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3. Antibody sequence determinants of viral antigen specificity

Author

Alexandra A. Abu-Shmais, Matthew J. Vukovich, Perry T. Wasdin, Yukthi P. Suresh, Toma M. Marinov, Scott A. Rush, Rebecca A. Gillespie, Rajeshwer S. Sankhala, Misook Choe, M. Gordon Joyce, Masaru Kanekiyo, Jason S. McLellan, and Ivelin S. Georgiev

Subjects
B-cell responses, public clonotype, antigen specificity, virus, antibody repertoire, B-cell repertoire, Microbiology, QR1-502
Abstract

ABSTRACT Throughout life, humans experience repeated exposure to viral antigens through infection and vaccination, resulting in the generation of diverse, antigen-specific antibody repertoires. A paramount feature of antibodies that enables their critical contributions in counteracting recurrent and novel pathogens, and consequently fostering their utility as valuable targets for therapeutic and vaccine development, is the exquisite specificity displayed against their target antigens. Yet, there is still limited understanding of the determinants of antibody-antigen specificity, particularly as a function of antibody sequence. In recent years, experimental characterization of antibody repertoires has led to novel insights into fundamental properties of antibody sequences but has been largely decoupled from at-scale antigen specificity analysis. Here, using the LIBRA-seq technology, we generated a large data set mapping antibody sequence to antigen specificity for thousands of B cells, by screening the repertoires of a set of healthy individuals against 20 viral antigens representing diverse pathogens of biomedical significance. Analysis uncovered virus-specific patterns in variable gene usage, gene pairing, somatic hypermutation, as well as the presence of convergent antiviral signatures across multiple individuals, including the presence of public antibody clonotypes. Notably, our results showed that, for B-cell receptors originating from different individuals but leveraging an identical combination of heavy and light chain variable genes, there is a specific CDRH3 identity threshold above which B cells appear to exclusively share the same antigen specificity. This finding provides a quantifiable measure of the relationship between antibody sequence and antigen specificity and further defines experimentally grounded criteria for defining public antibody clonality.IMPORTANCEThe B-cell compartment of the humoral immune system plays a critical role in the generation of antibodies upon new and repeated pathogen exposure. This study provides an unprecedented level of detail on the molecular characteristics of antibody repertoires that are specific to each of the different target pathogens studied here and provides empirical evidence in support of a 70% CDRH3 amino acid identity threshold in pairs of B cells encoded by identical IGHV:IGL(K)V genes, as a means of defining public clonality and therefore predicting B-cell antigen specificity in different individuals. This is of exceptional importance when leveraging public clonality as a method to annotate B-cell receptor data otherwise lacking antigen specificity information. Understanding the fundamental rules of antibody-antigen interactions can lead to transformative new approaches for the development of antibody therapeutics and vaccines against current and emerging viruses.

Published
2024
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5. The Predisposition for Type 2 Diabetes Mellitus and Metabolic Syndrome

Author

Zenoaga-Barbăroșie C, Berca L, Vassu-Dimov T, Toma M, Nica MI, Alexiu-Toma OA, Ciornei C, Albu A, Nica S, Nistor C, and Nica R

Subjects
ace id, enos vntr 4a/b, metabolic syndrome, g%29%22">oxtr (a>g), sod1 +35a/c, type 2 diabetes mellitus, Genetics, QH426-470
Abstract

Type 2 diabetes mellitus (T2DM) and metabolic syndrome (MetS) are diseases caused by the interaction of genetic and non-genetic factors. Therefore, the aim of our study was to investigate the association between six common genetic polymorphisms and T2DM and MetS in males. A total of 120 T2DM, 75 MetS, and 120 healthy controls (HC) were included in the study. ACE ID, eNOS 4a/b, ATR1 A1166C, OXTR (A>G), SOD1 +35A/C, CAT-21A/T gene polymorphisms were genotyped by PCR or PCR-RFLP techniques. T2DM was diagnosed at an earlier age compared to MetS (54 vs 55 years old, p=0.0003) and the difference was greater in carriers of the OXTR G allele (54 vs 56 years old, p=0.0002) or both OXTR G and eNOS b alleles (54 vs 56, p=0.00016). The SOD1 AA genotype (O.R.=0.11, p=0.0006) and the presence of both ACE I and OXTR1 A (O.R.=0.39, p=0.0005) alleles revealed to be protective for T2DM. SOD1 AA and AC genotypes were protective factors for triglyceride (p=0.0002 and p=0.0005, respectively) and HDL cholesterol (p=0.0002 and p=0.0004, respectively) levels in T2DM patients. ACE DD was identified more frequently in hypertensive T2DM patients (O.R.=3.77, p=0.0005) and in those who reported drinking alcohol (p=0.0001) comparing to HC and T2DM patients who did not drink alcohol, respectively. We observed that T2DM patients who reported drinking alcohol had an increased frequency of ACE DD and eNOS bb (p

Published
2023
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6. Diffusion Equation

Author

Santamaria, Fidel, Marinov, Toma M., Migliore, Michele, Section editor, Linster, Christiane, Section editor, Cavarretta, Francesco, Section editor, Jaeger, Dieter, editor, and Jung, Ranu, editor

Published
2022
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8. Empagliflozin in the treatment of heart failure with reduced ejection fraction in addition to background therapies and therapeutic combinations (EMPEROR-Reduced): a post-hoc analysis of a randomised, double-blind trial

Author

Packer, M, Anker, S, Butler, J, Filippatos, G, Pocock, S, Zannad, F, Ferreira, JP, Brueckmann, M, George, J, Jamal, W, Welty, FK, Palmer, M, Clayton, T, Parhofer, KG, Pedersen, TR, Greenberg, B, Konstam, MA, Lees, KR, Carson, P, Doehner, W, Miller, A, Haas, M, Pehrson, S, Komajda, M, Anand, I, Teerlink, J, Rabinstein, A, Steiner, T, Kamel, H, Tsivgoulis, G, Lewis, J, Freston, J, Kaplowitz, N, Mann, J, Petrie, J, Perrone, S, Nicholls, S, Janssens, S, Bocchi, E, Giannetti, N, Verma, S, Zhang, J, Spinar, J, Seronde, M-F, Boehm, M, Merkely, B, Chopra, V, Senni, M, Taddi, S, Tsutsui, H, Choi, D-J, Chuquiure, E, La Rocca, HPB, Ponikowski, P, Juanatey, JRG, Squire, I, Januzzi, J, Pina, I, Bernstein, R, Cheung, A, Green, J, Kaul, S, Lam, C, Lip, G, Marx, N, McCullough, P, Mehta, C, Rosenstock, J, Sattar, N, Scirica, B, Shah, S, Wanner, C, Aizenberg, D, Cartasegna, L, Colombo Berra, F, Colombo, H, Fernandez Moutin, M, Glenny, J, Alvarez Lorio, C, Anauch, D, Campos, R, Facta, A, Fernandez, A, Ahuad Guerrero, R, Lobo Márquez, L, Leon de la Fuente, RA, Mansilla, M, Hominal, M, Hasbani, E, Najenson, M, Moises Azize, G, Luquez, H, Guzman, L, Sessa, H, Amuchástegui, M, Salomone, O, Perna, E, Piskorz, D, Sicer, M, Perez de Arenaza, D, Zaidman, C, Nani, S, Poy, C, Resk, J, Villarreal, R, Majul, C, Smith Casabella, T, Sassone, S, Liberman, A, Carnero, G, Caccavo, A, Berli, M, Budassi, N, Bono, J, Alvarisqueta, A, Amerena, J, Kostner, K, Hamilton, A, Begg, A, Beltrame, J, Colquhoun, D, Gordon, G, Sverdlov, A, Vaddadi, G, Wong, J, Coller, J, Prior, D, Friart, A, Leone, A, Vervoort, G, Timmermans, P, Troisfontaines, P, Franssen, C, Sarens, T, Vandekerckhove, H, Van De Borne, P, Chenot, F, De Sutter, J, De Vuyst, E, Debonnaire, P, Dupont, M, Pereira Dutra, O, Canani, LH, Vieira Moreira, MdC, de Souza, W, Backes, LM, Maia, L, De Souza Paolino, B, Manenti, ER, Saporito, W, Villaça Guimarães Filho, F, Franco Hirakawa, T, Saliba, LA, Neuenschwander, FC, de Freitas Zerbini, CA, Gonçalves, G, Gonçalves Mello, Y, Ascenção de Souza, J, Beck da Silva Neto, L, Bocchi, EA, Da Silveira, J, de Moura Xavier Moraes Junior, JB, de Souza Neto, JD, Hernandes, M, Finimundi, HC, Sampaio, CR, Vasconcellos, E, Neves Mancuso, FJ, Noya Rabelo, MM, Rodrigues Bacci, M, Santos, F, Vidotti, M, Simões, MV, Gomes, FL, Vieira Nascimento, C, Precoma, D, Helfenstein Fonseca, FA, Ribas Fortes, JA, Leães, PE, Campos de Albuquerque, D, Kerr Saraiva, JF, Rassi, S, Alves da Costa, FA, Reis, G, Zieroth, S, Dion, D, Savard, D, Bourgeois, R, Constance, C, Anderson, K, Leblanc, M-H, Yung, D, Swiggum, E, Pliamm, L, Pesant, Y, Tyrrell, B, Huynh, T, Spiegelman, J, Lavoie, J-P, Hartleib, M, Bhargava, R, Straatman, L, Virani, S, Costa-Vitali, A, Hill, L, Heffernan, M, Khaykin, Y, Ricci, J, Senaratne, M, Zhai, A, Lubelsky, B, Toma, M, Yao, L, McKelvie, R, Noronha, L, Babapulle, M, Pandey, A, Curnew, G, Lavoie, A, Berlingieri, J, Kouz, S, Lonn, E, Chehayeb, R, Zheng, Y, Sun, Y, Cui, H, Fan, Z, Han, X, Jiang, X, Tang, Q, Zhou, J, Zheng, Z, Zhang, X, Zhang, N, Zhang, Y, Shen, A, Yu, J, Ye, J, Yao, Y, Yan, J, Xu, X, Wang, Z, Ma, J, Li, Y, Li, S, Lu, S, Kong, X, Song, Y, Yang, G, Yao, Z, Pan, Y, Guo, X, Sun, Z, Dong, Y, Zhu, J, Peng, D, Yuan, Z, Lin, J, Yin, Y, Jerabek, O, Burianova, H, Fiala, T, Hubac, J, Ludka, O, Monhart, Z, Vodnansky, P, Zeman, K, Foldyna, D, Krupicka, J, Podpera, I, Busak, L, Radvan, M, Vomacka, Z, Prosecky, R, Cifkova, R, Durdil, V, Vesely, J, Vaclavik, J, Cervinka, P, Linhart, A, Brabec, T, Miklik, R, Bourhaial, H, Olbrich, H-G, Genth-Zotz, S, Kemala, E, Lemke, B, Böhm, M, Schellong, S, Rieker, W, Heitzer, T, Ince, H, Faghih, M, Birkenfeld, A, Begemann, A, Ghanem, A, Ujeyl, A, von Haehling, S, Dorsel, T, Bauersachs, J, Prull, M, Weidemann, F, Darius, H, Nickenig, G, Wilke, A, Sauter, J, Rauch-Kroehnert, U, Frey, N, Schulze, CP, König, W, Maier, L, Menzel, F, Proskynitopoulos, N, Ebert, H-H, Sarnighausen, H-E, Düngen, H-D, Licka, M, Stellbrink, C, Winkelmann, B, Menck, N, López-Sendón, JL, de la Fuente Galán, L, Delgado Jiménez, JF, Manito Lorite, N, Pérez de Juan Romero, M, Galve Basilio, E, Cereto Castro, F, González Juanatey, JR, Gómez, JJ, Sanmartín Fernández, M, Garcia-Moll Marimon, X, Pascual Figal, D, Bover Freire, R, Bonnefoy Cudraz, E, Jobbe Duval, A, Tomasevic, D, Habib, G, Isnard, R, Picard, F, Khanoyan, P, Dubois-Rande, J-L, Galinier, M, Roubille, F, Alexandre, J, Babuty, D, Delarche, N, Berneau, J-B, Girerd, N, Saxena, M, Rosano, G, Yousef, Z, Clifford, C, Arden, C, Bakhai, A, Boos, C, Jenkins, G, Travill, C, Price, D, Koenyves, L, Lakatos, F, Matoltsy, A, Noori, E, Zilahi, Z, Andrassy, P, Kancz, S, Simon, G, Sydo, T, Vorobcsuk, A, Kiss, RG, Toth, K, Szakal, I, Nagy, L, Barany, T, Nagy, A, Szolnoki, E, Chopra, VK, Mandal, S, Rastogi, V, Shah, B, Mullasari, A, Shankar, J, Mehta, V, Oomman, A, Kaul, U, Komarlu, S, Kahali, D, Bhagwat, A, Vijan, V, Ghaisas, NK, Mehta, A, Kashyap, J, Kothari, Y, TaddeI, S, Scherillo, M, Zacà, V, Genovese, S, Salvioni, A, Fucili, A, Fedele, F, Cosmi, F, Volpe, M, Mazzone, C, Esposito, G, Doi, M, Yamamoto, H, Sakagami, S, Oishi, S, Yasaka, Y, Tsuboi, H, Fujino, Y, Matsuoka, S, Watanabe, Y, Himi, T, Ide, T, Ichikawa, M, Kijima, Y, Koga, T, Yuda, S, Fukui, K, Kubota, T, Manita, M, Fujinaga, H, Matsumura, T, Fukumoto, Y, Kato, R, Kawai, Y, Hiasa, G, Kazatani, Y, Mori, M, Ogimoto, A, Inoko, M, Oguri, M, Kinoshita, M, Okuhara, K, Watanabe, N, Ono, Y, Otomo, K, Sato, Y, Matsunaga, T, Takaishi, A, Miyagi, N, Uehara, H, Takaishi, H, Urata, H, Kataoka, T, Matsubara, H, Matsumoto, T, Suzuki, T, Takahashi, N, Imamaki, M, Yoshitama, T, Saito, T, Sekino, H, Furutani, Y, Koda, M, Shinozaki, T, Hirabayashi, K, Tsunoda, R, Yonezawa, K, Hori, H, Yagi, M, Arikawa, M, Hashizume, T, Ishiki, R, Koizumi, T, Nakayama, K, Taguchi, S, Nanasato, M, Yoshida, Y, Tsujiyama, S, Nakamura, T, Oku, K, Shimizu, M, Suwa, M, Momiyama, Y, Sugiyama, H, Kobayashi, K, Inoue, S, Kadokami, T, Maeno, K, Kawamitsu, K, Maruyama, Y, Nakata, A, Shibata, T, Wada, A, Cho, H-J, Na, JO, Yoo, B-S, Choi, J-O, Hong, SK, Shin, J-H, Cho, M-C, Han, SH, Jeong, J-O, Kim, J-J, Kang, SM, Kim, D-S, Kim, MH, Llamas Esperon, G, Illescas Díaz, J, Fajardo Campos, P, Almeida Alvarado, J, Bazzoni Ruiz, A, Echeverri Rico, J, Lopez Alcocer, I, Valle Molina, L, Hernandez Herrera, C, Calvo Vargas, C, Padilla Padilla, FG, Rodriguez Briones, I, Chuquiure Valenzuela, EJJR, Aguilera Real, ME, Carrillo Calvillo, J, Alpizar Salazar, M, Cervantes Escárcega, JL, Velasco Sanchez, R, Al - Windy, N, van Heerebeek, L, Bellersen, L, Brunner-La Rocca, H-P, Post, J, Linssen, GCM, van de Wetering, M, Peters, R, van Stralen, R, Groutars, R, Smits, P, Yilmaz, A, Kok, WEM, Van der Meer, P, Dijkmans, P, Troquay, R, van Alem, AP, Van de Wal, R, Handoko, L, Westendorp, ICD, van Bergen, PFMM, Rensing, BJWM, Hoogslag, P, Kietselaer, B, Kragten, JA, den Hartog, FR, Alings, A, Danilowicz-Szymanowicz, L, Raczak, G, Piesiewicz, W, Zmuda, W, Kus, W, Podolec, P, Musial, W, Drelich, G, Kania, G, Miekus, P, Mazur, S, Janik, A, Spyra, J, Peruga, J, Balsam, P, Krakowiak, B, Szachniewicz, J, Ginel, M, Grzybowski, J, Chrustowski, W, Wojewoda, P, Kalinka, A, Zurakowski, A, Koc, R, Debinski, M, Fil, W, Kujawiak, M, Forys, J, Kasprzak, M, Krol, M, Michalski, P, Mirek-Bryniarska, E, Radwan, K, Skonieczny, G, Stania, K, Skoczylas, G, Madej, A, Jurowiecki, J, Firek, B, Wozakowska-Kaplon, B, Cymerman, K, Neutel, J, Adams, K, Balfour, P, Deswal, A, Djamson, A, Duncan, P, Hong, M, Murray, C, Rinde-Hoffman, D, Woodhouse, S, MacNevin, R, Rama, B, Broome-Webster, C, Kindsvater, S, Abramov, D, Barettella, M, Pinney, S, Herre, J, Cohen, A, Vora, K, Challappa, K, West, S, Baum, S, Cox, J, Jani, S, Karim, A, Akhtar, A, Quintana, O, Paukman, L, Goldberg, R, Bhatti, Z, Budoff, M, Bush, E, Potler, A, Delgado, R, Ellis, B, Dy, J, Fialkow, J, Sangrigoli, R, Ferdinand, K, East, C, Falkowski, S, Donahoe, S, Ebrahimi, R, Kline, G, Harris, B, Khouzam, R, Jaffrani, N, Jarmukli, N, Kazemi, N, Koren, M, Friedman, K, Herzog, W, Silva Enciso, J, Cheung, D, Grover-McKay, M, Hauptman, P, Mikhalkova, D, Hegde, V, Hodsden, J, Khouri, S, McGrew, F, Littlefield, R, Bradley, P, McLaurin, B, Lupovitch, S, Labin, I, Rao, V, Leithe, M, Lesko, M, Lewis, N, Lombardo, D, Mahal, S, Malhotra, V, Dauber, I, Banerjee, A, Needell, J, Miller, G, Paladino, L, Munuswamy, K, Nanna, M, McMillan, E, Mumma, M, Napoli, M, Nelson, W, O'Brien, T, Adlakha, A, Onwuanyi, A, Serota, H, Schmedtje, J, Paraschos, A, Potu, R, Sai-Sudhakar, C, Saltzberg, M, Sauer, A, Shah, P, Skopicki, H, Bui, H, Carr, K, Stevens, G, Tahirkheli, N, Tallaj, J, Yousuf, K, Trichon, B, Welker, J, Tolerico, P, Vest, A, Vivo, R, Wang, X, Abadier, R, Dunlap, S, Weintraub, N, Malik, A, Kotha, P, Zaha, V, Kim, G, Uriel, N, Greene, T, Salacata, A, Arora, R, Gazmuri, R, Kobayashi, J, Iteld, B, Vijayakrishnan, R, Dab, R, Mirza, Z, Marques, V, Nallasivan, M, Bensimhon, D, Peart, B, Saint-Jacques, H, Barringhaus, K, Contreras, J, Gupta, A, Koneru, S, Nguyen, V, Verma, Subodh, Dhingra, Nitish K, Butler, Javed, Anker, Stefan D, Ferreira, Joao Pedro, Filippatos, Gerasimos, Januzzi, James L, Lam, Carolyn S P, Sattar, Naveed, Peil, Barbara, Nordaby, Matias, Brueckmann, Martina, Pocock, Stuart J, Zannad, Faiez, and Packer, Milton

Published
2022
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9. Predictive Models Refine Physician Prognostication: A Secondary Analysis Evaluating Integrated Model and Physician Prognostic Estimates in Heart Failure Patients with Reduced Left Ventricular Ejection Fraction

Author

Alba, A., primary, Buchan, T., additional, Saha, S., additional, Fan, C., additional, Poon, S., additional, Al-Hesayen, A., additional, Toma, M., additional, Zieroth, S., additional, Anderson, K., additional, Demers, C., additional, Amin, F., additional, Porepa, L., additional, Chih, S., additional, Giannetti, N., additional, Rac, V., additional, Ross, H., additional, and Guyatt, G., additional

Published
2024
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16. Membranous NECTIN-4 expression in metastasis versus matched primary tumor more accurately predicts enfortumab vedotin response

Author

Büttner, T., primary, Zschäbitz, S., additional, Bolenz, C., additional, Zengerling, F., additional, Heers, H., additional, Nagy, D., additional, Toma, M., additional, Kristiansen, G., additional, Ellinger, J., additional, Ritter, M., additional, Hartmann, A., additional, Hölzel, M., additional, Eckstein, M., additional, and Klümper, N., additional

Published
2024
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17. Preclinical evidence for the use of anti-TROP-2 antibody-drug conjugate Sacituzumab govitecan in cerebral metastasized castration-resistant prostate cancer

Author

Weiten, R., primary, Niemann, M., additional, Below, E., additional, Friker, L.L., additional, Ralser, D.J., additional, Toma, M., additional, Kristiansen, G., additional, Hahn, O., additional, Zechel, S., additional, Grünwald, V., additional, Bald, T., additional, Siewert, J., additional, Pietsch, T., additional, Ritter, M., additional, Hölzel, M., additional, Eckstein, M., additional, Alajati, A., additional, Krausewitz, P., additional, and Klümper, N., additional

Published
2024
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19. Präklinische Evidenz für den Einsatz des Anti-Trop-2-Antikörper-Wirkstoff-Konjugats Sacituzumab govitecan beim zerebral mCRPC

Author

Niemann, MJ, Weiten, R, Below, E, Friker, LL, Ralser, DJ, Toma, M, Kristiansen, G, Hahn, O, Zechel, S, Grünwald, V, Bald, T, Siewert, J, Pietsch, T, Ritter, M, Hölzel, M, Eckstein, M, Alajati, A, Krausewitz, P, Klümper, N, Niemann, MJ, Weiten, R, Below, E, Friker, LL, Ralser, DJ, Toma, M, Kristiansen, G, Hahn, O, Zechel, S, Grünwald, V, Bald, T, Siewert, J, Pietsch, T, Ritter, M, Hölzel, M, Eckstein, M, Alajati, A, Krausewitz, P, and Klümper, N

Published
2024

21. Die membranäre NECTIN-4-Expression in der Metastase prognostiziert das Ansprechen auf Enfortumab Vedotin besser als der korrespondierende Primärtumor

Author

Büttner, T, Zschäbitz, S, Bolenz, C, Zengerling, F, Heers, H, Nagy, D, Toma, M, Kristiansen, G, Ellinger, J, Ritter, M, Hartmann, A, Hölzel, M, Eckstein, M, Klümper, N, Büttner, T, Zschäbitz, S, Bolenz, C, Zengerling, F, Heers, H, Nagy, D, Toma, M, Kristiansen, G, Ellinger, J, Ritter, M, Hartmann, A, Hölzel, M, Eckstein, M, and Klümper, N

Published
2024

22. Status der Verfügbarkeit und Anwendung von „next generation sequencing“ (NGS) beim Harnblasenkarzinom – eine Umfrage in der Arbeitsgemeinschaft Uropathologie

Author

Ortiz-Brüchle, N., Muders, M., Toma, M., Esposito, I., Hartmann, A., Stöhr, R., Reis, H., Wild, P., Köllermann, J., Bremmer, F., Leichsenring, J., Stenzinger, A., Merkelbach-Bruse, S., Kirfel, S., Perner, S., Hartmann, N., Roth, W., Jung, A., Kirchner, T., Schwamborn, K., Pfarr, N., Dahl, E., Knüchel, R., and Gaisa, N. T.

Published
2020
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26. Risk assessment according to the presence of left heart disease phenotype in pulmonary arterial hypertension patients: a multicenter cohort study

Author

Toma, M, primary, Barbisan, D, additional, Lombardi, C M, additional, Airo, E, additional, Driussi, M, additional, Gentile, P, additional, Howard, L, additional, Moschella, M, additional, Di Poi, E, additional, Garascia, A, additional, Adamo, M, additional, Sinagra, G, additional, Lo Giudice, F, additional, Stolfo, D, additional, and Ameri, P, additional

Published
2023
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27. FACTORS IMPACTING PHYSICIAN PROGNOSTIC ACCURACY IN HEART FAILURE PATIENTS WITH REDUCED LEFT VENTRICULAR EJECTION FRACTION

Author

Alba, A., primary, Buchan, T., additional, Saha, S., additional, Fan, S., additional, Poon, S., additional, Mak, S., additional, Al-Hesayen, A., additional, Toma, M., additional, Zieroth, S., additional, Anderson, K., additional, Demers, C., additional, Porepa, L., additional, Chih, S., additional, Giannetti, N., additional, Rac, V., additional, Ross, H., additional, and Guyatt, G., additional

Published
2023
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28. Phenotype and outcome correlates of high dose loop diuretics in type 1 pulmonary hypertension

Author

Stolfo, D, primary, Barbisan, D, additional, Lo Giudice, F, additional, Lombardi, C M, additional, Airo', E, additional, Driussi, M, additional, Gentile, P, additional, Howard, L, additional, Giannoni, A, additional, Collini, V, additional, Toma, M, additional, Garascia, A, additional, Metra, M, additional, Sinagra, G, additional, and Ameri, P, additional

Published
2023
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33. Characterization of ZnO, Ga-Doped ZnO, and Nd-Ga-Doped ZnO Thin Films Synthesized by Radiofrequency Magnetron Sputtering.

Author

Toma, M., Domokos, R., Lung, C., Marconi, D., and Pop, M.

Abstract

Here is described the influence of deposition parameters of ZnO thin films doped with Ga and co-doped with (Ga + Nd) upon the structural, morphological, optical and electrical properties. The transparent conductive thin films were fabricated by radiofrequency (RF) magnetron sputtering using a power of 100 W and a deposition distance of 6 cm. The deposition was performed on glass substrates heated at 150 °C with a time deposition of 90 min. The influence of doping upon the structure of thin films was analyzed by x-ray diffraction (XRD). Optical transmission measurements showed an 85% transparency in the visible range for the undoped ZnO films and the transparency of these films decreased when the dopants were added. Micro-structural analysis obtained by atomic force microscopy (AFM) evidenced that the type of doping modify the microstructure of thin films. Raman and resistivity measurements emphasize the successful incorporation of dopants into the ZnO host material. [ABSTRACT FROM AUTHOR]

Published
2024
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35. Impact of COVID-19 pandemic on pediatric endoscopy: A multicenter study on behalf of the SIGENP Endoscopy Working Group

Author

Renzo S., Scarallo L., Antoniello L. M., Bramuzzo M., Chiaro A., Cisaro F., Contini A. C. I., De Angelis G. L., De Angelis P., Di Nardo G., Felici E., Iuliano S., Macchini F., Mantegazza C., Martelossi S., Oliva S., Parrinello F., Rea F., Pizzol A., Romano C., Russo G., Sansotta N., Lionetti P., Dabizzi E., Saccomani M. D., Di Toma M., Gatti S., Illiceto M. T., Isoldi S., Maino M., Pellegrino M., Strisciuglio C., Renzo, S., Scarallo, L., Antoniello, L. M., Bramuzzo, M., Chiaro, A., Cisaro, F., Contini, A. C. I., De Angelis, G. L., De Angelis, P., Di Nardo, G., Felici, E., Iuliano, S., Macchini, F., Mantegazza, C., Martelossi, S., Oliva, S., Parrinello, F., Rea, F., Pizzol, A., Romano, C., Russo, G., Sansotta, N., Lionetti, P., Dabizzi, E., Saccomani, M. D., Di Toma, M., Gatti, S., Illiceto, M. T., Isoldi, S., Maino, M., Pellegrino, M., and Strisciuglio, C.

Subjects
child, Hepatology, SARS-CoV-2, pediatric endoscopy, surveys and questionnaires, Gastroenterology, COVID-19, endoscopy, endoscopy, gastrointestinal, humans, pandemics, gastrointestinal, Endoscopy, Gastrointestinal
Abstract

Background: Aim of the present report was to investigate the repercussions of COVID-19 pandemic on the procedural volumes and on the main indications of pediatric digestive endoscopy in Italy. Methods: An online survey was distributed at the beginning of December 2020 to Italian digestive endoscopy centers. Data were collected comparing two selected time intervals: the first from 1st of February 2019 to 30th June 2019 and the second from 1st February 2020 to 30th June 2020. Results: Responses to the survey came from 24 pediatric endoscopy Units. Globally, a reduction of 37.2% was observed between 2019 and 2020 periods with a significant decrease in median number of procedures (111 vs 57, p < 0.001). Both the median number of procedures performed for new diagnoses and those for follow-up purposes significantly decreased in 2020 (63 vs 36, p < 0.001 and 42 vs 21, p< 0.001, respectively). We reported a drastic reduction of procedures performed for suspected Celiac Disease and Functional Gastrointestinal Disorders (55.1% and 58.0%, respectively). Diagnostic endoscopies for suspected IBD decreased of 15.5%, whereas procedures for Mucosal Healing (MH) assessment reduced of 48.3%. Conclusions: Our study provides real-world data outlining the meaningful impact of COVID-19 on pediatric endoscopy practice in Italy.

Published
2022
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37. Vergleich von Endobiliärer Photodynamischer Therapie und Endobiliärer Radiofrequenzablation bei Patienten mit Extrahepatischem Cholangiokarzinom unter systemischer Chemotherapie

Author

Möhring, C., additional, Khan, O., additional, Zhou, T., additional, Sadeghlar, F., additional, Mahn, R., additional, Kaczmarek, D. J., additional, Dold, L., additional, Toma, M., additional, Marinova, M., additional, Glowka, T., additional, Matthaei, H., additional, Manekeller, S., additional, Kalff, J. C., additional, Strassburg, C. P., additional, Weismüller, T., additional, and Gonzalez-Carmona, M. A., additional

Published
2023
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38. Overview of the European post-authorisation study register post-authorization studies performed in Europe from September 2010 to December 2018

Author

Sultana, J, Crisafulli, S, Almas, M, Antonazzo, I, Baan, E, Bartolini, C, Bertuccio, M, Bonifazi, F, Capuano, A, Didio, A, Ehrenstein, V, Felisi, M, Ferrajolo, C, Fontana, A, Francisca, R, Fourrier-Reglat, A, Fortuny, J, Gini, R, Hyeraci, G, Hoeve, C, Kontogiorgis, C, Isgro, V, Lalagkas, P, L'Abbate, L, Layton, D, Landi, A, Narduzzi, S, Roque Pereira, L, Poulentzas, G, Rafaniello, C, Roberto, G, Scondotto, G, Sportiello, L, Toma, M, Toussi, M, Verhamme, K, Volpe, E, Trifiro, G, Sultana J., Crisafulli S., Almas M., Antonazzo I. C., Baan E., Bartolini C., Bertuccio M. P., Bonifazi F., Capuano A., Didio A., Ehrenstein V., Felisi M., Ferrajolo C., Fontana A., Francisca R., Fourrier-Reglat A., Fortuny J., Gini R., Hyeraci G., Hoeve C., Kontogiorgis C., Isgro V., Lalagkas P. -N., L'Abbate L., Layton D., Landi A., Narduzzi S., Roque Pereira L., Poulentzas G., Rafaniello C., Roberto G., Scondotto G., Sportiello L., Toma M., Toussi M., Verhamme K., Volpe E., Trifiro G., Sultana, J, Crisafulli, S, Almas, M, Antonazzo, I, Baan, E, Bartolini, C, Bertuccio, M, Bonifazi, F, Capuano, A, Didio, A, Ehrenstein, V, Felisi, M, Ferrajolo, C, Fontana, A, Francisca, R, Fourrier-Reglat, A, Fortuny, J, Gini, R, Hyeraci, G, Hoeve, C, Kontogiorgis, C, Isgro, V, Lalagkas, P, L'Abbate, L, Layton, D, Landi, A, Narduzzi, S, Roque Pereira, L, Poulentzas, G, Rafaniello, C, Roberto, G, Scondotto, G, Sportiello, L, Toma, M, Toussi, M, Verhamme, K, Volpe, E, Trifiro, G, Sultana J., Crisafulli S., Almas M., Antonazzo I. C., Baan E., Bartolini C., Bertuccio M. P., Bonifazi F., Capuano A., Didio A., Ehrenstein V., Felisi M., Ferrajolo C., Fontana A., Francisca R., Fourrier-Reglat A., Fortuny J., Gini R., Hyeraci G., Hoeve C., Kontogiorgis C., Isgro V., Lalagkas P. -N., L'Abbate L., Layton D., Landi A., Narduzzi S., Roque Pereira L., Poulentzas G., Rafaniello C., Roberto G., Scondotto G., Sportiello L., Toma M., Toussi M., Verhamme K., Volpe E., and Trifiro G.

Abstract

Background: The European post-authorisation study (EU PAS) register is a repository launched in 2010 by the European Medicines Agency (EMA). All EMA-requested PAS, commonly observational studies, must be recorded in this register. Multi-database studies (MDS) leveraging secondary data have become an important strategy to conduct PAS in recent years, as reflected by the type of studies registered in the EU PAS register. Objectives: To analyse and describe PAS in the EU PAS register, with focus on MDS. Methods: Studies in the EU PAS register from inception to 31st December 2018 were described concerning transparency, regulatory obligations, scope, study type (e.g., observational study, clinical trial, survey, systematic review/meta-analysis), study design, type of data collection and target population. MDS were defined as studies conducted through secondary use of >1 data source not linked at patient-level. Data extraction was carried out independently by 14 centres with expertise in pharmacoepidemiology, using publicly available information in the EU PAS register including study protocol, whenever available, using a standardised data collection form. For validation purposes, a second revision of key fields for a 15% random sample of studies was carried out by a different centre. The inter-rater reliability (IRR) was then calculated. Finally, to identify predictors of primary data collection-based studies/versus those based on secondary use of healthcare databases) or MDS (vs. non-MDS), odds ratios (OR) and 95% confidence intervals (CI) were calculated fitting univariate logistic regression models. Results: Overall, 1426 studies were identified. Clinical trials (N = 30; 2%), systematic reviews/meta-analyses (N = 16; 1%) and miscellaneous study designs (N = 46; 3%) were much less common than observational studies (N = 1227; 86%). The protocol was available for 63% (N = 360) of 572 observational studies requested by a competent authority. Overall, 36% (N = 446) of ob

Published
2022

40. Pre-adipocyte-driven NRG1 promotes resistance to FGFR3 inhibition in urothelial carcinoma

Author

Hosni, S, Kilian, V, Klümper, N, Gabbia, D, Winkler, A, Saponaro, M, Schmidt, D, J. Ralser, D, Corvino, D, Toma, M, Kristiansen, G, Bald, T, Eckstein, M, Wachten, D, Ritter, M, Hölzel, M, Geyer, M, de Martin, S, Alajati, A, Hosni, S, Kilian, V, Klümper, N, Gabbia, D, Winkler, A, Saponaro, M, Schmidt, D, J. Ralser, D, Corvino, D, Toma, M, Kristiansen, G, Bald, T, Eckstein, M, Wachten, D, Ritter, M, Hölzel, M, Geyer, M, de Martin, S, and Alajati, A

Published
2023

42. 1453 LncRNA SNHG26 facilitates inflammatory to proliferative state transition of keratinocyte progenitors during wound healing

Author

Li, D., primary, Liu, Z., additional, Zhang, L., additional, Bian, X., additional, Wu, J., additional, Li, L., additional, Pan, L., additional, Xiao, Y., additional, Wang, J., additional, Zhang, X., additional, Wang, W., additional, Toma, M., additional, Piipponen, M., additional, Luo, L., additional, Sommar, P., additional, and Landén, N. Xu, additional

Published
2023
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48. Sacubitril/valsartan in real-life European patients with heart failure and reduced ejection fraction: a systematic review and meta-analysis

Author

Giovinazzo, S, Carmisciano, L, Toma, M, Benenati, S, Tomasoni, D, Sormani, M, Porto, I, Canepa, M, Senni, M, Metra, M, Ameri, P, Giovinazzo S, Carmisciano L, Toma M, Benenati S, Tomasoni D, Sormani MP, Porto I, Canepa M, Senni M, Metra M, Ameri P, Giovinazzo, S, Carmisciano, L, Toma, M, Benenati, S, Tomasoni, D, Sormani, M, Porto, I, Canepa, M, Senni, M, Metra, M, Ameri, P, Giovinazzo S, Carmisciano L, Toma M, Benenati S, Tomasoni D, Sormani MP, Porto I, Canepa M, Senni M, Metra M, and Ameri P

Abstract

Aims: We systematically reviewed the European real-world evidence (RWE) about sacubitril-valsartan for heart failure with reduced ejection fraction. Methods and results: Twenty-one articles, including 16 952 subjects, were identified until 31 October 2020. Taking as reference the PARADIGM-HF cohort, few baseline characteristics were presented in >80% of these studies, most often with high heterogeneity. In random-effects model meta-analysis, age was higher (mean difference +3.84, 95% CI 1.92–5.76), ischaemic aetiology (OR 0.76, 95% CI 0.64–0.91), hypertension (OR 0.55, 95% CI 0.37–0.82), and diabetes (OR 0.77, 95% CI 0.64–0.92) were less common, and the use of mineralocorticoid receptor antagonists was more frequent (OR 3.54, 95% CI 2.27–5.53) in real-life than in PARADIGM-HF. Other clinical and medical features were presented in 19–76% of the selected publications and suggested more severe heart failure with reduced ejection fraction. Sacubitril-valsartan was titrated to 97/103 mg b.i.d. in 35% (95% CI 23–47) and discontinued in 12.8% (95% CI 7.4–18.3) patients. When reported, the incidence of hyperkalaemia (six studies, no. 1076), all-cause mortality (five studies, no. 684), and any hospitalization (three studies, no. 390) was 12 (95% CI 5–19)/100 person-year, 8 (95% CI 4–12)/100 person-year, and 24 (95% CI 5–42)/100 person-year, respectively. Knowledge contribution, a metric measuring the proportion of RWE provided by each article based on the number of reported variables and the sample size, was 58.8% and 13.6% for the two biggest investigations (12 082 and 2037 patients), and <5% for all others (most with <100 subjects). Conclusions: Limited-quality RWE indicates that there are important differences between European patients prescribed sacubitril-valsartan and the PARADIGM-HF population, including the frequency of target dose achievement.

Published
2021

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