1,720,966 research outputs found
Calcium-driven therapeutic approaches in pleural mesothelioma
No full textAttualmente non esiste uno specifico trattamento terapeutico gold-standard per il mesotelioma pleurico (PM). Nei casi di malattia in fase iniziale con istotipo epitelioide, la terapia multimodale (che combina chirurgia, chemioterapia e radioterapia) è considerata l'opzione più efficace per migliorare la prognosi. Tuttavia, la sopravvivenza mediana rimane di circa 12 mesi indipendentemente dalla terapia scelta. Studi recenti hanno evidenziato che l'alterazione della segnalazione del calcio (Ca2+) nelle cellule tumorali influisce sullo sviluppo e sulla progressione delle neoplasie, influenzando il metabolismo e la morte cellulare. Sulla base di questi risultati, la ricerca si è ampliata per esaminare il metabolismo del Ca2+ nelle cellule PM e valutare la loro resistenza ai trattamenti farmacologici. I risultati ottenuti forniscono approfondimenti sul ruolo degli ioni calcio nella biologia del mesotelioma pleurico maligno (MPM) e sulle implicazioni per il miglioramento delle terapie standard. In primo luogo, abbiamo osservato che le cellule primarie di MPM presentano una capacità proliferativa significativamente ridotta rispetto alle cellule mesoteliali non tumorali. Sebbene questa caratteristica possa sembrare controintuitiva per un tumore aggressivo come il mesotelioma, potrebbe riflettere un adattamento metabolico o alterazioni nelle vie di segnalazione della sopravvivenza. Queste cellule sembrano mantenere la loro resistenza agli stimoli apoptotici, un segno distintivo delle neoplasie maligne. In questo contesto, le dinamiche del calcio intracellulare, sia a livello citosolico che mitocondriale, svolgono un ruolo centrale. La riduzione delle oscillazioni del calcio e dell'ampiezza del segnale nelle cellule di MPM non solo compromette la regolazione di processi fondamentali come il metabolismo energetico e l'apoptosi, ma può anche rappresentare un meccanismo adattativo che aiuta le cellule tumorali a sopravvivere in un ambiente ostile. L'analisi della risposta ai chemioterapici standard, pemetrexed e cisplatino, ha rivelato ulteriori differenze sostanziali tra cellule tumorali e non tumorali. Le cellule mesoteliali normali hanno mostrato una forte mobilitazione del calcio intracellulare in risposta al trattamento, accompagnata da una significativa attivazione delle vie apoptotiche. Al contrario, le cellule di mesotelioma pleurico sono risultate refrattarie a questi segnali, non mostrando variazioni significative nei livelli di calcio e non riuscendo a indurre apoptosi. Questi risultati suggeriscono che la resistenza delle cellule tumorali ai chemioterapici può essere mediata da alterazioni dei meccanismi di regolazione del calcio, compresi i canali ionici, le pompe e le proteine coinvolte nell'immagazzinamento e nel rilascio del calcio intracellulare. Un aspetto critico che emerge dai nostri esperimenti è il potenziale del calcio extracellulare per superare questa resistenza. L'aumento delle concentrazioni di calcio nel terreno di coltura ha sensibilizzato le cellule MPM, ripristinando la mobilizzazione del calcio intracellulare e attivando vie apoptotiche precedentemente inattive. Questo risultato sottolinea il ruolo cruciale del calcio come modulatore della sopravvivenza cellulare e suggerisce che puntare sull'omeostasi del calcio potrebbe rappresentare una strategia terapeutica efficace per il trattamento del mesotelioma. I risultati ottenuti nel modello murino di recidiva del mesotelioma rafforzano ulteriormente queste osservazioni. La combinazione della terapia standard con alte concentrazioni di calcio ha portato a una riduzione significativa della massa tumorale residua e a un miglioramento della sopravvivenza degli animali rispetto alla sola terapia standard. Questi risultati evidenziano il potenziale sinergico del calcio nel potenziare l'efficacia dei trattamenti chemioterapici convenzionali.Currently, no specific gold-standard therapeutic treatment exists for Pleural Mesothelioma (PM). In cases of early-stage disease with the epithelioid histotype, multimodal therapy (combining surgery, chemotherapy, and radiotherapy) is considered the most effective option for improving prognosis. However, median survival remains around 12 months regardless of the chosen therapy. The challenges in providing adequate treatment underscore the importance of pharmacological and experimental research aimed at developing therapies to make the disease more manageable and improve survival outcomes. Recent studies have highlighted that altered calcium (Ca2+) signaling in tumor cells affects the development and progression of neoplasms by influencing metabolism and cell death. Based on these findings, research has expanded to examine Ca2+ metabolism in PM cells and assess their resistance to pharmacological treatments. The results obtained in this study provide critical insights into the role of calcium ions in the biology of malignant pleural mesothelioma (MPM) and their implications for improving standard therapies. Firstly, we observed that primary MPM cells exhibit significantly reduced proliferative capacity compared to non-tumor mesothelial cells. While this characteristic may seem counterintuitive for an aggressive cancer like mesothelioma, it could reflect a metabolic adaptation or alterations in survival signaling pathways. These cells appear to retain their resistance to apoptotic stimuli, a hallmark of malignant neoplasms. In this context, intracellular calcium dynamics, both at the cytosolic and mitochondrial levels, play a central role. The reduction in calcium oscillations and signal amplitude in MPM cells not only compromises the regulation of fundamental processes such as energy metabolism and apoptosis but may also represent an adaptive mechanism that helps tumor cells survive in a hostile environment. Analysis of the response to standard chemotherapeutics, pemetrexed, and cisplatin further revealed substantial differences between tumor and non-tumor cells. Normal mesothelial cells exhibited robust intracellular calcium mobilization in response to treatment, accompanied by significant activation of apoptotic pathways. Conversely, pleural mesothelioma cells were refractory to these signals, showing no significant variations in calcium levels and failing to induce apoptosis. These findings suggest that tumor cell resistance to chemotherapeutics may be mediated by alterations in calcium regulation mechanisms, including ion channels, pumps, and proteins involved in intracellular calcium storage and release. A critical aspect emerging from our experiments is the potential of extracellular calcium to overcome this resistance. Increasing calcium concentrations in the culture medium sensitized MPM cells, restoring intracellular calcium mobilization and activating previously inactive apoptotic pathways. This finding underscores the crucial role of calcium as a modulator of cell survival and suggests that targeting calcium homeostasis could represent an effective therapeutic strategy for treating mesothelioma. The results obtained from the murine recurrence model of mesothelioma further reinforce these observations. Combining standard therapy with high calcium concentrations resulted in a significant reduction in residual tumor mass and improved animal survival compared to standard therapy alone. These findings highlight the synergistic potential of calcium in enhancing the efficacy of conventional chemotherapeutic treatments. Overall, our data suggest that calcium insensitivity and resistance to apoptosis are key mechanisms contributing to the aggressiveness and refractory nature of pleural mesothelioma. However, using calcium as a therapeutic adjuvant offers a promising perspective for overcoming these barriers and improving clinical outcomes
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
Integrating Functional Knowledge and Embedding Learning in New Product Launch: How Projects Helped EMI Music
No full textThe article investigates whether and how the use of project-based structures can address the challenges of knowledge creation, retention and transfer in new product development processes. These issues are particularly problematic in the so-called ‘creative’ industries (movies, music, publishing, etc.), where getting marketing to work together with the creative side is a complex task, and where traditional sequential models for NPD seem to perform badly. The article analyses a recent strategy by EMI Music to use projects for organizing the launch of promising new releases onto the music market. Through an indepth
qualitative analysis of two relevant cases, the article illustrates how projects assist in integrating marketing and creative people (and their knowledge) in a purposeful way, and disseminating the consequential learning across initiatives. Project forms in creative
industries are able to combine different types of knowledge and align different purposes across launch functions by synchronizing sequential activities and establishing joint decision making rules. They can also improve knowledge retention and diffusion among
sequential initiatives, by creating artefacts where knowledge can be stored and re-used in other launches, and by removing organizational disincentives to knowledge sharing
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
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
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