1,720,962 research outputs found
Alginate Self-Crosslinking Ink for 3D Extrusion-Based Cryoprinting and Application for Epirubicin-HCl Delivery on MCF-7 Cells
3D-printed hydrogels are particularly advantageous as drug-delivery platforms but their loading with water-soluble active compounds remains a challenge requiring the development of innovative inks. Here, we propose a new 3D extrusion-based approach that, by exploiting the internal gelation of the alginate, avoids the post-printing crosslinking process and allows the loading of epirubicin-HCl (EPI). The critical combinations of alginate, calcium carbonate and d-glucono-δ-lactone (GDL) combined with the scaffold production parameters (extrusion time, temperature, and curing time) were evaluated and discussed. The internal gelation in tandem with 3D extrusion allowed the preparation of alginate hydrogels with a complex shape and good handling properties. The dispersion of epirubicin-HCl in the hydrogel matrix confirmed the potential of this self-crosslinking alginate-based ink for the preparation of 3D-printed drug-delivery platforms. Drug release from 3D-printed hydrogels was monitored, and the cytotoxic activity was tested against MCF-7 cells. Finally, the change in the expression pattern of anti-apoptotic, pro-apoptotic, and autophagy protein markers was monitored by liquid-chromatography tandem-mass-spectrometry after exposure of MCF-7 to the EPI-loaded hydrogels
An innovative European Joint Research Center-submitted in vitro assay for screening Endocrine Disruptors effects on thyroid cell function:
3D Printed Chitosan/Alginate Hydrogels for the Controlled Release of Silver Sulfadiazine in Wound Healing Applications: Design, Characterization and Antimicrobial Activity
The growing demand for personalized medicine requires innovation in drug manufacturing to combine versatility with automation. Here, three-dimensional (3D) printing was explored for the production of chitosan (CH)/alginate (ALG)-based hydrogels intended as active dressings for wound healing. ALG hydrogels were loaded with 0.75% w/v silver sulfadiazine (SSD), selected as a drug model commonly used for the therapeutic treatment of infected burn wounds, and four different 3D CH/ALG architectures were designed to modulate the release of this active compound. CH/ALG constructs were characterized by their water content, elasticity and porosity. ALG hydrogels (Young’s modulus 0.582 ± 0.019 Mpa) were statistically different in terms of elasticity compared to CH (Young’s modulus 0.365 ± 0.015 Mpa) but very similar in terms of swelling properties (water content in ALG: 93.18 ± 0.88% and in CH: 92.76 ± 1.17%). In vitro SSD release tests were performed by using vertical diffusion Franz cells, and statistically significant different behaviors in terms of the amount and kinetics of drugs released were observed as a function of the construct. Moreover, strong antimicrobial potency (100% of growth inhibition) against Staphylococcus aureus and Pseudomonas aeruginosa was demonstrated depending on the type of construct, offering a proof of concept that 3D printing techniques could be efficiently applied to the production of hydrogels for controlled drug delivery
Going Beyond Counting First Authors in Author Co-citation Analysis
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
Variations on the Author
“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
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
Cromatografia Liquida-Spettrometria di Massa, Biomateriali e Stampa 3D in Applicazioni Analitiche
Liquid chromatography-mass spectrometry (LC-MS) is a powerful and versatile analytical technique widely used in life sciences. This thesis work aims to group different analytical applications, where LC-MS is the technique of choice to investigate biomarkers of biomedical interest. In this context targeted and untargeted LC-MS/MS approaches were adopted using different analytical instruments such as HPLC, nano-HPLC, electrospray, triple quadrupole, orbitrap and trapped ion mobility spectrometry. The other technology investigated and involved in some of the analytical applications reported in this work is three-dimensional (3D) printing, used for the fabrication of 3D hydrogels based on polysaccharide biomaterials, particularly alginate and hyaluronic acid. In detail, an extrusion 3D printer was used, which, by depositing the biomaterial-based ink, layer upon layer, enabled the construction of porous polymeric scaffolds with customized and tuneable properties. These 3D polymeric networks, sometimes functionalized with drugs, bacterial lysates, nanoparticles, have been used in applications of regenerative medicine, tissue regeneration, treatment of infected wounds and drug delivery.
This thesis paper has therefore been divided into 10 chapters.
The first chapter is a general introduction on the technologies used in the analytical applications reported; therefore, there are two sections: the first deals with LC-MS in proteomics and metabolomics, respectively; the second deals with the use of 3D printing extrusion-based technique for the manufacturing of natural polysaccharide hydrogels for applications in the biomedical field.
From Chapter II to Chapter IX the analytical applications with biomedical interest, developed during the PhD period, are described. Chapter II focuses on the European Horizon 2020 SCRENEED project (#825745) that aim to develop 3D in vitro assays for screening the effect of low doses of Endocrine Disruptors on thyroid cell function in a sex-specific manner. Chapter III reports the use of untargeted and targeted LC-MS for extracellular matrix proteins investigation on porcine tissues decellularized with different detergents. Chapters IV and V concern the development of simple and reliable analytical methods based on targeted LC-MS, for the quantification of the protein insulin like growth factor-1 (IGF-1) in bovine milk samples and, for the quantification of cholesterol metabolites 24-, 25- and 27-hydroxycholesterol in mouse brain and sera, respectively. Chapters VI, VII, VIII, IX, share both the use of targeted LC-MS for the analysis of proteins or lipid biomarkers, and the use of 3D printing to fabricate alginate-based hydrogels crosslinked by ionotropic external (chapters VI and VII) or internal (chapter VIII and IX) gelation. Chapter VI focuses on the development and characterization of 3D printed hydrogels based on alginate, nanocrystalline cellulose and silver nanoparticles to promote antimicrobial and cytotoxic effects. Chapter VII reports the study on the adaptation of lipid profile of human fibroblasts to 2D alginate films or 3D printed alginate scaffolds.
In chapter VIII, the development of new self-crosslinking alginate-based inks for 3D printing is described; this method, by exploiting the internal gelation of alginate, avoids the post-printing crosslinking process and allows the loading of water-soluble drugs, such as epirubicin-HCl. Chapter IX reports the development of 3D printed hydrogels based on alginate and hyaluronic acid, functionalized with two strains of Lactobacillus delbrueckii subs. bulgaricus derivatives that have been investigated for their potential in wound healing as advanced therapeutic solutions. In chapter X both conclusions and future perspectives of the various analytical applications discussed in this thesis have been summarized.La cromatografia liquida-spettrometria di massa (LC-MS) è una tecnica analitica potente e versatile ampiamente utilizzata nelle scienze della vita. Questo lavoro di tesi si propone di raggruppare diverse applicazioni analitiche, dove LC-MS è la tecnica di elezione scelta per studiare biomarcatori di interesse biomedico. In questo contesto sono stati adottati approcci LC-MS/MS target e non target utilizzando diversi strumenti analitici come HPLC, nano-HPLC, elettrospray, triplo quadrupolo, orbitrap e spettrometria di mobilità ionica intrappolata. L'altra tecnologia adottata in alcune delle applicazioni analitiche riportate in questo lavoro è la stampa tridimensionale (3D), utilizzata per la fabbricazione di idrogel 3D a base di biomateriali polisaccaridici, in particolare alginato e acido ialuronico. In dettaglio, è stata utilizzata una stampante 3D per estrusione che, depositando l'inchiostro a base di biomateriale, strato su strato, ha consentito la costruzione di scaffold polimerici porosi con proprietà personalizzate e regolabili. Queste reti polimeriche 3D, talvolta funzionalizzate con farmaci, lisati batterici, nanoparticelle, sono state utilizzate in applicazioni di medicina rigenerativa, rigenerazione tissutale, trattamento di ferite infette e rilascio di farmaci.
Questo lavoro di tesi è stato quindi suddiviso in 10 capitoli.
Il primo capitolo è un'introduzione generale sulle tecnologie utilizzate nelle applicazioni analitiche riportate; pertanto, ci sono due sezioni: la prima tratta rispettivamente di LC-MS in proteomica e metabolomica; la seconda riguarda l'utilizzo della stampa 3D ad estrusione per la produzione di idrogel a base di polisaccaridi naturali per applicazioni in campo biomedico.
Dal Capitolo II al Capitolo IX sono descritte le applicazioni analitiche di interesse biomedico, sviluppate durante il periodo di dottorato. Il capitolo II è incentrato sul progetto europeo SCREENEED Horizon 2020 (#825745) che mira a sviluppare saggi 3D in vitro per lo screening dell'effetto di basse dosi di interferenti endocrini sulla funzione delle cellule tiroidee in modo sesso specifico. Il capitolo III riporta l'uso di LC-MS non target e target per l'analisi delle proteine della matrice extracellulare su tessuti suini decellularizzati con diversi detergenti. I Capitoli IV e V riguardano lo sviluppo di metodi analitici semplici e affidabili basati su LC-MS target, per la quantificazione del fattore di crescita proteico simile all'insulina-1 (IGF-1) in campioni di latte bovino e, per la quantificazione dei metaboliti del colesterolo 24 -, 25- e 27-idrossicolesterolo rispettivamente nel cervello e nel siero di topo. I Capitoli VI, VII, VIII, IX condividono sia l'uso di LC-MS target per l'analisi di biomarcatori proteici o lipidici, sia l'uso della stampa 3D per fabbricare idrogel a base di alginato reticolati con gelificazione ionotropica esterna (capitoli VI e VII) o interna (capitoli VIII e IX). Il capitolo VI si concentra sullo sviluppo e la caratterizzazione di idrogel stampati in 3D a base di alginato, cellulosa nanocristallina e nanoparticelle d'argento per promuovere effetti antimicrobici e citotossici. Il capitolo VII riporta lo studio sull'adattamento del profilo lipidico dei fibroblasti umani a film di alginato 2D o scaffold di alginato stampati in 3D. Nel capitolo VIII viene descritto lo sviluppo di nuovi inchiostri a base di alginato autoreticolanti per la stampa 3D; questo metodo, sfruttando la gelificazione interna dell'alginato, evita il processo di reticolazione post-stampa e consente il caricamento di farmaci idrosolubili, come l'epirubicina-HCl. Il capitolo IX riporta lo sviluppo di idrogel stampati in 3D a base di alginato e acido ialuronico, funzionalizzati con derivati di due ceppi di Lactobacillus delbrueckii subs. bulgaricus che sono stati studiati per il loro potenziale nella guarigione delle ferite come soluzioni terapeutiche avanzate. Nel capitolo X sono state riassunte sia le conclusioni che le prospettive future delle varie applicazioni analitiche discusse in questa tesi
Dispelling the Myths Behind First-author Citation Counts
We 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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