Serum biomarkers and risk of hepatocellular carcinoma recurrence after liver transplantation

Liver transplantation (LT) is the only potentially curative treatment for selected patients with cirrhosis and hepatocellular carcinoma (HCC) who are not candidates for resection. When the Milan criteria are strictly applied, 75% to 85%of 3- to 4-year actuarial survival rates are achieved, but up to 20% of the patients experience HCC recurrence after transplantation. The Milan criteria are based on the preoperative tumor macromorphology, tumor size and number on computed tomography or magnetic resonance imaging that neither correlate well with posttransplant histological study of the liver explant nor accurately predict HCC recurrence after LT, since they do not include objective measures of tumor biology. Preoperative biological markers, including alpha-fetoprotein, desgamma- carboxiprothrombin or neutrophil-to-lymphocyte ratio and platelet-tolymphocyte ratio, can predict the risk for HCC recurrence after transplantation. These biomarkers have been proposed as surrogate markers of tumor differentiation and vascular invasion, with varied risk magnitudes depending on the defined cutoffs. Different studies have shown that the combination of one or several biomarkers integrated into prognostic models predict the risk of HCC recurrence after LT more accurately than Milan criteria alone. In this review, we focus on the potential utility of these serum biological markers to improve the performance of Milan criteria to identify patients at high risk of tumora

System Orchestration Support for a Collaborative Blended Learning Flow

Portable and interactive technologies are changing the nature of collaborative learning practices and open up new possibilities for Computer Supported Collaborative Learning (CSCL). Now, activities occurring in and beyond the classroom can be combined and integrated leading to a new type of complex collaborative blended learning scenarios. However, to organize and structure these scenarios is challenging and represent a workload for practitioners, which hinder the adoption of these technology-enhanced practices. As an approach to alleviate this workload, this paper proposes a proof of concept of a technological solution to overcome the limitations detected in an analysis of an actual collaborative blended learning experiment carried out in a previous study. The solution consists on a Unit of Learning suitable to be instantiated with IMS Learning Design and complemented by a GenericService Integration system. This chapter also discusses to which extent the proposed solution covers the limitations detected in the previous study and how useful could be for reducing the orchestration effort in future experiences.This work has been partially funded by the Project Learn3 (TIN2008- 05163/TSI) from the Plan Nacional I+D+I and "Investigación y Desarrollo de Tecnologías para el e-Learning en la Comunidad de Madrid” funded by the Madrid Regional Government under grant No. S2009/TIC-1650

Bayesian Knowledge Tracing for Navigation through Marzano’s Taxonomy

In this paper we propose a theoretical model of an ITS (Intelligent Tutoring Systems) capable of improving and updating computer-aided navigation based on Bloom’s taxonomy. For this we use the Bayesian Knowledge Tracing algorithm, performing an adaptive control of the navigation among different levels of cognition in online courses. These levels are defined by a taxonomy of educational objectives with a hierarchical order in terms of the control that some processes have over others, called Marzano’s Taxonomy, that takes into account the metacognitive system, responsible for the creation of goals as well as strategies to fulfill them. The main improvements of this proposal are: 1) An adaptive transition between individual assessment questions determined by levels of cognition. 2) A student model based on the initial response of a group of learners which is then adjusted to the ability of each learner. 3) The promotion of metacognitive skills such as goal setting and self-monitoring through the estimation of attempts required to pass the levels. One level of Marzano's taxonomy was left in the hands of the human teacher, clarifying that a differentiation must be made between the tasks in which an ITS can be an important aid and in which it would be more difficult

A Novel Circulating MicroRNA for the Detection of Acute Myocarditis.

The diagnosis of acute myocarditis typically requires either endomyocardial biopsy (which is invasive) or cardiovascular magnetic resonance imaging (which is not universally available). Additional approaches to diagnosis are desirable. We sought to identify a novel microRNA for the diagnosis of acute myocarditis. To identify a microRNA specific for myocarditis, we performed microRNA microarray analyses and quantitative polymerase-chain-reaction (qPCR) assays in sorted CD4+ T cells and type 17 helper T (Th17) cells after inducing experimental autoimmune myocarditis or myocardial infarction in mice. We also performed qPCR in samples from coxsackievirus-induced myocarditis in mice. We then identified the human homologue for this microRNA and compared its expression in plasma obtained from patients with acute myocarditis with the expression in various controls. We confirmed that Th17 cells, which are characterized by the production of interleukin-17, are a characteristic feature of myocardial injury in the acute phase of myocarditis. The microRNA mmu-miR-721 was synthesized by Th17 cells and was present in the plasma of mice with acute autoimmune or viral myocarditis but not in those with acute myocardial infarction. The human homologue, designated hsa-miR-Chr8:96, was identified in four independent cohorts of patients with myocarditis. The area under the receiver-operating-characteristic curve for this novel microRNA for distinguishing patients with acute myocarditis from those with myocardial infarction was 0.927 (95% confidence interval, 0.879 to 0.975). The microRNA retained its diagnostic value in models after adjustment for age, sex, ejection fraction, and serum troponin level. After identifying a novel microRNA in mice and humans with myocarditis, we found that the human homologue (hsa-miR-Chr8:96) could be used to distinguish patients with myocarditis from those with myocardial infarction. (Funded by the Spanish Ministry of Science and Innovation and others.).Supported by a grant (PI19/00545, to Dr. Martín) from the Ministry of Science and Innovation through the Carlos III Institute of Health–Fondo de Investigación Sanitaria; by a grant from the Biomedical Research Networking Center on Cardiovascular Diseases (to Drs. Martín, Sánchez-Madrid, and Ibáñez); by grants (S2017/BMD-3671-INFLAMUNE-CM, to Drs. Martín and Sánchez-Madrid; and S2017/BMD-3867-RENIM-CM, to Dr. Ibáñez) from Comunidad de Madrid; by a grant (20152330 31, to Drs. Martín, Sánchez-Madrid, and Alfonso) from Fundació La Marató de TV3; by grants (ERC-2011-AdG 294340-GENTRIS, to Dr. Sánchez-Madrid; and ERC-2018-CoG 819775-MATRIX, to Dr. Ibáñez) from the European Research Council; by grants (SAF2017-82886R, to Dr. Sánchez-Madrid; RETOS2019-107332RB-I00, to Dr. Ibáñez; and SAF2017-90604-REDT-NurCaMeIn and RTI2018-095928-BI00, to Dr. Ricote) from the Ministry of Science and Innovation; by Fondo Europeo de Desarrollo Regional (FEDER); and by a 2016 Leonardo Grant for Researchers and Cultural Creators from the BBVA Foundation to Dr. Martín. The National Center for Cardiovascular Research (CNIC) is supported by the Carlos III Institute of Health, the Ministry of Science and Innovation, the Pro CNIC Foundation, and by a Severo Ochoa Center of Excellence grant (SEV-2015-0505). Mr. Blanco-Domínguez is supported by a grant (FPU16/02780) from the Formación de Profesorado Universitario program of the Spanish Ministry of Education, Culture, and Sports. Ms. Linillos-Pradillo is supported by a fellowship (PEJD-2016/BMD-2789) from Fondo de Garantía de Empleo Juvenil de Comunidad de Madrid. Dr. Relaño is supported by a grant (BES-2015-072625) from Contratos Predoctorales Severo Ochoa para la Formación de Doctores of the Ministry of Economy and Competitiveness. Dr. Alonso-Herranz is supported by a fellowship from La Caixa–CNIC. Dr. Caforio is supported by Budget Integrato per la Ricerca dei Dipartimenti BIRD-2019 from Università di Padova. Dr. Das is supported by grants (UG3 TR002878 and R35 HL150807) from the National Institutes of Health and the American Heart Association through its Strategically Focused Research Networks.S

Early adipose deposits in sheep: comparative analysis of the perirenal fat ranscriptome of Assaf and Churra suckling lambs

13 páginas, 3 figuras, 2 tablas.Adipose deposits influence the quality of ruminant carcasses, and in suckling lambs, internal types of adipose deposits represent a notable proportion of total fat. The aim of this study was to perform a comparative analysis of the perirenal fat transcriptomes of suckling lambs from two breeds with different growth and carcass characteristics. The perirenal fat tissue from 14 suckling lambs (Assaf, n = 8; Churra, n = 6) was used for the RNA-seq analysis. The functional enrichment analysis of the 670 highly expressed genes (>150 fragments per kilobase of exon per million fragments mapped) in the perirenal fat transcriptome of both breeds revealed that the majority of these genes were involved in energy processes. The expression of the UCP1 gene, a classical biomarker of brown fat, and the presence of multilocular adipocytes in the two breeds supported the presence of brown fat at the transition stage towards white fat tissue. The differential expression analysis performed identified 373 differentially expressed genes (DEGs) between the two compared breeds. Brown/white fat gene biomarkers were not included in the list of DEGs. In Assaf lambs, DEGs were enriched in Gene Ontology (GO) biological processes related to fatty-acid oxidation, whereas in Churra lambs, the majority of the significantly enriched GO terms were related to cholesterol synthesis, which suggests that upregulated DEGs in Assaf lambs are implicated in fat burning, whereas the Churra upregulated DEGs are linked to fat accumulation. These results can help to increase knowledge of the genes controlling early fat deposition in ruminants and shed light on fundamental aspects of adipose tissue growth.This work was supported by the associated funding of aRamon y Cajal contract (RYC-2012-10230) from the Spanish Ministry of Economy, Industry and Competitiveness(MINECO). BGG is funded by the Ramon y Cajal Programme(RYC-2012-10230) from MINECO. We sincerely thank thestaff from the farm of the Faculty of Veterinary Sciences ofthe University of Leon for the management of lambs and the collaborating slaughterhousePeer reviewe

Diagnosis and clinical behavior in patients with Lynch-like syndrome

Introduction and aims: Lynch-like syndrome is diagnosed when there is an expression deficit in DNA mismatch repair proteins but a normal genetic study. The behavior and management of that pathology are currently a subject of debate. We present herein the characteristics of patients with Lynch-like syndrome, together with a surveillance proposal. Materials and methods: Immunohistochemistry was carried out on families suspected of presenting with Lynch syndrome. Germline analysis was done if there was loss of mismatch repair protein expression and no BRAF mutation. Results: Of the 148 patients that underwent immunohistochemistry testing, 23 presented with loss of mismatch repair protein expression. Seven of those patients were identified as having Lynch-like syndrome: 3 had colon cancer, 2 had endometrial tumor, and 2 were healthy, with an affected relative. Mean patient age was 56.9 years and only one patient presented with another tumor associated with Lynch syndrome. Conclusions: Until there is a better understanding of the etiology of that heterogeneous entity, intermediate surveillance is an adequate strategy. Resumen: Introducción y objetivos: La sospecha de síndrome de Lynch sin mutación conocida (SSL) se diagnostica cuando existe déficit de expresión de las proteínas reparadoras de ADN pero con estudio genético normal. El comportamiento y el manejo son controvertidos. Presentamos las características de pacientes con SSL y proponemos una vigilancia. Material y métodos: Se realiza análisis inmunohistoquímico (IMH) en familias con sospecha de síndrome de Lynch. Si existe pérdida de expresión, sin mutación BRAF, se procede al análisis germinal. Resultados: De ciento cuarenta y ocho pacientes en los que se realizó IMH, 23 presentaron pérdida de expresión. Siete fueron identificados como SSL: 3 con cáncer de colon, 2 con tumor endometrial y otros 2 sanos con familiar afectado. La edad media fue de 56.9 años y solo uno presentó otro tumor asociado al síndrome de Lynch. Conclusiones: Hasta que conozcamos mejor la etiología de esta entidad heterogénea, una vigilancia intermedia sería una estrategia adecuada. Keywords: Suspected Lynch syndrome, Immunohistochemistry, Genetic analysis, Risk for cancer, Surveillance, Palabras clave: Sospecha de síndrome de Lynch, Inmunohistoquímica, Análisis genético, Riesgo de cáncer, Vigilanci

Diagnóstico y comportamiento clínico de pacientes con sospecha de síndrome de Lynch sin mutación conocida

Resumen: Introducción y objetivos: La sospecha de síndrome de Lynch sin mutación conocida (SSL) se diagnostica cuando existe déficit de expresión de las proteínas reparadoras de ADN pero con estudio genético normal. El comportamiento y el manejo son controvertidos. Presentamos las características de pacientes con SSL y proponemos una vigilancia. Material y métodos: Se realiza análisis inmunohistoquímico (IMH) en familias con sospecha de síndrome de Lynch. Si existe pérdida de expresión, sin mutación BRAF, se procede al análisis germinal. Resultados: De ciento cuarenta y ocho pacientes en los que se realizó IMH, 23 presentaron pérdida de expresión. Siete fueron identificados como SSL: 3 con cáncer de colon, 2 con tumor endometrial y otros 2 sanos con familiar afectado. La edad media fue de 56.9 años y solo uno presentó otro tumor asociado al síndrome de Lynch. Conclusiones: Hasta que conozcamos mejor la etiología de esta entidad heterogénea, una vigilancia intermedia sería una estrategia adecuada. Abstract: Introduction and aims: Lynch-like syndrome is diagnosed when there is an expression deficit in DNA mismatch repair proteins but a normal genetic study. The behavior and management of that pathology are currently a subject of debate. We present herein the characteristics of patients with Lynch-like syndrome, together with a surveillance proposal. Materials and methods: Immunohistochemistry was carried out on families suspected of presenting with Lynch syndrome. Germline analysis was done if there was loss of mismatch repair protein expression and no BRAF mutation. Results: Of the 148 patients that underwent immunohistochemistry testing, 23 presented with loss of mismatch repair protein expression. Seven of those patients were identified as having Lynch-like syndrome: 3 had colon cancer, 2 had endometrial tumor, and 2 were healthy, with an affected relative. Mean patient age was 56.9 years and only one patient presented with another tumor associated with Lynch syndrome. Conclusions: Until there is a better understanding of the etiology of that heterogeneous entity, intermediate surveillance is an adequate strategy. Palabras clave: Sospecha de síndrome de Lynch, Inmunohistoquímica, Análisis genético, Riesgo de cáncer, Vigilancia, Keywords: Suspected Lynch syndrome, Immunohistochemistry, Genetic analysis, Risk for cancer, Surveillanc

The innovation cycle for sustainable ICT education

Ponencia de la conferencia "1st IFIP WG 3.4 International Conference on Sustainable ICT, Education, and Learning, SUZA 2019; Zanzibar; Tanzania; 25 April 2019 through 27 April 2019"Usually, the cycle of innovation is sold as a great progress in Education. However, in Education, the cycle of innovation does not exist as we might expect. Innovation is cyclical by itself. Each step of the structure can be modified, improved and complemented without waiting for a whole process that shows logic in other areas (engineering, logistics, and psychology, for instance) but that, in education, seems to be a luxury. This position paper shows why and how to perform a dynamic innovation cycle that enhances learning and teaching experiences, Worldwide, including North-North, North-South and South-South approaches, supported by initiatives by UNESCO, the International Council of Distance Education, Open Education Consortium, the European Commission and others

How to Integrate Formal and Informal Settings in Massive Open Online Courses Through a Transgenic Learning Approach

Capítulo del libro "Lecture Notes in Educational Technology"Formal and informal learning settings overlap quite often. Since the arrival and consolidation of 24/7 Internet services, contents, authoring tools and free storage, informal settings have become a powerful resource for learning. The combination of both scenarios is a reality that must be tackled: one with regular academic programmes, and the other one with mostly unstructured learning and information unit. However, successful engagement between them is not that common. Regular academic programmes deployed with learning management systems (LMS) keep a track of user activity and user performance. Sometimes these inputs are stored and processed to provide some useful feedback in the form of recommendation or advice to the very same user. However, there is usually no tracking of user activity on social media, external fora or other online services. This lack of awareness about user activity outside the LMS prevents the educational methodology or the pedagogical model from considering all the available information. It also restricts the analysis to just one area: official education. To this extent, MOOCs have become a crucial part of combined educational models that move between formal and informal settings, where they play a key role in the learning path of every user. However, this does not seem enough. The current educational landscape requires disruption to boost the learning-teaching process. We call this disruption transgenic learning. It is based on the user’s behaviour and interactions, along with efficient monitoring and personalised counselling by a tutor. It is focused on improving the user’s awareness of their real academic status and their related performance. In this book chapter, we discuss the specific implementation of a personalised eLearning model for restricted social networks and learning management systems, called LIME, which supports this approach. LIME is focused on massive enrolment and large datasets. We also present a framework and software prototype that implements the model (iLIME). Lastly, we show a successful practical case study that makes use of iLIME integrated with the Sakai CLE LMS. This case study depicts the technical issues, challenges and solutions involved in a successful deployment of the LIME model into a real university scenari