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2. Upgrade of the mechanically pumped CO[formula omitted] two-phase cooling system for the alpha magnetic spectrometer on the international space station

Author

Ambrosi, G., Bertucci, B., Bollweg, K., Burger, J., Cai, X., Capell, M., Chung, C.H., Chuang, Y.R., Clark, C., Ding, T., FanChiang, Y.J., Gargiulo, C., Gaggiotti, M., Guo, L., He, Z.H., Heil, M., Heilig, J., Karpinski, W., Koutsenko, V., Kulemzin, A., Lübelsmeyer, K., Martin, T., Mo, D.C., Morelli, G., Miao, J.Y., Mott, P., Mussolin, L., Schael, S., von Dratzig, A. Schutlz, Schwering, G., Scolieri, G., Siedenburg, T., Solano, C., Urban, T., Verlaat, B., Wang, S.H., Wlochal, M., Yan, J.J., Yang, Y., Yu, Y.M., Zeng, R.C., and Zhang, Z.

Published
2023
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3. Effect of centre volume on pathological outcomes and postoperative complications after surgery for colorectal cancer: results of a multicentre national study

Author

Rottoli, M, Spinelli, A, Pellino, G, Gori, A, Calini, G, Flacco, M, Manzoli, L, Poggioli, G, Romano, A, Belvedere, A, Lanci, A, Parlanti, D, Vago, G, Pezzuto, A, Canavese, A, Dajti, G, Cardelli, S, Catalioto, C, Russo, I, Violante, T, Morezzi, D, Maurino, L, Filippone, E, Cuicchi, D, Bernante, P, Jovine, E, Lombardi, R, Masetti, M, Cipressi, C, Offi, M, Larotonda, C, Puglisi, S, Barbosa, A, Vaiana, R, Bianchi, P, Tonti, C, Codignola, C, Zorcolo, L, Restivo, A, Deidda, S, Marchetti, M, Ippolito, L, Spolverato, G, Pucciarelli, S, Marchegiani, F, Ghio, G, Zagolin, G, Glavas, D, Tomassi, M, Rosati, R, Elmore, U, Gozzini, L, Calef, R, Puccetti, F, Cossu, A, Vignali, A, Morino, M, Allaix, M, Cannata, G, Lombardi, E, Ammirati, C, Piceni, C, Buccianti, P, Balestri, R, Puccini, M, Pezzati, D, D'Ischia, R, Asta, V, Sargenti, B, Taddei, G, Bonari, F, Boni, G, Ferrero, A, Mineccia, M, Gonella, F, Palisi, M, Danese, F, Cherubini, V, Perotti, S, Carvello, M, Carbone, F, Luberto, A, Calafiore, E, De Lucia, F, Sacchi, M, Sasia, D, Giuffrida, M, Ballauri, E, Cardile, M, Armentano, S, Beltrami, E, Preve, G, Vercellone, B, Mozzon, M, Folliero, C, Lirusso, C, Vecchiato, M, Ziccarelli, A, Gattesco, D, Moretti, L, Crestale, S, Banchini, F, Capelli, P, Romboli, A, Palmieri, G, Conti, L, Rizzi, N, Bonfili, D, De Manzini, N, Germani, P, Osenda, E, Cortinovis, S, Giunta, C, Fracon, S, Abdallah, H, Bogoni, S, Portolani, N, Nascimbeni, R, Molfino, S, Tiberio, G, Garosio, I, Lamperti, G, Rigosa, D, Ercolani, G, Solaini, L, Cavaliere, D, Avanzolini, A, D'Acapito, F, Chiarella, L, Di Pietrantonio, D, Annunziata, D, Piccolo, R, Sorrentino, M, Pansini, M, Cojutti, A, Graziano, M, Callegari, F, Balzarotti, L, Dameno, V, Cattaneo, A, Santolamazza, G, Altieri, C, Magarini, R, Pietrabissa, A, Dominioni, T, Pugliese, L, Peri, A, Botti, M, Salvetti, F, Boni, L, Cassinotti, E, Baldari, L, Messina, V, D'Abrosca, V, Cianci, P, Tumolo, R, Gattulli, D, Restini, E, Minafra, M, Sederino, M, Bottalico, B, Pilati, P, Franzato, B, Mattara, G, De Simoni, O, Barina, A, Tonello, M, Muratore, A, Calabro, M, Federico Pipitone, N, Cuzzola, B, Van Nood, E, Passuello, N, Frasson, A, Mammano, E, Faccio, L, Vittadello, F, Bressan, A, Sarzo, G, Tamini, N, Oldani, M, Cigagna, L, Carissimi, F, De Carlo, G, Baccalini, E, Nespoli, L, Giordano, A, Cantafio, S, Grifoni, L, Matani, D, Livi, S, Delogu, D, Scognamillo, F, Marrosu, A, Guerrini, L, Ugolini, G, Ghignone, F, Frascaroli, G, Albertini, N, Zattoni, D, Taffurelli, G, Montroni, I, Colombo, F, Danelli, P, Bondurri, A, Maffioli, A, Bonomi, A, Pezzoli, I, Cammarata, F, Goletti, O, Molteni, M, Assisi, A, Quartierini, G, Da Lio, C, Verdi, D, Mondi, I, Peluso, C, Macchi, L, Tanzanu, M, Zanzi, F, Pellegrini, S, Andreuccetti, J, D'Alessio, R, Pignata, G, De Capua, M, Canfora, I, Ottaviani, L, Lepiane, P, Balla, A, De Carlo, A, Saraceno, F, Scaramuzzo, R, Guida, A, Aguzzi, D, Bellora, P, Gentilli, S, Monni, M, Nikaj, H, Cillara, N, Cannavera, A, Deserra, A, Margiani, C, Cabula, R, Dettori, M, Gramignano, G, Lezoche, G, Ortenzi, M, Orlandoni, E, Curzi, F, Vitali, F, Capomagi, P, Palmieri, M, Del Rio, P, Bonati, E, Loderer, T, Cozzani, F, Rossini, M, Agnesi, S, Capolupo, G, Caricato, M, Carannante, F, Masciana, G, Marrelli, M, Miacci, V, Lauricella, S, Tonini, V, Cervellera, M, Pisconti, S, Lozito, C, Shahu, J, Mongelli, C, Morelli, G, Sartarelli, L, Sica, G, Siragusa, L, Bagaglini, G, Franceschilli, M, Bellato, V, Fiorani, C, Taddei, A, Risaliti, M, Bartolini, I, Ringressi, M, Tirloni, L, Laface, L, Abate, E, Casati, M, Gobbi, P, Opocher, E, Mariani, N, Ceretti, A, Giovenzana, M, Giuliani, B, Sironi, M, Grossi, U, Zanus, G, Santoro, G, Brizzolari, M, De Leo, E, Novello, S, Aquilino, K, Milardi, F, Olmi, S, Uccelli, M, Bonaldi, M, Cesana, G, Bindi, M, Galleano, R, Langone, A, Botto, M, Franceschi, A, Gambino, E, Ronconi, M, Casiraghi, S, Casole, G, Ciulla, S, Terrosu, G, Calandra, S, Scarpa, E, Cherchi, V, Martinuzzo, L, Clocchiatti, L, Muschitiello, D, Romanzi, A, Vignati, B, Vannelli, A, Scolaro, R, Milanesi, M, Rossi, F, Canonico, G, Anastasi, A, Nelli, T, Barlettai, M, Fratarcangeli, R, Di Martino, C, Damigella, A, Adinolfi, E, Birindelli, A, Taglietti, L, Dester, S, Fleres, F, Cucinotta, E, Viscosi, F, Biondo, S, Badessi, G, Catarsini, N, Mazzeo, C, Rega, D, Delrio, P, Cervone, C, Aversano, A, De Franciscis, S, Di Marzo, M, Marra, B, Pace, U, Amato, A, Batistotti, P, Mina, E, Serventi, A, Lapolla, P, Mingoli, A, Sapienza, P, Brachini, G, Cirillo, B, Fiori, E, Crocetti, D, Clementi, I, Martines, G, Picciariello, A, Tomasicchio, G, Dibra, R, Trigiante, G, Rinaldi, M, Lantone, G, Porcu, A, Perra, T, Scanu, A, Feo, C, Fancellu, A, Cossu, M, Ginesu, G, Patriti, A, Coletta, D, Petrelli, F, Greco, P, Spadoni, C, Cassiani, G, Bianchini, F, Arganini, M, Bianchini, M, Perotti, B, Palmeri, M, Scabini, S, Deiana, S, Carganico, G, Pertile, D, Soriero, D, Fioravanti, E, Sperotto, B, Nardo, B, Paglione, D, Crocco, V, Doni, M, Osso, M, Perri, R, Sampietro, G, Corbellini, C, Lorusso, L, Manzo, C, Cigognini, M, Baldi, C, Palomba, G, Aprea, G, Capuano, M, Basile, R, Tutino, R, Massani, M, Marinelli, L, Canitano, N, Pilia, T, Podda, M, Pisanu, A, Murzi, V, Incani, S, Frongia, F, Esposito, G, Luglio, G, Tropeano, F, Pagano, G, Spina, E, De Simone, G, Cricri, M, Catena, F, Vallicelli, C, Zanini, N, Ronconi, D, Favi, F, Mazzucchelli, C, Convertini, G, Vincenti, L, Andriola, V, Bizzoca, C, Fabbri, N, Fazzin, M, Pesce, A, Gennari, S, Torchiaro, M, Severi, S, Frontali, A, Bracchetti, G, Granieri, S, Cotsoglou, C, Carlini, M, Lisi, G, Spoletini, D, Mastrangeli, M, Campanelli, M, Manigrasso, M, Milone, M, De Palma, G, Vertaldi, S, Chini, A, Maione, F, Marello, A, Selvaggi, F, Sciaudone, G, Selvaggi, L, Tasselli, F, Fuschillo, G, Oddis, L, Grande, S, Grande, M, Ascanelli, S, Chimisso, L, Aisoni, F, Rossin, E, Pepe, F, Marchetti, F, Picardi, B, Rossi, S, Del Monte, S, Picarelli, M, Muttillo, I, Ratto, C, Marra, A, Parello, A, Litta, F, Campenni, P, De Simone, V, Pata, F, Riboni, C, Rausa, E, Celentano, V, Rottoli M., Spinelli A., Pellino G., Gori A., Calini G., Flacco M. E., Manzoli L., Poggioli G., Romano A., Belvedere A., Lanci A. L., Parlanti D., Vago G., Pezzuto A. P., Canavese A., Dajti G., Cardelli S., Catalioto C., Russo I. S., Violante T., Morezzi D., Maurino L., Filippone E., Cuicchi D., Bernante P., Jovine E., Lombardi R., Masetti M., Cipressi C., Offi M. F., Larotonda C., Puglisi S. B., Barbosa A., Vaiana R., Bianchi P. M., Tonti C., Codignola C., Zorcolo L., Restivo A., Deidda S., Marchetti M. E., Ippolito L., Spolverato G., Pucciarelli S., Marchegiani F., Ghio G., Zagolin G., Glavas D., Tomassi M., Rosati R., Elmore U., Gozzini L., Calef R., Puccetti F., Cossu A., Vignali A., Morino M., Allaix M. E., Cannata G., Lombardi E., Ammirati C. A., Piceni C., Buccianti P., Balestri R., Puccini M., Pezzati D., D'Ischia R., Asta V. F., Sargenti B., Taddei G., Bonari F., Boni G., Ferrero A., Mineccia M., Gonella F., Palisi M., Danese F., Cherubini V., Perotti S., Carvello M., Carbone F., Luberto A., Calafiore E., De Lucia F., Sacchi M., Sasia D., Giuffrida M. C., Ballauri E., Cardile M., Armentano S., Beltrami E., Preve G., Vercellone B., Mozzon M., Folliero C., Lirusso C., Vecchiato M., Ziccarelli A., Gattesco D., Moretti L., Crestale S., Banchini F., Capelli P., Romboli A., Palmieri G., Conti L., Rizzi N., Bonfili D., De Manzini N., Germani P., Osenda E., Cortinovis S., Giunta C., Fracon S., Abdallah H., Bogoni S., Portolani N., Nascimbeni R., Molfino S., Tiberio G. A. M., Garosio I., Lamperti G., Rigosa D., Ercolani G., Solaini L., Cavaliere D., Avanzolini A., D'Acapito F., Chiarella L. L., Di Pietrantonio D., Annunziata D., Piccolo R., Sorrentino M., Pansini M., Cojutti A., Graziano M., Callegari F., Balzarotti L., Dameno V. R., Cattaneo A., Santolamazza G., Altieri C., Magarini R., Pietrabissa A., Dominioni T., Pugliese L., Peri A., Botti M., Salvetti F., Boni L., Cassinotti E., Baldari L., Messina V., D'Abrosca V., Cianci P., Tumolo R., Gattulli D., Restini E., Minafra M., Sederino M. G., Bottalico B., Pilati P., Franzato B., Mattara G., De Simoni O., Barina A., Tonello M., Muratore A., Calabro M., Federico Pipitone N. S., Cuzzola B., Van Nood E. H., Passuello N., Frasson A., Mammano E., Faccio L., Vittadello F., Bressan A., Sarzo G., Tamini N., Oldani M., Cigagna L., Carissimi F., De Carlo G., Baccalini E., Nespoli L., Giordano A., Cantafio S., Grifoni L., Matani D., Livi S., Delogu D., Scognamillo F., Marrosu A., Guerrini L., Ugolini G., Ghignone F., Frascaroli G., Albertini N., Zattoni D., Taffurelli G., Montroni I., Colombo F., Danelli P., Bondurri A., Maffioli A., Bonomi A., Pezzoli I., Cammarata F., Goletti O., Molteni M., Assisi A., Quartierini G., Da Lio C., Verdi D., Mondi I., Peluso C., MacChi L., Tanzanu M., Zanzi F., Pellegrini S., Andreuccetti J., D'Alessio R., Pignata G., De Capua M., Canfora I., Ottaviani L., Lepiane P., Balla A., De Carlo A., Saraceno F., Scaramuzzo R., Guida A., Aguzzi D., Bellora P., Gentilli S., Monni M., Nikaj H., Cillara N., Cannavera A., Deserra A., Margiani C., Cabula R., Dettori M., Gramignano G., Lezoche G., Ortenzi M., Orlandoni E. S., Curzi F., Vitali F., Capomagi P., Palmieri M., Giuffrida M., Del Rio P., Bonati E., Loderer T., Cozzani F., Rossini M., Agnesi S., Capolupo G. T., Caricato M., Carannante F., Masciana G., Marrelli M., Miacci V., Lauricella S., Tonini V., Cervellera M., Pisconti S., Lozito C., Shahu J., Mongelli C., Morelli G., Sartarelli L., Sica G. S., Siragusa L., Bagaglini G., Guida A. M., Franceschilli M., Bellato V., Fiorani C., Taddei A., Risaliti M., Bartolini I., Ringressi M. N., Tirloni L., Laface L., Abate E., Casati M., Gobbi P., Opocher E., Mariani N. M., Ceretti A. P., Giovenzana M., Giuliani B., Sironi M., Grossi U., Zanus G., Santoro G. A., Brizzolari M., De Leo E., Novello S., Aquilino K., Milardi F., Olmi S., Uccelli M., Bonaldi M., Cesana G. C., Bindi M., Galleano R., Langone A., Botto M., Franceschi A., Gambino E., Ronconi M., Casiraghi S., Casole G., Ciulla S. L., Terrosu G., Calandra S., Scarpa E., Cherchi V., Martinuzzo L., Clocchiatti L., Muschitiello D., Romanzi A., Vignati B., Vannelli A., Scolaro R., Milanesi M., Rossi F., Canonico G., Anastasi A., Nelli T., Barlettai M., Fratarcangeli R., Di Martino C., Damigella A., Adinolfi E., Birindelli A., Taglietti L., Dester S. E., Fleres F., Cucinotta E., Viscosi F., Biondo S. A., Badessi G., Catarsini N., Mazzeo C., Rega D., Delrio P., Cervone C., Aversano A., De Franciscis S., Di Marzo M., Marra B., Pace U., Amato A., Batistotti P., Mina E., Serventi A., Lapolla P., Mingoli A., Sapienza P., Brachini G., Cirillo B., Fiori E., Crocetti D., Clementi I., Martines G., Picciariello A., Tomasicchio G., Dibra R., Trigiante G., Rinaldi M., Lantone G., Porcu A., Perra T., Scanu A. M., Feo C. F., Fancellu A., Cossu M. L., Ginesu G. C., Patriti A., Coletta D., Petrelli F., Greco P. A., Spadoni C., Cassiani G., Bianchini F., Arganini M., Bianchini M., Perotti B., Palmeri M., Scabini S., Deiana S., Carganico G., Pertile D., Soriero D., Fioravanti E., Sperotto B., Nardo B., Paglione D., Crocco V., Doni M., Osso M., Perri R., Sampietro G. M., Corbellini C., Lorusso L., Manzo C. A., Cigognini M., Baldi C., Palomba G., Aprea G., Capuano M., Basile R., Tutino R., Massani M., Marinelli L., Canitano N., Pilia T., Podda M., Pisanu A., Murzi V., Incani S., Frongia F., Esposito G., Luglio G., Tropeano F. P., Pagano G., Spina E., De Simone G., Cricri M., Catena F., Vallicelli C., Zanini N., Ronconi D., Favi F., Mazzucchelli C., Convertini G., Vincenti L., Andriola V., Bizzoca C., Feo C. V., Fabbri N., Fazzin M., Pesce A., Gennari S., Torchiaro M., Severi S., Frontali A., Bracchetti G., Granieri S., Cotsoglou C., Carlini M., Lisi G., Spoletini D., Mastrangeli M. R., Campanelli M., Manigrasso M., Milone M., De Palma G. D., Vertaldi S., Chini A., Maione F., Marello A., Selvaggi F., Sciaudone G., Selvaggi L., Tasselli F. M., Fuschillo G., Oddis L., Grande S., Grande M., Ascanelli S., Chimisso L., Aisoni F., Rossin E., Pepe F., Marchetti F., Picardi B., Rossi S., Del Monte S. R., Picarelli M., Muttillo I. A., Ratto C., Marra A. A., Parello A., Litta F., Campenni P., De Simone V., Pata F., Riboni C., Rausa E., Celentano V., Rottoli, M, Spinelli, A, Pellino, G, Gori, A, Calini, G, Flacco, M, Manzoli, L, Poggioli, G, Romano, A, Belvedere, A, Lanci, A, Parlanti, D, Vago, G, Pezzuto, A, Canavese, A, Dajti, G, Cardelli, S, Catalioto, C, Russo, I, Violante, T, Morezzi, D, Maurino, L, Filippone, E, Cuicchi, D, Bernante, P, Jovine, E, Lombardi, R, Masetti, M, Cipressi, C, Offi, M, Larotonda, C, Puglisi, S, Barbosa, A, Vaiana, R, Bianchi, P, Tonti, C, Codignola, C, Zorcolo, L, Restivo, A, Deidda, S, Marchetti, M, Ippolito, L, Spolverato, G, Pucciarelli, S, Marchegiani, F, Ghio, G, Zagolin, G, Glavas, D, Tomassi, M, Rosati, R, Elmore, U, Gozzini, L, Calef, R, Puccetti, F, Cossu, A, Vignali, A, Morino, M, Allaix, M, Cannata, G, Lombardi, E, Ammirati, C, Piceni, C, Buccianti, P, Balestri, R, Puccini, M, Pezzati, D, D'Ischia, R, Asta, V, Sargenti, B, Taddei, G, Bonari, F, Boni, G, Ferrero, A, Mineccia, M, Gonella, F, Palisi, M, Danese, F, Cherubini, V, Perotti, S, Carvello, M, Carbone, F, Luberto, A, Calafiore, E, De Lucia, F, Sacchi, M, Sasia, D, Giuffrida, M, Ballauri, E, Cardile, M, Armentano, S, Beltrami, E, Preve, G, Vercellone, B, Mozzon, M, Folliero, C, Lirusso, C, Vecchiato, M, Ziccarelli, A, Gattesco, D, Moretti, L, Crestale, S, Banchini, F, Capelli, P, Romboli, A, Palmieri, G, Conti, L, Rizzi, N, Bonfili, D, De Manzini, N, Germani, P, Osenda, E, Cortinovis, S, Giunta, C, Fracon, S, Abdallah, H, Bogoni, S, Portolani, N, Nascimbeni, R, Molfino, S, Tiberio, G, Garosio, I, Lamperti, G, Rigosa, D, Ercolani, G, Solaini, L, Cavaliere, D, Avanzolini, A, D'Acapito, F, Chiarella, L, Di Pietrantonio, D, Annunziata, D, Piccolo, R, Sorrentino, M, Pansini, M, Cojutti, A, Graziano, M, Callegari, F, Balzarotti, L, Dameno, V, Cattaneo, A, Santolamazza, G, Altieri, C, Magarini, R, Pietrabissa, A, Dominioni, T, Pugliese, L, Peri, A, Botti, M, Salvetti, F, Boni, L, Cassinotti, E, Baldari, L, Messina, V, D'Abrosca, V, Cianci, P, Tumolo, R, Gattulli, D, Restini, E, Minafra, M, Sederino, M, Bottalico, B, Pilati, P, Franzato, B, Mattara, G, De Simoni, O, Barina, A, Tonello, M, Muratore, A, Calabro, M, Federico Pipitone, N, Cuzzola, B, Van Nood, E, Passuello, N, Frasson, A, Mammano, E, Faccio, L, Vittadello, F, Bressan, A, Sarzo, G, Tamini, N, Oldani, M, Cigagna, L, Carissimi, F, De Carlo, G, Baccalini, E, Nespoli, L, Giordano, A, Cantafio, S, Grifoni, L, Matani, D, Livi, S, Delogu, D, Scognamillo, F, Marrosu, A, Guerrini, L, Ugolini, G, Ghignone, F, Frascaroli, G, Albertini, N, Zattoni, D, Taffurelli, G, Montroni, I, Colombo, F, Danelli, P, Bondurri, A, Maffioli, A, Bonomi, A, Pezzoli, I, Cammarata, F, Goletti, O, Molteni, M, Assisi, A, Quartierini, G, Da Lio, C, Verdi, D, Mondi, I, Peluso, C, Macchi, L, Tanzanu, M, Zanzi, F, Pellegrini, S, Andreuccetti, J, D'Alessio, R, Pignata, G, De Capua, M, Canfora, I, Ottaviani, L, Lepiane, P, Balla, A, De Carlo, A, Saraceno, F, Scaramuzzo, R, Guida, A, Aguzzi, D, Bellora, P, Gentilli, S, Monni, M, Nikaj, H, Cillara, N, Cannavera, A, Deserra, A, Margiani, C, Cabula, R, Dettori, M, Gramignano, G, Lezoche, G, Ortenzi, M, Orlandoni, E, Curzi, F, Vitali, F, Capomagi, P, Palmieri, M, Del Rio, P, Bonati, E, Loderer, T, Cozzani, F, Rossini, M, Agnesi, S, Capolupo, G, Caricato, M, Carannante, F, Masciana, G, Marrelli, M, Miacci, V, Lauricella, S, Tonini, V, Cervellera, M, Pisconti, S, Lozito, C, Shahu, J, Mongelli, C, Morelli, G, Sartarelli, L, Sica, G, Siragusa, L, Bagaglini, G, Franceschilli, M, Bellato, V, Fiorani, C, Taddei, A, Risaliti, M, Bartolini, I, Ringressi, M, Tirloni, L, Laface, L, Abate, E, Casati, M, Gobbi, P, Opocher, E, Mariani, N, Ceretti, A, Giovenzana, M, Giuliani, B, Sironi, M, Grossi, U, Zanus, G, Santoro, G, Brizzolari, M, De Leo, E, Novello, S, Aquilino, K, Milardi, F, Olmi, S, Uccelli, M, Bonaldi, M, Cesana, G, Bindi, M, Galleano, R, Langone, A, Botto, M, Franceschi, A, Gambino, E, Ronconi, M, Casiraghi, S, Casole, G, Ciulla, S, Terrosu, G, Calandra, S, Scarpa, E, Cherchi, V, Martinuzzo, L, Clocchiatti, L, Muschitiello, D, Romanzi, A, Vignati, B, Vannelli, A, Scolaro, R, Milanesi, M, Rossi, F, Canonico, G, Anastasi, A, Nelli, T, Barlettai, M, Fratarcangeli, R, Di Martino, C, Damigella, A, Adinolfi, E, Birindelli, A, Taglietti, L, Dester, S, Fleres, F, Cucinotta, E, Viscosi, F, Biondo, S, Badessi, G, Catarsini, N, Mazzeo, C, Rega, D, Delrio, P, Cervone, C, Aversano, A, De Franciscis, S, Di Marzo, M, Marra, B, Pace, U, Amato, A, Batistotti, P, Mina, E, Serventi, A, Lapolla, P, Mingoli, A, Sapienza, P, Brachini, G, Cirillo, B, Fiori, E, Crocetti, D, Clementi, I, Martines, G, Picciariello, A, Tomasicchio, G, Dibra, R, Trigiante, G, Rinaldi, M, Lantone, G, Porcu, A, Perra, T, Scanu, A, Feo, C, Fancellu, A, Cossu, M, Ginesu, G, Patriti, A, Coletta, D, Petrelli, F, Greco, P, Spadoni, C, Cassiani, G, Bianchini, F, Arganini, M, Bianchini, M, Perotti, B, Palmeri, M, Scabini, S, Deiana, S, Carganico, G, Pertile, D, Soriero, D, Fioravanti, E, Sperotto, B, Nardo, B, Paglione, D, Crocco, V, Doni, M, Osso, M, Perri, R, Sampietro, G, Corbellini, C, Lorusso, L, Manzo, C, Cigognini, M, Baldi, C, Palomba, G, Aprea, G, Capuano, M, Basile, R, Tutino, R, Massani, M, Marinelli, L, Canitano, N, Pilia, T, Podda, M, Pisanu, A, Murzi, V, Incani, S, Frongia, F, Esposito, G, Luglio, G, Tropeano, F, Pagano, G, Spina, E, De Simone, G, Cricri, M, Catena, F, Vallicelli, C, Zanini, N, Ronconi, D, Favi, F, Mazzucchelli, C, Convertini, G, Vincenti, L, Andriola, V, Bizzoca, C, Fabbri, N, Fazzin, M, Pesce, A, Gennari, S, Torchiaro, M, Severi, S, Frontali, A, Bracchetti, G, Granieri, S, Cotsoglou, C, Carlini, M, Lisi, G, Spoletini, D, Mastrangeli, M, Campanelli, M, Manigrasso, M, Milone, M, De Palma, G, Vertaldi, S, Chini, A, Maione, F, Marello, A, Selvaggi, F, Sciaudone, G, Selvaggi, L, Tasselli, F, Fuschillo, G, Oddis, L, Grande, S, Grande, M, Ascanelli, S, Chimisso, L, Aisoni, F, Rossin, E, Pepe, F, Marchetti, F, Picardi, B, Rossi, S, Del Monte, S, Picarelli, M, Muttillo, I, Ratto, C, Marra, A, Parello, A, Litta, F, Campenni, P, De Simone, V, Pata, F, Riboni, C, Rausa, E, Celentano, V, Rottoli M., Spinelli A., Pellino G., Gori A., Calini G., Flacco M. E., Manzoli L., Poggioli G., Romano A., Belvedere A., Lanci A. L., Parlanti D., Vago G., Pezzuto A. P., Canavese A., Dajti G., Cardelli S., Catalioto C., Russo I. S., Violante T., Morezzi D., Maurino L., Filippone E., Cuicchi D., Bernante P., Jovine E., Lombardi R., Masetti M., Cipressi C., Offi M. F., Larotonda C., Puglisi S. B., Barbosa A., Vaiana R., Bianchi P. M., Tonti C., Codignola C., Zorcolo L., Restivo A., Deidda S., Marchetti M. E., Ippolito L., Spolverato G., Pucciarelli S., Marchegiani F., Ghio G., Zagolin G., Glavas D., Tomassi M., Rosati R., Elmore U., Gozzini L., Calef R., Puccetti F., Cossu A., Vignali A., Morino M., Allaix M. E., Cannata G., Lombardi E., Ammirati C. A., Piceni C., Buccianti P., Balestri R., Puccini M., Pezzati D., D'Ischia R., Asta V. F., Sargenti B., Taddei G., Bonari F., Boni G., Ferrero A., Mineccia M., Gonella F., Palisi M., Danese F., Cherubini V., Perotti S., Carvello M., Carbone F., Luberto A., Calafiore E., De Lucia F., Sacchi M., Sasia D., Giuffrida M. C., Ballauri E., Cardile M., Armentano S., Beltrami E., Preve G., Vercellone B., Mozzon M., Folliero C., Lirusso C., Vecchiato M., Ziccarelli A., Gattesco D., Moretti L., Crestale S., Banchini F., Capelli P., Romboli A., Palmieri G., Conti L., Rizzi N., Bonfili D., De Manzini N., Germani P., Osenda E., Cortinovis S., Giunta C., Fracon S., Abdallah H., Bogoni S., Portolani N., Nascimbeni R., Molfino S., Tiberio G. A. M., Garosio I., Lamperti G., Rigosa D., Ercolani G., Solaini L., Cavaliere D., Avanzolini A., D'Acapito F., Chiarella L. L., Di Pietrantonio D., Annunziata D., Piccolo R., Sorrentino M., Pansini M., Cojutti A., Graziano M., Callegari F., Balzarotti L., Dameno V. R., Cattaneo A., Santolamazza G., Altieri C., Magarini R., Pietrabissa A., Dominioni T., Pugliese L., Peri A., Botti M., Salvetti F., Boni L., Cassinotti E., Baldari L., Messina V., D'Abrosca V., Cianci P., Tumolo R., Gattulli D., Restini E., Minafra M., Sederino M. G., Bottalico B., Pilati P., Franzato B., Mattara G., De Simoni O., Barina A., Tonello M., Muratore A., Calabro M., Federico Pipitone N. S., Cuzzola B., Van Nood E. H., Passuello N., Frasson A., Mammano E., Faccio L., Vittadello F., Bressan A., Sarzo G., Tamini N., Oldani M., Cigagna L., Carissimi F., De Carlo G., Baccalini E., Nespoli L., Giordano A., Cantafio S., Grifoni L., Matani D., Livi S., Delogu D., Scognamillo F., Marrosu A., Guerrini L., Ugolini G., Ghignone F., Frascaroli G., Albertini N., Zattoni D., Taffurelli G., Montroni I., Colombo F., Danelli P., Bondurri A., Maffioli A., Bonomi A., Pezzoli I., Cammarata F., Goletti O., Molteni M., Assisi A., Quartierini G., Da Lio C., Verdi D., Mondi I., Peluso C., MacChi L., Tanzanu M., Zanzi F., Pellegrini S., Andreuccetti J., D'Alessio R., Pignata G., De Capua M., Canfora I., Ottaviani L., Lepiane P., Balla A., De Carlo A., Saraceno F., Scaramuzzo R., Guida A., Aguzzi D., Bellora P., Gentilli S., Monni M., Nikaj H., Cillara N., Cannavera A., Deserra A., Margiani C., Cabula R., Dettori M., Gramignano G., Lezoche G., Ortenzi M., Orlandoni E. S., Curzi F., Vitali F., Capomagi P., Palmieri M., Giuffrida M., Del Rio P., Bonati E., Loderer T., Cozzani F., Rossini M., Agnesi S., Capolupo G. T., Caricato M., Carannante F., Masciana G., Marrelli M., Miacci V., Lauricella S., Tonini V., Cervellera M., Pisconti S., Lozito C., Shahu J., Mongelli C., Morelli G., Sartarelli L., Sica G. S., Siragusa L., Bagaglini G., Guida A. M., Franceschilli M., Bellato V., Fiorani C., Taddei A., Risaliti M., Bartolini I., Ringressi M. N., Tirloni L., Laface L., Abate E., Casati M., Gobbi P., Opocher E., Mariani N. M., Ceretti A. P., Giovenzana M., Giuliani B., Sironi M., Grossi U., Zanus G., Santoro G. A., Brizzolari M., De Leo E., Novello S., Aquilino K., Milardi F., Olmi S., Uccelli M., Bonaldi M., Cesana G. C., Bindi M., Galleano R., Langone A., Botto M., Franceschi A., Gambino E., Ronconi M., Casiraghi S., Casole G., Ciulla S. L., Terrosu G., Calandra S., Scarpa E., Cherchi V., Martinuzzo L., Clocchiatti L., Muschitiello D., Romanzi A., Vignati B., Vannelli A., Scolaro R., Milanesi M., Rossi F., Canonico G., Anastasi A., Nelli T., Barlettai M., Fratarcangeli R., Di Martino C., Damigella A., Adinolfi E., Birindelli A., Taglietti L., Dester S. E., Fleres F., Cucinotta E., Viscosi F., Biondo S. A., Badessi G., Catarsini N., Mazzeo C., Rega D., Delrio P., Cervone C., Aversano A., De Franciscis S., Di Marzo M., Marra B., Pace U., Amato A., Batistotti P., Mina E., Serventi A., Lapolla P., Mingoli A., Sapienza P., Brachini G., Cirillo B., Fiori E., Crocetti D., Clementi I., Martines G., Picciariello A., Tomasicchio G., Dibra R., Trigiante G., Rinaldi M., Lantone G., Porcu A., Perra T., Scanu A. M., Feo C. F., Fancellu A., Cossu M. L., Ginesu G. C., Patriti A., Coletta D., Petrelli F., Greco P. A., Spadoni C., Cassiani G., Bianchini F., Arganini M., Bianchini M., Perotti B., Palmeri M., Scabini S., Deiana S., Carganico G., Pertile D., Soriero D., Fioravanti E., Sperotto B., Nardo B., Paglione D., Crocco V., Doni M., Osso M., Perri R., Sampietro G. M., Corbellini C., Lorusso L., Manzo C. A., Cigognini M., Baldi C., Palomba G., Aprea G., Capuano M., Basile R., Tutino R., Massani M., Marinelli L., Canitano N., Pilia T., Podda M., Pisanu A., Murzi V., Incani S., Frongia F., Esposito G., Luglio G., Tropeano F. P., Pagano G., Spina E., De Simone G., Cricri M., Catena F., Vallicelli C., Zanini N., Ronconi D., Favi F., Mazzucchelli C., Convertini G., Vincenti L., Andriola V., Bizzoca C., Feo C. V., Fabbri N., Fazzin M., Pesce A., Gennari S., Torchiaro M., Severi S., Frontali A., Bracchetti G., Granieri S., Cotsoglou C., Carlini M., Lisi G., Spoletini D., Mastrangeli M. R., Campanelli M., Manigrasso M., Milone M., De Palma G. D., Vertaldi S., Chini A., Maione F., Marello A., Selvaggi F., Sciaudone G., Selvaggi L., Tasselli F. M., Fuschillo G., Oddis L., Grande S., Grande M., Ascanelli S., Chimisso L., Aisoni F., Rossin E., Pepe F., Marchetti F., Picardi B., Rossi S., Del Monte S. R., Picarelli M., Muttillo I. A., Ratto C., Marra A. A., Parello A., Litta F., Campenni P., De Simone V., Pata F., Riboni C., Rausa E., and Celentano V.

Abstract

Background: The association between volume, complications and pathological outcomes is still under debate regarding colorectal cancer surgery. The aim of the study was to assess the association between centre volume and severe complications, mortality, less-than-radical oncologic surgery, and indications for neoadjuvant therapy. Methods: Retrospective analysis of 16,883 colorectal cancer cases from 80 centres (2018-2021). Outcomes: 30-day mortality; Clavien-Dindo grade >2 complications; removal of ≥ 12 lymph nodes; non-radical resection; neoadjuvant therapy. Quartiles of hospital volumes were classified as LOW, MEDIUM, HIGH, and VERY HIGH. Independent predictors, both overall and for rectal cancer, were evaluated using logistic regression including age, gender, AJCC stage and cancer site. Results: LOW-volume centres reported a higher rate of severe postoperative complications (OR 1.50, 95% c.i. 1.15-1.096, P = 0.003). The rate of ≥ 12 lymph nodes removed in LOW-volume (OR 0.68, 95% c.i. 0.56-0.85, P < 0.001) and MEDIUM-volume (OR 0.72, 95% c.i. 0.62-0.83, P < 0.001) centres was lower than in VERY HIGH-volume centres. Of the 4676 rectal cancer patients, the rate of ≥ 12 lymph nodes removed was lower in LOW-volume than in VERY HIGH-volume centres (OR 0.57, 95% c.i. 0.41-0.80, P = 0.001). A lower rate of neoadjuvant chemoradiation was associated with HIGH (OR 0.66, 95% c.i. 0.56-0.77, P < 0.001), MEDIUM (OR 0.75, 95% c.i. 0.60-0.92, P = 0.006), and LOW (OR 0.70, 95% c.i. 0.52-0.94, P = 0.019) volume centres (vs. VERY HIGH). Conclusion: Colorectal cancer surgery in low-volume centres is at higher risk of suboptimal management, poor postoperative outcomes, and less-than-adequate oncologic resections. Centralisation of rectal cancer cases should be taken into consideration to optimise the outcomes.

Published
2024

5. Peptide-Based Hydrogels and Nanogels for Delivery of Doxorubicin

Author

Gallo E, Diaferia C, Rosa E, Smaldone G, Morelli G, and Accardo A

Subjects
hydrogels, nanogels, drug delivery, peptide materials, doxorubicin, in vitro assays., Medicine (General), R5-920
Abstract

Enrico Gallo,1 Carlo Diaferia,2 Elisabetta Rosa,2 Giovanni Smaldone,1 Giancarlo Morelli,2 Antonella Accardo2 1IRCCS SDN, Naples, 80143, Italy; 2Department of Pharmacy and Research Centre on Bioactive Peptides (CIRPeB), University of Naples “Federico II”, Naples, 80134, ItalyCorrespondence: Antonella AccardoDepartment of Pharmacy and Research Centre on Bioactive Peptides (CIRPeB), University of Naples “Federico II”, Via Mezzocannone 16, Naples, 80134, ItalyTel +39 0812532045Fax +39 0812536642Email antonella.accardo@unina.itIntroduction: The clinical use of the antitumoral drug doxorubicin (Dox) is reduced by its dose-limiting toxicity, related to cardiotoxic side effects and myelosuppression. In order to overcome these drawbacks, here we describe the synthesis, the structural characterization and the in vitro cytotoxicity assays of hydrogels (HGs) and nanogels (NGs) based on short peptide sequences loaded with Dox or with its liposomal formulation, Doxil.Methods: Fmoc-FF alone or in combination with (FY)3 or PEG8-(FY)3 peptides, at two different ratios (1/1 and 2/1 v/v), were used for HGs and NGs formulations. HGs were prepared according to the “solvent-switch” method, whereas NGs were obtained through HG submicronition by the top-down methodology in presence of TWEEN® 60 and SPAN® 60 as stabilizing agents. HGs gelation kinetics were assessed by Circular Dichroism (CD). Stability and size of NGs were studied using Dynamic Light Scattering (DLS) measurements. Cell viability of empty and filled Dox HGs and NGs was evaluated on MDA-MB-231 breast cancer cells. Moreover, cell internalization of the drug was evaluated using immunofluorescence assays.Results: Dox filled hydrogels exhibit a high drug loading content (DLC=0.440), without syneresis after 10 days. Gelation kinetics (20– 40 min) and the drug release (16– 28%) over time of HGs were found dependent on relative peptide composition. Dox filled NGs exhibit a DLC of 0.137 and a low drug release (20– 40%) after 72 h. Empty HGs and NGs show a high cell viability (> 95%), whereas Dox loaded ones significantly reduce cell viability after 24 h (49– 57%) and 72 h (7– 25%) of incubation, respectively. Immunofluorescence assays evidenced a different cell localization for Dox delivered through HGs and NGs with respect to the free drug.Discussion: A modulation of the Dox release can be obtained by changing the ratios of the peptide components. The different cellular localization of the drug loaded into HGs and NGs suggests an alternative internalization mechanism. The high DLC, the low drug release and preliminary in vitro results suggest a potential employment of peptide-based HGs and NGs as drug delivery tools.Keywords: hydrogels, nanogels, drug delivery, peptide materials, doxorubicin, in vitro assays

Published
2021

8. Transformative or market-driven? The Impact of Social and Solidarity Economy in the European Mediterranean City: An exploration of the aporias of value in the context of Bologna.

Author

Morelli, G, D'OVIDIO, MARIANNA, MORELLI, GABRIELE, Morelli, G, D'OVIDIO, MARIANNA, and MORELLI, GABRIELE

Abstract

L’Economia Sociale e Solidale (ESS) sta guadagnando slancio. Questo tentativo di mainstreaming (che deve essere esaminato attentamente in termini di conseguenze pratiche e politiche) è intrinsecamente carico di rischi e opportunità (Utting, 2016). Una prospettiva di economia comunitaria può aiutare in questo esame ponendo in primo piano nella discussione le questioni etiche sulla rinegoziazione delle nostre interdipendenze con esseri umani e non umani. La tesi esamina l’Economia Sociale e Solidale come una pratica potenzialmente trasformativa per una società post-capitalista, utilizzando l’approccio delle economie diverse e comunitarie. La ricerca si concentra sull’indagine degli aspetti pratici delle iniziative dell’ESS che portano a effetti trasformativi, creando in particolare un cambiamento sociale positivo nel loro contesto operativo. Applicando il riconoscimento di Flyvbjerg (2006: 223) secondo cui "nello studio delle questioni umane, sembra esistere solo una conoscenza dipendente dal contesto", questa elaborazione teorica viene utilizzata per analizzare il contesto urbano di Bologna nell'Europa meridionale. La ricerca si concentra su quattro casi di studio di organizzazioni pionieristiche dell’ESS che affrontano i bisogni sociali con obiettivi trasformativi, rilevanti in termini di innovazione sociale., The Social and Solidarity Economy (SSE) is gaining momentum. This tentative mainstreaming (which needs to be scrutinized in terms of its practical and political consequences) is inherently fraught with risks and opportunities (Utting, 2016). A community economies perspective can aid in this examination by placing ethical questions about renegotiating our interdependencies with humans and non-humans at the forefront of the discussion. The dissertation examines the Social and Solidarity Economy as a potentially transformative practice for a post-capitalist society, using the diverse and community economies approach. The research focuses on investigating the practical aspects of SSE initiatives that lead to transformative effects, specifically creating positive social change in their operating context. Applying Flyvbjerg's (2006: 223) recognition that 'in the study of human affairs, there appears to exist only context-dependent knowledge', this theoretical elaboration is used to analyze the urban context of Bologna in Southern Europe. The research focuses on four case studies of pioneering SSE organizations that address social needs with transformative goals, which is relevant in terms of social innovation.

Published
2024

12. A prospective validation of the Bova score in normotensive patients with acute pulmonary embolism

Author

Nazerian, P., Viviani, G., Crocco, F., De Morelli, G., Barrios, D., Quezada, A., Morello, F., Dentali, F., Dall' Arche, A., Brescianini, S., Sardo, L., Stea, F., Bucherini, E., Vastola, M., Barbar, S., Roncon, L., Giatti, S., Enea, I., Puato, M., Spinazzè, A., Poggioni, C., Bova, Carlo, Vanni, Simone, Prandoni, Paolo, Morello, Fulvio, Dentali, Francesco, Bernardi, Enrico, Mumoli, Nicola, Bucherini, Eugenio, Barbar, Sofia, Picariello, Claudio, Enea, Iolanda, Pesavento, Raffaele, Bottino, Fabrizio, and Jiménez, David

Published
2018
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14. A comment from SIGIS, SIE and SIAMS: “Puberty blockers in transgender adolescents—a matter of growing evidence and not of ideology”

Author

Ristori, J., primary, Motta, G., additional, Meriggiola, M. C., additional, Bettocchi, C., additional, Crespi, C., additional, Falcone, M., additional, Lombardo, F., additional, Maggi, M., additional, Morelli, G., additional, Colao, A. M., additional, Isidori, A. M., additional, and Fisher, A. D., additional

Published
2023
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15. IDegLira for the Real-World Treatment of Type 2 Diabetes in Italy: Protocol and Interim Results from the REX Observational Study

Author

Fadini, G, Buzzetti, R, Fittipaldi, M, D'Incau, F, Da Porto, A, Girelli, A, Simoni, L, Lastoria, G, Consoli, A, Iazzetta, N, Di Giovanni, G, Carbonara, O, Aragiusto, C, Carleo, D, Da Rosa, N, Martedi, E, Landolfi, L, Marracino, M, Tortora, A, De Morelli, G, Casarsa, V, Maddaloni, E, Siena, A, Pitocco, D, Tartaglione, L, Rizzi, A, Leonetti, F, Fasolo, M, Morsello, G, Bulzomi, R, Ruga, G, Bianconi, A, Torre, E, Rebora, A, Cecoli, F, Monti, E, Bonfadini, S, Dotti, S, Madaschi, S, Trevisan, R, Albizzi, M, Bellante, R, Corsi, A, Scaranna, C, De Cata, P, Liboa, F, Ghilotti, S, Tortato, E, Lanari, L, Turchi, F, Gabellieri, E, Lamacchia, O, Colucci, C, Mileti, G, Coluzzi, S, Carrieri, F, Rossetti, P, Anzaldi, M, Di Benedetto, A, Ruggeri, D, Scatena, A, Ranchelli, A, Ragusa, I, Gregori, G, Crisci, I, Mori, M, Baccetti, F, Anichini, R, Salutini, E, Vinci, C, Colletti, I, Zanon, M, Altomari, A, Bonora, B, Fadini G. P., Buzzetti R., Fittipaldi M. R., D'Incau F., Da Porto A., Girelli A., Simoni L., Lastoria G., Consoli A., Iazzetta N., Di Giovanni G., Carbonara O., Aragiusto C., Carleo D., Da Rosa N., Martedi E., Landolfi L., Marracino M., Tortora A., De Morelli G., Casarsa V., Maddaloni E., Siena A., Pitocco D., Tartaglione L., Rizzi A., Leonetti F., Fasolo M., Morsello G., Bulzomi R., Ruga G., Bianconi A., Torre E., Rebora A., Cecoli F., Monti E., Bonfadini S., Dotti S., Madaschi S., Trevisan R., Albizzi M., Bellante R., Corsi A., Scaranna C., De Cata P., Liboa F., Ghilotti S., Tortato E., Lanari L., Turchi F., Gabellieri E., Lamacchia O., Colucci C., Mileti G., Coluzzi S., Carrieri F., Rossetti P., Anzaldi M., Di Benedetto A., Ruggeri D., Scatena A., Ranchelli A., Ragusa I., Gregori G., Crisci I., Mori M., Baccetti F., Anichini R., Salutini E., Vinci C., Colletti I., Zanon M. S., Altomari A., Bonora B. M., Fadini, G, Buzzetti, R, Fittipaldi, M, D'Incau, F, Da Porto, A, Girelli, A, Simoni, L, Lastoria, G, Consoli, A, Iazzetta, N, Di Giovanni, G, Carbonara, O, Aragiusto, C, Carleo, D, Da Rosa, N, Martedi, E, Landolfi, L, Marracino, M, Tortora, A, De Morelli, G, Casarsa, V, Maddaloni, E, Siena, A, Pitocco, D, Tartaglione, L, Rizzi, A, Leonetti, F, Fasolo, M, Morsello, G, Bulzomi, R, Ruga, G, Bianconi, A, Torre, E, Rebora, A, Cecoli, F, Monti, E, Bonfadini, S, Dotti, S, Madaschi, S, Trevisan, R, Albizzi, M, Bellante, R, Corsi, A, Scaranna, C, De Cata, P, Liboa, F, Ghilotti, S, Tortato, E, Lanari, L, Turchi, F, Gabellieri, E, Lamacchia, O, Colucci, C, Mileti, G, Coluzzi, S, Carrieri, F, Rossetti, P, Anzaldi, M, Di Benedetto, A, Ruggeri, D, Scatena, A, Ranchelli, A, Ragusa, I, Gregori, G, Crisci, I, Mori, M, Baccetti, F, Anichini, R, Salutini, E, Vinci, C, Colletti, I, Zanon, M, Altomari, A, Bonora, B, Fadini G. P., Buzzetti R., Fittipaldi M. R., D'Incau F., Da Porto A., Girelli A., Simoni L., Lastoria G., Consoli A., Iazzetta N., Di Giovanni G., Carbonara O., Aragiusto C., Carleo D., Da Rosa N., Martedi E., Landolfi L., Marracino M., Tortora A., De Morelli G., Casarsa V., Maddaloni E., Siena A., Pitocco D., Tartaglione L., Rizzi A., Leonetti F., Fasolo M., Morsello G., Bulzomi R., Ruga G., Bianconi A., Torre E., Rebora A., Cecoli F., Monti E., Bonfadini S., Dotti S., Madaschi S., Trevisan R., Albizzi M., Bellante R., Corsi A., Scaranna C., De Cata P., Liboa F., Ghilotti S., Tortato E., Lanari L., Turchi F., Gabellieri E., Lamacchia O., Colucci C., Mileti G., Coluzzi S., Carrieri F., Rossetti P., Anzaldi M., Di Benedetto A., Ruggeri D., Scatena A., Ranchelli A., Ragusa I., Gregori G., Crisci I., Mori M., Baccetti F., Anichini R., Salutini E., Vinci C., Colletti I., Zanon M. S., Altomari A., and Bonora B. M.

Abstract

Introduction: IDegLira was shown to maintain glycemic control while reducing risk of hypoglycemia and body weight gain. The REX study was designed to generate real-world evidence on the use of IDegLira in Italian clinical practice in two different subgroups of patients, those switching to IDegLira from a basal insulin-supported oral therapy (BOT group) and those from a basal plus bolus insulin regimen (BB group). Methods: Adult patients with T2D diagnosed for at least 12 months and having started IDegLira 2–3 months prior to enrolment, coming from a BOT or BB regimen, were enrolled in this multicenter observational prospective cohort study conducted in 28 Italian centers. This paper presents the methodological framework of the REX study and provides the interim analysis results describing the patients’ baseline characteristics and the clinical reasons for IDegLira treatment initiation. Results: Of the 360 patients enrolled in the REX study, 331 were considered eligible for this interim analysis, 76.4% in the BOT and 23.6% in the BB group. Mean (SD) HbA1c was 8.5% (1.4) in the BOT and 8.2% (1.7) in the BB group. The most common T2D complications were diabetic macroangiopathy and diabetic nephropathy in both groups. The median (interquartile range) insulin daily dose before IDegLira was 15.0 (10.0–20.0) units in the BOT group and 42 (30.0–52.0) in the BB group. Oral antidiabetics were taken by 98% and 51.3% of patients, respectively. The main reason for switching to IDegLira was the inadequate glycemic control in the BOT group (86% of patients), and the intent to simplify the treatment in the BB group (66.7%). Conclusions: IdegLira is initiated after BOT in inadequately controlled patients to improve glycemic control, whereas in BB patients it is used to simplify the therapeutic regimen. Final results of the REX study will shed light on patients’ outcomes after IdegLira treatment under routine clinical care.

Published
2022

16. Effectiveness of Simeprevir Plus Sofosbuvir, With or Without Ribavirin, in Real-World Patients With HCV Genotype 1 Infection

Author

Afdhal, N., Alam, I., Ben-Ari, Z., Bredfeldt, J., Brown, R.S., Chung, R.T., Darling, J., Harlan, W., Di Bisceglie, A.M., Dickson, R.C., Elbeshbeshy, H.A., Everson, G., Feld, J., Fenkel, J.M., Fried, M.W., Galati, J., Gordon, S.C., Hassan, M., Hawkins, T.N., Hinestrosa, F., Jacobson, I.M., Kerr, C.A., Kuo, A., Kwo, P.Y., Levitsky, J., Lim, J., Lok, A.S., Mailliard, M., Manns, M.P., Morelli, G., Muir, A.J., Nelson, D., O’Leary, J.G., Pearlman, B.L., Pockros, P., Ramani, A., Reau, N., Reddy, K.R., Schiff, E.R., Sherman, K.E., Shiffman, M.L., Smith, C., Spivey, J.R., Sterling, R.K., Sulkowski, M.S., Szabo, G., Terrault, N.A., Trautwein, C., Vargas, H.E., Watts, K., Williams, A., Zeuzem, S., Sulkowski, Mark S., Vargas, Hugo E., Di Bisceglie, Adrian M., Kuo, Alexander, Reddy, K. Rajender, Lim, Joseph K., Morelli, Giuseppe, Darling, Jama M., Feld, Jordan J., Brown, Robert S., Frazier, Lynn M., Stewart, Thomas G., Fried, Michael W., Nelson, David R., and Jacobson, Ira M.

Published
2016
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18. Liposomes derivatized with multimeric copies of KCCYSL peptide as targeting agents for HER-2-overexpressing tumor cells

Author

Ringhieri P, Mannucci S, Conti G, Nicolato E, Fracasso G, Marzola P, Morelli G, and Accardo A

Subjects
anti-HER2 liposomes, target peptide, KCCYSL peptide, breast cancer, click chemistry, branched peptides, Medicine (General), R5-920
Abstract

Paola Ringhieri,1 Silvia Mannucci,2 Giamaica Conti,2 Elena Nicolato,2 Giulio Fracasso,3 Pasquina Marzola,4 Giancarlo Morelli,1 Antonella Accardo1 1Department of Pharmacy and Interuniversity Research Centre on Bioactive Peptides (CIRPeB), University of Naples “Federico II”, Napoli, 2Department of Neurological Biomedical and Movement Sciences, 3Section of Immunology, Department of Medicine, 4Department of Informatics, University of Verona, Verona, Italy Abstract: Mixed liposomes, obtained by coaggregation of 1,2-dioleoyl-sn-glycero-3-phosphocholine and of the synthetic monomer containing a gadolinium complex ([C18]2DTPA[Gd]) have been prepared. Liposomes externally decorated with KCCYSL (P6.1 peptide) sequence in its monomeric, dimeric, and tetrameric forms are studied as target-selective delivery systems toward cancer cells overexpressing human epidermal growth factor receptor-2 (HER-2) receptors. Derivatization of liposomal surface with targeting peptides is achieved using the postmodification method: the alkyne-peptide derivative Pra-KCCYSL reacts, through click chemistry procedures, with a synthetic surfactant modified with 1, 2, or 4 azido moieties previously inserted in liposome formulation. Preliminary in vitro data on MDA-MB-231 and BT-474 cells indicated that liposomes functionalized with P6.1 peptide in its tetrameric form had better binding to and uptake into BT-474 cells compared to liposomes decorated with monomeric or dimeric versions of the P6.1 peptide. BT-474 cells treated with liposomes functionalized with the tetrameric form of P6.1 showed high degree of liposome uptake, which was comparable with the uptake of anti-HER-2 antibodies such as Herceptin. Moreover, magnetic MRI experiments have demonstrated the potential of liposomes to act as MRI contrast agents. Keywords: anti-HER2 liposomes, target peptide, KCCYSL peptide, breast cancer, click chemistry, branched peptides

Published
2017

19. The psychosocial functioning in adolescents with severe obesity evaluated throughout the strengths and difficulties questionnaire (SDQ): a preliminary report

Author

Guerrini Usubini, Anna, Bottacchi, M., Morelli, G., Caroli, D., Marazzi, N., Castelnuovo, Gianluca, Sartorio, Alessandro, Guerrini Usubini A., Castelnuovo G. (ORCID:0000-0003-2633-9822), Sartorio A., Guerrini Usubini, Anna, Bottacchi, M., Morelli, G., Caroli, D., Marazzi, N., Castelnuovo, Gianluca, Sartorio, Alessandro, Guerrini Usubini A., Castelnuovo G. (ORCID:0000-0003-2633-9822), and Sartorio A.

Abstract

Introduction: Childhood obesity is associated with poor psychological adjustment. Severely impacts the psychological adjustment of young patients. To assess the psychological functioning of children and adolescents, several questionnaires have been proposed so far. Although the Strengths and Difficulties Questionnaire (SDQ) is one of the most well-used tools, its application in obesity research is scarce. The study is aimed at assessing the psychological profile of a sample of Italian children and adolescents seeking an in-hospital multidisciplinary body weight reduction program for obesity, via SDQ. Methods: One hundred and fourteen consecutive Italian children and adolescents with obesity (43 males/71 females, age range: 11–17 years, mean age ± SD: 15.1 ± 1.66, body mass index-BMI ± SD: 37.4 ± 6.13 kg/m2), were recruited at the Division of Auxology, Istituto Auxologico Italiano IRCCS, Piancavallo (VB). Results: Obese Females reported worse conditions of emotional symptoms (t = 5.48; p < 0.001) and peer problems (t = 2.34; p = 0.021), as well as higher which were associated with greater scores of pro-social behaviors than obese males (t = 3.07; p = 0.003). The total difficulties score (t = 4.00; p < 0.001) and the total impact score (t = 4.53; p < 0.001) were significantly higher in females than males. No statistically significant differences in SDQ variables were found in relation to the degree of obesity (BMI SDS: 2–2.99; BMI SDS: > 3). Discussion: These findings can contribute to understand the psychological condition of adolescents with obesity in a better way and also to develop effective interventions for the treatment of pediatric obesity which not only take into account the medical and physical aspects but also the emotional and social difficulties expressed by adolescents with obesity.

Published
2023

20. Upgrade of the mechanically pumped CO2 two-phase cooling system for the alpha magnetic spectrometer on the international space station

Author

Ambrosi, G., primary, Bertucci, B., additional, Bollweg, K., additional, Burger, J., additional, Cai, X., additional, Capell, M., additional, Chung, C.H., additional, Chuang, Y.R., additional, Clark, C., additional, Ding, T., additional, FanChiang, Y.J., additional, Gargiulo, C., additional, Gaggiotti, M., additional, Guo, L., additional, He, Z.H., additional, Heil, M., additional, Heilig, J., additional, Karpinski, W., additional, Koutsenko, V., additional, Kulemzin, A., additional, Lübelsmeyer, K., additional, Martin, T., additional, Mo, D.C., additional, Morelli, G., additional, Miao, J.Y., additional, Mott, P., additional, Mussolin, L., additional, Schael, S., additional, Schutlz von Dratzig, A., additional, Schwering, G., additional, Scolieri, G., additional, Siedenburg, T., additional, Solano, C., additional, Urban, T., additional, Verlaat, B., additional, Wang, S.H., additional, Wlochal, M., additional, Yan, J.j., additional, Yang, Y., additional, Yu, Y.M., additional, Zeng, R.C., additional, and Zhang, Z., additional

Published
2023
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21. Gli Smart Meters, una misura di sostenibilità verde

Author

Gurrieri, A. R., Morelli, G., Mele, M., and Magazzino, C.

Subjects
Europe, Smart meters, energy resources, Smart meters, energy resources, digital and social innovation, Europe, digital and social innovation
Published
2023

25. IDegLira for the Real-World Treatment of Type 2 Diabetes in Italy: Protocol and Interim Results from the REX Observational Study

Author

Fadini, G. P., Buzzetti, R., Fittipaldi, M. R., D'Incau, F., Da Porto, A., Girelli, A., Simoni, L., Lastoria, G., Consoli, A., Iazzetta, N., Di Giovanni, G., Carbonara, O., Aragiusto, C., Carleo, D., Da Rosa, N., Martedi, E., Landolfi, L., Marracino, M., Tortora, Annalisa, De Morelli, G., Casarsa, V., Maddaloni, E., Siena, Annunziata, Pitocco, Dario, Tartaglione, Linda, Rizzi, A., Leonetti, F., Fasolo, M., Morsello, G., Bulzomi, R., Ruga, G., Bianconi, A., Torre, Enza, Rebora, A., Cecoli, F., Monti, E., Bonfadini, S., Dotti, S., Madaschi, S., Trevisan, R., Albizzi, M., Bellante, R., Corsi, Alessandro, Scaranna, C., De Cata, P., Liboa, F., Ghilotti, S., Tortato, E., Lanari, L., Turchi, F., Gabellieri, E., Lamacchia, O., Colucci, C., Mileti, G., Coluzzi, Simone, Carrieri, F., Rossetti, P., Anzaldi, Mauro, Di Benedetto, A., Ruggeri, D., Scatena, A., Ranchelli, A., Ragusa, I., Gregori, G., Crisci, I., Mori, Marco Ernesto, Baccetti, F., Anichini, R., Salutini, E., Vinci, C., Colletti, I., Zanon, M. S., Altomari, A., Bonora, B. M., Fadini, G, Buzzetti, R, Fittipaldi, M, D'Incau, F, Da Porto, A, Girelli, A, Simoni, L, Lastoria, G, Consoli, A, Iazzetta, N, Di Giovanni, G, Carbonara, O, Aragiusto, C, Carleo, D, Da Rosa, N, Martedi, E, Landolfi, L, Marracino, M, Tortora, A, De Morelli, G, Casarsa, V, Maddaloni, E, Siena, A, Pitocco, D, Tartaglione, L, Rizzi, A, Leonetti, F, Fasolo, M, Morsello, G, Bulzomi, R, Ruga, G, Bianconi, A, Torre, E, Rebora, A, Cecoli, F, Monti, E, Bonfadini, S, Dotti, S, Madaschi, S, Trevisan, R, Albizzi, M, Bellante, R, Corsi, A, Scaranna, C, De Cata, P, Liboa, F, Ghilotti, S, Tortato, E, Lanari, L, Turchi, F, Gabellieri, E, Lamacchia, O, Colucci, C, Mileti, G, Coluzzi, S, Carrieri, F, Rossetti, P, Anzaldi, M, Di Benedetto, A, Ruggeri, D, Scatena, A, Ranchelli, A, Ragusa, I, Gregori, G, Crisci, I, Mori, M, Baccetti, F, Anichini, R, Salutini, E, Vinci, C, Colletti, I, Zanon, M, Altomari, A, and Bonora, B

Subjects
Type&nbsp, Real-world evidence, Endocrinology, Diabetes and Metabolism, IDegLira, Basal bolus therapy (BB), Basal insulin analogue, Basal oral therapy (BOT), Glycated hemoglobin (HbA1c), Oral antidiabetic drugs (OADs), Rapid insulin analogue, Type 2 diabetes, Settore MED/13 - ENDOCRINOLOGIA, Type 2 diabete, Type 2 diabetes, Internal Medicine, 2 diabetes
Abstract

Introduction: IDegLira was shown to maintain glycemic control while reducing risk of hypoglycemia and body weight gain. The REX study was designed to generate real-world evidence on the use of IDegLira in Italian clinical practice in two different subgroups of patients, those switching to IDegLira from a basal insulin-supported oral therapy (BOT group) and those from a basal plus bolus insulin regimen (BB group). Methods: Adult patients with T2D diagnosed for at least 12 months and having started IDegLira 2–3 months prior to enrolment, coming from a BOT or BB regimen, were enrolled in this multicenter observational prospective cohort study conducted in 28 Italian centers. This paper presents the methodological framework of the REX study and provides the interim analysis results describing the patients’ baseline characteristics and the clinical reasons for IDegLira treatment initiation. Results: Of the 360 patients enrolled in the REX study, 331 were considered eligible for this interim analysis, 76.4% in the BOT and 23.6% in the BB group. Mean (SD) HbA1c was 8.5% (1.4) in the BOT and 8.2% (1.7) in the BB group. The most common T2D complications were diabetic macroangiopathy and diabetic nephropathy in both groups. The median (interquartile range) insulin daily dose before IDegLira was 15.0 (10.0–20.0) units in the BOT group and 42 (30.0–52.0) in the BB group. Oral antidiabetics were taken by 98% and 51.3% of patients, respectively. The main reason for switching to IDegLira was the inadequate glycemic control in the BOT group (86% of patients), and the intent to simplify the treatment in the BB group (66.7%). Conclusions: IdegLira is initiated after BOT in inadequately controlled patients to improve glycemic control, whereas in BB patients it is used to simplify the therapeutic regimen. Final results of the REX study will shed light on patients’ outcomes after IdegLira treatment under routine clinical care.

Published
2022

26. Immune Algorithms with Aging Operators for the String Folding Problem and the Protein Folding Problem

Author

Cutello, V., Morelli, G., Nicosia, G., Pavone, M., Hutchison, David, editor, Kanade, Takeo, editor, Kittler, Josef, editor, Kleinberg, Jon M., editor, Mattern, Friedemann, editor, Mitchell, John C., editor, Naor, Moni, editor, Nierstrasz, Oscar, editor, Pandu Rangan, C., editor, Steffen, Bernhard, editor, Sudan, Madhu, editor, Terzopoulos, Demetri, editor, Tygar, Dough, editor, Vardi, Moshe Y., editor, Weikum, Gerhard, editor, Raidl, Günther R., editor, and Gottlieb, Jens, editor

Published
2005
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27. Self-assembled or mixed peptide amphiphile micelles from Herpes simplex virus glycoproteins as potential immunomodulatory treatment

Author

Accardo A, Vitiello M, Tesauro D, Galdiero M, Finamore E, Martora F, Mansi R, Ringhieri P, and Morelli G

Subjects
Medicine (General), R5-920
Abstract

Antonella Accardo,1 Mariateresa Vitiello,2,3 Diego Tesauro,1 Marilena Galdiero,2 Emiliana Finamore,2 Francesca Martora,2 Rosalba Mansi,1 Paola Ringhieri,1 Giancarlo Morelli11Department of Pharmacy, Interuniversitary Centre for Research on Bioactive peptides, CIRPeB, University of Naples "Federico II", Institute of Biostructures and Bioimaging IBB-CNR, Naples, Italy; 2Department of Experimental Medicine, Section of Microbiology and Clinical Microbiology, Second University of Naples, Naples, Italy; 3Department of Clinical Pathology and Transfusion Medicine, University Hospital “Ruggi d'Aragona”, Salerno, ItalyAbstract: The use of micelle aggregates formed from peptide amphiphiles (PAs) as potential synthetic self-adjuvant vaccines to treat Herpes simplex virus (HSV) infection are reported here. The PAs were based on epitopes gB409-505 and gD301-309, selected from HSV envelope glycoprotein B (gB) and glycoprotein D (gD), that had their N-terminus modified with hydrophobic moieties containing two C18 hydrocarbon chains. Pure and mixed micelles of gB and/or gD peptide epitopes were easily prepared after starting with the synthesis of corresponding PAs by solid phase methods. Structural characterization of the aggregates confirmed that they were sufficiently stable and compatible with in vivo use: critical micelle concentration values around 4.0 · 10-7 mol · Kg-1; hydrodynamic radii (RH) between 50–80 nm, and a zeta potential (ζ) around – 40 mV were found for all aggregates. The in vitro results indicate that both peptide epitopes and micelles, at 10 µM, triggered U937 and RAW 264.7 cells to release appreciable levels of cytokines. In particular, interleukin (IL)-23-, IL-6-, IL-8- or macrophage inflammatory protein (MIP)-2-, and tumor necrosis factor (TNF)-α-release increased considerably when cells were treated with the gB-micelles or gD-micelles compared with the production of the same cytokines when the stimulus was the single gB or gD peptide.Keywords: epitopes, self-adjuvant vaccine, HSV

Published
2014

28. Receptor binding peptides for target-selective delivery of nanoparticles encapsulated drugs

Author

Accardo A, Aloj L, Aurilio M, Morelli G, and Tesauro D

Subjects
Medicine (General), R5-920
Abstract

Antonella Accardo,1 Luigi Aloj,2 Michela Aurilio,2 Giancarlo Morelli,1 Diego Tesauro11Centro interuniversitario di Ricerca sui Peptidi Bioattivi (CIRPeB), Department of Pharmacy and Istituto di Biostrutture e Bioimmagini - Consiglio Nazionale delle Ricerche (IBB CNR), University of Naples “Federico II”, 2Department of Nuclear Medicine, Istituto Nazionale per lo Studio e la Cura dei Tumori, Fondazione “G. Pascale”, Napoli, ItalyAbstract: Active targeting by means of drug encapsulated nanoparticles decorated with targeting bioactive moieties represents the next frontier in drug delivery; it reduces drug side effects and increases the therapeutic index. Peptides, based on their chemical and biological properties, could have a prevalent role to direct drug encapsulated nanoparticles, such as liposomes, micelles, or hard nanoparticles, toward the tumor tissues. A considerable number of molecular targets for peptides are either exclusively expressed or overexpressed on both cancer vasculature and cancer cells. They can be classified into three wide categories: integrins; growth factor receptors (GFRs); and G-protein coupled receptors (GPCRs). Therapeutic agents based on nanovectors decorated with peptides targeting membrane receptors belonging to the GPCR family overexpressed by cancer cells are reviewed in this article. The most studied targeting membrane receptors are considered: somatostatin receptors; cholecystokinin receptors; receptors associated with the Bombesin like peptides family; luteinizing hormone-releasing hormone receptors; and neurotensin receptors. Nanovectors of different sizes and shapes (micelles, liposomes, or hard nanoparticles) loaded with doxorubicin or other cytotoxic drugs and externally functionalized with natural or synthetic peptides are able to target the overexpressed receptors and are described based on their formulation and in vitro and in vivo behaviors.Keywords: receptors binding peptides, drug delivery, nanoparticles, supramolecular aggregates, active targeting

Published
2014

29. Rare variants in Toll-like receptor 7 results in functional impairment and downregulation of cytokine-mediated signaling in COVID-19 patients

Author

Mantovani, S., Daga, S., Fallerini, C., Baldassarri, M., Benetti, E., Picchiotti, N., Fava, F., Galli, A., Zibellini, S., Bruttini, M., Palmieri, M., Croci, S., Amitrano, S., Alaverdian, D., Capitani, K., Furini, S., Mari, F., Meloni, I., Montagnani, F., Tumbarello, M., Rancan, I., Fabbiani, M., Rossetti, B., Bergantini, L., D'Alessandro, M., Cameli, P., Bennett, D., Anedda, F., Marcantonio, S., Scolletta, S., Franchi, F., Mazzei, M. A., Guerrini, S., Conticini, E., Cantarini, L., Frediani, B., Tacconi, D., Raffaelli, C. S., Feri, M., Donati, A., Scala, R., Guidelli, L., Spargi, G., Corridi, M., Nencioni, C., Croci, L., Caldarelli, G. P., Romani, D., Piacentini, P., Bandini, M., Desanctis, E., Cappelli, S., Canaccini, A., Verzuri, A., Anemoli, V., Pisani, M., Ognibene, A., Pancrazzi, A., Lorubbio, M., Vaghi, M., D'Arminio Monforte, A., Miraglia, F. G., Bruno, R., Vecchia, M., Girardis, M., Venturelli, S., Busani, S., Cossarizza, A., Antinori, A., Vergori, A., Emiliozzi, A., Rusconi, S., Siano, M., Gabrieli, A., Riva, A., Francisci, D., Schiaroli, E., Paciosi, F., Tommasi, A., Scotton, P. G., Andretta, F., Panese, S., Baratti, S., Scaggiante, R., Gatti, F., Parisi, S. G., Castelli, F., Quiros-Roldan, E., Degli Antoni, M., Antoni, M. D., Zanella, I., Della Monica, M., Piscopo, C., Capasso, M., Russo, R., Andolfo, I., Iolascon, A., Fiorentino, G., Carella, M., Castori, M., Aucella, F., Raggi, P., Perna, R., Bassetti, M., Di Biagio, A., Sanguinetti, M., Masucci, L., Guarnaccia, A., Valente, S., De Vivo, O., Doddato, G., Lista, M., Beligni, G., Valentino, F., Zguro, K., Tita, R., Giliberti, A., Mencarelli, M. A., Rizzo, C. L., Pinto, A. M., Ariani, F., Di Sarno, L., Bargagli, E., Mandala, M., Giorli, A., Salerni, L., Zucchi, P., Parravicini, P., Menatti, E., Trotta, T., Giannattasio, F., Coiro, G., Lena, F., Lacerenza, G., Mussini, C., Martinelli, E., Tavecchia, L., Belli, M. A., Crotti, L., Parati, G., Sanarico, M., Raimondi, F., Biscarini, F., Stella, A., Bachetti, T., La Rovere, M. T., Ludovisi, S., Bussotti, M., Dei, S., Ravaglia, S., Artuso, R., Andreucci, E., Gori, G., Pagliazzi, A., Fiorentini, E., Perrella, A., Bianchi, F., Bergomi, P., Catena, E., Colombo, R., Luchi, S., Morelli, G., Petrocelli, P., Iacopini, S., Modica, S., Baroni, S., Segala, F. V., Falcone, M., Tiseo, G., Barbieri, C., Matucci, T., Grassi, D., Ferri, C., Marinangeli, F., Brancati, F., Vincenti, A., Borgo, V., Lombardi, S., Lenzi, M., Di Pietro, M. A., Vichi, F., Romanin, B., Attala, L., Costa, C., Gabbuti, A., Mene, R., Colaneri, M., Casprini, P., Merla, G., Squeo, G. M., Maffezzoni, M., Frullanti, E., Mondelli, M. U., Renieri, A., Mantovani, S., Daga, S., Fallerini, C., Baldassarri, M., Benetti, E., Picchiotti, N., Fava, F., Galli, A., Zibellini, S., Bruttini, M., Palmieri, M., Croci, S., Amitrano, S., Alaverdian, D., Capitani, K., Furini, S., Mari, F., Meloni, I., Montagnani, F., Tumbarello, M., Rancan, I., Fabbiani, M., Rossetti, B., Bergantini, L., D'Alessandro, M., Cameli, P., Bennett, D., Anedda, F., Marcantonio, S., Scolletta, S., Franchi, F., Mazzei, M. A., Guerrini, S., Conticini, E., Cantarini, L., Frediani, B., Tacconi, D., Raffaelli, C. S., Feri, M., Donati, A., Scala, R., Guidelli, L., Spargi, G., Corridi, M., Nencioni, C., Croci, L., Caldarelli, G. P., Romani, D., Piacentini, P., Bandini, M., Desanctis, E., Cappelli, S., Canaccini, A., Verzuri, A., Anemoli, V., Pisani, M., Ognibene, A., Pancrazzi, A., Lorubbio, M., Vaghi, M., D'Arminio Monforte, A., Miraglia, F. G., Bruno, R., Vecchia, M., Girardis, M., Venturelli, S., Busani, S., Cossarizza, A., Antinori, A., Vergori, A., Emiliozzi, A., Rusconi, S., Siano, M., Gabrieli, A., Riva, A., Francisci, D., Schiaroli, E., Paciosi, F., Tommasi, A., Scotton, P. G., Andretta, F., Panese, S., Baratti, S., Scaggiante, R., Gatti, F., Parisi, S. G., Castelli, F., Quiros-Roldan, E., Antoni, M. D., Zanella, I., Della Monica, M., Piscopo, C., Capasso, M., Russo, R., Andolfo, I., Iolascon, A., Fiorentino, G., Carella, M., Castori, M., Aucella, F., Raggi, P., Perna, R., Bassetti, M., Di Biagio, A., Sanguinetti, M., Masucci, L., Guarnaccia, A., Valente, S., De Vivo, O., Doddato, G., Lista, M., Beligni, G., Valentino, F., Zguro, K., Tita, R., Giliberti, A., Mencarelli, M. A., Rizzo, C. L., Pinto, A. M., Ariani, F., Di Sarno, L., Bargagli, E., Mandala, M., Giorli, A., Salerni, L., Zucchi, P., Parravicini, P., Menatti, E., Trotta, T., Giannattasio, F., Coiro, G., Lena, F., Lacerenza, G., Mussini, C., Martinelli, E., Tavecchia, L., Belli, M. A., Crotti, L., Parati, G., Sanarico, M., Raimondi, F., Biscarini, F., Stella, A., Bachetti, T., La Rovere, M. T., Ludovisi, S., Bussotti, M., Dei, S., Ravaglia, S., Artuso, R., Andreucci, E., Gori, G., Pagliazzi, A., Fiorentini, E., Perrella, A., Bianchi, F., Bergomi, P., Catena, E., Colombo, R., Luchi, S., Morelli, G., Petrocelli, P., Iacopini, S., Modica, S., Baroni, S., Segala, F. V., Falcone, M., Tiseo, G., Barbieri, C., Matucci, T., Grassi, D., Ferri, C., Marinangeli, F., Brancati, F., Vincenti, A., Borgo, V., Lombardi, S., Lenzi, M., Di Pietro, M. A., Vichi, F., Romanin, B., Attala, L., Costa, C., Gabbuti, A., Mene, R., Colaneri, M., Casprini, P., Merla, G., Squeo, G. M., Maffezzoni, M., Frullanti, E., Mondelli, M. U., Renieri, A., Mantovani, S, Daga, S, Fallerini, C, Baldassarri, M, Benetti, E, Picchiotti, N, Fava, F, Galli, A, Zibellini, S, Bruttini, M, Palmieri, M, Croci, S, Amitrano, S, Alaverdian, D, Capitani, K, Furini, S, Mari, F, Meloni, I, Montagnani, F, Tumbarello, M, Rancan, I, Fabbiani, M, Rossetti, B, Bergantini, L, D'Alessandro, M, Cameli, P, Bennett, D, Anedda, F, Marcantonio, S, Scolletta, S, Franchi, F, Mazzei, M, Guerrini, S, Conticini, E, Cantarini, L, Frediani, B, Tacconi, D, Raffaelli, C, Feri, M, Donati, A, Scala, R, Guidelli, L, Spargi, G, Corridi, M, Nencioni, C, Croci, L, Caldarelli, G, Romani, D, Piacentini, P, Bandini, M, Desanctis, E, Cappelli, S, Canaccini, A, Verzuri, A, Anemoli, V, Pisani, M, Ognibene, A, Pancrazzi, A, Lorubbio, M, Vaghi, M, D'Arminio Monforte, A, Miraglia, F, Bruno, R, Vecchia, M, Girardis, M, Venturelli, S, Busani, S, Cossarizza, A, Antinori, A, Vergori, A, Emiliozzi, A, Rusconi, S, Siano, M, Gabrieli, A, Riva, A, Francisci, D, Schiaroli, E, Paciosi, F, Tommasi, A, Scotton, P, Andretta, F, Panese, S, Baratti, S, Scaggiante, R, Gatti, F, Parisi, S, Castelli, F, Quiros-Roldan, E, Antoni, M, Zanella, I, Della Monica, M, Piscopo, C, Capasso, M, Russo, R, Andolfo, I, Iolascon, A, Fiorentino, G, Carella, M, Castori, M, Aucella, F, Raggi, P, Perna, R, Bassetti, M, Di Biagio, A, Sanguinetti, M, Masucci, L, Guarnaccia, A, Valente, S, De Vivo, O, Doddato, G, Lista, M, Beligni, G, Valentino, F, Zguro, K, Tita, R, Giliberti, A, Mencarelli, M, Rizzo, C, Pinto, A, Ariani, F, Di Sarno, L, Bargagli, E, Mandala, M, Giorli, A, Salerni, L, Zucchi, P, Parravicini, P, Menatti, E, Trotta, T, Giannattasio, F, Coiro, G, Lena, F, Lacerenza, G, Mussini, C, Martinelli, E, Tavecchia, L, Belli, M, Crotti, L, Parati, G, Sanarico, M, Raimondi, F, Biscarini, F, Stella, A, Bachetti, T, La Rovere, M, Ludovisi, S, Bussotti, M, Dei, S, Ravaglia, S, Artuso, R, Andreucci, E, Gori, G, Pagliazzi, A, Fiorentini, E, Perrella, A, Bianchi, F, Bergomi, P, Catena, E, Colombo, R, Luchi, S, Morelli, G, Petrocelli, P, Iacopini, S, Modica, S, Baroni, S, Segala, F, Falcone, M, Tiseo, G, Barbieri, C, Matucci, T, Grassi, D, Ferri, C, Marinangeli, F, Brancati, F, Vincenti, A, Borgo, V, Lombardi, S, Lenzi, M, Di Pietro, M, Vichi, F, Romanin, B, Attala, L, Costa, C, Gabbuti, A, Mene, R, Colaneri, M, Casprini, P, Merla, G, Squeo, G, Maffezzoni, M, Frullanti, E, Mondelli, M, and Renieri, A

Subjects
Male, COVID-19, Cytokines, Down-Regulation, Humans, Leukocytes, Mononuclear, SARS-CoV-2, Toll-Like Receptor 7, Toll-Like Receptor 8. [MeSH], toll-like receptor 7, Immunology, Mononuclear, virus diseases, rare variants, Brief Communication, Toll-Like Receptor 8, Settore BIO/12 - BIOCHIMICA CLINICA E BIOLOGIA MOLECOLARE CLINICA, covid-19, Genetics, Leukocytes, Genetics (clinical)
Abstract

Toll-like receptors (TLR) are crucial components in the initiation of innate immune responses to a variety of pathogens, triggering the production of pro-inflammatory cytokines and type I and II interferons, which are responsible for innate antiviral responses. Among the different TLRs, TLR7 recognizes several single-stranded RNA viruses including SARS-CoV-2. We and others identified rare loss-of-function variants in X-chromosomal TLR7 in young men with severe COVID-19 and with no prior history of major chronic diseases, that were associated with impaired TLR7 signaling as well as type I and II IFN responses. Here, we performed RNA sequencing to investigate transcriptome variations following imiquimod stimulation of peripheral blood mononuclear cells isolated from patients carrying previously identified hypomorphic, hypofunctional, and loss-of-function TLR7 variants. Our investigation revealed a profound impairment of the TLR7 pathway in patients carrying loss-of-function variants. Of note, a failure in IFNγ upregulation following stimulation was also observed in cells harboring the hypofunctional and hypomorphic variants. We also identified new TLR7 variants in severely affected male patients for which a functional characterization of the TLR7 pathway was performed demonstrating a decrease in mRNA levels in the IFNα, IFNγ, RSAD2, ACOD1, IFIT2, and CXCL10 genes.

Published
2021
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32. Peptide-modified liposomes for selective targeting of bombesin receptors overexpressed by cancer cells: a potential theranostic agent

Author

Accardo A, Salsano G, Morisco A, Aurilio M, Parisi A, Maione F, Cicala C, Tesauro D, Aloj L, De Rosa G, and Morelli G

Subjects
Medicine (General), R5-920
Abstract

Antonella Accardo1,2*, Giuseppina Salsano3*, Anna Morisco4, Michela Aurilio4, Antonio Parisi5, Francesco Maione5, Carla Cicala5, Diego Tesauro1,2, Luigi Aloj4, Giuseppe De Rosa3, Giancarlo Morelli1,21CIRPeB, Department of Biological Sciences and IBB CNR, University of Naples “Federico II”, 2Invectors srl, 3Department of Pharmaceutical Chemistry, University of Naples “Federico II”, 4Department of Nuclear Medicine, Istituto Nazionale per lo Studio e la Cura dei Tumori, Fondazione “G. Pascale”, 5Department of Experimental Pharmacology, University of Naples “Federico II”, Napoli, Italy*These authors contributed equally to this workObjectives: Drug delivery systems consisting of liposomes displaying a cell surface receptor-targeting peptide are being developed to specifically deliver chemotherapeutic drugs to tumors overexpressing a target receptor. This study addresses novel liposome composition approaches to specifically target tissues overexpressing bombesin (BN) receptors.Methods: A new amphiphilic peptide derivative (MonY-BN) containing the BN(7–14) peptide, the DTPA (diethylenetriaminepentaacetate) chelating agent, a hydrophobic moiety with two C18 alkyl chains, and polyethylene glycol spacers, has been synthesized by solid-phase methods. Liposomes have been generated by co-aggregation of MonY-BN with 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC). The structural and biological properties of these new target-selective drug-delivery systems have been characterized.Results: Liposomes with a DSPC/MonY-BN (97/3 molar ratio) composition showed a diameter of 145.5 ± 31.5 nm and a polydispersity index of 0.20 ± 0.05. High doxorubicin (Dox) loading was obtained with the remote pH gradient method using citrate as the inner buffer. Specific binding to PC-3 cells of DSPC/MonY-BN liposomes was obtained (2.7% ± 0.3%, at 37°C), compared with peptide-free DSPC liposomes (1.4% ± 0.2% at 37°C). Incubation of cells with DSPC/MonY-BN/Dox showed significantly lower cell survival compared with DSPC/Dox-treated cells, in the presence of 100 ng/mL and 300 ng/mL drug amounts, in cytotoxicity experiments. Intravenous treatment of PC-3 xenograft-bearing mice with DSPC/MonY-BN/Dox at 10 mg/kg Dox dose produced higher tumour growth inhibition (60%) compared with nonspecific DSPC/Dox liposomes (36%) relative to control animals.Conclusion: The structural and loading properties of DSPC/MonY-BN liposomes along with the observed in-vitro and in-vivo activity are encouraging for further development of this approach for target-specific cancer chemotherapy.Keywords: bombesin peptide, doxorubicin delivery, gastrin-releasing peptide receptors, PC-3 cells, theranostic applications

Published
2012

33. An explainable model of host genetic interactions linked to COVID-19 severity

Author

Onoja, A., Picchiotti, N., Fallerini, C., Baldassarri, M., Fava, F., Mari, F., Daga, S., Benetti, E., Bruttini, M., Palmieri, Marco, Croci, S., Amitrano, S., Meloni, I., Frullanti, E., Doddato, G., Lista, Maddalena, Beligni, G., Valentino, Francesca, Zguro, K., Tita, R., Giliberti, A., Mencarelli, Marta, Rizzo, C. L., Pinto, A. M., Ariani, F., Di Sarno, Lorenzo, Montagnani, F., Tumbarello, Mario, Rancan, I., Fabbiani, M., Rossetti, Barbara, Bergantini, L., D'Alessandro, Michele, Cameli, P., Bennett, D., Anedda, F., Marcantonio, S., Scolletta, S., Franchi, Francesca, Mazzei, M. A., Guerrini, S., Conticini, E., Cantarini, L., Frediani, B., Tacconi, D., Raffaelli, C. S., Feri, M., Donati, Andrea, Scala, R., Guidelli, L., Spargi, G., Corridi, M., Nencioni, C., Croci, L., Caldarelli, G. P., Romani, D., Piacentini, P., Bandini, M., Desanctis, E., Cappelli, S., Canaccini, A., Verzuri, A., Anemoli, V., Pisani, M., Ognibene, A., Pancrazzi, A., Lorubbio, M., Vaghi, M., D'Arminio Monforte, A., Miraglia, F. G., Bruno, R., Vecchia, M., Girardis, M., Venturelli, S., Busani, S., Cossarizza, A., Antinori, Armando, Vergori, A., Emiliozzi, A., Rusconi, S., Siano, M., Gabrieli, A., Riva, A., Francisci, D., Schiaroli, E., Paciosi, F., Tommasi, A., Zuccon, U., Vietri, L., Scotton, P. G., Andretta, F., Panese, S., Baratti, S., Scaggiante, R., Gatti, F., Parisi, S. G., Castelli, F., Quiros-Roldan, E., Antoni, M. D., Zanella, I., Della Monica, M., Piscopo, C., Capasso, Monica, Russo, R., Andolfo, I., Iolascon, A., Fiorentino, Giuseppe, Carella, M., Castori, M., Aucella, F., Raggi, P., Perna, Raffaella, Bassetti, M., Di Biagio, Anna, Sanguinetti, Maurizio, Masucci, Luca, Guarnaccia, A., Valente, S., De Vivo, O., Bargagli, E., Mandala, M., Giorli, A., Salerni, L., Zucchi, P., Parravicini, P., Menatti, E., Trotta, T., Giannattasio, F., Coiro, G., Lena, Francesco, Lacerenza, G., Coviello, D. A., Mussini, C., Martinelli, E., Tavecchia, L., Belli, M. A., Crotti, L., Parati, G., Sanarico, M., Biscarini, F., Stella, A., Rizzi, M., Maggiolo, F., Ripamonti, D., Suardi, C., Bachetti, T., La Rovere, M. T., Sarzi-Braga, S., Bussotti, M., Capitani, K., Dei, S., Ravaglia, S., Artuso, R., Andreucci, E., Gori, Giovanni Cristiano, Pagliazzi, A., Fiorentini, E., Perrella, A., Bianchi, F., Bergomi, P., Catena, E., Colombo, R., Luchi, S., Morelli, G., Petrocelli, Paolo, Iacopini, S., Modica, S., Baroni, Silvia, Segala, F. V., Menichetti, F., Falcone, M., Tiseo, G., Barbieri, Cristiano, Matucci, T., Grassi, D., Ferri, C., Marinangeli, F., Brancati, F., Vincenti, A., Borgo, V., Lombardi, S., Lenzi, M., Di Pietro, Maria Luisa, Vichi, F., Romanin, B., Attala, L., Costa, C., Gabbuti, A., Mene, R., Colaneri, M., Casprini, P., Merla, G., Squeo, G. M., Maffezzoni, M., Mantovani, Susanna, Mondelli, M. U., Ludovisi, S., Colombo, F., Chiaromonte, F., Renieri, A., Furini, S., Raimondi, F., Palmieri M. (ORCID:0000-0001-8263-336X), Lista M., Valentino F., Mencarelli M. A., Di Sarno L., Tumbarello M. (ORCID:0000-0002-9519-8552), Rossetti B., D'Alessandro M., Franchi F., Donati A., Antinori A. (ORCID:0000-0002-6019-2417), Capasso M., Fiorentino G., Perna R., Di Biagio A., Sanguinetti M. (ORCID:0000-0002-9780-7059), Masucci L. (ORCID:0000-0002-8358-6726), Lena F. (ORCID:0000-0001-5528-319X), Gori G. (ORCID:0000-0002-3308-5309), Petrocelli P., Barbieri C., Di Pietro M. A. (ORCID:0000-0002-3893-8788), Mantovani S., Onoja, A., Picchiotti, N., Fallerini, C., Baldassarri, M., Fava, F., Mari, F., Daga, S., Benetti, E., Bruttini, M., Palmieri, Marco, Croci, S., Amitrano, S., Meloni, I., Frullanti, E., Doddato, G., Lista, Maddalena, Beligni, G., Valentino, Francesca, Zguro, K., Tita, R., Giliberti, A., Mencarelli, Marta, Rizzo, C. L., Pinto, A. M., Ariani, F., Di Sarno, Lorenzo, Montagnani, F., Tumbarello, Mario, Rancan, I., Fabbiani, M., Rossetti, Barbara, Bergantini, L., D'Alessandro, Michele, Cameli, P., Bennett, D., Anedda, F., Marcantonio, S., Scolletta, S., Franchi, Francesca, Mazzei, M. A., Guerrini, S., Conticini, E., Cantarini, L., Frediani, B., Tacconi, D., Raffaelli, C. S., Feri, M., Donati, Andrea, Scala, R., Guidelli, L., Spargi, G., Corridi, M., Nencioni, C., Croci, L., Caldarelli, G. P., Romani, D., Piacentini, P., Bandini, M., Desanctis, E., Cappelli, S., Canaccini, A., Verzuri, A., Anemoli, V., Pisani, M., Ognibene, A., Pancrazzi, A., Lorubbio, M., Vaghi, M., D'Arminio Monforte, A., Miraglia, F. G., Bruno, R., Vecchia, M., Girardis, M., Venturelli, S., Busani, S., Cossarizza, A., Antinori, Armando, Vergori, A., Emiliozzi, A., Rusconi, S., Siano, M., Gabrieli, A., Riva, A., Francisci, D., Schiaroli, E., Paciosi, F., Tommasi, A., Zuccon, U., Vietri, L., Scotton, P. G., Andretta, F., Panese, S., Baratti, S., Scaggiante, R., Gatti, F., Parisi, S. G., Castelli, F., Quiros-Roldan, E., Antoni, M. D., Zanella, I., Della Monica, M., Piscopo, C., Capasso, Monica, Russo, R., Andolfo, I., Iolascon, A., Fiorentino, Giuseppe, Carella, M., Castori, M., Aucella, F., Raggi, P., Perna, Raffaella, Bassetti, M., Di Biagio, Anna, Sanguinetti, Maurizio, Masucci, Luca, Guarnaccia, A., Valente, S., De Vivo, O., Bargagli, E., Mandala, M., Giorli, A., Salerni, L., Zucchi, P., Parravicini, P., Menatti, E., Trotta, T., Giannattasio, F., Coiro, G., Lena, Francesco, Lacerenza, G., Coviello, D. A., Mussini, C., Martinelli, E., Tavecchia, L., Belli, M. A., Crotti, L., Parati, G., Sanarico, M., Biscarini, F., Stella, A., Rizzi, M., Maggiolo, F., Ripamonti, D., Suardi, C., Bachetti, T., La Rovere, M. T., Sarzi-Braga, S., Bussotti, M., Capitani, K., Dei, S., Ravaglia, S., Artuso, R., Andreucci, E., Gori, Giovanni Cristiano, Pagliazzi, A., Fiorentini, E., Perrella, A., Bianchi, F., Bergomi, P., Catena, E., Colombo, R., Luchi, S., Morelli, G., Petrocelli, Paolo, Iacopini, S., Modica, S., Baroni, Silvia, Segala, F. V., Menichetti, F., Falcone, M., Tiseo, G., Barbieri, Cristiano, Matucci, T., Grassi, D., Ferri, C., Marinangeli, F., Brancati, F., Vincenti, A., Borgo, V., Lombardi, S., Lenzi, M., Di Pietro, Maria Luisa, Vichi, F., Romanin, B., Attala, L., Costa, C., Gabbuti, A., Mene, R., Colaneri, M., Casprini, P., Merla, G., Squeo, G. M., Maffezzoni, M., Mantovani, Susanna, Mondelli, M. U., Ludovisi, S., Colombo, F., Chiaromonte, F., Renieri, A., Furini, S., Raimondi, F., Palmieri M. (ORCID:0000-0001-8263-336X), Lista M., Valentino F., Mencarelli M. A., Di Sarno L., Tumbarello M. (ORCID:0000-0002-9519-8552), Rossetti B., D'Alessandro M., Franchi F., Donati A., Antinori A. (ORCID:0000-0002-6019-2417), Capasso M., Fiorentino G., Perna R., Di Biagio A., Sanguinetti M. (ORCID:0000-0002-9780-7059), Masucci L. (ORCID:0000-0002-8358-6726), Lena F. (ORCID:0000-0001-5528-319X), Gori G. (ORCID:0000-0002-3308-5309), Petrocelli P., Barbieri C., Di Pietro M. A. (ORCID:0000-0002-3893-8788), and Mantovani S.

Abstract

We employed a multifaceted computational strategy to identify the genetic factors contributing to increased risk of severe COVID-19 infection from a Whole Exome Sequencing (WES) dataset of a cohort of 2000 Italian patients. We coupled a stratified k-fold screening, to rank variants more associated with severity, with the training of multiple supervised classifiers, to predict severity based on screened features. Feature importance analysis from tree-based models allowed us to identify 16 variants with the highest support which, together with age and gender covariates, were found to be most predictive of COVID-19 severity. When tested on a follow-up cohort, our ensemble of models predicted severity with high accuracy (ACC = 81.88%; AUCROC = 96%; MCC = 61.55%). Our model recapitulated a vast literature of emerging molecular mechanisms and genetic factors linked to COVID-19 response and extends previous landmark Genome-Wide Association Studies (GWAS). It revealed a network of interplaying genetic signatures converging on established immune system and inflammatory processes linked to viral infection response. It also identified additional processes cross-talking with immune pathways, such as GPCR signaling, which might offer additional opportunities for therapeutic intervention and patient stratification. Publicly available PheWAS datasets revealed that several variants were significantly associated with phenotypic traits such as “Respiratory or thoracic disease”, supporting their link with COVID-19 severity outcome.

Published
2022

34. An explainable model of host genetic interactions linked to COVID-19 severity

Author

Anthony, O, Nicola, P, Chiara, F, Margherita, B, Francesca, F, Francesca, C, Alessandra, R, Simone, F, Francesco, R, Mari, F, Daga, S, Benetti, E, Bruttini, M, Palmieri, M, Croci, S, Amitrano, S, Meloni, I, Frullanti, E, Doddato, G, Lista, M, Beligni, G, Valentino, F, Zguro, K, Tita, R, Giliberti, A, Antonietta Mencarelli, M, Lo Rizzo, C, Maria Pinto, A, Ariani, F, Di Sarno, L, Montagnani, F, Tumbarello, M, Rancan, I, Fabbiani, M, Rossetti, B, Bergantini, L, D’Alessandro, M, Cameli, P, Bennett, D, Anedda, F, Marcantonio, S, Scolletta, S, Franchi, F, Antonietta Mazzei, M, Guerrini, S, Conticini, E, Cantarini, L, Frediani, B, Tacconi, D, Spertilli Raffaelli, C, Feri, M, Donati, A, Scala, R, Guidelli, L, Spargi, G, Corridi, M, Nencioni, C, Croci, L, Piero Caldarelli, G, Romani, D, Piacentini, P, Bandini, M, Desanctis, E, Cappelli, S, Canaccini, A, Verzuri, A, Anemoli, V, Pisani, M, Ognibene, A, Pancrazzi, A, Lorubbio, M, Vaghi, M, D’Arminio Monforte, A, Gaia Miraglia, F, Bruno, R, Vecchia, M, Girardis, M, Venturelli, S, Busani, S, Cossarizza, A, Antinori, A, Vergori, A, Emiliozzi, A, Rusconi, S, Siano, M, Gabrieli, A, Riva, A, Francisci, D, Schiaroli, E, Paciosi, F, Tommasi, A, Zuccon, U, Vietri, L, Giorgio Scotton, P, Andretta, F, Panese, S, Baratti, S, Scaggiante, R, Gatti, F, Giuseppe Parisi, S, Castelli, F, Quiros-Roldan, E, Degli Antoni, M, Zanella, I, Della Monica, M, Piscopo, C, Capasso, M, Russo, R, Andolfo, I, Iolascon, A, Fiorentino, G, Carella, M, Castori, M, Aucella, F, Raggi, P, Perna, R, Bassetti, M, Di Biagio, A, Sanguinetti, M, Masucci, L, Guarnaccia, A, Valente, S, De Vivo, O, Bargagli, E, Mandalà, M, Giorli, A, Salerni, L, Zucchi, P, Parravicini, P, Menatti, E, Trotta, T, Giannattasio, F, Coiro, G, Lena, F, Lacerenza, G, Coviello, D, Mussini, C, Martinelli, E, Tavecchia, L, Ann Belli, M, Crotti, L, Parati, G, Sanarico, M, Biscarini, F, Stella, A, Rizzi, M, Maggiolo, F, Ripamonti, D, Suardi, C, Bachetti, T, Teresa La Rovere, M, Sarzi-Braga, S, Bussotti, M, Capitani, K, Dei, S, Ravaglia, S, Artuso, R, Andreucci, E, Gori, G, Pagliazzi, A, Fiorentini, E, Perrella, A, Bianchi, F, Bergomi, P, Catena, E, Colombo, R, Luchi, S, Morelli, G, Petrocelli, P, Iacopini, S, Modica, S, Baroni, S, Vladimiro Segala, F, Menichetti, F, Falcone, M, Tiseo, G, Barbieri, C, Matucci, T, Grassi, D, Ferri, C, Marinangeli, F, Brancati, F, Vincenti, A, Borgo, V, Lombardi, S, Lenzi, M, Antonio Di Pietro, M, Vichi, F, Romanin, B, Attala, L, Costa, C, Gabbuti, A, Menè, R, Colaneri, M, Casprini, P, Merla, G, Maria Squeo, G, Maffezzoni, M, Mantovani, S, Mondelli &amp, M, Ludovisi, S, Onoja, Anthony, Picchiotti, Nicola, Fallerini, Chiara, Baldassarri, Margherita, Fava, Francesca, Colombo, Francesca, Chiaromonte, Francesca, Renieri, Alessandra, Furini, Simone, Raimondi Francesco, Francesca Mari, Sergio Daga, Elisa Benetti, Mirella Bruttini, Maria Palmieri, Susanna Croci, Sara Amitrano, Ilaria Meloni, Elisa Frullanti, Gabriella Doddato, Mirjam Lista, Giada Beligni, Floriana Valentino, Kristina Zguro, Rossella Tita, Annarita Giliberti, Maria Antonietta Mencarelli, Caterina Lo Rizzo, Anna Maria Pinto, Francesca Ariani, Laura Di Sarno, Francesca Montagnani, Mario Tumbarello, Ilaria Rancan, Massimiliano Fabbiani, Barbara Rossetti, Laura Bergantini, Miriana D’Alessandro, Paolo Cameli, David Bennett, Federico Anedda, Simona Marcantonio, Sabino Scolletta, Federico Franchi, Maria Antonietta Mazzei, Susanna Guerrini, Edoardo Conticini, Luca Cantarini, Bruno Frediani, Danilo Tacconi, Chiara Spertilli Raffaelli, Marco Feri, Alice Donati, Raffaele Scala, Luca Guidelli, Genni Spargi, Marta Corridi, Cesira Nencioni, Leonardo Croci, Gian Piero Caldarelli, Davide Romani, Paolo Piacentini, Maria Bandini, Elena Desanctis, Silvia Cappelli, Anna Canaccini, Agnese Verzuri, Valentina Anemoli, Manola Pisani, Agostino Ognibene, Alessandro Pancrazzi, Maria Lorubbio, Massimo Vaghi, Antonella D’Arminio Monforte, Federica Gaia Miraglia, Raffaele Bruno, Marco Vecchia, Massimo Girardis, Sophie Venturelli, Stefano Busani, Andrea Cossarizza, Andrea Antinori, Alessandra Vergori, Arianna Emiliozzi, Stefano Rusconi, Matteo Siano, Arianna Gabrieli, Agostino Riva, Daniela Francisci, Elisabetta Schiaroli, Francesco Paciosi, Andrea Tommasi, Umberto Zuccon, Lucia Vietri, Pier Giorgio Scotton, Francesca Andretta, Sandro Panese, Stefano Baratti, Renzo Scaggiante, Francesca Gatti, Saverio Giuseppe Parisi, Francesco Castelli, Eugenia Quiros-Roldan, Melania Degli Antoni, Isabella Zanella, Matteo Della Monica, Carmelo Piscopo, Mario Capasso, Roberta Russo, Immacolata Andolfo, Achille Iolascon, Giuseppe Fiorentino, Massimo Carella, Marco Castori, Filippo Aucella, Pamela Raggi, Rita Perna, Matteo Bassetti, Antonio Di Biagio, Maurizio Sanguinetti, Luca Masucci, Alessandra Guarnaccia, Serafina Valente, Oreste De Vivo, Elena Bargagli, Marco Mandalà, Alessia Giorli, Lorenzo Salerni, Patrizia Zucchi, Pierpaolo Parravicini, Elisabetta Menatti, Tullio Trotta, Ferdinando Giannattasio, Gabriella Coiro, Fabio Lena, Gianluca Lacerenza, Domenico A. Coviello, Cristina Mussini, Enrico Martinelli, Luisa Tavecchia, Mary Ann Belli, Lia Crotti, Gianfranco Parati, Maurizio Sanarico, Filippo Biscarini, Alessandra Stella, Marco Rizzi, Franco Maggiolo, Diego Ripamonti, Claudia Suardi, Tiziana Bachetti, Maria Teresa La Rovere, Simona Sarzi-Braga, Maurizio Bussotti, Katia Capitani, Simona Dei, Sabrina Ravaglia, Rosangela Artuso, Elena Andreucci, Giulia Gori, Angelica Pagliazzi, Erika Fiorentini, Antonio Perrella, Francesco Bianchi, Paola Bergomi, Emanuele Catena, Riccardo Colombo, Sauro Luchi, Giovanna Morelli, Paola Petrocelli, Sarah Iacopini, Sara Modica, Silvia Baroni, Francesco Vladimiro Segala, Francesco Menichetti, Marco Falcone, Giusy Tiseo, Chiara Barbieri, Tommaso Matucci, Davide Grassi, Claudio Ferri, Franco Marinangeli, Francesco Brancati, Antonella Vincenti, Valentina Borgo, Stefania Lombardi, Mirco Lenzi, Massimo Antonio Di Pietro, Francesca Vichi, Benedetta Romanin, Letizia Attala, Cecilia Costa, Andrea Gabbuti, Roberto Menè, Marta Colaneri, Patrizia Casprini, Giuseppe Merla, Gabriella Maria Squeo, Marcello Maffezzoni, Stefania Mantovani, Mario U. Mondelli &, Serena Ludovisi, Anthony, O, Nicola, P, Chiara, F, Margherita, B, Francesca, F, Francesca, C, Alessandra, R, Simone, F, Francesco, R, Mari, F, Daga, S, Benetti, E, Bruttini, M, Palmieri, M, Croci, S, Amitrano, S, Meloni, I, Frullanti, E, Doddato, G, Lista, M, Beligni, G, Valentino, F, Zguro, K, Tita, R, Giliberti, A, Antonietta Mencarelli, M, Lo Rizzo, C, Maria Pinto, A, Ariani, F, Di Sarno, L, Montagnani, F, Tumbarello, M, Rancan, I, Fabbiani, M, Rossetti, B, Bergantini, L, D’Alessandro, M, Cameli, P, Bennett, D, Anedda, F, Marcantonio, S, Scolletta, S, Franchi, F, Antonietta Mazzei, M, Guerrini, S, Conticini, E, Cantarini, L, Frediani, B, Tacconi, D, Spertilli Raffaelli, C, Feri, M, Donati, A, Scala, R, Guidelli, L, Spargi, G, Corridi, M, Nencioni, C, Croci, L, Piero Caldarelli, G, Romani, D, Piacentini, P, Bandini, M, Desanctis, E, Cappelli, S, Canaccini, A, Verzuri, A, Anemoli, V, Pisani, M, Ognibene, A, Pancrazzi, A, Lorubbio, M, Vaghi, M, D’Arminio Monforte, A, Gaia Miraglia, F, Bruno, R, Vecchia, M, Girardis, M, Venturelli, S, Busani, S, Cossarizza, A, Antinori, A, Vergori, A, Emiliozzi, A, Rusconi, S, Siano, M, Gabrieli, A, Riva, A, Francisci, D, Schiaroli, E, Paciosi, F, Tommasi, A, Zuccon, U, Vietri, L, Giorgio Scotton, P, Andretta, F, Panese, S, Baratti, S, Scaggiante, R, Gatti, F, Giuseppe Parisi, S, Castelli, F, Quiros-Roldan, E, Degli Antoni, M, Zanella, I, Della Monica, M, Piscopo, C, Capasso, M, Russo, R, Andolfo, I, Iolascon, A, Fiorentino, G, Carella, M, Castori, M, Aucella, F, Raggi, P, Perna, R, Bassetti, M, Di Biagio, A, Sanguinetti, M, Masucci, L, Guarnaccia, A, Valente, S, De Vivo, O, Bargagli, E, Mandalà, M, Giorli, A, Salerni, L, Zucchi, P, Parravicini, P, Menatti, E, Trotta, T, Giannattasio, F, Coiro, G, Lena, F, Lacerenza, G, Coviello, D, Mussini, C, Martinelli, E, Tavecchia, L, Ann Belli, M, Crotti, L, Parati, G, Sanarico, M, Biscarini, F, Stella, A, Rizzi, M, Maggiolo, F, Ripamonti, D, Suardi, C, Bachetti, T, Teresa La Rovere, M, Sarzi-Braga, S, Bussotti, M, Capitani, K, Dei, S, Ravaglia, S, Artuso, R, Andreucci, E, Gori, G, Pagliazzi, A, Fiorentini, E, Perrella, A, Bianchi, F, Bergomi, P, Catena, E, Colombo, R, Luchi, S, Morelli, G, Petrocelli, P, Iacopini, S, Modica, S, Baroni, S, Vladimiro Segala, F, Menichetti, F, Falcone, M, Tiseo, G, Barbieri, C, Matucci, T, Grassi, D, Ferri, C, Marinangeli, F, Brancati, F, Vincenti, A, Borgo, V, Lombardi, S, Lenzi, M, Antonio Di Pietro, M, Vichi, F, Romanin, B, Attala, L, Costa, C, Gabbuti, A, Menè, R, Colaneri, M, Casprini, P, Merla, G, Maria Squeo, G, Maffezzoni, M, Mantovani, S, Mondelli &amp, M, Ludovisi, S, Onoja, Anthony, Picchiotti, Nicola, Fallerini, Chiara, Baldassarri, Margherita, Fava, Francesca, Colombo, Francesca, Chiaromonte, Francesca, Renieri, Alessandra, Furini, Simone, Raimondi Francesco, Francesca Mari, Sergio Daga, Elisa Benetti, Mirella Bruttini, Maria Palmieri, Susanna Croci, Sara Amitrano, Ilaria Meloni, Elisa Frullanti, Gabriella Doddato, Mirjam Lista, Giada Beligni, Floriana Valentino, Kristina Zguro, Rossella Tita, Annarita Giliberti, Maria Antonietta Mencarelli, Caterina Lo Rizzo, Anna Maria Pinto, Francesca Ariani, Laura Di Sarno, Francesca Montagnani, Mario Tumbarello, Ilaria Rancan, Massimiliano Fabbiani, Barbara Rossetti, Laura Bergantini, Miriana D’Alessandro, Paolo Cameli, David Bennett, Federico Anedda, Simona Marcantonio, Sabino Scolletta, Federico Franchi, Maria Antonietta Mazzei, Susanna Guerrini, Edoardo Conticini, Luca Cantarini, Bruno Frediani, Danilo Tacconi, Chiara Spertilli Raffaelli, Marco Feri, Alice Donati, Raffaele Scala, Luca Guidelli, Genni Spargi, Marta Corridi, Cesira Nencioni, Leonardo Croci, Gian Piero Caldarelli, Davide Romani, Paolo Piacentini, Maria Bandini, Elena Desanctis, Silvia Cappelli, Anna Canaccini, Agnese Verzuri, Valentina Anemoli, Manola Pisani, Agostino Ognibene, Alessandro Pancrazzi, Maria Lorubbio, Massimo Vaghi, Antonella D’Arminio Monforte, Federica Gaia Miraglia, Raffaele Bruno, Marco Vecchia, Massimo Girardis, Sophie Venturelli, Stefano Busani, Andrea Cossarizza, Andrea Antinori, Alessandra Vergori, Arianna Emiliozzi, Stefano Rusconi, Matteo Siano, Arianna Gabrieli, Agostino Riva, Daniela Francisci, Elisabetta Schiaroli, Francesco Paciosi, Andrea Tommasi, Umberto Zuccon, Lucia Vietri, Pier Giorgio Scotton, Francesca Andretta, Sandro Panese, Stefano Baratti, Renzo Scaggiante, Francesca Gatti, Saverio Giuseppe Parisi, Francesco Castelli, Eugenia Quiros-Roldan, Melania Degli Antoni, Isabella Zanella, Matteo Della Monica, Carmelo Piscopo, Mario Capasso, Roberta Russo, Immacolata Andolfo, Achille Iolascon, Giuseppe Fiorentino, Massimo Carella, Marco Castori, Filippo Aucella, Pamela Raggi, Rita Perna, Matteo Bassetti, Antonio Di Biagio, Maurizio Sanguinetti, Luca Masucci, Alessandra Guarnaccia, Serafina Valente, Oreste De Vivo, Elena Bargagli, Marco Mandalà, Alessia Giorli, Lorenzo Salerni, Patrizia Zucchi, Pierpaolo Parravicini, Elisabetta Menatti, Tullio Trotta, Ferdinando Giannattasio, Gabriella Coiro, Fabio Lena, Gianluca Lacerenza, Domenico A. Coviello, Cristina Mussini, Enrico Martinelli, Luisa Tavecchia, Mary Ann Belli, Lia Crotti, Gianfranco Parati, Maurizio Sanarico, Filippo Biscarini, Alessandra Stella, Marco Rizzi, Franco Maggiolo, Diego Ripamonti, Claudia Suardi, Tiziana Bachetti, Maria Teresa La Rovere, Simona Sarzi-Braga, Maurizio Bussotti, Katia Capitani, Simona Dei, Sabrina Ravaglia, Rosangela Artuso, Elena Andreucci, Giulia Gori, Angelica Pagliazzi, Erika Fiorentini, Antonio Perrella, Francesco Bianchi, Paola Bergomi, Emanuele Catena, Riccardo Colombo, Sauro Luchi, Giovanna Morelli, Paola Petrocelli, Sarah Iacopini, Sara Modica, Silvia Baroni, Francesco Vladimiro Segala, Francesco Menichetti, Marco Falcone, Giusy Tiseo, Chiara Barbieri, Tommaso Matucci, Davide Grassi, Claudio Ferri, Franco Marinangeli, Francesco Brancati, Antonella Vincenti, Valentina Borgo, Stefania Lombardi, Mirco Lenzi, Massimo Antonio Di Pietro, Francesca Vichi, Benedetta Romanin, Letizia Attala, Cecilia Costa, Andrea Gabbuti, Roberto Menè, Marta Colaneri, Patrizia Casprini, Giuseppe Merla, Gabriella Maria Squeo, Marcello Maffezzoni, Stefania Mantovani, Mario U. Mondelli &, and Serena Ludovisi

Abstract

We employed a multifaceted computational strategy to identify the genetic factors contributing to increased risk of severe COVID-19 infection from a Whole Exome Sequencing (WES) dataset of a cohort of 2000 Italian patients. We coupled a stratified k-fold screening, to rank variants more associated with severity, with the training of multiple supervised classifiers, to predict severity based on screened features. Feature importance analysis from tree-based models allowed us to identify 16 variants with the highest support which, together with age and gender covariates, were found to be most predictive of COVID-19 severity. When tested on a follow-up cohort, our ensemble of models predicted severity with high accuracy (ACC = 81.88%; AUCROC = 96%; MCC = 61.55%). Our model recapitulated a vast literature of emerging molecular mechanisms and genetic factors linked to COVID-19 response and extends previous landmark Genome-Wide Association Studies (GWAS). It revealed a network of interplaying genetic signatures converging on established immune system and inflammatory processes linked to viral infection response. It also identified additional processes cross-talking with immune pathways, such as GPCR signaling, which might offer additional opportunities for therapeutic intervention and patient stratification. Publicly available PheWAS datasets revealed that several variants were significantly associated with phenotypic traits such as “Respiratory or thoracic disease”, supporting their link with COVID-19 severity outcome.

Published
2022

45. Endothelial damage in septic shock patients as evidenced by circulating syndecan-1, sphingosine-1-phosphate and soluble VE-cadherin: a substudy of ALBIOS

Author

Piotti, A., Novelli, D., Meessen, J. M. T. A., Ferlicca, D., Coppolecchia, S., Marino, A., Salati, G., Savioli, M., Grasselli, G., Bellani, G., Pesenti, A., Masson, S., Caironi, P., Gattinoni, L., Gobbi, M., Fracasso, C., Latini, R., Bruzzone, P., Pagan, F., Russo, R., Confalonieri, A., Abbruzzese, C., Vergnano, B., Faenza, S., Siniscalchi, A., Pierucci, E., Noto, A., Pezzi, A., Spanu, P., Parrini, V., Oggioni, R., Pasetti, G. S., Casadio, M. C., Buontempo, R., Carrer, S., Piccoli, F., Rizzi, T., Caricato, A., La Sala, M., Antonaci, A., Fassini, P., Paganini, S., Porta, V., Moise, G., Marell, S., Furia, M., Urbano, M. C., Carobbi, R., Poleni, S., Kandil, H., Ballotta, A., Bettini, F., Sanseverino, M., Gatta, A., Cecchini, F., Guatteri, L., Ciceri, G., Raimondi, F., Colombo, R., Ferraris, S., Borelli, M., Bellato, V., Cancellieri, F., Senni, S., Bertocchi, E., Ferri, P., Moioli, G., Fedele, A., Molin, A., Salsi, P., Brunori, E., Elisei, D., Maggio, G., Nicola, F. G., Cavana, M., Morelli, G., Guarino, A., Isetta, M., Tulli, G., Mangani, V., Rossi, N., Ferrari, M., Bona, F., Vay, M., Bartoli, T., Gallo, M., Vettoretto, K., Morte, M. D., Boselli, E., Puscio, D., Bovo, M., Galzerano, A., Carli, M., Zagara, G., Piotti, A, Novelli, D, Meessen, J, Ferlicca, D, Coppolecchia, S, Marino, A, Salati, G, Savioli, M, Grasselli, G, Bellani, G, Pesenti, A, Masson, S, Caironi, P, Gattinoni, L, Gobbi, M, Fracasso, C, and Latini, R

Subjects
Male, Letter, medicine.medical_treatment, 030204 cardiovascular system & hematology, Critical Care and Intensive Care Medicine, Gastroenterology, 0302 clinical medicine, VE-cadherin, Sphingosine, Septic shock, 80 and over, Medicine, Endothelial dysfunction, Phosphorylation, Aged, 80 and over, lcsh:Medical emergencies. Critical care. Intensive care. First aid, Shock, Biomarker, Glycocalyx, Sphingosine-1-phosphate, Syndecan-1, Aged, Antigens, CD, Biomarkers, Cadherins, Endothelium, Female, Humans, Italy, Lysophospholipids, Middle Aged, Retrospective Studies, Shock, Septic, Extravasation, 3. Good health, CD, Endothelial stem cell, medicine.medical_specialty, Sepsis, 03 medical and health sciences, Internal medicine, Albumins, Settore MED/41 - ANESTESIOLOGIA, Renal replacement therapy, Antigens, business.industry, Septic, Research, Albumin, 030208 emergency & critical care medicine, lcsh:RC86-88.9, medicine.disease, business
Abstract

Background Septic shock is characterized by breakdown of the endothelial glycocalyx and endothelial damage, contributing to fluid extravasation, organ failure and death. Albumin has shown benefit in septic shock patients. Our aims were: (1) to identify the relations between circulating levels of syndecan-1 (SYN-1), sphingosine-1-phosphate (S1P) (endothelial glycocalyx), and VE-cadherin (endothelial cell junctions), severity of the disease, and survival; (2) to evaluate the effects of albumin supplementation on endothelial dysfunction in patients with septic shock. Methods This was a retrospective analysis of a multicenter randomized clinical trial on albumin replacement in severe sepsis or septic shock (the Albumin Italian Outcome Sepsis Trial, ALBIOS). Concentrations of SYN-1, S1P, soluble VE-cadherin and other biomarkers were measured on days 1, 2 and 7 in 375 patients with septic shock surviving up to 7 days after randomization. Results Plasma concentrations of SYN-1 and VE-cadherin rose significantly over 7 days. SYN-1 and VE-cadherin were elevated in patients with organ failure, and S1P levels were lower. SYN-1 and VE-cadherin were independently associated with renal replacement therapy requirement during ICU stay, but only SYN-1 predicted its new occurrence. Both SYN-1 and S1P, but not VE-cadherin, predicted incident coagulation failure. Only SYN-1 independently predicted 90-day mortality. Albumin significantly reduced VE-cadherin, by 9.5% (p = 0.003) at all three time points. Conclusion Circulating components of the endothelial glycocalyx and of the endothelial cell junctions provide insights into severity and progression of septic shock, with special focus on incident coagulation and renal failure. Albumin supplementation lowered circulating VE-cadherin consistently over time. Clinical Trial Registration: ALBIOS ClinicalTrials.gov number NCT00707122.

Published
2021

48. Analogue Geothermal Systems In Mexico: Insights Into The Deep Part Of Los Humeros Geothermal Field From The Las Minas Mining Area (Eastern Mexico)

Author

Liotta D.[1], Bastesen E.[2], Bianco C.[1], Brogi A.[1], Caggianelli A.[1], Garduño-Monroy V.H.[3], Gonzalez-Partida E.[4], Jimenez-Haro A.[3], Kozdrój W.[5], Lacinska A.[6], Lepillier B.[7], Morelli G.[8], Nawrocki J.[5], Olvera-Garcia E.[1], Panczyk-Nawrocka M.[5], Rochelle C.[6], Ruggieri G.[8], Torabi A.[2], Ventruti G.[1], Wheeler H.W.[2], Wójcik K.[5], Zió?kowska-Kozdrój M.[5], and Zucchi M.[1]

Subjects
interdisciplinary approach, structural geology, geochronology, fluid inclusions, petrology, analogue geothermal system
Abstract

This study is part of the H2020-GEMex Project, a collaboration between Europe and Mexico for investigating super-hot geothermal systems. The novelty of this work is in its integrated methodological approach which bridges the past to the present and contributes to the reconstruction of conceptual models of deep geothermal systems, thus favoring appropriate strategies for deep exploration. The Las Minas mining area (Veracruz State) where Cu-Fe-Au ore-deposits have been historically exploited, is considered as an exhumed Neogene geothermal system analogous to the deeper part of the Los Humeros geothermal field (Puebla State). We used an integrated approach, which involved structural and kinematic, petrological, geochemical, geochronological and fluid inclusion analyses of the pre-volcanic Paleozoic-Cretaceous succession, intruded by Miocene-Pliocene granitoids and mafic dykes. Our emphasis was on the (paleo) fluid-rocks interaction and the related structural control. The results indicate that saline and hypersaline fluids (up to 70 wt. % NaCl equiv.) of magmatic derivation and aqueous-carbonic fluids issued during metamorphic or metasomatic reactions with T up to 600-650°C were channeled along and in the intersection between the NW- and NE-trending faults and their damage zones. The faults are characterized by strike-slip to oblique-slip/normal movements. Fluids were also stored in carbonate rock-volumes at the contact with the granitoids. The distribution of the ore-deposits and hydrothermal alteration related to the interaction of geothermal fluids and hosting rocks indicates the importance of conduits (such as fractures and faults) in the reservoirs. Hence, understanding the relationships between ore-deposits, hydrothermal alteration and structures can increase our knowledge of the present geothermal fluids' deep circulation in the Los Humeros geothermal field.

Published
2021

49. Urban Investigations in the Heart of Rome: The Rome Transformed project

Author

Kay S., Haynes I., Liverani P., Piro S., Pomar E., and Morelli G.

Subjects
Rome Transformed Project, Electrical Resistivity Tomography, Ground Penetrating Radar, Integrated geophysical methods
Abstract

Rome Transformed' is a five-year ERC funded research project that began in 2019 with the aim of developing an understanding of Rome and its place in cultural change across the Mediterranean world by mapping political, military and religious changes to the eastern Caelian from the first to eight centuries. The project has brought together a team of specialists in non-invasive methodologies for the investigation of complex modern urban environments. Beginning with extensive archival and bibliographic research, the project is conducting detailed structural analysis of all the standing monuments in the area. This includes structures such as the Aurelian Walls, the Claudio-Neronian aqueduct and the Sessorian Palace complex. A central component of these investigations is the high-resolution geophysical prospection of the study area which covers around 13.7km2 in central Rome. The use of these non-invasive methodologies in central Rome led to several challenges, in particular the significant topographical changes that have occurred since antiquity. To the west, underneath the Basilica of Saint John Lateran, nine metres of vertical stratigraphy are preserved, ranging from Republican houses at the lower level through to the Castra Nova of Septimius Severus and the Constantine Basilica. This paper, as well as presenting preliminary results of the geophysical surveys, will also discuss some of the solutions for geophysical prospection in complex urban environments. For the study of the Eastern Caelian, the collation of information regarding previous excavations has been fundamental, which has been greatly assisted by a collaboration with the municipal authority archaeological service and access to their ArcheoSITAR database.

Published
2021

50. PCSK9 is associated with mortality in patients with septic shock: data from the ALBIOS study

Author

Vecchie, A., Bonaventura, A., Meessen, J., Novelli, D., Minetti, S., Elia, E., Ferrara, D., Ansaldo, A. M., Scaravilli, V., Villa, S., Ferla, L., Caironi, P., Latini, R., Carbone, F., Montecucco, F., Bruzzone, P., Pagan, F., Russo, R., Confalonieri, A., Abbruzzese, C., Vergnano, B., Faenza, S., Siniscalchi, A., Pierucci, E., Noto, A., Pezzi, A., Spanu, P., Parrini, V., Oggioni, R., Pasetti, G. S., Casadio, M. C., Buontempo, R., Carrer, S., Piccoli, F., Rizzi, T., Caricato, A., La Sala, M., Antonaci, A., Fassini, P., Paganini, S., Porta, V., Moise, G., Marell, S., Furia, M., Urbano, M. C., Carobbi, R., Poleni, S., Kandil, H., Ballotta, A., Bettini, F., Sanseverino, M., Gatta, A., Cecchini, F., Guatteri, L., Ciceri, G., Raimondi, F., Colombo, R., Ferraris, S., Borelli, M., Bellato, V., Cancellieri, F., Senni, S., Sacchi, N., Ferri, P., Moioli, G., Fedele, A., Molin, A., Salati, G., Salsi, P., Brunori, E., Elisei, D., Maggio, G., Nicola, F. G., Cavana, M., Morelli, G., Guarino, A., Isetta, M., Tulli, G., Mangani, V., Rossi, N., Ferrari, M., Bona, F., Vay, M., Bartoli, T., Gallo, M., Morte, M. D., Boselli, E., Puscio, D., Galzerano, A., Carli, M., and Zagara, G.

Subjects
0301 basic medicine, Male, medicine.medical_specialty, Inflammation, 030204 cardiovascular system & hematology, Gastroenterology, Sepsis, PCSK9, sepsis, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Settore MED/41 - ANESTESIOLOGIA, Internal Medicine, Medicine, Humans, pentraxin 3, Aged, business.industry, Proportional hazards model, Septic shock, Septic, Mortality rate, mortality, septic shock, Biomarkers, C-Reactive Protein, Female, Italy, Middle Aged, Proprotein Convertase 9, Serum Amyloid P-Component, Shock, Septic, Shock, PTX3, medicine.disease, 030104 developmental biology, Quartile, Biomarker (medicine), medicine.symptom, business
Abstract

Background Pro-protein convertase subtilisin/kexin 9 (PCSK9) is a proenzyme primarily known to regulate low-density lipoprotein receptor re-uptake on hepatocytes. Whether PCSK9 can concurrently trigger inflammation or not remains unclear. Here, we investigated the potential association between circulating levels of PCSK9 and mortality in patients with severe sepsis or septic shock. Methods Plasma PCSK9 levels at days 1, 2 and 7 were measured in 958 patients with severe sepsis or septic shock previously enrolled in the Albumin Italian Outcome Sepsis (ALBIOS) trial. Correlations between levels of PCSK9 and pentraxin 3 (PTX3), a biomarker of disease severity, were evaluated with ranked Spearman's coefficients. Cox proportional hazards models were used to assess the association of PCSK9 levels at day 1 with 28- and 90-day mortality. Results Median plasma PCSK9 levels were 278 [182-452] ng mL-1 on day 1. PCSK9 correlated positively with PTX3 at the three time-points, and patients with septic shock within the first quartile of PCSK9 showed higher levels of PTX3. Similar mortality rates were observed in patients with severe sepsis across PCSK9 quartiles. Patients with septic shock with lower PCSK9 levels on day 1 (within the first quartile) showed the highest 28- and 90-day mortality rate as compared to other quartiles. Conclusion In our sub-analysis of the ALBIOS trial, we found that patients with septic shock presenting with lower plasma PCSK9 levels experienced higher mortality rate. Further studies are warranted to better evaluate the pathophysiological role of PCSK9 in sepsis.

Published
2021

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