1,721,013 research outputs found
Targeted treatments for cirrhosis
No full textThe causes of hepatic scarring (fibrosis) are protean but, unchecked, all result in a common fate--the development of cirrhosis--with gross disruption of the normal liver architecture. Subsequent liver cell dysfunction and portal hypertension give rise to major systemic complications and premature death. Cirrhosis and its sequelae represent a huge, and global, healthcare burden. The success of liver transplantation and the development of efficacious antiviral regimens for hepatitis B and C should not be underestimated, but they also serve to highlight our current inability to manipulate the underlying fibrotic process in many patients with liver disease. Moreover, transplantation as a treatment is limited by organ availability, among other factors. The development of antifibrotic therapies is urgently needed and for this we require a mechanistic and evidence-based approach. Accumulating data from clinical and laboratory studies demonstrate that even advanced fibrosis and cirrhosis are potentially reversible. The hepatic stellate cells have been identified as the pivotal effector cells orchestrating the fibrotic process and, furthermore, reversibility appears to hinge upon their elimination. This review draws on recent scientific advances, and highlights emerging therapeutic interventions in liver fibrosis
Misclassification of coffee consumption data and the development of a standardised coffee unit measure.
Full text linkBackground Associations of coffee consumption with multiple health outcomes have been researched extensively. Coffee consumption, usually reported in cups a day, is a heterogeneous measure due to numerous preparation methods and cup sizes, leading to misclassification. This paper develops a new ‘unit’ measure of coffee and uses coffee consumption data from a representative sample of the UK population to assess the degree of misclassification when cup volume and preparation type are not taken into account. Methods A coffee unit measure was created using published estimates of caffeine and chlorogenic acid concentrations, and applied across volumes and preparation types. Four-day food diary data in adults from the UK National Diet and Nutrition Survey (NDNS; 2012-16) were used to quantify coffee intake. Participant self-reported cups a day were compared with cups a day standardised by a) 227mL volume and b) 227mL instant coffee equivalents (unit measure), and the degree of misclassification was derived. Sensitivity analyses were conducted to model coffee drinking preferences of different populations and caffeine:chlorogenic acid weighting assumptions of the unit measure. Results The NDNS sample consisted of 2832 adult participants. Coffee was consumed by 62% of participants. Types varied, with 75% of caffeinated coffee cups being instant, 17% filter, 3% latte, 2% cappuccino, 2% espresso and <1% other types. Comparing reported cups to volume-standardised cups, 84% of participants had correct classification, and 73% when using the coffee unit measure, 22% underestimated and 5% overestimated, largely by 1 cup. Misclassification varied by gender, age and income. Sensitivity analysis highlighted the benefits of using the unit measure over volume alone to cater for different populations, and the stability of the unit composition assumption. Conclusion Cup volume and preparation type should be taken into account, through application of a standardised coffee unit measure, when coffee consumption is classified in future research studies
Scar-associated macrophages are a major source of hepatic matrix metalloproteinase-13 and facilitate the resolution of murine hepatic fibrosis
No full textBoth the identity and source of the rodent collagenase(s) that mediates matrix remodeling in liver fibrosis remain elusive. We have recently demonstrated an unequivocal role for scar-associated macrophages (SAMs) in the spontaneous resolution of liver fibrosis and sought to determine whether SAMs are the source of matrix metalloproteinase (MMP) 13 (collagenase 3), considered to be the primary interstitial collagenase in rodents. In this study, we demonstrate an association between MMP13 expression and the presence of SAMs in the regression of experimental liver fibrosis. mmp13 gene expression was restricted to regions of fibrosis that were rich in SAMs. Both MMP13 mRNA and protein colocalized to large phagocytes within and directly apposed to hepatic scars. Using the CD11b-DTR-transgenic mouse to deplete SAMs in a model of chronic CCl(4) injury, we found that SAM depletion resulted in a 5-fold reduction in mmp13 message (p = 0.005). Furthermore, resolution of CCl(4)-induced fibrosis was retarded in MMP13-deficient mice. Thus, SAMs selectively, during resolution of fibrosis induce and use the major collagenase MMP13 to mediate the resorption of interstitial matrix and successfully remodel the fibrotic liver
All coffee types decrease the risk of adverse clinical outcomes in chronic liver disease: a UK Biobank study
Full text linkAbstract Background Chronic liver disease (CLD) is a growing cause of morbidity and mortality worldwide, particularly in low to middle-income countries with high disease burden and limited treatment availability. Coffee consumption has been linked with lower rates of CLD, but little is known about the effects of different coffee types, which vary in chemical composition. This study aimed to investigate associations of coffee consumption, including decaffeinated, instant and ground coffee, with chronic liver disease outcomes. Methods A total of 494,585 UK Biobank participants with known coffee consumption and electronic linkage to hospital, death and cancer records were included in this study. Cox regression was used to estimate hazard ratios (HR) of incident CLD, incident CLD or steatosis, incident hepatocellular carcinoma (HCC) and death from CLD according to coffee consumption of any type as well as for decaffeinated, instant and ground coffee individually. Results Among 384,818 coffee drinkers and 109,767 non-coffee drinkers, there were 3600 cases of CLD, 5439 cases of CLD or steatosis, 184 cases of HCC and 301 deaths from CLD during a median follow-up of 10.7 years. Compared to non-coffee drinkers, coffee drinkers had lower adjusted HRs of CLD (HR 0.79, 95% CI 0.72–0.86), CLD or steatosis (HR 0.80, 95% CI 0.75–0.86), death from CLD (HR 0.51, 95% CI 0.39–0.67) and HCC (HR 0.80, 95% CI 0.54–1.19). The associations for decaffeinated, instant and ground coffee individually were similar to all types combined. Conclusion The finding that all types of coffee are protective against CLD is significant given the increasing incidence of CLD worldwide and the potential of coffee as an intervention to prevent CLD onset or progression
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
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