Three-dimensional Reconstruction of the Caspe Geological Structure (Spain) for Evaluation as a Potential CO2 Storage Site

The Caspe geological structure was formed by the convergence of the Iberian Range and the Catalonian Coastal Range, during the Tertiary compression. Traditionally, the Caspe structure has been interpreted from seismic profiles without considering surface structural data. The aim of this study is to build a 3D geological model taking into account the structural data from the geological map, stress fields and lineaments, and evaluate its possibility as potential CO2 storage site. Four surfaces have been modelled: Buntsandstein Top, Muschelkalk-I Top, Muschelkalk-II Top and Cenozoic Bottom. Considering the geometry and depth for storage the target reservoir was considered to be the Buntsandstein facies. The available seismic data indicate that the Buntsandstein facies top is at approximately 500 m depth and hosts a deep saline aquifer. The target reservoir series include the conglomerate and sandstone of the Hoz del Gallo and Cañizar Fms (Buntsandstein Facies) with an average thickness of 500 m and 21% porosity. The seal comprises the shales and silts of the Röt Fm with an average thickness of 100-150 m. The structure volume was calculated based on the -500 mbsl for the Buntsandstein top deepest closed contour lines. The estimated volume is 5, 800 Mm3 with most of CO2 in gaseous state

Immune Checkpoint Inhibitors: The Emerging Cornerstone in Cholangiocarcinoma Therapy?

Background: Cholangiocarcinoma (CCA) encompasses a heterogeneous group of malignant tumors with dismal prognosis and increasing incidence worldwide. Both late diagnosis due to the lack of early symptoms and the refractory nature of these tumors seriously compromise patients' welfare and outcomes. Summary: During the last decade, immunotherapy and, more specifically, modulation of immune checkpoints-mediated signaling pathways have been under the spotlight in the field of oncology, emerging as a potential therapeutic approach for the treatment of several cancers, including CCA. Generally, high expression levels of immune checkpoints in patients with CCA have been associated with worse clinical outcomes, particularly with shorter overall survival and relapse-free survival. Thus, immune checkpoint inhibitors (ICIs), which mainly constitute different monoclonal antibodies, have been developed in order to hamper the immune checkpoint-mediated pathways. Interestingly, chemotherapy may increase the expression of immune checkpoints, while other therapeutic approaches such as ablative and targeted therapies may enhance their antitumor activity. In this sense, several clinical trials evaluated the safety and efficacy of ICIs for CCA, both as a monotherapy and in combination with other ICIs or loco-regional and systemic therapies. Additionally, many other clinical trials are currently ongoing and results are eagerly awaited. Here, we summarize the key aspects of immune checkpoint molecules as prognostic factors and therapeutic targets in CCA, highlighting the most recent advances in the field and future research directions. Key messages: (1) Effective therapeutic approaches for CCA are urgently needed. (2) Expression levels of immune checkpoints in patients with CCA have been proposed to be related with clinical outcomes. (3) Combination of different ICIs may outperform the efficacy of ICI monotherapy for CCA treatment. (4) Recent studies point toward the combination of ICIs and other common therapies, especially chemotherapy, as a promising strategy for treatment of CCA patients

Interactive web application for the teaching-learning process of the topics Cell and Basic Tissues

Introducción: en el mundo actual, la enseñanza médica se ha visto favorecida por el impetuoso avance de la tecnología educacional. En Cuba se ha realizado un arduo trabajo en lo referente a la incorporación masiva de las TIC en la educación superior y se ha dotado de estos medios a todos los centros docentes.Objetivo: desarrollar una aplicación Web interactiva relacionada con el proceso de enseñanza-aprendizaje de los temas Célula y Tejidos Básicos, correspondiente a la asignatura Célula, Tejidos y Sistema Tegumentario.Métodos: se realizó una investigación de desarrollo tecnológico que obedece a un estudio en el primer año de la carrera Medicina de la Facultad de Ciencias Médicas “Ernesto Che Guevara” correspondiente los temas Célula y Tejidos Básicos de la asignatura Célula, Tejidos y Sistema Tegumentario. El universo se integra por todos los estudiantes de primer año, y la muestra aquellos que participaron en la investigación.Resultado: se obtuvieron resultados en cuanto a los procesos fundamentales de enseñanza-aprendizaje de los temas Célula y Tejidos Básicos, que favorecen el desarrollo del sistema de habilidades requerido para la comprensión de los contenidos esenciales de histología en estudiantes de primer año de la carrera Medicina.Conclusiones: el trabajo realizado, constituye la base fundamental para la informatización de los procesos fundamentales de enseñanza-aprendizaje los temas Célula y Tejidos Básicos. Un diseño eficiente de la estructura de la asignatura a través de una aplicación web interactiva facilitará la obtención y reafirmación de conocimientos, para garantizar la obtención de la asignatura de forma rápida y efectiva. Introduction: in today's world, medical education has been favored by the large advance of educational technology. In Cuba, an arduous work has been carried out regarding the massive incorporation of ICTs in higher education and all teaching centers have been equipped with these means.Objective: to develop an interactive Web application related to the teaching-learning process of the topics Cell and Basic Tissues, corresponding to the subject Cell, Tissues and Integumentary System.Methods: a technological development research was carried out, which complies with a study in the first academic year of Medicine major at Ernesto Che Guevara School of Medical Sciences, corresponding to the topics Cell and Basic Tissues of the subject Cell, Tissues and Integumentary System. The target group comprised all first-academic year students, and the sample included those who participated in the research.Results: results were obtained regarding the basic teaching-learning processes of the subjects Cell and Basic Tissues, which favor the development of the system of skills required for the understanding of the essential contents of histology in first-academic year students of Medicine major.Conclusions: the work carried out constitutes the most important basis for the computerization of the basic teaching-learning processes of the topics Cell and Basic Tissues. An efficient design of the structure of the subject through an interactive web application will facilitate the acquisition and reaffirmation of knowledge, guaranteeing the achievement of the subject in a fast and effective way.

Towards 3D databases and harmonized 3D models at IGME-CSIC

IGME-CSIC has a highly relevant geological and geophysical database that includes a continuous digital geological cartography at 1:50000; 1:200000 and 1:1000000 scales and a fair amount of geophysical data: gravity, magnetic, well-logs in tiff and LAS format, seismic lines in tiff and SEG-Y format, borehole and petrophysical data, together with other geophysical and geological studies. Since the 2004, an important effort has been done to undertake 3D geological and geophysical modelling ranging from local studies (mineral exploration or CO2 storage sites) to regional geology for a better understanding of the subsurface structure and its geodynamic evolution as a base for other studies on natural hazards or mineral resources. These studies were ¿stand alone¿ and now IGME is designing a new strategy. It includes the available data and models harmonization (stratigraphy sequences, structural interpretations, faults distribution, seismic velocity models, spatial distribution of physical properties such as density and magnetic susceptibility, workflows, methodologies, evaluation of uncertainties, visualization, etc.) to comply with the FAIR (Findable, Accessible, Interoperable and Reusable) data standardization. In this way, the new 3D models will be easily integrated and available from the databases. This strategy includes collaboration with the Bureau de Recherches Géologiques et Minières of France (BRGM) and Laboratório Nacional de Energia e Geologia of Portugal (LNEG) in order to harmonize the Spanish geological data and models with their neighbours across national borders. The first step is being done in the framework of GeoERA projects. Plain-language Summary IGME-CSIC owns a large database that includes a highly valuable geological and geophysical data and geophysical studies containing the interpretation of some of the data of Spain (onshore and offshore) Since 2004 the authors of this work have been working in 3D geological and geophysical modelling that includes local (mineral exploration or CO2 storage sites) and regional studies. The goal is to improve our understanding of the subsurface structures and processes as a base for deepening our knowledge in how the natural hazards occur, how to improve the exploration for mineral resources, etc. These studies were made ad hoc within different projects and now IGME-CSIC is designing a workflow to harmonize these models in order to comply with the FAIR (Findable, Accessible, Interoperable and Reusable) data standardization so the models will be available to being used beyond the initial objectives that generated their creation. This strategy includes collaboration with other European institutions like the Bureau de Recherches Géologiques et Minières of France (BRGM) and Laboratório Nacional de Energia e Geologia of Portugal (LNEG) in order to harmonize the models across national borders. The first step is already being done in the framework of the GeoERA projects

Beneficial effect of ursodeoxycholic acid in patients with acyl-CoA oxidase 2 (ACOX2) deficiency-associated hypertransaminasemia

Background and aims: A variant (p.Arg225Trp) of peroxisomal acyl-CoA oxidase 2 (ACOX2), involved in bile acid (BA) side-chain shortening, has been associated with unexplained persistent hypertransaminasemia and accumulation of C27-BAs, mainly 3?,7?,12?-trihydroxy-5?-cholestanoic acid (THCA). We aimed to investigate the prevalence of ACOX2 deficiency-associated hypertransaminasemia (ADAH), its response to ursodeoxycholic acid (UDCA), elucidate its pathophysiological mechanism and identify other inborn errors that could cause this alteration. Methods and results: Among 33 patients with unexplained hypertransaminasemia from 11 hospitals and 13 of their relatives, seven individuals with abnormally high C27-BA levels (>50% of total BAs) were identified by high-performance liquid chromatography-mass spectrometry. The p.Arg225Trp variant was found in homozygosity (exon amplification/sequencing) in two patients and three family members. Two additional nonrelated patients were heterozygous carriers of different alleles: c.673C>T (p.Arg225Trp) and c.456_459del (p.Thr154fs). In patients with ADAH, impaired liver expression of ACOX2, but not ACOX3, was found (immunohistochemistry). Treatment with UDCA normalized aminotransferase levels. Incubation of HuH-7 hepatoma cells with THCA, which was efficiently taken up, but not through BA transporters, increased reactive oxygen species production (flow cytometry), endoplasmic reticulum stress biomarkers (GRP78, CHOP, and XBP1-S/XBP1-U ratio), and BAX? expression (reverse transcription followed by quantitative polymerase chain reaction and immunoblot), whereas cell viability was decreased (tetrazolium salt-based cell viability test). THCA-induced cell toxicity was higher than that of major C24-BAs and was not prevented by UDCA. Fourteen predicted ACOX2 variants were generated (site-directed mutagenesis) and expressed in HuH-7 cells. Functional tests to determine their ability to metabolize THCA identified six with the potential to cause ADAH. Conclusions: Dysfunctional ACOX2 has been found in several patients with unexplained hypertransaminasemia. This condition can be accurately identified by a noninvasive diagnostic strategy based on plasma BA profiling and ACOX2 sequencing. Moreover, UDCA treatment can efficiently attenuate liver damage in these patients.Funding information: This study was supported by the following grants: CIBERehd (EHD15PI05/2016); Fondo de Investigaciones Sanitarias, Instituto de Salud Carlos III, Spain (PI19/00819 and PI20/00189), co-funded by European Regional Development Fund/European Social Fund, “Investing in your future”; “Junta de Castilla y León” (SA074P20); Fundació Marato TV3 (201916–31); AECC Scientific Foundation (2017/2020), Spain; and “Centro Internacional sobre el Envejecimiento” (OLD-HEPAMARKER, 0348_CIE_6_E), Spain. We also acknowledge support from grants PID2019-111669RBI-100, PID2020-115055RB-I00 from Plan Nacional de I+D funded by the “Agencia Estatal de Investigación” (AEI) and the center grant P50AA011999 Southern California Research Center for ALPD and Cirrhosis funded by NIAAA/NIH, as well as support from AGAUR of the “Generalitat de Catalunya” SGR-2017-1112, European Cooperation in Science & Technology (COST) ACTION CA17112 Prospective European Drug-Induced Liver Injury Network. Marta Alonso-Peña was the recipient of a predoctoral fellowship from “Ministerio de Educación, Cultura y Deporte” (BOE-A-2015-9456; FPU-14/00214) and a Mobility Grant for Short Stays from “Ministerio de Ciencia, Innovación y Universidades” (EST17/00186). Ricardo Espinosa-Escudero is the recipient of a predoctoral fellowship from “Junta de Castilla y León” and “Fondo Social Europeo” (EDU/574/2018). The funding sources were not involved in the research design or preparation of the article

Development and Validation of Hepamet Fibrosis Scoring System A Simple, Noninvasive Test to Identify Patients With Nonalcoholic Fatty Liver Disease With Advanced Fibrosis

Background & Aims Fibrosis affects prognoses for patients with nonalcoholic fatty liver disease (NAFLD). Several non-invasive scoring systems have aimed to identify patients at risk for advanced fibrosis, but inconclusive results and variations in features of patients (diabetes, obesity and older age) reduce their diagnostic accuracy. We sought to develop a scoring system based on serum markers to identify patients with NAFLD at risk for advanced fibrosis. Methods We collected data from 2452 patients with NAFLD at medical centers in Italy, France, Cuba, and China. We developed the Hepamet fibrosis scoring system using demographic, anthropometric, and laboratory test data, collected at time of liver biopsy, from a training cohort of patients from Spain (n = 768) and validated the system using patients from Cuba (n = 344), Italy (n = 288), France (n = 830), and China (n = 232). Hepamet fibrosis score (HFS) were compared with those of previously developed fibrosis scoring systems (the NAFLD fibrosis score [NFS] and FIB-4). The diagnostic accuracy of the Hepamet fibrosis scoring system was assessed based on area under the receiver operating characteristic (AUROC) curve, sensitivity, specificity, diagnostic odds ratio, and positive and negative predictive values and likelihood ratios. Results Variables used to determine HFS were patient sex, age, homeostatic model assessment score, presence of diabetes, levels of aspartate aminotransferase, and albumin, and platelet counts; these were independently associated with advanced fibrosis. HFS discriminated between patients with and without advanced fibrosis with an AUROC curve value of 0.85 whereas NFS or FIB-4 did so with AUROC values of 0.80 (P = .0001). In the validation set, cut-off HFS of 0.12 and 0.47 identified patients with and without advanced fibrosis with 97.2% specificity, 74% sensitivity, a 92% negative predictive value, a 76.3% positive predictive value, a 13.22 positive likelihood ratio, and a 0.31 negative likelihood ratio. HFS were not affected by patient age, body mass index, hypertransaminasemia, or diabetes. The Hepamet fibrosis scoring system had the greatest net benefit in identifying patients who should undergo liver biopsy analysis and led to significant improvements in reclassification, reducing the number of patients with undetermined results to 20% from 30% for the FIB-4 and NFS systems (P < .05). Conclusions Using clinical and laboratory data from patients with NAFLD, we developed and validated the Hepamet fibrosis scoring system, which identified patients with advanced fibrosis with greater accuracy than the FIB-4 and NFS systems. the Hepamet system provides a greater net benefit for the decision-making process to identify patients who should undergo liver biopsy analysis

A Study of Learning-by-Doing in MOOCs through the Integration of Third-Party External Tools:Comparison of Synchronous and Asynchronous Running Modes

Many MOOCs are being designed replicating traditional passive teaching approaches but using video lectures as the means of transmitting information. However, it is well known that learning-by-doing increases retention rates and, thus, allows achieving a more effective learning. To this end, it is worth exploring which tools fit best in the context of each MOOC to enrich learners' experience, including built-in tools already available in the MOOC platform, and third-party external tools which can be integrated in the MOOC platform. This paper presents an example of the integration of a software development tool, called Codeboard, in three MOOCs which serve as an introduction to programming with Java. We analyze the effect this tool has on learners' interaction and engagement when running the MOOCs in synchronous (instructor-paced) or asynchronous (self-paced) modes. Results show that the overall use of the tool is similar, regardless of the course running mode, although in the case of the synchronous mode the use of the tool is concentrated in a shorter period of time. Results also show that in the synchronous mode there is a higher percentage of accesses to the tool from registered learners (who can save their advances and continue the work later); this finding suggests that learners in the synchronous running mode are more engaged with the MOOC.The authors acknowledge the eMadrid Network, which is funded by the Madrid Regional Government (Comunidad de Madrid) with grant No. S2013/ICE-2715. This work also received partial support from the Spanish Ministry of Economy, Industry and Competitiveness, Project RESET (TIN2014-53199-C3-1-R), Project SYMBHYO-TIC (PTQ-15-07505), Project SIMLAP (RTC-2014-2811-1), Project SMARTLET (TIN2017-85179-C3-1-R), and from the European Commission through Erasmus+ projects MOOC-Maker (561533-EPP-1-2015-1-ESEPPKA2-CBHE-JP), SHEILA (562080-EPP-1-2015-1-BEEPPKA3-PI-FORWARD), COMPASS (2015-1-EL01-KA203-014033), and COMPETEN-SEA (574212-EPP-1-2016-1-NLEPPKA2-CBHE-JP)

Controlled clinical trial comparing the effectiveness of a mindfulness and self-compassion 4-session programme versus an 8-session programme to reduce work stress and burnout in family and community medicine physicians and nurses: MINDUUDD study protocol

Background: Health personnel are susceptible to high levels of work stress and burnout due to the psychological and emotional demands of their work, as well as to other aspects related to the organisation of that work. This paper describes the rationale and design of the MINDUUDD study, the aim of which is to evaluate the effectiveness of a mindfulness and self-compassion 4-session programme versus the standard 8-session programme to reduce work stress and burnout in Family and Community Medicine and Nursing tutors and residents. Methods: The MINDUDD study is a multicentre cluster randomised controlled trial with three parallel arms. Six Teaching Units will be randomised to one of the three study groups: 1) Experimental Group-8 (EG8); 2) Experimental Group-4 (EG4) Control group (CG). At least 132 subjects will participate (66 tutors/66 residents), 44 in the EG8, 44 in the EG4, and 44 in the CG. Interventions will be based on the Mindfulness-Based Stress Reduction (MBSR) program, including some self-compassion practices of the Mindful Self-Compassion (MSC) programme. The EG8 intervention will be implemented during 8 weekly face-to-face sessions of 2.5 h each, while the EG4 intervention will consist of 4 sessions of 2.5 h each. The participants will have to practice at home for 30 min/day in the EG8 and 15 min/day in the EG4. The Five Facet Mindfulness Questionnaire (FFMQ), Self-Compassion Scale (SCS), Perceived Stress Questionnaire (PSQ), Maslach Burnout Inventory (MBI), Jefferson Scale of Physician Empathy (JSPE), and Goldberg Anxiety-Depression Scale (GADS) will be administered. Measurements will be taken at baseline, at the end of the programs, and at three months after completion. The effect of the interventions will be evaluated by bivariate and multivariate analyses (Multiple Linear Regression). Discussion: If the abbreviated mindfulness programme is at least as effective as the standard program, its incorporation into the curriculum and training plans will be easier and more appropriate. It will also be more easily applied and accepted by primary care professionals because of the reduced resources and means required for its implementation, and it may also extend beyond care settings to academic and teaching environments as well

Multicenter evaluation of the Panbio™ COVID-19 rapid antigen-detection test for the diagnosis of SARS-CoV-2 infection

Objetives: The standard RT-PCR assay for coronavirus disease 2019 (COVID-19) is laborious and time-consuming, limiting testing availability. Rapid antigen-detection tests are faster and less expensive; however, the reliability of these tests must be validated before they can be used widely. The objective of this study was to determine the performance of the Panbio™ COVID-19 Ag Rapid Test Device (PanbioRT) (Abbott) in detecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in nasopharyngeal swab specimens. Methods: This prospective multicentre study was carried out in ten Spanish university hospitals and included individuals with clinical symptoms or epidemiological criteria of COVID-19. Only individuals with ≤7 days from the onset of symptoms or from exposure to a confirmed case of COVID-19 were included. Two nasopharyngeal samples were taken to perform the PanbioRT as a point-of-care test and a diagnostic RT-PCR test. Results: Among the 958 patients studied, 325 (90.5%) had true-positive results. The overall sensitivity and specificity for the PanbioRT were 90.5% (95%CI 87.5-93.6) and 98.8% (95%CI 98-99.7), respectively. Sensitivity in participants who had a threshold cycle (CT) < 25 for the RT-PCR test was 99.5% (95%CI 98.4-100), and in participants with ≤5 days of the clinical course it was 91.8% (95%CI 88.8-94.8). Agreement between techniques was 95.7% (κ score 0.90; 95%CI 0.88-0.93). Conclusions: The PanbioRT performs well clinically, with even more reliable results for patients with a shorter clinical course of the disease or a higher viral load. The results must be interpreted based on the local epidemiological context.S