333 results on '"RAVARINO, A."'
Search Results
2. Third national surgical consensus conference of the Italian Association of Breast Surgeons (ANISC) on management after neoadjuvant chemotherapy: The difficulty in reaching a consensus
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Zanotti, Simone, Ceccarossi, Virginia, Massaza, Lauretta, Cosentino, Luigi Marino, Amaturo, Giuseppe, Curcio, Annalisa, Bondioli, Paola, Meattini, Icro, Luca, Alessandro De, Garcia-Etienne, Carlos Alberto, Gala, Antonia, Thodas, Alexios, Lozupone, Antonia, Botticella, Maria Antonietta, Grassi, Massimo, Santoro, Valeria, Ala, Ada, Tessa, Cristina La, D'onghia, Giuliano, Carfora, Elisabetta, Cappelli, Sonia, Nunzi, Martina, Mastropietro, Tiziana, Meneghini, Graziano, Morichetti, Doriana, Sanna, Paola Angela, Pozzi, Giada, Soatti, Carlo Pietro, Pellegrini, Alba, Puccica, Ilaria, Frati, Sara, Leone, Alba Di, Giuliani, Giuliana, Conte, Anna Maria, Zamagni, Claudio, Seriau, Luca, Minischetti, Monica, Foroni, Moira, Valli, Mariacarla, Lippi, Andrea, Ravarino, Alberto, Giaccherini, Lucia, Calzolaro, Adele, Neri, Anna, Carli, Luciano, Mambelli, Laura, Prisco, Agnese, Di Marzio, Enrico, Venturini, Annalisa, Gattuso, Maria Ilaria, Sicignano, Margherita, Amabile, Maria Ida, Baldissera, Antonella, Sibilio, Andrea, Chiavilli, Stefano, Gennari, Roberto, Melina, Marica, D'aponte, Maria Luisa, Germano, Alessandro, Baldoni, Giulia, Santurro, Letizia, Busani, Massimo, Bonanni, Alessio, Tondo, Salvatore, Marchetti, Vania, Cassinotti, Michela, Serra, Margherita, Stani, Simonetta, Firpo, Emma, Grendele, Sara, Spolveri, Federico, Custodero, Olindo, Pellegrini, Francesco, Cremonini, Anna, De Tullio, Damiano, Sorbo, Grazia, Combi, Francesca, Aristei, Cynthia, Roncella, Manuela, Folli, Secondo, Nesi, Silvia, Gentile, Damiano, Burlizzi, Stefano, Galimberti, Viviana, Trapani, Anna, Curella, Luciano, Panizza, Pietro, Nanez, Jose Andres Diaz, Sgarella, Adele, Pensa, Anna, Gasperoni, Marco, Marino, Lorenza, Marzetti, Alice, De Rosa, Antonia, Borri, Filippo, Camilletti, Anna Chiara, Ruggieri, Annamaria, Andrulli, Angela Damiana, Silvia, Asioli, Terribile, Daniela Andreina, Accardo, Giuseppe, Patrone, Francesco, Raviele, Paola Rafaniello, Santini, Donatella, Costarelli, Leopoldo, Angelini, Lucia, Reitano, Renato, Polistena, Andrea, Palma, Enza, Santoni, Marcello, Magni, Carla, Cima, Simona, Foglietta, Jennifer, Minafra, Marina, Rizzo, Antonio, Milanesio, Michela Camilla, Giorgini, Sara, Grossi, Simona, Cumbo, Jacopo, Campanella, Barbara, Fante, Rossella, Pinta, Massimo La, Manna, Elena, Santini, Elena, Mascioni, Francesca, Teggi, Silvia, Galasso, Maria Grazia, Sanguinetti, Alessandro, Fenocchio, Daniela, Giacobbe, Felicia, Pellegrini, Alice, Papi, Simona, Pieroni, Marzia, Villa, Elisa, Querzoli, Patrizia, Guadagno, Elia, Perfetti, Alessandra, Balzarotti, Laura, Ciriotto, Davide, Guida, Giovanna, Canova, Elisa, Lunardi, Maria, Vignutelli, Patrizia, Apicella, Giuseppina, Natale, Maria, Ghilli, Matteo, Troilo, Vito Leopoldo, Rocco, Nicola, Schiavone, Alfonso, Ventimiglia, Fabrizio, Zarba Meli, Emanuele, Taffurelli, Mario, Caruso, Francesco, Gentilini, Oreste Davide, Del Mastro, Lucia, Livi, Lorenzo, Castellano, Isabella, Bernardi, Daniela, Minelli, Mauro, and Fortunato, Lucio
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- 2024
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3. Ultra-Short Peptide Nanomaterials
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Giuri, Demetra, Ravarino, Paolo, Tomasini, Claudia, and Elsawy, Mohamed A., editor
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- 2023
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4. Transparent Organogels as a Medium for the Light-Induced Conversion from Spiropyran to Merocyanine
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Demetra Giuri, Paolo Ravarino, and Claudia Tomasini
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organogel ,self-assembly ,low-molecular-weight gelator ,peptides ,spiropyran ,merocyanine ,Science ,Chemistry ,QD1-999 ,Inorganic chemistry ,QD146-197 ,General. Including alchemy ,QD1-65 - Abstract
Low-molecular-weight peptide gelators are a versatile class of compounds able to form gels under a variety of conditions, even via simple ultrasound sonication. In this paper, the ability of Boc-L-Phe-D-Oxd-L-Phe-OBn to gelate three organic solvents (toluene, tert-butyl methyl ether, and ethanol) was evaluated. The rheological behaviour of the materials was assessed via strain sweep analysis, while the fibrous network was analysed via optical microscopy on the wet gels. The gel obtained from toluene is a highly transparent material, and the one from ethanol appears translucent, while the one from tert-butyl methyl ether is opaque. These gels were used to study the reversible light-induced transformation from spyropiran (SP) to merocyanine (MC) and back, as a model system to check the effect of the gel medium onto the rection kinetic. We observed that the solvent used to form the organogels has a crucial effect on the reaction, as gels from aprotic solvents stabilize the SP form, while the ones from protic solvents stabilize the MC form. We thus obtained a solid support to stabilize the two photochromic species just by changing the solvent polarity. Moreover, we could demonstrate that the self-assembled gels do not interfere with the light-driven conversion process, either starting from SP or MC, thus representing a valid and economical photochromic material.
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- 2023
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5. Inter‐observer agreement for the histological diagnosis of invasive lobular breast carcinoma
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Matthias Christgen, Leonie Donata Kandt, Wiebke Antonopoulos, Stephan Bartels, Mieke R VanBockstal, Martin Bredt, Maria Jose Brito, Henriette Christgen, Cecile Colpaert, Bálint Cserni, Gábor Cserni, Maximilian E Daemmrich, Raihanatou Danebrock, Franceska Dedeurwaerdere, Carolien HM vanDeurzen, Ramona Erber, Christine Fathke, Henning Feist, Maryse Fiche, Claudia Aura Gonzalez, Natalie D terHoeve, Loes Kooreman, Till Krech, Glen Kristiansen, Janina Kulka, Florian Laenger, Marcel Lafos, Ulrich Lehmann, Maria Dolores Martin‐Martinez, Sophie Mueller, Enrico Pelz, Mieke Raap, Alberto Ravarino, Tanja Reineke‐Plaass, Nora Schaumann, Anne‐Marie Schelfhout, Maxim DeSchepper, Jerome Schlue, Koen Van de Vijver, Wim Waelput, Axel Wellmann, Monika Graeser, Oleg Gluz, Sherko Kuemmel, Ulrike Nitz, Nadia Harbeck, Christine Desmedt, Giuseppe Floris, Patrick WB Derksen, Paul J vanDiest, Anne Vincent‐Salomon, and Hans Kreipe
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lobular breast carcinoma ,diagnosis ,quality assurance ,beta‐catenin ,p120‐catenin ,tubular elements ,Pathology ,RB1-214 - Abstract
Abstract Invasive lobular breast carcinoma (ILC) is the second most common breast carcinoma (BC) subtype and is mainly driven by loss of E‐cadherin expression. Correct classification of BC as ILC is important for patient treatment. This study assessed the degree of agreement among pathologists for the diagnosis of ILC. Two sets of hormone receptor (HR)‐positive/HER2‐negative BCs were independently reviewed by participating pathologists. In set A (61 cases), participants were provided with hematoxylin/eosin (HE)‐stained sections. In set B (62 cases), participants were provided with HE‐stained sections and E‐cadherin immunohistochemistry (IHC). Tumor characteristics were balanced. Participants classified specimens as non‐lobular BC versus mixed BC versus ILC. Pairwise inter‐observer agreement and agreement with a pre‐defined reference diagnosis were determined with Cohen's kappa statistics. Subtype calls were correlated with molecular features, including CDH1/E‐cadherin mutation status. Thirty‐five pathologists completed both sets, providing 4,305 subtype calls. Pairwise inter‐observer agreement was moderate in set A (median κ = 0.58, interquartile range [IQR]: 0.48–0.66) and substantial in set B (median κ = 0.75, IQR: 0.56–0.86, p
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- 2022
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6. Interobserver variability in the assessment of stromal tumor-infiltrating lymphocytes (sTILs) in triple-negative invasive breast carcinoma influences the association with pathological complete response: the IVITA study
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Van Bockstal, Mieke R., François, Aline, Altinay, Serdar, Arnould, Laurent, Balkenhol, Maschenka, Broeckx, Glenn, Burguès, Octavio, Colpaert, Cecile, Dedeurwaerdere, Franceska, Dessauvagie, Benjamin, Duwel, Valérie, Floris, Giuseppe, Fox, Stephen, Gerosa, Clara, Hastir, Delfyne, Jaffer, Shabnam, Kurpershoek, Eline, Lacroix-Triki, Magali, Laka, Andoni, Lambein, Kathleen, MacGrogan, Gaëtan Marie, Marchiò, Caterina, Martin Martinez, Maria-Dolores, Nofech-Mozes, Sharon, Peeters, Dieter, Ravarino, Alberto, Reisenbichler, Emily, Resetkova, Erika, Sanati, Souzan, Schelfhout, Anne-Marie, Schelfhout, Vera, Shaaban, Abeer, Sinke, Renata, Stanciu-Pop, Claudia M., van Deurzen, Carolien H. M., Van de Vijver, Koen K., Van Rompuy, Anne-Sophie, Vincent-Salomon, Anne, Wen, Hannah Y., Wong, Serena, Bouzin, Caroline, and Galant, Christine
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- 2021
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7. Delivery of Active Peptides by Self-Healing, Biocompatible and Supramolecular Hydrogels
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Seyedeh Rojin Shariati Pour, Sara Oddis, Marianna Barbalinardo, Paolo Ravarino, Massimiliano Cavallini, Jessica Fiori, Demetra Giuri, and Claudia Tomasini
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Franz diffusion cells ,hydrogels ,low-molecular-weight gelators ,peptides ,self-assembly ,Organic chemistry ,QD241-441 - Abstract
Supramolecular and biocompatible hydrogels with a tunable pH ranging from 5.5 to 7.6 lead to a wide variety of formulations useful for many different topical applications compatible with the skin pH. An in vitro viability/cytotoxicity test of the gel components demonstrated that they are non-toxic, as the cells continue to proliferate after 48 h. An analysis of the mechanical properties demonstrates that the hydrogels have moderate strength and an excellent linear viscoelastic range with the absence of a proper breaking point, confirmed with thixotropy experiments. Two cosmetic active peptides (Trifluoroacetyl tripeptide-2 and Palmitoyl tripeptide-5) were successfully added to the hydrogels and their transdermal permeation was analysed with Franz diffusion cells. The liquid chromatography-mass spectrometry (HPLC-MS) analyses of the withdrawn samples from the receiving solutions showed that Trifluoroacetyl tripeptide-2 permeated in a considerable amount while almost no transdermal permeation of Palmitoyl tripeptide-5 was observed.
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- 2023
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8. Interobserver variability in upfront dichotomous histopathological assessment of ductal carcinoma in situ of the breast: the DCISion study
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Dano, Hélène, Altinay, Serdar, Arnould, Laurent, Bletard, Noella, Colpaert, Cecile, Dedeurwaerdere, Franceska, Dessauvagie, Benjamin, Duwel, Valérie, Floris, Giuseppe, Fox, Stephen, Gerosa, Clara, Jaffer, Shabnam, Kurpershoek, Eline, Lacroix-Triki, Magali, Laka, Andoni, Lambein, Kathleen, MacGrogan, Gaëtan Marie, Marchió, Caterina, Martinez, Dolores Martin, Nofech-Mozes, Sharon, Peeters, Dieter, Ravarino, Alberto, Reisenbichler, Emily, Resetkova, Erika, Sanati, Souzan, Schelfhout, Anne-Marie, Schelfhout, Vera, Shaaban, Abeer M., Sinke, Renata, Stanciu-Pop, Claudia Maria, Stobbe, Claudia, van Deurzen, Carolien H.M., Van de Vijver, Koen, Van Rompuy, Anne-Sophie, Verschuere, Stephanie, Vincent-Salomon, Anne, Wen, Hannah, Bouzin, Caroline, Galant, Christine, and Van Bockstal, Mieke R.
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- 2020
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9. Transparent Organogels as a Medium for the Light-Induced Conversion from Spiropyran to Merocyanine
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Giuri, Demetra, primary, Ravarino, Paolo, additional, and Tomasini, Claudia, additional
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- 2023
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10. Metabolomic analysis of plasma from breast tumour patients. A pilot study
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Carola Politi, Claudia Fattuoni, Alessandra Serra, Antonio Noto, Silvia Loi, Andrea Casanova, Gavino Faa, Alberto Ravarino, and Luca Saba
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Breast cancer ,mammography ,metabolomics ,plasma ,GC-MS ,Public aspects of medicine ,RA1-1270 - Abstract
Background: Patients at risk of breast cancer are submitted to mammography, resulting in a classification of the lesions following the Breast Imaging Reporting and Data System (BI-RADS®). Due to BI-RADS 3 classification problems and the great uncertainty of the possible evolution of this kind of tumours, the integration of mammographic imaging with other techniques and markers of pathology, as metabolic information, may be advisable. Design and Methods: Our study aims to evaluate the possibility to quantify by gas chromatography-mass spectrometry (GC-MS) specific metabolites in the plasma of patients with mammograms classified from BI-RADS 3 to BI-RADS 5, to find similarities or differences in their metabolome. Samples from BI-RADS 3 to 5 patients were compared with samples from a healthy control group. This pilot project aimed at establishing the sensitivity of the metabolomic classification of blood samples of patients undergoing breast radiological analysis and to support a better classification of mammographic cases. Results: Metabolomic analysis revealed a panel of metabolites more abundant in healthy controls, as 3-aminoisobutyric acid, cholesterol, cysteine, stearic, linoleic and palmitic fatty acids. The comparison between samples from BI-RADS 3 and BI-RADS 5 patients, revealed the importance of 4-hydroxyproline, found in higher amount in BI-RADS 3 subjects. Conclusion: Although the low sample number did not allow the attainment of high validated statistical models, some interesting data were obtained, revealing the potential of metabolomics for an improvement in the classification of different mammographic lesions.
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- 2021
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11. Controlled Hydrolysis of Odorants Schiff Bases in Low-Molecular-Weight Gels
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Gloria Nicastro, Louise Mary Black, Paolo Ravarino, Simone d’Agostino, Davide Faccio, Claudia Tomasini, and Demetra Giuri
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Schiff base ,hydrolysis ,gel ,self-assembly ,fragrance ,perfumery ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Imines or Schiff bases (SB) are formed by the condensation of an aldehyde or a ketone with a primary amine, with the removal of a water molecule. Schiff bases are central molecules in several biological processes for their ability to form and cleave by small variation of the medium. We report here the controlled hydrolysis of four SBs that may be applied in the fragrance industry, as they are profragrances all containing odorant molecules: methyl anthranilate as primary amine, and four aldehydes (cyclamal, helional, hydroxycitronellal and triplal) that are very volatile odorants. The SB stability was assessed over time by HPLC-MS in neutral or acidic conditions, both in solution and when trapped in low molecular weight gels. Our results demonstrate that it is possible to control the hydrolysis of the Schiff bases in the gel environment, thus tuning the quantity of aldehyde released and the persistency of the fragrance.
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- 2022
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12. Fluorine Effect in the Gelation Ability of Low Molecular Weight Gelators
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Paolo Ravarino, Nadia Di Domenico, Marianna Barbalinardo, Davide Faccio, Giuseppe Falini, Demetra Giuri, and Claudia Tomasini
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fibers ,fluorine atom ,gelator ,supramolecular gel ,thixotropy ,transparency ,Science ,Chemistry ,QD1-999 ,Inorganic chemistry ,QD146-197 ,General. Including alchemy ,QD1-65 - Abstract
The three gelators presented in this work (Boc-D-Phe-L-Oxd-OH F0, Boc-D-F1Phe-L-Oxd-OH F1 and Boc-D-F2Phe-L-Oxd-OH F2) share the same scaffold and differ in the number of fluorine atoms linked to the aromatic ring of phenylalanine. They have been applied to the preparation of gels in 0.5% or 1.0% w/v concentration, using three methodologies: solvent switch, pH change and calcium ions addition. The general trend is an increased tendency to form structured materials from F0 to F1 and F2. This property ends up in the formation of stronger materials when fluorine atoms are present. Some samples, generally formed by F1 or F2 in 0.5% w/v concentration, show high transparency but low mechanical properties. Two gels, both containing fluorine atoms, show increased stiffness coupled with high transparency. The biocompatibility of the gelators was assessed exposing them to fibroblast cells and demonstrated that F1 and F2 are not toxic to cells even in high concentration, while F0 is not toxic to cells only in a low concentration. In conclusion, the presence of even only one fluorine atom improves all the gelators properties: the gelation ability of the compound, the rheological properties and the transparency of the final materials and the gelator biocompatibility.
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- 2022
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13. A short oxazolidine-2-one containing peptide forms supramolecular hydrogels under controlled conditions
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Paolo Ravarino, Demetra Giuri, Claudia Tomasini, Ravarino, Paolo, Giuri, Demetra, and Tomasini, Claudia
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Pharmacology ,Structural Biology ,tripeptide ,Organic Chemistry ,Drug Discovery ,oxazolidin-2-one ,supramolecular material ,Molecular Medicine ,General Medicine ,hydrogel ,self-aggregation ,Molecular Biology ,Biochemistry - Abstract
Low-molecular-weight hydrogels are made of a small percentage of small organic molecules dispersed in an aqueous medium, which may aggregate in several manners using different methods. However, often the organic gelator in water has poor solubility, so the addition of a solubilising agent is required. In the case of acidic gelators, this mainly consists of the addition of a strong base, that is sodium hydroxide, that deprotonates the acidic moiety, so the gelator molecules become more soluble and tend to assemble into micelles, forming a dispersion. Some gelators, however, are sensitive to the harsh pH and get hydrolysed. This is the case of some molecules presenting carbamates in their features, like Fmoc-protected or oxazolidinone-containing peptides. In this paper, we present a valid alternative to sodium hydroxide, by dissolving a tripeptide containing an oxazolidinone moiety in a phosphate buffer (PB) medium at pH 7.4. The results obtained with the NaOH dissolution are compared with the ones with PB, as both methods present advantages and drawbacks. The use of NaOH produces transparent but weak hydrogels, as it exposes the gelator to harsh conditions that end up in its partial hydrolysis, which is more pronounced at high concentrations (≥10 mM). Using PB to dissolve the gelator, this problem is completely avoided as no hydrolysis product has been detected in the hydrogels, which are very stiff although more opaque. By tuning the preparation conditions, we can obtain a wide variety of hydrogels, with the properties required by the final application.
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- 2023
14. Zinc as a Drug for Wilson’s Disease, Non-Alcoholic Liver Disease and COVID-19-Related Liver Injury
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Pierpaolo Coni, Giuseppina Pichiri, Joanna Izabela Lachowicz, Alberto Ravarino, Francesca Ledda, Daniela Fanni, Clara Gerosa, Monica Piras, Ferdinando Coghe, Yukio Gibo, Flaviana Cau, Massimo Castagnola, Peter Van Eyken, Luca Saba, Marco Piludu, and Gavino Faa
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zinc ,COVID-19 ,Wilson’s disease ,non-alcoholic liver disease ,drug therapy ,Organic chemistry ,QD241-441 - Abstract
Zinc is the second most abundant trace element in the human body, and it plays a fundamental role in human physiology, being an integral component of hundreds of enzymes and transcription factors. The discovery that zinc atoms may compete with copper for their absorption in the gastrointestinal tract let to introduce zinc in the therapy of Wilson’s disease, a congenital disorder of copper metabolism characterized by a systemic copper storage. Nowadays, zinc salts are considered one of the best therapeutic approach in patients affected by Wilson’s disease. On the basis of the similarities, at histological level, between Wilson’s disease and non-alcoholic liver disease, zinc has been successfully introduced in the therapy of non-alcoholic liver disease, with positive effects both on insulin resistance and oxidative stress. Recently, zinc deficiency has been indicated as a possible factor responsible for the susceptibility of elderly patients to undergo infection by SARS-CoV-2, the coronavirus responsible for the COVID-19 pandemic. Here, we present the data correlating zinc deficiency with the insurgence and progression of Covid-19 with low zinc levels associated with severe disease states. Finally, the relevance of zinc supplementation in aged people at risk for SARS-CoV-2 is underlined, with the aim that the zinc-based drug, classically used in the treatment of copper overload, might be recorded as one of the tools reducing the mortality of COVID-19, particularly in elderly people.
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- 2021
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15. Low Malignant Potential Tumors
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Sismondi, Piero, Daniele, Alberto, Ferrero, Annamaria, Ravarino, Nicoletta, Biglia, Nicoletta, Genazzani, Andrea R., Series Editor, and Fauser, Bart C. J. M., editor
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- 2015
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16. Designing a Transparent and Fluorine Containing Hydrogel
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Paolo Ravarino, Demetra Giuri, Davide Faccio, and Claudia Tomasini
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fluorine ,hydrogel ,pH change ,rheology ,thixotropy ,Science ,Chemistry ,QD1-999 ,Inorganic chemistry ,QD146-197 ,General. Including alchemy ,QD1-65 - Abstract
Physical hydrogels are supramolecular materials obtained by self-assembly of small molecules called gelators. Aromatic amino acids and small peptides containing aromatic rings are good candidates as gelators due to their ability to form weak bonds as π-π interactions and hydrogen bonds between NH and CO of the peptide chain. In this paper we show our results in the preparation of a transparent hydrogel that was obtained by self-assembly of a fluorine-containing dipeptide that relies on the additional formation of halogen bonds due to the fluorine atoms contained in the dipeptide. We used Boc-D-F2Phe-L-Oxd-OH (F2Phe = 3,4-difluorophenylalainine; Oxd = 4-methyl-5-carboxy-oxazolidin-2-one) that formed a strong and transparent hydrogel in 0.5% w/w concentration at pH = 4.2. The formation of a hydrogel made of unnatural fluorinated amino acids may be of great interest in the evaluation of patients with parkinsonian syndromes and may be used for controlled release.
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- 2021
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17. Delivery of Active Peptides by Self-Healing, Biocompatible and Supramolecular Hydrogels
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Shariati Pour, Seyedeh Rojin, primary, Oddis, Sara, additional, Barbalinardo, Marianna, additional, Ravarino, Paolo, additional, Cavallini, Massimiliano, additional, Fiori, Jessica, additional, Giuri, Demetra, additional, and Tomasini, Claudia, additional
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- 2023
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18. A short oxazolidine‐2‐one containing peptide forms supramolecular hydrogels under controlled conditions
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Ravarino, Paolo, primary, Giuri, Demetra, additional, and Tomasini, Claudia, additional
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- 2023
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19. Enel Grid+: the advanced platform for network analysis and planning
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Licasale, G., primary, Scarantino, R., additional, Viapiana, F., additional, Vermigli, A., additional, Alloni, M., additional, Bianchi, P., additional, and Ravarino, G., additional
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- 2023
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20. Placental Calcification Score: a new semiquantitative method to assess pattern and grading of placental calcifications
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Cristiana Rossi, Clara Gerosa, Pietro Pampaloni, Melania Puddu, Alberto Ravarino, Stefano Angioni, Daniela Fanni, and Gavino Faa
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placental calcifications ,calcification pattern ,calcification grading ,placental calcification score ,intervillous calcifications ,intravillous calcifications ,Medicine ,Pediatrics ,RJ1-570 - Abstract
The relationship between placental calcifications and pregnancy outcome is still controversial. In this study, we examined the occurrence of placental calcifications, and we proposed a histopathological score system, Placental Calcification Score (PCS). We assigned a score (from 1 to 3) to calcifications according to their pattern (dusty = 1; single = 2; cluster = 3) and grading (low = 1; moderate = 2; high = 3). Multiplying the pattern score with that of grading, we obtained a score. After that, summing the score of each one of the three calcification patterns, we achieved the PCS. We examined 47 consecutive monochorionic placentas, searching calcifications in placental parenchyma (PP) (in which we distinguished four subsites: intervillous, intravillous, sub-amniotic fetal floor and decidua), extraplacental membranes and Wharton jelly of the umbilical cord. We collected clinical data relative to 47 mothers (age, gestational age at delivery, kind of gestation and hypertension) and 51 products of conception (kind of products of conception, gender, preterm birth, and intrauterine growth restriction [IUGR]), corresponding to the 47 placentas. We found calcifications in all placentas examined (47/47 = 100%), and all placentas showed calcifications in PP (47/47 = 100%). Calcifications were more frequent, respectively, in intravillous (36/47 = 77%) and intervillous (47/47 = 100%) subsite of PP. Besides, our preliminary data showed a mean PCS higher in mothers ≥ 35 years, with gestational age ≥ 37 W + 0 D and suffering from hypertension, than in mothers < 35 years, with gestational age < 37 W + 0 D and without hypertension. Not preterm newborns, male gender, and presence of IUGR were associated with a mean PCS higher than preterm newborns, female gender, and absence of IUGR. PCS is a new histopathological tool that might be useful to clarify the correlation between placental calcifications and clinical data of mothers and products of conception. Further investigations are needed, with a large number of placentas, to confirm the trend shown by our data.
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- 2019
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21. How challenging could be preoperative and intraoperative diagnosis of endometrial cancer?
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FERRERO, Annamaria, ATTIANESE, Daniela, VILLA, Michela, RAVARINO, Nicoletta, MENATO, Guido, and VOLPI, Eugenio
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ENDOMETRIAL cancer ,OBESITY ,DIAGNOSIS - Published
- 2023
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22. Controlled Annealing in Adaptive Multicomponent Gels
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Ravarino, Paolo, primary, Panja, Santanu, additional, Bianco, Simona, additional, Koev, Todor, additional, Wallace, Matthew, additional, and Adams, Dave J., additional
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- 2022
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23. <scp>l</scp>-Dopa in small peptides: an amazing functionality to form supramolecular materials
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Claudia Tomasini, Paolo Ravarino, Demetra Giuri, Giuri D., Ravarino P., and Tomasini C.
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Catechol ,Hydrogen bond ,Reducing agent ,Organic Chemistry ,Supramolecular chemistry ,Ring (chemistry) ,Biochemistry ,Metal Chelator ,Combinatorial chemistry ,L-Dopa, hydrogels, nanotubes, adhesives ,Levodopa ,chemistry.chemical_compound ,chemistry ,Moiety ,Molecule ,Physical and Theoretical Chemistry - Abstract
l-Dopa (3,4-dihydroxyphenylalanine) is a chiral amino acid generated via biosynthesis from l-tyrosine in plants and some animals. The presence of multiple interacting sites makes l-Dopa a multifunctional building block for the preparation of supramolecular materials. The possibility to form hydrogen bonds and the presence of the aromatic ring allow l-Dopa molecules to interact through a series of non-covalent interactions. The additional presence of the catechol moiety really makes this compound unique: not only does it have implications in the self-assembly process of Dopa itself and with other substrates, but also it highly increases the number of applications of the final material, since it works as an antioxidant, radical trapper, metal chelator, reducing agent and adhesive. l-Dopa and catechol containing derivatives have been extensively introduced inside both synthetic and natural polymers to obtain amazing functional materials. In this review we report the preparation of small peptides containing l-Dopa, focusing on the supramolecular materials that can be obtained with them, ranging from fibrils to fibres, gels, films and coatings, all having the different applications mentioned above and many others.
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- 2021
24. Low vascularization of the nephrogenic zone of the fetal kidney suggests a major role for hypoxia in human nephrogenesis
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Gerosa, C., Fanni, D., Faa, A., Van Eyken, P., Ravarino, A., Fanos, V., and Faa, G.
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- 2017
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25. Controlled Annealing in Adaptive Multicomponent Gels
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Paolo Ravarino, Santanu Panja, Simona Bianco, Todor Koev, Matthew Wallace, and Dave J. Adams
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General Chemistry ,General Medicine ,Catalysis - Abstract
We use a pH-driven annealing process to convert between co-assembled and self-sorted networks in multicomponent gels. The initially formed gels at low pH are co-assembled, with the two components coexisting within the same self-assembled structures. We use an enzymatic approach to increase the pH, resulting in a gel-to-sol transition, followed by a hydrolysis to lower the pH once again. As the pH decreases, a self-sorted network is formed by a two-stage gelation process determined by the pKa of each component. This approach can be expanded to layered systems to generate many varied systems by changing composition and rates of pH change, adapting their microstructure and so allowing access to a far greater range of morphologies and complexity than can be achieved in single component systems.
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- 2022
26. Water Remediation from Pollutant Agents by the Use of an Environmentally Friendly Supramolecular Hydrogel
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Demetra Giuri, Simone D'Agostino, Paolo Ravarino, Davide Faccio, Giuseppe Falini, Claudia Tomasini, Giuri D., D'Agostino S., Ravarino P., Faccio D., Falini G., and Tomasini C.
- Subjects
Biomaterials ,Renewable Energy, Sustainability and the Environment ,Materials Chemistry ,aromatic-free peptide ,Energy Engineering and Power Technology ,water remediation ,hydrogel ,crystal - Abstract
The removal of Diclofenac sodium from waste waters has a high relevance since it belongs to the therapeutic group most commonly found in wastes. An aromatic-free and low-impact technology that efficiently entraps aqueous pollutants is highly desirable. We synthesised two Boc-protected and aromatic-free tripeptides (Boc-L-Ala-Aib-L-Val-OH and Boc-L-Val-Aib-L-Val-OH) and studied their ability to form gels with mixtures of water and alcohols, such as methanol, ethanol and 2-propanol. Boc-L-Ala-Aib-L-Val-OH forms a strong hydrogel in 2-propanol/water mixtures able to trap up to 97.8% of Eosin Y model molecule and up to 92.0% of Diclofenac sodium from aqueous solutions. The hydrogel is also thixotropic, thermoreversible and biocompatible. This outcome is very encouraging and paves the way to a new approach for developing new materials using aromatic-free hydrogels, useful for water remediation.
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- 2022
27. Spatiotemporal control over base‐catalyzed hydrogelation using a bilayer system
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Ravarino, Paolo, Panja, Santanu, and Adams, Dave J.
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Diffusion ,Polymers and Plastics ,Organic Chemistry ,Materials Chemistry ,Hydrogels ,Rheology ,Catalysis - Abstract
Controlling the formation and directional growth of hydrogels is a challenge. In this paper, a new methodology to program the gel formation both over space and time is proposed, using the diffusion and subsequent hydrolysis of 1,1'-carbonyldiimidazole from an immiscible organic solution to the aqueous gel media.
- Published
- 2022
28. The role of fetal programming in human carcinogenesis - May the Barker hypothesis explain interindividual variability in susceptibility to cancer insurgence and progression?
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F, Coghe, D, Fanni, C, Gerosa, A, Ravarino, M, Mureddu, G, Cerrone, P, Coni, G, Pichiri, T, Congiu, M, Piras, F, Cau, V, Aimola, A, Balestrieri, E, Lai, M, Manchia, A, Scano, G, Orrù, G, La Nasa, P, Van Eyken, L, Saba, M, Scartozzi, M, Castagnola, and G, Faa
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Epigenomics ,Fetal Development ,Carcinogenesis ,Pregnancy ,Neoplasms ,Infant, Newborn ,Birth Weight ,Humans ,Female - Abstract
The growing incidence of cancers is pushing oncologists to find out new explanations other than the somatic mutation theory, based on the accumulation of DNA mutations. In particular, the embryo-fetal exposure to an increasing number of environmental factors during gestation might represent a trigger able to influence the susceptibility of the newborn to develop cancer later in life. This idea agrees with the fetal programming theory, also known as the Barker hypothesis. Here the role of insulin-like growth factors, thymosin beta-4, and epigenome are discussed as mediators of cancer in prenatal human development. The role of epigenetic factors that during gestation increase the predisposition to develop cancer and the similarities in the gene expression (like MMP9, OPN, TP53 and CDKN2A) between embryonic development and cancer are key factors. Likewise, maternal obesity might be able to re-program embryo-fetal development with long-term changes, including an increased risk to develop neuroblastoma and acute leukemia. Birth weight alone and birth weight corrected for gestational age are proposed as important variables capable of predicting the vulnerability to develop cancers. According to the findings here reported, we hypothesize that cancer prevention should start during gestation by improving the quality of maternal diet. In conclusion, the Barker hypothesis should be applied to cancer as well. Therefore, the identification of the epigenetic factors of cancer appears mandatory, so that the cancer prevention might start in the womb before birth.
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- 2022
29. Interobserver variability in the assessment of stromal tumor-infiltrating lymphocytes (sTILs) in triple-negative invasive breast carcinoma influences the association with pathological complete response: the IVITA study
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Caroline Bouzin, Serdar Altinay, Gaëtan MacGrogan, Serena Wong, Anne Vincent-Salomon, Claudia Maria Stanciu-Pop, Laurent Arnould, Franceska Dedeurwaerdere, Delfyne Hastir, Alberto Ravarino, Stephen B. Fox, Valérie Duwel, Caterina Marchiò, Hannah Y Wen, Renata Sinke, Dieter Peeters, Clara Gerosa, Emily Reisenbichler, Benjamin F. Dessauvagie, Maschenka Balkenhol, Magali Lacroix-Triki, Aline François, Christine Galant, Carolien H.M. van Deurzen, S Sanati, Kathleen Lambein, Octavio Burguès, Eline Kurpershoek, Sharon Nofech-Mozes, Andoni Laka, Anne-Sophie Van Rompuy, Mieke R Van Bockstal, Abeer M Shaaban, Glenn Broeckx, Cecile Colpaert, Vera R. J. Schelfhout, Shabnam Jaffer, Anne Marie Schelfhout, Maria Dolores Martin Martinez, Koen Van de Vijver, Erika Resetkova, Giuseppe Floris, UCL - SSS/IREC/MORF - Pôle de Morphologie, UCL - SSS/IREC/MONT - Pôle Mont Godinne, UCL - SSS/IREC/SLUC - Pôle St.-Luc, UCL - (SLuc) Service d'anatomie pathologique, UCL - (MGD) Service d'anatomie pathologique, and Pathology
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Oncology ,Adult ,medicine.medical_specialty ,Pathology ,interobserver variability ,Intraclass correlation ,Clinical Decision-Making ,Triple Negative Breast Neoplasms ,Article ,Tumor-infiltrating lymphocytes ,Pathology and Forensic Medicine ,Breast cancer ,Lymphocytes, Tumor-Infiltrating ,SDG 3 - Good Health and Well-being ,Predictive Value of Tests ,Internal medicine ,Biopsy ,medicine ,Tumor Microenvironment ,Humans ,Neoplasm Invasiveness ,Stromal tumor ,Pathological ,Triple negative ,Complete response ,Mastectomy ,Aged ,Aged, 80 and over ,Observer Variation ,medicine.diagnostic_test ,business.industry ,Australia ,Cancer ,Reproducibility of Results ,Middle Aged ,medicine.disease ,Neoadjuvant Therapy ,Women's cancers Radboud Institute for Health Sciences [Radboudumc 17] ,Europe ,Treatment Outcome ,Chemotherapy, Adjuvant ,North America ,triple-negative breast cancer ,pathological complete response ,Female ,Human medicine ,Stromal Cells ,business ,neoadjuvant chemotherapy - Abstract
Contains fulltext : 245198.pdf (Publisher’s version ) (Closed access) High stromal tumor-infiltrating lymphocytes (sTILs) in triple-negative breast cancer (TNBC) are associated with pathological complete response (pCR) after neoadjuvant chemotherapy (NAC). Histopathological assessment of sTILs in TNBC biopsies is characterized by substantial interobserver variability, but it is unknown whether this affects its association with pCR. Here, we aimed to investigate the degree of interobserver variability in an international study, and its impact on the relationship between sTILs and pCR. Forty pathologists assessed sTILs as a percentage in digitalized biopsy slides, originating from 41 TNBC patients who were treated with NAC followed by surgery. Pathological response was quantified by the MD Anderson Residual Cancer Burden (RCB) score. Intraclass correlation coefficients (ICCs) were calculated per pathologist duo and Bland-Altman plots were constructed. The relation between sTILs and pCR or RCB class was investigated. The ICCs ranged from -0.376 to 0.947 (mean: 0.659), indicating substantial interobserver variability. Nevertheless, high sTILs scores were significantly associated with pCR for 36 participants (90%), and with RCB class for eight participants (20%). Post hoc sTILs cutoffs at 20% and 40% resulted in variable associations with pCR. The sTILs in TNBC with RCB-II and RCB-III were intermediate to those of RCB-0 and RCB-I, with lowest sTILs observed in RCB-I. However, the limited number of RCB-I cases precludes any definite conclusions due to lack of power, and this observation therefore requires further investigation. In conclusion, sTILs are a robust marker for pCR at the group level. However, if sTILs are to be used to guide the NAC scheme for individual patients, the observed interobserver variability might substantially affect the chance of obtaining a pCR. Future studies should determine the 'ideal' sTILs threshold, and attempt to fine-tune the patient selection for sTILs-based de-escalation of NAC regimens. At present, there is insufficient evidence for robust and reproducible sTILs-guided therapeutic decisions.
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- 2021
30. Ultrastructural findings of lung injury due to Vaccine-induced Immune Thrombotic Thrombo- cytopenia (VITT) following COVID-19 vaccination: a scanning electron microscopic study
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T, Congiu, D, Fanni, M, Piras, C, Gerosa, F, Cau, D, Barcellona, E, D'Aloja, R, Demontis, A, Chighine, M, Nioi, P, Coni, A, Ravarino, G, Cerrone, V, Aimola, C, Botta, A, Scano, G, Orrù, F, Coghe, P, Van Eyken, G, La Nasa, L, Saba, J S, Suri, G, Faa, and F, Marongiu
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Male ,Fibrin ,Purpura, Thrombocytopenic, Idiopathic ,ChAdOx1 nCoV-19 ,Vaccination ,Microscopy, Electron, Scanning ,COVID-19 ,Humans ,Lung Injury ,Middle Aged ,Parenchymal Tissue - Abstract
Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare new syndrome occurring after the ChAdOx1 nCoV-19 vaccine immunization. Patients with VITT are characterized by a variable clinical presentation, likewise also the outcome of these patients is very variable. Here we report the lung ultrastructural findings in the course of VITT of a 58-year-old male patient. Alveoli were mainly dilated, irregular in shape, and occupied by a reticular network of fibrin, while interalveolar septa appeared thickened. The proliferation of small capillaries gave rise to plexiform structures and pulmonary capillary hemangiomatosis-like features. Near the alveoli occupied by a dense fibrin network, the medium-sized arteries showed a modified wall and an intraluminal thrombus. This scenario looks quite similar to that found during COVID-19, where the lungs suffer from the attack of the antigen-antibodies complexes and the virus respectively. In both diseases, the final outcome is a severe inflammation, activation of the haemostatic system and fibrinolysis.
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- 2022
31. Distribution planning methodology for network integration of EV
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G. Ravarino, A. Galati, C. A. Baquedano, L. Consiglio, and G. Licasale
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- 2022
32. Designing a Transparent and Fluorine Containing Hydrogel
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Claudia Tomasini, Paolo Ravarino, Demetra Giuri, Davide Faccio, Ravarino P., Giuri D., Faccio D., and Tomasini C.
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Polymers and Plastics ,Supramolecular chemistry ,Bioengineering ,Peptide ,02 engineering and technology ,010402 general chemistry ,01 natural sciences ,Article ,thixotropy ,Biomaterials ,lcsh:Chemistry ,chemistry.chemical_compound ,lcsh:General. Including alchemy ,fluorine ,Polymer chemistry ,Aromatic amino acids ,lcsh:Inorganic chemistry ,pH change ,lcsh:Science ,chemistry.chemical_classification ,Dipeptide ,Hydrogen bond ,Organic Chemistry ,Aromaticity ,021001 nanoscience & nanotechnology ,lcsh:QD146-197 ,0104 chemical sciences ,chemistry ,lcsh:QD1-999 ,Self-healing hydrogels ,Halogen ,rheology ,lcsh:Q ,hydrogel ,0210 nano-technology ,lcsh:QD1-65 - Abstract
Physical hydrogels are supramolecular materials obtained by self-assembly of small molecules called gelators. Aromatic amino acids and small peptides containing aromatic rings are good candidates as gelators due to their ability to form weak bonds as π-π interactions and hydrogen bonds between NH and CO of the peptide chain. In this paper we show our results in the preparation of a transparent hydrogel that was obtained by self-assembly of a fluorine-containing dipeptide that relies on the additional formation of halogen bonds due to the fluorine atoms contained in the dipeptide. We used Boc-D-F2Phe-L-Oxd-OH (F2Phe = 3,4-difluorophenylalainine, Oxd = 4-methyl-5-carboxy-oxazolidin-2-one) that formed a strong and transparent hydrogel in 0.5% w/w concentration at pH = 4.2. The formation of a hydrogel made of unnatural fluorinated amino acids may be of great interest in the evaluation of patients with parkinsonian syndromes and may be used for controlled release.
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- 2021
33. Stereocontrolled synthesis of four diastereomeric C-aryl manno- and talofuranosides
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Ravarino, Elisa, Jana, Sunit Kumar, Fröhlich, Roland, and Holl, Ralph
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- 2012
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34. Controlled Annealing in Adaptive Multicomponent Gels.
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Ravarino, Paolo, Panja, Santanu, Bianco, Simona, Koev, Todor, Wallace, Matthew, and Adams, Dave J.
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GELATION , *MICROSTRUCTURE , *HYDROLYSIS , *RHEOLOGY - Abstract
We use a pH‐driven annealing process to convert between co‐assembled and self‐sorted networks in multicomponent gels. The initially formed gels at low pH are co‐assembled, with the two components coexisting within the same self‐assembled structures. We use an enzymatic approach to increase the pH, resulting in a gel‐to‐sol transition, followed by a hydrolysis to lower the pH once again. As the pH decreases, a self‐sorted network is formed by a two‐stage gelation process determined by the pKa of each component. This approach can be expanded to layered systems to generate many varied systems by changing composition and rates of pH change, adapting their microstructure and so allowing access to a far greater range of morphologies and complexity than can be achieved in single component systems. [ABSTRACT FROM AUTHOR]
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- 2023
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35. Controlled Hydrolysis of Odorants Schiff Bases in Low-Molecular-Weight Gels
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Nicastro, Gloria, primary, Black, Louise Mary, additional, Ravarino, Paolo, additional, d’Agostino, Simone, additional, Faccio, Davide, additional, Tomasini, Claudia, additional, and Giuri, Demetra, additional
- Published
- 2022
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36. Water Remediation from Pollutant Agents by the Use of an Environmentally Friendly Supramolecular Hydrogel
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Giuri, Demetra, primary, D'Agostino, Simone, additional, Ravarino, Paolo, additional, Faccio, Davide, additional, Falini, Giuseppe, additional, and Tomasini, Claudia, additional
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- 2022
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- View/download PDF
37. Fluorine Effect in the Gelation Ability of Low Molecular Weight Gelators
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Ravarino, Paolo, primary, Di Domenico, Nadia, additional, Barbalinardo, Marianna, additional, Faccio, Davide, additional, Falini, Giuseppe, additional, Giuri, Demetra, additional, and Tomasini, Claudia, additional
- Published
- 2022
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- View/download PDF
38. How challenging could be preoperative and intraoperative diagnosis of endometrial cancer?
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FERRERO, Annamaria, primary, ATTIANESE, Daniela, additional, VILLA, Michela, additional, RAVARINO, Nicoletta, additional, MENATO, Guido, additional, and VOLPI, Eugenio, additional
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- 2022
- Full Text
- View/download PDF
39. Distribution planning methodology for network integration of EV
- Author
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Ravarino, G., primary, Galati, A., additional, Baquedano, C. A., additional, Consiglio, L., additional, and Licasale, G., additional
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- 2022
- Full Text
- View/download PDF
40. Stem/progenitor cells in the developing human cerebellum: an immunohistochemical study
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V. Pibiri, A. Ravarino, C. Gerosa, M.C. Pintus, V. Fanos, and G. Faa
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Human cerebellum ,human fetus ,immunohistochemistry ,stem cells ,human development ,cerebellar niches. ,Biology (General) ,QH301-705.5 - Abstract
The aim of this study was to analyze, by immunohistochemistry, the occurrence of stem/progenitor cells localized in the different niches of the developing human cerebellum. To this end, cerebellar samples were obtained from 3 fetuses and 3 newborns ranging, respectively, from 11 to 24 and from 30 to 38 weeks of gestation. Specimens were 10% formalin-fixed, routinely processed and paraffin-embedded; 3 μm-tick sections were immunostained with anti-SOX2 and PAX6 antibodies. Our study evidenced SOX2 and PAX6 immunoreactivity in precursors cells in all six developing human cerebella. SOX2 was expressed in precursors of different neural cell types, including Purkinje neurons, stellate cells, basket cells and Golgi cells. In the cerebellar cortex, SOX2 expression changed during gestation, being highly expressed from the 20th up to the 24th week, whereas at the 30th and at the 34th week SOX2 immunoreactivity was restricted to the Purkinje cell layer and the inner zone. Cerebellar human cortex was negative at the 38th week of gestation. PAX6 immunoreactivity was restricted to granule cell precursors in the external granule layer (EGL), being detected at all gestational ages. Our study indicates SOX2 and PAX6 as two useful markers of stem/progenitor cells that highlight the different germinative zones in the developing human cerebellum.
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- 2016
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41. The small intestinal mucosa and its stem cells
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Rossano Ambu, Clara Gerosa, Giorgia Locci, Eleonora Obinu, Alberto Ravarino, Anna De Magistris, Alessandra Reali, Peter Van Eyken, Gavino Faa, Silvia Nati, and Laura Vinci
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small intestinal mucosa ,embryogenesis ,crypt-villus axis ,stem cells ,signaling pathways ,regenerative medicine ,Medicine ,Pediatrics ,RJ1-570 - Abstract
In the first part of this review a brief summary of the embryology and histology of the gastrointestinal tract is provided. In the second part intestinal stem cells (ISCs) are discussed. Several signaling pathways play a crucial role in the crypt base in the regulation of ISC proliferation and self-renewal; Wnt, Notch, BMP, Ephrin, JAK/STAT1, PTEN, AKT, PI3K and many more. Numerous investigators are involved in studying the location, number, and behavior of ISCs within the base of the intestinal crypts. Several markers are espressed by ISCs. Among these, Leucine-rich-repeat-containing G-protein-coupled receptor-5 (Lgr5), Sox9, Prominin-1, DCAMKL-1, EphB2, p-PTEN, p-AKT, Fgfr3, m-TER, and CD44. Stem cell therapy has shown promise for the treatment of some diseases characterized by tissue damage with ischemic and inflammatory lesions like inflammatory bowel disease (IBD) and necrotizing enterocolitis (NEC). Proceedings of the 2nd International Course on Perinatal Pathology (part of the 11th International Workshop on Neonatology · October 26th-31st, 2015) · Cagliari (Italy) · October 31st, 2015 · Stem cells: present and future Guest Editors: Gavino Faa, Vassilios Fanos, Antonio Giordano
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- 2016
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42. Introduction to embryonic and adult neural stem cells: from the metabolic circuits of the niches to the metabolome
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Maria Antonietta Marcialis, Elisabetta Coni, Maria Cristina Pintus, Alberto Ravarino, Vassilios Fanos, Carlo Coni, and Gavino Faa
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neural stem cells ,metabolomics ,metabolism ,neurogenesis ,mitochondria ,Medicine ,Pediatrics ,RJ1-570 - Abstract
Metabolomics has provided new insight into the biology that drives the phenotype of stem cells. During the recent years, metabolic circuits of embryonic and neural stem cells (NSCs) have been better elucidated. Many factors contribute to stem cell determination fate: metabolism, transcriptional signaling, epigenetics, extrinsic mechanisms such as short-range signals from the niche and humoral signals. The metabolism decides if a cell proliferates, differentiates or remains quiescent. Embryonic and adult NSCs share two features: they generate at least one daughter cell and can differentiate into specialized cells. NSCs use different pathways depending on their stage of differentiation: glycolysis is highest in proliferating stem cells and it is essential for stemness. Conversely, oxidative phosphorylation supports differentiated cells. Moreover, lipid metabolism maintains proliferation and neurogenesis; indeed, fatty acid oxidation and fatty acid synthesis represent a component of stem cell fate regulation. Proceedings of the 2nd International Course on Perinatal Pathology (part of the 11th International Workshop on Neonatology · October 26th-31st, 2015) · Cagliari (Italy) · October 31st, 2015 · Stem cells: present and future Guest Editors: Gavino Faa, Vassilios Fanos, Antonio Giordano
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- 2016
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43. Stem/progenitor cells in the cerebral cortex of the human preterm: a resource for an endogenous regenerative neuronal medicine?
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Laura Vinci, Alberto Ravarino, Clara Gerosa, Maria Cristina Pintus, Maria Antonietta Marcialis, Viviana Marinelli, Gavino Faa, Vassilios Fanos, and Rossano Ambu
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cerebral cortex ,human preterm ,stem cells ,neurogenesis ,regenerative medicine ,immunohistochemical markers ,Medicine ,Pediatrics ,RJ1-570 - Abstract
The development of the central nervous system represents a very delicate period of embryogenesis. Premature interruption of neurogenesis in human preterm newborns can lead to motor deficits, including cerebral palsy, and significant cognitive, behavioral or sensory deficits in childhood. Preterm infants also have a higher risk of developing neurodegenerative diseases later in life. In the last decade, great importance has been given to stem/progenitor cells and their possible role in the development and treatment of several neurological disorders. Several studies, mainly carried out on experimental models, evidenced that immunohistochemistry may allow the identification of different neural and glial precursors inside the developing cerebral cortex. However, only a few studies have been performed on markers of human stem cells in the embryonic period. This review aims at illustrating the importance of stem/progenitor cells in cerebral cortex during pre- and post-natal life. Defining the immunohistochemical markers of stem/progenitor cells in the human cerebral cortex during development may be important to develop an “endogenous” target therapy in the perinatal period. Proceedings of the 2nd International Course on Perinatal Pathology (part of the 11th International Workshop on Neonatology · October 26th-31st, 2015) · Cagliari (Italy) · October 31st, 2015 · Stem cells: present and future Guest Editors: Gavino Faa, Vassilios Fanos, Antonio Giordano
- Published
- 2016
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44. Immunohistochemical markers of neural progenitor cells in the early embryonic human cerebral cortex
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L. Vinci, A. Ravarino, V. Fanos, A.G. Naccarato, G. Senes, C. Gerosa, G. Bevilacqua, G. Faa, and R. Ambu
- Subjects
Cerebral cortex ,human embryo ,human development ,immunohistochemistry ,fetal stem cells. ,Biology (General) ,QH301-705.5 - Abstract
The development of the human central nervous system represents a delicate moment of embryogenesis. The purpose of this study was to analyze the expression of multiple immunohistochemical markers in the stem/progenitor cells in the human cerebral cortex during the early phases of development. To this end, samples from cerebral cortex were obtained from 4 human embryos of 11 weeks of gestation. Each sample was formalin-fixed, paraffin embedded and immunostained with several markers including GFAP, WT1, Nestin, Vimentin, CD117, S100B, Sox2, PAX2, PAX5, Tβ4, Neurofilament, CD44, CD133, Synaptophysin and Cyclin D1. Our study shows the ability of the different immunohistochemical markers to evidence different zones of the developing human cerebral cortex, allowing the identification of the multiple stages of differentiation of neuronal and glial precursors. Three important markers of radial glial cells are evidenced in this early gestational age: Vimentin, Nestin and WT1. Sox2 was expressed by the stem/progenitor cells of the ventricular zone, whereas the postmitotic neurons of the cortical plate were immunostained by PAX2 and NSE. Future studies are needed to test other important stem/progenitor cells markers and to better analyze differences in the immunohistochemical expression of these markers during gestation.
- Published
- 2016
- Full Text
- View/download PDF
45. Interobserver variability in upfront dichotomous histopathological assessment of ductal carcinoma in situ of the breast: the DCISion study
- Author
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Gaëtan MacGrogan, Valérie Duwel, Alberto Ravarino, Stephen B. Fox, Renata Sinke, Eline Kurpershoek, Noella Bletard, Caroline Bouzin, Anne Marie Schelfhout, Hélène Dano, Koen Van de Vijver, Anne Vincent-Salomon, Claudia Maria Stanciu-Pop, Laurent Arnould, Serdar Altinay, Souzan Sanati, Magali Lacroix-Triki, Franceska Dedeurwaerdere, Carolien H.M. van Deurzen, Kathleen Lambein, Anne-Sophie Van Rompuy, Claudia Stobbe, Hannah Wen, Mieke R. Van Bockstal, Vera Schelfhout, Erika Resetkova, Cecile Colpaert, Stephanie Verschuere, Giuseppe Floris, Dolores Martin Martinez, Caterina Marchiò, Sharon Nofech-Mozes, Shabnam Jaffer, Andoni Laka, Dieter Peeters, Clara Gerosa, Emily Reisenbichler, Christine Galant, Abeer M Shaaban, Benjamin F. Dessauvagie, UCL - (SLuc) Service d'anatomie pathologique, UCL - SSS/IREC/MONT - Pôle Mont Godinne, UCL - (MGD) Service d'anatomie pathologique, UCL - SSS/IREC/SLUC - Pôle St.-Luc, UCL - SSS/IREC/MORF - Pôle de Morphologie, and Pathology
- Subjects
0301 basic medicine ,Pathology ,Biopsy ,0302 clinical medicine ,Risk Factors ,REPRODUCIBILITY ,Medicine ,Nuclear atypia ,Observer Variation ,RISK ,medicine.diagnostic_test ,Calcinosis ,Prognosis ,CANCER ,GRADE ,030220 oncology & carcinogenesis ,Predictive value of tests ,RELIABILITY ,Female ,PATHOLOGISTS ,Life Sciences & Biomedicine ,RADIOTHERAPY ,medicine.medical_specialty ,Concordance ,Breast Neoplasms ,LOCAL RECURRENCE ,Risk Assessment ,Article ,CLASSIFICATION ,Pathology and Forensic Medicine ,CONSISTENCY ,Necrosis ,03 medical and health sciences ,Lymphocytes, Tumor-Infiltrating ,Breast cancer ,Predictive Value of Tests ,Carcinoma ,Humans ,Cell Nucleus ,Science & Technology ,business.industry ,Reproducibility of Results ,Ductal carcinoma ,medicine.disease ,Pathologists ,Carcinoma, Intraductal, Noninfiltrating ,030104 developmental biology ,business ,Nuclear medicine ,Kappa - Abstract
Histopathological assessment of ductal carcinoma in situ, a nonobligate precursor of invasive breast cancer, is characterized by considerable interobserver variability. Previously, post hoc dichotomization of multicategorical variables was used to determine the "ideal" cutoffs for dichotomous assessment. The present international multicenter study evaluated interobserver variability among 39 pathologists who performed upfront dichotomous evaluation of 149 consecutive ductal carcinomas in situ. All pathologists independently assessed nuclear atypia, necrosis, solid ductal carcinoma in situ architecture, calcifications, stromal architecture, and lobular cancerization in one digital slide per lesion. Stromal inflammation was assessed semiquantitatively. Tumor-infiltrating lymphocytes were quantified as percentages and dichotomously assessed with a cutoff at 50%. Krippendorff's alpha (KA), Cohen's kappa and intraclass correlation coefficient were calculated for the appropriate variables. Lobular cancerization (KA = 0.396), nuclear atypia (KA = 0.422), and stromal architecture (KA = 0.450) showed the highest interobserver variability. Stromal inflammation (KA = 0.564), dichotomously assessed tumor-infiltrating lymphocytes (KA = 0.520), and comedonecrosis (KA = 0.539) showed slightly lower interobserver disagreement. Solid ductal carcinoma in situ architecture (KA = 0.602) and calcifications (KA = 0.676) presented with the lowest interobserver variability. Semiquantitative assessment of stromal inflammation resulted in a slightly higher interobserver concordance than upfront dichotomous tumor-infiltrating lymphocytes assessment (KA = 0.564 versus KA = 0.520). High stromal inflammation corresponded best with dichotomously assessed tumor-infiltrating lymphocytes when the cutoff was set at 10% (kappa = 0.881). Nevertheless, a post hoc tumor-infiltrating lymphocytes cutoff set at 20% resulted in the highest interobserver agreement (KA = 0.669). Despite upfront dichotomous evaluation, the interobserver variability remains considerable and is at most acceptable, although it varies among the different histopathological features. Future studies should investigate its impact on ductal carcinoma in situ prognostication. Forthcoming machine learning algorithms may be useful to tackle this substantial diagnostic challenge. ispartof: MODERN PATHOLOGY vol:33 issue:3 pages:354-366 ispartof: location:United States status: published
- Published
- 2020
46. Inter-observer agreement for the histological diagnosis of invasive lobular breast carcinoma
- Author
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Matthias Christgen, Leonie Donata Kandt, Wiebke Antonopoulos, Stephan Bartels, Mieke R Bockstal, Martin Bredt, Maria Jose Brito, Henriette Christgen, Cecile Colpaert, Bálint Cserni, Gábor Cserni, Maximilian E Daemmrich, Raihanatou Danebrock, Franceska Dedeurwaerdere, Carolien HM Deurzen, Ramona Erber, Christine Fathke, Henning Feist, Maryse Fiche, Claudia Aura Gonzalez, Natalie D Hoeve, Loes Kooreman, Till Krech, Glen Kristiansen, Janina Kulka, Florian Laenger, Marcel Lafos, Ulrich Lehmann, Maria Dolores Martin‐Martinez, Sophie Mueller, Enrico Pelz, Mieke Raap, Alberto Ravarino, Tanja Reineke‐Plaass, Nora Schaumann, Anne‐Marie Schelfhout, Maxim Schepper, Jerome Schlue, Koen Van de Vijver, Wim Waelput, Axel Wellmann, Monika Graeser, Oleg Gluz, Sherko Kuemmel, Ulrike Nitz, Nadia Harbeck, Christine Desmedt, Giuseppe Floris, Patrick WB Derksen, Paul J Diest, Anne Vincent‐Salomon, Hans Kreipe, Supporting clinical sciences, Experimental Pathology, Pathology, MUMC+: DA Pat Pathologie (9), RS: GROW - R2 - Basic and Translational Cancer Biology, UCL - SSS/IREC/SLUC - Pôle St.-Luc, and UCL - (SLuc) Service d'anatomie pathologique
- Subjects
diagnosis ,Breast Neoplasms ,quality assurance ,PHENOTYPE ,Pathology and Forensic Medicine ,p120‐catenin ,E-CADHERIN EXPRESSION ,REPRODUCIBILITY ,Medicine and Health Sciences ,Pathology ,TUBULOLOBULAR CARCINOMA ,Biomarkers, Tumor ,RB1-214 ,Humans ,ddc:610 ,skin and connective tissue diseases ,beta‐catenin ,Observer Variation ,Science & Technology ,CATENIN ,lobular breast carcinoma ,beta-catenin ,p120-catenin ,tubular elements ,CANCER ,Immunohistochemistry ,ELBCC/LOBSTERPOT consortium ,body regions ,Carcinoma, Lobular ,MORPHOLOGY ,GROWTH ,Female ,Life Sciences & Biomedicine - Abstract
Invasive lobular breast carcinoma (ILC) is the second most common breast carcinoma (BC) subtype and is mainly driven by loss of E-cadherin expression. Correct classification of BC as ILC is important for patient treatment. This study assessed the degree of agreement among pathologists for the diagnosis of ILC. Two sets of hormone receptor (HR)-positive/HER2-negative BCs were independently reviewed by participating pathologists. In set A (61 cases), participants were provided with hematoxylin/eosin (HE)-stained sections. In set B (62 cases), participants were provided with HE-stained sections and E-cadherin immunohistochemistry (IHC). Tumor characteristics were balanced. Participants classified specimens as non-lobular BC versus mixed BC versus ILC. Pairwise inter-observer agreement and agreement with a pre-defined reference diagnosis were determined with Cohen's kappa statistics. Subtype calls were correlated with molecular features, including CDH1/E-cadherin mutation status. Thirty-five pathologists completed both sets, providing 4,305 subtype calls. Pairwise inter-observer agreement was moderate in set A (median κ = 0.58, interquartile range [IQR]: 0.48-0.66) and substantial in set B (median κ = 0.75, IQR: 0.56-0.86, p
- Published
- 2021
47. Thrombotic sinusoiditis and local diffuse intrasinusoidal coagulation in the liver of subjects affected by COVID-19: the evidence from histology and scanning electron microscopy
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D, Fanni, G, Cerrone, L, Saba, R, Demontis, T, Congiu, M, Piras, C, Gerosa, J S, Suri, P, Coni, A, Caddori, M, Piga, G, Mancosu, D, Barcellona, A, Ravarino, A, Chighine, F, Cau, A, Scano, A, Balestrieri, F, Coghe, G, Orrù, P, Van Eyken, G, La Nasa, E, D'Aloia, F, Marongiu, and G, Faa
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Male ,Fibrin ,Erythrocytes ,Biopsy ,Liver Diseases ,COVID-19 ,Thrombosis ,Blood Coagulation Disorders ,Middle Aged ,Young Adult ,Liver ,Hepatocytes ,Microscopy, Electron, Scanning ,Humans ,Autopsy ,Aged - Abstract
Liver injury has been reported in patients with COVID-19. This condition is characterized by severe outcome and could be related with the ability of SARS-CoV-2 to activate cytotoxic T cells. The purpose of this study is to show the histological and scanning electron microscopy features of liver involvement in COVID-19 to characterize the liver changes caused by the activation of multiple molecular pathways following this infection.Liver biopsies from 4 patients (3 post-mortems and 1 in vivo) with COVID-19 were analyzed with histology and by scanning electron microscopy.The liver changes showed significant heterogeneity. The first case showed ground glass hepatocytes and scattered fibrin aggregates in the sinusoidal lumen. The second evidenced intra-sinusoidal thrombi. The third was characterized by sinusoidal dilatation, atrophy of hepatocytes, Disse's spaces dilatation and intra-sinusoidal aggregates of fibrin and red blood cells. The fourth case exhibited diffuse fibrin aggregates in the dilated Disse spaces and microthrombi in the sinusoidal lumen.In COVID-19-related liver injury, a large spectrum of pathological changes was observed. The most peculiar features were very mild inflammation, intra-sinusoidal changes, including sinusoidal dilatation, thrombotic sinusoiditis and diffuse intra-sinusoidal fibrin deposition. These findings suggested that a thrombotic sinusoiditis followed by a local diffuse intra-vascular (intra-sinusoidal) coagulation could be the typical features of the SARS-CoV-2-related liver injury.
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- 2021
48. Fetal programming of COVID-19: may the barker hypothesis explain the susceptibility of a subset of young adults to develop severe disease?
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C, Gerosa, G, Faa, D, Fanni, M, Manchia, J S, Suri, A, Ravarino, D, Barcellona, G, Pichiri, P, Coni, T, Congiu, M, Piras, G, Cerrone, F, Cau, F, Ledda, V, Aimola, F, Coghe, M, Porcu, R, Cau, G, Orru', P, Van Eyken, G, La Nasa, M, Castagnola, F, Marongiu, and L, Saba
- Subjects
Fetal Development ,Young Adult ,Fetal Growth Retardation ,COVID-19 ,Humans ,Disease Susceptibility ,Infant, Low Birth Weight ,Severity of Illness Index - Abstract
The risk stratification of young adults between subjects who will develop a mild form COVID-19 and subjects who will undergo a severe disease remains inaccurate. In this review, we propose that the Barker hypothesis might explain the increased susceptibility to severe forms of COVID-19 in subjects who underwent intrauterine growth restriction (IUGR). In this paper evidence indicating an association between a low birth weight and an adult phenotype which might favor a severe outcome of SARS-CoV-2 infection are presented: lower lung functional capacity; increased respiratory morbidity; changes in fibrinogen and Factor VII serum levels and dysregulation of the hemostasis and thrombosis system; acquisition of a pro-thrombotic phenotype; low nephron number, with decreased ability to sustain renal function and increased renal morbidity; heart remodeling, with a less efficient cardiac function; endothelial dysfunction, a risk factor for the insurgence of the multiple organ failure; remodeling of arteries, with changes in the elastic properties of the arterial wall, predisposing to the insurgence and progression of atherosclerosis; dysfunction of the innate immune system, a risk factor for immune diseases in adulthood. These data suggest that young and adult subjects born too small (IUGR) or too early (pre-terms) might represent a subgroup of "at risk subjects", more susceptible toward severe forms of COVID-19. Given that LBW may be considered a surrogate of IUGR, this phenotypic marker should be included among the indispensable clinical data collected in every patient presenting with SARS-COV-2 infection, irrespectively of his/her age.
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- 2021
49. Angiogenesis and molecular markers in advanced epithelial ovarian cancer: A retrospective study
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Ferrero, Annamaria, Dompè, Daniela, Ravarino, Nicoletta, Ramella, Angela, Fuso, Luca, Maggiorotto, Furio, Tripodi, Elisa, and Zola, Paolo
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- 2011
- Full Text
- View/download PDF
50. Inter‐observer agreement for the histological diagnosis of invasive lobular breast carcinoma
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Christgen, Matthias, primary, Kandt, Leonie Donata, additional, Antonopoulos, Wiebke, additional, Bartels, Stephan, additional, Bockstal, Mieke R, additional, Bredt, Martin, additional, Brito, Maria Jose, additional, Christgen, Henriette, additional, Colpaert, Cecile, additional, Cserni, Bálint, additional, Cserni, Gábor, additional, Daemmrich, Maximilian E, additional, Danebrock, Raihanatou, additional, Dedeurwaerdere, Franceska, additional, Deurzen, Carolien HM, additional, Erber, Ramona, additional, Fathke, Christine, additional, Feist, Henning, additional, Fiche, Maryse, additional, Gonzalez, Claudia Aura, additional, Hoeve, Natalie D, additional, Kooreman, Loes, additional, Krech, Till, additional, Kristiansen, Glen, additional, Kulka, Janina, additional, Laenger, Florian, additional, Lafos, Marcel, additional, Lehmann, Ulrich, additional, Martin‐Martinez, Maria Dolores, additional, Mueller, Sophie, additional, Pelz, Enrico, additional, Raap, Mieke, additional, Ravarino, Alberto, additional, Reineke‐Plaass, Tanja, additional, Schaumann, Nora, additional, Schelfhout, Anne‐Marie, additional, Schepper, Maxim, additional, Schlue, Jerome, additional, Van de Vijver, Koen, additional, Waelput, Wim, additional, Wellmann, Axel, additional, Graeser, Monika, additional, Gluz, Oleg, additional, Kuemmel, Sherko, additional, Nitz, Ulrike, additional, Harbeck, Nadia, additional, Desmedt, Christine, additional, Floris, Giuseppe, additional, Derksen, Patrick WB, additional, Diest, Paul J, additional, Vincent‐Salomon, Anne, additional, and Kreipe, Hans, additional
- Published
- 2021
- Full Text
- View/download PDF
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