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3. Kidney and Cardiovascular Effects of Canagliflozin According to Age and Sex

Author

Tae Won Yi, Brendan Smyth, Gian Luca Di Tanna, Clare Arnott, Kathryn Cardoza, Amy Kang, Carol Pollock, Rajiv Agarwal, George Bakris, David M. Charytan, Dick de Zeeuw, Hiddo J.L. Heerspink, Bruce Neal, David C. Wheeler, Christopher P. Cannon, Hong Zhang, Bernard Zinman, Vlado Perkovic, Adeera Levin, Kenneth W. Mahaffey, Meg Jardine, Barry M. Brenner, Tom Greene, Meg J. Jardine, Gary Meininger, Nicole Li, Inna Kolesnyk, Diego Aizenberg, Roberto Pecoits-Filho, David Cherney, Gregorio Obrador, Glenn Chertow, Tara Chang, Carmel Hawley, Linong Ji, Takashi Wada, Vivekanand Jha, Soo Kun Lim, Mary Anne Lim-Abrahan, Florence Santos, Dong-Wan Chae, Shang-Jyh Hwang, Evgueniy Vazelov, Ivan Rychlík, Samy Hadjadj, Vera Krane, László Rosivall, Luca De Nicola, Alexander Dreval, Michał Nowicki, Adalbert Schiller, Larry Distiller, Jose L. Górriz, Mykola Kolesnyk, null David, C. Wheeler, Rodolfo Andres Ahuad Guerrero, Juan Pablo Albisu, Andres Alvarisqueta, Ines Bartolacci, Mario Alberto Berli, Anselmo Bordonava, Pedro Calella, Maria Cecilia Cantero, Luis Rodolfo Cartasegna, Esteban Cercos, Gabriela Cecilia Coloma, Hugo Colombo, Victor Commendatore, Jesus Cuadrado, Carlos Alberto Cuneo, Ana Maria Cusumano, Walter Guillermo Douthat, Ricardo Dario Dran, Eduardo Farias, Maria Florencia Fernandez, Hernan Finkelstein, Guillermo Fragale, Jose Osvaldo Fretes, Nestor Horacio Garcia, Anibal Gastaldi, Elizabeth Gelersztein, Jorge Archibaldo Glenny, Joaquin Pablo Gonzalez, Patricia del Carmen Gonzalez Colaso, Claudia Goycoa, Gustavo Cristian Greloni, Adrian Guinsburg, Sonia Hermida, Luis Isaias Juncos, Maria Isabel Klyver, Florencia Kraft, Fernando Krynski, Paulina Virginia Lanchiotti, Ricardo Alfonso Leon de la Fuente, Nora Marchetta, Pablo Mele, Silvia Nicolai, Pablo Antonio Novoa, Silvia Ines Orio, Fabian Otreras, Alejandra Oviedo, Pablo Raffaele, Jorge Hector Resk, Lucas Rista, Nelson Rodriguez Papini, Jorgelina Sala, Juan Carlos Santos, Lilia Beatriz Schiavi, Horacio Sessa, Tomas Smith Casabella, Maria Rosa Ulla, Maria Valdez, Augusto Vallejos, Adriana Villarino, Virginia Esther Visco, Alfredo Wassermann, Cesar Javier Zaidman, Ngai Wah Cheung, Carolyn Droste, Ian Fraser, David Johnson, Peak Mann Mah, Kathy Nicholls, David Packham, Joseph Proietto, Anthony Roberts, Simon Roger, Venessa Tsang, Roberto Abrão Raduan, Fernando Augusto Alves da Costa, Celso Amodeo, Luiz Alberto Andreotti Turatti, Rachel Bregman, Fernanda Cristina Camelo Sanches, Luis Henrique Canani, Antônio Roberto Chacra, João Lindolfo Cunha Borges, Sérgio Alberto Cunha Vêncio, Roberto Jorge da Silva Franco, Domingos d’Avila, Evandro de Souza Portes, Pedro de Souza, Luciane Mônica Deboni, Fadlo Fraige Filho, Bruno Geloneze Neto, Marcus Gomes, Suely Keiko Kohara, Elizete Keitel, Jose Francisco Kerr Saraiva, Hugo Roberto Kurtz Lisboa, Fabiana Loss de Carvalho Contieri, Rosângela Milagres, Renan Montenegro Junior, Claudia Moreira de Brito, Miguel Nasser Hissa, Ângela Regina Nazario Sabbag, Irene Noronha, Daniel Panarotto, Roberto Pecoits Filho, Márcio Antônio Pereira, Wladmir Saporito, Antonio Scafuto Scotton, Tiago Schuch, Roberto Simões de Almeida, Cássio Slompo Ramos, João Soares Felício, Fernando Thomé, Jean Carlo Tibes Hachmann, Sérgio Yamada, Cesar Yoiti Hayashida, Tarissa Beatrice Zanata Petry, Maria Teresa Zanella, Viktoria Andreeva, Angelina Angelova, Stefan Dimitrov, Veselka Genadieva, Gabriela Genova-Hristova, Kiril Hristozov, Zdravko Kamenov, Atanas Koundurdjiev, Lachezar Lozanov, Viktor Margaritov, Boyan Nonchev, Rangel Rangelov, Alexander Shinkov, Margarita Temelkova, Ekaterina Velichkova, Andrian Yakov, Naresh Aggarwal, Ronnie Aronson, Harpreet Bajaj, Guy Chouinard, James Conway, Serge Cournoyer, Gerald DaRoza, Sacha De Serres, François Dubé, Ronald Goldenberg, Anil Gupta, Milan Gupta, Sam Henein, Hasnain Khandwala, Lawrence Leiter, François Madore, Alan McMahon, Norman Muirhead, Vincent Pichette, Remi Rabasa-Lhoret, Andrew Steele, Navdeep Tangri, Ali Torshizi, Vincent Woo, Nadia Zalunardo, María Alicia Fernández Montenegro, Juan Gonzalo Godoy Jorquera, Marcelo Medina Fariña, Victor Saavedra Gajardo, Margarita Vejar, Nan Chen, Qinkai Chen, Shenglian Gan, Yaozhong Kong, Detian Li, Wenge Li, Xuemei Li, Hongli Lin, Jian Liu, Weiping Lu, Hong Mao, Yan Ren, Weihong Song, Jiao Sun, Lin Sun, Ping Tu, Guixia Wang, Jinkui Yang, Aiping Yin, Xueqing Yu, Minghui Zhao, Hongguang Zheng, Jose Luis Accini Mendoza, Edgar Arcos, Jorge Avendano, Jorge Ernesto Andres Diaz Ruiz, Luis Hernando Garcia Ortiz, Alexander Gonzalez, Eric Hernandez Triana, Juan Diego Higuera, Natalia Malaver, Dora Inés Molina de Salazar, Ricardo Rosero, Monica Alexandra Terront Lozano, Luis Valderrama Cometa, Alex Valenzuela, Ruben Dario Vargas Alonso, Ivan Villegas, Hernan Yupanqui, Dagmar Bartaskova, Petr Barton, Jana Belobradkova, Lenka Dohnalova, Tomas Drasnar, Richard Ferkl, Katarina Halciakova, Vera Klokocnikova, Richard Kovar, Jiri Lastuvka, Martin Lukac, Satu Pesickova, Karel Peterka, Jiri Pumprla, Ivan Rychlik, Frantisek Saudek, Vladimir Tesar, Martin Valis, Pavel Weiner, Stanislav Zemek, Eric Alamartine, Sophie Borot, Bertrand Cariou, Bertrand Dussol, Jean-Pierre Fauvel, Pierre Gourdy, Alexandre Klein, Yannick Le Meur, Alfred Penfornis, Ronan Roussel, Pierre-Jean Saulnier, Eric Thervet, Philippe Zaoui, Volker Burst, Markus Faghih, Grit Faulmann, Hermann Haller, Reinhold Jerwan-Keim, Stephan Maxeiner, Björn Paschen, Georg Plassmann, Ludger Rose, Ronaldo Arturo Gonzalez Orellana, Franklin Paul Haase, Juan Pablo Moreira Diaz, Luis Alberto Ramirez Roca, Jose Antonio Sánchez Arenales, José Vicente Sanchez Polo, Erick Turcios Juarez, Gyongyi Csecsei, Botond Csiky, Peter Danos, Laszlo Deak, Mihaly Dudas, Eleonora Harcsa, Katalin Keltai, Sandor Keresztesi, Krisztian Kiss, Laszlo Konyves, Lajos Major, Margit Mileder, Marta Molnar, Janos Mucsi, Tamas Oroszlan, Ivan Ory, Gyorgy Paragh, Eva Peterfai, Gizella Petro, Katalin Revesz, Robert Takacs, Sandor Vangel, Szilard Vasas, Marianna Zsom, Oomman Abraham, Raju Sree Bhushan, Dewan Deepak, Fernando M. Edwin, Natarajan Gopalakrishnan, Noble Gracious, Alva Hansraj, Dinesh Jain, C.B. Keshavamurthy, Dinesh Khullar, Sahay Manisha, Jayameena Peringat, Narayan Prasad, Rao K. Satyanarayana, Reddy Sreedhar, Melemadathil Sreelatha, Bhimavarapu Sudhakar, Ramesh Chandra Vyasam, Riccardo Bonadonna, Pietro Castellino, Antonio Ceriello, Luca Chiovato, Salvatore De Cosmo, Giuseppe Derosa, Alberto Di Carlo, Graziano Di Cianni, Giovanni Frascà, Giorgio Fuiano, Giovanni Gambaro, Giacomo Garibotto, Carlo Giorda, Fabio Malberti, Marcora Mandreoli, Edoardo Mannucci, Emanuela Orsi, Piermarco Piatti, Domenico Santoro, Ferdinando Carlo Sasso, Gaetano Serviddio, Andrea Stella, Roberto Trevisan, Anna Maria Veronelli, Luca Zanoli, Hitoshi Akiyama, Hiromi Aoki, Akimichi Asano, Tadashi Iitsuka, Shizuo Kajiyama, Susumu Kashine, Toshio Kawada, Takamoto Kodera, Hiroshi Kono, Kazunori Koyama, Yasuro Kumeda, Shozo Miyauchi, Kazuyuki Mizuyama, Tetsuji Niiya, Hiroko Oishi, Satoshi Ota, Terue Sakakibara, Masahiko Takai, Osamu Tomonaga, Mitsuru Tsujimoto, Masakiyo Wakasugi, Yasushi Wakida, Takayuki Watanabe, Masayo Yamada, Kazuhiro Yanagida, Toshihiko Yanase, Wataru Yumita, Egle Gaupsiene, Dalia Kozloviene, Antanas Navickas, Egle Urbanaviciene, Rohana Abdul Ghani, Khalid Abdul Kadir, Norsiah Ali, Mohd Daud Che Yusof, Chye Lee Gan, Mastura Ismail, Wei Yen Kong, Swee Win Lam, Li Yuan Lee, Chek Loong Loh, Anita Bhajan Manocha, Kee Sing Ng, Nik Nur Fatnoon Nik Ahmad, Vanassa Ratnasingam, Saiful Shahrizal Bin Shudim, Paranthaman Vengadasalam, Luis David Abraira Munoz, Melchor Alpizar Salazar, Juan Baas Cruz, Mario Burgos Soto, Jose Chevaile Ramos, Alfredo Chew Wong, Jose Ricardo Correa Rotter, Tonatiu Diaz Escalante, Favio Edmundo Enriquez Sosa, Fernando Flores Lozano, Luis Fernando Flota Cervera, Paul Frenk Baron, Cecilia Garcia Ballesteros, Jose David Gomez Rangel, Luis Enrique Herrera Jimenez, Sergio Saul Irizar Santana, Fernando Jimenez Flores, Hugo Laviada Molina, Rosa Isela Luna Ceballos, Belia Martin del Campo Blanco, Guadalupe Morales Franco, Oscar Tarsicio Moreno Loza, Cynthia Mustieles Rocha, Gregorio Obrador Vera, Ricardo Orozco Castellanos, Juan Peralta Calcaneo, Miguel Angel Reyes Rosano, Hiromi Rodriguez Pattzi, Juan Rosas Guzman, Isabel Erika Rucker Joerg, Sandra Berenice Saavedra Sanchez, Jose Hector Sanchez Mijangos, Pablo Serrano Sanson, Juan Alfredo Tamayo y Orozco, Eloisa Tellez Chavez, Alejandro Valdes Cepeda, Luis Venegas Carrillo, Juan Villagordoa Mesa, Rolando Zamarripa Escobedo, John Baker, Paul Noonan, Russell Scott, Robert Walker, Edward Watson, Michael Williams, Simon Young, Zaynab Abejuela, Jeimeen Agra, Grace Aquitania, Clodoaido Caringal, Rhea Severina Comia, Lalaine Delos Santos, Olivert Gomez, Cecilia Jimeno, Gerry Tan, Marsha Tolentino, Christy Yao, Yvette Ethel Yap, Ma. Dovie Lallaine Ygpuara, Renata Bijata-Bronisz, Lucyna Hotlos, Andrzej Januszewicz, Barbara Kaczmarek, Anna Kaminska, Lech Lazuka, Andrzej Madej, Stanislaw Mazur, Dorota Mlodawska-Choluj, Michal Nowicki, Grazyna Orlowska-Kowalik, Grazyna Popenda, Barbara Rewerska, Dariusz Sowinski, Liliana Monica Angelescu, Veronica Anghel, Rodica-Ioana Avram, Mihaela-Magdalena Busegeanu, Adriana Cif, Dana Cosma, Carmen Crisan, Luiza Despina Demian, Ioana Emilia Ferariu, Ildiko Halmagyi, Nicolae Hancu, Mircea Munteanu, Doru Negru, Adriana Gabriela Onaca, Ligia Petrica, Amorin Remus Popa, Aurelian-Emil Ranetti, Cristian Serafinceanu, Cristina Toarba, Alina Agafyina, Olga Barbarash, Olga Barysheva, Daniil Chizhov, Vladimir Dobronravov, Irina Glinkina, Elena Grineva, Vladimir Khirmanov, Elena Kolmakova, Tatiana Koroleva, Liudmila Kvitkova, Viacheslav Marasaev, Ashot Mkrtumyan, Tatiana Morugova, Galina Nagibovich, Oleg Nagibovich, Sergei Nedogoda, Irina Osipova, Tatiana Raskina, Yulia Samoylova, Olga Sazonova, Minara Shamkhalova, Elena Shutemova, Yuriy Shwartz, Oleg Uriasyev, Sergey Vorobyev, Anna Zateyshchikova, Dmitry Zateyshshikov, Tatyana Zykova, Slobodan Antic, Miodrag Djordjevic, Aleksandra Kendereski, Katarina Lalic, Nebojsa Lalic, Vesna Popovic-Radinovic, Jana Babikova, Olga Benusova, Ingrid Buganova, Jan Culak, Andrej Dzupina, Jana Dzuponova, Peter Fulop, Adriana Ilavska, Emil Martinka, Zuzana Ochodnicka, Daniel Pella, Iveta Smatanova, Fayzal Ahmed, Aysha Badat, Johannes Breedt, Lawrence Distiller, Vimladhevi Govender, Ravendran Govender, Mukesh Joshi, Jaco Jurgens, Gulam Latiff, Landman Lombard, Mohamed Mookadam, Nomangesi Ngcakani, Hendrik Nortje, Helena Oosthuizen, Larisha Pillay-Ramaya, Hans Prozesky, Jeevren Reddy, Paul Rheeder, Mary Seeber, Young Min Cho, In-Kyung Jeong, Sin Gon Kim, Yeong Hoon Kim, Hyuk-Sang Kwon, Min Jeong Kwon, Byung-Wan Lee, JungEun Lee, Moon-Kyu Lee, Moon-Suk Nam, Kook-Hwan Oh, Cheol- Young Park, Sun-Hee Park, Kun Ho Yoon, Pere Alvarez Garcia, Luis Asmarats Mercadal, Clara Barrios, Fernando Cereto Castro, Secundino Cigarran Guldris, Marta Dominguez Lopez, Jesus Egido de los Rios, Gema Fernandez Fresnedo, Antonio Galan Serrano, Isabel Garcia, Francisco Javier Gonzalez Martinez, Jose Esteban Jodar Gimeno, Manuel Lopez Mendoza, Tamara Malek Marin, Cristobal Morales Portillo, Maria Antonia Munar Vila, Manuel Muñoz Torres, Javier Nieto Iglesias, Jonay Pantoja Perez, Merce Perez Vera, Jose M. Portoles Perez, María Angustias Quesada Simón, Rafael Simo Canonge, Alfonso Soto Gonzalez, Manel Terns Riera, Francisco Jose Tinahones Madueno, Mercedes Velo Plaza, Chwen-Tzuei Chang, Lee-Ming Chuang, Te-Lin Hsia, Chang-Hsun Hsieh, Chih-Ching Lin, Yung- Chuan Lu, Wayne H-H Sheu, Olga Barna, Svitlana D. Bilyk, Volodymyr Botsyurko, Iryna Dudar, Ivan Fushtey, Olga Godlevska, Oleksandr Golovchenko, Olga Gyrina, Anatoliy Kazmirchuk, Iuliia Komisarenko, Oleksii Korzh, Nonna Kravchun, Oleg Legun, Borys Mankovskyy, Liliya Martynyuk, Yuriy Mostovoy, Nataliia Pashkovska, Larysa Pererva, Tetyana Pertseva, Oleksandr Samoylov, Ivan Smirnov, Yevgeniya Svyshchenko, Halyna Tomashkevych, Ivan Topchii, Nadiya Tryshchuk, Vira Tseluyko, Vadym Vizir, Maryna Vlasenko, Tetiana Zlova, Liliia Zub, Salah Abusnana, Mohamed Railey, Kamal Abouglila, Paul Ainsworth, Zishan Ali, Vijayaraman Arutchelvam, Maria Barnard, Srikanth Bellary, Emyr Davies, Mark Davies, Simon Davies, Alison Dawson, Mohsen El Kossi, Patrick English, Donald Fraser, Luigi Gnudi, Anthony Gunstone, Timothy Hall, Wasim Hanif, Alan Jackson, Andrew Johnson, Franklin Joseph, Singhan Krishnan, Mick Kumwenda, Iain MacDougall, Paul Nixon, Joseph O'Hare, Sam Philip, Shenaz Ramtoola, Manish Saxena, Davesh Sennik, Godwin Simon, Baldev Singh, Jeffrey Stephens, Anna Strzelecka, Rehan Symonds, Wayne Turner, Mona Wahba, John Wakeling, David Wheeler, Peter Winocour, Joseph Abdallah, Raied Abdullah, Matthew Abramowitz, Idalia Acosta, Joseph Aiello, Laura Akright, Ayim Akyea-Djamson, Rajendran Alappan, Radica Alicic, Amer Al-Karadsheh, Dale Crawford Allison, Carlos Arauz-Pacheco, Shahabul Arfeen, Ahmed Arif, Moogali Arvind, Naveen Atray, Ahmed Awad, Peggy Barnhill, Elizabeth Barranco, Carlos Barrera, Matthew Beacom, Venkata Behara, Diogo Belo, Rhonda Bentley-Lewis, Ramon Berenguer, Lidia Bermudez, Marializa Bernardo, Mihaela Biscoveanu, Cynthia Bowman-Stroud, Donald Brandon, Osvaldo Brusco, Robert Busch, Yamil Canaan, Alicia Chilito, Tom Christensen, Cynthia Christiano, Elena Christofides, Caroucel Chuateco, Kenneth Cohen, Robert Cohen, Debbie Cohen-Stein, Charles Cook, Daniel Coyne, Nizar Daboul, Riad Darwish, Adarsh Daswani, Kenneth Deck, Cyrus Desouza, Devasmita Dev, Monika Dhillon, Sohan Dua, Frank Eder, Ana Maria Elosegui, Mohamed El-Shahawy, John Ervin, Alberto Esquenazi, John Evans, Steven Fishbane, Juan Frias, Eugenia Galindo-Ramos, Claude Galphin, Adline Ghazi, Enrique Gonzalez, David Gorson, Anupama Gowda, Barbara Greco, Stephen Grubb, Rakesh Gulati, Jamal Hammoud, Stuart Handelsman, Israel Hartman, Kenneth Hershon, Daniel Hiser, George Hon, Radu Jacob, Maria Jaime, Aamir Jamal, Charles Kaupke, Gerald Keightley, Elizabeth Kern, Rakhi Khanna, Zeid Khitan, Sun Kim, Nelson Kopyt, Csaba Kovesdy, Gopal Krishna, Jeffrey (Jay) Kropp, Amrendra Kumar, Jayant Kumar, Neil Kumar, Jorge Kusnir, Wendy Lane, Mary Lawrence, Lawrence Lehrner, John Lentz, Dennis Levinson, Derek Lewis, Kenneth Liss, Andreas Maddux, Hiralal Maheshwari, Sreedhar Mandayam, Isam Marar, Bhasker Mehta, John Middleton, Jorge Mordujovich, Ramon Moreda, Moustafa Moustafa, Samuel Mujica Trenche, Mohanram Narayanan, Javier Narvarte, Tareq Nassar, George Newman, Brian Nichol, Philip Nicol, Josier Nisnisan, A. Kaldun Nossuli, Chamberlain Obialo, Sarah Olelewe, Michael Oliver, Andrew O'Shaughnessy, John Padron, Rohit Pankhaniya, Reginald Parker, Devesh Patel, Gnyandev Patel, Nina Patel, Humberto Pavon, Armando Perez, Carlos Perez, Alan Perlman, Karlton Pettis, Walter Pharr, Andrea Phillips, Raman Purighalla, Luis Quesada-Suarez, Rajiv Ranjan, Sanjeev Rastogi, Jakkidi Reddy, Marc Rendell, Lisa Rich, Michael Robinson, Hector Rodriguez, Sylvia Rosas, Fadi Saba, Rallabhandi Sankaram, Ravi Sarin, Robert Schreiman, David Scott, Mohamed Sekkarie, John Sensenbrenner, Muhammad Shakeel, Michael Shanik, Sylvia Shaw, Stephen Smith, Richard Solomon, Amy Sprague, Leslie Spry, Pusadee Suchinda, Senan Sultan, Prasanth Surampudi, Sherry Sussman, Anjanette Tan, Antonio Terrelonge, Michael Thompson, Fernando Trespalacios, Bruce Trippe, Pilar Trueba, Marcel Twahirwa, John Updegrove, Peter Van Buren, Mark Vannorsdall, Freemu Varghese, Pedro Velasquez-Mieyer, Sailaja Ventrapragada, Goga Vukotic, Khurram Wadud, Mark Warren, Henry Watson, Ronald Watts, Daniel Weiner, James Welker, Jean Welsh, Shelley Williams, and Michelle Zaniewski-Singh

Subjects
age, diabetes, Nephrology, kidney outcomes, sex, Diabetic kidney disease, canagliflozin, cardiovascular outcomes, chronic kidney disease, sodium/glucose cotransporter 2 inhibitors
Abstract

Rationale & Objective: It is unclear whether the effect of canagliflozin on adverse kidney and cardiovascular events in those with diabetic kidney disease varies by age and sex. We assessed the effects of canagliflozin among age group categories and between sexes in the Canagliflozin and Renal Endpoints in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) study.Study Design: Secondary analysis of a randomized controlled trial.Setting & Participants: Participants in the CREDENCE trial.Intervention: Participants were randomly assigned to receive canagliflozin 100 mg/d or placebo.Outcomes: Primary composite outcome of kidney failure, doubling of serum creatinine concentration, or death due to kidney or cardiovascular disease. Prespecified secondary and safety outcomes were also analyzed. Outcomes were evaluated by age at baseline (Results: The mean age of the cohort was 63.0 ± 9.2 years, and 34% were female. Older age and female sex were independently associated with a lower risk of the composite of adverse kidney outcomes. There was no evidence that the effect of canagliflozin on the primary outcome (a composite of kidney failure, a doubling of serum creatinine concentration, or death from kidney or cardiovascular causes) differed between age groups (HRs, 0.67 [95% CI, 0.52-0.87], 0.63 [0.48-0.82], and 0.89 [0.61-1.29] for ages Limitations: This was a post hoc analysis with multiple comparisons.Conclusions: Canagliflozin consistently reduced the relative risk of kidney events in people with diabetic kidney disease in both sexes and across age subgroups. As a result of greater background risk, the absolute reduction in adverse kidney outcomes was greater in younger participants.Funding: This post hoc analysis of the CREDENCE trial was not funded. The CREDENCE study was sponsored by Janssen Research and Development and was conducted collaboratively by the sponsor, an academic-led steering committee, and an academic research organization, George Clinical.Trial Registration: The original CREDENCE trial was registered at ClinicalTrials.gov with study number NCT02065791.

Published
2023
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6. Age-associated differences in the human lung extracellular matrix

Author

M.L. Koloko Ngassie, M. De Vries, T. Borghuis, W. Timens, Don D. Sin, D. Nickle, P. Joubert, P. Horvatovich, G. Marko-Varga, J.J. Teske, J.M. Vonk, R. Gosens, Y.S. Prakash, J.K. Burgess, and C.A. Brandsma

Subjects
Pulmonary and Respiratory Medicine, Adult, Proteomics, Adolescent, Physiology, Lung Diseases/metabolism, Cell Biology, Extracellular Matrix/metabolism, Lung/metabolism, Middle Aged, Extracellular Matrix Proteins/genetics, Young Adult, Physiology (medical), 80 and over, Humans, Aged
Abstract

IntroductionExtracellular matrix (ECM) remodelling has been associated with chronic lung diseases. However, information about specific age-associated differences in lung ECM is currently limited. In this study we aimed to identify and localize age-associated ECM differences in human lung using comprehensive transcriptomic, proteomic and immunohistochemical analyses.MethodsOur previously identified age-associated gene expression signature of the lung was re-analysed limiting it to an aging signature based on 270 control patients (37-80 years) and focused on the Matrisome core geneset using geneset enrichment analysis. To validate the age-associated transcriptomic differences on protein level, we compared the age-associated ECM genes (F ResultsComparative analysis of transcriptomic and proteomic data identified 7 ECM proteins with higher expression with age at both gene and protein level: COL1A1, COL6A1, COL6A2, COL14A1, FBLN2, LTBP4 and LUM. With immunohistochemistry we demonstrated higher protein expression with age for COL6A2 in whole tissue, parenchyma, airway wall and blood vessel, for COL14A1 in bronchial epithelium and blood vessel, and for FBLN2 and COL1A1 in lung parenchyma.ConclusionOur study revealed that higher age is associated with lung ECM remodelling, with specific differences occurring in defined regions within the lung. These differences may affect lung structure and physiology with aging and as such may increase susceptibility for developing chronic lung diseases.Key messagesWhat is already known on this topicsummarise the state of scientific knowledge on this subject before you did your study and why this study needed to be done.❖ In animal models, it has been demonstrated that aging alters the composition of the lung ECM, with more deposition of collagen and degradation of elastin. Similar ECM differences have been observed in age-associated chronic lung diseases, including COPD; moreover, we observed in lung tissue that several ECM genes associate differently with age in COPD patients compared to non-COPD controls(1). Detailed knowledge on age-associated changes in specific ECM proteins as well as regional differences within the lung is lacking.What this study addssummarise what we now know as a result of this study that we did not know before.❖ We identified 7 age-associated ECM proteins i.e. COL1A1, COL6A1, COL6A2 COL14A1, FBLN2, LTBP4 and LUM with higher transcript and protein levels in human lung tissue with age. Extensive immunohistochemical analysis revealed significant age-associated differences for 3 of these ECM proteins in specific compartments of the lung, with the most notable differences in the blood vessels and parenchyma.How this study might affect research, practice, or policysummarise the implications of this study.❖ The identification of age-associated differences in specific human lung ECM proteins lays a new foundation for the investigation of ECM differences in age-associated chronic lung diseases. Additionally, examining the function of these age-associated ECM proteins and their cellular interactions in lung injury and repair responses may provide novel insight in mechanisms underlying chronic lung diseases.

Published
2023

9. VoiceTalk: Multimedia-IoT Applications for Mixing Mandarin, Taiwanese, and English

Author

Yi-Bing Lin, Yuan-Fu Liao, Sin-Horng Chen, Shaw-Hwa Hwang, and Yih-Ru Wang

Subjects
Computer Networks and Communications
Abstract

The voice-based Internet of Multimedia Things (IoMT) is the combination of IoT interfaces and protocols with associated voice-related information, which enables advanced applications based on human-to-device interactions. An example is Automatic Speech Recognition (ASR) for live captioning and voice translation. Three major issues of ASR for IoMT are IoT development cost, speech recognition accuracy, and execution time complexity. For the first issue, most non-voice IoT applications are upgraded with the ASR feature through hard coding, which are error prone. For the second issue, recognition accuracy must be improved for ASR. For the third issue, many multimedia IoT services are real-time applications and, therefore, the ASR delay must be short. This article elaborates on the above issues based on an IoT platform called VoiceTalk. We built the largest Taiwanese spoken corpus to train VoiceTalk ASR (VT-ASR) and show how the VT-ASR mechanism can be transparently integrated with existing IoT applications. We consider two performance measures for VoiceTalk: speech recognition accuracy and VT-ASR delay. For the acoustic tests of PAL-Labs, VT-ASR's accuracy is 96.47%, while Google's accuracy is 94.28%. We are the first to develop an analytic model to investigate the probability that the VT-ASR delay for the first speaker is complete before the second speaker starts talking. From the measurements and analytic modeling, we show that the VT-ASR delay is short enough to result in a very good user experience. Our solution has won several important government and commercial TV contracts in Taiwan. VT-ASR has demonstrated better Taiwanese Mandarin speech recognition accuracy than famous commercial products (including Google and Iflytek) in Formosa Speech Recognition Challenge 2018 (FSR-2018) and was the best among all participating ASR systems for Taiwanese recognition accuracy in FSR-2020.

Published
2023
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11. Women in Legislative Studies: Improving Gender Equality

Author

Eleanor Neff Powell, Leslie Schwindt-Bayer, and Gisela Sin

Subjects
Sociology and Political Science
Abstract

Representation of women in the field of legislative politics is remarkably small and the absence of women has wide-ranging ramifications. In Fall 2019, we surveyed 361 women that we identified as studying legislative politics within political science to understand why women’s representation in legislative studies is so low and what we can do about it. We found that many women study legislatures, but they do not always identify as scholars of legislative studies, often do not join the Legislative Studies Section, and tend to prioritize other journals over Legislative Studies Quarterly, the official journal of the section. In this article, we discuss several solutions to the problem of women’s underrepresentation in legislative studies, including the new Women in Legislative Studies initiative.

Published
2023
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12. A real-time heart rate estimation framework based on a facial video while wearing a mask

Author

Jong Song, Ryu, Sun Chol, Hong, Shili, Liang, Sin Il, Pak, Lei, Zhang, Suqiu, Wang, and Yueqi, Lian

Subjects
Biomaterials, Biomedical Engineering, Biophysics, Health Informatics, Bioengineering, Information Systems
Abstract

BACKGROUND: The imaging photoplethysmography (iPPG) method is a non-invasive, non-contact measurement method that uses a camera to detect physiological indicators. On the other hand, wearing a mask has become essential today when COVID-19 is rampant, which has become a new challenge for heart rate (HR) estimation from facial videos recorded by a camera. OBJECTIVE: The aim is to propose an iPPG-based method that can accurately estimate HR with or without a mask. METHODS: First, the facial regions of interest (ROI) were divided into two sub-ROIs, and the original signal was obtained through spatial averaging with different weights according to the result of judging whether wearing a mask or not, and the CDF, which emphasizes the main component signal, was combined with the improved POS suitable for real-time HR estimation to obtain the noise-removed BVP signal. RESULTS: For self-collected data while wearing a mask, MAE, RMSE, and ACC were 1.09 bpm, 1.44 bpm, and 99.08%, respectively. CONCLUSION: Experimental results show that the proposed framework can estimate HR stably in real-time in both cases of wearing a mask or not. This study expands the application range of HR estimation based on facial videos and has very practical value in real-time HR estimation in daily life.

Published
2023
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13. NeRFahedron

Author

Zackary P. T. Sin, Peter H. F. Ng, and Hong Va Leong

Subjects
Computer Graphics and Computer-Aided Design, Computer Science Applications
Abstract

Neural rendering is an exciting topic injecting machine learning methodologies into the classical computer graphics rendering pipeline. Although recent works have achieved remarkable fidelity, discussion on how to enable it for interactive scenarios like video games seems to be lacking. Aside from an editable 3D model and UV-mapping, an interactive application will demand the neural rendering to handle animatable 3D content with interactive speed. This is currently a gap in neural rendering and our solution to this problem is a novel neural rendering pipeline involving a primitive named NeRFahedron. It localizes a NeRF field and as such effectively reduces the number of expensive network sampling operations to improve speed. Our pipeline involves tetrahedron rasterization, localized ray marching and near-surface particle sampling. The result is a method that can enable animatable content for neural rendering with interactive speed, which has been shown to be competitive in rendering animation. We will also showcase its ability to enable interactive applications via a real-time demo.

Published
2023
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14. A cochleate formulation optimized by D-optimal mixture design enhances oral bioavailability of Revaprazan

Author

Goo, Yoon Tae, Kim, Min Song, Choi, Ji Yeh, Sin, Gi Hyeong, Hong, Sun Ho, Kim, Chang Hyun, and Choi, Young Wook

Subjects
Pharmaceutical Science
Abstract

A cochleate formulation was developed to enhance the oral bioavailability of revaprazan (RVP). Dimyristoyl phosphatidylcholine (DMPC) liposome containing dicetyl phosphate (DCP) successfully formed a cochleate after treatment with CaCl2, whereas that containing sodium deoxycholate did not. Cochleate was optimised using a D-optimal mixture design with three independent variables—DMPC (X1, 70.58 mol%), cholesterol (X2, 22.54 mol%), and DCP (X3, 6.88 mol%)—and three response variables: encapsulation efficiency (Y1, 76.92%), released amount of free fatty acid at 2 h (Y2, 39.82%), and released amount of RVP at 6 h (Y3, 73.72%). The desirability function was 0.616, showing an excellent agreement between the predicted and experimental values. The cylindrical morphology of the optimised cochleate was visualised, and laurdan spectroscopy confirmed the dehydrated membrane interface, showing an increased generalised polarisation value (approximately 0.5) over small unilamellar vesicle of RVP (RVP-SUV; approximately 0.1). The optimised cochleate showed greater resistance to pancreatic enzyme than RVP-SUV. RVP was released in a controlled manner, achieving approximately 94% release in 12 h. Following oral administration in rats, the optimised cochleate improved the relative bioavailability of RVP by approximately 274%, 255%, and 172% compared to RVP suspension, a physical mixture of RVP and the cochleate, and RVP-SUV, respectively. Thus, the optimised cochleate formulation might be a good candidate for the practical development of RVP.

Published
2023
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22. Influence of an abnormal ankle-brachial index on ischemic and bleeding events in patients undergoing percutaneous coronary intervention

Author

Hangyul Kim, Seung Do Lee, Hyo Jin Lee, Hye Ree Kim, Kyehwan Kim, Jin-Sin Koh, Seok-Jae Hwang, Jin-Yong Hwang, Jong-Hwa Ahn, Yongwhi Park, Young-Hoon Jeong, Jeong Rang Park, and Min Gyu Kang

Subjects
General Medicine
Abstract

Background/Aims: Bleeding events after percutaneous coronary intervention (PCI) have important prognostic implications. Data on the influence of an abnormal ankle-brachial index (ABI) on both ischemic and bleeding events in patients undergoing PCI are limited.Methods: We included patients who underwent PCI with available ABI data (abnormal ABI, ≤ 0.9 or > 1.4). The primary endpoint was the composite of all-cause death, myocardial infarction (MI), stroke, and major bleeding.Results: Among 4,747 patients, an abnormal ABI was observed in 610 patients (12.9%). During follow-up (median, 31 months), the 5-year cumulative incidence of adverse clinical events was higher in the abnormal ABI group than in the normal ABI group: primary endpoint (36.0% vs. 14.5%, log-rank test, p < 0.001); all-cause death (19.4% vs. 5.1%, log-rank test, p < 0.001); MI (6.3% vs. 4.1%, log-rank test, p = 0.013); stroke (6.2% vs. 2.7%, log-rank test, p = 0.001); and major bleeding (8.9% vs. 3.7%, log-rank test, p < 0.001). An abnormal ABI was an independent risk factor for all-cause death (hazard ratio [HR], 3.05; p < 0.001), stroke (HR, 1.79; p = 0.042), and major bleeding (HR, 1.61; p = 0.034).Conclusions: An abnormal ABI is a risk factor for both ischemic and bleeding events after PCI. Our study findings may be helpful in determining the optimal method for secondary prevention after PCI.

Published
2023
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29. Benefits of leisure-related physical activity and association between sedentary time and risk for hypertension and type 2 diabetes

Author

Yen Sin Koh, PV Asharani, Fiona Devi, Kumarasan Roystonn, Peizhi Wang, Edimansyah Abdin, Chee Fang Sum, Eng Sing Lee, Siow Ann Chong, and Mythily Subramaniam

Subjects
General Medicine
Abstract

Introduction: Lifestyle modifications can reduce the risk of type 2 diabetes mellitus (T2DM) and hypertension. Our study investigated whether domain-specific physical activity (such as work, transport and leisure) and sedentary behaviour were associated with T2DM and hypertension, and whether these associations were moderated by sex and age. Method: For this cross-sectional study, data were obtained from a population survey in Singapore (n=2,867) conducted from February 2019 to March 2020. T2DM and hypertension were self-reported. Global physical activity questionnaire was used to assess domain-specific physical activity (in metabolic equivalent of task [MET]-minutes) and sedentary time (in hours). Logistic regression models were generated to examine the abovementioned associations, and adjusted for age, sex, education, ethnicity, personal income, body mass index, diet and hypertension/diabetes. Interaction terms were included individually to investigate whether age and sex moderated the associations. Results: Individuals with >826 MET-minutes of leisure-related physical activity had lower odds of having T2DM (odds ratio [OR] 0.46, 95% confidence interval [CI] 0.24–0.86) and hypertension (OR 0.59, 95% CI 0.37–0.94) than those with no leisure-related physical activity. Individuals with >8 hours of sedentary time had higher odds of having hypertension (OR 1.69, 95% CI 1.06–2.69) than those with 0–5 hours of sedentary time. Logistic regression models including interaction terms showed that the association between leisure-related physical activity and hypertension was significant for those aged 18–34 (OR 0.15, 95% CI 0.03–0.66) and 50–64 years (OR 0.44, 95% CI 0.21–0.91). The association between sedentary time and hypertension was significant for those aged 18–34 years (OR 15.07, 95% CI 1.69–133.92). Conclusion: Our results support the widespread promotion of an active lifestyle to lower the prevalence of diabetes and hypertension in Singapore. Keywords: Active lifestyle, domain-specific physical activity, global physical activity questionnaire

Published
2023
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33. Liquid-Metal-Printed Ultrathin Oxides for Atomically Smooth 2D Material Heterostructures

Author

Yiyu Zhang, Dasari Venkatakrishnarao, Michel Bosman, Wei Fu, Sarthak Das, Fabio Bussolotti, Rainer Lee, Siew Lang Teo, Ding Huang, Ivan Verzhbitskiy, Zhuojun Jiang, Zhuoling Jiang, Jianwei Chai, Shi Wun Tong, Zi-En Ooi, Calvin Pei Yu Wong, Yee Sin Ang, Kuan Eng Johnson Goh, and Chit Siong Lau

Subjects
General Engineering, General Physics and Astronomy, General Materials Science
Published
2023
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37. Hospital Burden of Chronic Obstructive Pulmonary Disease in Hong Kong – The Trend from 2006 to 2014

Author

Hok Sum Chan, Fanny Wai San Ko, Johnny Wai Man Chan, Kah Lin Choo, Loletta Kit Ying So, David Chi Leung Lam, Kit Man Sin, Wei Yin Wong, Yuk Lun Cheng, and Maureen Mo Lin Wong

Subjects
General Medicine, International Journal of Chronic Obstructive Pulmonary Disease
Abstract

Hok Sum Chan,1 Fanny Wai San Ko,2 Johnny Wai Man Chan,3 Kah Lin Choo,4 Loletta Kit Ying So,5 David Chi Leung Lam,6 Kit Man Sin,7 Wei Yin Wong,8 Yuk Lun Cheng,1 Maureen Mo Lin Wong9 1Department of Medicine, Alice Ho Miu Ling Nethersole Hospital, Hong Kong Special Administrative Region (HKSAR), People’s Republic of China; 2Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong Special Administrative Region (HKSAR), People’s Republic of China; 3Department of Medicine, Queen Elizabeth Hospital, Hong Kong Special Administrative Region (HKSAR), People’s Republic of China; 4Department of Medicine, North District Hospital, Hong Kong Special Administrative Region (HKSAR), People’s Republic of China; 5Department of Medicine, Pamela Youde Nethersole Eastern Hospital, Hong Kong Special Administrative Region (HKSAR), People’s Republic of China; 6Department of Medicine, Queen Mary Hospital, University of Hong Kong, Hong Kong Special Administrative Region (HKSAR), People’s Republic of China; 7Department of Medicine and Geriatrics, Tuen Mun Hospital, Hong Kong Special Administrative Region (HKSAR), People’s Republic of China; 8Department of Medicine, Haven of Hope Hospital, Hong Kong Special Administrative Region (HKSAR), People’s Republic of China; 9Department of Medicine and Geriatrics, Caritas Medical Centre, Hong Kong Special Administrative Region (HKSAR), People’s Republic of ChinaCorrespondence: Hok Sum Chan, Department of Medicine, 6/F, Block J, Alice Ho Miu Ling Nethersole Hospital, 11 Chuen On Road, Tai Po, NT, Hong Kong Special Administrative Region (HKSAR), People’s Republic of China, Email chanhs@ha.org.hkBackground: Chronic obstructive pulmonary disease (COPD) is a common cause for hospital admission. This study aims to review the hospital burden of COPD in Hong Kong (HK) and the trend from year 2006 to 2014.Methods: A multi-center, retrospective study of the characteristics of COPD patients discharged from the public hospitals of HK from year 2006 to 2014. Anonymized data retrieval and analysis were performed. The demographic data of the subjects, use of health-care resources, ventilatory support, medications used and mortality of the subjects were analyzed.Results: Total patient headcount (HC) and admission number reduced from 10,425 and 23,362 in year 2006 to 9613 and 19,771, respectively, in 2014. There was a progressive reduction of female COPD HC from 2193 (21%) in year 2006 to 1517 (16%) in 2014. The utilization of non-invasive ventilation (NIV) increased rapidly and peaked in 2010 (29%) and decreased thereafter. There was a rapid increase in the prescription of long-acting bronchodilators (from 15% to 64%). COPD and pneumonia were the top causes of death, but death due to pneumonia was rapidly increasing while death due to COPD was progressively decreasing over the period.Conclusion: COPD HC and admission number (particularly in female patients) decreased progressively from year 2006 to 2014. There was also a decreasing trend of severity of disease as reflected by lower NIV use (after year 2010) and lower mortality rate due to COPD. Reduced smoking prevalence and tuberculosis (TB) notification rate in the community in the past might have reduced the incidence and severity of COPD and the hospital burden of disease. We observed an increasing trend of mortality due to pneumonia in COPD patients. Appropriate and timely vaccination programs are recommended for COPD patients as in the general elderly population.Keywords: hospital burden, mortality, smoking, old tuberculosis, pneumonia

Published
2023
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39. Precise Metabolomics Defines Systemic Metabolic Dysregulation Distinct to Acute Myocardial Infarction Associated With Diabetes

Author

Jing-gang Xia, Bowen Li, Hao Zhang, Qin-xue Li, Sin Man Lam, Chun-lin Yin, He Tian, and Guanghou Shui

Subjects
Cardiology and Cardiovascular Medicine
Abstract

Background: Acute myocardial infarction (AMI) is a leading cause of death and disability. Diabetes is an important risk factor and a common comorbidity in AMI patients. The higher mortality risk of diabetes-AMI relative to nondiabetes-AMI indicates a need for specific treatment to improve clinical outcome. However, the global metabolic dysregulation of AMI complicated with diabetes is still unclear. We aim to systematically interrogate changes in the metabolic microenvironment immediate to AMI episodes in the absence or presence of diabetes. Methods: In this work, quantitative metabolomics was used to investigate plasma metabolic differences between diabetes-AMI (n=59) and nondiabetes-AMI (n=59) patients. A diverse array of perturbed metabolic pathways involving carbohydrate metabolism, lipid metabolism, glycolysis, tricarboxylic acid cycle, and amino acid metabolism emerged. Results: In all, our omics-oriented approach defined a metabolic signature of afflicted mitochondrial function aggravated by concurrent diabetes in AMI patients. In particular, our analyses uncovered N-lactoyl-phenylalanine and lysophosphatidylcholines as key functional metabolites that skewed the metabolic picture of diabetes-AMI relative to nondiabetes-AMI. N-lactoyl-phenylalanine was strongly associated with metabolic indicators reflective of mitochondrial overload and negatively correlated with HbA1c (glycosylated hemoglobin, type A1C) specifically in hyperglycemic AMI, suggestive of its central role in glucose utilization and mitochondrial energy production instrumental to the clinical outcome of diabetes-AMI. Reductions in lysophosphatidylcholines, which were negatively correlated with blood glucose and inflammatory markers, might further compromise glucose expenditure and aggravate inflammation leading to poorer prognosis in diabetes-AMI. Conclusions: As circulating metabolite levels are amenable to therapeutic intervention, such shifts in metabolic signatures provide new clues and potential therapeutic targets specific to the treatment of diabetes-AMI.

Published
2023
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40. Compact Multilayer Extension Actuators for Reconfigurable Soft Robots

Author

Jonathan William Ambrose, Nicholas Zhang Rong Chiang, Dylan Sin You Cheah, and Chen-Hua Yeow

Subjects
Artificial Intelligence, Control and Systems Engineering, Biophysics
Abstract

Soft robotic pneumatic actuators generally excel in the specific application they were designed for but lack the versatility to be redeployed to other applications. This study presents a novel and versatile soft compact multilayer extension actuator (MEA) to overcome this limitation. We use the MEA linear output in different hybrid configurations to achieve this versatility. The unique design and fabrication of the MEA allow for a compact elastomeric actuator with innate tension, capable of reverting to its initial state without the need for external stimulus. The MEA is made from alternating elastomers with different Young's modulus, bestowing the MEA with high durability, force, and extension capabilities. In addition, the MEA is lightweight at 4 g, capable of a high force-to-weight ratio of 1000 and an extension ratio of 525%. We also explored varying the MEA parameters, such as its material and dimension, which further enhance its properties. Subsequently, we showed four different design configurations encompassing the MEA to produce four basic motions, that is, push, pull, bend, and twist. Finally, we demonstrated three possible hybrid configurations for manipulation, locomotion, and assistive applications that highlight the versatility, manipulability, and modularity of the MEA.

Published
2023
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41. The Importance of Early Chronic Obstructive Pulmonary Disease: A Lecture from 2022 Asian Pacific Society of Respirology

Author

Don D. Sin

Subjects
Pulmonary and Respiratory Medicine, Infectious Diseases
Abstract

Chronic obstructive pulmonary disease (COPD) affects close to 400 million people worldwide. COPD is characterized by significant airflow limitation on spirometry. Most patients with COPD are diagnosed in their fifth or sixth decades of life. However, the disease begins much earlier. By the time airflow limitation is detected on spirometry, patients with COPD have lost close to 50% of their small airways. Thus, identification of patients with early COPD, defined as persons with preserved spirometry, who demonstrate pathologic or functional hallmarks of COPD, is essential for disease modification and ultimately disease elimination. This paper provides an up-to-date overview of the current case definition of early COPD, its importance, the novel technologies required for its detection in young adults and future directions in therapeutics for treatment.

Published
2023
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42. Does Generalized Joint Laxity Affect Postoperative Alignment and Clinical Outcomes Following Medial Opening-Wedge High Tibial Osteotomy?

Author

Man Soo Kim, Jae Jung Kim, Ki Ho Kang, Kyung Jun Sin, and Yong In

Subjects
Orthopedics and Sports Medicine
Abstract

The purpose of this study was to investigate whether generalized joint laxity affects the postoperative alignment and clinical outcomes of medial opening-wedge high tibial osteotomy (MOWHTO).A total of 198 patients who underwent MOWHTO was divided into two groups according to absence or presence of generalized joint laxity. Generalized joint laxity was measured using the Beighton and Horan criteria, and a score of 4 or more out of 9 was defined as generalized joint laxity. A weight bearing line (WBL) ratio of 55% to 70% was considered an acceptable postoperative lower limb alignment range; WBL over 70% was defined as overcorrection and less than 55% as undercorrection. The WBL ratio was investigated before and 2 years after surgery, and the Western Ontario McMaster University Osteoarthritis Index scale score (WOMAC) was evaluated for patient-reported outcomes (PRO) of MOWHTO. There were 147 (73.7%) patients in the nongeneralized joint laxity group and 51 (26.3%) in the generalized joint laxity group. Preoperatively, there was no difference between the two groups in hip-knee-ankle (HKA) angle or WBL ratio (all P.05).At 2 years postoperatively, the generalized joint laxity group showed significantly higher HKA angle and WBL ratio than the nongeneralized joint laxity group (all P.05). There was a significant difference in the distribution ratio of undercorrection, normocorrection, and overcorrection patients between the two groups (P.05). There were no differences between the two groups in preoperative and postoperative WOMAC scores (all, P.05).The generalized joint laxity significantly affected postoperative over correction of alignment following MOWHTO. However, there was no significant difference in PRO between the patients who did and did not have generalized joint laxity after MOWHTO until 2 years.

Published
2023
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46. Motivation for Meditation and its Association with Meditation Practice in a National Sample of Internet Users

Author

Zishan Jiwani, Sin U Lam, Richard J. Davidson, and Simon B. Goldberg

Subjects
Health (social science), Social Psychology, Developmental and Educational Psychology, Experimental and Cognitive Psychology, Applied Psychology
Abstract

There is limited understanding of what motivates people to initiate and sustain a meditation practice. This study investigates initial and current motivations for meditation, demographic variability in motivations, and associations with ongoing and lifetime meditation practice.A national sample of internet users were recruited to examine initial and current motivations for meditation practice.953 participants completed initial screening and 470 (49.3%) reported exposure to meditation practice. 434 (92.3%) completed a follow-up assessment. Participants most frequently reported mental health/stress alleviation as an initial motivation (While meditation started as a tool for spiritual attainment, findings suggest that it is predominantly used in the U.S. for mental health support and to manage stress. Findings suggest that both type and number of motivations may relate to the course of practice.

Published
2023

47. A multi-layer functional genomic analysis to understand noncoding genetic variation in lipids

Author

Ramdas, Shweta, Judd, Jonathan, Graham, Sarah E, Kanoni, Stavroula, Wang, Yuxuan, Surakka, Ida, Wenz, Brandon, Clarke, Shoa L, Chesi, Alessandra, Wells, Andrew, Bhatti, Konain Fatima, Vedantam, Sailaja, Winkler, Thomas W, Locke, Adam E, Marouli, Eirini, Zajac, Greg J M, Wu, Kuan-Han H, Ntalla, Ioanna, Hui, Qin, Klarin, Derek, Hilliard, Austin T, Wang, Zeyuan, Xue, Chao, Thorleifsson, Gudmar, Helgadottir, Anna, Gudbjartsson, Daniel F, Holm, Hilma, Olafsson, Isleifur, Hwang, Mi Yeong, Han, Sohee, Akiyama, Masato, Sakaue, Saori, Terao, Chikashi, Kanai, Masahiro, Zhou, Wei, Brumpton, Ben M, Rasheed, Humaira, Havulinna, Aki S, Veturi, Yogasudha, Pacheco, Jennifer Allen, Rosenthal, Elisabeth A, Lingren, Todd, Feng, QiPing, Kullo, Iftikhar J, Narita, Akira, Takayama, Jun, Martin, Hilary C, Hunt, Karen A, Trivedi, Bhavi, Haessler, Jeffrey, Giulianini, Franco, Bradford, Yuki, Miller, Jason E, Campbell, Archie, Lin, Kuang, Millwood, Iona Y, Rasheed, Asif, Hindy, George, Faul, Jessica D, Zhao, Wei, Weir, David R, Turman, Constance, Huang, Hongyan, Graff, Mariaelisa, Choudhury, Ananyo, Sengupta, Dhriti, Mahajan, Anubha, Brown, Michael R, Zhang, Weihua, Yu, Ketian, Schmidt, Ellen M, Pandit, Anita, Gustafsson, Stefan, Yin, Xianyong, Luan, Jian'an, Zhao, Jing-Hua, Matsuda, Fumihiko, Jang, Hye-Mi, Yoon, Kyungheon, Medina-Gomez, Carolina, Pitsillides, Achilleas, Hottenga, Jouke Jan, Wood, Andrew R, Ji, Yingji, Gao, Zishan, Haworth, Simon, Mitchell, Ruth E, Chai, Jin Fang, Aadahl, Mette, Bjerregaard, Anne A, Yao, Jie, Manichaikul, Ani, Lee, Wen-Jane, Hsiung, Chao Agnes, Warren, Helen R, Ramirez, Julia, Bork-Jensen, Jette, Kårhus, Line L, Goel, Anuj, Sabater-Lleal, Maria, Noordam, Raymond, Mauro, Pala, Matteo, Floris, McDaid, Aaron F, Marques-Vidal, Pedro, Wielscher, Matthias, Trompet, Stella, Sattar, Naveed, Møllehave, Line T, Munz, Matthias, Zeng, Lingyao, Huang, Jianfeng, Yang, Bin, Poveda, Alaitz, Kurbasic, Azra, Schönherr, Sebastian, Forer, Lukas, Scholz, Markus, Galesloot, Tessel E, Bradfield, Jonathan P, Ruotsalainen, Sanni E, Daw, E Warwick, Zmuda, Joseph M, Mitchell, Jonathan S, Fuchsberger, Christian, Christensen, Henry, Brody, Jennifer A, Le, Phuong, Feitosa, Mary F, Wojczynski, Mary K, Hemerich, Daiane, Preuss, Michael, Mangino, Massimo, Christofidou, Paraskevi, Verweij, Niek, Benjamins, Jan W, Engmann, Jorgen, Noah, Tsao L, Verma, Anurag, Slieker, Roderick C, Lo, Ken Sin, Zilhao, Nuno R, Kleber, Marcus E, Delgado, Graciela E, Huo, Shaofeng, Ikeda, Daisuke D, Iha, Hiroyuki, Yang, Jian, Liu, Jun, Demirkan, Ayşe, Leonard, Hampton L, Marten, Jonathan, Emmel, Carina, Schmidt, Börge, Smyth, Laura J, Cañadas-Garre, Marisa, Wang, Chaolong, Nakatochi, Masahiro, Wong, Andrew, Hutri-Kähönen, Nina, Sim, Xueling, Xia, Rui, Huerta-Chagoya, Alicia, Fernandez-Lopez, Juan Carlos, Lyssenko, Valeriya, Nongmaithem, Suraj S, Sankareswaran, Alagu, Irvin, Marguerite R, Oldmeadow, Christopher, Kim, Han-Na, Ryu, Seungho, Timmers, Paul R H J, Arbeeva, Liubov, Dorajoo, Rajkumar, Lange, Leslie A, Prasad, Gauri, Lorés-Motta, Laura, Pauper, Marc, Long, Jirong, Li, Xiaohui, Theusch, Elizabeth, Takeuchi, Fumihiko, Spracklen, Cassandra N, Loukola, Anu, Bollepalli, Sailalitha, Warner, Sophie C, Wang, Ya Xing, Wei, Wen B, Nutile, Teresa, Ruggiero, Daniela, Sung, Yun Ju, Chen, Shufeng, Liu, Fangchao, Yang, Jingyun, Kentistou, Katherine A, Banas, Bernhard, Morgan, Anna, Meidtner, Karina, Bielak, Lawrence F, Smith, Jennifer A, Hebbar, Prashantha, Farmaki, Aliki-Eleni, Hofer, Edith, Lin, Maoxuan, Concas, Maria Pina, Vaccargiu, Simona, van der Most, Peter J, Pitkänen, Niina, Cade, Brian E, van der Laan, Sander W, Chitrala, Kumaraswamy Naidu, Weiss, Stefan, Bentley, Amy R, Doumatey, Ayo P, Adeyemo, Adebowale A, Lee, Jong Young, Petersen, Eva R B, Nielsen, Aneta A, Choi, Hyeok Sun, Nethander, Maria, Freitag-Wolf, Sandra, Southam, Lorraine, Rayner, Nigel W, Wang, Carol A, Lin, Shih-Yi, Wang, Jun-Sing, Couture, Christian, Lyytikäinen, Leo-Pekka, Nikus, Kjell, Cuellar-Partida, Gabriel, Vestergaard, Henrik, Hidalgo, Bertha, Giannakopoulou, Olga, Cai, Qiuyin, Obura, Morgan O, van Setten, Jessica, He, Karen Y, Tang, Hua, Terzikhan, Natalie, Shin, Jae Hun, Jackson, Rebecca D, Reiner, Alexander P, Martin, Lisa Warsinger, Chen, Zhengming, Li, Liming, Kawaguchi, Takahisa, Thiery, Joachim, Bis, Joshua C, Launer, Lenore J, Li, Huaixing, Nalls, Mike A, Raitakari, Olli T, Ichihara, Sahoko, Wild, Sarah H, Nelson, Christopher P, Campbell, Harry, Jäger, Susanne, Nabika, Toru, Al-Mulla, Fahd, Niinikoski, Harri, Braund, Peter S, Kolcic, Ivana, Kovacs, Peter, Giardoglou, Tota, Katsuya, Tomohiro, de Kleijn, Dominique, de Borst, Gert J, Kim, Eung Kweon, Adams, Hieab H H, Ikram, M Arfan, Zhu, Xiaofeng, Asselbergs, Folkert W, Kraaijeveld, Adriaan O, Beulens, Joline W J, Shu, Xiao-Ou, Rallidis, Loukianos S, Pedersen, Oluf, Hansen, Torben, Mitchell, Paul, Hewitt, Alex W, Kähönen, Mika, Pérusse, Louis, Bouchard, Claude, Tönjes, Anke, Ida Chen, Yii-Der, Pennell, Craig E, Mori, Trevor A, Lieb, Wolfgang, Franke, Andre, Ohlsson, Claes, Mellström, Dan, Cho, Yoon Shin, Lee, Hyejin, Yuan, Jian-Min, Koh, Woon-Puay, Rhee, Sang Youl, Woo, Jeong-Taek, Heid, Iris M, Stark, Klaus J, Zimmermann, Martina E, Völzke, Henry, Homuth, Georg, Evans, Michele K, Zonderman, Alan B, Polasek, Ozren, Pasterkamp, Gerard, Hoefer, Imo E, Redline, Susan, Pahkala, Katja, Oldehinkel, Albertine J, Snieder, Harold, Biino, Ginevra, Schmidt, Reinhold, Schmidt, Helena, Bandinelli, Stefania, Dedoussis, George, Thanaraj, Thangavel Alphonse, Peyser, Patricia A, Kato, Norihiro, Schulze, Matthias B, Girotto, Giorgia, Böger, Carsten A, Jung, Bettina, Joshi, Peter K, Bennett, David A, De Jager, Philip L, Lu, Xiangfeng, Mamakou, Vasiliki, Brown, Morris, Caulfield, Mark J, Munroe, Patricia B, Guo, Xiuqing, Ciullo, Marina, Jonas, Jost B, Samani, Nilesh J, Kaprio, Jaakko, Pajukanta, Päivi, Tusié-Luna, Teresa, Aguilar-Salinas, Carlos A, Adair, Linda S, Bechayda, Sonny Augustin, de Silva, H Janaka, Wickremasinghe, Ananda R, Krauss, Ronald M, Wu, Jer-Yuarn, Zheng, Wei, den Hollander, Anneke I, Bharadwaj, Dwaipayan, Correa, Adolfo, Wilson, James G, Lind, Lars, Heng, Chew-Kiat, Nelson, Amanda E, Golightly, Yvonne M, Wilson, James F, Penninx, Brenda, Kim, Hyung-Lae, Attia, John, Scott, Rodney J, Rao, D C, Arnett, Donna K, Walker, Mark, Scott, Laura J, Koistinen, Heikki A, Chandak, Giriraj R, Mercader, Josep M, Villalpando, Clicerio Gonzalez, Orozco, Lorena, Fornage, Myriam, Tai, E Shyong, van Dam, Rob M, Lehtimäki, Terho, Chaturvedi, Nish, Yokota, Mitsuhiro, Liu, Jianjun, Reilly, Dermot F, McKnight, Amy Jayne, Kee, Frank, Jöckel, Karl-Heinz, McCarthy, Mark I, Palmer, Colin N A, Vitart, Veronique, Hayward, Caroline, Simonsick, Eleanor, van Duijn, Cornelia M, Jin, Zi-Bing, Lu, Fan, Hishigaki, Haretsugu, Lin, Xu, März, Winfried, Gudnason, Vilmundur, Tardif, Jean-Claude, Lettre, Guillaume, T Hart, Leen M, Elders, Petra J M, Rader, Daniel J, Damrauer, Scott M, Kumari, Meena, Kivimaki, Mika, van der Harst, Pim, Spector, Tim D, Loos, Ruth J F, Province, Michael A, Parra, Esteban J, Cruz, Miguel, Psaty, Bruce M, Brandslund, Ivan, Pramstaller, Peter P, Rotimi, Charles N, Christensen, Kaare, Ripatti, Samuli, Widén, Elisabeth, Hakonarson, Hakon, Grant, Struan F A, Kiemeney, Lambertus, de Graaf, Jacqueline, Loeffler, Markus, Kronenberg, Florian, Gu, Dongfeng, Erdmann, Jeanette, Schunkert, Heribert, Franks, Paul W, Linneberg, Allan, Jukema, J Wouter, Khera, Amit V, Männikkö, Minna, Jarvelin, Marjo-Riitta, Kutalik, Zoltan, Francesco, Cucca, Mook-Kanamori, Dennis O, Willems van Dijk, Ko, Watkins, Hugh, Strachan, David P, Grarup, Niels, Sever, Peter, Poulter, Neil, Huey-Herng Sheu, Wayne, Rotter, Jerome I, Dantoft, Thomas M, Karpe, Fredrik, Neville, Matt J, Timpson, Nicholas J, Cheng, Ching-Yu, Wong, Tien-Yin, Khor, Chiea Chuen, Li, Hengtong, Sabanayagam, Charumathi, Peters, Annette, Gieger, Christian, Hattersley, Andrew T, Pedersen, Nancy L, Magnusson, Patrik K E, Boomsma, Dorret I, de Geus, Eco J C, Cupples, L Adrienne, van Meurs, Joyce B J, Ikram, Arfan, Ghanbari, Mohsen, Gordon-Larsen, Penny, Huang, Wei, Kim, Young Jin, Tabara, Yasuharu, Wareham, Nicholas J, Langenberg, Claudia, Zeggini, Eleftheria, Tuomilehto, Jaakko, Kuusisto, Johanna, Laakso, Markku, Ingelsson, Erik, Abecasis, Goncalo, Chambers, John C, Kooner, Jaspal S, de Vries, Paul S, Morrison, Alanna C, Hazelhurst, Scott, Ramsay, Michèle, North, Kari E, Daviglus, Martha, Kraft, Peter, Martin, Nicholas G, Whitfield, John B, Abbas, Shahid, Saleheen, Danish, Walters, Robin G, Holmes, Michael V, Black, Corri, Smith, Blair H, Baras, Aris, Justice, Anne E, Buring, Julie E, Ridker, Paul M, Chasman, Daniel I, Kooperberg, Charles, Tamiya, Gen, Yamamoto, Masayuki, van Heel, David A, Trembath, Richard C, Wei, Wei-Qi, Jarvik, Gail P, Namjou, Bahram, Hayes, M Geoffrey, Ritchie, Marylyn D, Jousilahti, Pekka, Salomaa, Veikko, Hveem, Kristian, Åsvold, Bjørn Olav, Kubo, Michiaki, Kamatani, Yoichiro, 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Subjects
regulatory mechanism, Vascular damage Radboud Institute for Health Sciences [Radboudumc 16], post-GWAS, Medizin, complex traits, fine-mapping, functional genomics, lipid biology, variant prioritization, Medical and Health Sciences, Polymorphism, Single Nucleotide, Sensory disorders Donders Center for Medical Neuroscience [Radboudumc 12], Article, INTEGRATIVE ANALYSIS, WIDE ASSOCIATION, 3D GENOME, VARIANTS, CHOLESTEROL, ANNOTATION, OBESITY, COMMON, LOCI, EXPRESSION, functional genomic, Genetics, 2.1 Biological and endogenous factors, Humans, Genetics(clinical), Polymorphism, Aetiology, Genetics (clinical), Genetics & Heredity, Chromatin/genetics, Genome-Wide Association Study, Genomics, Lipids/genetics, Polymorphism, Single Nucleotide/genetics, Human Genome, Million Veterans Program, Global Lipids Genetics Consortium, Single Nucleotide, Biological Sciences, Lipids, Chromatin, complex trait, Urological cancers Radboud Institute for Health Sciences [Radboudumc 15], 3111 Biomedicine, Biotechnology
Abstract

A major challenge of genome-wide association studies (GWASs) is to translate phenotypic associations into biological insights. Here, we integrate a large GWAS on blood lipids involving 1.6 million individuals from five ancestries with a wide array of functional genomic datasets to discover regulatory mechanisms underlying lipid associations. We first prioritize lipid-associated genes with expression quantitative trait locus (eQTL) colocalizations and then add chromatin interaction data to narrow the search for functional genes. Polygenic enrichment analysis across 697 annotations from a host of tissues and cell types confirms the central role of the liver in lipid levels and highlights the selective enrichment of adipose-specific chromatin marks in high-density lipoprotein cholesterol and triglycerides. Overlapping transcription factor (TF) binding sites with lipid-associated loci identifies TFs relevant in lipid biology. In addition, we present an integrative framework to prioritize causal variants at GWAS loci, producing a comprehensive list of candidate causal genes and variants with multiple layers of functional evidence. We highlight two of the prioritized genes, CREBRF and RRBP1, which show convergent evidence across functional datasets supporting their roles in lipid biology. Xiang Zhu is supported by the Stein Fellowship from Stanford University and Institute for Computational and Data Sciences Seed Grant from The Pennsylvania State University. C.D.B. is supported by the NIH (R01-HL133218). Funding for the Global Lipids Genetics Consortium was provided by the NIH (R01-HL127564). This research was conducted using the UK Biobank Resource under application number 24460. This research is based on data from the Million Veteran Program, Office of Research and Development, Veterans Health Administration, and was supported by awards 2I01BX003362-03A1 and 1I01BX004821-01A1. This publication does not represent the views of the Department of Veteran Affairs or the United States Government. We thank Bethany Klunder for administrative support. Study-specific acknowledgments are provided in the supplemental information.

Published
2022
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48. Sensitivity of ventricular systolic function to afterload during veno‐arterial extracorporeal membrane oxygenation

Author

Pauline Yeung, Ng, Tammy Sin Kwan, Ma, April, Ip, Man Kei, Lee, Andrew Kei-Yan, Ng, Chun Wai, Ngai, Wai Ming, Chan, Chung Wah, Siu, and Wai Ching, Sin

Subjects
Adult, Extracorporeal Membrane Oxygenation, Echocardiography, Hemodynamics, Humans, Stroke Volume, Cardiology and Cardiovascular Medicine, Ventricular Function, Left
Abstract

Veno-arterial extracorporeal membrane oxygenation (V-A ECMO) increases afterload to the injured heart and may hinder myocardial recovery. We aimed to compare the sensitivity of left ventricular (LV) systolic function to the afterload effects of peripheral V-A ECMO during the acute and delayed stages of acute myocardial dysfunction.A total of 46 adult patients who were supported by peripheral V-A ECMO between April 2019 and June 2021 were analysed. Serial cardiac performance parameters were measured by transthoracic echocardiography (TTE) on mean day 1 ± 1 of V-A ECMO initiation (n = 45, 'acute phase') and mean day 4 ± 2 of V-A ECMO initiation (n = 36, 'delayed phase'). Measurements were obtained at 100%, 120%, and 50% of ECMO target blood flow (TBF). LV global longitudinal strain (GLS) significantly improved from -6.1 (-8.9 to -4.0)% during 120% TBF to -8.8 (-11.5 to -6.0)% during 50% TBF (P 0.001). The sensitivity of LV GLS to changes in ECMO flow was significantly greater in the acute phase of myocardial injury compared with the delayed phase [median (IQR) percentage change: 72.7 (26.8-100.0)% vs. 22.5 (14.9-43.8)%, P 0.001]. Findings from other echocardiographic parameters including LV ejection fraction [43.0 (29.1-56.8)% vs. 22.8 (9.2-42.2)%, P = 0.012] and LV outflow tract velocity-time integral [45.8 (18.6-58.7)% vs. 24.2 (12.6-34.0)%, P = 0.001] were similar. A total of 24 (52.2%) patients were weaned off ECMO successfully.We demonstrated that LV systolic function was significantly more sensitive to the afterload effects of V-A ECMO during the acute stage of myocardial dysfunction compared with the delayed phase. Understanding the evolution of the heart-ECMO interaction over the course of acute myocardial dysfunction informs the clinical utility of echocardiographic assessment in patients on V-A ECMO.

Published
2022
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