1,721,099 research outputs found
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
Fetal haemoglobin (HbF) induction as a strategy to improve life quality in thalassemia: characterisation of HbF inducing products and preclinical models to predict therapeutic response
No full textBeta thalassemia is due to mutations in one or both of the beta globin genes, leading to abnormal
red blood cells. The different types of beta thalassemia include: (a) Beta Thalassemia Trait,
including subjects that only show microcytosis and a possible mild anemia. This gene mutation
can be passed on to an individual’s children. (b) Thalassemia Intermedia, including subjects with
anemia requiring medical treatment. (c) Thalassemia Major (known also as Cooley's Anemia),
including subjects with anemia requiring lifelong regular blood transfusions and considerable
ongoing medical care. The dividing line between thalassemia intermedia and thalassemia major is
the degree of anemia and the number and frequency of blood transfusions required to treat it.
Those with thalassemia intermedia may need occasional transfusions. Beta thalassemia is most
common in persons of Mediterranean, African and Southeast Asian descent, where thalassemia
trait affects 5 to 30 percent of persons. It has been estimated that about 1.5% of the global
population are carriers of beta thalassemia trait, with about 60,000 symptomatic individuals born
annually, the great majority in the developing world. The total annual incidence of symptomatic
individuals is estimated at 1 in 100,000 throughout the world and 1 in 10,000 people in the
European Union
TREATMENT OF BETA-THALASSEMIA PATIENTS WITH RAPAMYCIN (SIROLIMUS): FROM PRE-CLINICAL RESERCH TO A CLINICAL TRIAL
No full textBeta-thalassemias are hereditary blood disorders caused by reduced or absent synthesis of hemoglobin beta chains,
resulting in severe anemia. Treatment of beta-thalassemia is based on regular blood transfusion and iron chelation therapy. Survival is
increased in most countries, but the quality of life is still poor for most patients and complication(s) of frequent transfusions is/are a major
problem. In some beta-thalassemia patients, an anomalous expression of gamma-globin genes has been observed, with a consequent
rise in HbF (Fetal Hemoglobin) levels. The cases with very high HbF levels display a clinical phenotype known as “Hereditary
Persistence of Fetal Hemoglobin” and exhibit a positive clinical status, since the activation of gamma-globin genes is associated with
HbF increase, and this partly overcomes the problems caused by the lack of adult hemoglobin.
Objectives. The overall aim of the project is a reduction of transfusions in beta-thalassemia patients, through a pharmacologically
mediated increased levels of HbF. There is strong evidence that Sirolimus is able to induce HbF production in vitro in erythroid precursor
cells (ErPCs) from beta-thalassemia and sickle-cell patients and in vivo in transgenic mice. Therefore, the THALA-RAP objective is to
verify whether HbF increases occur in beta-thalassemia patients treated with Sirolimus in peripheral blood and isolated ErPCs. A second
list of parameters is the lifespan and the oxidative stress status of the beta-thalassemia red blood cells. Both outcomes support the
possible clinical relevance of in vivo effects of Sirolimus. Furthermore, a cost-effectiveness analysis of the patients’treatment toward the
conventional one is conducted.
Methods.
(a) Short-term treatment. We plan to apply for the first trial an initial dose of 1 mg/day. Sirolimus whole blood concentrations will be
measured in about 10 days, with dosage adjustment to maintain at maximum concentrations between 2.5-5 ng/mL. Response to
Sirolimus in terms of HbF will be measured in two ways: analysis of (a) HbF level in peripheral blood and (b) gamma globin RNA and
HbF production by isolated ErPCs. These analyses will be performed after 20/30, 40/60 and 60/90 days of administration. OMICS
(transcriptomic, proteomic) analyses will be useful to determine the effects of the overall gene expression, including assessment of
potentials risks.
(b) Long term treatment. After a first period of treatment, if HbF is increased by Sirolimus in a limited number of patients, we will continue
treatment in the responding patients in order to reach a duration of 12 months. We will also add more patients, to test more than one
dose, defining the other ones on the basis of the ongoing observations. An observation period of 12 months is necessary to verify if in
some patients, initially responding, sirolimus loses efficacy rapidly.
(c) Non responders. All the beta-thalassemia patients who did not respond to the first Sirolimus treatment will be treated with increasing
Sirolimus dosages (up to a maximum dose of 2 mg/day).
(d) The THALA-RAP large clinical trial. In the case of response demonstrating a Sirolimus in vivo “activity” or “efficacy” (focused also on
identification and validation of optimal doses of Sirolimus) a large trial will be proposed in the future with the EMA protocol assistance.
With regard to a most important end point, on the basis of the available clinical data on HU and experimental data on Sirolimus, we
estimate that a significant decrease in transfusion need can be measured analyzing about 40-60 patients treated with Sirolimus for a
period of one year.
Expected results. The outcomes of the trial will be assessed in terms of “activity” of Sirolimus treatment (i.e. the demonstration that
Sirolimus induces significant changes on specific parameters) as well as “efficacy” of the treatment (i.e. the achievement of clear-cut
clinically relevant outcomes) and cost-effectiveness
Natural substances in the treatment of cystic fibrosis
No full textThe research on the biological activity of natural products and biomaterials is becoming year by year more competitive and complex, and involves experts in different research fields, including chemists, biochemists, molecular biologists, immunologists and bioinformatics. While unfractionated natural products exhibit “per se” biological properties relevant for alternative therapeutic treatments of human diseases, the identification of lead compounds within these products, the characterization of molecular targets and studies of structurally-related molecules are key processes to develop novel therapeutic strategies. Cystic fibrosis is a genetic disease caused by mutations of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene. It is well established that three major fields of therapeutic intervention should be considered, targeting CFTR, bacterial infection and inflammation. In this review, we describe natural products reported to be very useful tools for correction of pathological conditions related to cystic fibrosis. The main topics are (a) CFTR potentiation and correction using natural products, (b) natural products as antibacterial agents and (c) natural products exhibiting anti-inflammatory activity. The recent issues of waste utilization and drug repurposing are also discussed in the context of the development of possible therapeutic approaches for cystic fibrosis
Possible effects of sirolimus treatment on the long‐term efficacy of COVID‐19 vaccination in patients with β‐thalassemia: A theoretical perspective
No full textThe pandemic caused by the severe acute respiratory syndrome coronavirus (SARS‐CoV‐2), responsible for coronavirus disease 2019 (COVID‐19) has posed a major challenge for global health. In order to successfully combat SARS‐CoV‐2, the development of effective COVID‐19 vaccines is crucial. In this context, recent studies have highlighted a high COVID‐19 mortality rate in patients affected by β‐thalassemia, probably due to their co‐existent immune deficiencies. In addition to a role in the severity of SARS‐CoV‐2 infection and in the mortality rate of COVID‐19‐infected patients with thalassemia, immunosuppression is expected to deeply affect the effectivity of anti‐COVID‐19 vaccines. In the context of the interplay between thalassemia‐associated immunosuppression and the effectiveness of COVID‐19 vaccines, the employment of immunomodulatory molecules is hypothesized. For instance, short‐term treatment with mammalian target of rapamycin inhibitors (such as everolimus and sirolimus) has been found to improve responses to influenza vaccination in adults, with benefits possibly persisting for a year following treatment. Recently, sirolimus has been considered for the therapy of hemoglobinopathies (including β‐thalassemia). Sirolimus induces the expression of fetal hemoglobin (and this may contribute to the amelioration of the clinical parameters of patients with β‐thalassemia) and induces autophagy (thereby reducing the excessive levels of α‐globin). It may also finally contribute to the mobilization of erythroid cells from the bone marrow (thereby reducing anemia). In the present study, the authors present the hypothesis that sirolimus treatment, in addition to its beneficial effects on erythroid‐related parameters, may play a crucial role in sustaining the effects of COVID‐19 vaccination in patients with β‐thalassemia. This hypothesis is based on several publications demonstrating the effects of sirolimus treatment on the immune system
Ultra sensitive plasmonic devices for early cancer diagnosis
No full textULTRAPLACAD aims at the development of a novel robust in vitro diagnostic system for early cancer
diagnosis, prognosis, patient follow-up and therapy efficacy assessment based on molecular analysis
of peripheral blood (liquid biopsy). Although the platform may find wide applications in oncology,
ULTRAPLACAD will focus solely on colorectal cancer (CRC) that is the second most frequently occurring
cancer in the EU with an equal distribution among women and men. ULTRAPLACAD will provide
unique and up to now not existing platform for the comprehensive detection of nucleic acids and protein
CRC biomarkers in blood plasma.
The extremely low concentration of most cancer biomarkers in blood imposes a stringent barrier to the wide
applicability of the liquid biopsy for CRC diagnosis. The ULTRAPLACAD will deliver a disruptive
diagnostic platform for the analysis of cancer biomarkers in blood plasma with unprecedented
sensitivity and reliability. Reaching ULTRAPLACAD goals will significantly contribute to wider spread of
diagnostic and prognostic protocols based on liquid biopsy – an emerging and rapidly developing cancer
diagnostic approach.
The use of innovative optical analytical techniques that take advantage of plasmonic metallic
nanostructures (nanostructure-enhanced surface plasmon resonance imaging -NESPRI – and plasmonenhanced
fluorescence spectroscopy imaging – PEFSI) will advance the state-of-art of CRC biomarkers
detection (Figure 1)
Phenyl-substituted aminomethylene-bisphosphonates inhibit human P5C reductase and show antiproliferative activity against proline-hyperproducing tumour cells
No full textIn certain cancers, such as breast, prostate and some lung and skin cancers, the gene for the enzyme catalysing the second and last step in proline synthesis, δ1-pyrroline-5-carboxylate (P5C) reductase, has been found upregulated. This leads to a higher proline content that exacerbates the effects of the so-called proline-P5C cycle, with tumour cells effectively using this method to increase cell survival. If a method of reducing or inhibiting P5C reductase could be discovered, it would provide new means of treating cancer. To address this point, the effect of some phenyl-substituted derivatives of aminomethylene-bisphosphonic acid, previously found to interfere with the catalytic activity of plant and bacterial P5C reductases, was evaluated in vitro on the human isoform 1 (PYCR1), expressed in E. coli and affinity purified. The 3.5-dibromophenyl- and 3.5-dichlorophenyl-derivatives showed a remarkable effectiveness, with IC50 values lower than 1 μM and a mechanism of competitive type against both P5C and NADPH. The actual occurrence in vivo of enzyme inhibition was assessed on myelogenous erythroleukemic K562 and epithelial breast cancer MDA-MB-231 cell lines, whose growth was progressively impaired by concentrations of the dibromo derivative ranging from 10−6 to 10−4M. Interestingly, growth inhibition was not relieved by the exogenous supply of proline, suggesting that the effect relies on the interference with the proline-P5C cycle, and not on proline starvation
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