1,720,976 research outputs found
Hepatocellular carcinoma in viral and autoimmune liver diseases: Role of CD4+ CD25+ Foxp3+ regulatory T cells in the immune microenvironment
Get PDFMore than 90% of cases of hepatocellular carcinoma (HCC) occurs in patients with cirrhosis, of which hepatitis B virus and hepatitis C virus are the leading causes, while the tumor less frequently arises in autoimmune liver diseases. Advances in understanding tumor immunity have led to a major shift in the treatment of HCC, with the emergence of immunotherapy where therapeutic agents are used to target immune cells rather than cancer cells. Regulatory T cells (Tregs) are the most abundant suppressive cells in the tumor microenvironment and their presence has been correlated with tumor progression, invasiveness, as well as metastasis. Tregs are characterized by the expression of the transcription factor Foxp3 and various mechanisms ranging from cell-to-cell contact to secretion of inhibitory molecules have been implicated in their function. Notably, Tregs amply express checkpoint molecules such as cytotoxic T lymphocyte-associated antigen 4 and programmed cell-death 1 receptor and therefore represent a direct target of immune checkpoint inhibitor (ICI) immunotherapy. Taking into consideration the critical role of Tregs in maintenance of immune homeostasis as well as avoidance of autoimmunity, it is plausible that targeting of Tregs by ICI immunotherapy results in the development of immune-related adverse events (irAEs). Since the use of ICI becomes common in oncology, with an increasing number of new ICI currently under clinical trials for cancer treatment, the occurrence of irAEs is expected to dramatically rise. Herein, we review the current literature focusing on the role of Tregs in HCC evolution taking into account their opposite etiological function in viral and autoimmune chronic liver disease, and we discuss their involvement in irAEs due to the new immunotherapies
The evolving phenotype of autoimmune hepatitis across the millennium: The 40-year experience of a referral centre in Italy
Get PDFBackground and Aims: During recent years, there have been major insight into the pathogenesis, diagnosis and treatment of autoimmune hepatitis (AIH). We aim to evaluate modifications of the clinical-epidemiological phenotype of AIH patients from 1980 to our days. Methods: Single-centre, tertiary care retrospective study on 507 consecutive Italian patients with AIH. Patients were divided into four subgroups according to the decade of diagnosis: 1981–1990, 1991–2000, 2001–2010 and 2011–2020. We assessed clinical, laboratory and histological features at diagnosis, response to treatment and clinical outcomes. Acute presentation is defined as transaminase levels >10-fold the upper limit and/or bilirubin >5 mg/dL. Complete response is defined as the normalization of transaminases and IgG after 12 months. Clinical progression is defined as the development of cirrhosis in non-cirrhotic patients and hepatic decompensation/hepatocellular carcinoma development in compensated cirrhosis. Results: Median age at diagnosis increased across decades (24, 31, 39, 52 years, p <.001). Acute onset became more common (39.6%, 44.4%, 47.7%, 59.5%, p =.019), while cirrhosis at diagnosis became less frequent (36.5%, 16.3%, 10.8%, 8.7%, p <.001). Complete response rates rose (11.1%, 49.4%, 72.7% 76.2%, p <.001) and clinical progression during follow-up decreased (54.3%, 29.9%, 16.9%, 11.2%, p <.001). Anti-nuclear antibodies positivity increased (40.7%, 52.0%, 73.7%, 79.3%, p <.001), while IgG levels/upper limit progressively decreased (1.546, 1.515, 1.252, 1.120, p <.001). Liver-related death and liver transplantation reduced from 17.1% to 2.1% (p <.001). Conclusions: In the new millennium, the typical AIH patient in Italy is older at diagnosis, more often presents with acute hepatitis, cirrhosis is less frequent and response to treatment is more favourable
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe 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
Paraneoplastic Anti-Tif1-gamma Autoantibody-positive Dermatomyositis as Clinical Presentation of Hepatocellular Carcinoma Recurrence
Get PDFHepatocellular carcinoma (HCC) is rarely associated with autoimmune paraneoplastic syndromes. We report a case of anti-transcriptional intermediary factor-1 gamma (TIF1-??)-positive dermatomyositis (DM) as clinical presentation of HCC recurrence in a 72-year-old male patient admitted to our hospital due to fatigue, myalgia, and typical skin rash. His medical history was notable for hepatitis C-related cir-rhosis, successful treatment with direct-acting antiviral agents, and previously efficacious treatment of HCC. Labo-ratory testing showed significant rhabdomyolysis with anti-TIF1-?? antibodies at high titer, and DM was diagnosed. After a careful diagnostic workup, HCC recurrence was diagnosed. After first-line corticosteroid treatment, azathioprine and in-travenous immunoglobulin treatments were administered; unfortunately, he mounted only partial response. Owing to the compromised performance status, no HCC treatment was feasible, and, according to international guidelines, he received only best supportive care. Here, we discuss the diagnostic, prognostic, and pathogenic roles of anti-TIF1-?? antibodies associated with paraneoplastic DM and the scant literature data on its occurrence in HCC patients. Consider-ing the TIF1 gene family???s established role in oncogenesis, we also review the role of TIF1-?? as a tumor-related neo-antigen, leading to the development of clinically overt anti-TIF1-?? antibodies-positive DM
Variations on the Author
Get PDF“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
Get PDFWe 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
Get PDFWe 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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