1,916 research outputs found

    Multidimensional integration of RDF datasets

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    Data providers have been uploading RDF datasets on the web to aid researchers and analysts in finding insights. These datasets, made available by different data providers, contain common characteristics that enable their integration. However, since each provider has their own data dictionary, identifying common concepts is not trivial and we require costly and complex entity resolution and transformation rules to perform such integration. In this paper, we propose a novel method, that given a set of independent RDF datasets, provides a multidimensional interpretation of these datasets and integrates them based on a common multidimensional space (if any) identified. To do so, our method first identifies potential dimensional and factual data on the input datasets and performs entity resolution to merge common dimensional and factual concepts. As a result, we generate a common multidimensional space and identify each input dataset as a cuboid of the resulting lattice. With such output, we are able to exploit open data with OLAP operators in a richer fashion than dealing with them separately.This research has been funded by the European Commission through the Erasmus Mundus Joint Doctorate Information Technologies for Business Intelligence-Doctoral College (IT4BI-DC) program.Peer ReviewedPostprint (author's final draft

    Non-cirrhotic thrombocytopenic patients with hepatitis C virus: characteristics and outcome of antiviral therapy.

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    Background and Aim: Thrombocytopenia is frequently observed in patients with chronic hepatitis C virus (HCV) infection and cirrhosis, although it can also be observed in patients without cirrhosis by a virus-mediated phenomenon. This study assessed the prevalence, characteristics, and outcomes of antiviral therapy in patients with chronic HCV infection and thrombocytopenia not associated with cirrhosis. Methods: The study included 1268 patients with HCV infection and thrombocytopenia enrolled in the phase 3 ENABLE studies that assessed the impact of eltrombopag on achieving a sustained virologic response to pegylated interferon and ribavirin. The study population was subdivided according to baseline FibroSURE test results into patients with non-cirrhosis (FibroSURE < 0.4) and cirrhosis-related (FibroSURE 65 0.75) thrombocytopenia. Results: Compared with patients with cirrhosis-related thrombocytopenia (n = 995; 78.5%), non-cirrhotic patients with thrombocytopenia (n = 59; 4.6%) were younger (mean age [95% confidence interval (CI)]: 43.9 [40.7\u201347.2] vs 52.7 [52.2\u201353.3] years; P < 0.0001), predominantly female (64% [51\u201376] vs 30% [27\u201333]; P < 0.0001), and less frequently had a Model for End-Stage Liver Disease score 65 10 (24% [14\u201337] vs 45% [42\u201349]; P = 0.0012), low albumin levels ( 64 35 g/L; 2% [0\u20139] vs 32% [29\u201335]; P < 0.0001), and prevalence of diabetes mellitus (3% [0\u201312] vs 21% [19\u201324]; P = 0.0005). The sustained virologic response rate was higher in non-cirrhotic patients with thrombocytopenia (46% [95% CI, 33\u201359] vs 16% [14\u201318]; P < 0.0001). Conclusions: Patients with thrombocytopenia associated with HCV who have lower FibroSURE test results may have better preserved liver function and higher sustained virologic response rates than patients with cirrhosis

    Cumplimiento, conocimiento y automedicaciĂłn como factores asociados a los resultados clĂ­nicos negativos de la farmacoterapia

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    The patient plays a fundamental role in the attainment of good results in pharmacotherapy. Noncompliance,self-medication, or insufficient knowledge of the therapy being employed may provide asource for the causes of these negative clinical outcomes, otherwise known as medicine related problems(MRP). he Dader method was used in the evaluation, identification and classification of MRP. Theassociation of variables was established through the statistical Chi square test. Patient knowledge of themedicine, degree of compliance to therapy and self-medication were studied as causes of the negativeoutcomes encountered. 2556 patients were interviewed throughout the year that the study took place,giving a total of 2261 of valid cases. 33% presented an MRP as the cause of his/her visit to the hospitalemergency ward. Knowledge of the medicine, compliance and self-medication were only studied in thepopulation that presented an MRP and in this work it is demonstrated that these are aspects that areassociated with different dimensions of MRP. It is not possible to establish an association between theexistence or not of negative clinical outcomes in patients with the factors of knowledge of medication,compliance and self-medication. This is due to the fact that these variables are not attributable to thepatient himself, but rather are associated with the characteristics of each medicine.El paciente juega un papel primordial en la consecuciĂłn de los resultados terapĂŠuticos. El incumplimiento,la automedicaciĂłn, o la falta de conocimiento del la farmacoterapia pueden ser causas de esosresultados clĂ­nicos negativos, denominados en ocasiones problemas relacionados con medicamentos(PRM). El mĂŠtodo DĂĄder se utilizĂł para la evaluaciĂłn, identificaciĂłn y clasificaciĂłn de PRM. LaasociaciĂłn de variables se estableciĂł mediante el estadĂ­stico chi cuadrado. El conocimiento de la medicaciĂłn,el cumplimiento y la automedicaciĂłn fueron estudiados como causa de estos resultados negativosde la medicaciĂłn. Fueron entrevistados 2556 pacientes durante el aĂąo de estudio, resultando 2261 casosvĂĄlidos. El 33 % presentaron un PRM como causa de visita a urgencias. El conocimiento de la medicaciĂłn,el cumplimiento y la automedicaciĂłn fueron estudiados solo en la poblaciĂłn que presentĂł unPRM y se demuestra que son aspectos asociados a las distintas dimensiones de PRM. No es posibleestablecer asociaciĂłn entre la existencia o no de resultados clĂ­nicos negativos en los pacientes con elconocimiento de la medicaciĂłn, el cumplimiento y la automedicaciĂłn, debido a que estas variables noson atributos del paciente sino que estĂĄn asociadas a cada medicamento

    Novel insights into the cardio-protective effects of FGF21 in lean and obese rat hearts

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    Aims: Fibroblast growth factor 21 (FGF21) is a hepatic metabolic regulator with pleotropic actions. Its plasma concentrations are increased in obesity and diabetes; states associated with an increased incidence of cardiovascular disease. We therefore investigated the direct effect of FGF21 on cardio-protection in obese and lean hearts in response to ischemia. Methods and Results: FGF21, FGF21-receptor 1 (FGFR1) and beta-Klotho (βKlotho) were expressed in rodent, human hearts and primary rat cardiomyocytes. Cardiac FGF21 was expressed and secreted (real time RT-PCR/western blot and ELISA) in an autocrine-paracrine manner, in response to obesity and hypoxia, involving FGFR1-βKlotho components. Cardiac-FGF21 expression and secretion were increased in response to global ischemia. In contrast βKlotho was reduced in obese hearts. In isolated adult rat cardiomyocytes, FGF21 activated PI3K/Akt (phosphatidylinositol 3-kinase/Akt), ERK1/2(extracellular signal-regulated kinase) and AMPK (AMP-activated protein kinase) pathways. In Langendorff perfused rat [adult male wild-type wistar] hearts, FGF21 administration induced significant cardio-protection and restoration of function following global ischemia. Inhibition of PI3K/Akt, AMPK, ERK1/2 and ROR-ι (retinoic-acid receptor alpha) pathway led to significant decrease of FGF21 induced cardio-protection and restoration of cardiac function in response to global ischemia. More importantly, this cardio-protective response induced by FGF21 was reduced in obesity, although the cardiac expression profiles and circulating FGF21 levels were increased. Conclusion: In an ex vivo Langendorff system, we show that FGF21 induced cardiac protection and restoration of cardiac function involving autocrine-paracrine pathways, with reduced effect in obesity. Collectively, our findings provide novel insights into FGF21-induced cardiac effects in obesity and ischemia

    Translational Medicine is developing in China: A new venue for collaboration

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    Translational Medicine is an emerging area comprising multidisciplinary Research from basic sciences to medical applications well summarized by the Bench-to-Beside concept; this entails close collaboration between clinicians and basic scientists across institutes. We further clarified that Translational Medicine should be regarded as a two-way road: Bench-to-Bedside and Bedside-to-Bench, to complement testing of novel therapeutic strategies in humans with feedback understanding of how they respond to them. It is, therefore, critical and important to define and promote Translational Medicine among clinicians, basic Researchers, biotechnologists, politicians, ethicists, sociologists, investors and coordinate these efforts among different Countries, fostering aspects germane only to this type of Research such as, as recently discussed, biotechnology entrepreneurship. Translational Medicine as an inter-disciplinary science is developing rapidly and widely and, in this article, we will place a special emphasis on China

    Orlistat after initial dietary/behavioural treatment: changes in body weight and dietary maintenance in subjects with sleep related breathing disorders

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    <p>Abstract</p> <p>Background</p> <p>Sleep related breathing disorders (SRBD) are associated with increased morbidity and mortality and weight loss is recommended to overweight or obese patients with SRBD. However, maintenance of weight loss is difficult to achieve and strategies for weight loss maintenance is needed. Orlistat is a pharmacological agent that reduces the intestinal absorption of fat and may favour long-term weight maintenance.</p> <p>Objective</p> <p>To examine the change in body weight and dietary intake during a 1-year treatment with orlistat after an initial weight loss in obese subjects with SRBD. Furthermore, to explore the dietary determinants of weight maintenance during treatment with orlistat.</p> <p>Methods</p> <p>Men and women with SRBD aged 32-62 years (n = 63) participated in a 3-month dietary intervention to increase intake of vegetables and fruit. After an initial weight loss of 3.4 kg they achieved a mean body mass index of 34.3 Âą 4.7 kg/m2. Subsequently they were treated with orlistat for 1 year. During this year, dietary and behavioural interventions to attain weight loss were provided in the course of 14 group sessions. Dietary intake, energy density and food choices were assessed with a food frequency questionnaire before and after orlistat treatment.</p> <p>Results</p> <p>With orlistat, body weight decreased by a mean of 3.5 kg (95% CI 1.5, 5.5). The dietary E% from saturated fat, intake of fatty dairy products and energy density increased after 1 year while intakes of oils, fish and vegetables decreased (all P < 0.05). After multivariate adjustments, weight loss was associated with E% protein (R2<sub>adj </sub>= 0.19 [95% CI 0.10, 0.46]), and inversely associated with E% saturated fat (R2<sub>adj </sub>= 0.20 [95% CI 0.12, 0.47]) and fatty dairy products (R2<sub>adj </sub>= 0.23 [95% CI 0.12, 0.49]).</p> <p>Conclusions</p> <p>Orlistat induced further weight loss, but dietary compliance declined with time. Increasing dietary protein and restricting saturated fat and fatty dairy products may facilitate weight loss with orlistat.</p

    β1 Integrin-Mediated Adhesion Signalling Is Essential for Epidermal Progenitor Cell Expansion

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    Background: There is a major discrepancy between the in vitro and in vivo results regarding the role of b1 integrins in the maintenance of epidermal stem/progenitor cells. Studies of mice with skin-specific ablation of b1 integrins suggested that epidermis can form and be maintained in their absence, while in vitro data have shown a fundamental role for these adhesion receptors in stem/progenitor cell expansion and differentiation. Methodology/Principal Findings: To elucidate this discrepancy we generated hypomorphic mice expressing reduced b1 integrin levels on keratinocytes that developed similar, but less severe defects than mice with b1-deficient keratinocytes. Surprisingly we found that upon aging these abnormalities attenuated due to a rapid expansion of cells, which escaped or compensated for the down-regulation of b1 integrin expression. A similar phenomenon was observed in aged mice with a complete, skin-specific ablation of the b1 integrin gene, where cells that escaped Cre-mediated recombination repopulated the mutant skin in a very short time period. The expansion of b1 integrin expressing keratinocytes was even further accelerated in situations of increased keratinocyte proliferation such as wound healing. Conclusions/Significance: These data demonstrate that expression of b1 integrins is critically important for the expansion of epidermal progenitor cells to maintain epidermal homeostasis

    Characterisation of a divergent progenitor cell sub-populations in human osteoarthritic cartilage: the role of telomere erosion and replicative senescence

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    In recent years it has become increasingly clear that articular cartilage harbours a viable pool ofprogenitor cells and interest has focussed on their role during development and disease. Analysis ofprogenitor numbers using fluorescence-activated sorting techniques has resulted in wide-rangingestimates, which may be the result of context-dependent expression of cell surface markers. Wehave used a colony-forming assay to reliably determine chondroprogenitor numbers in normal andosteoarthritic cartilage where we observed a 2-fold increase in diseased tissue (P &#60; 0.0001). Intriguingly,cell kinetic analysis of clonal isolates derived from single and multiple donors of osteoarthritic cartilagerevealed the presence of a divergent progenitor subpopulation characterised by an early senescentphenotype. Divergent sub-populations displayed increased senescence-associated β–galactosidaseactivity, lower average telomere lengths but retained the capacity to undergo multi-lineagedifferentiation. Osteoarthritis is an age-related disease and cellular senescence is predicted to be asignificant component of the pathological process. This study shows that although early senescenceis an inherent property of a subset of activated progenitors, there is also a pool of progenitors withextended viability and regenerative potential residing within osteoarthritic cartilage
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