Clinical relevance of biomarkers in cholangiocarcinoma: critical revision and future directions

Cholangiocarcinoma (CCA) is a malignant tumour arising from the biliary system. In Europe, this tumour frequently presents as a sporadic cancer in patients without defined risk factors and is usually diagnosed at advanced stages with a consequent poor prognosis. Therefore, the identification of biomarkers represents an utmost need for patients with CCA. Numerous studies proposed a wide spectrum of biomarkers at tissue and molecular levels. With the present paper, a multidisciplinary group of experts within the European Network for the Study of Cholangiocarcinoma discusses the clinical role of tissue biomarkers and provides a selection based on their current relevance and potential applications in the framework of CCA. Recent advances are proposed by dividing biomarkers based on their potential role in diagnosis, prognosis and therapy response. Limitations of current biomarkers are also identified, together with specific promising areas (ie, artificial intelligence, patient-derived organoids, targeted therapy) where research should be focused to develop future biomarkers

Avaliação da resistência ao cisalhamento da união entre duas ligas a base de CoCr e uma cerâmica

INTRODUCTION: Based on the importance of the integrity of the metal/ceramic interface, the purpose of this work was to evaluate the shear bond strength of the metal-ceramic union of two Co-Cr alloys (Wirobond C, Bego; Remanium 2000, Dentaurum) combined with Omega 900 ceramic (Vita Zahnfabrik). MATERIAL and METHOD: Eleven cylindrical matrixes were made for each alloy, and the metallic portion was obtained with the lost wax casting technique with standardized waxing of 4mm of height and of 4mm of diameter. The ceramic was applied according to the manufacturer’s recommendations with the aid of a teflon matrix that allowed its dimension to be standardized in the same size as the metallic portion. The specimens were submitted to the shear bond test in an universal testing machine (EMIC), with the aid of a device developed for such intention, and constant speed of 0.5mm/min. RESULTS and CONCLUSIONS: The mean resistance was 48.387MPa for Wirobond C alloy, with standard deviation of 17.718, and 55.956MPa for Remanium 2000, with standard deviation of 17.198. No statistically significant difference was observed between the shear strength of the two metal-ceramic alloys. ______________________________________________________________________________________________________________ RESUMOINTRODUÇÃO: Baseados na importância da integridade da interface metal-cerâmica, este trabalho tem como objetivo avaliar a resistência ao cisalhamento da união metal-cerâmica de duas ligas de Co-Cr (Wirobond C, Bego; Remanium 2000, Dentaurum) combinadas com a cerâmica Omega 900 (Vita Zahnfabrik). MATERIAIS E MÉTODOS: Foram confeccionados 11 corpos-de-prova cilíndricos para cada liga utilizada, sendo que a porção metálica foi obtida por fundição pela técnica da cera perdida, através de enceramentos padronizados com 4mm de altura por 4mm de diâmetro. A aplicação da cerâmica foi realizada segundo recomendações do fabricante, com auxílio de uma matriz de teflon que permitia sua padronização com as mesmas dimensões da porção metálica. Os corpos-de-prova foram submetidos ao ensaio de resistência ao cisalhamento em máquina de ensaios universal (EMIC), com auxílio de dispositivo desenvolvido para tal propósito, sob velocidade constante de 0,5mm/ min. RESULTADOS E CONCLUSÕES: As médias de resistência obtidas foram 48,387 MPa para a liga Wirobond C, com desvio padrão de 17,718, e 55,956 MPa para a Remanium 2000, com desvio padrão de 17,198. Após análise de variância foi possível observar que não há diferença estatisticamente significante entre os valores de resistência ao cisalhamento das duas ligas metalocerâmicas

Evaluation of silages of sweet potato vine

O presente trabalho teve como objetivo selecionar clones de batata-doce com potencial para uso na alimenta??o animal. O experimento foi conduzido em blocos ao acaso, com 11 clones e quatro repeti??es. Os clones avaliados fazem parte do banco de germoplasma da Universidade Federal dos Vales do Jequitinhonha e Mucuri, sendo: BD-06, BD-25, BD-15, BD-38, Cambraia, BD-31-TO, BD-67, BD-45, BD-42, BD-54 e a cultivar Brazl?ndia Rosada. Nas ramas coletadas do experimento foram avaliados o teor de mat?ria seca e as produtividades de massa verde e massa seca. Nas silagens de ramas foram avaliados o pH e os teores de mat?ria seca (MS), prote?na bruta (PB), fibra em detergente neutro (FDN), fibra em detergente ?cido (FDA), nutrientes digest?veis totais (NDT), f?sforo, c?lcio e s?dio. N?o houve diferen?a significativa para a produtividade de massa verde e de massa seca das ramas entre os clones de batata-doce. As silagens produzidas caracterizam-se como volumosos de boa qualidade, apresentando teores satisfat?rios de prote?na bruta (11,59%), FDN (31,98 a 39,68%), FDA (29,65 a 35,45%) e NDT (62,90 a 66,91%), comprovando o potencial de utiliza??o das ramas da batata-doce na forma de silagem.Funda??o de Amparo ? Pesquisa do Estado de Minas Gerais (FAPEMIG)Empresa de Pesquisa Agropecu?ria de Minas Gerais (EPAMIG)Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico (CNPq)Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior (CAPES)The objective of this study was to select potential clones of sweet potato for animal feeding purposes. The experiment was carried out in a randomized block design with four replications. Eleven clones BD-06, BD-25, BD-15, BD-38, Cambraia, BD-31-TO, BD-67, BD-45, BD-42, BD-54 and the cultivar Brazl?ndia Rosada belonging to germplasm bank of the Federal University of Vales do Jequitinhonha and Mucuri (UFVJM) were evaluated. We estimated the dry matter content and the productivity of green and dry mass of the vine. The traits pH, dry matter, crude protein phosphorus, calcium and sodium were estimated in the evaluation of silages quality. There was no significant difference in productivity of green mass and dry mass among the clones of sweet potato. The obtained silages had sufficient levels of crude protein (11.59%), neutral detergent fiber (31.98 to 39.68%), acid detergent fiber (29.65 to 35.45%) and total digestible nutrients (62.90 to 66.91%) proving the potential use of the sweet potato vine as silage in animal feeding

Impact of safety-related dose reductions or discontinuations on sustained virologic response in HCV-infected patients: Results from the GUARD-C Cohort

BACKGROUND: Despite the introduction of direct-acting antiviral agents for chronic hepatitis C virus (HCV) infection, peginterferon alfa/ribavirin remains relevant in many resource-constrained settings. The non-randomized GUARD-C cohort investigated baseline predictors of safety-related dose reductions or discontinuations (sr-RD) and their impact on sustained virologic response (SVR) in patients receiving peginterferon alfa/ribavirin in routine practice. METHODS: A total of 3181 HCV-mono-infected treatment-naive patients were assigned to 24 or 48 weeks of peginterferon alfa/ribavirin by their physician. Patients were categorized by time-to-first sr-RD (Week 4/12). Detailed analyses of the impact of sr-RD on SVR24 (HCV RNA <50 IU/mL) were conducted in 951 Caucasian, noncirrhotic genotype (G)1 patients assigned to peginterferon alfa-2a/ribavirin for 48 weeks. The probability of SVR24 was identified by a baseline scoring system (range: 0-9 points) on which scores of 5 to 9 and <5 represent high and low probability of SVR24, respectively. RESULTS: SVR24 rates were 46.1% (754/1634), 77.1% (279/362), 68.0% (514/756), and 51.3% (203/396), respectively, in G1, 2, 3, and 4 patients. Overall, 16.9% and 21.8% patients experienced 651 sr-RD for peginterferon alfa and ribavirin, respectively. Among Caucasian noncirrhotic G1 patients: female sex, lower body mass index, pre-existing cardiovascular/pulmonary disease, and low hematological indices were prognostic factors of sr-RD; SVR24 was lower in patients with 651 vs. no sr-RD by Week 4 (37.9% vs. 54.4%; P = 0.0046) and Week 12 (41.7% vs. 55.3%; P = 0.0016); sr-RD by Week 4/12 significantly reduced SVR24 in patients with scores <5 but not 655. CONCLUSIONS: In conclusion, sr-RD to peginterferon alfa-2a/ribavirin significantly impacts on SVR24 rates in treatment-naive G1 noncirrhotic Caucasian patients. Baseline characteristics can help select patients with a high probability of SVR24 and a low probability of sr-RD with peginterferon alfa-2a/ribavirin

TRY plant trait database - enhanced coverage and open access

Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives

The Interaction Properties of the Human Rab GTPase Family – A Comparative Analysis Reveals Determinants of Molecular Binding Selectivity

Rab GTPases constitute the largest subfamily of the Ras protein superfamily. Rab proteins regulate organelle biogenesis and transport, and display distinct binding preferences for effector and activator proteins, many of which have not been elucidated yet. The underlying molecular recognition motifs, binding partner preferences and selectivities are not well understood.Comparative analysis of the amino acid sequences and the three-dimensional electrostatic and hydrophobic molecular interaction fields of 62 human Rab proteins revealed a wide range of binding properties with large differences between some Rab proteins. This analysis assists the functional annotation of Rab proteins 12, 14, 26, 37 and 41 and provided an explanation for the shared function of Rab3 and 27. Rab7a and 7b have very different electrostatic potentials, indicating that they may bind to different effector proteins and thus, exert different functions. The subfamily V Rab GTPases which are associated with endosome differ subtly in the interaction properties of their switch regions, and this may explain exchange factor specificity and exchange kinetics.We have analysed conservation of sequence and of molecular interaction fields to cluster and annotate the human Rab proteins. The analysis of three dimensional molecular interaction fields provides detailed insight that is not available from a sequence-based approach alone. Based on our results, we predict novel functions for some Rab proteins and provide insights into their divergent functions and the determinants of their binding partner selectivity

Performance of CMS muon reconstruction in pp collision events at sqrt(s) = 7 TeV

The performance of muon reconstruction, identification, and triggering in CMS has been studied using 40 inverse picobarns of data collected in pp collisions at sqrt(s) = 7 TeV at the LHC in 2010. A few benchmark sets of selection criteria covering a wide range of physics analysis needs have been examined. For all considered selections, the efficiency to reconstruct and identify a muon with a transverse momentum pT larger than a few GeV is above 95% over the whole region of pseudorapidity covered by the CMS muon system, abs(eta) < 2.4, while the probability to misidentify a hadron as a muon is well below 1%. The efficiency to trigger on single muons with pT above a few GeV is higher than 90% over the full eta range, and typically substantially better. The overall momentum scale is measured to a precision of 0.2% with muons from Z decays. The transverse momentum resolution varies from 1% to 6% depending on pseudorapidity for muons with pT below 100 GeV and, using cosmic rays, it is shown to be better than 10% in the central region up to pT = 1 TeV. Observed distributions of all quantities are well reproduced by the Monte Carlo simulation.Comment: Replaced with published version. Added journal reference and DO