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161. Successes and Pitfalls in Scoring Molecular Interactions

Author

Muniz, Heloisa S., Nascimento, Alessandro S., Hutchison, David, Series editor, Kanade, Takeo, Series editor, Kittler, Josef, Series editor, Kleinberg, Jon M., Series editor, Kobsa, Alfred, Series editor, Mattern, Friedemann, Series editor, Mitchell, John C., Series editor, Naor, Moni, Series editor, Nierstrasz, Oscar, Series editor, Pandu Rangan, C., Series editor, Steffen, Bernhard, Series editor, Terzopoulos, Demetri, Series editor, Tygar, Doug, Series editor, Weikum, Gerhard, Series editor, Istrail, Sorin, Series editor, Pevzner, Pavel, Series editor, Waterman, Michael S., Series editor, Ortuño, Francisco, editor, and Rojas, Ignacio, editor

Published
2015
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162. An alternative conformation of ERβ bound to estradiol reveals H12 in a stable antagonist position

Author

Paulo C. T. Souza, Larissa C. Textor, Denise C. Melo, Alessandro S. Nascimento, Munir S. Skaf, and Igor Polikarpov

Subjects
Medicine, Science
Abstract

Abstract The natural ligand 17β-estradiol (E2) is so far believed to induce a unique agonist-bound active conformation in the ligand binding domain (LBD) of the estrogen receptors (ERs). Both subtypes, ERα and ERβ, are transcriptionally activated in the presence of E2 with ERβ being somewhat less active than ERα under similar conditions. The molecular bases for this intriguing behavior are mainly attributed to subtype differences in the amino-terminal domain of these receptors. However, structural details that confer differences in the molecular response of ER LBDs to E2 still remain elusive. In this study, we present a new crystallographic structure of the ERβ LBD bound to E2 in which H12 assumes an alternative conformation that resembles antagonist ERs structures. Structural observations and molecular dynamics simulations jointly provide evidence that alternative ERβ H12 position could correspond to a stable conformation of the receptor under physiological pH conditions. Our findings shed light on the unexpected role of LBD in the lower functional response of ERβ subtype.

Published
2017
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163. Author response: SARS-CoV-2 uses CD4 to infect T helper lymphocytes

Author

Brunetti, Natalia S, primary, Davanzo, Gustavo G, primary, de Moraes, Diogo, primary, Ferrari, Allan JR, primary, Souza, Gabriela F, primary, Muraro, Stéfanie Primon, primary, Knittel, Thiago L, primary, Boldrini, Vinicius O, primary, Monteiro, Lauar B, primary, Virgílio-da-Silva, João Victor, primary, Profeta, Gerson S, primary, Wassano, Natália S, primary, Nunes Santos, Luana, primary, Carregari, Victor C, primary, Dias, Artur HS, primary, Veras, Flavio P, additional, Tavares, Lucas A, additional, Forato, Julia, additional, Castro, Icaro MS, additional, Silva-Costa, Lícia C, additional, Palma, André C, additional, Mansour, Eli, additional, Ulaf, Raisa G, additional, Bernardes, Ana F, additional, Nunes, Thyago A, additional, Ribeiro, Luciana C, additional, Agrela, Marcus V, additional, Moretti, Maria Luiza, additional, Buscaratti, Lucas I, additional, Crunfli, Fernanda, additional, Ludwig, Raissa G, additional, Gerhardt, Jaqueline A, additional, Munhoz-Alves, Natália, additional, Marques, Ana Maria, additional, Sesti-Costa, Renata, additional, Amorim, Mariene R, additional, Toledo-Teixeira, Daniel A, additional, Parise, Pierina Lorencini, additional, Martini, Matheus Cavalheiro, additional, Bispos-dos-Santos, Karina, additional, Simeoni, Camila L, additional, Granja, Fabiana, additional, Silvestrini, Virgínia C, additional, de Oliveira, Eduardo B, additional, Faca, Vitor M, additional, Carvalho, Murilo, additional, Castelucci, Bianca G, additional, Pereira, Alexandre B, additional, Coimbra, Laís D, additional, Dias, Marieli MG, additional, Rodrigues, Patricia B, additional, Gomes, Arilson Bernardo SP, additional, Pereira, Fabricio B, additional, Santos, Leonilda MB, additional, Bloyet, Louis-Marie, additional, Stumpf, Spencer, additional, Pontelli, Marjorie C, additional, Whelan, Sean, additional, Sposito, Andrei C, additional, Carvalho, Robson F, additional, Vieira, André S, additional, Vinolo, Marco AR, additional, Damasio, André, additional, Velloso, Licio, additional, Figueira, Ana Carolina M, additional, da Silva, Luis LP, additional, Cunha, Thiago Mattar, additional, Nakaya, Helder I, additional, Marques-Souza, Henrique, additional, Marques, Rafael E, additional, Martins-de-Souza, Daniel, additional, Skaf, Munir S, additional, Proenca-Modena, Jose Luiz, additional, Moraes-Vieira, Pedro MM, additional, Mori, Marcelo A, additional, and Farias, Alessandro S, additional

Published
2023
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164. P-387 Exploring the Potential of Artificial Intelligence in Providing Infertility Consultations and Answers: can it replace the infertility specialist? A hybrid study.

Author

Buzzaccarini, G, primary, Grecchi, G, additional, Papa, G A, additional, Carnemolla, G, additional, Salmeri, N, additional, Villanacci, R, additional, Giardina, P, additional, D'Alessandro, S, additional, Molgora, M, additional, Marzanati, D, additional, Pagliardini, L, additional, Vanni, V S, additional, Alteri, A, additional, Candiani, M, additional, and Papaleo, E, additional

Published
2023
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167. Phenotypic changes in low-density lipoprotein particles as markers of adverse clinical outcomes in COVID-19

Author

Carmo, Helison Rafael P., primary, Yoshinaga, Marcos Y., additional, Castillo, Alejandro Rosell, additional, Britto Chaves-Filho, Adriano, additional, Bonilha, Isabella, additional, Barreto, Joaquim, additional, Muraro, Stéfanie Primon, additional, de Souza, Gabriela Fabiano, additional, Davanzo, Gustavo Gastão, additional, Perroud, Maurício W., additional, Lukhna, Kishal, additional, Ntsekhe, Mpiko, additional, Davidson, Sean, additional, Velloso, Licio A., additional, Nadruz, Wilson, additional, Carvalho, Luiz Sérgio F., additional, Sáinz-Jaspeado, Miguel, additional, Farias, Alessandro S., additional, Proença-Módena, José Luiz, additional, Moraes-Vieira, Pedro M., additional, Karathanasis, Sotirios K., additional, Yellon, Derek, additional, Miyamoto, Sayuri, additional, Remaley, Alan T., additional, and Sposito, Andrei C., additional

Published
2023
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168. SARS-CoV-2 uses CD4 to infect T helper lymphocytes

Author

Brunetti, Natalia S, Davanzo, Gustavo G, de Moraes, Diogo, Ferrari, Allan JR, Souza, Gabriela F, Muraro, Stéfanie Primon, Knittel, Thiago L, Boldrini, Vinicius O, Monteiro, Lauar B, Virgílio-da-Silva, João Victor, Profeta, Gerson S, Wassano, Natália S, Nunes Santos, Luana, Carregari, Victor C, Dias, Artur HS, Veras, Flavio P, Tavares, Lucas A, Forato, Julia, Castro, Icaro MS, Silva-Costa, Lícia C, Palma, André C, Mansour, Eli, Ulaf, Raisa G, Bernardes, Ana F, Nunes, Thyago A, Ribeiro, Luciana C, Agrela, Marcus V, Moretti, Maria Luiza, Buscaratti, Lucas I, Crunfli, Fernanda, Ludwig, Raissa G, Gerhardt, Jaqueline A, Munhoz-Alves, Natália, Marques, Ana Maria, Sesti-Costa, Renata, Amorim, Mariene R, Toledo-Teixeira, Daniel A, Parise, Pierina Lorencini, Martini, Matheus Cavalheiro, Bispos-dos-Santos, Karina, Simeoni, Camila L, Granja, Fabiana, Silvestrini, Virgínia C, de Oliveira, Eduardo B, Faca, Vitor M, Carvalho, Murilo, Castelucci, Bianca G, Pereira, Alexandre B, Coimbra, Laís D, Dias, Marieli MG, Rodrigues, Patricia B, Gomes, Arilson Bernardo SP, Pereira, Fabricio B, Santos, Leonilda MB, Bloyet, Louis-Marie, Stumpf, Spencer, Pontelli, Marjorie C, Whelan, Sean, Sposito, Andrei C, Carvalho, Robson F, Vieira, André S, Vinolo, Marco AR, Damasio, André, Velloso, Licio, Figueira, Ana Carolina M, da Silva, Luis LP, Cunha, Thiago Mattar, Nakaya, Helder I, Marques-Souza, Henrique, Marques, Rafael E, Martins-de-Souza, Daniel, Skaf, Munir S, Proenca-Modena, Jose Luiz, Moraes-Vieira, Pedro MM, Mori, Marcelo A, Farias, Alessandro S, Brunetti, Natalia S, Davanzo, Gustavo G, de Moraes, Diogo, Ferrari, Allan JR, Souza, Gabriela F, Muraro, Stéfanie Primon, Knittel, Thiago L, Boldrini, Vinicius O, Monteiro, Lauar B, Virgílio-da-Silva, João Victor, Profeta, Gerson S, Wassano, Natália S, Nunes Santos, Luana, Carregari, Victor C, Dias, Artur HS, Veras, Flavio P, Tavares, Lucas A, Forato, Julia, Castro, Icaro MS, Silva-Costa, Lícia C, Palma, André C, Mansour, Eli, Ulaf, Raisa G, Bernardes, Ana F, Nunes, Thyago A, Ribeiro, Luciana C, Agrela, Marcus V, Moretti, Maria Luiza, Buscaratti, Lucas I, Crunfli, Fernanda, Ludwig, Raissa G, Gerhardt, Jaqueline A, Munhoz-Alves, Natália, Marques, Ana Maria, Sesti-Costa, Renata, Amorim, Mariene R, Toledo-Teixeira, Daniel A, Parise, Pierina Lorencini, Martini, Matheus Cavalheiro, Bispos-dos-Santos, Karina, Simeoni, Camila L, Granja, Fabiana, Silvestrini, Virgínia C, de Oliveira, Eduardo B, Faca, Vitor M, Carvalho, Murilo, Castelucci, Bianca G, Pereira, Alexandre B, Coimbra, Laís D, Dias, Marieli MG, Rodrigues, Patricia B, Gomes, Arilson Bernardo SP, Pereira, Fabricio B, Santos, Leonilda MB, Bloyet, Louis-Marie, Stumpf, Spencer, Pontelli, Marjorie C, Whelan, Sean, Sposito, Andrei C, Carvalho, Robson F, Vieira, André S, Vinolo, Marco AR, Damasio, André, Velloso, Licio, Figueira, Ana Carolina M, da Silva, Luis LP, Cunha, Thiago Mattar, Nakaya, Helder I, Marques-Souza, Henrique, Marques, Rafael E, Martins-de-Souza, Daniel, Skaf, Munir S, Proenca-Modena, Jose Luiz, Moraes-Vieira, Pedro MM, Mori, Marcelo A, and Farias, Alessandro S

Abstract

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the agent of a major global outbreak of respiratory tract disease known as Coronavirus Disease 2019 (COVID-19). SARS-CoV-2 infects mainly lungs and may cause several immune-related complications, such as lymphocytopenia and cytokine storm, which are associated with the severity of the disease and predict mortality. The mechanism by which SARS-CoV-2 infection may result in immune system dysfunction is still not fully understood. Here, we show that SARS-CoV-2 infects human CD4+ T helper cells, but not CD8+ T cells, and is present in blood and bronchoalveolar lavage T helper cells of severe COVID-19 patients. We demonstrated that SARS-CoV-2 spike glycoprotein (S) directly binds to the CD4 molecule, which in turn mediates the entry of SARS-CoV-2 in T helper cells. This leads to impaired CD4 T cell function and may cause cell death. SARS-CoV-2-infected T helper cells express higher levels of IL-10, which is associated with viral persistence and disease severity. Thus, CD4-mediated SARS-CoV-2 infection of T helper cells may contribute to a poor immune response in COVID-19 patients.

Published
2023

170. Comparison of different percutaneous revascularisation timing strategies in patients undergoing transcatheter aortic valve implantation

Author

Rheude, Tobia, Costa, Giuliano, Ribichini, Flavio Luciano, Pilgrim, Thoma, Amat Santos, Ignacio J, De Backer, Ole, Kim, Won-Keun, Ribeiro, Henrique Barbosa, Saia, Francesco, Bunc, Matjaz, Tchetche, Didier, Garot, Philippe, Mylotte, Darren, Burzotta, Francesco, Watanabe, Yusuke, Bedogni, Francesco, Tesorio, Tullio, Tocci, Marco, Franzone, Anna, Valvo, Roberto, Savontaus, Mikko, Wienemann, Hendrik, Porto, Italo, Gandolfo, Caterina, Iadanza, Alessandro, Bortone, Alessandro S, Mach, Marku, Latib, Azeem, Biasco, Luigi, Taramasso, Maurizio, Zimarino, Marco, Tomii, Daijiro, Nuyens, Philippe, Sondergaard, Lar, Camara, Sergio F, Palmerini, Tullio, Orzalkiewicz, Mateusz, Steblovnik, Klemen, Degrelle, Bastien, Gautier, Alexandre, Del Sole, Paolo Alberto, Mainardi, Andrea, Pighi, Michele, Lunardi, Mattia, Kawashima, Hideyuki, Criscione, Enrico, Cesario, Vincenzo, Biancari, Fausto, Zanin, Federico, Esposito, Giovanni, Adam, Matti, Grube, Eberhard, Baldus, Stephan, De Marzo, Vincenzo, Piredda, Elisa, Cannata, Stefano, Iacovelli, Fortunato, Andreas, Martin, Frittitta, Valentina, Dipietro, Elena, Reddavid, Claudia, Strazzieri, Orazio, Motta, Silvia, Angellotti, Domenico, Sgroi, Carmelo, Xhepa, Erion, Kargoli, Faraj, Tamburino, Corrado, Joner, Michael, Barbanti, Marco, Burzotta, Francesco (ORCID:0000-0002-6569-9401), Porto, Italo (ORCID:0000-0002-9854-5046), Rheude, Tobia, Costa, Giuliano, Ribichini, Flavio Luciano, Pilgrim, Thoma, Amat Santos, Ignacio J, De Backer, Ole, Kim, Won-Keun, Ribeiro, Henrique Barbosa, Saia, Francesco, Bunc, Matjaz, Tchetche, Didier, Garot, Philippe, Mylotte, Darren, Burzotta, Francesco, Watanabe, Yusuke, Bedogni, Francesco, Tesorio, Tullio, Tocci, Marco, Franzone, Anna, Valvo, Roberto, Savontaus, Mikko, Wienemann, Hendrik, Porto, Italo, Gandolfo, Caterina, Iadanza, Alessandro, Bortone, Alessandro S, Mach, Marku, Latib, Azeem, Biasco, Luigi, Taramasso, Maurizio, Zimarino, Marco, Tomii, Daijiro, Nuyens, Philippe, Sondergaard, Lar, Camara, Sergio F, Palmerini, Tullio, Orzalkiewicz, Mateusz, Steblovnik, Klemen, Degrelle, Bastien, Gautier, Alexandre, Del Sole, Paolo Alberto, Mainardi, Andrea, Pighi, Michele, Lunardi, Mattia, Kawashima, Hideyuki, Criscione, Enrico, Cesario, Vincenzo, Biancari, Fausto, Zanin, Federico, Esposito, Giovanni, Adam, Matti, Grube, Eberhard, Baldus, Stephan, De Marzo, Vincenzo, Piredda, Elisa, Cannata, Stefano, Iacovelli, Fortunato, Andreas, Martin, Frittitta, Valentina, Dipietro, Elena, Reddavid, Claudia, Strazzieri, Orazio, Motta, Silvia, Angellotti, Domenico, Sgroi, Carmelo, Xhepa, Erion, Kargoli, Faraj, Tamburino, Corrado, Joner, Michael, Barbanti, Marco, Burzotta, Francesco (ORCID:0000-0002-6569-9401), and Porto, Italo (ORCID:0000-0002-9854-5046)

Abstract

Background: The optimal timing to perform percutaneous coronary interventions (PCI) in transcatheter aortic valve implantation (TAVI) patients remains unknown. Aims: We sought to compare different PCI timing strategies in TAVI patients. Methods: The REVASC-TAVI registry is an international registry including patients undergoing TAVI with significant, stable coronary artery disease (CAD) at preprocedural workup. In this analysis, patients scheduled to undergo PCI before, after or concomitantly with TAVI were included. The main endpoints were all-cause death and a composite of all-cause death, stroke, myocardial infarction (MI) or rehospitalisation for congestive heart failure (CHF) at 2 years. Outcomes were adjusted using the inverse probability treatment weighting (IPTW) method. Results: A total of 1,603 patients were included. PCI was performed before, after or concomitantly with TAVI in 65.6% (n=1,052), 9.8% (n=157) or 24.6% (n=394), respectively. At 2 years, all-cause death was significantly lower in patients undergoing PCI after TAVI as compared with PCI before or concomitantly with TAVI (6.8% vs 20.1% vs 20.6%; p<0.001). Likewise, the composite endpoint was significantly lower in patients undergoing PCI after TAVI as compared with PCI before or concomitantly with TAVI (17.4% vs 30.4% vs 30.0%; p=0.003). Results were confirmed at landmark analyses considering events from 0 to 30 days and from 31 to 720 days. Conclusions: In patients with severe aortic stenosis and stable coronary artery disease scheduled for TAVI, performance of PCI after TAVI seems to be associated with improved 2-year clinical outcomes compared with other revascularisation timing strategies. These results need to be confirmed in randomised clinical trials.

Published
2023

171. Evaluating the Influence of PMUT Mechanical Support Properties on Power Conversion Efficiency in Ultrasonically Powered Implants

Author

Savoia, Alessandro S. (author), Giustiniano, Domenico (author), Prelini, Carlo (author), Saccher, M. (author), Rashidi, A. (author), Leotti, Alberto (author), Giagka, Vasiliki (author), Ferrera, Marco (author), Savoia, Alessandro S. (author), Giustiniano, Domenico (author), Prelini, Carlo (author), Saccher, M. (author), Rashidi, A. (author), Leotti, Alberto (author), Giagka, Vasiliki (author), and Ferrera, Marco (author)

Abstract

Micromachined Ultrasonic Transducers (MUTs) are being explored as power converters in wirelessly powered biomedical implants. This paper investigates the role of mechanical support properties in piezoelectric MUTs (PMUTs) on their power conversion efficiency. For this purpose, a finite element model (FEM) of a PMUT array was developed and integrated with an equivalent circuit model (ECM). The study considered different mechanical support scenarios, from rigidly clamped to completely free. These were numerically analyzed and validated by impedance measurements and acoustic power transfer experiments on PMUT prototypes. The results show that reducing the mass of the mechanical support increases the Q factor, leading to a significant improvement in power conversion efficiency, with an efficiency increase factor of 5.6x from the clamped to the free case. This approach can potentially enhance overall power conversion efficiency, reduce the need for matching networks, and enable miniaturization in ultrasonically powered implants., Green Open Access added to TU Delft Institutional Repository 'You share, we take care!' - Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public., Electronic Components, Technology and Materials, Bio-Electronics

Published
2023
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172. Comparison of different percutaneous revascularisation timing strategies in patients undergoing transcatheter aortic valve implantation

Author

Rheude, Tobias, Costa, Giuliano, Ribichini, Flavio Luciano, Pilgrim, Thomas, Amat-Santos, Ignacio J., De Backer, Ole, Kim, Won Keun, Ribeiro, Henrique Barbosa, Saia, Francesco, Bunc, Matjaz, Tchétché, Didier, Garot, Philippe, Mylotte, Darren, Burzotta, Francesco, Watanabe, Yusuke, Bedogni, Francesco, Tesorio, Tullio, Tocci, Marco, Franzone, Anna, Valvo, Roberto, Savontaus, Mikko, Wienemann, Hendrik, Porto, Italo, Gandolfo, Caterina, Iadanza, Alessandro, Bortone, Alessandro S., Mach, Markus, Latib, Azeem, Biasco, Luigi, Taramasso, Maurizio, Zimarino, Marco, Tomii, Daijiro, Nuyens, Philippe, Sondergaard, Lars, Camara, Sergio F., Palmerini, Tullio, Orzalkiewicz, Mateusz, Steblovnik, Klemen, Degrelle, Bastien, Gautier, Alexandre, Del Sole, Paolo Alberto, Mainardi, Andrea, Pighi, Michele, Lunardi, Mattia, Kawashima, Hideyuki, Criscione, Enrico, Cesario, Vincenzo, Biancari, Fausto, Zanin, Federico, Esposito, Giovanni, Adam, Matti, Grube, Eberhard, Baldus, Stephan, De Marzo, Vincenzo, Piredda, Elisa, Cannata, Stefano, Iacovelli, Fortunato, Andreas, Martin, Frittitta, Valentina, Dipietro, Elena, Reddavid, Claudia, Strazzieri, Orazio, Motta, Silvia, Angellotti, Domenico, Sgroi, Carmelo, Xhepa, Erion, Kargoli, Faraj, Tamburino, Corrado, Joner, Michael, Barbanti, Marco, Rheude, Tobias, Costa, Giuliano, Ribichini, Flavio Luciano, Pilgrim, Thomas, Amat-Santos, Ignacio J., De Backer, Ole, Kim, Won Keun, Ribeiro, Henrique Barbosa, Saia, Francesco, Bunc, Matjaz, Tchétché, Didier, Garot, Philippe, Mylotte, Darren, Burzotta, Francesco, Watanabe, Yusuke, Bedogni, Francesco, Tesorio, Tullio, Tocci, Marco, Franzone, Anna, Valvo, Roberto, Savontaus, Mikko, Wienemann, Hendrik, Porto, Italo, Gandolfo, Caterina, Iadanza, Alessandro, Bortone, Alessandro S., Mach, Markus, Latib, Azeem, Biasco, Luigi, Taramasso, Maurizio, Zimarino, Marco, Tomii, Daijiro, Nuyens, Philippe, Sondergaard, Lars, Camara, Sergio F., Palmerini, Tullio, Orzalkiewicz, Mateusz, Steblovnik, Klemen, Degrelle, Bastien, Gautier, Alexandre, Del Sole, Paolo Alberto, Mainardi, Andrea, Pighi, Michele, Lunardi, Mattia, Kawashima, Hideyuki, Criscione, Enrico, Cesario, Vincenzo, Biancari, Fausto, Zanin, Federico, Esposito, Giovanni, Adam, Matti, Grube, Eberhard, Baldus, Stephan, De Marzo, Vincenzo, Piredda, Elisa, Cannata, Stefano, Iacovelli, Fortunato, Andreas, Martin, Frittitta, Valentina, Dipietro, Elena, Reddavid, Claudia, Strazzieri, Orazio, Motta, Silvia, Angellotti, Domenico, Sgroi, Carmelo, Xhepa, Erion, Kargoli, Faraj, Tamburino, Corrado, Joner, Michael, and Barbanti, Marco

Abstract

Background: The optimal timing to perform percutaneous coronary interventions (PCI) in transcatheter aortic valve implantation (TAVI) patients remains unknown. Aims: We sought to compare different PCI timing strategies in TAVI patients. Methods: The REVASC-TAVI registry is an international registry including patients undergoing TAVI with significant, stable coronary artery disease (CAD) at preprocedural workup. In this analysis, patients scheduled to undergo PCI before, after or concomitantly with TAVI were included. The main endpoints were all-cause death and a composite of all-cause death, stroke, myocardial infarction (MI) or rehospitalisation for congestive heart failure (CHF) at 2 years. Outcomes were adjusted using the inverse probability treatment weighting (IPTW) method. Results: A total of 1,603 patients were included. PCI was performed before, after or concomitantly with TAVI in 65.6% (n=1,052), 9.8% (n=157) or 24.6% (n=394), respectively. At 2 years, all-cause death was significantly lower in patients undergoing PCI after TAVI as compared with PCI before or concomitantly with TAVI (6.8% vs 20.1% vs 20.6%; p<0.001). Likewise, the composite endpoint was significantly lower in patients undergoing PCI after TAVI as compared with PCI before or concomitantly with TAVI., Background: The optimal timing to perform percutaneous coronary interventions (PCI) in transcatheter aortic valve implantation (TAVI) patients remains unknown. Aims: We sought to compare different PCI timing strategies in TAVI patients. Methods: The REVASC-TAVI registry is an international registry including patients undergoing TAVI with significant, stable coronary artery disease (CAD) at preprocedural workup. In this analysis, patients scheduled to undergo PCI before, after or concomitantly with TAVI were included. The main endpoints were all-cause death and a composite of all-cause death, stroke, myocardial infarction (MI) or rehospitalisation for congestive heart failure (CHF) at 2 years. Outcomes were adjusted using the inverse probability treatment weighting (IPTW) method. Results: A total of 1,603 patients were included. PCI was performed before, after or concomitantly with TAVI in 65.6% (n=1,052), 9.8% (n=157) or 24.6% (n=394), respectively. At 2 years, all-cause death was significantly lower in patients undergoing PCI after TAVI as compared with PCI before or concomitantly with TAVI (6.8% vs 20.1% vs 20.6%; p<0.001). Likewise, the composite endpoint was significantly lower in patients undergoing PCI after TAVI as compared with PCI before or concomitantly with TAVI (17.4% vs 30.4% vs 30.0%; p=0.003). Results were confirmed at landmark analyses considering events from 0 to 30 days and from 31 to 720 days. Conclusions: In patients with severe aortic stenosis and stable coronary artery disease scheduled for TAVI, performance of PCI after TAVI seems to be associated with improved 2-year clinical outcomes compared with other revascularisation timing strategies. These results need to be confirmed in randomised clinical trials.

Published
2023

174. Defective Induction of IL-27-Mediated Immunoregulation by Myeloid DCs in Multiple Sclerosis

Author

Felipe von Glehn, Nathalie Pochet, Bibek Thapa, Radhika Raheja, Maria A. Mazzola, Sushrut Jangi, Vanessa Beynon, Junning Huang, Alessandro S. Farias, Anu Paul, Leonilda M. B. Santos, Roopali Gandhi, Gopal Murugaiyan, Howard L. Weiner, and Clare M. Baecher-Allan

Subjects
Inorganic Chemistry, relapsing-remitting multiple sclerosis (RRMS), IL-27, myeloid dendritic cells (mDCs), lymphoproliferative assay, Programmed Death Ligand 2 (PD-L2), Programmed Death 1 receptor (PD1), innate immune response, Organic Chemistry, General Medicine, Physical and Theoretical Chemistry, Molecular Biology, Spectroscopy, Catalysis, Computer Science Applications
Abstract

The purpose of this study was to examine whether myeloid dendritic cells (mDCs) from patients with multiple sclerosis (MS) and healthy controls (HCs) become similarly tolerogenic when exposed to IL-27 as this may represent a potential mechanism of autoimmune dysregulation. Our study focused on natural mDCs that were isolated from HCs and MS patient peripheral blood mononuclear cells (PBMCs). After a 24-h treatment with IL-27 ± lipopolysaccharide (LPS), the mDCs were either harvested to identify IL-27-regulated gene expression or co-cultured with naive T-cells to measure how the treated DC affected T-cell proliferation and cytokine secretion. mDCs isolated from HCs but not untreated MS patients became functionally tolerogenic after IL-27 treatment. Although IL-27 induced both HC and untreated MS mDCs to produce similar amounts of IL-10, the tolerogenic HC mDCs expressed PD-L2, IDO1, and SOCS1, while the non-tolerogenic untreated MS mDCs expressed IDO1 and IL-6R. Cytokine and RNA analyses identified two signature blocks: the first identified genes associated with mDC tolerizing responses to IL-27, while the second was associated with the presence of MS. In contrast to mDCs from untreated MS patients, mDCs from HCs and IFNb-treated MS patients became tolerogenic in response to IL-27. The genes differentially expressed in the different donor IL-27-treated mDCs may contain targets that regulate mDC tolerogenic responses.

Published
2023
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175. Random Telegraph Noise in 3D NAND Flash Memories

Author

Alessandro S. Spinelli, Gerardo Malavena, Andrea L. Lacaita, and Christian Monzio Compagnoni

Subjects
3D NAND Flash memories, random telegraph noise, Flash memory reliability, Mechanical engineering and machinery, TJ1-1570
Abstract

In this paper, we review the phenomenology of random telegraph noise (RTN) in 3D NAND Flash arrays. The main features of such arrays resulting from their mainstream integration scheme are first discussed, pointing out the relevant role played by the polycrystalline nature of the string silicon channels on current transport. Starting from that, experimental data for RTN in 3D arrays are presented and explained via theoretical and simulation models. The attention is drawn, in particular, to the changes in the RTN dependences on the array working conditions that resulted from the transition from planar to 3D architectures. Such changes are explained by considering the impact of highly-defective grain boundaries on percolative current transport in cell channels in combination with the localized nature of the RTN traps.

Published
2021
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176. Defining Treatment Response and Symptom Remission for Anxiety Disorders in Pediatric Autism Spectrum Disorders Using the Pediatric Anxiety Rating Scale

Author

Johnco, Carly J., De Nadai, Alessandro S., and Lewin, Adam B.

Abstract

This study examined optimal guidelines to assess treatment response and remission for anxiety in youth with autism spectrum disorders (ASD) using the Pediatric Anxiety Rating Scale (PARS). Data was collected for 108 children aged 7-16 years with comorbid anxiety and ASD before and after receiving cognitive behavior therapy. Optimal cut-offs on the PARS were assessed using signal detection analyses using receiver operating characteristic methods. Maximum agreement with response criteria was achieved at 15% reduction in symptoms on the PARS. Maximum agreement with remission criteria was achieved at 40% reduction in symptoms, or at a score of 10 or below at post-treatment. Results have implications for standardizing criteria used in research trials and clinical practice.

Published
2015
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179. Defining brain-based OCD patient profiles using task-based fMRI and unsupervised machine learning

Author

Alessandro S. De Nadai, Kate D. Fitzgerald, Luke J. Norman, Stefanie R. Russman Block, Kristin A. Mannella, Joseph A. Himle, and Stephan F. Taylor

Subjects
Adult, Pharmacology, Young Adult, Obsessive-Compulsive Disorder, Brain Mapping, Psychiatry and Mental health, Adolescent, Humans, Brain, Middle Aged, Child, Magnetic Resonance Imaging, Unsupervised Machine Learning
Abstract

While much research has highlighted phenotypic heterogeneity in obsessive compulsive disorder (OCD), less work has focused on heterogeneity in neural activity. Conventional neuroimaging approaches rely on group averages that assume homogenous patient populations. If subgroups are present, these approaches can increase variability and can lead to discrepancies in the literature. They can also obscure differences between various subgroups. To address this issue, we used unsupervised machine learning to identify subgroup clusters of patients with OCD who were assessed by task-based fMRI. We predominantly focused on activation of cognitive control and performance monitoring neurocircuits, including three large-scale brain networks that have been implicated in OCD (the frontoparietal network, cingulo-opercular network, and default mode network). Participants were patients with OCD (n = 128) that included both adults (ages 24-45) and adolescents (ages 12-17), as well as unaffected controls (n = 64). Neural assessments included tests of cognitive interference and error processing. We found three patient clusters, reflecting a "normative" cluster that shared a brain activation pattern with unaffected controls (65.9% of clinical participants), as well as an "interference hyperactivity" cluster (15.2% of clinical participants) and an "error hyperactivity" cluster (18.9% of clinical participants). We also related these clusters to demographic and clinical correlates. After post-hoc correction for false discovery rates, the interference hyperactivity cluster showed significantly longer reaction times than the other patient clusters, but no other between-cluster differences in covariates were detected. These findings increase precision in patient characterization, reframe prior neurobehavioral research in OCD, and provide a starting point for neuroimaging-guided treatment selection.

Published
2022
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181. Safety and Outcomes Associated with the Pharmacological Inhibition of the Kinin–Kallikrein System in Severe COVID-19

Author

Eli Mansour, Andre C. Palma, Raisa G. Ulaf, Luciana C. Ribeiro, Ana Flavia Bernardes, Thyago A. Nunes, Marcus V. Agrela, Bruna Bombassaro, Milena Monfort-Pires, Rafael L. Camargo, Eliana P. Araujo, Natalia S. Brunetti, Alessandro S. Farias, Antônio Luís E. Falcão, Thiago Martins Santos, Plinio Trabasso, Rachel P. Dertkigil, Sergio S. Dertkigil, Maria Luiza Moretti, and Licio A. Velloso

Subjects
angiotensin converting enzyme 2, bradykinin, coronavirus, inflammation, lung, Microbiology, QR1-502
Abstract

Background: Coronavirus disease 19 (COVID-19) can develop into a severe respiratory syndrome that results in up to 40% mortality. Acute lung inflammatory edema is a major pathological finding in autopsies explaining O2 diffusion failure and hypoxemia. Only dexamethasone has been shown to reduce mortality in severe cases, further supporting a role for inflammation in disease severity. SARS-CoV-2 enters cells employing angiotensin-converting enzyme 2 (ACE2) as a receptor, which is highly expressed in lung alveolar cells. ACE2 is one of the components of the cellular machinery that inactivates the potent inflammatory agent bradykinin, and SARS-CoV-2 infection could interfere with the catalytic activity of ACE2, leading to the accumulation of bradykinin. Methods: In this case control study, we tested two pharmacological inhibitors of the kinin–kallikrein system that are currently approved for the treatment of hereditary angioedema, icatibant, and inhibitor of C1 esterase/kallikrein, in a group of 30 patients with severe COVID-19. Results: Neither icatibant nor inhibitor of C1 esterase/kallikrein resulted in changes in time to clinical improvement. However, both compounds were safe and promoted the significant improvement of lung computed tomography scores and increased blood eosinophils, which are indicators of disease recovery. Conclusions: In this small cohort, we found evidence for safety and a beneficial role of pharmacological inhibition of the kinin–kallikrein system in two markers that indicate improved disease recovery.

Published
2021
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182. First Evidence of SET-Like Behavior of 3-D NAND Flash Cells in the Deep-Cryogenic Regime

Author

Refaldi, David G., Malavena, Gerardo, Giulianini, Mattia, Chiavarone, Luca, Spinelli, Alessandro S., and Compagnoni, Christian Monzio

Abstract

In this article, we report the first experimental investigation of the behavior of the 3-D NAND Flash memory technology in the deep-cryogenic regime (temperature ${T} &lt; {50}$ K). Clear evidence is provided to demonstrate that, in that ${T}$ regime, the reduction of the Read bitline voltage gives rise to a paradigm shift in the current–voltage characteristics of the memory cells, consisting of the appearance of single-electron transistor (SET)-like conduction schemes. The phenomenon is traced back to nonuniformities in the electrostatic inversion of cell channel, producing, at that deep-cryogenic ${T}$ , a landscape of conductive quantum dots separated by energy barriers where electron transport is affected by Coulomb blockade. The results represent a first step toward innovative applications of 3-D NAND Flash memories.

Published
2024
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191. Intervention cost-effectiveness for pediatric anxiety and OCD: A systematic review and integrated database model

Author

Maureen F. Monahan, Kaitlyn Westerberg, Alessandro S. De Nadai, Tara B. Little, Sean Gregory, Eric A. Storch, Kevin C. Patyk, and Troy Quast

Subjects
Obsessive-Compulsive Disorder, medicine.medical_specialty, Cost effectiveness, Cost-Benefit Analysis, medicine.medical_treatment, Psychological intervention, Anxiety, Quality of life (healthcare), Intervention (counseling), medicine, Humans, Child, Psychiatry, health care economics and organizations, business.industry, Mental illness, medicine.disease, Anxiety Disorders, Cognitive behavioral therapy, Clinical trial, Psychiatry and Mental health, Clinical Psychology, Quality of Life, medicine.symptom, business
Abstract

Background : While multiple treatments for pediatric anxiety and obsessive compulsive disorder (OCD) are efficacious, little is known about their cost-effectiveness. In response, we sought to provide relevant information through systematic review and cost-effectiveness simulation. Methods : We evaluated the cost-effectiveness of treatment for pediatric anxiety and OCD in two ways. First, we conducted a systematic review following PRISMA guidelines. Second, we evaluated cost-effectiveness for antidepressant medication, cognitive behavioral therapy, and their combination via a simulation that integrated information from the Truven MarketScan database and the NIMH National Database for Clinical Trials Related to Mental Illness. Results : Both systematic review and simulation found antidepressant medication and cognitive behavioral therapy to be cost-effective for pediatric anxiety and OCD. Antidepressant medication was the least costly approach, and cognitive behavioral therapy provided additional cost-effectiveness, especially for OCD. Limitations : During systematic review, relatively few articles provided information about both costs and effectiveness. While there was a notable margin of error to support multiple interventions as cost-effective, limited prior research decreased precision of point estimates and comparisons between interventions. Conclusions : Both antidepressant medication and cognitive behavioral therapy were found to be cost-effective for pediatric anxiety and OCD. Results supported investment from third party payers, who serve as critical gatekeepers that can increase treatment dissemination. However, more precise information would better inform the exact amount of investment needed, especially with regard to selection decisions between active interventions. Cost-effectiveness research would benefit from systematic collection of data on treatment costs and quality of life in future clinical trials.

Published
2022
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192. Conservation and divergence of the G‐interfaces of Drosophila melanogaster septins

Author

Adriano de Freitas Fernandes, Diego Antonio Leonardo, Italo Augusto Cavini, Higor Vinícius Dias Rosa, Jhon Antoni Vargas, Humberto D'Muniz Pereira, Alessandro S. Nascimento, and Richard Charles Garratt

Subjects
Structural Biology, Cell Biology
Abstract

Septins possess a conserved guanine nucleotide-binding (G) domain that participates in the stabilization of organized hetero-oligomeric complexes which assemble into filaments, rings and network-like structures. The fruit fly, Drosophila melanogaster, has five such septin genes encoding Sep1, Sep2, Sep4, Sep5 and Pnut. Here, we report the crystal structure of the heterodimer formed between the G-domains of Sep1 and Sep2, the first from an insect to be described to date. A G-interface stabilizes the dimer (in agreement with the expected arrangement for the Drosophila hexameric particle) and this bears significant resemblance to its human counterparts, even down to the level of individual amino acid interactions. On the other hand, a model for the G-interface formed between the two copies of Pnut which occupy the centre of the hexamer, shows important structural differences, including the loss of a highly favourable bifurcated salt-bridge network. Whereas wild-type Pnut purifies as a monomer, the reintroduction of the salt-bridge network results in stabilizing the dimeric interface in solution as shown by size exclusion chromatography and thermal stability measurements. Adaptive steered molecular dynamics reveals an unzipping mechanism for dimer dissociation which initiates at a point of electrostatic repulsion within the switch II region. Overall, the data contribute to a better understanding of the molecular interactions involved in septin assembly/disassembly.

Published
2023
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193. sj-pdf-1-cep-10.1177_03331024231183166 - Supplemental material for The effect of blood pressure lowering medications on the prevention of episodic migraine: A systematic review and meta-analysis

Author

Carcel, Cheryl, Haghdoost, Faraidoon, Shen, Joanne, Nanda, Puneet, Bai, Yu, Atkins, Emily, Torii-Yoshimura, Takako, Clough, Alexander J., Davies, Leo, Cordato, Dennis, Griffiths, Lyn R., Balicki, Grace, Wang, Xia, Vidyasagar, Kota, Malavera, Alejandra, Anderson, Craig S., Zagami, Alessandro S., Delcourt, Candice, and Rodgers, Anthony

Subjects
FOS: Psychology, FOS: Clinical medicine, 170199 Psychology not elsewhere classified, 110319 Psychiatry (incl. Psychotherapy), 110306 Endocrinology, 111599 Pharmacology and Pharmaceutical Sciences not elsewhere classified, 110904 Neurology and Neuromuscular Diseases, Neuroscience
Abstract

Supplemental material, sj-pdf-1-cep-10.1177_03331024231183166 for The effect of blood pressure lowering medications on the prevention of episodic migraine: A systematic review and meta-analysis by Cheryl Carcel, Faraidoon Haghdoost, Joanne Shen, Puneet Nanda, Yu Bai, Emily Atkins, Takako Torii-Yoshimura, Alexander J. Clough, Leo Davies, Dennis Cordato, Lyn R. Griffiths, Grace Balicki, Xia Wang, Kota Vidyasagar, Alejandra Malavera, Craig S. Anderson, Alessandro S. Zagami, Candice Delcourt and Anthony Rodgers in Cephalalgia

Published
2023
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