The Reachability problem in constructive geometric constraint solving based dynamic geometry

An important issue in dynamic geometry is the reachability problem that asks whether there is a continuos path that, from a given starting geometric configuration, continuously leads to an ending configuration. In this work we report on a technique to compute a continuous evaluation path, if one exists, that solves the reachability problem for geometric constructions with one variant parameter. The technique is developed in the framework of a constructive geometric constraint-based dynamic geometry system, uses the A* algorithm and minimizes the variant parameter arc length.Postprint (published version

Geometric constraint problems and solution instances

Geometric constraint solving is a growing field devoted to solve geometric problems defined by relationships, called constraints, established between the geometric elements. In this work we show that what characterizes a geometric constraint problem is the set of geometric elements on which the problem is defined. If the problem is wellconstrained, a given solution instance to the geometric constraint problem admits different representations defined by measuring geometric relationships in the solution instance.Postprint (published version

h-graphs : a new representation for tree decompositions of graphs

In geometric constraint solving, 2D well constrained geometric problems can be abstracted as Laman graphs. If the graph is tree decomposable, the constraint-based geometric problem can be solved by a Decomposition-Recombination planner based solver. In general decomposition and recombination steps can be completed only when steps on which they are dependent have already been completed. This fact naturally defines a hierarchy in the decomposition-recombination steps that traditional tree decomposition representations do not capture explicitly.; In this work we introduce h-graphs, a new representation for decompositions of tree decomposable Laman graphs, which captures dependence relations between different tree decomposition steps. We show how h-graphs help in efficiently computing parameter ranges for which solution instances to well constrained, tree decomposable geometric constraint problems with one degree of freedom can actually be constructed. (C) 2015 Elsevier Ltd. All rights reserved.Postprint (published version

Por sus basuras los reconoceréis: La identificación arqueozoológica de una comunidad ḏimmí cristiana en la Qurṭuba tardoandalusí (Cercadilla, siglo XII)

This article presents the results of the zooarchae- ological analysis of the faunal material recovered from a domestic and agro-industrial unit located in the Archaeological Area of Cercadilla, in the outskirts of madinah Qurṭuba, that was inhabited during the 12th century. The data source is twofold: on the one hand, a sample of animal bones from a closed context identified as food refuse; on the other, a pierced right scallop shell from a living floor. The high frequency of pig remains indicates the consumption of pork, a behavior that implies a transgression of the main dietary rule of the Islamic orthopraxis, whereas the scallop was identified as a pilgrim shell linked to the symbolic sphere of the medieval Christian world. Both results, along with the occupational history of Cercadilla, allow to suggest the Christian identity of this community, enriching our conception of the social landscape during the late Andalusi period

Microenvironmental hCAP-18/LL-37 promotes pancreatic ductal adenocarcinoma by activating its cancer stem cell compartment

This is the peer reviewed version of the following article: Microenvironmental hCAP-18/LL-37 promotes pancreatic ductal adenocarcinoma by activating its cancer stem cell compartment. Gut 64.12 (2015): 1921-1935 and which has been published in final form at http://dx.doi.org/10.1136/gutjnl-2014-308935OBJECTIVES: The tumour stroma/microenvironment not only provides structural support for tumour development, but more importantly it provides cues to cancer stem cells (CSCs) that regulate their self-renewal and metastatic potential. This is certainly true for pancreatic ductal adenocarcinomas (PDAC), where tumour-associated fibroblasts, pancreatic stellate cells and immune cells create an abundant paracrine niche for CSCs via microenvironment-secreted factors. Thus understanding the role that tumour stroma cells play in PDAC development and CSC biology is of utmost importance. DESIGN: Microarray analyses, tumour microarray immunohistochemical assays, in vitro co-culture experiments, recombinant protein treatment approaches and in vivo intervention studies were performed to understand the role that the immunomodulatory cationic antimicrobial peptide 18/LL-37 (hCAP-18/LL-37) plays in PDAC biology. RESULTS: We found that hCAP-18/LL-37 was strongly expressed in the stroma of advanced primary and secondary PDAC tumours and is secreted by immune cells of the stroma (eg, tumour-associated macrophages) in response to tumour growth factor-β1 and particularly CSC-secreted Nodal/ActivinA. Treatment of pancreatic CSCs with recombinant LL-37 increased pluripotency-associated gene expression, self-renewal, invasion and tumourigenicity via formyl peptide receptor 2 (FPR2)- and P2X purinoceptor 7 receptor (P2X7R)-dependent mechanisms, which could be reversed by inhibiting these receptors. Importantly, in a genetically engineered mouse model of K-Ras-driven pancreatic tumourigenesis, we also showed that tumour formation was inhibited by either reconstituting these mice with bone marrow from cathelicidin-related antimicrobial peptide (ie, murine homologue of hCAP-18/LL-37) knockout mice or by pharmacologically inhibiting FPR2 and P2X7R. CONCLUSIONS: Thus, hCAP-18/LL-37 represents a previously unrecognised PDAC microenvironment factor that plays a critical role in pancreatic CSC-mediated tumourigenesis.CH: ERC Advanced Investigator Grant (Pa-CSC 233460), European Community's Seventh Framework Programme (FP7/2007-2013) under grant agreement n° 256974 (EPC-TM-NET) and n° 602783 (CAM-PaC), the Subdirección General de Evaluación y Fomento de la Investigación, Fondo de Investigación Sanitaria (PS09/02129 & PI12/02643) and the Programa Nacional de Internacionalización de la I+D, Subprogramma: FCCI 2009 (PLE2009-0105; both Ministerio de Economía y Competitividad (es), Spain), BSJr: Rámon y Cajal Merit Award from the Ministerio de Economía y Competitividad, Spain and Clinic and Laboratory Integration Program (CLIP) grant from the Cancer Research Institute, NY, NY. MC: La Caixa Predoctoral Fellowshi

Babelomics 5.0: functional interpretation for new generations of genomic data

This article has been accepted for publication in Nucleic Acids Research Published by Oxford University Press.Babelomics has been running for more than one decade offering a user-friendly interface for the functional analysis of gene expression and genomic data. Here we present its fifth release, which includes support for Next Generation Sequencing data including gene expression (RNA-seq), exome or genome resequencing. Babelomics has simplified its interface, being now more intuitive. Improved visualization options, such as a genome viewer as well as an interactive network viewer, have been implemented. New technical enhancements at both, client and server sides, makes the user experience faster and more dynamic. Babelomics offers user-friendly access to a full range of methods that cover: (i) primary data analysis, (ii) a variety of tests for different experimental designs and (iii) different enrichment and network analysis algorithms for the interpretation of the results of such tests in the proper functional context. In addition to the public server, local copies of Babelomics can be downloaded and installed. Babelomics is freely available at: http://www.babelomics.org.Spanish Ministry of Economy and Competitiveness [BIO2011-27069], Conselleria d'Educacio of the Valencian Community [PROMETEOII/2014/025]; EU FP7-PEOPLE Project MLPM [316861]; Fundació la Marató TV3 [151/C/2013]. Funding for open access charge: Spanish Ministry of Economy and Competitiveness [BIO2011-27069]

Tratamiento hormonal del cáncer de mama

Hormonal therapy has been the first systemic treatment against breast cancer. Up to now Tamoxifen and ovarian supression/ablation were the best optionts we had to treat early breast cancer as advancer disease. The advent of aromatase inhibitors, new SERMS and antistrogen Fulvestrant have supoused a great advance in the treatment of this disease and at the same time have complicated the election of the optimal drug for each patient. This article tries to review the aviable treatment options insiting on its indications

Identification of circulating microRNA profiles associated with pulmonary function and radiologic features in survivors of SARS-CoV-2-induced ARDS

There is a limited understanding of the pathophysiology of postacute pulmonary sequelae in severe COVID-19. The aim of current study was to define the circulating microRNA (miRNA) profiles associated with pulmonary function and radiologic features in survivors of SARS-CoV-2-induced ARDS. The study included patients who developed ARDS secondary to SARS-CoV-2 infection (n = 167) and a group of infected patients who did not develop ARDS (n = 33). Patients were evaluated 3 months after hospital discharge. The follow-up included a complete pulmonary evaluation and chest computed tomography. Plasma miRNA profiling was performed using RT-qPCR. Random forest was used to construct miRNA signatures associated with lung diffusing capacity for carbon monoxide (DLCO) and total severity score (TSS). Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analyses were conducted. DLCO < 80% predicted was observed in 81.8% of the patients. TSS showed a median [P25;P75] of 5 [2;8]. The miRNA model associated with DLCO comprised miR-17-5p, miR-27a-3p, miR-126-3p, miR-146a-5p and miR-495-3p. Concerning radiologic features, a miRNA signature composed by miR-9-5p, miR-21-5p, miR-24-3p and miR-221-3p correlated with TSS values. These associations were not observed in the non-ARDS group. KEGG pathway and GO enrichment analyses provided evidence of molecular mechanisms related not only to profibrotic or anti-inflammatory states but also to cell death, immune response, hypoxia, vascularization, coagulation and viral infection. In conclusion, diffusing capacity and radiological features in survivors from SARS-CoV-2-induced ARDS are associated with specific miRNA profiles. These findings provide novel insights into the possible molecular pathways underlying the pathogenesis of pulmonary sequelae.This work is supported by Instituto de Salud Carlos III (COV20/00110), co-funded by European Regional Development Fund (ERDF)/“A way to make Europe”. CIBERES is an initiative of the Instituto de Salud Carlos III. Suported by: Programa de donaciones “estar preparados” UNESPA (Madrid, Spain) and Fundación Francisco Soria Melguizo (Madrid, Spain). Supported by La Fundació La Marató de TV3, projecte amb codi 202108-30/-31. COVIDPONENT is funded by Institut Català de la Salut and Gestió de Serveis Sanitaris. MM is the recipient of a predoctoral fellowship (PFIS: FI21/00187) from Instituto de Salud Carlos III. MCGH is the recipient of a predoctoral fellowship from “University of Lleida”. DdGC has received financial support from Instituto de Salud Carlos III (Miguel Servet 2020: CP20/00041), co-funded by the European Social Fund (ESF)/“Investing in your future”. AC acknowledges receiving financial support from Instituto de Salud Carlos III (ISCIII; Sara Borrell 2021: CD21/00087). ENL and GL were funded by COVID1005 and ACT210085 from National Agency of Investigation & Development & Development (ANID), Chil

Genome-wide transcriptional profiling of pulmonary functional sequelae in ARDS- secondary to SARS-CoV-2 infection

Background: Up to 80% of patients surviving acute respiratory distress syndrome (ARDS) secondary to SARS-CoV- 2 infection present persistent anomalies in pulmonary function after hospital discharge. There is a limited un-derstanding of the mechanistic pathways linked to post-acute pulmonary sequelae. Aim: To identify the molecular underpinnings associated with severe lung diffusion involvement in survivors of SARS-CoV-2-induced ARDS. Methods: Survivors attended to a complete pulmonary evaluation 3 months after hospital discharge. RNA sequencing (RNA-seq) was performed using Illumina technology in whole-blood samples from 50 patients with moderate to severe diffusion impairment (DLCO<60%) and age- and sex-matched individuals with mild-normal lung function (DLCO≥60%). A transcriptomic signature for optimal classification was constructed using random forest. Transcriptomic data were analyzed for biological pathway enrichment, cellular deconvolution, cell/tissue-specific gene expression and candidate drugs. Results: RNA-seq identified 1357 differentially expressed transcripts. A model composed of 14 mRNAs allowed the optimal discrimination of survivors with severe diffusion impairment (AUC=0.979). Hallmarks of lung sequelae involved cell death signaling, cytoskeleton reorganization, cell growth and differentiation and the immune response. Resting natural killer (NK) cells were the most important immune cell subtype for the pre-diction of severe diffusion impairment. Components of the signature correlated with neutrophil, lymphocyte and monocyte counts. A variable expression profile of the transcripts was observed in lung cell subtypes and bodily tissues. One upregulated gene, TUBB4A, constitutes a target for FDA-approved drugs. Conclusions: This work defines the transcriptional programme associated with post-acute pulmonary sequelae and provides novel insights for targeted interventions and biomarker development.MCGH is the recipient of a predoctoral fellowship from the University of Lleida. MM is the recipient of a predoctoral fellowship (PFIS: FI21/00187) from Instituto de Salud Carlos III. AC is supported by Instituto de Salud Carlos III (Sara Borrell 2021: CD21/00087). DdGC has received financial support from Instituto de Salud Carlos III (Miguel Servet 2020: CP20/00041), co-funded by the European Social Fund (ESF) “Investing in your future”. IML is supported by a Miguel Servet contract (CPII20/00029) from the Instituto de Salud Carlos III, co-funded by the European Social Fund (ESF) “Investing in your future”. CIBERES is an initiative of the Instituto de Salud Carlos III. This work is supported by the Instituto de Salud Carlos III (COV20/00110), co-funded by the European Regional Development Fund (ERDF) “A way to make Europe”. Supported by: Programa de donaciones "estar preparados"; UNESPA (Madrid, Spain) and Fundación Francisco Soria Melguizo (Madrid, Spain). Funded by: La Fundació La Marató de TV3, project with code 202108–30/ 31. COVIDPONENT is funded by the Institut Català de la Salut and Gestió de Serveis Sanitaris. This research was funded in part by a grant (PI19/01805) from the Instituto de Salud Carlos III, co-funded by the European Regional Development Fund (ERDF) “A way to build Europe” and by the Fundación Rioja Salu

Multiplex protein profiling of bronchial aspirates reveals disease-, mortality- and respiratory sequelae-associated signatures in critically ill patients with ARDS secondary to SARS-CoV-2 infection

Introduction: Bronchial aspirates (BAS) obtained during invasive mechanical ventilation (IMV) constitutes a useful tool for molecular phenotyping and decision making. Aim: To identify the proteomic determinants associated with disease pathogenesis, all-cause mortality and respiratory sequelae in BAS samples from critically ill patients with SARS-CoV-2-induced ARDS. Methods: Multicenter study including 74 critically ill patients with COVID-19 and non-COVID-19 ARDS. BAS were obtained by bronchoaspiration after IMV initiation. Three hundred sixty-four proteins were quantified using proximity extension assay (PEA) technology. Random forest models were used to assess predictor importance. Results: After adjusting for confounding factors, CST5, NADK, SRPK2 and TGFa were differentially detected in COVID-19 and non-COVID-19 patients. In random forest models for COVID-19, CST5, DPP7, NADK, KYAT1 and TYMP showed the highest variable importance. In COVID-19 patients, reduced levels of ENTPD2 and PTN were observed in nonsurvivors of ICU stay, even after adjustment. AGR2, NQO2, IL-1a, OSM and TRAIL showed the strongest associations with in-ICU mortality and were used to construct a proteinbased prediction model. Kaplan-Meier curves revealed a clear separation in mortality risk between subgroups of PTN, ENTPD2 and the prediction model. Cox regression models supported these findings. In survivors, the levels of FCRL1, NTF4 and THOP1 in BAS samples obtained during the ICU stay correlated with lung function (i.e., DLCO levels) 3 months after hospital discharge. Similarly, Flt3L and THOP1 levels were correlated with radiological features (i.e., TSS). These proteins are expressed in immune and nonimmune lung cells. Poor host response to viral infectivity and an inappropriate reparative mechanism seem to be linked with the pathogenesis of the disease and fatal outcomes, respectively. Conclusion: BAS proteomics identified novel factors associated with the pathology of SARS-CoV-2-induced ARDS and its adverse outcomes. BASbased protein testing emerges as a novel tool for risk assessment in the ICU