Compatibilitat en Àlgebra, en Lògica i en Informàtica

S'exposa una visió actual de l'estudi algebraic de la Lògica, especialment de les lògiques no clàssiques, prenent com a eix alguns conceptes purament algebraics com els de compatibilitat, congruència de Leibniz, i operador de Leibniz. Es mostra com aquests conceptes permeten definir una jerarquia de lògiques i classificar-les pel seu capteniment envers la seva algebrització, és a dir, per les relacions que mantenen amb els seus models algebraics, i per les propietats d'aquests models. Al final s'esmenten algunes de les línies de recerca més recents, en el context del camp emergent actualment anomenat Lògica Algebraica Abstracta.This paper introduces the current view on the algebraic studies in Logic, especially in the domain of non-classical logics. The paper is organized around some pure algebraic concepts such as compatibility, Leibniz congruence, and the Leibniz operator. It is shown how these concepts allow to define a hierarchy of logics and to classify them according to their behaviour as far as their algebraization is concerned, that is, by the kind of relation they have with their algebraic models, and by the properties of these models. The paper ends with a brief survey of some of the most recent research lines in the context of the emerging field now called Abstract Algebraic Logic

Translational medicine in Catalonia: the case of liver oncology

La recerca biomèdica ha millorat notablement a Catalunya durant la darrera dècada de tal manera que el nostre país es considera un pol de recerca internacionalment reconegut. Les polítiques endegades pel Govern de la Generalitat amb la creació del programa ICREA per a l'atracció de talent internacional han estat molt exitoses. En el meu cas, vaig tornar l'any 2006 de Nova York per organitzar un grup de recerca translacional en oncologia hepàtica al IDIBAPS-Hospital Clínic de Barcelona. Els avenços del nostre grup han estat possibles atès l'entorn científic que ofereix la institució pel que fa a recerca en malalties hepàtiques i en recerca translacional. El present article analitza alguns dels avenços en recerca translacional, recerca hepàtica i recerca translacional en oncologia hepàtica assolits al nostre país en la darrera dècada.Biomedical research has improved during the last decade in Catalonia, which is currently a well-recognized international biomedical scientific hub. The policy of head-hunting and attraction of talent fostered by the Catalan Government through the ICREA Professorship initiative has been successful. In 2006, I was appointed as ICREA Professor and started a research group in Translational research in liver oncology at IDIBAPS-Hospital Clínic in Barcelona. This appointment was possible due to a suitable environment in this institution, both regarding liver and translational medical research. This article summarizes some of the major advancements in translational medicine, liver research and translational hepatic oncology achieved during the last dècade

Compatibilitat en àlgebra, en lògica i en informàtica

S'exposa una visió actual de l'estudi algebraic de la Lògica, especialment de les lògiques no clàssiques, prenent com a eix alguns conceptes purament algebraics com els de compatibilitat, congruència de Leibniz, i operador de Leibniz. Es mostra com aquests conceptes permeten definir una jerarquia de lògiques i classificar-les pel seu capteniment envers la seva algebrització, és a dir, per les relacions que mantenen amb els seus models algebraics, i per les propietats d'aquests models. Al final s'esmenten algunes de les línies de recerca més recents, en el context del camp emergent actualment anomenat Lògica Algebraica Abstracta

Immune Exclusion-Wnt/CTNNB1 Class Predicts Resistance to Immunotherapies in HCC

Next-generation sequencing has provided information on actionable targets and biomarkers of response in oncology. In hepatocellular carcinoma (HCC), Wnt/CTNNB1 mutations characterize the immune-excluded class (cold tumors) and might represent the biomarkers predicting resistance to immune checkpoint inhibitors. Large-scale validation of these data is needed to customize immunotherapy in advanced HCC.See related article by Harding et al.©2019 American Association for Cancer Research

Molecular therapies and precision medicine for hepatocellular carcinoma

The global burden of hepatocellular carcinoma (HCC) is increasing and might soon surpass an annual incidence of 1 million cases. Genomic studies have established the landscape of molecular alterations in HCC; however, the most common mutations are not actionable, and only ~25% of tumours harbour potentially targetable drivers. Despite the fact that surveillance programmes lead to early diagnosis in 40–50% of patients, at a point when potentially curative treatments are applicable, almost half of all patients with HCC ultimately receive systemic therapies. Sorafenib was the first systemic therapy approved for patients with advanced-stage HCC, after a landmark study revealed an improvement in median overall survival from 8 to 11 months. New drugs — lenvatinib in the frontline and regorafenib, cabozantinib, and ramucirumab in the second line — have also been demonstrated to improve clinical outcomes, although the median overall survival remains ~1 year; thus, therapeutic breakthroughs are still needed. Immune-checkpoint inhibitors are now being incorporated into the HCC treatment armamentarium and combinations of molecularly targeted therapies with immunotherapies are emerging as tools to boost the immune response. Research on biomarkers of a response or primary resistance to immunotherapies is also advancing. Herein, we summarize the molecular targets and therapies for the management of HCC and discuss the advancements expected in the near future, including biomarker-driven treatments and immunotherapies

Liver Cancer Cell of Origin, Molecular Class, and Effects on Patient Prognosis

Primary liver cancer is the second leading cause of cancer-related death worldwide and therefore a major public health challenge. We review hypotheses of the cell of origin of liver tumorigenesis and clarify the classes of liver cancer based on molecular features and how they affect patient prognosis. Primary liver cancer comprises hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (iCCA), and other rare tumors, notably fibrolamellar carcinoma and hepatoblastoma. The molecular and clinical features of HCC versus iCCA are distinct, but these conditions have overlapping risk factors and pathways of oncogenesis. A better understanding of the cell types originating liver cancer can aid in exploring molecular mechanisms of carcinogenesis and therapeutic options. Molecular studies have identified adult hepatocytes as the cell of origin. These cells have been proposed to transform directly into HCC cells (via a sequence of genetic alterations), to dedifferentiate into hepatocyte precursor cells (which then become HCC cells that express progenitor cell markers), or to transdifferentiate into biliary-like cells (which give rise to iCCA). Alternatively, progenitor cells also give rise to HCCs and iCCAs with markers of progenitor cells. Advances in genome profiling and next-generation sequencing have led to the classification of HCCs based on molecular features and assigned them to categories such as proliferation-progenitor, proliferation-transforming growth factor β, and Wnt-catenin β1. iCCAs have been assigned to categories of proliferation and inflammation. Overall, proliferation subclasses are associated with a more aggressive phenotype and poor outcome of patients, although more specific signatures have refined our prognostic abilities. Analyses of genetic alterations have identified those that might be targeted therapeutically, such as fusions in the FGFR2 gene and mutations in genes encoding isocitrate dehydrogenases (in approximately 60% of iCCAs) or amplifications at 11q13 and 6p21 (in approximately 15% of HCCs). Further studies of these alterations are needed before they can be used as biomarkers in clinical decision making

Liver cancer: Approaching a personalized care

The knowledge and understanding of all aspects of liver cancer [this including hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA)] have experienced a major improvement in the last decades. New laboratory technologies have identified several molecular abnormalities that, at the very end, should provide an accurate stratification and optimal treatment of patients diagnosed with liver cancer. The seminal discovery of the TP53 hotspot mutation [1,2] was an initial landmark step for the future classification and treatment decision using conventional clinical criteria blended with molecular data. At the same time, the development of ultrasound, computed tomography (CT) and magnetic resonance (MR) has been instrumental for earlier diagnosis, accurate staging and treatment advances. Several treatment options with proven survival benefit if properly applied are now available. Major highlights include: i) acceptance of liver transplantation for HCC if within the Milan criteria [3], ii) recognition of ablation as a potentially curative option [4,5], iii) proof of benefit of chemoembolization (TACE), [6] and iv) incorporation of sorafenib as an effective systemic therapy [7]. These options are part of the widely endorsed BCLC staging and treatment model (Fig. 1) [8,9]. This is clinically useful and it will certainly keep evolving to accommodate new scientific evidence. This review summarises the data which are the basis for the current recommendations for clinical practice, while simultaneously exposes the areas where more research is needed to fulfil the still unmet needs (Table 1)

Nota sobre el significado lógico de ciertas estructuras residuadas elementales

Starting from an abelian grupoid which is ordered and residuated we study the logical significance of the 'residue' operation, specially if we add the most natural algebraic properties to the base structure, obtaining then several well-Known structures of mathematical logic, such as the deductively-complete algebras and the algebras of Sales,Hilbert,Abbott,Wajsberg and Boole .We also give some properties of the deductive systems and obtain an special version of the deduction theorem of Pla( [3] )

Cost-effectiveness of adjuvant therapy for hepatocellular carcinoma during the waiting list for liver transplantation.

Background: Survival after liver transplantation for early hepatocellular carcinoma (HCC) is worsened by the increasing dropout rate while waiting for a donor. Aims: To assess the cost effectiveness of adjuvant therapy while waiting for liver transplantation in HCC patients. Method: Using a Markov model, a hypothetical cohort of cirrhotic patients with early HCC was considered for: (1) adjuvant treatment—resection was limited to Child-Pugh's A patients with single tumours, and percutaneous treatment was considered for Child-Pugh's A and B patients with single tumours unsuitable for resection or with up to three nodules < 3 cm; and (2) standard management. Length of waiting time ranged from six to 24 months. Results: Surgical resection increased the transplantation rate (>10%) and provided gains in life expectancy of 4.8–6.1 months with an acceptable cost ($40 000/ year of life gained) for waiting lists ≥1 year whereas it was not cost effective ($74 000/life of year gained) for shorter waiting times or high dropout rate scenarios. Percutaneous treatment increased life expectancy by 5.2–6.7 months with a marginal cost of approximately $20 000/year of life gained in all cases, remaining cost effective for all waiting times. Conclusions: Adjuvant therapies for HCC while waiting for liver transplantation provide moderate gains in life expectancy and are cost effective for waiting lists of one year or more. For shorter waiting times, only percutaneous treatment confers a relevant survival advantage

Hepatocellular carcinoma

Liver cancer is the second leading cause of cancer-related deaths globally and has an incidence of approximately 850,000 new cases per year. Hepatocellular carcinoma (HCC) represents approximately 90% of all cases of primary liver cancer. The main risk factors for developing HCC are well known and include hepatitis B and C virus infection, alcohol intake and ingestion of the fungal metabolite aflatoxin B1. Additional risk factors such as non-alcoholic steatohepatitis are also emerging. Advances in the understanding of the molecular pathogenesis of HCC have led to identification of critical driver mutations; however, the most prevalent of these are not yet druggable targets. The molecular classification of HCC is not established, and the Barcelona Clinic Liver Cancer staging classification is the main clinical algorithm for the stratification of patients according to prognosis and treatment allocation. Surveillance programmes enable the detection of early-stage tumours that are amenable to curative therapies - resection, liver transplantation or local ablation. At more developed stages, only chemoembolization (for intermediate HCC) and sorafenib (for advanced HCC) have shown survival benefits. There are major unmet needs in HCC management that might be addressed through the discovery of new therapies and their combinations for use in the adjuvant setting and for intermediate- and advanced-stage disease. Moreover, biomarkers for therapy stratification, patient-tailored strategies targeting driver mutations and/or activating signalling cascades, and validated measurements of quality of life are needed. Recent failures in the testing of systemic drugs for intermediate and advanced stages have indicated a need to refine trial designs and to define novel approaches