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    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The 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

    Different significance of ret/PTC(1) and ret/PTC(3) rearrangements in thyroid carcinogenesis: lesson from two subgroups of patients with papillary thyroid carcinomas showing the highest incidence of ret/PTC activation

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    Different Significance of ret/PTC1 and ret/PTC3 Rearrangements in Thyroid Carcinogenesis: Lesson from Two Subgroups of Patients with Papillary Thyroid Carcinomas Showing the Highest Incidence of ret/PTC Activation* To the editor: The recent paper by Thomas et al. (1) shows that: 1) ret/PTC activation plays a central role in the pathogenesis of papillary thyroid carcinomas (TCs) occurring in children from Ukraine and Belarus after the Chernobyl accident (60.7% of the Ukrainian and 51.3% of the Belarussian cases); and 2) these patients have an increased incidence of the ret/PTC3 isoform (ret fusion with RGF gene) vs. the more frequent ret/PTC1 (ret fusion with H4 gene). In particular, a strong correlation was observed between the ret/PTC3 isoform and the solid-follicular subtype of papillary TC, which was present in 46 of 67 cases. This morphological variant has been considered as evidence of a more malignant phenotype (2). Nineteen of the 24 ret/PTC-positive solid-follicular TCs harbored a ret/PTC3 rearrangement, whereas only 5 had a ret/PTC1 rearrangement. The authors suggest that: 1) “there are good reasons to believe that there is a causal link between radiation exposure and ret/PTC rearrangements” because (a) the prevalence of ret/PTC in post-Chernobyl TCs is higher than the highest frequencies reported in the literature in nonexposed subjects (25–40%); (b) ionizing radiation can induce ret/PTC rearrangement “in vitro ” (3) and patients exposed to external radiation show a high frequency of ret/PTC rearrangements (4); and 2) “there is a strong correlation between the morphological subtype of papillary carcinoma and the type of ret rearrangement,” either in humans or transgenic animals. In fact, the targeted expression of ret/PTC1 to the thyroid gland caused the generation of TCs of the classic type (5), whereas ret/PTC3 mice developed aggressive TCs with a prevalent solid component, which were highly prone to metastasize to regional lymph nodes (6). The authors hypothesize that “although the ret component of the 2 chimeric proteins is identical, some functional differences between the two ret fusion partners may contribute to the different neoplastic phenotypes” (1). Thomas et al. (1) correctly acknowledge that whether ret/PTC activation is “linked primarily to the nature of the carcinogenetic agent (radiation or environmental factors) or the age of the patients (ranging between 6–18 yr in their series) remains to be determined.” In the last 5 yr we have collected the largest series of a very rare subgroup of patients with papillary TCs, namely those associated with familial adenomatous polyposis (FAP), an inherited multitumoral syndrome due to germ-line mutations of the APC gene (7). Ninety-seven patients have been collected from the literature, and 15 personal cases, who had detection of the APC germ-line mutation, have been added (7). Eight of nine of these patients (89%) had ret/PTC activation (8, 9). In particular, an unusual histological variant, the so-called cribriform variant, was very frequent (8), and the ret/PTC1 isoform was always found (9). All these patients were very young (mean age, 24 yr; range, 20–36 yr). All of them were followed up for long time (5–17 yr). A particularly indolent biological behavior was observed, which is in accordance with the low malignancy of the entire series (only 2 of 112 patients had distant metastases; Refs. 7 and 8). Interestingly, the only patient who, after lobectomy and isthmusectomy, had recurrence 17 yr after initial surgery, in addition to ret/PTC1, which was already present in the first tumor, also had ret/PTC3 both in the thyroid and in the regional lymph nodes. p53 mutations were concomitantly found in the thyroid tumoral tissue of this patient (8, 10). The group of patients with FAP-associated (or genetically determined) TC confirms that young age [mean age, 24 yr (in our series)] is a quite constant finding in groups with a high rate of ret/PTC activation. Additional factors could be early detection, due to intensive screening of high-risk populations (siblings of an index case with FAP, subjects exposed to nuclear radiation) and/or small diameter of tumors (,1 cm in three of six subjects of the Italian series). On the contrary, there is less evidence that the histological variant is also predetermined by the type of ret/PTC isoform. In fact, some patients with ret/PTC1 had the solid variant, and some of those with ret/PTC3 had variants other than the solid one. In particular, among patients with FAP-associated TCs, three members of the same kindred with the same germ-line mutation of the APC gene and ret/PTC1 activation had three different variants: classic papillary, cribriform, and follicular, respectively (11). Cumulative data in both groups of patients support the view that: 1) ret activation is highly prevalent in young subjects with small tumors or in patients belonging to special subgroups who are intensively screened for TC; 2) patients with ret/PTC1 isoform usually show an indolent behavior, whereas ret/PTC3 is associated with a more aggressive biological behavior (8, 10); 3) ret/PTC1 may coexist with ret/PTC3 in the same tumor; in particular, ret/PTC3 may develop with age or become more prevalent in patients with previous ret/PTC1 activation, and determine a more aggressive behavior; 4) the solid variant is usually, but not always, associated with ret/PTC3; and 5) whereas the link with radiation is evident in children from Belarus, it is not proven in FAP patients, even if patients from the latter subgroup could have a greater susceptibility to environmental radiation (12). In FAP patients APC mutations alone do not seem sufficient to cause TC (lack of loss of heterozygosity of the APC gene in the thyroid tumoral tissue) (8), but concomitant cofactors [modifier genes, sex-related factors (F:M 5 17:1) or environmental factors] are always required (12). A detailed genetic and clinicopathological analysis, also including long-term follow-up, of these two rare subgroups of patients with papillary TC, namely post- Chernobyl and FAP associated, could give a better insight into the relative role of genetic and environmental factors in thyroid carcinogenesis

    Oxidative stress and small, dense low-density lipoproteins: Current and future perspectives

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    Small, dense low-density lipoproteins (LDLs) are more susceptible to oxidation than their larger, more buoyant counterparts and therefore the biological modification of these LDL particles may, in part, be responsible for their atherogenic properties. Kotani et al. found that at multiple regression analysis there was an independent and significant inverse correlation between the mean LDL particle size and the oxidative stress status; notably, the authors adjusted not only for the traditional cardiovascular risk factors, but also for drug treatments. Higher levels of small, dense LDL concentrations significantly contribute to atherosclerosis, and lipoprotein size and subfractions may refine cardiovascular disease risk assessment

    PIVKAII Utility in Diagnosis and Post-therapeutic Monitoring of Hepatocellular Carcinoma

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    Background: Protein induced by vitamin K absence (PIVKA-II), also known as des-gamma-carboxyprothrombin, has been described in relation to HCC being released in association with vitamin K deficiency in the presence of HCC. Serum alpha-fetoprotein (AFP) is the traditional biomarker for HCC detection and follow up but it doesn’t have high sensitivity and specificity. Therefore, there is great interest in identifying new more powerful biomarkers. Materials and methods: One hundred and fourteen subjects were divided into four groups: Group 1 included 58 patients (38M, 20 F) with HCC, mean age 73.5; Group 2 included 38 patients (28M, 10F) with liver cirrhosis (LC), mean age 63.7; Group 3 included 28 control healthy subjects (25M, 3F), mean age 54.7 and Group 4 included 16 HCC patients (8M, 8F) who underwent to TACE as therapy for HCC. PIVKA II levels were dosed in an overnight fasting blood sample with commercially available chemiluminescent assay (Architect 1000i System, Abbott, USA). Statistical analysis: data were expressed as mean ± SD when distribution was normal, otherwise as median (min-max). Student’s t, Mann Whitney U, Chi-square tests and Pearson linear regression analysis were used when appropriate. Results: PIVKA II levels were higher in HCC group (82.3 mAU/ml) with respect to LC (31.5 mAU/ml) and healthy control (19.7 mAU/ml ) groups and in particular HCC vs controls (p<0.0001), LC vs controls (p<0.0001), HCC vs LC (p<0.005). Moreover, if using a cut off value of 50.9 mAU/ml none in the control group had PIVKA II levels above the cut off, while about 30% of LC and more than 50% of HCC patients had PIVKA II values higher than the cut off. PIVKA II levels in HCC patients who underwent to TACE treatment were higher after the treatment than at baseline. In particular at baseline 31% of HCC patients had PIVKA II levels higher than cut off, while after TACE they became 75% and this behaviour was observed in particular in non responders patients. Conclusions: Our results confirm data from the literature that hypothesize a role for PIVKA II as a better marker than the traditionally used however its role in monitoring the response to therapies needs further evaluations on larger sample

    Variations on the Author

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    “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

    Screening for celiac disease in patients with chronic liver disease

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    Dear Sir:We read with interest the paper of Kaukinen et al. reporting anelevated frequency of celiac disease (CD) (4.3%) in patients with previousliver transplantation due to severe hepatic dysfunction.1However, wewould like to report our experience of the serologic assays for CDdiagnosis in patients with chronic liver disease and comment on thescreening methods for CD used in that study. Between January andOctober 2001, we studied 96 consecutive subjects (65 male, 31 female,age range 18–87 years, median 42) with chronic hypertransaminasemiawho were attending for thefirst time the outpatients clinic for liverdisease at the Internal Medicine Division of the University Hospital ofPalermo. All patients underwent a complete work-up including routineliver function tests, serologic screening for viral hepatitis, presence ofserum autoantibodies, copper- and iron-related indexes,1-antitrypsinlevels, liver ultrasonography, and percutaneous liver biopsy. We foundchronic hepatitis in 70 cases, liver cirrhosis in 20 patients, nonalcoholicsteatohepatitis in 3 patients, and primary biliary cirrhosis in 3 patients.In all cases, serological screening for CD was also performed by deter-mining the values of total immunoglobulin (to exclude selective IgAdeficiency), IgA class anti-endomysial antibody (EmA) using monkey’sesophagus as the substrate, and IgA class anti-human transglutaminaseantibody (Anti-tTG). Both the serum EmA and anti-tTG assays wereperformed with commercially available assays as previously described andthe threshold value for serum anti-tTG was7%.2We found 3 of 96patients positive for serum anti-tTG, but only one of them was positivefor serum EmA. This last patient, an 18-year-old girl, had mild chronichepatitis due to hepatitis B virus; she had never reported gastrointestinalsymptoms or anemia and her body mass index was normal. She under-went the duodenal biopsy and the histology study, performed as previ-ously described,3which showed severe atrophy of the mucosa (villi/cryptsratio 0.5) with an elevated intraepithelial lymphocytes count, thus con-firming the CD diagnosis. The 2 other patients, positive for serumanti-tTG but negative for EmA, had mild chronic hepatitis and livercirrhosis respectively, both due to hepatitis C virus infection. These 2patients accepted to undergo the intestinal biopsy but their intestinalhistology was normal (villi/crypts ratio3.5, normal intraepitheliallymphocytes count). Furthermore, both these patients were negative forthe presence of the HLA-DQ2 and HLA-DQ8 antigens, which charac-terize CD patients. The 2 patients with false positive anti-tTG results didnot differ from all the other subjects included in the study with regard toliver histology grading and staging, severity of liver function impair-ment, serum-globulin, and etiology of the liver disease. Furthermore,both were negative for serum auto-antibodies. In total, we consequentlyfound 1% frequency of CD and 2% of false positive anti-tTG results forCD diagnosis in our group of patients with chronic liver disease.Kaukinen et al. reported a much higher frequency of CD (4.3%)very probably linked to the high frequency of autoimmune liverdisease (primary biliary cirrhosis, primary sclerosing cholangitis, au-toimmune hepatitis) in their series.1However, although our dataindicated that the frequency of CD was lower in consecutive patientswith chronic liver disease, not including exclusively subjects withend-stage liver disease, we think that CD screening should be per-formed in any case as Kaukinen et al. clearly demonstrated thatdietary treatment in CD patients may prevent the progression tohepatic failure.1In regard to the serologic screening for CD, in theFinnish study there was a 2-fold higher frequency of false positiveanti-tTG results (8 of 185 cases, 4.3%) than in our study. This wasprobably in part due to the use of an anti-tTG ELISA based on tTGfrom guinea pig liver as the antigen4; in fact, we have previouslydemonstrated that in patients with chronic liver disease this systemgives a higher number of false positive results than the anti-tTGELISA based on human recombinant tTG as the antigen and shouldnot be used as a screening tool for CD.5However, our present dataunderlined that in patients with chronic liver diseases, false positiveanti-tTG results can also be observed using the anti-tTG assay basedon human antigen. Consequently, we suggest that when EmA assay doesnot confirm the positivity of the anti-tTG assay, determination of theHLA haplotype should be the subsequent step and only DQ2 or DQ8positive subjects should undergo intestinal biopsy for CD diagnosis

    Appropriate Similarity Measures for Author Cocitation Analysis

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    We 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
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