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4. The nervous heart

Author

Ripplinger, Crystal M, Noujaim, Sami F, and Linz, Dominik

Subjects
Biochemistry and Cell Biology, Biological Sciences, Heart Disease, Spinal Cord Injury, Neurodegenerative, Neurosciences, Cardiovascular, 2.1 Biological and endogenous factors, Aetiology, Animals, Heart Atria, Heart Diseases, Heart Ventricles, Humans, Nervous System Physiological Phenomena, Cardiac nerves, Autonomic control, Atrial fibrillation, Ventricular tachycardia/fibrillation, Biophysics, Biochemistry and cell biology
Abstract

Many cardiac electrophysiological abnormalities are accompanied by autonomic nervous system dysfunction. Here, we review mechanisms by which the cardiac nervous system controls normal and abnormal excitability and may contribute to atrial and ventricular tachyarrhythmias. Moreover, we explore the potential antiarrhythmic and/or arrhythmogenic effects of modulating the autonomic nervous system by several strategies, including ganglionated plexi ablation, vagal and spinal cord stimulations, and renal sympathetic denervation as therapies for atrial and ventricular arrhythmias.

Published
2016

9. Galectin-3 Regulates Atrial Fibrillation Remodeling and Predicts Catheter Ablation Outcomes

Author

Takemoto, Yoshio, Ramirez, Rafael J., Yokokawa, Miki, Kaur, Kuljeet, Ponce-Balbuena, Daniela, Sinno, Mohamad C., Willis, B. Cicero, Ghanbari, Hamid, Ennis, Steven R., Guerrero-Serna, Guadalupe, Henzi, Bettina C., Latchamsetty, Rakesh, Ramos-Mondragon, Roberto, Musa, Hassan, Martins, Raphael P., Pandit, Sandeep V., Noujaim, Sami F., Crawford, Thomas, Jongnarangsin, Krit, Pelosi, Frank, Bogun, Frank, Chugh, Aman, Berenfeld, Omer, Morady, Fred, Oral, Hakan, and Jalife, José

Published
2016
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12. Contributors

Author

Aagaard, Philip, primary, Abrams, Dominic James, additional, Abriel, Hugues, additional, Adkisson, Wayne O., additional, Agullo-Pascual, Esperanza, additional, Alvarado, Francisco J., additional, Amin, Ahmad S., additional, Antzelevitch, Charles, additional, Anumonwo, Justus M.B., additional, Armaganijan, Luciana, additional, Arya, Arash, additional, Asirvatham, Samuel, additional, Atienza, Felipe, additional, Backx, Peter H., additional, Ballou, Lisa M., additional, Balse, Elise, additional, Balulad, Sujata, additional, Barbuti, Andrea, additional, Bardy, Gust H., additional, Bassil, Guillaume, additional, Benditt, David G., additional, Berenfeld, Omer, additional, Bers, Donald M., additional, Binah, Ofer, additional, Bogun, Frank, additional, Bongianino, Rossana, additional, Boyle, Noel G., additional, Boyle, Patrick M., additional, Breithardt, Günter, additional, Brini, Marisa, additional, Brink, Peter R., additional, Brugada, Pedro, additional, Buch, Eric, additional, Bukauskas, Feliksas F., additional, Calkins, Hugh, additional, Callans, David J., additional, Caples, Sean M., additional, Carafoli, Ernesto, additional, Catterall, William A., additional, Cerrone, Marina, additional, Chaumeil, Arnaud, additional, Chen, Caressa, additional, Chen, Lan S., additional, Chen, Peng-Sheng, additional, Cheng, Jianding, additional, Chiamvimonvat, Nipavan, additional, Christini, David J., additional, Chugh, Aman, additional, Climent, Andreu M., additional, Cohen, Ira S., additional, Connolly, Stuart J., additional, Cooper, Lebron, additional, Crespo, Eric M., additional, Crotti, Lia, additional, Csepe, Thomas A., additional, Cuoco, Frank, additional, Curtis, Anne B., additional, Damiano, Ralph J., additional, Darbar, Dawood, additional, Das, Mithilesh K., additional, d’Avila, Andre, additional, Delmar, Mario, additional, Delpón, Eva, additional, Denegri, Marco, additional, Denis, Arnaud, additional, Derval, Nicolas, additional, Deschênes, Isabelle, additional, Deshmukh, Abhishek, additional, Di Biase, Luigi, additional, Dickfeld, Timm M., additional, Dierckx, Hans, additional, Dinov, Borislav, additional, Dixit, Sanjay, additional, Dobrev, Dobromir, additional, Dubois, Remi, additional, Eckardt, Lars, additional, Edwards, Andrew G., additional, Ellenbogen, Kenneth A., additional, Ellinor, Patrick T., additional, Estes, N.A. Mark, additional, Fabritz, Larissa, additional, Fedorov, Vadim V., additional, Fernandez, Antonio B., additional, Teijeira Fernández, Elvis, additional, Filgueiras-Rama, David, additional, Fishbein, Michael C., additional, Fishman, Glenn I., additional, Frankel, David S., additional, Friedman, Paul, additional, Frontera, Antonio, additional, Gami, Apoor S., additional, Garabelli, Paul, additional, George, Alfred L., additional, Gerstenfeld, Edward P., additional, Gizurarson, Sigfus, additional, Gold, Michael R., additional, Goldberger, Jeffrey J., additional, Grace, Andrew, additional, Grassi, Guido, additional, Greenfield, Ruth Ann, additional, Gross, Wendy L., additional, Grubb, Blair P., additional, Guillem, María S., additional, Györke, Sándor, additional, Haïssaguerre, Michel, additional, Hake, Johan, additional, Halperin, Henry R., additional, Hansen, Brian J., additional, Hatem, Stéphane, additional, Hayes, David L., additional, Heijman, Jordi, additional, Herron, Todd J., additional, Hindricks, Gerhard, additional, Hocini, Mélèze, additional, Hohnloser, Stefan H., additional, Holmes, David R., additional, Hoshijima, Masahiko, additional, Hund, Thomas J., additional, Hutchinson, Mathew D., additional, Ilkhanoff, Leonard, additional, Ingles, Jodie, additional, Ip, James E., additional, Jackman, Warren M., additional, Jackson, Nicholas, additional, Jaïs, Pierre, additional, Jalife, José, additional, Jhun, Bong Sook, additional, John, Roy M., additional, Jongbloed, Monique, additional, Jordaens, Luc, additional, Kalman, Jonathan M., additional, Kamp, Timothy J., additional, Kanj, Mohamed H., additional, Kapa, Suraj, additional, Karabin, Beverly, additional, Karakikes, Ioannis, additional, Katritsis, Demosthenes G., additional, Kaur, Kuljeet, additional, Kirchhof, Paulus, additional, Kléber, André G., additional, Klein, George J., additional, Kohl, Peter, additional, Koneru, Jayanthi N., additional, Koruth, Jacob S., additional, Krahn, Andrew D., additional, Krogh-Madsen, Trine, additional, Kuck, Karl Heinz, additional, Kumar, Saurabh, additional, Kushnir, Alexander, additional, Lakdawala, Neal K., additional, Laksman, Zachary W.M., additional, Latchamsetty, Rakesh, additional, Lau, Dennis H., additional, Lerman, Bruce B., additional, Lin, Richard Z., additional, Lin, Shien-Fong, additional, Link, Mark S., additional, Liu, Bin, additional, Liu, Christopher F., additional, Lockwood, Deborah J., additional, Lopatin, Anatoli N., additional, Lubitz, Steven A., additional, Mahajan, Rajiv, additional, Makielski, Jonathan C., additional, Malik, Marek, additional, Marchlinski, Francis E., additional, Markowitz, Steven M., additional, Maron, Barry J., additional, Maron, Martin S., additional, Marx, Steven O., additional, Massé, Stéphane, additional, McCulloch, Andrew D., additional, McKelvie-Sebileau, Pippa, additional, Melby, Spencer J., additional, Metzner, Andreas, additional, Michailova, Anushka P., additional, Michaud, Gregory F., additional, Miller, John M., additional, Mishra, Jyotsna, additional, Mitrani, Raul D., additional, Mohler, Peter J., additional, Morady, Fred, additional, Myerburg, Robert J., additional, Nakagawa, Hiroshi, additional, Nalliah, Chrishan Joseph, additional, Nanthakumar, Kumaraswamy, additional, Napolitano, Carlo, additional, Narayan, Sanjiv M., additional, Natale, Andrea, additional, Nattel, Stanley, additional, Nazarian, Saman, additional, Nguyen, Thao P., additional, Nogami, Akihiko, additional, Noujaim, Sami F., additional, Nubret Le Coniat, Karine, additional, Olshansky, Brian, additional, O-Uchi, Jin, additional, Oudit, Gavin Y., additional, Ouyang, Feifan, additional, Ozcan, Cevher, additional, Packer, Douglas L., additional, Pandit, Sandeep V., additional, Panfilov, Alexander V., additional, Park, David S., additional, Patocskai, Bence, additional, Pauza, Dainius H., additional, Pauziene, Neringa, additional, Piccini, Jonathan P., additional, Pitt, Geoffrey S., additional, Po, Sunny S., additional, Prasad, Abhiram, additional, Priori, Silvia G., additional, Radwański, Przemysław B., additional, Rappel, Wouter-Jan, additional, Reiser, Michelle, additional, Restrepo, Alejandro Jimenez, additional, Robinson, Richard B., additional, Roden, Dan M., additional, Rosen, Michael R., additional, Rosso, Raphael, additional, Rudy, Yoram, additional, Rysevaite-Kyguoliene, Kristina, additional, Sabbah, Hani N., additional, Sacher, Frederic, additional, Sachse, Frank B., additional, Saguner, Ardan M., additional, Sanders, Prashanthan, additional, Sanguinetti, Michael C., additional, Santangeli, Pasquale, additional, Sarraf, Mohammad, additional, Satin, Jonathan, additional, Schalij, Martin Jan, additional, Scherlag, Benjamin J., additional, Schill, Matthew R., additional, Schleifer, J. William, additional, Schuessler, Richard B., additional, Schwartz, Peter J., additional, Seeger, Timon, additional, Semsarian, Christopher, additional, Seravalle, Gino, additional, Shah, Ashok J., additional, Shaw, Robin M., additional, Shen, Mark J., additional, Shen, Win–Kuang, additional, Sheu, Shey-Shing, additional, Shivkumar, Kalyanam, additional, Silva, Jennifer N.A., additional, Skanes, Allan C., additional, Soejima, Kyoko, additional, Somers, Virend K., additional, Sorajja, Dan, additional, Stavrakis, Stavros, additional, Steinberg, Christian, additional, Stevenson, Lynne Warner, additional, Stevenson, William G., additional, Sweeney, Michael O., additional, Swerdlow, Charles, additional, Takigawa, Masateru, additional, Tamargo, Juan, additional, Tandri, Harikrishna, additional, Tedrow, Usha B., additional, Thompson, Nathaniel, additional, Thompson, Paul D., additional, Tomaselli, Gordon F., additional, Towbin, Jeffrey A., additional, Trayanova, Natalia A., additional, Tristani-Firouzi, Martin, additional, Tseng, Zian H., additional, Ueda, Akiko, additional, Valdivia, Héctor H., additional, Valiunas, Virginijus, additional, van der Werf, Christian, additional, Van Hare, George F., additional, Vidmar, David, additional, Viskin, Sami, additional, Voigt, Niels, additional, Walsh, Edward P., additional, Wang, Paul J., additional, Wehrens, Xander H.T., additional, Weiss, Mark S., additional, Wilde, Arthur A.M., additional, Wilkoff, Bruce L., additional, Woo, Y. Joseph, additional, Wu, Joseph C., additional, Yee, Raymond, additional, Zaman, Junaid A.B., additional, Zarzoso, Manuel, additional, Zeitler, Emily P., additional, Zeppenfeld, Katja, additional, Zghaib, Tarek, additional, Zhang, Xiao-Dong, additional, and Zipes, Douglas P., additional

Published
2018
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14. Bioengineered peptibodies as blockers of ion channels

Author

Chidipi, Bojjibabu, primary, Chang, Mengmeng, additional, Cui, Meng, additional, Abou-Assali, Obada, additional, Reiser, Michelle, additional, Pshenychnyi, Sergii, additional, Logothetis, Diomedes E., additional, Teng, Michael N., additional, and Noujaim, Sami F., additional

Published
2022
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17. Neonatal Scn1b-null mice have sinoatrial node dysfunction, altered atrial structure, and atrial fibrillation

Author

Ramos-Mondragon, Roberto, primary, Edokobi, Nnamdi, additional, Hodges, Samantha L., additional, Wang, Shuyun, additional, Bouza, Alexandra A., additional, Canugovi, Chandrika, additional, Scheuing, Caroline, additional, Juratli, Lena, additional, Abel, William R., additional, Noujaim, Sami F., additional, Madamanchi, Nageswara R., additional, Runge, Marschall S., additional, Lopez-Santiago, Luis F., additional, and Isom, Lori L., additional

Published
2022
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24. Mechanism of PKCε regulation of cardiac GIRK channel gating.

Author

Gada, Kirin D., Mengmeng Chang, Chandrashekar, Aishwarya, Plant, Leigh D., Noujaim, Sami F., and Logothetis, Diomedes E.

Subjects
ATRIAL fibrillation, PROTEIN kinases, PROTEIN kinase C, ATRIUMS (Architecture)
Abstract

G-protein-gated inwardly rectifying potassium (GIRK) channel activity is regulated by the membrane phospholipid, phosphatidylinositol-4,5-bisphosphate (PI 4,5P2). Constitutive activity of cardiac GIRK channels in atrial myocytes, that is implicated in atrial fibrillation (AF), is mediated via a protein kinase C-e (PKCe)-dependent mechanism. The novel PKC isoform, PKCe, is reported to enhance the activity of cardiac GIRK channels. Here, we report that PKCe stimulation leads to activation of GIRK channels in mouse atria and in human stem cell-derived atrial cardiomyocytes (iPSCs). We identified residue GIRK4(S418) which when mutated to Ala abolished, or to Glu, mimicked the effects of PKCe on GIRK currents. PKCe strengthened the interactions of the cardiac GIRK isoforms, GIRK4 and GIRK1/4 with PIP2, an effect that was reversed in the GIRK4(S418A) mutant. This mechanistic insight into the PKCe-mediated increase in channel activity because of GIRK4(S418) phosphorylation, provides a precise druggable target to reverse AF-related pathologies due to GIRK overactivity. [ABSTRACT FROM AUTHOR]

Published
2023
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26. Contributors

Author

Abriel, Hugues, primary, Adkisson, Wayne O., additional, Agullo-Pascual, Esperanza, additional, Ajijola, Olujimi A., additional, Al-Ahmad, Amin, additional, Alli, Oluseun, additional, Altman, Robert K., additional, Anter, Elad, additional, Antzelevitch, Charles, additional, Anumonwo, Justus M.B., additional, Armaganijan, Luciana, additional, Ashikaga, Hiroshi, additional, Atienza, Felipe, additional, Avula, Uma Mahesh R., additional, Backx, Peter H., additional, Balse, Elise, additional, Barrett, Conor D., additional, Benditt, David G., additional, Berenfeld, Omer, additional, Bers, Donald M., additional, Berul, Charles I., additional, Blank, A. Christian, additional, Bloise, Raffaella, additional, Bogun, Frank Matthias, additional, Borggrefe, Martin, additional, Boyle, Noel G., additional, Breithardt, Günter, additional, Brini, Marisa, additional, Brink, Peter R., additional, Brugada, Josep, additional, Brugada, Pau, additional, Brugada, Pedro, additional, Brugada, Ramon, additional, Brugada, Victoria, additional, Buch, Eric, additional, Bukauskas, Feliksas F., additional, Burkhardt, J. David, additional, Bursac, Nenad, additional, Calkins, Hugh, additional, Callans, David J., additional, Campuzano, Oscar, additional, Caples, Sean M., additional, Carafoli, Ernesto, additional, Castellanos, Augustin, additional, Catterall, William, additional, Cerrone, Marina, additional, Chen, Lan S., additional, Chen, Lei, additional, Chen, Peng-Sheng, additional, Chin, Ashley, additional, Chugh, Aman, additional, Cohen, Ira S., additional, Connolly, Stuart J., additional, Constantino, Jason, additional, Crotti, Lia, additional, Cuoco, Frank A., additional, Curtis, Anne B., additional, Damiano, Ralph J., additional, Darbar, Dawood, additional, Das, Mithilesh K., additional, Delmar, Mario, additional, Delpón, Eva, additional, Di Biase, Luigi, additional, Dixit, Sanjay, additional, Dobrev, Dobromir, additional, Dosdall, Derek J., additional, Dyer, John W., additional, Eckardt, Lars, additional, Edwards, Andrew G., additional, Efimov, Igor R., additional, Ellenbogen, Kenneth A., additional, Ellinor, Patrick T., additional, Entcheva, Emilia, additional, Estes, N.A. Mark, additional, Fischmeister, Rodolphe, additional, Fisher, John D., additional, Fishman, Glenn I., additional, Frankel, David S., additional, Franz, Michael R., additional, Friedman, Paul A., additional, Froelicher, Victor F., additional, Gami, Apoor S., additional, George, Alfred L., additional, Gerstenfeld, Edward P., additional, Gold, Michael R., additional, Goldberger, Jeffrey J., additional, Grandi, Eleonora, additional, Gray, Richard A., additional, Groh, William J., additional, Grubb, Blair P., additional, Haissaguerre, Michel, additional, Hake, Johan, additional, Halperin, Henry R., additional, Harris, Louise, additional, Hatem, Stéphane, additional, Hayes, David L., additional, Hocini, Meleze, additional, Hohnloser, Stefan H., additional, Holmes, David Richard, additional, Hoshijima, Masahiko, additional, Hu, Yuxuan, additional, Hund, Thomas J., additional, Hutchinson, Mathew D., additional, Hwang, Hye Jin, additional, Ideker, Raymond E., additional, Ilkhanoff, Leonard, additional, Ingles, Jodie, additional, Jackman, Warren M., additional, Jais, Pierre, additional, Jalife, José, additional, Jhun, Bong Sook, additional, John, Roy M., additional, Jongbloed, Monique, additional, Josephson, Mark E., additional, Kadish, Alan H., additional, Kalifa, Jérôme, additional, Kalman, Jonathan M., additional, Kamp, Timothy J., additional, Kanj, Mohamed Hani, additional, Karabin, Beverly, additional, Kass, Robert S., additional, Katritsis, Demosthenes G., additional, Kaur, Kuljeet, additional, Kim, Jong J., additional, Kirchhof, Paulus, additional, Kléber, André G., additional, Klein, George J., additional, Kohl, Peter, additional, Kolandaivelu, Aravindan, additional, Krahn, Andrew D., additional, Krumerman, Andrew, additional, Kumar, Saurabh, additional, Kuck, Karl-Heinz, additional, Lakatta, Edward G., additional, Latchamsetty, Rakesh, additional, Lau, Dennis H., additional, Lerman, Bruce B., additional, Leroy, Jérôme, additional, Lewis, William R., additional, Lin, Shien-Fong, additional, Link, Mark S., additional, Liu, Christopher F., additional, Lockwood, Deborah J., additional, Loh, Peter, additional, Lopatin, Anatoli N., additional, Lopshire, John C., additional, Lubitz, Steven A., additional, Madias, Christopher, additional, Mahajan, Aman, additional, Makielski, Jonathan C., additional, Malik, Marek, additional, Maltsev, Victor A., additional, Marchlinski, Francis E., additional, Marelli, Ariane J., additional, Markowitz, Steven M., additional, Maron, Barry J., additional, Martens, Jeffrey R., additional, Marx, Steven O., additional, McCulloch, Andrew D., additional, Metzner, Andreas, additional, Michailova, Anuska P., additional, Miller, John Michael, additional, Milstein, Michelle Lynne, additional, Mohler, Peter, additional, Morady, Fred, additional, Myerburg, Robert J., additional, Nakagawa, Hiroshi, additional, Napolitano, Carlo, additional, Narayan, Sanjiv M., additional, Natale, Andrea, additional, Nattel, Stanley, additional, Nazarian, Saman, additional, Nerbonne, Jeanne M., additional, Ng, Fu Siong, additional, Nogami, Akihiko, additional, Noujaim, Sami F., additional, Olshansky, Brian, additional, Oral, Hakan, additional, O-Uchi, Jin, additional, Ouyang, Feifan, additional, Ozcan, Cevher, additional, Packer, Douglas L., additional, Pahlm, Olle, additional, Pandit, Sandeep V., additional, Park, David S., additional, Pitt, Geoffrey S., additional, Po, Sunny S., additional, Priori, Silvia G., additional, Rappel, Wouter-Jan, additional, Reddy, Vivek Y., additional, Robertson, Jason O., additional, Robinson, Richard B., additional, Roden, Dan M., additional, Rose, Robert A., additional, Rosen, Michael R., additional, Rosso, Raphael, additional, Rudy, Yoram, additional, Ruskin, Jeremy N., additional, Sabbah, Hani N., additional, Sachse, Frank B., additional, Saint, Lindsey L., additional, Saiz, Javier, additional, Sánchez-Chapula, José A., additional, Sanders, Prashanthan, additional, Sanguinetti, Michael C., additional, Santangeli, Pasquale, additional, Sarquella-Brugada, Georgia, additional, Satin, Jonathan, additional, Schalij, Martin Jan, additional, Scherlag, Benjamin J., additional, Schimpf, Rainer, additional, Schmidt, Georg, additional, Schwartz, Peter J., additional, Semsarian, Christopher, additional, Shah, Ashok J., additional, Shaw, Robin, additional, Sheu, Shey Shing, additional, Shivkumar, Kalyanam, additional, Skanes, Allan C., additional, Somers, Virend K., additional, Stambler, Bruce S., additional, Stein, Adam B., additional, Stevenson, Lynne Warner, additional, Stevenson, William G., additional, Sun, Jian, additional, Sutton, Richard, additional, Sweeney, Michael O., additional, Swerdlow, Charles, additional, Tamargo, Juan, additional, Tandri, Harikrishna, additional, Tawil, Rabi, additional, Tedrow, Usha, additional, Terrenoire, Cecile, additional, Tobón, Catalina, additional, Towbin, Jeffrey A., additional, Trayanova, Natalia A., additional, Tristani-Firouzi, Martin, additional, Trohman, Richard G., additional, Tseng, Zian H., additional, Turakhia, Mintu P., additional, Vaidyanathan, Ravi, additional, Valdivia, Héctor H., additional, Valiunas, Virginijus, additional, van der Heyden, Marcel A.G., additional, van der Werf, Christian, additional, Van, George F., additional, Vaseghi, Marmar, additional, Veltmann, Christian, additional, Vetter, Victoria L., additional, Viskin, Sami, additional, Voigt, Niels, additional, Vos, Marc A., additional, Wagner, Galen S., additional, Wang, Paul J., additional, Weerasooriya, Rukshen, additional, Wilde, Arthur A.M., additional, Wilkoff, Bruce L., additional, Wissner, Erik, additional, Woo, Y. Joseph, additional, Yamazaki, Masatoshi, additional, Yang, Felix, additional, Yaniv, Yael, additional, Yap, Sing-Chien, additional, Yee, Raymond, additional, Zarzoso, Manuel, additional, Zeppenfeld, Katja, additional, and Zipes, Douglas P., additional

Published
2014
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29. Immuno-Electrophysiological Mechanisms of Functional Electrical Connections Between Recipient and Donor Heart in Patients With Orthotopic Heart Transplantation Presenting With Atrial Arrhythmias

Author

Universitat Politècnica de València. Departamento de Ingeniería Electrónica - Departament d'Enginyeria Electrònica, Generalitat Valenciana, National Institutes of Health, EEUU, Herweg, Bengt, Nellaiyappan, Madhan, Welter-Frost, Allan M., Tran, Thanh, Mabry, George, Weston, Kathryn, Tobón, Catalina, Saiz Rodríguez, Francisco Javier, Noujaim, Sami, Weston, Mark W., Universitat Politècnica de València. Departamento de Ingeniería Electrónica - Departament d'Enginyeria Electrònica, Generalitat Valenciana, National Institutes of Health, EEUU, Herweg, Bengt, Nellaiyappan, Madhan, Welter-Frost, Allan M., Tran, Thanh, Mabry, George, Weston, Kathryn, Tobón, Catalina, Saiz Rodríguez, Francisco Javier, Noujaim, Sami, and Weston, Mark W.

Abstract

[EN] BACKGROUND: The formation of recipient-to donor atrio-atrial connections (AAC) in patients after orthotopic heart transplantation (OHT) is poorly understood. We sought to investigate the mechanisms of atrial tachyarrhythmias after OHT, the role of AACs, and their relationship to the immunologic match. METHODS: In a large series of OHT patients, we performed a retrospective review of 42 patients who underwent catheter ablation for atrial arrhythmias. A realistic 3-dimensional computer model of human atria was used to study AAC conductivity. RESULTS: Patient age was 55 +/- 15 years (71% male). Biatrial anastomosis was present in 24/42 patients (57%). An AAC was found in 9/42 patients (21%, right-sided in 5 patients with biatrial anastomosis, left-sided in 4 patients). The AAC became apparent at the time of the electrophysiology study 10.1 +/- 7.6 years after OHT (range, 0.3-22.2 years). Donor-specific antibodies were present in no patient with AAC but were present in 69% of patients without AAC, P=0.002. In all patients with AAC, a recipient atrial tachycardia propagated via AAC to the donor atrium (4 patients presented with atrial fibrillation). Simulations showed AAC conduction requires an isthmus of >= 2 mm and is cycle length and location dependent. Patients without AAC (n=13) frequently presented with donor atrial arrhythmias, in 77% cavo-tricuspid isthmus flutter was ablated. The procedural success was high, although, 12 patients (29%) required reablation. CONCLUSIONS: AACs are found in 21% of OHT patients with atrial tachyarrhythmias and can manifest very early after OHT. Immune privilege characterized by the absence of donor-specific antibodies may facilitate AAC formation. Propagation across an AAC is width, cycle length, and location dependent. Patients with AAC present with focal atrial tachycardias or atrial fibrillation originating from the recipient atria; patients without most frequently present with cavo-tricuspid isthmus dependent atrial flutter.

Published
2021

30. Loss of H3K4 methylation destabilizes gene expression patterns and physiological functions in adult murine cardiomyocytes

Author

Stein, Adam B., Jones, Thomas A., Herron, Todd J., Patel, Sanjeevkumar R., Day, Sharlene M., Noujaim, Sami F., Milstein, Michelle L., Klos, Matthew, Furspan, Philip B., Jalife, Jose, and Dressler, Gregory R.

Subjects
Gene expression -- Physiological aspects -- Research, Methylation -- Research, Histones -- Physiological aspects -- Research, Heart cells -- Physiological aspects -- Genetic aspects -- Research, Methyltransferases -- Physiological aspects -- Research, Health care industry
Abstract

Histone H3 lysine 4 (H3K4me) methyltransferases and their cofactors are essential for embryonic development and the establishment of gene expression patterns in a cell-specific and heritable manner. However, the importance [...]

Published
2011
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31. Immuno-Electrophysiological Mechanisms of Functional Electrical Connections Between Recipient and Donor Heart in Patients With Orthotopic Heart Transplantation Presenting With Atrial Arrhythmias

Author

Herweg, Bengt, primary, Nellaiyappan, Madhan, additional, Welter-Frost, Allan M., additional, Tran, Thanh, additional, Mabry, George, additional, Weston, Kathryn, additional, Tobón, Catalina, additional, Saiz, Javier, additional, Noujaim, Sami, additional, and Weston, Mark W., additional

Published
2021
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32. Molecular Mechanism of the Potent Benzopyran-G1 Blocker of Heteromeric G-Protein Gated Potassium Channels

Author

Cui, Meng, primary, Alhamshari, Yaser, additional, Cantwell, Lucas, additional, EI-Haou, Said, additional, Eptaminitaki, Giasemi C., additional, Chang, Mengmeng, additional, Abou-Assali, Obada, additional, Tan, Haozhou, additional, Xu, Keman, additional, Masotti, Meghan, additional, Plant, Leigh D., additional, Thakur, Ganesh, additional, Noujaim, Sami, additional, Milnes, James T., additional, and Logothetis, Diomedes E., additional

Published
2021
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34. A benzopyran with antiarrhythmic activity is an inhibitor of Kir3.1-containing potassium channels

Author

Cui, Meng, primary, Alhamshari, Yaser, additional, Cantwell, Lucas, additional, EI-Haou, Said, additional, Eptaminitaki, Giasemi C., additional, Chang, Mengmeng, additional, Abou-Assali, Obada, additional, Tan, Haozhou, additional, Xu, Keman, additional, Masotti, Meghan, additional, Plant, Leigh D., additional, Thakur, Ganesh A., additional, Noujaim, Sami F., additional, Milnes, James, additional, and Logothetis, Diomedes E., additional

Published
2021
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37. Contributors

Author

Abdula, Raushan, primary, Ackerman, Michael J., additional, Akhtar, Masood, additional, Anand, Rishi, additional, Anderson, Kelley, additional, Antzelevitch, Charles, additional, Auricchio, Angelo, additional, Badhwar, Nitish, additional, Bailey, Shane, additional, Barrett, Conor D., additional, de Luna, Antonio Bayes, additional, Belk, Paul, additional, Benditt, David G., additional, Benito, Begoña, additional, Bennett, Matthew T., additional, Bharati, Saroja, additional, Bharucha, David B., additional, Bonney, William J., additional, Bowles, Neil E., additional, Boyden, Penelope A., additional, Bozorgnia, Babak, additional, Breithardt, Günter, additional, Brugada, Josep, additional, Brugada, Pedro, additional, Brugada, Ramon, additional, Burkart, Thomas Adam, additional, Burkhardt, J. David, additional, Calkins, Hugh, additional, Camm, A. John, additional, Cecchi, Franco, additional, Cerrone, Marina, additional, Chattipakorn, Nipon, additional, Chen, Shih-Ann, additional, Chicos, Alexandru B., additional, Choudhuri, Indrajit, additional, Clauss, Sebastien, additional, Conti, Jamie Beth, additional, Cordeiro, Jonathan M., additional, Cuneo, Bettina F., additional, Cunha, Shane R., additional, Curtis, Anne B., additional, Cutler, Michael J., additional, Cygankiewicz, Iwona, additional, Damiano, Ralph J., additional, Daubert, James P., additional, Daubert, Jean-Claude, additional, Davies, D. Wyn, additional, Deedwania, Prakash, additional, DeGroot, Paul J., additional, Derval, Nicolas, additional, Biase, Luigi Di, additional, Dickfeld, Timm-Michael, additional, Dobrev, Dobromir, additional, Domanski, Michael, additional, Dorian, Paul, additional, Doshi, Hiten, additional, Duffy, Heather S., additional, Eckardt, Lars, additional, Eisner, David, additional, Ellenbogen, Kenneth A., additional, Elliott, Perry M., additional, El-Sherif, Nabil, additional, Ernst, Sabine, additional, Estes, N.A. Mark, additional, Ezekowitz, Michael D., additional, Fisher, John D., additional, Fishman, Glenn I., additional, Forclaz, Andrei, additional, Gallinghouse, G. Joseph, additional, Garlitski, Ann C., additional, Gerstenfeld, Edward P., additional, Gill, Jaswinder, additional, Gillis, Anne M., additional, Goebel, Jason A., additional, Gold, Michael R., additional, Goldman, Pamela S.N., additional, Goldschlager, Nora, additional, Gula, Lorne J., additional, Haïssaguerre, Michel, additional, Hamel, John-John, additional, Hegland, Donald D., additional, Hettrick, Douglas, additional, Ho, Siew Yen, additional, Hocini, Mélèze, additional, Homoud, Munther K., additional, Horton, Rodney, additional, Huizar, Jose F., additional, Hund, Thomas J., additional, Ideker, Raymond E., additional, Iyer, Ramesh, additional, Jackson, Kevin P., additional, Jadidi, Amir, additional, Jaïs, Pierre, additional, Jalife, José, additional, Janse, Michiel, additional, Jordaens, Luc, additional, Jung, Werner, additional, Kääb, Stefan, additional, Kadish, Alan H., additional, Kalman, Jonathan M., additional, Kantharia, Bharat K., additional, Kaszala, Karoly, additional, Katritsis, Demosthenes G., additional, Kaufman, Elizabeth S., additional, Kim, Susan S., additional, Kirubakaran, Senthil, additional, Klein, George J., additional, Klein, Helmut, additional, Knecht, Sébastien, additional, Knight, Bradley, additional, Knops, Paul, additional, Koruth, Jacob S., additional, Kowey, Peter R., additional, Krahn, Andrew D., additional, Krumerman, Andrew, additional, Kuriachan, Vikas, additional, Kusumoto, Fred, additional, Lardizabal, Joel A., additional, Lau, Chu-Pak, additional, Lau, David H., additional, Lazzara, Ralph, additional, Lee, Anson M., additional, Leong-Sit, Peter, additional, Levy, Samuel, additional, Lewalter, Thorsten, additional, Li, Hua, additional, Lindsay, Bruce D., additional, Linton, Nick W.F., additional, Madan, Nandini, additional, Mahomed, Yousuf, additional, Malcolme-Lawes, Louisa, additional, Marchlinski, Frank, additional, Maron, Barry J., additional, McBride, Ruth, additional, McKenna, William J., additional, Mehra, Rahul, additional, Mehta, Anjlee M., additional, Miller, John M., additional, Mitchell, L. Brent, additional, Mohler, Peter J., additional, Morillo, Carlos A., additional, Muir, Alison R., additional, Myazaki, Shisuke, additional, Myerburg, Robert J., additional, Naccarelli, Gerald V., additional, Nagarakanti, Rangadham, additional, Nanda, Navin C., additional, Napolitano, Carlo, additional, Natale, Andrea, additional, Nattel, Stanley, additional, Nault, Isabelle, additional, Noujaim, Sami F., additional, Olivotto, Iacopo, additional, Omran, Heyder, additional, Padeletti, Luigi, additional, Page, Richard L., additional, Park, David S., additional, Preminger, Mark, additional, Priori, Silvia G., additional, Quan, Kara J., additional, Raj, Satish R., additional, Rawlins, John, additional, Razak, Shakeeb, additional, Reddy, Shantanu, additional, Reddy, Vivek Y., additional, Rho, Robert W., additional, Rhodes, Larry A., additional, Rivero, Abel, additional, Robinson, Melissa, additional, Robotis, Dionyssios, additional, Roden, Dan M., additional, Root, Michael J., additional, Rosen, Michael R., additional, Rosenbaum, David, additional, Ruskin, Jeremy, additional, Sacher, Frédéric, additional, Sakaguchi, Scott, additional, Saksena, Sanjeev, additional, Sanchez, Javier, additional, Santageli, Pasquale, additional, Savelieva, Irina, additional, Schoenfeld, Mark H., additional, Schwartz, Peter J., additional, Schweikert, Robert, additional, Segal, Oliver R., additional, Shah, Dipen, additional, Shah, Maully, additional, Sharma, Arjun, additional, Sharma, Sanjay, additional, Sheldon, Robert S., additional, Shinagawa, Kaori, additional, Singh, Bramah N., additional, Singh, Steven, additional, Siu, Chung-Wah, additional, Skadsberg, Nicholas D., additional, Skanes, Allan C., additional, Slee, April, additional, Sra, Jasbir, additional, Steinbeck, Gerhard, additional, Steinhaus, David, additional, Stevenson, William G., additional, Strasburger, Janette F., additional, Sy, Raymond W., additional, Teh, Andrew W., additional, Tester, David J., additional, Tomaselli, Gordon, additional, Towbin, Jeffrey A., additional, Turgeon, Jacques, additional, Turitto, Gioia, additional, Tzou, Wendy, additional, van Dijk, J. Gert, additional, Van Hare, George F., additional, Van Houzen, Nathan, additional, Vatta, Matteo, additional, Vedantham, Vasanth, additional, Vetter, Victoria L., additional, Voeller, Rochus K., additional, Wagner, Galen, additional, Wakili, Reza, additional, Walker, Mariah L., additional, Wang, Paul J., additional, Wit, Andrew L., additional, Wright, Matthew, additional, Yee, Raymond, additional, Zagrodsky, Jason D., additional, Zareba, Wojciech, additional, Zellerhoff, Stephan, additional, and Ziegler, Paul, additional

Published
2012
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41. Human influenza A virus causes myocardial and cardiac-specific conduction system infections associated with early inflammation and premature death

Author

Filgueiras-Rama, David, primary, Vasilijevic, Jasmina, additional, Jalife, Jose, additional, Noujaim, Sami F, additional, Alfonso, Jose M, additional, Nicolas-Avila, Jose A, additional, Gutierrez, Celia, additional, Zamarreño, Noelia, additional, Hidalgo, Andres, additional, Bernabé, Alejandro, additional, Cop, Christopher Pablo, additional, Ponce-Balbuena, Daniela, additional, Guerrero-Serna, Guadalupe, additional, Calle, Daniel, additional, Desco, Manuel, additional, Ruiz-Cabello, Jesus, additional, Nieto, Amelia, additional, and Falcon, Ana, additional

Published
2020
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42. The small molecule GAT1508 activates brain-specific GIRK1/2 channel heteromers and facilitates conditioned fear extinction in rodents

Author

Xu, Yu, primary, Cantwell, Lucas, additional, Molosh, Andrei I., additional, Plant, Leigh D., additional, Gazgalis, Dimitris, additional, Fitz, Stephanie D., additional, Dustrude, Erik T., additional, Yang, Yuchen, additional, Kawano, Takeharu, additional, Garai, Sumanta, additional, Noujaim, Sami F., additional, Shekhar, Anantha, additional, Logothetis, Diomedes E., additional, and Thakur, Ganesh A., additional

Published
2020
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46. The Antimalarial Chloroquine Reduces the Burden of Persistent Atrial Fibrillation

Author

Universitat Politècnica de València. Departamento de Ingeniería Electrónica - Departament d'Enginyeria Electrònica, Generalitat Valenciana, National Institutes of Health, EEUU, Association for Computing Machinery's Special Interest Group on High Performance Computing, Tobón, Catalina, Palacio, Laura C., Chidipi, Bojjibadu, Slough, Diana P., Tran, Thanh, Tran, Nhi, Reiser, Michelle, Lin, Yu-Shan, Herweg, Bengt, Sayad, Dany, Saiz Rodríguez, Francisco Javier, Noujaim, Sami, Universitat Politècnica de València. Departamento de Ingeniería Electrónica - Departament d'Enginyeria Electrònica, Generalitat Valenciana, National Institutes of Health, EEUU, Association for Computing Machinery's Special Interest Group on High Performance Computing, Tobón, Catalina, Palacio, Laura C., Chidipi, Bojjibadu, Slough, Diana P., Tran, Thanh, Tran, Nhi, Reiser, Michelle, Lin, Yu-Shan, Herweg, Bengt, Sayad, Dany, Saiz Rodríguez, Francisco Javier, and Noujaim, Sami

Abstract

[EN] In clinical practice, reducing the burden of persistent atrial fibrillation by pharmacological means is challenging. We explored if blocking the background and the acetylcholine-activated inward rectifier potassium currents (I-K1 and I-KACh) could be antiarrhythmic in persistent atrial fibrillation. We thus tested the hypothesis that blocking I-K1 and I-KACh with chloroquine decreases the burden of persistent atrial fibrillation. We used patch clamp to determine the IC50 of I-K1 and I-KACh block by chloroquine and molecular modeling to simulate the interaction between chloroquine and Kir2.1 and Kir3.1, the molecular correlates of I-K1 and I-KACh. We then tested, as a proof of concept, if oral chloroquine administration to a patient with persistent atrial fibrillation can decrease the arrhythmia burden. We also simulated the effects of chloroquine in a 3D model of human atria with persistent atrial fibrillation. In patch clamp the IC50 of I-K1 block by chloroquine was similar to that of I-KACh. A 14-day regimen of oral chloroquine significantly decreased the burden of persistent atrial fibrillation in a patient. Mathematical simulations of persistent atrial fibrillation in a 3D model of human atria suggested that chloroquine prolonged the action potential duration, leading to failure of reentrant excitation, and the subsequent termination of the arrhythmia. The combined block of I-K1 and I-KACh can be a targeted therapeutic strategy for persistent atrial fibrillation.

Published
2019

49. Contributors

Author

Abrams, Dominic, Abriel, Hugues, Adkisson, Wayne O., Ajijola, Olujimi A., Alvarado, Francisco J., Amin, Ahmad S., André, Clémentine, Anter, Elad, Antzelevitch, Charles, Ariga, Rina, Arora, Rishi, Arya, Arash, Asirvatham, Samuel, Atienza, Felipe, Atluri, Pavan, Balse, Elise, Basso, Cristina, Benditt, David G., Bennett, Richard, Berenfeld, Omer, Berruezo, Antonio, Bers, Donald M., Bhaskaran, Ashwin, Bogun, Frank, Bose, Rupan, Botzer, Lior, Boyle, Patrick M., Bradfield, Jason S., Brini, Marisa, Brugada, Pedro, Caldwell, Jessica L., Calkins, Hugh, Poindexter, Catherine Ellen, Callans, David J., Carafoli, Ernesto, Catterall, William A., Cerrone, Marina, Chandler, Stephanie, Chauvel, Remi, Chen, Lan S., Chen, Peng-Sheng, Cheniti, Ghassen, Cheung, Christopher C., Chiamvimonvat, Nipavan, Chiang, David Y., Chorin, Ehud, Christini, David J., Christoffels, Vincent M., Christoph, Jan, Clancy, Colleen E., Climent, Andreu M., Cochet, Hubert, Coetzee, William A., Crossley, George H., Crotti, Lia, Cuculich, Phillip S., Curtis, Anne B., Dagradi, Federica, Damiano, Ralph J., Jr, Darbar, Dawood, Das, Mithilesh K., Delmar, Mario, Delpón, Eva, Derval, Nicolas, Deshmukh, Abhishek, Dherange, Parinita, Dickfeld, Timm M., Dierckx, Hans, Dinov, Borislav, Divakaran, Sanjay, Dixit, Sanjay, Dubois, Rémi, Duchateau, Josselin, Edwards, Andrew G., Ellenbogen, Kenneth A., Ellinor, Patrick T., Ellis, Christopher R., Enriquez, Andres, Estes III, N.A. Mark, Etheridge, Susan P., Everett, Thomas H., Fedorov, Vadim V., Filgueiras-Rama, David, Fishbein, Michael, Fishman, Glenn I., Fradley, Michael, Gami, Apoor S., Gando, Ivan, Garabelli, Paul James, Garcia, Fermin, George, Alfred L., Jr, Gerstenfeld, Edward P., Goldberger, Jeffrey J., Gourdie, Robert G., Grace, Andrew, Grubb, Blair P., Guerrier, Karine, Guillem, María S., Györke, Sándor, Haines, David E., Halperin, Henry R., Hatem, Stéphane, Haïssaguerre, Michel, Herron, Todd J., Hindricks, Gerhard, Hocini, Mélèze, Hoffman, Jacob, Hund, Thomas J., Hutchinson, Mathew D., Iliceto, Sabino, Ilkhanoff, Leonard, Ingles, Jodie, Ip, James E., Jackman, Warren M., Jalife, Jose, Jaïs, Pierre, Jhun, Bong Sook, Restrepo, Alejandro Jimenez, John, Roy M., Johnson, Jason, Jongbloed, Monique, Jáuregui, Beatriz, Kalman, Jonathan M., Kalyanasundaram, Anuradha, Kamp, Timothy J., Kanagasundram, Arvindh N., Kang, Po Wei, Kanj, Mohamed H., Kapa, Suraj, Kapur, Sunil, Karabin, Beverly, Kernik, Divya C., Klein, George J., Kléber, André G., Knight, Bradley P., Koenig, Sara N., Kohl, Peter, Konecny, Thomas, Koneru, Jayanthi N., Krahn, Andrew D., Krishnappa, Darshan, Krogh-Madsen, Trine, Kumar, Saurabh, Kusayama, Takashi, Kushnir, Alexander, Kwak, Brenda R., Lador, Adi, Lakatta, Edward G., Laksman, Zachary W.M., Latchamsetty, Rakesh, Lau, Dennis H., Lee, Byron K., Lenaeus, Michael J., Lerman, Bruce B., Li, Ning, Lin, Shien-Fong, Link, Mark S., Liu, Bin, Liu, Christopher F., Lockwood, Deborah J., Loeys, Bart, Lubitz, Steven A., Prof-Dr, Stefan Luther, Lyon, Aurore, MacGregor, Robert M., MacRae, Calum A., Maher, Timothy, Maltsev, Victor, Man, Joyce C.K., Marchlinski, Francis E., Markowitz, Steven M., Maron, Barry J., Maron, Martin S., Marra, Martina Perazzolo, Marx, Steven O., Mazzanti, Andrea, McCulloch, Andrew D., Mehta, Nishaki K., Melby, Spencer J., Mellor, Greg, Michaud, Gregory F., Miles, William M., Miller, Jennifer C., Miller, John M., Mitrani, Raul D., Mohler, Peter J., Montgomery, Jay A., Moreno, Jonathan D., Murray, Katherine T., Myerburg, Robert J., Nakagawa, Hiroshi, Naksuk, Niyada, Nalliah, Chrishan Joseph, Napolitano, Carlo, Narayan, Sanjiv M., Nazarian, Saman, Nerbonne, Jeanne M., Nery, Pablo B., Nguyen, Thao P., Nichols, Colin G., Nielsen, Morten S., Nogami, Akihiko, Noujaim, Sami F., Nubret, Karine, O-Uchi, Jin, Olgin, Jeffrey E., Olshansky, Brian, Ozcan, Cevher, Pambrun, Thomas, Panfilov, Alexander V., Pang, Paul D., Park, David S., Parlitz, Ulrich, Patocskai, Bence, Pauziene, Neringa, Pauža, Dainius H., Penela, Diego, Peyronnet, Rémi, Pfenniger, Anna, Phillips, S. Tyler, Picard, François, Ploux, Sylvain, Po, Sunny S., Poelzing, Steven, Polina, Iuliia, Porta-Sánchez, Andreu, Prasad, Abhiram, Priori, Silvia G., Pérez-Hernández, Marta, Qian, Pierre C., Quintanilla, MScEng, Jorge G., Radwański, Przemysław B., Ramirez, F. Daniel, Rappel, Wouter-Jan, Richardson, Travis D., Ripplinger, Crystal M., Robinson, Clifford G., Roden, Dan M., Rodrigo, Miguel, Rodriguez, Blanca, Rosso, Raphael, Rowin, Ethan J., Rudy, Yoram, Rysevaite-Kyguoliene, Kristina, Sacher, Frédéric, Sadek, Mouhannad M., Sanders, Prashanthan, Satin, Jonathan, Sauer, William H., Saxon, Leslie A., Schalij, Martin Jan, Schepers, Dorien, Scherlag, Benjamin J., Schleifer, J. William, Schmidt, Ehud J., Schröder-Schetelig, Johannes, Schuessler, Richard B., Schwartz, Peter J., Semsarian, Christopher, Shaw, Robin M., Shen, Win-Kuang, Sheu, Shey-Shing, Shivkumar, Kalyanam, Sieliwonczyk, Ewa, Silva, Jonathan R., Skanes, Allan C., Smyth, James W., Sobie, Eric A., Soejima, Kyoko, Somers, Virend K., Sorajja, Dan, Sroubek, Jakub, Stavrakis, Stavros, Steinberg, Christian, Stevenson, William G., Supple, Gregory E., Swerdlow, Charles, Tandri, Harikrishna, Tedrow, Usha, Thai, Phung N., Thiene, Gaetano, Tixier, Romain, Tomaselli, Gordon F., Towbin, Jeffrey A., Trayanova, Natalia A., Tristani-Firouzi, Martin, Tseng, Zian H., Tung, Roderick, Ueda, Akiko, Upadhyay, Gaurav A., Valderrábano, Miguel, Valdivia, Héctor H., van den Brink, Jonas, van der Werf, Christian, van Opbergen, Chantal J.M., Vaseghi, Marmar, Vautier, R. Ashton, Vera Pedrosa, Maria Linarejos, Verma, Nishant, Vermij, Sarah H., Virk, Sohaib, Viskin, Sami, Vlachos, Konstantinos, Walsh, Edward P., Wang, Paul J., Welte, Nicolas, Wilde, Arthur A.M., Wilkoff, Bruce L., Wu, Joseph C., Yang, Hua-Qian, Yee, Raymond, Zaman, Junaid A.B., Zeppenfeld, Katja, Zghaib, Tarek, Zhang, Jianhua, Zhang, Xiao-Dong, and Zimetbaum, Peter

Published
2022
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