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Management of hepatoblastoma (HB), the most frequent pediatric liver cancer, is based on surgical resection and perioperative chemotherapy regimens. In this study, we aimed to identify actionable targets in HB and assess the efficacy of molecular therapies in preclinical models of HB. Paired tumor and adjacent tissues from 31 HBs and a validation set of 50 HBs were analyzed using RNA-seq, SNP, and methylation arrays. IGF2 overexpression was identified as the top targetable HB driver, present in 71% of HBs (22/31). IGF2high tumors displayed progenitor cell features and shorter recurrence-free survival. IGF2 overexpression was associated in 91% of cases with fetal promoter hypomethylation, ICR1 deregulation, 11p15.5 loss of heterozygosity or miR483-5p overexpression. The antitumor effect of xentuzumab (a monoclonal antibody targeting IGF1/2) alone or in combination with the conventional therapeutic agent cisplatin was assessed in HB cell lines, in PDX-derived HB organoids and in a xenograft HB murine model. The combination of xentuzumab with cisplatin showed strong synergistic antitumor effects in organoids and in IGF2high cell lines. In mice (n = 55), the combination induced a significant decrease in tumor volume and improved survival compared with cisplatin alone. These results suggest that IGF2 is an HB actionable driver and that, in preclinical models of HB, the combination of IGF1/2 inhibition with cisplatin induces superior antitumor effects than cisplatin monotherapy. Overall, our study provides a rationale for testing IGF2 inhibitors in combination with cisplatin in HB patients with IGF2 overexpression.

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Management of hepatoblastoma (HB), the most frequent pediatric liver cancer, is based on surgical resection and perioperative chemotherapy regimens. In this study, we aimed to identify actionable targets in HB and assess the efficacy of molecular therapies in preclinical models of HB. Paired tumor and adjacent tissues from 31 HBs and a validation set of 50 HBs were analyzed using RNA-seq, SNP, and methylation arrays. IGF2 overexpression was identified as the top targetable HB driver, present in 71% of HBs (22/31). IGF2high tumors displayed progenitor cell features and shorter recurrence-free survival. IGF2 overexpression was associated in 91% of cases with fetal promoter hypomethylation, ICR1 deregulation, 11p15.5 loss of heterozygosity or miR483-5p overexpression. The antitumor effect of xentuzumab (a monoclonal antibody targeting IGF1/2) alone or in combination with the conventional therapeutic agent cisplatin was assessed in HB cell lines, in PDX-derived HB organoids and in a xenograft HB murine model. The combination of xentuzumab with cisplatin showed strong synergistic antitumor effects in organoids and in IGF2high cell lines. In mice (n = 55), the combination induced a significant decrease in tumor volume and improved survival compared with cisplatin alone. These results suggest that IGF2 is an HB actionable driver and that, in preclinical models of HB, the combination of IGF1/2 inhibition with cisplatin induces superior antitumor effects than cisplatin monotherapy. Overall, our study provides a rationale for testing IGF2 inhibitors in combination with cisplatin in HB patients with IGF2 overexpression.

To enrich spatio-temporal information on the distribution of alien, cryptogenic, and neonative species in the Mediterranean and the Black Sea, a collective effort by 173 marine scientists was made to provide unpublished records and make them open access to the scientific community. Through this effort, we collected and harmonized a dataset of 12, 649 records. It includes 247 taxa, of which 217 are Animalia, 25 Plantae and 5 Chromista, from 23 countries surrounding the Mediterranean and the Black Sea. Chordata was the most abundant taxonomic group, followed by Arthropoda, Mollusca, and Annelida. In terms of species records, Siganus luridus, Siganus rivulatus, Saurida lessepsianus, Pterois miles, Upeneus moluccensis, Charybdis (Archias) longicollis, and Caulerpa cylindracea were the most numerous. The temporal distribution of the records ranges from 1973 to 2022, with 44% of the records in 2020–2021. Lethrinus borbonicus is reported for the first time in the Mediterranean Sea, while Pomatoschistus quagga, Caulerpa cylindracea, Grateloupia turuturu, and Misophria pallida are first records for the Black Sea ; Kapraunia schneideri is recorded for the second time in the Mediterranean and for the first time in Israel ; Prionospio depauperata and Pseudonereis anomala are reported for the first time from the Sea of Marmara. Many first country records are also included, namely: Amathia verticillata (Montenegro), Ampithoe valida (Italy), Antithamnion amphigeneum (Greece), Clavelina oblonga (Tunisia and Slovenia), Dendostrea cf. folium (Syria), Epinephelus fasciatus (Tunisia), Ganonema farinosum (Montenegro), Macrorhynchia philippina (Tunisia), Marenzelleria neglecta (Romania), Paratapes textilis (Tunisia), and Botrylloides diegensis (Tunisia).

Childhood liver cancers hepatoblastoma (HB) and hepatocellular carcinoma (HCC) are rare diseases but with a rising incidence. HEMNOS (Hepatocellular malignant neoplasm, not otherwise specified) is a recent entity with histopathological features of HB and HCC. Current chemotherapy treatments are effective to shrink tumor before surgery, nonetheless can cause severe lifelong adverse effects and are not effective for patients with aggressive and metastatic HB or HCC (~20% die due to the disease). The HB and HCC diagnosis is key to assign therapeutic regimens in the ongoing Pediatric Hepatic International Tumor Trial (PHITT); however, differential diagnosis for some patients is challenging due to the lack of specific biomarkers. Nowadays, there is an urgent need to identify diagnostic and prognostic biomarkers to improve the clinical management of childhood liver cancer. Herein, we aimed to uncover the proteomic profiles of different types of childhood liver cancer and identify new biomarkers for improving tumor diagnosis and early detection of the most aggressive cases. For this, 99 frozen tissue samples from 71 patients (mean age: 54.5 months, 60.6% boys, 40.9% metastasis, 23.7% deaths) including 70 primary tumors (57 HB, 8 HCC and 5 HEM-NOS), 22 non-tumors and 7 metastases were analyzed by label free mass spectrometry analysis. A total of 5,417 proteins were sequenced in the different samples. Through supervised analysis, we identified a total of 1302 differential expressed proteins in tumors as compared to non-tumor livers (FC +2 and FDR 2) was defined for HB, HCC and HEM-NOS, respectively. Hierarchical unsupervised clustering and principal component analysis showed two main cluster of tumors: one including HB and HEM-NOS and another one with a mixture of HB, HEM-NOS and HCC. Interestingly, this second cluster was associated with clinical and molecular features of aggressive tumors such as multifocality (p = 0.029), Epigenetic Epi-CB subclass (p = 0.006), high-risk Molecular Risk Stratification (p = 0.009) and poor survival (log rank test=0.012). A total of 2082 proteins were found to be differently expressed between the two prognostic clusters (FC +2 and FDR < 0.01); the GEO enrichment analysis revealed that these proteins were significantly enriched in post-transcriptional gene silencing and RNA splicing mechanisms (FDR 6 and FDR < 10−14). In conclusion, we identified a list of potential diagnostic and prognostic protein biomarkers that after a validation in large patient cohort, could be used to improve the clinical management of childhood liver cancer. Citation Format: Álvaro Del Río-Álvarez, Juan Carrillo-Reixach, Laura Royo, Montse Domingo-Sàbat, Mikel Azkargorta, Roland Kapler, Stefano Cairo, Christian Vokuhl, Ronald de Krijger, Rita Alaggio, Marta Garrido, Gabriela Guillen, Constantino Sábado, Laura Guerra, Francisco Hernandez, Maria Elena Mateos, Manuel López-Satamaría, Barbara Torres, Maria Pilar Abad, Bajčiová Viera, Piotr Czauderna, Marie Annick Buendia, Felix Elortza, Keith Wheatley, Bruce Morland, Carolina Armengol. Proteomic profiling of childhood liver cancer: identification of novel diagnostic and prognostic biomarkers [abstract]. In: Proceedings of the AACR Special Conference: Advances in the Pathogenesis and Molecular Therapies of Liver Cancer; 2022 May 5-8; Boston, MA. Philadelphia (PA): AACR; Clin Cancer Res 2022;28(17_Suppl):Abstract nr PO011.

Background and Aims: Management of hepatoblastoma (HB), the most frequent pediatric liver cancer, is based on surgical resection and perioperative chemotherapy regimens, commonly cisplatin. Here, we aimed to identify actionable targets in HB and assess the efficacy of molecular therapies in preclinical models of HB.Methods: Paired tumor and adjacent tissues from 31 resected HBs and a validation set of 50 HBs were analyzed at the transcriptomic, genomic and epigenomic level using RNAseq, SNP and methylation arrays, respectively. The main targetable driver in HB was identified by gene co-expression network analysis (GCN) and its overexpression was confirmed by qRT-PCR. The anti-tumor effect of driver inhibition with molecular therapies alone or in combination with cisplatin was assessed in cell lines, patient-derived HB organoids and in a HB xenograft murine model.Results: Seven network modules were significantly deregulated in tumors compared to non-tumoral samples, including IGF2 signaling pathway, cell cycle and survival and immune response. IGF2 overexpression (FC> 4 vs adjacent tissue) was identified as the top targetable HB driver (study cohort: 71%, 22/31; independent validation cohorts: 78% and 76%). IGF2high tumors displayed progenitor cell features and were significantly enriched in molecular classes with aggressive phenotypes and CTNNB1 mutations, while IGF2low tumors were enriched in inflammatory and TGF-β signaling. IGF2high tumors correlated with shorter recurrence-free survival after resection (median 34 months vs not reached for IGF2low; p = 0.02). IGF2 overexpression correlated in most cases (86%) with fetal promoter hypomethylation (50%), 11p15.5 loss of heterozygosity (LOH, 57%) or overexpression of miR483 (55%). Xentuzumab (anti-IGF1/2 mAb) alone or combined with cisplatin reduced proliferation and clonogenic capacity in IGF2high cell lines. The combination of xentuzumab and cisplatin exhibited synergistic effects in terms of cell viability in organoids derived from IGF2high human HBs. The combination treatment induced apoptosis and reduced IGF2 pathway activation in vitro. In mice (n = 13-14 per arm), this combination induced a significant decrease in the viable tumor volume (p < 0.01), extended survival compared to cisplatin alone (p < 0.05) and inhibited tumor angiogenesis (p < 0.05).Conclusion: IGF2 is an actionable driver in HB and its overexpression was associated with fetal promoter hypomethylation, LOH or miR483 overexpression. The combination of a mAb against IGF1/2 (xentuzumab) with cisplatin led to remarkable anti-tumoral effects in pre-clinical models, providing the rationale for exploring this regimen in IGF2high HB patients. Citation Format: Jordi Abril-Fornaguera, Laura Torrens, Juan Carrillo-Reixach, Alex Rialdi, Ugne Balaseviciute, Júlia Huguet-Pradell, Carla Montironi, Philipp Haber, Álvaro Del Río-Álvarez, Montserrat Domingo-Sàbat, Laura Royo, Nicholas Akers, Catherine E Willoughby, Judit Peix, Miguel Torres-Martin, Marc Puigvehi, Roser Pinyol, Stefano Cairo, Margaret Childs, Rudolf Maibach, Rita Alaggio, Piotr Czauderna, Bruce Morland, Bojan Losic, Vincenzo Mazzaferro, Ernesto Guccione, Daniela Sia, Carolina Armengol, Josep M Llovet. Identification of IGF2 as genomic driver and actionable therapeutic target in hepatoblastoma [abstract]. In: Proceedings of the AACR Special Conference: Advances in the Pathogenesis and Molecular Therapies of Liver Cancer; 2022 May 5-8; Boston, MA. Philadelphia (PA): AACR; Clin Cancer Res 2022;28(17_Suppl):Abstract nr PO009.

Background: The main pediatric liver tumors are hepatoblastoma (HB) and, to a lesser extent, pediatric hepatocellular carcinoma (HCC). HB appears at an early age (8 years) or adolescents and it is usually associated to underlying metabolic diseases. HEM-NOS (Hepatocellular malignant neoplasm, not otherwise specified) is a recent entity with histopathological features of HB and HCC. Due to the rarity of the disease ( Citation Format: Juan Carrillo-Reixach, Álvaro del Río-Álvarez, Laura Royo, Montserrat Domingo-Sàbat, Rita Alaggio, Ronald de Krijger, Christian Vokuhl, Marta Garrido, Laura Guerra, Constantino Sábado, Francisco Hernández, Manuel López-Santamaría, Viera Bajčiová, Rudolf Maibach, Margaret Childs, Piotr Czauderna, Keith Wheatley, Roland Kappler, Stefano Cairo, Bruce Morland, Margarita Sala, Maria Rosa Sarrias, Carolina Armengol. Molecular characterization of pediatric hepatocellular carcinoma: genomic, methylomic and transcriptomic analysis [abstract]. In: Proceedings of the AACR Special Conference: Advances in the Pathogenesis and Molecular Therapies of Liver Cancer; 2022 May 5-8; Boston, MA. Philadelphia (PA): AACR; Clin Cancer Res 2022;28(17_Suppl):Abstract nr PO010.

Background and Aims: Management of hepatoblastoma (HB), the most frequent pediatric liver cancer, is based on surgical resection and perioperative platin-based regimens, commonly cisplatin. Here, we aimed to identify actionable targets in HB and assess the efficacy of molecular therapies in HB cell lines, organoids and murine models. Methods: Paired tumor and adjacent tissues from 31 resected HBs and a validation set of 50 HBs were analyzed at the transcriptomic, genomic and epigenomic level using RNAseq, SNP and methylation arrays, respectively. The main targetable driver in HB was identified by gene co-expression network analysis (GCN) and its overexpression was confirmed by qRT-PCR. The anti-tumor effect of driver inhibition with molecular therapies alone or in combination with cisplatin was assessed in cell lines, patient-derived HB organoids and in a HB xenograft murine model. Results: IGF2 overexpression (FC> 4 vs adjacent tissue) was identified as the top targetable HB driver (71%, 22/31). IGF2high tumors displayed progenitor cell features and were significantly enriched in molecular classes with aggressive phenotypes and CTNNB1 mutations, while IGF2low tumors were enriched in inflammatory and TGF-β signaling. IGF2high tumors correlated with shorter recurrence-free survival after resection (median 34 months vs not reached for IGF2low; p = 0.02). IGF2 overexpression correlated in most cases (86%) with fetal promoter hypomethylation (50%), 11p15.5 loss of heterozygosity (LOH, 57%) or overexpression of miR483 (55%). Xentuzumab (anti-IGF1/2 mAb) alone or combined with cisplatin reduced proliferation and clonogenic capacity in IGF2high cell lines. The combination of xentuzumab and cisplatin exhibited synergistic effects in terms of cell viability in organoids derived from IGF2high human HBs. In mice, this combination induced a significant decrease in the viable tumor volume and extended survival compared to cisplatin alone (n = 13-14 per arm, p = 0.04). Conclusion: IGF2 is an actionable driver in HB and its overexpression was associated with fetal promoter hypomethylation, LOH or miR483 overexpression. The combination of a mAb against IGF1/2 (xentuzumab) with cisplatin led to remarkable anti-tumoral effects in pre-clinical models, providing the rationale for exploring this regimen in IGF2high HB patients. Citation Format: Jordi Abril-Fornaguera, Laura Torrens, Juan Carrillo-Reixach, Alexander Rialdi, Ugne Balaseviciute, Carla Montironi, Philipp Haber, Álvaro Del Río-Álvarez, Montserrat Domingo-Sàbat, Laura Royo, Nicholas Akers, Catherine E. Willoughby, Judit Peix, Miguel Torres-Martin, Marc Puigvehi, Roser Pinyol, Stefano Cairo, Margaret Childs, Rudolf Maibach, Rita Alaggio, Piotr Czauderna, Bruce Morland, Bojan Losic, Vincenzo Mazzaferro, Ernesto Guccione, Daniela Sia, Carolina Armengol, Josep M. Llovet. Identification of IGF2 as genomic driver and actionable therapeutic target in hepatoblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 4005.

Este artículo contiene 13 páginas, 5 figutas, 3 tablas., The resilience of an ecological unit encompasses resistance during adverse conditions and the capacity to recover. We adopted a ‘resistance-recovery’ framework to experimentally partition the resilience of a foundation species (the seagrass Cymodocea nodosa). The shoot abundances of nine seagrass meadows were followed before, during and after simulated light reduction conditions. We determined the significance of ecological, environmental and genetic drivers on seagrass resistance (% of shoots retained during the light deprivation treatments) and recovery (duration from the end of the perturbed state back to initial conditions). To identify whether seagrass recovery was linearly related to prior resistance, we then established the connection between trajectories of resistance and recovery. Finally, we assessed whether recovery patterns were affected by biological drivers (production of sexual products—seeds—and asexual propagation) at the meadow-scale. Resistance to shading significantly increased with the genetic diversity of the meadow and seagrass recovery was conditioned by initial resistance during shading. A threshold in resistance (here, at a ca. 70% of shoot abundances retained during the light deprivation treatments) denoted a critical point that considerably delays seagrass recovery if overpassed. Seed densities, but not rhizome elongation rates, were higher in meadows that exhibited large resistance and quick recovery, which correlated positively with meadow genetic diversity. Our results highlight the critical role of resistance to a disturbance for persistence of a marine foundation species. Estimation of critical trade-offs between seagrass resistance and recovery is a promising field of research to better manage impacts on seagrass meadows., This work was funded by a project (RESIGRASS, CGL2014- 58829) supported by the Secretaría de Estado de Investigación, Desarrollo e Innovación (MINECO, Government of Spain).

Este artículo contiene 18 páginas, 4 figuras., Good datasets of geo-referenced records of alien species are a prerequisite for assessing the spatio-temporal dynamics of biological invasions, their invasive potential, and the magnitude of their impacts. However, with the exception of first records on a country level or wider regions, observations of species presence tend to remain unpublished, buried in scattered repositories or in the personal databases of experts. Through an initiative to collect, harmonize and make such unpublished data for marine alien and cryptogenic species in the Mediterranean Sea available, a large dataset comprising 5376 records was created. It includes records of 239 alien or cryptogenic taxa (192 Animalia, 24 Plantae, 23 Chromista) from 19 countries surrounding the Mediterranean Sea. In terms of records, the most reported Phyla in descending order were Chordata, Mollusca, Chlorophyta, Arthropoda, and Rhodophyta. The most recorded species was Caulerpa cylindracea, followed by Siganus luridus, Magallana sp. (cf. gigas or angulata) and Pterois miles. The dataset includes records from 1972 to 2020, with the highest number of records observed in 2018. Among the records of the dataset, Dictyota acutiloba is a first record for the Mediterranean Sea. Nine first country records are also included: the alga Caulerpa taxifolia var. distichophylla, the cube boxfish Ostracion cubicus, and the cleaner shrimp Urocaridella pulchella from Israel; the sponge Paraleucilla magna from Libya and Slovenia; the lumpfish Cyclopterus lumpus from Cyprus; the bryozoan Celleporaria vermiformis and the polychaetes Prionospio depauperata and Notomastus aberans from Malta., The publication of this article is supported by the Open Access Publishing Fund of the International Association for Open Knowledge on Invasive Alien Species (INVASIVESNET; www.invasivesnet.org). Stelios Katsanevakis, Maria Sini and Konstantinos Tsirintanis were supported by the Hellenic Foundation for Research and Innovation (H.F.R.I.) under the “First Call for H.F.R.I. Research Projects to support Faculty members and Researchers and the procurement of high-cost research equipment grant” (Project Number: HFRI-FM17-1597). Enalia Physis acknowledges Pantelis Patsalou for his support with field-logistics and links with fishers. Fiona Tomas would like to acknowledge funding from FECYT FCT- 14-9319 (¡OJO A LAS INVASORAS! BIODIVERSIDAD Y ESPECIES INVASORAS DEL MEDITERRÁNEO BALEAR). Vasilis Gerovasileiou, Thanos Dailianis and Maria Sini acknowledge the support by the MARISCA project (www.marisca.eu), co-funded (85%) by EEA GRANTS, 2009–2014, and the Public Investments Program (PIP) of the Hellenic Republic (15%). Razy Hoffman acknowledges funding by Yad-Hanadiv foundation, through the Israel Society of Ecology and Environmental Sciences and Israel Nature and Parks Authority (An integrated program for establishing biological baselines and monitoring protocols for marine reserves in the Israeli Mediterranean Sea). Argyro Zenetos and Paraskevi K. Karachle would like to thank the citizenscientists collaborating with the Ellenic Network on Aquatic Invasive Species (ELNAIS – elnais.hcmr.gr). Nikolaos Doumpas, Ioannis Giovos, Periklis Kleirou and Francesco Tiralongo would like to thank all the citizen-scientists that contributed with their shared records and data in the citizen-science project “Is it alien to you? Share it!!!” (https://www.facebook.com/ groups/104915386661854/). Data from Gyaros Island marine reserve were collected under the “GyarosMPA” project, funded by “MAVA Fondation pour la Nature”. Data from Corsica coastline were mainly collected in the framework of the “Corsica Alien Network” initiated by “Office de l’Environnement de la Corse”. Carla Morri and Carlo Nike Bianchi received financial support from FFARB (funds for basic research activities) by the Italian Ministry of Education, University and Research. Ergün Taşkın has been supported by TÜBİTAK, Ankara, Turkey (Project Number: 114Y238). The Slovenian authors would like to acknowledge their financial support from the Slovenian Research Agency (research core funding No. P1-0237) and the Ministry of Agriculture, Forestry and Food of the Republic of Slovenia. Mehmet Fatih Huseyinoglu thanks University of Kyrenia’s Scientific Research Project numbered GRN-20191-004. Fabio Crocetta was funded by the COST (European Cooperation in Science and Technology) Action TD1209 Alien Challenge project. The FRI (HAO DEMETER) team is very grateful to the Marine Strategy Project for financial support. Records of NIS in Jbel Moussa, the National Park of Al Hoceima and Cap des Trois Fourches sites from Morocco were obtained during surveys conducted within the framework of the MedKeyHabitats and the MedMPAnet Projects implemented by UNEP/MAP-RAC/SPA in close collaboration with the Haut Commissariat aux Eaux et Forêts et à la Lutte Contre la Désertification (HCEFLCD) and financially supported by RAC/SPA, Tunisia and the MAVA Foundation, Switzerland (MedKeyHabitats Project) and the European Commission (EC), the Spanish Agency for International Cooperation to Development (AECID), and the French Global Environment Facility (MedMPAnet Project). Jamila Ben Souissi was partially funded by BiodivMex /Chantier MISTRALS. Konstantinos Tsiamis sampling records were retrieved during his post in the Hellenic Centre for Marine Research, which he would like to thank for. Periklis Kleitou and Demetris Kletou were supported by the LIFE financial instrument of the European Union – RELIONMED project [Grant Agreement LIFE16 NAT/ CY/000832]. Some of the data included in the dataset were obtained through the marine citizen science platform Observadores del Mar www.observadoresdelmar.es with the support of FECYT FCT-17-12469, LIFE IP Intemares and Fundació Marilles, and through the citizen science site of the Italian Marine Protected Area of “Regno di Nettuno” (islands of Ischia, Procida and Vivara): www.citizensciencerdn.org. Most data from Lebanon were retrieved from social media dedicated to citizen science (Facebook group: Sea Lebanon https://www.facebook.com/ groups/109615625861815/) or fishers and scuba divers WhatsApp groups). Jamila Rizgalla wishes to thank the administration of Regatta for granting a free pass to conduct field surveys and the security personnel for providing a safe environment. Anna Occhipinti-Ambrogi was supported by European Community’s Seventh Framework Program VECTORS (Vectors of Change in Oceans and Seas Marine Life, Impact on Economic Sectors). The long lasting collaboration with the ICES Working Group on Introductions and Transfer of Marine Organisms (WGITMO) has been a good forum where many information and ideas could be exchanged within some of the authors (Anna Occhipinti-Ambrogi, Argyro Zenetos, Agnese Marchini, and a wider community of scientists working on biological invasions). A. Rosso and R. Sanfilippo received grants from the Catania University Research Plan 2016/2018. Data from Kuriat island were collected under the “Kuriat project”, funded by “MAVA Fondation pour la Nature” executed by SPA/RAC in partnership with the Coastal Protection and Management Agency (APAL) and Notre Grand Bleu (NGB) NGO. The AIS/ERA (Environment and Resources Authority) Maltese data were obtained from the EU funded project EMFF 8.3.1 under the European Maritime and Fisheries Fund 2014–2020 with a total cost of €1.6 million in public eligible EMFF funds (75% EU 25% MT), managed by AIS/ERA (Environment and Resources Authority). The ultimate goals of this European Maritime and Fisheries Fund (EMFF 2014–2020) project are to devise a holistic approach towards marine monitoring and develop a comprehensive database of data collected about the Maltese waters., With the funding support of the ‘Severo Ochoa Centre of Excellence’ accreditation (CEX2019-000928-S), of the Spanish Research Agency (AEI)

Background & Aims: Hepatoblastoma (HB) is a rare disease. Nevertheless, it is the predominant pediatric liver cancer, with limited therapeutic options for patients with aggressive tumors. Herein, we aimed to uncover the mechanisms of HB pathobiology and to identify new biomarkers and therapeutic targets in a move towards precision medicine for patients with advanced HB. Methods: We performed a comprehensive genomic, transcriptomic and epigenomic characterization of 159 clinically annotated samples from 113 patients with HB, using high-throughput technologies. Results: We discovered a widespread epigenetic footprint of HB that includes hyperediting of the tumor suppressor BLCAP concomitant with a genome-wide dysregulation of RNA editing and the overexpression of mainly non-coding genes of the oncogenic 14q32 DLK1-DIO3 locus. By unsupervised analysis, we identified 2 epigenomic clusters (Epi-CA, Epi-CB) with distinct degrees of DNA hypomethylation and CpG island hypermethylation that are associated with the C1/C2/C2B transcriptomic subtypes. Based on these findings, we defined the first molecular risk stratification of HB (MRS-HB), which encompasses 3 main prognostic categories and improves the current clinical risk stratification approach. The MRS-3 category (28%), defined by strong 14q32 locus expression and Epi-CB methylation features, was characterized by CTNNB1 and NFE2L2 mutations, a progenitor-like phenotype and clinical aggressiveness. Finally, we identified choline kinase alpha as a promising therapeutic target for intermediate and high-risk HBs, as its inhibition in HB cell lines and patient-derived xenografts strongly abrogated tumor growth. Conclusions: These findings provide a detailed insight into the molecular features of HB and could be used to improve current clinical stratification approaches and to develop treatments for patients with HB. Lay summary: Hepatoblastoma is a rare childhood liver cancer that has been understudied. We have used cutting-edge technologies to expand our molecular knowledge of this cancer. Our biological findings can be used to improve clinical management and pave the way for the development of novel therapies for this cancer. (c) 2020 European Association for the Study of the Liver. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)., This article was possible thanks to the inputs from the Instituto de Salud Carlos III, ISCIII (PI09/00751, PI10/02082, PI13/02340). The project has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No 668596 (ChiLTERN) and grant agreement No 826121 (iPC). JCR is supported by the Catalan Agency for Management of University and Research Grants (AGAUR, 2019 FI_B01024). LT is supported by an Accelerator Award (CRUCK, AECC, AIRC) (HUNTER, C9380/A26813). DS is supported by the Gilead Research Scholar in Liver Disease. JML is supported by the European Union's Horizon 2020 research and innovation programme (HEPCAR, 667273-2), Institucio Catalana de Recerca i Estudis Avancats (ICREA), U.S. Department of Defense (CA150272P3), an Accelerator Award (CRUCK, AECC, AIRC) (HUNTER, C9380/A26813), National Cancer Institute, Tisch Cancer Institute (P30-CA196521), Samuel Waxman Cancer Research Foundation, Spanish National Health Institute (SAF2016-76390) and AGAUR (SGR-1358). CA and MRS were supported by Ramon y Cajal (RYC-2010-07249) and Miguel Servet (CPII14/00021) programs of the Ministry of Science and Innovation of Spain and ISCIII, respectively. CA, MRS and MS received funding from CIBERehd (CB06/04/0033) and AGAUR (2017-SGR-490). IGTP is a member of the CERCA network of institutes. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Seagrasses constitute a key coastal habitat world-wide, but are exposed to multiple perturbations. Understanding elements affecting seagrass resistance to disturbances is critical for conservation. Distinct biogeographical scenarios are intrinsically linked with varying ecological and evolution backgrounds shaped across millennia. We addressed whether the resistance (change in shoot abundances) and performance (change in leaf morphology and growth) of the seagrass Cymodocea nodosa to a local stressor, light reduction, varied across three regions (Southeast Iberia, the Balearic Sea, and the Canaries) within the temperate northern Atlantic realm. We hypothesized that distinct biogeographical scenarios, in terms of distinct ecological/environmental conditions and genetic diversity of meadows, would affect seagrass resistance and performance, with flow-on effects on associated epifauna. The same experiments, in terms of shading intensities, timing and duration, were replicated at three seagrass meadows within each region. Results demonstrated inter-regional variation in the resistance and performance of C. nodosa. Under moderate and high shading, shoot abundance was abruptly decreased, relative to controls, in the Canaries with concurrent, but less accentuated, changes in leaf morphology and no changes in growth. In the other two regions, however, moderate and high shading had a negligible effect on shoot abundance, leaf morphology, and growth. Shading had no overall effect over the total abundance and assemblage structure of epifauna; these faunal attributes, however, varied between regions. Low seagrass resistance at the Canaries is linked with the peripheral distribution of the species there, favouring isolation and decreased genetic diversity. Synthesis. Different biogeographical scenarios shape seagrass resistance to local perturbations. From a conservation perspective, if resistance differs among biogeographical scenarios, universal conservation rules for seagrasses are challenging., This work was funded by a project (RESIGRASS, CGL2014‐58829) supported by the Secretaría de Estado de Investigación, Desarrollo e Innovación (MINECO, Government of Spain) to F.T. and F.T.

Seagrasses are key habitat-forming species of coastal areas. While previous research has demonstrated considerable small-scale variation in seagrass abundance and structure, studies teasing apart local from large-scale variation are scarce. We determined how different biogeographic scenarios, under varying environmental and genetic variation, explained variation in the abundance and structure (morphology and biomass allocation), epiphytes and sexual reproduction intensity of the seagrass Cymodocea nodosa. Regional and local-scale variation, including their temporal variability, contributed to differentially explain variation in seagrass attributes. Structural, in particular morphological, attributes of the seagrass leaf canopy, most evidenced regional seasonal variation. Allocation to belowground tissues was, however, mainly driven by local-scale variation. High seed densities were observed in meadows of large genetic diversity, indicative of sexual success, which likely resulted from the different evolutionary histories undergone by the seagrass at each region. Our results highlight that phenotypic plasticity to local and regional environments need to be considered to better manage and preserve seagrass meadows., This research was supported by a Doctoral fellowship from Universidad de Los Lagos (Chile) to Julia Máñez-Crespo and the work was funded by a project (RESIGRASS, CGL 2014-58829) supported by the Secretaría de Estado de Investigación, Desarrollo e Innovación (MINECO, Government of Spain) to F. Tomas and F. Tuya.

INTRODUCTION: Since 2009, influenza A H1N1pdm09 coexists with seasonal influenza (H3N2). The aim of this study was to describe the severity differences between both. METHODS: A retrospective study from January to March 2014 in Hospital Miguel Servet, Zaragoza, Spain. We studied hospitalized adults with influenza A, and compared radiologic, clinical manifestations and outcomes. Multivariable analysis was performed for severity, defined as the presence of bilateral or multilobar pneumonia, septic shock, intensive care unit (ICU) admission, acute respiratory distress syndrome (ARDS) and intrahospitalary mortality. RESULTS: Out of 234 patients, 146 had A-H1N1 and 88 A-H3N2, and everyone received Oseltamivir within 24 h from admittance. The median age was 64 years old in H1N1 and 77 in H3N2 (P

This paper puts forward a multi-disciplinary field project, set up in 1989 at the Parc Natural de s’Albufera in Mallorca, Balearic Islands, Spain, as an example of a cost effective model for integrating science and volunteer participation in a coastal protected area. Outcomes include the provision of a science base for the effective management of the site; training of Balearic and international biologists and protected area managers; and providing information materials for public awareness, education and general dissemination purposes. This has been achieved at low cost by using the voluntary sector. The project incorporates scientists, wetland managers, students, scholars and other citizens under the auspices of an international volunteer network (TAIB), working in partnership with the Parc management team. Long-term monitoring over a 25-year span of subjects as varied as insects, birds, land and aquatic ecosystems and communities has led to an improved ecological understanding of socio-economic as well as environmental impacts and threats for the catchment. This paper illustrates the added value of a long-term ecological knowledge base for decision making and capacity building in protected areas in order to reduce environmental impacts from socio-economic development in surrounding coastal zones. It describes how the science base has been used as a means of communication to encourage early action by policy makers to avoid negative outcomes of costly future impact on the public purse; and highlights how the economic value of long-term monitoring as an early warning system far outweighs the modest cost to society of an integrated participatory project based in the volunteer sector. The Albufera experience is offered as a cost effective model for other coastal and island sites. Este artigo apresenta um projeto de campo multidisciplinar implementado em 1989 no Parque Natural de Albufera (Maiorca, Ilhas Baleares, Espanha) que pode ser considerado como um modelo exemplar em termos de custo, eficiência e benefício para a integração da ciência com a participação voluntária em processos de gestão de áreas protegidas costeiras. Os principais resultados deste projeto incluíram a produção de uma base científica para a gestão adequada do sítio; a formação de biólogos e gestores de áreas protegidas locais e internacionais; e a produção de materiais para educação, sensibilização e consciencialização ambiental da população local e grande público. Estes objetivos foram atingidos a baixo custo devido ao recurso ao voluntariado. Este projeto integrou cientistas, gestores de áreas protegidas, estudantes, bolseiros e outros cidadãos sob a égide de uma rede internacional de voluntariado (TAIB), que tem colaborado ativamente com a equipa de gestão do Parque Natural. A monitorização integrada a longo prazo durante um período de 25 anos em domínios científicos como a entomologia, ornitologia, ecologia terrestre e ecologia aquática, permitiu melhorar substancialmente o nível de conhecimento ecológico associado à componente sócio-económica da área de estudo, assim como os seus impactes ambientais e as ameaças que daí decorrem para a bacia hidrográfica. Este artigo demonstra a importância de uma monitorização ecológica integrada a longo prazo para apoio à decisão e para a capacitação de recursos em áreas protegidas, de modo a reduzir os impactes ambientais decorrentes do desenvolvimento sócio-económico das áreas costeiras da zona. Este trabalho descreve também como a ciência foi usada como meio de comunicação e sensibilização para estimular os decisores a agir antecipadamente, de modo a evitar os altos custos ambientais e financeiros para o erário público decorrentes dos impactes ambientais e sócio-económicos das políticas adotadas. Finalmente, este estudo realça a excelente relação custo-eficiência-benefício associada à monitorização ecológica integrada a longo prazo assente num projeto participativo integrado baseado em voluntariado, constituindo também um sistema de alerta precoce eficiente, de baixo custo e com elevado benefício para a sociedade. A experiência de Albufera é assim proposta como um modelo válido apto para ser aplicado com sucesso noutros sítios costeiros e pequenas ilhas.

En este trabajo se abordará el análisis de dos de los principales programas alimentarios de la Ciudad de Buenos Aires, Ticket Social y Ciudadanía Porteña. Estos serán analizados desde una perspectiva macrosocial, sobre la base de un análisis crítico de los aspectos socioeconómicos y los principales nudos problemáticos que presenta su desarrollo. This paper addresses the analysis of two major food programs implemented by the City of Buenos Aires, Ticket Social and Ciudadanía Porteña. They will be examined from a macro perspective, based on a critical analysis of their main socioeconomic characteristics and the problematic issues in their development. Fil: Bermúdez, Ángeles. Universidad de Buenos Aires. Facultad de Derecho; Argentina Fil: Carmona Barrenechea, Verónica Inés. Universidad de Buenos Aires. Facultad de Derecho; Argentina Fil: Messina, Giuseppe Manuel. Universidad de Buenos Aires. Facultad de Derecho; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Royo, Laura. Universidad de Buenos Aires. Facultad de Derecho; Argentina