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5,307 results on '"Bonora"'

1. Individual upright physiological traits in an apple 'Guyot' training system

Author

Bortolotti, G., Perulli, G., Boini, A., Bresilla, K., Bonora, A., Venturi, M., Manfrini, L., Bortolotti, G., Perulli, G., Boini, A., Bresilla, K., Bonora, A., Venturi, M., and Manfrini, L.

Subjects
Horticulture, planar cordon, 2d canopy system, leaf gas exchanges, stem girdling, Precise Orchard Management (POM), Future Orchard Planting Systems (FOPS)
Published
2022

2. GRAd-COV2 vaccine provides potent and durable humoral and cellular immunity to SARS-CoV-2 in randomized placebo-controlled phase 2 trial

Author

Capone S., Fusco F. M., Milleri S., Borre S., Carbonara S., Lo Caputo S., Leone S., Gori G., Maggi P., Cascio A., Lichtner M., Cauda R., Dal Zoppo S., Cossu M. V., Gori A., Roda S., Confalonieri P., Bonora S., Missale G., Codeluppi M., Mezzaroma I., Capici S., Pontali E., Libanore M., Diani A., Lanini S., Battella S., Contino A. M., Piano Mortari E., Genova F., Parente G., Dragonetti R., Colloca S., Visani L., Iannacone C., Carsetti R., Folgori A., Camerini R., Ziviani L., Malescio F., Turrini I., Lawlor R., Romano A., Nunziata M., Armato S., Mazzeo N., Carleo M. A., Dell'Isola C., Pisapia R., Pontarelli A., Olivani A., Grasselli S., Laccabue D., Leoni M. C., Paolillo F., Mancini A., Ruaro B., Confalonieri M., Salton F., Mancarella G., Marocco R., De Masi M., Belvisi V., Lamonica S., Cingolani A., Seguiti C., Brambilla P., Ferraresi A., Lupi M., Ludovisi S., Renisi G., Massafra R., Pellicciotta M., Armiento L., Vimercati S., Piacenza M., Bonfanti P., Columpsi P., Cazzaniga M. E., Rovelli C., Ceresini M., Previtali L., Trentini L., Alcantarini C., Rugge W., Biffi S., Poletti F., Rostagno R., Moglia R., De Negri F., Fini E., Cangialosi A., Bruno S. R., Rizzo M., Niglio M., Stritto A. D., Matano A., Petruzziello A., Valsecchi P., Pieri T., Altamura M., Calamo A., Giannelli A., Menolascina S., Di Bari S., Mauro V., Aronica R., Segala D., Cultrera R., Sighinolfi L., Abbott M., Gizzi A., Marascia F. G., Valenti G., Feasi M., Bobbio N., Del Puente F., Nicosia A., Frasca M., Mazzoleni M., Garofalo N., Ammendola V., Grazioli F., Napolitano F., Vitelli A., Marcellini V., Capone, Stefania, Fusco, Francesco M, Milleri, Stefano, Borrè, Silvio, Carbonara, Sergio, Lo Caputo, Sergio, Leone, Sebastiano, Gori, Giovanni, Maggi, Paolo, Cascio, Antonio, Lichtner, Miriam, Cauda, Roberto, Dal Zoppo, Sarah, Cossu, Maria V, Gori, Andrea, Roda, Silvia, Confalonieri, Paola, Bonora, Stefano, Missale, Gabriele, Codeluppi, Mauro, Mezzaroma, Ivano, Capici, Serena, Pontali, Emanuele, Libanore, Marco, Diani, Augusta, Lanini, Simone, Battella, Simone, Contino, Alessandra M, Piano Mortari, Eva, Genova, Francesco, Parente, Gessica, Dragonetti, Rosella, Colloca, Stefano, Visani, Luigi, Iannacone, Claudio, Carsetti, Rita, Folgori, Antonella, Camerini, Roberto, Capone, S, Fusco, F, Milleri, S, Borre, S, Carbonara, S, Lo Caputo, S, Leone, S, Gori, G, Maggi, P, Cascio, A, Lichtner, M, Cauda, R, Dal Zoppo, S, Cossu, M, Gori, A, Roda, S, Confalonieri, P, Bonora, S, Missale, G, Codeluppi, M, Mezzaroma, I, Capici, S, Pontali, E, Libanore, M, Diani, A, Lanini, S, Battella, S, Contino, A, Piano Mortari, E, Genova, F, Parente, G, Dragonetti, R, Colloca, S, Visani, L, Iannacone, C, Carsetti, R, Folgori, A, Camerini, R, Ziviani, L, Malescio, F, Turrini, I, Lawlor, R, Romano, A, Nunziata, M, Armato, S, Mazzeo, N, Carleo, M, Dell'Isola, C, Pisapia, R, Pontarelli, A, Olivani, A, Grasselli, S, Laccabue, D, Leoni, M, Paolillo, F, Mancini, A, Ruaro, B, Confalonieri, M, Salton, F, Mancarella, G, Marocco, R, De Masi, M, Belvisi, V, Lamonica, S, Cingolani, A, Seguiti, C, Brambilla, P, Ferraresi, A, Lupi, M, Ludovisi, S, Renisi, G, Massafra, R, Pellicciotta, M, Armiento, L, Vimercati, S, Piacenza, M, Bonfanti, P, Columpsi, P, Cazzaniga, M, Rovelli, C, Ceresini, M, Previtali, L, Trentini, L, Alcantarini, C, Rugge, W, Biffi, S, Poletti, F, Rostagno, R, Moglia, R, De Negri, F, Fini, E, Cangialosi, A, Bruno, S, Rizzo, M, Niglio, M, Stritto, A, Matano, A, Petruzziello, A, Valsecchi, P, Pieri, T, Altamura, M, Calamo, A, Giannelli, A, Menolascina, S, Di Bari, S, Mauro, V, Aronica, R, Segala, D, Cultrera, R, Sighinolfi, L, Abbott, M, Gizzi, A, Marascia, F, Valenti, G, Feasi, M, Bobbio, N, Del Puente, F, Nicosia, A, Frasca, M, Mazzoleni, M, Garofalo, N, Ammendola, V, Grazioli, F, Napolitano, F, Vitelli, A, and Marcellini, V

Subjects
immunological memory, phase 2 clinical trial, safety, Sars-CoV-2 vaccine, COVID-19, CD8, T cell response, simian adenoviral vector, General Biochemistry, Genetics and Molecular Biology, CD4, neutralizing antibodie
Abstract

The ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic and heterologous immunization approaches implemented worldwide for booster doses call for diversified vaccine portfolios. GRAd-COV2 is a gorilla adenovirus-based COVID-19 vaccine candidate encoding prefusion-stabilized spike. The safety and immunogenicity of GRAd-COV2 is evaluated in a dose- and regimen-finding phase 2 trial (COVITAR study, ClinicalTrials.gov: NCT04791423) whereby 917 eligible participants are randomized to receive a single intramuscular GRAd-COV2 administration followed by placebo, or two vaccine injections, or two doses of placebo, spaced over 3weeks. Here, we report that GRAd-COV2 is well tolerated and induces robust immune responses after a single immunization; a second administration increases binding and neutralizing antibody titers. Potent, variant of concern (VOC) cross-reactive spike-specific Tcell response peaks after the first dose and is characterized by high frequencies of CD8s. Tcells maintain immediate effector functions and high proliferative potential over time. Thus, GRAd vector is a valuable platform for genetic vaccine development, especially when robust CD8 response is needed.

Published
2023

4. The ‘scientist’, the ‘analyst’ and the ‘novelist’: science or metrics?

Author

Enzo BONORA

Subjects
Endocrinology, Diabetes and Metabolism, Internal Medicine
Abstract

An overwhelming number of meta-analyses and reviews are published by scientific journals. In part this may reflect some preference of editors and publishers for these types of papers, which are more frequently cited and can increase the impact factor of their journals. Meta-analyses and reviews are also attractive for investigators looking for a greater chance of having successful publications with several citations, and therefore an improved personal h-index. This greater ‘promise of success’ might have a deleterious effect on the intellectual maturation of investigators, particularly early career investigators, who might neglect original research and concentrate their efforts on meta-analyses and reviews. However, while meta-analyses and reviews are useful for emphasising data and disseminating concepts, progress in science requires original ideas, original experiments and original papers. ‘Analysts’ and ‘novelists’ are welcome, but ‘scientists’ are indispensable.

Published
2022

6. Exploring the role of neutrophil-to-lymphocyte ratio and blood chemistry in head and neck adenoid cystic carcinomas treated with carbon ion radiotherapy

Author

Amelia Barcellini, Giulia Fontana, Daria Maria Filippini, Sara Ronchi, Maria Bonora, Barbara Vischioni, Rossana Ingargiola, Anna Maria Camarda, Pierre Loap, Nadia Facchinetti, Lisa Licitra, Guido Baroni, and Ester Orlandi

Subjects
Oncology, Radiology, Nuclear Medicine and imaging, Hematology
Abstract

In recent years, there is an emerging interest in the prognostic role of chemistry blood biomarkers in oncological patients but their role in adenoid cystic carcinomas (ACCs) is still unknown. This study aims to assess the prognostic significance of baseline neutrophil-to-lymphocyte ratio (NLR) and blood chemistry in a series of head and neck ACC patients treated with carbon ion radiotherapy (CIRT).We retrospectively retrieved the data of 49 consecutive head and neck ACC patients treated with CIRT. Univariable and multivariable Cox proportional hazard regression (Cox-ph) analyses were performed to look for a potential association of NLR, and other blood biomarker values, with disease-free survival (DFS), Local Control (LC), Metastasis Free Survival (MFS) and overall survival (OS).No significant association between NLR 2,5 and DFS, LC, MFS and OS was found with univariable analysis although a trend was reported for DFS (Hazard ratio [HR]: 2,10, 95 % CI: 0,85 - 5,08, p-value = 0,11). Patients with hemoglobin (hb) ≤ 14 g/dL showed significantly better DFS, MFS and OS. Multivariable regression Cox-ph analysis for DFS, adjusted for margin status, clinical target volume and Absolute Number of Monocytes, reported the following statistically significant HRs, for both NLR 2,5 and hb 14 g/dL respectively: 4,850 (95 % CI = 1,408 - 16,701, p = 0,012) and 3,032 (95 % CI = 1,095 - 8,393, p = 0,033). Moreover, hb 14 with HR = 3,69 (95 % CI: 1,23 - 11,07, p-value = 0,02), was a negative independent prognostic predictor for MFS.Pre-treatment NLR and hb values seem to be independent prognostic predictor for clinical outcomes in head and neck ACC patients. If their role will be validated in a larger prospective cohort, they might be worthwhile for a pre-treatment risk stratification in patients treated with CIRT.

Published
2022

7. Risk for non-AIDS-defining and AIDS-defining cancer of early versus delayed initiation of antiretroviral therapy

Author

Chammartin, F., Lodi, S., Logan, R., Ryom, L., Mocroft, A., Kirk, O., D'Arminio Monforte, A., Reiss, P., Phillips, A., El-Sadr, W., Hatleberg, C. I., Pradier, C., Bonnet, F., Law, M., De Wit, S., Sabin, C., Lundgren, J. D., Bucher, H. C., Calvo, G., Dabis, F., Morfeldt, L., Weber, R., Lind-Thomsen, A., Salbol Brandt, R., Hillebreght, M., Zaheri, S., Wit, F. W. N. M., Scherrer, A., Schoni-Affolter, F., Rickenbach, M., Tavelli, A., Fanti, I., Leleux, O., Mourali, J., Le Marec, F., Boerg, E., Thulin, E., Sundstrom, A., Bartsch, G., Thompsen, G., Necsoi, C., Delforge, M., Fontas, E., Caissotti, C., Dollet, K., Mateu, S., Torres, F., Petoumenos, K., Blance, A., Huang, R., Puhr, R., Gronborg Laut, K., Kristensen, D., Kamara, D. A., Smith, C. J., Raben, D., Matthews, C., Bojesen, A., Grevsen, A. L., Powderly, B., Shortman, N., Moecklinghoff, C., Reilly, G., Smit, C., Ross, M., Fux, C. A., Morlat, P., Friis-Moller, N., Kowalska, J., Bohlius, J., Bower, M., Fatkenheuer, G., Grulich, A., Sjol, A., Meidahl, P., Iversen, J. S., Hillebregt, M., Prins, J. M., Kuijpers, T. W., Scherpbier, H. J., Van Der Meer, J. T. M., Godfried, M. H., Van Der Poll, T., Nellen, F. J. B., Geerlings, S. E., Van Vugt, M., Pajkrt, D., Bos, J. C., Wiersinga, W. J., Van Der Valk, M., Goorhuis, A., Hovius, J. W., Van Eden, J., Henderiks, A., Van Hes, A. M. H., Mutschelknauss, M., Nobel, H. E., Pijnappel, F. J. J., Jurriaans, S., Back, N. K. T., Zaaijer, H. L., Berkhout, B., Cornelissen, M. T. E., Schinkel, C. J., Thomas, X. V., Van Den Berge, M., Stegeman, A., Baas, S., Hage De Looff, L., Versteeg, D., Pronk, M. J. H., Ammerlaan, H. S. M., de Munnik, E. S., Jansz, A. R., Tjhie, J., Wegdam, M. C. A., Deiman, B., Scharnhorst, V., Van Der Plas, A., Weijsenfeld, A. M., Van Der Ende, M. E., de Vries-Sluijs, T. E. M. S., van Gorp, E. C. M., Schurink, C. A. M., Nouwen, J. L., Verbon, A., Rijnders, B. J. A., Bax, H. I., Van Der Feltz, M., Bassant, N., Van Beek, J. E. A., Vriesde, M., Van Zonneveld, L. M., De Oude-Lubbers, A., Van Den Berg-Cameron, H. J., Bruinsma-Broekman, F. B., de Groot, J., De Zeeuw-De Man, M., Boucher, C. A. B., Koopmans, M. P. G., van Kampen, J. J. A., Pas, S. D., Driessen, G. J. A., van Rossum, A. M. C., Van Der Knaap, L. C., Visser, E., Branger, J., Rijkeboer-Mes, A., Duijf-Van De Ven, C. J. H. M., Schippers, E. F., van Nieuwkoop, C., van IJperen, J. M., Geilings, J., van der Hut, G., Franck, P. F. H., Van Eeden, A., Brokking, W., Groot, M., Elsenburg, L. J. M., Damen, M., Kwa, I. S., Groeneveld, P. H. P., Bouwhuis, J. W., Van Den Berg, J. F., Van Hulzen, A. G. W., Van Der Bliek, G. L., Bor, P. C. J., Bloembergen, P., Wolfhagen, M. J. H. M., Ruijs, G. J. H. M., Kroon, F. P., De Boer, M. G. J., Bauer, M. P., Jolink, H., Vollaard, A. M., Dorama, W., Van Holten, N., Claas, E. C. J., Wessels, E., Den Hollander, J. G., Pogany, K., Roukens, A., Kastelijns, M., Smit, J. V., Smit, E., Struik-Kalkman, D., Tearno, C., Bezemer, M., van Niekerk, T., Pontesilli, O., Lowe, S. H., Oude Lashof, A. M. L., Posthouwer, D., Ackens, R. P., Schippers, J., Vergoossen, R., Weijenberg-Maes, B., van Loo, I. H. M., Havenith, T. R. A., Leyten, E. M. S., Gelinck, L. B. S., van Hartingsveld, A., Meerkerk, C., Wildenbeest, G. S., Mutsaers, J. A. E. M., Jansen, C. L., Mulder, J. W., Vrouenraets, S. M. E., Lauw, F. N., van Broekhuizen, M. C., Paap, H., Vlasblom, D. J., Smits, P. H. M., Weijer, S., El Moussaoui, R., Bosma, A. S., van Vonderen, M. G. A., van Houte, D. P. F., Kampschreur, L. M., Dijkstra, K., Faber, S., Weel, J., Kootstra, G. J., Delsing, C. E., van der Burg-Van de Plas, M., Heins, H., Lucas, E., Kortmann, W., van Twillert, G., Cohen Stuart, J. W. T., Diederen, B. M. W., van Truijen-Oud, F. A., van der Reijden, W. A., Jansen, R., Brinkman, K., van den Berk, G. E. L., Blok, W. L., Frissen, P. H. J., Lettinga, K. D., Schouten, W. E. M., Veenstra, J., Brouwer, J. C., Geerders, F. G., Hoeksema, K., Kleene, J. M., van der Meche, B. I., Spelbrink, M., Sulman, H., Toonen, A. J. M., Wijnands, S., Kwa, D., Witte, E., Koopmans, P. P., Keuter, M., van der Ven, A. J. A. M., ter Hofstede, H. J. M., Dofferhoff, A. S. M., van Crevel, R., Albers, M., Bosch, M. E. W., Grintjes-Huisman, K. J. T., Zomer, J. B., Stelma, F. F., Rahamat-Langendoen, J., Burger, D., Richter, C., Gisolf, H. E., Hassing, J. R., ter Beest, G., van Bentum, P. H. M., Langebeek, N., Tiemessen, R., Swanink, C. M. A., van Lelyveld, S. F. L., Soetekouw, R., Hulshoff, N., van der Prijt, L. M. M., van der Swaluw, J., Bermon, N., Herpers, B. L., Veenendaal, D., Verhagen, W. D. M., van Wijk, M., van Kasteren, M. E. E., Brouwer, E. A., de Kruijf-Van de Wiel, B. A. F. M., Kuipers, M., Santegoets, R. M. W. J., van der Ven, B., Marcelis, H. J., Buiting, A. G. M., Kabel, J. P., Bierman, W. F. W., Scholvinck, H., Wilting, R. K., Stienstra, Y., de Groot-De Jonge, H., van der Meulen, A. P., de Weerd, A. D., Ludwig-Roukema, J., Niesters, H. G. M., Riezebos-Brilman, A., van Leer-Buter, C. C., Knoester, M., Hoepelman, A. I. M., Mudrikova, T., Ellerbroek, M. P., Oosterheert, J. J., Arends, E. J., Barth, E. R., Wassenberg, M. W. M., Schadd, M. E., van Elst-Laurijssen, D. H. M., van Oers-Hazelzet, B. E., Vervoort, S., van Berkel, M., Schuurman, R., Verduyn-Lunel, F., Wensing, A. M. J., Peters, E. J. G., van Agtmael, A. M., Bomers, M., de Vocht, J., Heitmuller, M., Laan, M. L., Pettersson, M. A., Vandenbroucke-Grauls, C. M. J. E., Ang, W. C., Geelen, S. P. M., Wolfs, T. F. W., Bont, J. L., Nauta, N., Bezemer, O. D., van Sighem, I. A., Boender, S. T., de Jong, A., Bergsma, D., Hoekstra, P., de Lang, A., Grivell, S., Jansen, A., Rademaker, J. M., Raethke, M., Meijering, R., Schnorr, S., de Groot, L., van den Akker, M., Bakker, Y., Claessen, E., El Berkaoui, A., Koops, J., Kruijne, E., Lodewijk, C., Munjishvili, L., Peeck, B., Ree, C., Regtop, R., Ruijs, Y., Rutkens, T., van de Sande, L., Schoorl, M., Timmerman, A., Tuijn, E., Veenenberg, L., van der Vliet, S., Wisse, A., Woudstra, T., Tuk, B., Dupon, M., Gaborieau, V., Lacoste, D., Malvy, D., Mercie, P., Neau, D., Pellegrin, L. J., Tchamgoue, S., Lazaro, E., Cazanave, C., Vandenhende, M., Vareil, O. M., Gerard, Y., Blanco, P., Bouchet, S., Breilh, D., Fleury, H., Pellegrin, I., Chene, G., Thiebaut, R., Wittkop, L., Lawson-Ayayi, S., Gimbert, A., Desjardin, S., Lacaze-Buzy, L., Petrov-Sanchez, V., Andre, N., Bernard, K., Caubet, O., Caunegre, L., Chossat, I., Courtault, C., Dauchy, A. F., Dondia, D., Duffau, P., Dutronc, H., Farbos, S., Faure, I., Ferrand, H., Greib, C., Hessamfar, M., Imbert, Y., Lataste, P., Marie, J., Mechain, M., Monlun, E., Ochoa, A., Pistone, T., Raymond, I., Receveur, C. M., Rispal, P., Sorin, L., Valette, C., Viallard, J. F., Wille, H., Wirth, G., Lafon, M., Trimoulet, P., Bellecave, P., Tumiotto, C., Haramburu, F., Miremeont-Salame, G., Blaizeau, J. M., Decoin, M., Hannapier, C., Lenaud, E., Pougetoux, A., Delveaux, S., D'Ivernois, C., Diarra, F., Uwamaliya-Nziyumvira, B., Palmer, G., Conte, V., Sapparrart, V., Moore, R., Edwards, S., Hoy, J., Watson, K., Roth, N., Lau, H., Bloch, M., Baker, D., Carr, A., Cooper, D., O'Sullivan, M., Nolan, D., Guelfi, G., Domingo, P., Sambeat, A. M., Gatell, J., Del Cacho, E., Cadafalch, J., Fuster, M., Codina, C., Sirera, G., Vaque, A., Clumeck, N., Gennotte, F. A., Gerard, M., Kabeya, K., Konopnicki, D., Libois, A., Martin, C., Payen, C. M., Semaille, P., Van Laethem, Y., Neaton, J., El-Sadr, M. W., Krum, E., Thompson, G., Wentworth, D., Luskin-Hawk, R., Telzak, E., Abrams, I. D., Cohn, D., Markowitz, N., Arduino, R., Mushatt, D., Friedland, G., Perez, G., Tedaldi, E., Fisher, E., Gordin, F., Crane, R. L., Sampson, J., Baxter, J., Gazzard, B., Horban, A., Karpov, I., Pedersen, C., Ristola, M., Rockstroh, J., Peters, L., Fischer, H. A., Larsen, F. J., Podlekareva, D., Cozzi-Lepri, A., Shepherd, L., Schultze, A., Amele, S., Losso, M., Kundro, M., Schmied, B., Zangerle, R., Vassilenko, A., Mitsura, M. V., Paduto, D., Florence, E., Vandekerckhove, L., Hadziosmanovic, V., Begovac, J., Machala, L., Jilich, D., Sedlacek, D., Kronborg, G., Benfield, T., Gerstoft, J., Katzenstein, T., Moller, F. N., Ostergaard, L., Wiese, L., Nielsen, N. L., Zilmer, K., Smidt, J., Aho, I., Viard, J. P., Girard, P. M., Duvivier, C., Schmidt, R., Degen, O., Stellbrink, J. H., Stefan, C., Bogner, J., Chkhartishvili, N., Gargalianos, P., Xylomenos, G., Armenis, K., Sambatakou, H., Szlavik, J., Gottfredsson, M., Mulcahy, F., Yust, I., Turner, D., Burke, M., Shahar, E., Hassoun, G., Elinav, H., Haouzi, M., Elbirt, D., Sthoeger, M. Z., Esposito, R., Mazeu, I., Mussini, C., Mazzotta, F., Gabbuti, A., Vullo, V., Lichtner, M., Zaccarelli, M., Antinori, A., Acinapura, R., Plazzi, M., Lazzarin, A., Castagna, A., Gianotti, N., Galli, M., Ridolfo, A., Rozentale, B., Uzdaviniene, V., Matulionyte, R., Staub, T., Hemmer, R., Ormaasen, V., Maeland, A., Bruun, J., Knysz, B., Gasiorowski, J., Inglot, M., Bakowska, E., Flisiak, R., Grzeszczuk, A., Parczewski, M., Maciejewska, K., Aksak-Was, B., Beniowski, M., Mularska, E., Smiatacz, T., Gensing, M., Jablonowska, E., Malolepsza, E., Wojcik, K., Mozer-Lisewska, I., Caldeira, L., Mansinho, K., Maltez, F., Radoi, R., Oprea, C., Panteleev, A., Panteleev, O., Yakovlev, A., Trofimora, T., Khromova, I., Kuzovatova, E., Borodulina, E., Vdoushkina, E., Jevtovic, D., Tomazic, J., Miro, M. J., Moreno, S., Rodriguez, J. M., Clotet, B., Jou, A., Paredes, R., Tural, C., Puig, J., Bravo, I., Gutierrez, M., Mateo, G., Laporte, M. J., Falconer, K., Thalme, A., Sonnerborg, A., Blaxhult, A., Flamholc, L., Cavassini, M., Calmy, A., Furrer, H., Battegay, M., Schmid, P., Kuznetsova, A., Kyselyova, G., Sluzhynska, M., Johnson, A. M., Simons, E., Orkin, C., Weber, J., Scullard, G., Clarke, A., Leen, C., Thulin, G., Akerlund, B., Koppel, K., Karlsson, A., Hakangard, C., Castelli, F., Cauda, R., Di Perri, G., Iardino, R., Ippolito, G., Marchetti, C. G., Perno, F. C., von Schloesser, F., Viale, P., Ceccherini-Silberstein, F., Girardi, E., Lo Caputo, S., Puoti, M., Andreoni, M., Ammassari, A., Balotta, C., Bandera, A., Bonfanti, P., Bonora, S., Borderi, M., Calcagno, A., Calza, L., Capobianchi, R. M., Cingolani, A., Cinque, P., De Luca, A., Di Biagio, A., Gori, A., Guaraldi, G., Lapadula, G., Madeddu, G., Maggiolo, F., Marcotullio, S., Monno, L., Nozza, S., Quiros Roldan, E., Rossotti, R., Rusconi, S., Santoro, M. M., Saracino, A., Galli, L., Lorenzini, P., Rodano, A., Shanyinde, M., Carletti, F., Carrara, S., Di Caro, A., Graziano, S., Petrone, F., Prota, G., Quartu, S., Truffa, S., Giacometti, A., Costantini, A., Barocci, V., Angarano, G., Santoro, C., Suardi, C., Donati, V., Verucchi, G., Minardi, C., Quirino, T., Abeli, C., Manconi, E. P., Piano, P., Cacopardo, B., Celesia, B., Vecchiet, J., Falasca, K., Pan, A., Lorenzotti, S., Sighinolfi, L., Segala, D., Vichi, F., Cassola, G., Viscoli, C., Alessandrini, A., Bobbio, N., Mazzarello, G., Mastroianni, C., Belvisi, V., Caramma, I., Chiodera, A., Milini, P., Rizzardini, G., Moioli, C. M., Piolini, R., Ridolfo, L. A., Salpietro, S., Tincati, C., Puzzolante, C., Abrescia, N., Chirianni, A., Borgia, G., Orlando, R., Bonadies, G., Di Martino, F., Gentile, I., Maddaloni, L., Cattelan, M. A., Marinello, S., Cascio, A., Colomba, C., Baldelli, F., Schiaroli, E., Parruti, G., Sozio, F., Magnani, G., Ursitti, A. M., Cristaudo, A., Baldin, G., Capozzi, M., Cicalini, S., Fontanelli Sulekova, L., Iaiani, G., Latini, A., Mastrorosa, I., Savinelli, S., Vergori, A., Cecchetto, M., Viviani, F., Bagella, P., Rossetti, B., Franco, A., Fontana Del Vecchio, R., Francisci, D., Di Giuli, C., Caramello, P., Orofino, C. G., Sciandra, M., Bassetti, M., Londero, A., Pellizzer, G., Manfrin, V., Starnini, G., Ialungo, A., Dellamonica, P., Bernard, E., Courjon, J., Cua, E., De Salvador-Guillouet, F., Durant, J., Etienne, C., Ferrando, S., Mondain-Miton, V., Naqvi, A., Perbost, I., Pillet, S., Prouvost-Keller, B., Pugliese, P., Rio, V., Risso, K., Roger, M. P., Aubert, V., Bernasconi, E., Ciuffi, A., Dollenmaier, G., Egger, M., Elzi, L., Fehr, J., Fellay, J., Gunthard, F. H., Haerry, D., Hasse, B., Hirsch, H. H., Hoffmann, M., Hosli, I., Kahlert, C., Kaiser, L., Keiser, O., Klimkait, T., Kouyos, D. R., Kovari, H., Ledergerber, B., Martinetti, G., Martinez de Tejada, B., Marzolini, C., Metzner, J. K., Muller, N., Nicca, D., Pantaleo, G., Paioni, P., Rauch, A., Rudin, C., Speck, R., Stockle, M., Tarr, P., Trkola, A., Vernazza, P., Wandeler, G., Yerly, S., Global Health, Infectious diseases, AII - Infectious diseases, APH - Aging & Later Life, Chammartin F., Lodi S., Logan R., Ryom L., Mocroft A., Kirk O., D'Arminio Monforte A., Reiss P., Phillips A., El-Sadr W., Hatleberg C.I., Pradier C., Bonnet F., Law M., De Wit S., Sabin C., Lundgren J.D., Bucher H.C., Calvo G., Dabis F., Morfeldt L., Weber R., Lind-Thomsen A., Salbol Brandt R., Hillebreght M., Zaheri S., Wit F.W.N.M., Scherrer A., Schoni-Affolter F., Rickenbach M., Tavelli A., Fanti I., Leleux O., Mourali J., Le Marec F., Boerg E., Thulin E., Sundstrom A., Bartsch G., Thompsen G., Necsoi C., Delforge M., Fontas E., Caissotti C., Dollet K., Mateu S., Torres F., Petoumenos K., Blance A., Huang R., Puhr R., Gronborg Laut K., Kristensen D., Kamara D.A., Smith C.J., Raben D., Matthews C., Bojesen A., Grevsen A.L., Powderly B., Shortman N., Moecklinghoff C., Reilly G., Smit C., Ross M., Fux C.A., Morlat P., Friis-Moller N., Kowalska J., Bohlius J., Bower M., Fatkenheuer G., Grulich A., Sjol A., Meidahl P., Iversen J.S., Hillebregt M., Prins J.M., Kuijpers T.W., Scherpbier H.J., Van Der Meer J.T.M., Godfried M.H., Van Der Poll T., Nellen F.J.B., Geerlings S.E., Van Vugt M., Pajkrt D., Bos J.C., Wiersinga W.J., Van Der Valk M., Goorhuis A., Hovius J.W., Van Eden J., Henderiks A., Van Hes A.M.H., Mutschelknauss M., Nobel H.E., Pijnappel F.J.J., Jurriaans S., Back N.K.T., Zaaijer H.L., Berkhout B., Cornelissen M.T.E., Schinkel C.J., Thomas X.V., Van Den Berge M., Stegeman A., Baas S., Hage De Looff L., Versteeg D., Pronk M.J.H., Ammerlaan H.S.M., de Munnik E.S., Jansz A.R., Tjhie J., Wegdam M.C.A., Deiman B., Scharnhorst V., Van Der Plas A., Weijsenfeld A.M., Van Der Ende M.E., de Vries-Sluijs T.E.M.S., van Gorp E.C.M., Schurink C.A.M., Nouwen J.L., Verbon A., Rijnders B.J.A., Bax H.I., Van Der Feltz M., Bassant N., Van Beek J.E.A., Vriesde M., Van Zonneveld L.M., De Oude-Lubbers A., Van Den Berg-Cameron H.J., Bruinsma-Broekman F.B., de Groot J., De Zeeuw-De Man M., Boucher C.A.B., Koopmans M.P.G., van Kampen J.J.A., Pas S.D., Driessen G.J.A., van Rossum A.M.C., Van Der Knaap L.C., Visser E., Branger J., Rijkeboer-Mes A., Duijf-Van De Ven C.J.H.M., Schippers E.F., van Nieuwkoop C., van IJperen J.M., Geilings J., van der Hut G., Franck P.F.H., Van Eeden A., Brokking W., Groot M., Elsenburg L.J.M., Damen M., Kwa I.S., Groeneveld P.H.P., Bouwhuis J.W., Van Den Berg J.F., Van Hulzen A.G.W., Van Der Bliek G.L., Bor P.C.J., Bloembergen P., Wolfhagen M.J.H.M., Ruijs G.J.H.M., Kroon F.P., De Boer M.G.J., Bauer M.P., Jolink H., Vollaard A.M., Dorama W., Van Holten N., Claas E.C.J., Wessels E., Den Hollander J.G., Pogany K., Roukens A., Kastelijns M., Smit J.V., Smit E., Struik-Kalkman D., Tearno C., Bezemer M., van Niekerk T., Pontesilli O., Lowe S.H., Oude Lashof A.M.L., Posthouwer D., Ackens R.P., Schippers J., Vergoossen R., Weijenberg-Maes B., van Loo I.H.M., Havenith T.R.A., Leyten E.M.S., Gelinck L.B.S., van Hartingsveld A., Meerkerk C., Wildenbeest G.S., Mutsaers J.A.E.M., Jansen C.L., Mulder J.W., Vrouenraets S.M.E., Lauw F.N., van Broekhuizen M.C., Paap H., Vlasblom D.J., Smits P.H.M., Weijer S., El Moussaoui R., Bosma A.S., van Vonderen M.G.A., van Houte D.P.F., Kampschreur L.M., Dijkstra K., Faber S., Weel J., Kootstra G.J., Delsing C.E., van der Burg-Van de Plas M., Heins H., Lucas E., Kortmann W., van Twillert G., Cohen Stuart J.W.T., Diederen B.M.W., van Truijen-Oud F.A., van der Reijden W.A., Jansen R., Brinkman K., van den Berk G.E.L., Blok W.L., Frissen P.H.J., Lettinga K.D., Schouten W.E.M., Veenstra J., Brouwer J.C., Geerders F.G., Hoeksema K., Kleene J.M., van der Meche B.I., Spelbrink M., Sulman H., Toonen A.J.M., Wijnands S., Kwa D., Witte E., Koopmans P.P., Keuter M., van der Ven A.J.A.M., ter Hofstede H.J.M., Dofferhoff A.S.M., van Crevel R., Albers M., Bosch M.E.W., Grintjes-Huisman K.J.T., Zomer J.B., Stelma F.F., Rahamat-Langendoen J., Burger D., Richter C., Gisolf H.E., Hassing J.R., ter Beest G., van Bentum P.H.M., Langebeek N., Tiemessen R., Swanink C.M.A., van Lelyveld S.F.L., Soetekouw R., Hulshoff N., van der Prijt L.M.M., van der Swaluw J., Bermon N., Herpers B.L., Veenendaal D., Verhagen W.D.M., van Wijk M., van Kasteren M.E.E., Brouwer E.A., de Kruijf-Van de Wiel B.A.F.M., Kuipers M., Santegoets R.M.W.J., van der Ven B., Marcelis H.J., Buiting A.G.M., Kabel J.P., Bierman W.F.W., Scholvinck H., Wilting R.K., Stienstra Y., de Groot-De Jonge H., van der Meulen A.P., de Weerd A.D., Ludwig-Roukema J., Niesters H.G.M., Riezebos-Brilman A., van Leer-Buter C.C., Knoester M., Hoepelman A.I.M., Mudrikova T., Ellerbroek M.P., Oosterheert J.J., Arends E.J., Barth E.R., Wassenberg M.W.M., Schadd M.E., van Elst-Laurijssen D.H.M., van Oers-Hazelzet B.E., Vervoort S., van Berkel M., Schuurman R., Verduyn-Lunel F., Wensing A.M.J., Peters E.J.G., van Agtmael A.M., Bomers M., de Vocht J., Heitmuller M., Laan M.L., Pettersson M.A., Vandenbroucke-Grauls C.M.J.E., Ang W.C., Geelen S.P.M., Wolfs T.F.W., Bont J.L., Nauta N., Bezemer O.D., van Sighem I.A., Boender S.T., de Jong A., Bergsma D., Hoekstra P., de Lang A., Grivell S., Jansen A., Rademaker J.M., Raethke M., Meijering R., Schnorr S., de Groot L., van den Akker M., Bakker Y., Claessen E., El Berkaoui A., Koops J., Kruijne E., Lodewijk C., Munjishvili L., Peeck B., Ree C., Regtop R., Ruijs Y., Rutkens T., van de Sande L., Schoorl M., Timmerman A., Tuijn E., Veenenberg L., van der Vliet S., Wisse A., Woudstra T., Tuk B., Dupon M., Gaborieau V., Lacoste D., Malvy D., Mercie P., Neau D., Pellegrin L.J., Tchamgoue S., Lazaro E., Cazanave C., Vandenhende M., Vareil O.M., Gerard Y., Blanco P., Bouchet S., Breilh D., Fleury H., Pellegrin I., Chene G., Thiebaut R., Wittkop L., Lawson-Ayayi S., Gimbert A., Desjardin S., Lacaze-Buzy L., Petrov-Sanchez V., Andre N., Bernard K., Caubet O., Caunegre L., Chossat I., Courtault C., Dauchy A.F., Dondia D., Duffau P., Dutronc H., Farbos S., Faure I., Ferrand H., Greib C., Hessamfar M., Imbert Y., Lataste P., Marie J., Mechain M., Monlun E., Ochoa A., Pistone T., Raymond I., Receveur C.M., Rispal P., Sorin L., Valette C., Viallard J.F., Wille H., Wirth G., Lafon M., Trimoulet P., Bellecave P., Tumiotto C., Haramburu F., Miremeont-Salame G., Blaizeau J.M., Decoin M., Hannapier C., Lenaud E., Pougetoux A., Delveaux S., D'Ivernois C., Diarra F., Uwamaliya-Nziyumvira B., Palmer G., Conte V., Sapparrart V., Moore R., Edwards S., Hoy J., Watson K., Roth N., Lau H., Bloch M., Baker D., Carr A., Cooper D., O'Sullivan M., Nolan D., Guelfi G., Domingo P., Sambeat A.M., Gatell J., Del Cacho E., Cadafalch J., Fuster M., Codina C., Sirera G., Vaque A., Clumeck N., Gennotte F.A., Gerard M., Kabeya K., Konopnicki D., Libois A., Martin C., Payen C.M., Semaille P., Van Laethem Y., Neaton J., El-Sadr M.W., Krum E., Thompson G., 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O, D'Arminio Monforte, A, Reiss, P, Phillips, A, El-Sadr, W, Hatleberg, C, Pradier, C, Bonnet, F, Law, M, De Wit, S, Sabin, C, Lundgren, J, Bucher, H, Calvo, G, Dabis, F, Morfeldt, L, Weber, R, Lind-Thomsen, A, Salbol Brandt, R, Hillebreght, M, Zaheri, S, Wit, F, Scherrer, A, Schoni-Affolter, F, Rickenbach, M, Tavelli, A, Fanti, I, Leleux, O, Mourali, J, Le Marec, F, Boerg, E, Thulin, E, Sundstrom, A, Bartsch, G, Thompsen, G, Necsoi, C, Delforge, M, Fontas, E, Caissotti, C, Dollet, K, Mateu, S, Torres, F, Petoumenos, K, Blance, A, Huang, R, Puhr, R, Gronborg Laut, K, Kristensen, D, Kamara, D, Smith, C, Raben, D, Matthews, C, Bojesen, A, Grevsen, A, Powderly, B, Shortman, N, Moecklinghoff, C, Reilly, G, Smit, C, Ross, M, Fux, C, Morlat, P, Friis-Moller, N, Kowalska, J, Bohlius, J, Bower, M, Fatkenheuer, G, Grulich, A, Sjol, A, Meidahl, P, Iversen, J, Hillebregt, M, Prins, J, Kuijpers, T, Scherpbier, H, Van Der Meer, J, Godfried, M, Van Der Poll, T, Nellen, F, Geerlings, S, Van Vugt, M, 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M, Elsenburg, L, Damen, M, Kwa, I, Groeneveld, P, Bouwhuis, J, Van Den Berg, J, Van Hulzen, A, Van Der Bliek, G, Bor, P, Bloembergen, P, Wolfhagen, M, Ruijs, G, Kroon, F, De Boer, M, Bauer, M, Jolink, H, Vollaard, A, Dorama, W, Van Holten, N, Claas, E, Wessels, E, Den Hollander, J, Pogany, K, Roukens, A, Kastelijns, M, Smit, J, Smit, E, Struik-Kalkman, D, Tearno, C, Bezemer, M, van Niekerk, T, Pontesilli, O, Lowe, S, Oude Lashof, A, Posthouwer, D, Ackens, R, Schippers, J, Vergoossen, R, Weijenberg-Maes, B, van Loo, I, Havenith, T, Leyten, E, Gelinck, L, van Hartingsveld, A, Meerkerk, C, Wildenbeest, G, Mutsaers, J, Jansen, C, Mulder, J, Vrouenraets, S, Lauw, F, van Broekhuizen, M, Paap, H, Vlasblom, D, Smits, P, Weijer, S, El Moussaoui, R, Bosma, A, van Vonderen, M, van Houte, D, Kampschreur, L, Dijkstra, K, Faber, S, Weel, J, Kootstra, G, Delsing, C, van der Burg-Van de Plas, M, Heins, H, Lucas, E, Kortmann, W, van Twillert, G, Cohen Stuart, J, Diederen, B, van Truijen-Oud, F, van der Reijden, W, Jansen, R, Brinkman, K, van den Berk, G, Blok, W, Frissen, P, Lettinga, K, Schouten, W, Veenstra, J, Brouwer, J, Geerders, F, Hoeksema, K, Kleene, J, van der Meche, B, Spelbrink, M, Sulman, H, Toonen, A, Wijnands, S, Kwa, D, Witte, E, Koopmans, P, Keuter, M, van der Ven, A, ter Hofstede, H, Dofferhoff, A, van Crevel, R, Albers, M, Bosch, M, Grintjes-Huisman, K, Zomer, J, Stelma, F, Rahamat-Langendoen, J, Burger, D, Richter, C, Gisolf, H, Hassing, J, ter Beest, G, van Bentum, P, Langebeek, N, Tiemessen, R, Swanink, C, van Lelyveld, S, Soetekouw, R, Hulshoff, N, van der Prijt, L, van der Swaluw, J, Bermon, N, Herpers, B, Veenendaal, D, Verhagen, W, van Wijk, M, van Kasteren, M, Brouwer, E, de Kruijf-Van de Wiel, B, Kuipers, M, Santegoets, R, van der Ven, B, Marcelis, H, Buiting, A, Kabel, J, Bierman, W, Scholvinck, H, Wilting, R, Stienstra, Y, de Groot-De Jonge, H, van der Meulen, A, de Weerd, A, Ludwig-Roukema, J, Niesters, H, Riezebos-Brilman, A, van Leer-Buter, C, Knoester, M, Hoepelman, A, Mudrikova, T, Ellerbroek, M, Oosterheert, J, Arends, E, Barth, E, Wassenberg, M, Schadd, M, van Elst-Laurijssen, D, van Oers-Hazelzet, B, Vervoort, S, van Berkel, M, Schuurman, R, Verduyn-Lunel, F, Wensing, A, Peters, E, van Agtmael, A, Bomers, M, de Vocht, J, Heitmuller, M, Laan, M, Pettersson, M, Vandenbroucke-Grauls, C, Ang, W, Geelen, S, Wolfs, T, Bont, J, Nauta, N, Bezemer, O, van Sighem, I, Boender, S, de Jong, A, Bergsma, D, Hoekstra, P, de Lang, A, Grivell, S, Jansen, A, Rademaker, J, Raethke, M, Meijering, R, Schnorr, S, de Groot, L, van den Akker, M, Bakker, Y, Claessen, E, El Berkaoui, A, Koops, J, Kruijne, E, Lodewijk, C, Munjishvili, L, Peeck, B, Ree, C, Regtop, R, Ruijs, Y, Rutkens, T, van de Sande, L, Schoorl, M, Timmerman, A, Tuijn, E, Veenenberg, L, van der Vliet, S, Wisse, A, Woudstra, T, Tuk, B, Dupon, M, Gaborieau, V, Lacoste, D, Malvy, D, Mercie, P, Neau, D, Pellegrin, L, Tchamgoue, S, Lazaro, E, Cazanave, C, Vandenhende, M, Vareil, O, Gerard, Y, Blanco, P, Bouchet, S, Breilh, D, Fleury, H, Pellegrin, I, Chene, G, Thiebaut, R, Wittkop, L, Lawson-Ayayi, S, Gimbert, A, Desjardin, S, Lacaze-Buzy, L, Petrov-Sanchez, V, Andre, N, Bernard, K, Caubet, O, Caunegre, L, Chossat, I, Courtault, C, Dauchy, A, Dondia, D, Duffau, P, Dutronc, H, Farbos, S, Faure, I, Ferrand, H, Greib, C, Hessamfar, M, Imbert, Y, Lataste, P, Marie, J, Mechain, M, Monlun, E, Ochoa, A, Pistone, T, Raymond, I, Receveur, C, Rispal, P, Sorin, L, Valette, C, Viallard, J, Wille, H, Wirth, G, Lafon, M, Trimoulet, P, Bellecave, P, Tumiotto, C, Haramburu, F, Miremeont-Salame, G, Blaizeau, J, Decoin, M, Hannapier, C, Lenaud, E, Pougetoux, A, Delveaux, S, D'Ivernois, C, Diarra, F, Uwamaliya-Nziyumvira, B, Palmer, G, Conte, V, Sapparrart, V, Moore, R, Edwards, S, Hoy, J, Watson, K, Roth, N, Lau, H, Bloch, M, Baker, D, Carr, A, Cooper, D, O'Sullivan, M, Nolan, D, Guelfi, G, Domingo, P, Sambeat, A, Gatell, J, Del Cacho, E, Cadafalch, J, Fuster, M, Codina, C, Sirera, G, Vaque, A, Clumeck, N, Gennotte, F, Gerard, M, Kabeya, K, Konopnicki, D, Libois, A, Martin, C, Payen, C, Semaille, P, Van Laethem, Y, Neaton, J, El-Sadr, M, Krum, E, Thompson, G, Wentworth, D, Luskin-Hawk, R, Telzak, E, Abrams, I, Cohn, D, Markowitz, N, Arduino, R, Mushatt, D, Friedland, G, Perez, G, Tedaldi, E, Fisher, E, Gordin, F, Crane, R, Sampson, J, Baxter, J, Gazzard, B, Horban, A, Karpov, I, Pedersen, C, Ristola, M, Rockstroh, J, Peters, L, Fischer, H, Larsen, F, Podlekareva, D, Cozzi-Lepri, A, Shepherd, L, Schultze, A, Amele, S, Losso, M, Kundro, M, Schmied, B, Zangerle, R, Vassilenko, A, Mitsura, M, Paduto, D, Florence, E, Vandekerckhove, L, Hadziosmanovic, V, Begovac, J, Machala, L, Jilich, D, Sedlacek, D, Kronborg, G, Benfield, T, Gerstoft, J, Katzenstein, T, Moller, F, Ostergaard, L, Wiese, L, Nielsen, N, Zilmer, K, Smidt, J, Aho, I, Viard, J, Girard, P, Duvivier, C, Schmidt, R, Degen, O, Stellbrink, J, Stefan, C, Bogner, J, Chkhartishvili, N, Gargalianos, P, Xylomenos, G, Armenis, K, Sambatakou, H, Szlavik, J, Gottfredsson, M, Mulcahy, F, Yust, I, Turner, D, Burke, M, Shahar, E, Hassoun, G, Elinav, H, Haouzi, M, Elbirt, D, Sthoeger, M, Esposito, R, Mazeu, I, Mussini, C, Mazzotta, F, Gabbuti, A, Vullo, V, Lichtner, M, Zaccarelli, M, Antinori, A, Acinapura, R, Plazzi, M, Lazzarin, A, Castagna, A, Gianotti, N, Galli, M, Ridolfo, A, Rozentale, B, Uzdaviniene, V, Matulionyte, R, Staub, T, Hemmer, R, Ormaasen, V, Maeland, A, Bruun, J, Knysz, B, Gasiorowski, J, Inglot, M, Bakowska, E, Flisiak, R, Grzeszczuk, A, Parczewski, M, Maciejewska, K, Aksak-Was, B, Beniowski, M, Mularska, E, Smiatacz, T, Gensing, M, Jablonowska, E, Malolepsza, E, Wojcik, K, Mozer-Lisewska, I, Caldeira, L, Mansinho, K, Maltez, F, Radoi, R, Oprea, C, Panteleev, A, Panteleev, O, Yakovlev, A, Trofimora, T, Khromova, I, Kuzovatova, E, Borodulina, E, Vdoushkina, E, Jevtovic, D, Tomazic, J, Miro, M, Moreno, S, Rodriguez, J, Clotet, B, Jou, A, Paredes, R, Tural, C, Puig, J, Bravo, I, Gutierrez, M, Mateo, G, Laporte, M, Falconer, K, Thalme, A, Sonnerborg, A, Blaxhult, A, Flamholc, L, Cavassini, M, Calmy, A, Furrer, H, Battegay, M, Schmid, P, Kuznetsova, A, Kyselyova, G, Sluzhynska, M, Johnson, A, Simons, E, Orkin, C, Weber, J, Scullard, G, Clarke, A, Leen, C, Thulin, G, Akerlund, B, Koppel, K, Karlsson, A, Hakangard, C, Castelli, F, Cauda, R, Di Perri, G, Iardino, R, Ippolito, G, Marchetti, C, Perno, F, von Schloesser, F, Viale, P, Ceccherini-Silberstein, F, Girardi, E, Lo Caputo, S, Puoti, M, Andreoni, M, Ammassari, A, Balotta, C, Bandera, A, Bonfanti, P, Bonora, S, Borderi, M, Calcagno, A, Calza, L, Capobianchi, R, Cingolani, A, Cinque, P, De Luca, A, Di Biagio, A, Gori, A, Guaraldi, G, Lapadula, G, Madeddu, G, Maggiolo, F, Marcotullio, S, Monno, L, Nozza, S, Quiros Roldan, E, Rossotti, R, Rusconi, S, Santoro, M, Saracino, A, Galli, L, Lorenzini, P, Rodano, A, Shanyinde, M, Carletti, F, Carrara, S, Di Caro, A, Graziano, S, Petrone, F, Prota, G, Quartu, S, Truffa, S, Giacometti, A, Costantini, A, Barocci, V, Angarano, G, Santoro, C, Suardi, C, Donati, V, Verucchi, G, Minardi, C, Quirino, T, Abeli, C, Manconi, E, Piano, P, Cacopardo, B, Celesia, B, Vecchiet, J, Falasca, K, Pan, A, Lorenzotti, S, Sighinolfi, L, Segala, D, Vichi, F, Cassola, G, Viscoli, C, Alessandrini, A, Bobbio, N, Mazzarello, G, Mastroianni, C, Belvisi, V, Caramma, I, Chiodera, A, Milini, P, Rizzardini, G, Moioli, C, Piolini, R, Ridolfo, L, Salpietro, S, Tincati, C, Puzzolante, C, Abrescia, N, Chirianni, A, Borgia, G, Orlando, R, Bonadies, G, Di Martino, F, Gentile, I, Maddaloni, L, Cattelan, M, Marinello, S, Cascio, A, Colomba, C, Baldelli, F, Schiaroli, E, Parruti, G, Sozio, F, Magnani, G, Ursitti, A, Cristaudo, A, Baldin, G, Capozzi, M, Cicalini, S, Fontanelli Sulekova, L, Iaiani, G, Latini, A, Mastrorosa, I, Savinelli, S, Vergori, A, Cecchetto, M, Viviani, F, Bagella, P, Rossetti, B, Franco, A, Fontana Del Vecchio, R, Francisci, D, Di Giuli, C, Caramello, P, Orofino, C, Sciandra, M, Bassetti, M, Londero, A, Pellizzer, G, Manfrin, V, Starnini, G, Ialungo, A, Dellamonica, P, Bernard, E, Courjon, J, Cua, E, De Salvador-Guillouet, F, Durant, J, Etienne, C, Ferrando, S, Mondain-Miton, V, Naqvi, A, Perbost, I, Pillet, S, Prouvost-Keller, B, Pugliese, P, Rio, V, Risso, K, Roger, M, Aubert, V, Bernasconi, E, Ciuffi, A, Dollenmaier, G, Egger, M, Elzi, L, Fehr, J, Fellay, J, Gunthard, F, Haerry, D, Hasse, B, Hirsch, H, Hoffmann, M, Hosli, I, Kahlert, C, Kaiser, L, Keiser, O, Klimkait, T, Kouyos, D, Kovari, H, Ledergerber, B, Martinetti, G, Martinez de Tejada, B, Marzolini, C, Metzner, J, Muller, N, Nicca, D, Pantaleo, G, Paioni, P, Rauch, A, Rudin, C, Speck, R, Stockle, M, Tarr, P, Trkola, A, Vernazza, P, Wandeler, G, Yerly, S, Internal medicine, Pediatric surgery, Medical Microbiology and Infection Prevention, Amsterdam Gastroenterology Endocrinology Metabolism, Faculteit Medische Wetenschappen/UMCG, Microbes in Health and Disease (MHD), and Molecular Pharmacology

Subjects
Male, HIV AIDS, HIV Infections, 0302 clinical medicine, Interquartile range, Risk Factors, Neoplasms, Medicine, 030212 general & internal medicine, Prospective Studies, Prospective cohort study, 0303 health sciences, Incidence, Absolute risk reduction, Drugs, General Medicine, Middle Aged, Viral Load, Antiretroviral therapy, 3. Good health, AIDS, Cancer treatment, Prevention policy and public health, Cohort, Infectious diseases, Cohort studies, Female, Viral load, Adult, medicine.medical_specialty, Anti-HIV Agents, HIV Infections/drug therapy, Socio-culturale, Time-to-Treatment, 03 medical and health sciences, Acquired immunodeficiency syndrome (AIDS), SDG 3 - Good Health and Well-being, Internal medicine, Internal Medicine, Humans, Adverse effect, 030306 microbiology, business.industry, HIV, Cancer, medicine.disease, CD4 Lymphocyte Count, Anti-HIV Agents/therapeutic use, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Neoplasms/epidemiology
Abstract

BACKGROUND: Immediate initiation of antiretroviral therapy (ART) regardless of CD4 cell count reduces risk for AIDS and non-AIDS-related events in asymptomatic, HIV-positive persons and is the standard of care. However, most HIV-positive persons initiate ART when their CD4 count decreases below 500 × 10 9 cells/L. Consequences of delayed ART on risk for non-AIDS-defining and AIDS-defining cancer, one of the most common reasons for death in HIV, are unclear. OBJECTIVE: To estimate the long-term risk difference for cancer with the immediate ART strategy.DESIGN: Multinational prospective cohort study.SETTING: The D:A:D (Data collection on Adverse events of anti-HIV Drugs) study, which included HIV-positive persons from Europe, Australia, and the United States.PARTICIPANTS: 8318 HIV-positive persons with at least 1 measurement each of CD4 cell count and viral load while ART-naive (study period, 2006 to 2016).MEASUREMENTS: The parametric g-formula was used, with adjustment for baseline and time-dependent confounders (CD4 cell count and viral load), to assess the 10-year risk for non-AIDS-defining and AIDS-defining cancer of immediate versus deferred (at CD4 counts RESULTS: During 64 021 person-years of follow-up, 231 cases of non-AIDS-defining cancer and 272 of AIDS-defining cancer occurred among HIV-positive persons with a median age of 36 years (interquartile range, 29 to 43 years). With immediate ART, the 10-year risk for non-AIDS-defining cancer was 2.97% (95% CI, 2.37% to 3.50%) and that for AIDS-defining cancer was 2.50% (CI, 2.37% to 3.38%). Compared with immediate ART initiation, the 10-year absolute risk differences when deferring ART to CD4 counts less than 500 × 10 9 cells/L and less than 350 × 10 9 cells/L were 0.12 percentage point (CI, -0.01 to 0.26 percentage point) and 0.29 percentage point (CI, -0.03 to 0.73 percentage point), respectively, for non-AIDS-defining cancer and 0.32 percentage point (CI, 0.21 to 0.44 percentage point) and 1.00 percentage point (CI, 0.67 to 1.44 percentage points), respectively, for AIDS-defining cancer. LIMITATION: Potential residual confounding due to observational study design.CONCLUSION: In this young cohort, effects of immediate ART on 10-year risk for cancer were small, and further supportive data are needed for non-AIDS-defining cancer.PRIMARY FUNDING SOURCE: Highly Active Antiretroviral Therapy Oversight Committee.

Published
2021

8. PML at mitochondria-associated membranes governs a trimeric complex with NLRP3 and P2X7R that modulates the tumor immune microenvironment

Author

Sonia Missiroli, Mariasole Perrone, Roberta Gafà, Francesco Nicoli, Massimo Bonora, Giampaolo Morciano, Caterina Boncompagni, Saverio Marchi, Magdalena Lebiedzinska-Arciszewska, Bianca Vezzani, Giovanni Lanza, Franz Kricek, Alessandro Borghi, Francesco Fiorica, Keisuke Ito, Mariusz R. Wieckowski, Francesco Di Virgilio, Luigi Abelli, Paolo Pinton, and Carlotta Giorgi

Subjects
Cell Biology, Molecular Biology
Abstract

Uncontrolled inflammatory response arising from the tumor microenvironment (TME) significantly contributes to cancer progression, prompting an investigation and careful evaluation of counter-regulatory mechanisms. We identified a trimeric complex at the mitochondria-associated membranes (MAMs), in which the purinergic P2X7 receptor - NLRP3 inflammasome liaison is fine-tuned by the tumor suppressor PML. PML downregulation drives an exacerbated immune response due to a loss of P2X7R-NLRP3 restraint that boosts tumor growth. PML mislocalization from MAMs elicits an uncontrolled NLRP3 activation, and consequent cytokines blast fueling cancer and worsening the tumor prognosis in different human cancers. New mechanistic insights are provided for the PML-P2X7R-NLRP3 axis to govern the TME in human carcinogenesis, fostering new targeted therapeutic approaches.

Published
2022

9. Inflammation and intracellular exposure of dolutegravir, darunavir, tenofovir and emtricitabine in people living with HIV

Author

Micol Ferrara, Jessica Cusato, Elena Salvador, Alice Trentalange, Chiara Alcantarini, Mattia Trunfio, Elvira Stefania Cannizzo, Valeria Bono, Silvia Nozza, Amedeo De Nicolò, Alice Ianniello, Elisa De Vivo, Antonio D'Avolio, Giovanni Di Perri, Stefano Bonora, Giulia Marchetti, and Andrea Calcagno

Subjects
immunology, Pharmacology, pharmacotherapy, inflammation, drug transporters, Pharmacology (medical), infectious diseases, antiretrovirals, pharmacokinetics
Abstract

Antiretroviral (ARV) therapy reduces inflammation and immune activation in people with HIV, but not down to the levels observed in people without HIV. Limited drug penetration within tissues has been argued as a potential mechanism of persistent inflammation. Data on the inflammation role on ARV plasma/intracellular (IC) pharmacokinetics (PK) through to expression of cytochrome P450 3A/membrane transporters are limited. The aim of this study was to investigate the correlation between inflammation markers (IM) and plasma/IC PK of ARV regimen in HIV-positive patients.We included ART-experienced patients switching to three different ARV regimens. Plasma and IC ARV drug concentration means at the end of dosing interval (TPlasma and IC drug concentrations were measured in 60 samples. No significative differences between CRP, sCD14, IL-6 and LPS values in the three arms were observed. A significant inverse correlation between tenofovir plasma concentration and sCD14 (rho = -0.79, P .001), and between DRV IC/plasma ratio and LogOur preliminary data support the hypothesis of lower DRV and DTG IC concentrations and lower TFV plasma exposure in patients with higher plasma IM suggesting an interplay between HIV drug penetration and persistent inflammation in cART-treated HIV-positive patients.

Published
2022

10. Novel Eulerian Approach with Cellular Automata Modelling to Estimate Water Quality in a Drinking Water Network

Author

M. A. Bonora, G. Capano, A. De Rango, and Mario Maiolo

Subjects
Water Science and Technology, Civil and Structural Engineering
Abstract

The forecast analysis of the exposure to the contamination risk in a water distribution network requires increasing the quality of the applied input/outputs modeling. This need involves using non-traditional models responding to the increasingly high computation requirements. In this scenario, the Cellular Automata paradigm represents a new frontier with considerable potential. Specifically, this paper describes the Eulerian Water quAlity Modeling—Cellular Automata (EWAM-CA) model, aimed at simulating the sodium hypochlorite (chlorine) injection, transport, and reaction phase in a medium-sized drinking water network. The EWAM-CA accuracy was compared with the Epanet software on a Fossolo water network, in Bologna town (Italy), considering a constant and an impulsive input respectively. Due to CA's intrinsic aptitude for parallel computing, a parallel version of EWAM-CA was developed. Moreover, using the capability of the cellular automata to manage the modeling asynchronously, improving the computational efficiency, we propose a novel approach based on activation/deactivation asynchronous rules, avoiding unnecessary calculations in nodes or pipes where no pollution occurs. The different EWAM-CA versions were compared for the case study, and the parallel EWAM-CA approach coupled with asynchronous functionality significantly improved computational performance.

Published
2022

12. Real-life Evidence of Lower Lung Virulence in COVID-19 Inpatients Infected with SARS-CoV-2 Omicron Variant Compared to Wild-Type and Delta SARS-CoV-2 Pneumonia

Author

Trunfio, Mattia, Portesani, Francesca, Vicinanza, Sabrina, Nespoli, Paola, Traverso, Federico, Cortese, Giancarlo, Bonora, Stefano, Calcagno, Andrea, and Di Perri, Giovanni

Subjects
Pulmonary and Respiratory Medicine, Inpatients, ARDS, Omicron, Pneumonia, SARS-CoV-2, Variants of Concern, Virulence, Animals, Humans, Lung, COVID-19, Respiratory Insufficiency
Abstract

In vitro and animal models described lower replication capacity and virulence of SARS-CoV-2 Omicron lineage in lower respiratory airways compared to wild type and other variants of concern (oVOCs). Among adult subjects admitted to our hospital (Turin, Italy) due to wild type, oVOCs, and Omicron SARS-CoV-2-related pneumonia (n = 100 for each lineage), the cases of Omicron pneumonia showed lower degree of lung parenchyma involvement (aβ -1.471, p = 0.037), less tendency to parenchyma consolidation (aOR 0.500, p = 0.011), and better respiratory functions (assessed by ambient air arterial blood gas analysis). After adjusting for demographic, previous immunity, and comorbidities, Omicron pneumonia still associated with lower risk of respiratory failure (for severe respiratory failure, Wild-type versus Omicron aOR 15.6, p = 0.005 and oVOCs versus Omicron aOR 31.7, p 0.001). These observations are in line with preliminary findings from in vitro and animal models and could explain why Omicron infection has been associated with lower mortality and hospitalization in human.

Published
2022

13. Test Results of the MQYYM: A 90 Mm NbTi Quadrupole Magnet Option for HL-LHC

Author

D. Simon, S. Perraud, H. Felice, R. Godon, R. Correia Machado, J.-M. Gheller, D. Bouziat, V. Stepanov, A. Madur, M Segreti, F. Molinie, B Hervieu, P. De Antoni, Q. Guihard, J. Relland, J. C. Perez, A. Foussat, C. Petrone, L. Fiscarelli, M. Bonora, E. Todesco, Institut de Recherches sur les lois Fondamentales de l'Univers (IRFU), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay

Subjects
magnetic field, LHC quadrupole MQY, field quality measurements, rotation, size 90.0 Mm, tunneling, CEA, strain gauges, titanium alloys, Superconducting magnets, CERN, quadrupole, temperature 4.2 K, Magnetic tunneling, quench detection, vertical cryogenic station, accelerator, magnet, luminosity, upgrade, Condensed Matter Physics, single aperture short model magnet, quadrupole lens, beam, width, Electronic, Optical and Magnetic Materials, magnet, superconductivity, cryogenics, quality, magnetic length, performance, HL-LHC project, coil, superconductivity, superconducting accelerator magnet, CERN Lab, double aperture quadrupole magnet, NbTi, [PHYS.PHYS.PHYS-ACC-PH]Physics [physics]/Physics [physics]/Accelerator Physics [physics.acc-ph], quenching, Magnetic field measurement, LHC luminosity upgrade, Apertures, Training, CERN LHC Coll, upgrade, Electrical and Electronic Engineering, titanium, alloy, niobium, alloy, mechanical measurements, superconducting coils, temperature, Coils, Heating systems, NbTi quadrupole magnet option, size 1.215 m, rotating probe, operating gradient, MQYYM cold test, temperature 1.9 K, niobium alloys, accelerator magnets, accelerator, superconductivity, size 70.0 mm
Abstract

International audience; For the HL-LHC project, a 90 mm NbTi cos(2θ) double aperture quadrupole magnet with an operating gradient of 120 T/m at 1.9 K has been designed as an option to replace the 70 mm aperture LHC quadrupole MQY. CEA in collaboration with CERN designed and manufactured a single aperture short model magnet with a magnetic length of 1.215 m at 1.9 K called MQYYM. The MQYYM cold test occurred at CEA at 4.2 K in a vertical cryogenic station. During the power test, the operating gradient at 1.9 K has been reached after two training quenches. All along the test, magnetic and mechanical measurements were done using respectively a rotating probe and strain gauges. This paper describes the performance of the MQYYM at 4.2 K and gives an analysis of the data acquired during the test, including training behavior, quench detection, protection and field quality measurements.

Published
2022

14. Effects of Semaglutide on Glycemic Control and Weight Loss in a Patient with Prader-Willi Syndrome: A Case Report

Author

Elena Sani, Giuliana Da Prato, Maria Grazia Zenti, Andrea Bordugo, Maddalena Trombetta, and Enzo Bonora

Subjects
Endocrinology, Diabetes and Metabolism, Immunology and Allergy
Abstract

Background: Prader-Willi syndrome is the most frequent genetic cause of obesity and is often complicated by glucose metabolism alterations. Conventional therapies prescribed for type 2 diabetes frequently failed to achieve adequate glycemic control in patients with Prader-Willi syndrome. Beneficial effects of glucagon like peptide-1 receptor agonists exenatide and liraglutide have been reported for the management of type 2 diabetes in Prader-Willi syndrome, but no data are currently available in this population on the use of semaglutide. Case Presentation: We report for the first time the use of semaglutide 1 mg per week in a 33-yearold man with Prader-Will syndrome complicated by poorly controlled diabetes and severe obesity. After 12 months of semaglutide treatment, we observed an important reduction in glycated hemoglobin levels (11.1% to 7.2%) and body weight (99.5 kg to 94.3 kg), with a notable decrease in fat mass and insulin requirements. Interestingly, our patient had already tried liraglutide therapy in adjunction to metformin and insulin therapy, reporting no substantial efficacy. Conclusions: The beneficial effects of semaglutide on glycemic control and weight reduction provide a promising treatment for diabetes and obesity in Prader-Willi syndrome, even where other glucagons like peptide-1 receptor agonists have failed. Further studies are required to confirm the efficacy and safety of semaglutide in patients with Prader-Willi syndrome.

Published
2022

15. VIRTUAL INSPECTION BASED ON 3D SURVEY SUPPORTING RISKS DETACHMENT ANALYSIS IN PIETRAFORTE STONE BUILT HERITAGE

Author

Bonora, V., Centauro, I., Fiorini, L., Conti, A., Salvatici, T., Calandra, S., Raffa, R., Intrieri, E., Garzonio, C. A., and Tucci, G.

Abstract

The paper presents the first results of a multidisciplinary research project launched to support the conservation and restoration of the stone façades of the Pitti Palace in Florence with innovative techniques from the fields of geomatics and diagnostic analysis. Monitoring campaigns are periodically conducted on the façades of the palace to identify stone elements in critical conditions; such surveys primarily require close and careful observation of the façade, for which a crane basket is required. The paper proposes first attempt to compare results obtained through a traditional workflow with those coming from a deeper use of the high-resolution 3D model to conduct a virtual inspection and to map elements of vulnerability on a GIS.On a test area, the analysis of the factors considered relevant to the risk of detachment was carried out on the digital model and compared with what the experts observed on-site by carrying out Non-Destructive diagnostic tests. Traditionally conducted monitoring and diagnostic surveys are assumed to validate the proposed method, which, following a simple data analysis, remotely identifies all blocks detected as vulnerable by the in-situ inspection, potentially drastically reducing fieldwork. It is therefore proposed as a preliminary screening useful to better address further analysis.

Published
2023

16. RECORDING MICHELANGELO'S DAVID: ULTRA-HIGH RESOLUTION 3D SCANNING AND MODELING FOR DIGITAL AND PHYSICAL REPRODUCTION

Author

Tucci, G., Conti, A., Bonora, V., Fiorini, L., and Pagliaricci, G.

Abstract

In the twentieth century, the physical reproduction of a work of art was considered only a business activity and a replica would rarely be on display in a museum. In recent decades, however, as high-resolution digital sampling and fabrication techniques have become popular in all fields, the various ways in which they can be applied to cultural heritage are leading to a more articulated approach to their use. They are no longer considered fakes or imitations, but as artefacts specially designed and built to facilitate the dissemination of heritage or perform simulations without damaging the originals. This case study describes the process of creating the replica of Michelangelo's David that has been displayed in the Italian Pavilion at EXPO 2020 in Dubai. Starting with the planning of the survey, the instruments and facilities used, and the fieldwork process are described. The resulting data have been then processed to produce a model optimised for replication on a large format additive manufacturing printer. Finally, the challenges of processing and managing ultra-high-resolution data are outlined.

Published
2023

17. BETWEEN SPATIAL AND ARCHIVAL DATA: DIGITAL HUMANITIES FOR THE HISTORY OF A STAIRCASE OF PITTI PALACE

Author

Fiorini, L., Conti, A., Meucci, A., Bonora, V., and Tucci, G.

Abstract

In the last decades, surveys produced with geomatic techniques are increasingly used for the study and conservation of the built heritage because they automatically collect large amounts of data with an accuracy and objectivity that could not be achieved with traditional techniques. As in other fields of digital and spatial humanities, the combination of spatial data with archival and secondary sources provides new tools for reconstructing the history, construction, and transformation of a historic architecture.The new digital survey of Pitti Palace, which was carried out between 2019 and 2021, has revealed aspects neglected by previous surveys and historical studies. Pitti Palace is the largest historical civil building in Florence. In the 16th century, Bartolomeo Ammannati carried out important extensions, including the so-called "spiral staircase", one of the most important staircases in the palace. This staircase, of which there is little documentation, although it is considered a masterpiece, was demolished at the beginning of the 19th century by Pasquale Poccianti to make way for the "New Secondary Staircase", on which previous studies have focused mainly on stylistic and decorative aspects.Using digital spatial data as a primary source, the research aimed to explain the construction history of the new staircase built by Poccianti, allowing a precise comparison between the archive documents and the actual geometry of the building elements.It also highlights previously undocumented features, including the evidence for the Ammannati staircase and the important changes made during the construction of the new staircase. The article shows how the insertion of the new staircase profoundly altered the design, structure and layout of a wing of the Pitti Palace. It also suggests how a more transdisciplinary and holistic approach helps the study of historical architecture.

Published
2023

18. A Novel UHPLC-MS/MS Method for the Quantification of Seven Opioids in Different Human Tissues

Author

D’Avolio, Alessandra Manca, Amedeo De Nicolò, Elisa Delia De Vivo, Micol Ferrara, Sharon Oh, Sahar Khalili, Niamh Higgins, Robert G. Deiss, Stefano Bonora, Jessica Cusato, Alice Palermiti, Jacopo Mula, Sara Gianella, and Antonio

Subjects
LC-MS, tissue, morphine, fentanyl, opioids
Abstract

Background: Opioids are considered the cornerstone of pain management: they show good efficacy as a first-line therapy for moderate to severe cancer pain. Since pharmacokinetic/pharmacodynamic information about the tissue-specific effect and toxicity of opioids is still scarce, their quantification in post-mortem autoptic specimens could give interesting insights. Methods: We describe an ultra-high-performance liquid chromatography coupled with tandem mass spectrometry method for the simultaneous quantification of methadone, morphine, oxycodone, hydrocodone, oxymorphone, hydromorphone and fentanyl in several tissues: liver, brain, kidney, abdominal adipose tissue, lung and blood plasma. The presented method has been applied on 28 autoptic samples from different organs obtained from four deceased PLWH who used opioids for palliative care during terminal disease. Results: Sample preparation was based on tissue weighing, disruption, sonication with drug extraction medium and a protein precipitation protocol. The extracts were then dried, reconstituted and injected onto the LX50 QSight 220 (Perkin Elmer, Milan, Italy) system. Separation was obtained by a 7 min gradient run at 40 °C with a Kinetex Biphenyl 2.6 µm, 2.1 × 100 mm. Concerning the analyzed samples, higher opioids concentrations were observed in tissues than in plasma. Particularly, O-MOR and O-COD showed higher concentrations in kidney and liver than other tissues (>15–20 times greater) and blood plasma (>100 times greater). Conclusions: Results in terms of linearity, accuracy, precision, recovery and matrix effect fitted the recommendations of FDA and EMA guidelines, and the sensitivity was high enough to allow successful application on human autoptic specimens from an ethically approved clinical study, confirming its eligibility for post-mortem pharmacological/toxicological studies.

Published
2023
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20. Library Indoor microclimate monitoring with and without heating system. A bologna university library case study

Author

Andrea Boeri, Danila Longo, Kristian Fabbri, Marco Pretelli, Anna Bonora, Saveria Boulanger, Boeri, Andrea, Longo, Danila, Fabbri, Kristian, Pretelli, Marco, Bonora, Anna, and Boulanger, Saveria

Subjects
Library, Heritage microclimate risk, Archeology, Monitoring, Book, 060102 archaeology, 020209 energy, Materials Science (miscellaneous), 06 humanities and the arts, 02 engineering and technology, Conservation, Heritage building, Prediction risk damage, Chemistry (miscellaneous), Microclimate risk, 11. Sustainability, 0202 electrical engineering, electronic engineering, information engineering, Historic indoor microclimate, 0601 history and archaeology, General Economics, Econometrics and Finance, Spectroscopy
Abstract

This paper aims to illustrate and give an interpretation of the results emerged from a pilot activity developed within the ROCK project, by the Department of Architecture of the University of Bologna, Alma Mater Studiorum. Through this activity, we studied the indoor microclimate of the University Library of Bologna (BUB), in the Archive and in the Lecture Hall, with the aim to detect how these spaces are affected by the influence of factors such as the outdoor climate and the cooling and heating systems. Moreover, the paper presents the customisation of the probes’ alert system and of the probes itself, used for a one-year monitoring campaign started on the 20th of December 2018. In addition, we calculated the Heritage Microclimate Risk index, to verify the level of risk to which the heritage in the Library is exposed due to the indoor microclimate, and the Predicted Risk of Damage index, that evaluate the more specific risks of damage to which precise objects hosted in there are exposed. Therefore, this paper enriches the research field of Historic Indoor Microclimate, started in 2013, which concerns issues as preventive conservation and restoration in historic buildings. The new insights about the Bologna University Library facilitate the possibility to draw up a specific ‘Indoor Microclimate Management Protocol (IMMP)’ aimed at the preventive conservation of manuscripts and books in historical libraries.

Published
2022

21. Aberrant upregulation of the glycolytic enzyme PFKFB3 in CLN7 neuronal ceroid lipofuscinosis

Author

Irene Lopez-Fabuel, Marina Garcia-Macia, Costantina Buondelmonte, Olga Burmistrova, Nicolo Bonora, Paula Alonso-Batan, Brenda Morant-Ferrando, Carlos Vicente-Gutierrez, Daniel Jimenez-Blasco, Ruben Quintana-Cabrera, Emilio Fernandez, Jordi Llop, Pedro Ramos-Cabrer, Aseel Sharaireh, Marta Guevara-Ferrer, Lorna Fitzpatrick, Christopher D. Thompton, Tristan R. McKay, Stephan Storch, Diego L. Medina, Sara E. Mole, Peter O. Fedichev, Angeles Almeida, Juan P. Bolaños, European Commission, Agencia Estatal de Investigación (España), Instituto de Salud Carlos III, Junta de Castilla y León, Fundación BBVA, Fundación Ramón Areces, Lopez-Fabuel, I., Garcia-Macia, M., Buondelmonte, C., Burmistrova, O., Bonora, N., Alonso-Batan, P., Morant-Ferrando, B., Vicente-Gutierrez, C., Jimenez-Blasco, D., Quintana-Cabrera, R., Fernandez, E., Llop, J., Ramos-Cabrer, P., Sharaireh, A., Guevara-Ferrer, M., Fitzpatrick, L., Thompton, C. D., Mckay, T. R., Storch, S., MEDINA SANABRIA, Diego Lui, Mole, S. E., Fedichev, P. O., Almeida, A., and Bolanos, J. P.

Subjects
Male, Phosphofructokinase-2, Science, General Physics and Astronomy, Membrane Transport Protein, Lysosome-Associated Membrane Glycoprotein, Molecular neuroscience, General Biochemistry, Genetics and Molecular Biology, Article, Mice, Lysosomal Storage Disease, Neuronal Ceroid-Lipofuscinoses, Autophagy, Animals, Humans, Neurons, Multidisciplinary, Animal, Lysosome-Associated Membrane Glycoproteins, Membrane Transport Proteins, General Chemistry, Neuron, Lysosome, Mitochondria, Up-Regulation, Lysosomal Storage Diseases, Mice, Inbred C57BL, Disease Models, Animal, Mechanisms of disease, Child, Preschool, Female, Neuronal Ceroid-Lipofuscinose, Lysosomes, Neurological disorders, Human
Abstract

CLN7 neuronal ceroid lipofuscinosis is an inherited lysosomal storage neurodegenerative disease highly prevalent in children. CLN7/MFSD8 gene encodes a lysosomal membrane glycoprotein, but the biochemical processes affected by CLN7-loss of function are unexplored thus preventing development of potential treatments. Here, we found, in the Cln7∆ex2 mouse model of CLN7 disease, that failure in autophagy causes accumulation of structurally and bioenergetically impaired neuronal mitochondria. In vivo genetic approach reveals elevated mitochondrial reactive oxygen species (mROS) in Cln7∆ex2 neurons that mediates glycolytic enzyme PFKFB3 activation and contributes to CLN7 pathogenesis. Mechanistically, mROS sustains a signaling cascade leading to protein stabilization of PFKFB3, normally unstable in healthy neurons. Administration of the highly selective PFKFB3 inhibitor AZ67 in Cln7∆ex2 mouse brain in vivo and in CLN7 patients-derived cells rectifies key disease hallmarks. Thus, aberrant upregulation of the glycolytic enzyme PFKFB3 in neurons may contribute to CLN7 pathogenesis and targeting PFKFB3 could alleviate this and other lysosomal storage diseases., CLN7 neuronal ceroid lipofuscinosis is an inherited lysosomal storage disease typically with childhood onset of neurodegenerative symptoms. Here the authors report that in a mouse model of CLN7 disease neuronal reactive oxygen species and the activity of glycolytic enzyme PFKFB3 are increased, while PFKFB3 inhibition ameliorates hallmarks of pathology.

Published
2022

22. RePIM in LOD: semantic technologies to manage, preserve, and disseminate knowledge about Italian secular music and lyric poetry from the 16th-17th centuries

Author

Bonora P., Pompilio A., and Bonora, P., Pompilio, A.

Subjects
Linked Open Data, Semantic Web, CIDOC-CRM, FRBRoo, digital knowledge preservation, madrigal
Abstract

The PIM in LOD project aimed to publish the "Repertorio della Poesia Italiana in Musica, 1500-1700" (RePIM) as Linked Open Data (LOD) dataset. For the extent and detail of its contents, RePIM is a reference archive for research on Italian secular music from the 16th-17th centuries. In recent years, scholars have been able to access it through a public web-based application. Due to the obsolescence of its information technology platform, the RePIM repository was set to be taken offline. To preserve this precious source, the project migrated its contents into a knowledge base (KB) adopting semantic technologies and designed an up-to-date end-user application. The paper illustrates the challenges of managing information about madrigal tradition and the digital knowledge preservation of bibliographic and philological information in the field of Italian secular music and lyric poetry of the 16th-17th centuries., Umanistica Digitale, No. 14 (2022)

Published
2023
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23. Correlations between molecular alterations, histopathological characteristics, and poor prognosis in esophageal adenocarcinoma

Author

Orsini, Arianna, Mastracci, Luca, Bozzarelli, Isotta, Ferrari, Anna, Isidori, Federica, Fiocca, Roberto, Lugaresi, Marialuisa, D’Errico, Antonietta, Malvi, Deborah, Cataldi-Stagetti, Erica, Spaggiari, Paola, Tomezzoli, Anna, Albarello, Luca, Ristimäki, Ari, Bottiglieri, Luca, Krishnadath, Kausilia K., Rosati, Riccardo, Romario, Uberto Fumagalli, Manzoni, Giovanni De, Räsänen, Jari, Martinelli, Giovanni, Mattioli, Sandro, Bonora, Elena, Consortium, on behalf of the EACSGE Consortium on behalf of the EACSGE, EACSGE Consortium, and Arianna Orsini, Luca Mastracci, Isotta Bozzarelli, Anna Ferrari, Federica Isidori, Roberto Fiocca, Marialuisa Lugaresi, Antonietta D’Errico, Deborah Malvi, Erica Cataldi-Stagetti, Paola Spaggiari, Anna Tomezzoli, Luca Albarello, Ari Ristimäki, Luca Bottiglieri, Kausilia K. Krishnadath, Riccardo Rosati, Uberto Fumagalli Romario, Giovanni De Manzoni, Jari Räsänen, Giovanni Martinelli, Sandro Mattioli, Elena Bonora, EACSGE Consortium

Subjects
Cancer Research, HNF1alpha, esophageal adenocarcinoma, Oncology, TP53, SMAD4, Human medicine
Abstract

Simple Summary The molecular heterogeneity of esophageal adenocarcinoma (EAC), a severe malignancy with increasing incidence and low survival rates, misperceives the underlying biology of tumor onset and development. However, advances in high-throughput next-generation sequencing (NGS) technologies have highlighted the potential role of somatic DNA sequence markers for new diagnostic techniques or constitute novel therapeutic targets. Thus, in order to identify a molecular and prognostic signature in EAC patients, we decided to integrate the sequencing of specimens from naive patients (not treated with chemo-radiotherapy) with histological classification, with the aim of identification of potential biomarkers, and patient stratification. Combining different approaches paves the way for early identification and the selection of better therapy. Esophageal adenocarcinoma (EAC) is a severe malignancy with increasing incidence, poorly understood pathogenesis, and low survival rates. We sequenced 164 EAC samples of naive patients (without chemo-radiotherapy) with high coverage using next-generation sequencing technologies. A total of 337 variants were identified across the whole cohort, with TP53 as the most frequently altered gene (67.27%). Missense mutations in TP53 correlated with worse cancer-specific survival (log-rank p = 0.001). In seven cases, we found disruptive mutations in HNF1alpha associated with other gene alterations. Moreover, we detected gene fusions through massive parallel sequencing of RNA, indicating that it is not a rare event in EAC. In conclusion, we report that a specific type of TP53 mutation (missense changes) negatively affected cancer-specific survival in EAC. HNF1alpha was identified as a new EAC-mutated gene.

Published
2023

24. Calcium and Reactive Oxygen Species Signaling Interplays in Cardiac Physiology and PathologiesCalcium and Reactive Oxygen Species Signaling Interplays in Cardiac Physiology and Pathologies

Author

Bianca De Nicolo, Erica Cataldi-Stagetti, Chiara Diquigiovanni, Elena Bonora, and Bianca De Nicolo, Erica Cataldi-Stagetti, Chiara Diquigiovanni, Elena Bonora

Subjects
mitochondria, cardiomyopathies, calcium, mitochondrial dysfunction, drug, ROS
Abstract

Mitochondria are key players in energy production, critical activity for the smooth functioning of energy-demanding organs such as the muscles, brain, and heart. Therefore, dysregulation or alterations in mitochondrial bioenergetics primarily perturb these organs. Within the cell, mitochondria are the major site of reactive oxygen species (ROS) production through the activity of different enzymes since it is one of the organelles with the major availability of oxygen. ROS can act as signaling molecules in a number of different pathways by modulating calcium (Ca2+) signaling. Interactions among ROS and calcium signaling can be considered bidirectional, with ROS regulating cellular Ca2+ signaling, whereas Ca2+ signaling is essential for ROS production. In particular, we will discuss how alterations in the crosstalk between ROS and Ca2+ can lead to mitochondrial bioenergetics dysfunctions and the consequent damage to tissues at high energy demand, such as the heart. Changes in Ca2+ can induce mitochondrial alterations associated with reduced ATP production and increased production of ROS. These changes in Ca2+ levels and ROS generation completely paralyze cardiac contractility. Thus, ROS can hinder the excitation–contraction coupling, inducing arrhythmias, hypertrophy, apoptosis, or necrosis of cardiac cells. These interplays in the cardiovascular system are the focus of this review.

Published
2023

26. Doravirine and Rilpivirine Intra Cellular Accumulation in the Clinical Setting

Author

Ferrara M, Trevisan G, Marinaro L, Accardo G, Fantino S, Alladio F, Drappero E, Tettoni M, De Vivo E, Ianniello A, De Nicolò A, D’Avolio A, Calcagno A, and Bonora S

Subjects
General Medicine, General Chemistry
Abstract

Background: Doravirine (DOR) and Rilpivirine (RPV) are the NNRTIs currently most used in the clinical setting, in dual and triple drug regimens (2DR and 3DR). Intracellular (IC) Pharmacokinetics (PK) of these drugs has not been fully elucidated. Our aim was to compare plasma PK and IC accumulation in real-life experienced patients (pts). Methods: Pts on DOR- and RPV-including Antiretroviral (ARV) regimen were considered. DOR and RPV plasma and IC (PBMCs) concentrations were measured at 12 (37%) (T12) and 24 ± 4 hours (63%) (T24) after last drug intake by means of UHPLC-MSMS validated methods. Results: 90 pts (65% on 3DR and 35% on 2DR) were included: 52% on DOR- and 48% on RPV-containing ARV. RPV IC/plasma ratio was significantly higher than DOR IC/plasma ratio: 6.034 (4.878-7.186) vs. 1.479 (1.256-1.702) (p=0.001) independently from timing T12 (p=0.003) and T24 (p

Published
2022

27. La pandemia diabete in Italia

Author

Enzo Bonora

Abstract

SommarioIn Italia vivono circa 4 milioni di persone con il diabete e ogni anno ci sono circa 350 mila nuove diagnosi. Le persone con diabete ricevono prescrizioni di farmaci, esami di laboratorio e strumentali e richiedono ricoveri ospedalieri più spesso delle persone senza il diabete. Il diabete è gravato da aumentata mortalità e accorcia la vita, soprattutto nelle persone di media età. La qualità della cura nelle persone con diabete è subottimale, soprattutto fra chi non è assistito nei centri diabetologici (che, peraltro, rappresentano dei luoghi “salvavita”). Il diabete contribuisce fortemente alla spesa sanitaria e comporta ingenti spese, non tutte specificamente sanitarie. Nonostante tutto questo e nonostante leggi nazionali e regionali, documenti di indirizzo nazionali e regionali, PDTA regionali e locali, promesse e proponimenti di varia provenienza, la pandemia diabete non riceve le attenzioni che merita.

Published
2022

29. CTCF-mediated insulation and chromatin environment modulate Car5b escape from X inactivation

Author

He Fang, Ana R. Tronco, Giancarlo Bonora, Truong Nguyen, Jitendra Thakur, Joel B. Berletch, Galina N. Filippova, Steven Henikoff, Jay Shendure, William S. Noble, Christine M. Disteche, and Xinxian Deng

Subjects
Article
Abstract

BackgroundThe number and escape levels of genes that escape X chromosome inactivation (XCI) in female somatic cells vary among tissues and cell types, potentially contributing to specific sex differences. Here we investigate the role of CTCF, a master chromatin conformation regulator, in regulating escape from XCI. CTCF binding profiles and epigenetic features were systematically examined at constitutive and facultative escape genes using mouse allelic systems to distinguish the inactive X (Xi) and active X (Xa) chromosomes.ResultsWe found that escape genes are located inside domains flanked by convergent arrays of CTCF binding sites, consistent with the formation of loops. In addition, strong and divergent CTCF binding sites often located at the boundaries between escape genes and adjacent neighbors subject to XCI would help insulate domains. Facultative escapees show clear differences in CTCF binding dependent on their XCI status in specific cell types/tissues. Concordantly, deletion but not inversion of a CTCF binding site at the boundary between the facultative escape geneCar5band its silent neighborSiah1bresulted in loss ofCar5bescape. Reduced CTCF binding and enrichment of a repressive mark overCar5bin cells with a boundary deletion indicated loss of looping and insulation. In mutant lines in which either the Xi-specific compact structure or its H3K27me3 enrichment was disrupted, escape genes showed an increase in gene expression and associated active marks, supporting the roles of the 3D Xi structure and heterochromatic marks in constraining levels of escape.ConclusionOur findings indicate that escape from XCI is modulated both by looping and insulation of chromatin via convergent arrays of CTCF binding sites and by compaction and epigenetic features of the surrounding heterochromatin.

Published
2023

30. Lower heart rate variability, an index of worse autonomic function, is associated with worse beta cell response to a glycemic load in vivo—The Maastricht Study

Author

Elisabetta Rinaldi, Frank CT Heide, Enzo Bonora, Maddalena Trombetta, Chiara Zusi, Abraham A Kroon, Miranda T Schram, Carla JH Kallen, Anke Wesselius, Riccardo Bonadonna, Andrea Mari, Casper G Schalkwijk, Marleen MJ Greevenbroek, and Coen DA Stehouwer

Subjects
Endocrinology, Diabetes and Metabolism, SECRETION, Cardiology and Cardiovascular Medicine, NERVOUS-SYSTEM, DYSFUNCTION, GLUCOSE
Abstract

Objective We investigated, using population-based data, whether worse autonomic function, estimated from lower 24-hour heart rate variability (HRV), was associated with beta cell function, assessed from beta cell response during an oral glucose tolerance test (OGTT). Research design and methods We used cross-sectional data from The Maastricht Study, a population-based cohort study (N = 2,007; age, mean ± SD:60 ± 8 years; 52% men; and 24% with type 2 diabetes). We used linear regression analyses with adjustment for potential confounders (demographic, cardiovascular, and lifestyle factors) to study the associations of time- and frequency-domain HRV (composite scores) with overall beta cell response (estimated from a composite score calculated from: C-peptidogenic index, overall insulin secretion, beta cell glucose sensitivity, beta cell potentiation factor, and beta cell rate sensitivity). In addition, we tested for interaction by sex and glucose metabolism status. Results After full adjustment, lower time- and frequency-domain HRV was significantly associated with lower overall beta cell response composite score (standardized beta, -0.055 [-0.098; -0.011] and − 0.051 [-0.095; -0.007], respectively). These associations were not modified by sex and there was no consistent pattern of interaction by glucose metabolism status. Conclusion The present etiological study found that worse autonomic function, estimated from lower HRV, was associated with worse beta cell function, estimated from a composite score in a population-based sample which covered the entire spectrum of glucose metabolism. Hence, autonomic dysfunction may contribute to beta cell dysfunction and, ultimately, to the alteration of glucose metabolism status from normal glucose metabolism to prediabetes and type 2 diabetes.

Published
2023

31. Integration, harmonization, and processing of geomatic data for bridge health assessment: the Lastra a Signa case study

Author

Francesco Mugnai, Valentina Bonora, and Grazia Tucci

Subjects
Geography, Planning and Development, Earth and Planetary Sciences (miscellaneous), Environmental Science (miscellaneous), Engineering (miscellaneous)
Abstract

A visual inspection, which entails field surveying, such as photodocumentation and footage, is the first step of a multi-level approach to bridge health assessment. Furthermore, the use of surface models, CAD drawings, and orthophotos, guarantees complete and accurate documentation, thus allowing for a better understanding of the environment, the anthropic structures, and their relationships. All the georeferenced surveys’ outputs are especially advisable within a prespective of periodical monitoring, as forseen by national legislation. The work is aimed to study two adjacent bridges over the Arno River in Lastra a Signa, Italy. One of the bridges, Ponte nuovo sull’Arno, is an overpass for motor vehicles. The other one, which is called Passarella sull’Arno, is a pedestrian viaduct. A topographic reference network has been settled using the GNSS survey technique. 3D point clouds of the bridges have been acquired by performing a Laser Scanning survey. A bathymetric survey has been carried out to acquire a 3D point cloud of submerged bridges’ parts and the riverbed. Through a Photogrammetric survey from RPAS, an orthophoto of the area has been built. Finally, evidence of historical submerged bridge structures has been identified thanks to the multi beam survey. The work’s objective is to integrate surveying geomatics techniques to create a reliable survey of the bridges, the surrounding area, and the riverbed, as support to the most common structural health assessment methods.

Published
2023

32. A Structured Telephone Interview for collecting Geriatric health domains in Older People with HIV during COVID era

Author

Micol Ferrara, Jovana Milic, Michela Belli, Maria Venuta, Luca Micai, Stefania Arsuffi, Davide Minisci, Benedetta Fumarola, Stefano Bonora, Emanuele Focà, Giovanni Guaraldi, and Andrea Calcagno

Abstract

Background Elderly people living with HIV show a significant prevalence of multimorbidity, polypharmacy and frailty that increase the risk of disability. Telehealth has been suggested as a new tool to monitor people living with HIV in the COVID era, but its effectiveness in elderly is unknown. The aim of this study was two-fold: to explore feasibility of a telephone interview and its capability to collect relevant geriatric outcomes. Methods Assessed health domains included comorbidities, falls, urinary incontinence, antiretroviral drugs exposure and comedications (polypharmacy), and the following patient reported outcomes: quality of life, intrinsic capacity, and resilience. Results 214 (70.6%) answered and completed the interview. During confinement period, 57 (26.7%) of people switched antiretroviral therapy : 119 (55.4%) to dual therapy regimens and 95 (44.6%) to triple regimens. Prevalence of geriatric syndromes were falls in 31 cases (14.7%), urinary incontinence in 48 cases (22.7%) and polypharmacy 122 cases (57.2%). Mean Health-related Quality of Life score was mildly impaired (0,88%) with good concordance of Helath-related Quality of Life self-perception in a visual analogue scale (8/10) (r=+0.348; p Conclusions A structured telephone call was feasible in elderly people living with HIV and allowed to collect clinically meaningful geriatric health domains when face-to-face visits are not needed or discouraged.

Published
2023

33. The presence of resistance‐associated mutations in reverse transcriptase gene is associated with cerebrospinal fluid HIV‐1 escape: A multicentric retrospective analysis

Author

Mattia Trunfio, Carmela Pinnetti, Stefania Arsuffi, Francesca Bai, Luigi Celani, Gabriella D'Ettorre, Jaime Vera H, Antonella Darminio, Emanuele Focà, Valeria Ghisetti, stefano bonora, Andrea Antinori, and Andrea Calcagno

Subjects
cerebrospinal fluid viral escape, resistance-associated mutations, Infectious Diseases, central nervous system penetration effectiveness score, genotype resistance testing, Virology, reverse transcriptase, dual therapy
Abstract

Background: We assessed whether the association between the risk of cerebrospinal fluid escape (CVE) and specific antiretroviral (ARV) classes, such as protease inhibitors, is due to suboptimal pharmacological profile generated by archived resistance-associated mutations (RAMs). Methods: A retrospective multicentric study on 300 adult people with HIV on antiretroviral therapy (ART) and available historical plasma genotype resistance testing (HGRT) for reverse transcriptase (RT) and protease genes between 2001 and 2021. The odds ratio for demographic, clinic-, and ART-related variables and CVE was estimated by multivariable modelling. HGRT-adjusted central nervous system effectiveness penetration (CPE) score was computed in modelling the risk. Results: Median age, plasma VL, and CD4 count were 49 years, , p=0.003). CVE risk decreased by 40% per each point increase in HGRT-adjusted CPE score in multivariable models (pConclusions: Viruses harboring mutations appear to favor CVE and the impact of single ARV classes or type of ART regimens may lose significance when adjusted for the presence and effect of specific RAMs.

Published
2023

34. SMovie S4 from Accelerated Tumor Progression in Mice Lacking the ATP Receptor P2X7

Author

Francesco Di Virgilio, Vito Pistoia, Lizzia Raffaghello, Laura Emionite, Luigi Abelli, Niklas R. Jorgensen, Paolo Pinton, Domenica Corigliano, Susanne Syberg, Massimo Bonora, Alba C. Sarti, Alessandra Rotondo, Anna L. Giuliani, Simonetta Falzoni, Alessia Franceschini, Marina Capece, and Elena Adinolfi

Abstract

SMovie S4. Migration of wt N13 microglial cells from both sides of a wounded monolayer after scratching with a plastic pipette tip.

Published
2023

35. Figure S2 from Accelerated Tumor Progression in Mice Lacking the ATP Receptor P2X7

Author

Francesco Di Virgilio, Vito Pistoia, Lizzia Raffaghello, Laura Emionite, Luigi Abelli, Niklas R. Jorgensen, Paolo Pinton, Domenica Corigliano, Susanne Syberg, Massimo Bonora, Alba C. Sarti, Alessandra Rotondo, Anna L. Giuliani, Simonetta Falzoni, Alessia Franceschini, Marina Capece, and Elena Adinolfi

Abstract

Figure S2. Core necrosis in B16 melanomas. Representative images of central necrosis of B16 melanoma masses in P2X7R-KO (A and B) or wt (C and D) mice. Specimens were fixed and stained with haematoxylin-eosin as described in Materials and Methods.

Published
2023

36. SMovie S5 from Accelerated Tumor Progression in Mice Lacking the ATP Receptor P2X7

Author

Francesco Di Virgilio, Vito Pistoia, Lizzia Raffaghello, Laura Emionite, Luigi Abelli, Niklas R. Jorgensen, Paolo Pinton, Domenica Corigliano, Susanne Syberg, Massimo Bonora, Alba C. Sarti, Alessandra Rotondo, Anna L. Giuliani, Simonetta Falzoni, Alessia Franceschini, Marina Capece, and Elena Adinolfi

Abstract

SMovie S5. N13R microglial cells are unable to migrate in response to wounding.

Published
2023

37. Figure S3 from Accelerated Tumor Progression in Mice Lacking the ATP Receptor P2X7

Author

Francesco Di Virgilio, Vito Pistoia, Lizzia Raffaghello, Laura Emionite, Luigi Abelli, Niklas R. Jorgensen, Paolo Pinton, Domenica Corigliano, Susanne Syberg, Massimo Bonora, Alba C. Sarti, Alessandra Rotondo, Anna L. Giuliani, Simonetta Falzoni, Alessia Franceschini, Marina Capece, and Elena Adinolfi

Abstract

Figure S3. Effect of P2X7R deletion on VEGF release. A, in vitro VEGF release from wt or P2X7R-silenced B16 cells. B, intra-tumor VEGF content of B16-wt or P2X7R-silenced tumors grown in wt or P2X7R-KO mice. VEGF was measured by ELISA. A, * p < 0.05 for B16 shRNA vs B16-wt. B, * p < 0.05 for P2X7R-wt + B16 shRNA vs P2X7R-wt + B16-wt; {section sign}{section sign} p < 0.01 for P2X7R-KO + B16 shRNA vs P2X7R-KO + B16-wt. C-F, VEGF staining of tumors from P2X7R-KO (C and D) or wt (E and F) mice. Specimens were fixed and stained with the anti-VEGF Ab as described in Materials and Methods.

Published
2023

38. Figure S1 from Accelerated Tumor Progression in Mice Lacking the ATP Receptor P2X7

Author

Francesco Di Virgilio, Vito Pistoia, Lizzia Raffaghello, Laura Emionite, Luigi Abelli, Niklas R. Jorgensen, Paolo Pinton, Domenica Corigliano, Susanne Syberg, Massimo Bonora, Alba C. Sarti, Alessandra Rotondo, Anna L. Giuliani, Simonetta Falzoni, Alessia Franceschini, Marina Capece, and Elena Adinolfi

Abstract

Figure S1. Characterization of P2X7R shRNA B16 cells. A, densitometry of P2X7R protein expression. B, representative Western blot. C, Fura-2 measurement of Benzoyl ATP (BzATP)-triggered intracellular Ca2+ increase. D, Averages intracellular Ca2+ increases in wt and P2X7R-silenced B16 cells. Data are averages + SEM, n = 5. ***, p < 0.001. E, rate of proliferation of wt and P2X7R-silenced B16 cell cultures. Intracellular Ca2+ changes and proliferation rates were measured as described in Adinolfi et al., 2005, Mol Biol Cell 16:3260-3272.

Published
2023

40. Data from Accelerated Tumor Progression in Mice Lacking the ATP Receptor P2X7

Author

Francesco Di Virgilio, Vito Pistoia, Lizzia Raffaghello, Laura Emionite, Luigi Abelli, Niklas R. Jorgensen, Paolo Pinton, Domenica Corigliano, Susanne Syberg, Massimo Bonora, Alba C. Sarti, Alessandra Rotondo, Anna L. Giuliani, Simonetta Falzoni, Alessia Franceschini, Marina Capece, and Elena Adinolfi

Abstract

The ATP receptor P2X7 (P2X7R or P2RX7) has a key role in inflammation and immunity, but its possible roles in cancer are not firmly established. In the present study, we investigated the effect of host genetic deletion of P2X7R in the mouse on the growth of B16 melanoma or CT26 colon carcinoma cells. Tumor size and metastatic dissemination were assessed by in vivo calliper and luciferase luminescence emission measurements along with postmortem examination. In P2X7R-deficient mice, tumor growth and metastatic spreading were accelerated strongly, compared with wild-type (wt) mice. Intratumoral IL-1β and VEGF release were drastically reduced, and inflammatory cell infiltration was abrogated nearly completely. Similarly, tumor growth was also greatly accelerated in wt chimeric mice implanted with P2X7R-deficient bone marrow cells, defining hematopoietic cells as a sufficient site of P2X7R action. Finally, dendritic cells from P2X7R-deficient mice were unresponsive to stimulation with tumor cells, and chemotaxis of P2X7R-less cells was impaired. Overall, our results showed that host P2X7R expression was critical to support an antitumor immune response, and to restrict tumor growth and metastatic diffusion. Cancer Res; 75(4); 635–44. ©2014 AACR.

Published
2023

41. Preharvest factors affecting quality and antioxidant levels on Abate Fétel pears: study of superficial scald with a multivariate statistical approach and neural networks

Author

Bonora, Alessandro <1993> and Corelli Grappadelli, Luca

Subjects
AGR/03 Arboricoltura generale e coltivazioni arboree
Abstract

There are only a few insights concerning the influence that agronomic and management variability may have on superficial scald (SS) in pears. Abate Fétel pears were picked during three seasons (2018, 2019 and 2020) from thirty commercial orchards in the Emilia Romagna region, Italy. Using a multivariate statistical approach, high heterogeneity between farms for SS development after cold storage with regular atmosphere was demonstrated. Indeed, some factors seem to affect SS in all growing seasons: high yields, soil texture, improper irrigation and Nitrogen management, use of plant growth regulators, late harvest, precipitations, Calcium and cow manure, presence of nets, orchard age, training system and rootstock. Afterwards, we explored the spatio/temporal variability of fruit attributes in two pear orchards. Environmental and physiological spatial variables were recorded by a portable RTK GPS. High spatial variability of the SS index was observed. Through a geostatistical approach, some characteristics, including soil electrical conductivity and fruit size, have been shown to be negatively correlated with SS. Moreover, regression tree analyses were applied suggesting the presence of threshold values of antioxidant capacity, total phenolic content, and acidity against SS. High pulp firmness and IAD values before storage, denoting a more immature fruit, appeared to be correlated with low SS. Finally, a convolution neural networks (CNN) was tested to detect SS and the starch pattern index (SPI) in pears for portable device applications. Preliminary statistics showed that the model for SS had low accuracy but good precision, and the CNN for SPI denoted good performances compared to the Ctifl and Laimburg scales. The major conclusion is that Abate Fétel pears can potentially be stored in different cold rooms, according to their origin and quality features, ensuring the best fruit quality for the final consumers. These results might lead to a substantial improvement in the Italian pear industry.

Published
2023

42. Transient Plasma Viral Rebound After Sars-cov-2 Vaccination in an Exceptional Hiv-1 Elite Controller Woman

Author

Laura Di Girolamo, Micol Ferrara, Giulia Trevisan, Bianca Maria Longo, Tiziano Allice, Elisa Burdino, Francesca Alladio, Silvia Fantino, Giovanni Di Perri, Andrea Calcagno, and Stefano Bonora

Abstract

Background Elite controllers are able to control viral replication without antiretroviral therapy. Exceptional elite controllers do not show disease progression for more than 25 years. Different mechanisms have been proposed and several elements of both innate and adaptive immunity are implicated. Vaccines are immune stimulating agents that can promote HIV-RNA transcription; transient plasma HIV-RNA detectability has been described within 7-14 days after different vaccinations. The most reliable mechanism involved in virosuppressed people living with HIV is a generalized inflammatory response that activates bystander cells harboring latent HIV. So far no data about viral load increase in elite controllers after SARS-CoV-2 vaccination are reported in literature. Case Presentation We report the case of a 65-year-old woman of European ancestry, diagnosed with HIV-1/HCV co-infection more than 25 years ago. Since then, HIV-RNA remained undetectable and she never received ARV therapy. In 2021 she was vaccinated with mRNA-BNT162b2 vaccine (Pfizer-BioNTech®). She was administered with three doses in June, July and October 2021, respectively. The last available viral load was undetectable in March 2021. We observed an increase of VL at 32 cp/ml and 124 cp/mL, two and seven months after the first vaccine dose, respectively. During monthly follow-up, HIV-RNA gradually and spontaneously dropped becoming undetectable without ARV intervention. COVID-19 serology was positive with IgG 535 BAU/mL, showing response to vaccination. We measured total HIV-DNA at different time-points and we found it detectable both at the time of the higher plasma HIV-RNA (30 cp/10^6 PBMCs) and when it was undetectable (13 cp/10^6 PBMCs), in reduction. Conclusions This case is the first report, to our knowledge, describing a rebound of plasma HIV-RNA in an elite controller after three doses of mRNA-BNT162b2 vaccine for SARS-CoV-2. Concomitantly with a spontaneous reduction of plasma HIV-RNA ten months after the third dose of mRNA-BNT162b2 vaccine (Pfizer-BioNTech®) without antiretroviral therapy intervention, we observed a reduction of total HIV-DNA in peripheral mononuclear cells. The potential role of vaccinations in altering HIV reservoir, even in elite controllers population when plasma HIV-RNA is undetectable, could be a valuable aspect to take into account for the future HIV eradication interventions.

Published
2023

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