SST in terms of alterations detected, treatment with targeted-therapies and clinical-trial enrollment, and could be considered a cost-effective strategy., This work was funded by Roche Farma S.A., Peer reviewed

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