1,721,128 research outputs found
CAR-T Therapy for Pediatric High-Grade Gliomas: Peculiarities, Current Investigations and Future Strategies
No full textHigh-Grade Gliomas (HGG) are among the deadliest malignant tumors of central nervous system (CNS) in pediatrics. Despite aggressive multimodal treatment - including surgical resection, radiotherapy and chemotherapy - long-term prognosis of patients remains dismal with a 5-year survival rate less than 20%. Increased understanding of genetic and epigenetic features of pediatric HGGs (pHGGs) revealed important differences with adult gliomas, which need to be considered in order to identify innovative and more effective therapeutic approaches. Immunotherapy is based on different techniques aimed to redirect the patient own immune system to fight specifically cancer cells. In particular, T-lymphocytes can be genetically modified to express chimeric proteins, known as chimeric antigen receptors (CARs), targeting selected tumor-associated antigens (TAA). Disialoganglioside GD2 (GD-2) and B7-H3 are highly expressed on pHGGs and have been evaluated as possible targets in pediatric clinical trials, in addition to the antigens common to adult glioblastoma – such as interleukin-13 receptor alpha 2 (IL-13α2), human epidermal growth factor receptor 2 (HER-2) and erythropoietin-producing human hepatocellular carcinoma A2 receptor (EphA2). CAR-T therapy has shown promise in preclinical model of pHGGs but failed to achieve the same success obtained for hematological malignancies. Several limitations, including the immunosuppressive tumor microenvironment (TME), the heterogeneity in target antigen expression and the difficulty of accessing the tumor site, impair the efficacy of T-cells. pHGGs display an immunologically cold TME with poor T-cell infiltration and scarce immune surveillance. The secretion of immunosuppressive cytokines (TGF-β, IL-10) and the presence of immune-suppressive cells – like tumor-associated macrophages/microglia (TAMs) and myeloid-derived suppressor cells (MDSCs) - limit the effectiveness of immune system to eradicate tumor cells. Innovative immunotherapeutic strategies are necessary to overcome these hurdles and improve ability of T-cells to eradicate tumor. In this review we describe the distinguishing features of HGGs of the pediatric population and of their TME, with a focus on the most promising CAR-T therapies overcoming these hurdles
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
NS-01PEDIATRIC INTRAOPERATIVE NEUROPHYSIOLOGICAL MONITORING IN POSTERIOR FOSSA SURGERY
No full textIntraoperative neurophysiological monitoring (IOM) has recently become a promising tool in neurosurgery. Experiences in children are scattered and the real contribution of this technique to extent of resection and post-operative neurological impairment prevention has not be fully determined yet. We describe our experience in 33 consecutive posterior fossa surgical procedures (30 patients, 19 males and 11 females) in the last two years. Standard monitoring setting included trans-cranial motor evoked potentials (tcMEP), somatosensory evoked potentials (SEP), continuous electromyography (EMG) and brainstem evoked potentials (BAEPs). Relevant IOM information was recorded and correlated to tumor characteristics, intraoperative modifications of surgical strategy, post-operative neurological deficits. Spontaneous EMG activations were observed in 100% of brainstem lesion, in 80% of those infiltrating the floor of the IV ventricle and in less than 50% of cerebellar hemispheric ones. Brainstem infiltration was found to be highly predictive for transient EMG activation (94% in infiltrating vs 37% in non-infiltrating lesions). Transient EMG activation was highly predictive of early post-operative neurological impairment (84% at 72 hours) but did not correlate with long term neurological deficits (35% at 3 months). MEP modifications were only found in presence of brainstem infiltration and resulted in modification of surgical strategy. 75% of patients showing potential drops were found to suffer early motor impairment after surgery. SEP modifications were also rare (12%) but correlated to early post-operative sensibility/motor deficit (75%). No significant variation of BAEPs was observed in our study. No specific IOM pattern was observed in the two patients with post-operative posterior fossa syndrome
Intrathecal liposomal cytarabine and leptomeningeal medulloblastoma relapse: a valuable therapeutic option.
No full textRelapsed medulloblastoma (MB) is a highly lethal disease, requiring for new effective treatment strategies. Intrathecal (IT) therapy both for de novo or relapsed brain tumors with meningeal metastasis is rarely used in first line and relapse protocols.We report on three cases of children with relapsed MB treated with IT liposomal cytarabine administered after mild sedation every 15 days.The treatment was well-tolerated in all patients, achieving a prolonged progression-free survival (4-11 months) with a good quality of life.This experience suggests the need for a phase II trial in brain embryonal tumors with leptomeningeal metastasis to better evaluate the efficacy of IT liposomal cytarabine
Magnetic resonance imaging patterns of treatment-related toxicity in the pediatric brain: an update and review of the literature
No full textTreatment-related neurotoxicity is a potentially life-threatening clinical condition that can represent a diagnostic challenge. Differentiating diagnoses between therapy-associated brain injury and recurrent disease can be difficult, and the immediate recognition of neurotoxicity is crucial to providing correct therapeutic management, ensuring damage reversibility. For these purposes, the knowledge of clinical timing and specific treatment protocols is extremely important for interpreting MRI patterns. Neuroradiologic findings are heterogeneous and sometimes overlapping, representing the compounding effect of the different treatments. Moreover, MRI patterns can be acute, subacute or delayed and involve different brain regions, depending on (1) the mechanism of action of the specific medication and (2) which brain regions are selectively vulnerable to specific toxic effects. This review illustrates the most common radiologic appearance of radiotherapy, chemotherapy and medication-associated brain injury in children, with special focus on the application of advanced MRI techniques (diffusion, perfusion and proton spectroscopy) in the diagnosis of the underlying processes leading to brain toxicity
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