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1. Unveiling the black box: imperative for explainable AI in cardiovascular disease (CVD) prevention–author reply

Author: Mayank Dalakoti, Scott Wong, and Roger Foo
Subjects: Public aspects of medicine, RA1-1270
Published: 2024
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2. Incorporating AI into cardiovascular diseases prevention–insights from Singapore

Author: Mayank Dalakoti, Scott Wong, Wayne Lee, James Lee, Hayang Yang, Shaun Loong, Poay Huan Loh, Sara Tyebally, Andie Djohan, Jeanne Ong, James Yip, Kee Yuan Ngiam, and Roger Foo
Subjects: Artificial intelligence, Preventive cardiology, Primary care, Primary prevention, Cardiovascular disease, Cardiovascular risk factors, Public aspects of medicine, RA1-1270
Abstract: Summary: Improved upstream primary prevention of cardiovascular disease (CVD) would enable more individuals to lead lives free of CVD. However, there remain limitations in the current provision of CVD primary prevention, where artificial intelligence (AI) may help to fill the gaps. Using the data informatics capabilities at the National University Health System (NUHS), Singapore, empowered by the Endeavour AI system, and combined large language model (LLM) tools, our team has created a real-time dashboard able to capture and showcase information on cardiovascular risk factors at both individual and geographical level- CardioSight. Further insights such as medication records and data on area-level socioeconomic determinants allow a whole-of-systems approach to promote healthcare delivery, while also allowing for outcomes to be tracked effectively. These are paired with interventions, such as the CHronic diseAse Management Program (CHAMP), to coordinate preventive cardiology care at a pilot stage within our university health system. AI tools in synergy allow the identification of at-risk patients and actionable steps to mitigate their health risks, thereby closing the gap between risk identification and effective patient care management in a novel CVD prevention workflow.
Published: 2024
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3. Clinical phenotypes and outcomes in children with multisystem inflammatory syndrome across SARS-CoV-2 variant eras: a multinational study from the 4CE consortiumResearch in context

Author: Francesca Sperotto, Alba Gutiérrez-Sacristán, Simran Makwana, Xiudi Li, Valerie N. Rofeberg, Tianxi Cai, Florence T. Bourgeois, Gilbert S. Omenn, David A. Hanauer, Carlos Sáez, Clara-Lea Bonzel, Emily Bucholz, Audrey Dionne, Matthew D. Elias, Noelia García-Barrio, Tomás González González, Richard W. Issitt, Kate F. Kernan, Jessica Laird-Gion, Sarah E. Maidlow, Kenneth D. Mandl, Taha Mohseni Ahooyi, Cinta Moraleda, Michele Morris, Karyn L. Moshal, Miguel Pedrera-Jiménez, Mohsin A. Shah, Andrew M. South, Anastasia Spiridou, Deanne M. Taylor, Guillaume Verdy, Shyam Visweswaran, Xuan Wang, Zongqi Xia, Joany M. Zachariasse, Jane W. Newburger, Paul Avillach, James R. Aaron, Atif Adam, Giuseppe Agapito, Adem Albayrak, Giuseppe Albi, Mario Alessiani, Anna Alloni, Danilo F. Amendola, François Angoulvant, Li LLJ. Anthony, Bruce J. Aronow, Fatima Ashraf, Andrew Atz, Vidul Ayakulangara Panickan, Paula S. Azevedo, Rafael Badenes, James Balshi, Ashley Batugo, Brendin R. Beaulieu-Jones, Brett K. Beaulieu-Jones, Douglas S. Bell, Antonio Bellasi, Riccardo Bellazzi, Vincent Benoit, Michele Beraghi, José Luis Bernal-Sobrino, Mélodie Bernaux, Romain Bey, Surbhi Bhatnagar, Alvar Blanco-Martínez, Martin Boeker, John Booth, Silvano Bosari, Robert L. Bradford, Gabriel A. Brat, Stéphane Bréant, Nicholas W. Brown, Raffaele Bruno, William A. Bryant, Mauro Bucalo, Anita Burgun, Mario Cannataro, Aldo Carmona, Anna Maria Cattelan, Charlotte Caucheteux, Julien Champ, Jin Chen, Krista Y. Chen, Luca Chiovato, Lorenzo Chiudinelli, Kelly Cho, James J. Cimino, Tiago K. Colicchio, Sylvie Cormont, Sébastien Cossin, Jean B. Craig, Juan Luis Cruz-Bermúdez, Jaime Cruz-Rojo, Arianna Dagliati, Mohamad Daniar, Christel Daniel, Priyam Das, Batsal Devkota, Rui Duan, Julien Dubiel, Scott L. DuVall, Loic Esteve, Hossein Estiri, Shirley Fan, Robert W. Follett, Thomas Ganslandt, Lana X. Garmire, Nils Gehlenborg, Emily J. Getzen, Alon Geva, Rachel SJ. Goh, Tobias Gradinger, Alexandre Gramfort, Romain Griffier, Nicolas Griffon, Olivier Grisel, Pietro H. Guzzi, Larry Han, Christian Haverkamp, Derek Y. Hazard, Bing He, Darren W. Henderson, Martin Hilka, Yuk-Lam Ho, John H. Holmes, Jacqueline P. Honerlaw, Chuan Hong, Kenneth M. Huling, Meghan R. Hutch, Anne Sophie Jannot, Vianney Jouhet, Mundeep K. Kainth, Kernan F. Kate, Ramakanth Kavuluru, Mark S. Keller, Chris J. Kennedy, Daniel A. Key, Katie Kirchoff, Jeffrey G. Klann, Isaac S. Kohane, Ian D. Krantz, Detlef Kraska, Ashok K. Krishnamurthy, Sehi L'Yi, Judith Leblanc, Guillaume Lemaitre, Leslie Lenert, Damien Leprovost, Molei Liu, Ne Hooi Will Loh, Qi Long, Sara Lozano-Zahonero, Yuan Luo, Kristine E. Lynch, Sadiqa Mahmood, Adeline Makoudjou, Alberto Malovini, Chengsheng Mao, Anupama Maram, Monika Maripuri, Patricia Martel, Marcelo R. Martins, Jayson S. Marwaha, Aaron J. Masino, Maria Mazzitelli, Diego R. Mazzotti, Arthur Mensch, Marianna Milano, Marcos F. Minicucci, Bertrand Moal, Jason H. Moore, Jeffrey S. Morris, Sajad Mousavi, Danielle L. Mowery, Douglas A. Murad, Shawn N. Murphy, Thomas P. Naughton, Carlos Tadeu Breda Neto, Antoine Neuraz, Jane Newburger, Kee Yuan Ngiam, Wanjiku FM. Njoroge, James B. Norman, Jihad Obeid, Marina P. Okoshi, Karen L. Olson, Nina Orlova, Brian D. Ostasiewski, Nathan P. Palmer, Nicolas Paris, Lav P. Patel, Ashley C. Pfaff, Emily R. Pfaff, Danielle Pillion, Sara Pizzimenti, Tanu Priya, Hans U. Prokosch, Robson A. Prudente, Andrea Prunotto, Víctor Quirós-González, Rachel B. Ramoni, Maryna Raskin, Siegbert Rieg, Gustavo Roig-Domínguez, Pablo Rojo, Nekane Romero-Garcia, Paula Rubio-Mayo, Paolo Sacchi, Elisa Salamanca, Malarkodi Jebathilagam Samayamuthu, L. Nelson Sanchez-Pinto, Arnaud Sandrin, Nandhini Santhanam, Janaina C.C. Santos, Fernando J. Sanz Vidorreta, Maria Savino, Emily R. Schriver, Petra Schubert, Juergen Schuettler, Luigia Scudeller, Neil J. Sebire, Pablo Serrano-Balazote, Patricia Serre, Arnaud Serret-Larmande, Zahra Shakeri Hossein Abad, Domenick Silvio, Piotr Sliz, Jiyeon Son, Charles Sonday, Zachary H. Strasser, Amelia LM. Tan, Bryce W.Q. Tan, Byorn W.L. Tan, Suzana E. Tanni, Ana I. Terriza-Torres, Valentina Tibollo, Patric Tippmann, Emma MS. Toh, Carlo Torti, Enrico M. Trecarichi, Andrew K. Vallejos, Gael Varoquaux, Margaret E. Vella, Jill-Jênn Vie, Michele Vitacca, Kavishwar B. Wagholikar, Lemuel R. Waitman, Demian Wassermann, Griffin M. Weber, Martin Wolkewitz, Scott Wong, Xin Xiong, Ye Ye, Nadir Yehya, William Yuan, Janet J. Zahner, Alberto Zambelli, Harrison G. Zhang, Daniela Zöller, Valentina Zuccaro, and Chiara Zucco
Subjects: Multisystem inflammatory syndrome, Paediatric inflammatory multisystem syndrome, COVID-19, SARS-CoV-2, Variants, Pediatrics, Medicine (General), R5-920
Abstract: Summary: Background: Multisystem inflammatory syndrome in children (MIS-C) is a severe complication of SARS-CoV-2 infection. It remains unclear how MIS-C phenotypes vary across SARS-CoV-2 variants. We aimed to investigate clinical characteristics and outcomes of MIS-C across SARS-CoV-2 eras. Methods: We performed a multicentre observational retrospective study including seven paediatric hospitals in four countries (France, Spain, U.K., and U.S.). All consecutive confirmed patients with MIS-C hospitalised between February 1st, 2020, and May 31st, 2022, were included. Electronic Health Records (EHR) data were used to calculate pooled risk differences (RD) and effect sizes (ES) at site level, using Alpha as reference. Meta-analysis was used to pool data across sites. Findings: Of 598 patients with MIS-C (61% male, 39% female; mean age 9.7 years [SD 4.5]), 383 (64%) were admitted in the Alpha era, 111 (19%) in the Delta era, and 104 (17%) in the Omicron era. Compared with patients admitted in the Alpha era, those admitted in the Delta era were younger (ES −1.18 years [95% CI −2.05, −0.32]), had fewer respiratory symptoms (RD −0.15 [95% CI −0.33, −0.04]), less frequent non-cardiogenic shock or systemic inflammatory response syndrome (SIRS) (RD −0.35 [95% CI −0.64, −0.07]), lower lymphocyte count (ES −0.16 × 109/uL [95% CI −0.30, −0.01]), lower C-reactive protein (ES −28.5 mg/L [95% CI −46.3, −10.7]), and lower troponin (ES −0.14 ng/mL [95% CI −0.26, −0.03]). Patients admitted in the Omicron versus Alpha eras were younger (ES −1.6 years [95% CI −2.5, −0.8]), had less frequent SIRS (RD −0.18 [95% CI −0.30, −0.05]), lower lymphocyte count (ES −0.39 × 109/uL [95% CI −0.52, −0.25]), lower troponin (ES −0.16 ng/mL [95% CI −0.30, −0.01]) and less frequently received anticoagulation therapy (RD −0.19 [95% CI −0.37, −0.04]). Length of hospitalization was shorter in the Delta versus Alpha eras (−1.3 days [95% CI −2.3, −0.4]). Interpretation: Our study suggested that MIS-C clinical phenotypes varied across SARS-CoV-2 eras, with patients in Delta and Omicron eras being younger and less sick. EHR data can be effectively leveraged to identify rare complications of pandemic diseases and their variation over time. Funding: None.
Published: 2023
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4. Characterization of long COVID temporal sub-phenotypes by distributed representation learning from electronic health record data: a cohort studyResearch in Context

Author: Arianna Dagliati, Zachary H. Strasser, Zahra Shakeri Hossein Abad, Jeffrey G. Klann, Kavishwar B. Wagholikar, Rebecca Mesa, Shyam Visweswaran, Michele Morris, Yuan Luo, Darren W. Henderson, Malarkodi Jebathilagam Samayamuthu, Bryce W.Q. Tan, Guillame Verdy, Gilbert S. Omenn, Zongqi Xia, Riccardo Bellazzi, Shawn N. Murphy, John H. Holmes, Hossein Estiri, James R. Aaron, Giuseppe Agapito, Adem Albayrak, Giuseppe Albi, Mario Alessiani, Anna Alloni, Danilo F. Amendola, François Angoulvant, Li L.L.J. Anthony, Bruce J. Aronow, Fatima Ashraf, Andrew Atz, Paul Avillach, Paula S. Azevedo, James Balshi, Brett K. Beaulieu-Jones, Douglas S. Bell, Antonio Bellasi, Vincent Benoit, Michele Beraghi, José Luis Bernal-Sobrino, Mélodie Bernaux, Romain Bey, Surbhi Bhatnagar, Alvar Blanco-Martínez, Clara-Lea Bonzel, John Booth, Silvano Bosari, Florence T. Bourgeois, Robert L. Bradford, Gabriel A. Brat, Stéphane Bréant, Nicholas W. Brown, Raffaele Bruno, William A. Bryant, Mauro Bucalo, Emily Bucholz, Anita Burgun, Tianxi Cai, Mario Cannataro, Aldo Carmona, Charlotte Caucheteux, Julien Champ, Jin Chen, Krista Y. Chen, Luca Chiovato, Lorenzo Chiudinelli, Kelly Cho, James J. Cimino, Tiago K. Colicchio, Sylvie Cormont, Sébastien Cossin, Jean B. Craig, Juan Luis Cruz-Bermúdez, Jaime Cruz-Rojo, Mohamad Daniar, Christel Daniel, Priyam Das, Batsal Devkota, Audrey Dionne, Rui Duan, Julien Dubiel, Scott L. DuVall, Loic Esteve, Shirley Fan, Robert W. Follett, Thomas Ganslandt, Noelia García- Barrio, Lana X. Garmire, Nils Gehlenborg, Emily J. Getzen, Alon Geva, Tobias Gradinger, Alexandre Gramfort, Romain Griffier, Nicolas Griffon, Olivier Grisel, Alba Gutiérrez-Sacristán, Larry Han, David A. Hanauer, Christian Haverkamp, Derek Y. Hazard, Bing He, Martin Hilka, Yuk-Lam Ho, Chuan Hong, Kenneth M. Huling, Meghan R. Hutch, Richard W. Issitt, Anne Sophie Jannot, Vianney Jouhet, Ramakanth Kavuluru, Mark S. Keller, Chris J. Kennedy, Daniel A. Key, Katie Kirchoff, Isaac S. Kohane, Ian D. Krantz, Detlef Kraska, Ashok K. Krishnamurthy, Sehi L'Yi, Trang T. Le, Judith Leblanc, Guillaume Lemaitre, Leslie Lenert, Damien Leprovost, Molei Liu, Ne Hooi Will Loh, Qi Long, Sara Lozano-Zahonero, Kristine E. Lynch, Sadiqa Mahmood, Sarah E. Maidlow, Adeline Makoudjou, Alberto Malovini, Kenneth D. Mandl, Chengsheng Mao, Anupama Maram, Patricia Martel, Marcelo R. Martins, Jayson S. Marwaha, Aaron J. Masino, Maria Mazzitelli, Arthur Mensch, Marianna Milano, Marcos F. Minicucci, Bertrand Moal, Taha Mohseni Ahooyi, Jason H. Moore, Cinta Moraleda, Jeffrey S. Morris, Karyn L. Moshal, Sajad Mousavi, Danielle L. Mowery, Douglas A. Murad, Thomas P. Naughton, Carlos Tadeu Breda Neto, Antoine Neuraz, Jane Newburger, Kee Yuan Ngiam, Wanjiku F.M. Njoroge, James B. Norman, Jihad Obeid, Marina P. Okoshi, Karen L. Olson, Nina Orlova, Brian D. Ostasiewski, Nathan P. Palmer, Nicolas Paris, Lav P. Patel, Miguel Pedrera-Jiménez, Emily R. Pfaff, Ashley C. Pfaff, Danielle Pillion, Sara Pizzimenti, Hans U. Prokosch, Robson A. Prudente, Andrea Prunotto, Víctor Quirós-González, Rachel B. Ramoni, Maryna Raskin, Siegbert Rieg, Gustavo Roig-Domínguez, Pablo Rojo, Paula Rubio-Mayo, Paolo Sacchi, Carlos Sáez, Elisa Salamanca, L. Nelson Sanchez-Pinto, Arnaud Sandrin, Nandhini Santhanam, Janaina C.C. Santos, Fernando J. Sanz Vidorreta, Maria Savino, Emily R. Schriver, Petra Schubert, Juergen Schuettler, Luigia Scudeller, Neil J. Sebire, Pablo Serrano-Balazote, Patricia Serre, Arnaud Serret-Larmande, Mohsin Shah, Domenick Silvio, Piotr Sliz, Jiyeon Son, Charles Sonday, Andrew M. South, Anastasia Spiridou, Amelia L.M. Tan, Byorn W.L. Tan, Suzana E. Tanni, Deanne M. Taylor, Ana I. Terriza-Torres, Valentina Tibollo, Patric Tippmann, Emma M.S. Toh, Carlo Torti, Enrico M. Trecarichi, Yi-Ju Tseng, Andrew K. Vallejos, Gael Varoquaux, Margaret E. Vella, Guillaume Verdy, Jill-Jênn Vie, Michele Vitacca, Lemuel R. Waitman, Xuan Wang, Demian Wassermann, Griffin M. Weber, Martin Wolkewitz, Scott Wong, Xin Xiong, Ye Ye, Nadir Yehya, William Yuan, Alberto Zambelli, Harrison G. Zhang, Daniela Zo¨ller, Valentina Zuccaro, and Chiara Zucco
Subjects: Post-acute sequelae of SARS-CoV-2, PASC, COVID-19, SARS-CoV-2, Electronic health records, Medicine (General), R5-920
Abstract: Summary: Background: Characterizing Post-Acute Sequelae of COVID (SARS-CoV-2 Infection), or PASC has been challenging due to the multitude of sub-phenotypes, temporal attributes, and definitions. Scalable characterization of PASC sub-phenotypes can enhance screening capacities, disease management, and treatment planning. Methods: We conducted a retrospective multi-centre observational cohort study, leveraging longitudinal electronic health record (EHR) data of 30,422 patients from three healthcare systems in the Consortium for the Clinical Characterization of COVID-19 by EHR (4CE). From the total cohort, we applied a deductive approach on 12,424 individuals with follow-up data and developed a distributed representation learning process for providing augmented definitions for PASC sub-phenotypes. Findings: Our framework characterized seven PASC sub-phenotypes. We estimated that on average 15.7% of the hospitalized COVID-19 patients were likely to suffer from at least one PASC symptom and almost 5.98%, on average, had multiple symptoms. Joint pain and dyspnea had the highest prevalence, with an average prevalence of 5.45% and 4.53%, respectively. Interpretation: We provided a scalable framework to every participating healthcare system for estimating PASC sub-phenotypes prevalence and temporal attributes, thus developing a unified model that characterizes augmented sub-phenotypes across the different systems. Funding: Authors are supported by National Institute of Allergy and Infectious Diseases, National Institute on Aging, National Center for Advancing Translational Sciences, National Medical Research Council, National Institute of Neurological Disorders and Stroke, European Union, National Institutes of Health, National Center for Advancing Translational Sciences.
Published: 2023
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5. Virology under the Microscope—a Call for Rational Discourse

Author: Felicia Goodrum, Anice C. Lowen, Seema Lakdawala, James Alwine, Arturo Casadevall, Michael J. Imperiale, Walter Atwood, Daphne Avgousti, Joel Baines, Bruce Banfield, Lawrence Banks, Sumita Bhaduri-McIntosh, Deepta Bhattacharya, Daniel Blanco-Melo, David Bloom, Adrianus Boon, Steeve Boulant, Curtis Brandt, Andrew Broadbent, Christopher Brooke, Craig Cameron, Samuel Campos, Patrizia Caposio, Gary Chan, Anna Cliffe, John Coffin, Kathleen Collins, Blossom Damania, Matthew Daugherty, Kari Debbink, James DeCaprio, Terence Dermody, Jimmy Dikeakos, Daniel DiMaio, Rhoel Dinglasan, W. Paul Duprex, Rebecca Dutch, Nels Elde, Michael Emerman, Lynn Enquist, Bentley Fane, Ana Fernandez-Sesma, Michelle Flenniken, Lori Frappier, Matthew Frieman, Klaus Frueh, Michaela Gack, Marta Gaglia, Tom Gallagher, Denise Galloway, Adolfo García-Sastre, Adam Geballe, Britt Glaunsinger, Stephen Goff, Alexander Greninger, Meaghan Hancock, Eva Harris, Nicholas Heaton, Mark Heise, Ekaterina Heldwein, Brenda Hogue, Stacy Horner, Edward Hutchinson, Joseph Hyser, William Jackson, Robert Kalejta, Jeremy Kamil, Stephanie Karst, Frank Kirchhoff, David Knipe, Timothy Kowalik, Michael Lagunoff, Laimonis Laimins, Ryan Langlois, Adam Lauring, Benhur Lee, David Leib, Shan-Lu Liu, Richard Longnecker, Carolina Lopez, Micah Luftig, Jennifer Lund, Balaji Manicassamy, Grant McFadden, Michael McIntosh, Andrew Mehle, W. Allen Miller, Ian Mohr, Cary Moody, Nathaniel Moorman, Anne Moscona, Bryan Mounce, Joshua Munger, Karl Münger, Eain Murphy, Mojgan Naghavi, Jay Nelson, Christopher Neufeldt, Janko Nikolich, Christine O'Connor, Akira Ono, Walter Orenstein, David Ornelles, Jing-hsiung Ou, John Parker, Colin Parrish, Andrew Pekosz, Philip Pellett, Julie Pfeiffer, Richard Plemper, Stephen Polyak, John Purdy, Dohun Pyeon, Miguel Quinones-Mateu, Rolf Renne, Charles Rice, John Schoggins, Richard Roller, Charles Russell, Rozanne Sandri-Goldin, Martin Sapp, Luis Schang, Scott Schmid, Stacey Schultz-Cherry, Bert Semler, Thomas Shenk, Guido Silvestri, Viviana Simon, Gregory Smith, Jason Smith, Katherine Spindler, Megan Stanifer, Kanta Subbarao, Wesley Sundquist, Mehul Suthar, Troy Sutton, Andrew Tai, Vera Tarakanova, Benjamin tenOever, Scott Tibbetts, Stephen Tompkins, Zsolt Toth, Koenraad van Doorslaer, Marco Vignuzzi, Nicholas Wallace, Derek Walsh, Michael Weekes, Jason Weinberg, Matthew Weitzman, Sandra Weller, Sean Whelan, Elizabeth White, Bryan Williams, Christiane Wobus, Scott Wong, and Andrew Yurochko
Subjects: COVID-19, Coronavirus, DURC, Gain of function, SARS-CoV-2, biosafety, Microbiology, QR1-502
Abstract: ABSTRACT Viruses have brought humanity many challenges: respiratory infection, cancer, neurological impairment and immunosuppression to name a few. Virology research over the last 60+ years has responded to reduce this disease burden with vaccines and antivirals. Despite this long history, the COVID-19 pandemic has brought unprecedented attention to the field of virology. Some of this attention is focused on concern about the safe conduct of research with human pathogens. A small but vocal group of individuals has seized upon these concerns – conflating legitimate questions about safely conducting virus-related research with uncertainties over the origins of SARS-CoV-2. The result has fueled public confusion and, in many instances, ill-informed condemnation of virology. With this article, we seek to promote a return to rational discourse. We explain the use of gain-of-function approaches in science, discuss the possible origins of SARS-CoV-2 and outline current regulatory structures that provide oversight for virological research in the United States. By offering our expertise, we – a broad group of working virologists – seek to aid policy makers in navigating these controversial issues. Balanced, evidence-based discourse is essential to addressing public concern while maintaining and expanding much-needed research in virology.
Published: 2023
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6. Long-term kidney function recovery and mortality after COVID-19-associated acute kidney injury: An international multi-centre observational cohort studyResearch in context

Author: Byorn W.L. Tan, Bryce W.Q. Tan, Amelia L.M. Tan, Emily R. Schriver, Alba Gutiérrez-Sacristán, Priyam Das, William Yuan, Meghan R. Hutch, Noelia García Barrio, Miguel Pedrera Jimenez, Noor Abu-el-rub, Michele Morris, Bertrand Moal, Guillaume Verdy, Kelly Cho, Yuk-Lam Ho, Lav P. Patel, Arianna Dagliati, Antoine Neuraz, Jeffrey G. Klann, Andrew M. South, Shyam Visweswaran, David A. Hanauer, Sarah E. Maidlow, Mei Liu, Danielle L. Mowery, Ashley Batugo, Adeline Makoudjou, Patric Tippmann, Daniela Zöller, Gabriel A. Brat, Yuan Luo, Paul Avillach, Riccardo Bellazzi, Luca Chiovato, Alberto Malovini, Valentina Tibollo, Malarkodi Jebathilagam Samayamuthu, Pablo Serrano Balazote, Zongqi Xia, Ne Hooi Will Loh, Lorenzo Chiudinelli, Clara-Lea Bonzel, Chuan Hong, Harrison G. Zhang, Griffin M. Weber, Isaac S. Kohane, Tianxi Cai, Gilbert S. Omenn, John H. Holmes, Kee Yuan Ngiam, James R. Aaron, Giuseppe Agapito, Adem Albayrak, Giuseppe Albi, Mario Alessiani, Anna Alloni, Danilo F. Amendola, François Angoulvant, Li L.L.J. Anthony, Bruce J. Aronow, Fatima Ashraf, Andrew Atz, Vidul Ayakulangara Panickan, Paula S. Azevedo, James Balshi, Brett K. Beaulieu-Jones, Brendin R. Beaulieu-Jones, Douglas S. Bell, Antonio Bellasi, Vincent Benoit, Michele Beraghi, José Luis Bernal-Sobrino, Mélodie Bernaux, Romain Bey, Surbhi Bhatnagar, Alvar Blanco-Martínez, Martin Boeker, John Booth, Silvano Bosari, Florence T. Bourgeois, Robert L. Bradford, Stéphane Bréant, Nicholas W. Brown, Raffaele Bruno, William A. Bryant, Mauro Bucalo, Emily Bucholz, Anita Burgun, Mario Cannataro, Aldo Carmona, Anna Maria Cattelan, Charlotte Caucheteux, Julien Champ, Jin Chen, Krista Y. Chen, James J. Cimino, Tiago K. Colicchio, Sylvie Cormont, Sébastien Cossin, Jean B. Craig, Juan Luis Cruz-Bermúdez, Jaime Cruz-Rojo, Mohamad Daniar, Christel Daniel, Batsal Devkota, Audrey Dionne, Rui Duan, Julien Dubiel, Scott L. DuVall, Loic Esteve, Hossein Estiri, Shirley Fan, Robert W. Follett, Thomas Ganslandt, Noelia García-Barrio, Lana X. Garmire, Nils Gehlenborg, Emily J. Getzen, Alon Geva, Tomás González González, Tobias Gradinger, Alexandre Gramfort, Romain Griffier, Nicolas Griffon, Olivier Grisel, Pietro H. Guzzi, Larry Han, Christian Haverkamp, Derek Y. Hazard, Bing He, Darren W. Henderson, Martin Hilka, Jacqueline P. Honerlaw, Kenneth M. Huling, Richard W. Issitt, Anne Sophie Jannot, Vianney Jouhet, Ramakanth Kavuluru, Mark S. Keller, Chris J. Kennedy, Kate F. Kernan, Daniel A. Key, Katie Kirchoff, Ian D. Krantz, Detlef Kraska, Ashok K. Krishnamurthy, Sehi L'Yi, Trang T. Le, Judith Leblanc, Guillaume Lemaitre, Leslie Lenert, Damien Leprovost, Molei Liu, Qi Long, Sara Lozano-Zahonero, Kristine E. Lynch, Sadiqa Mahmood, Simran Makwana, Kenneth D. Mandl, Chengsheng Mao, Anupama Maram, Monika Maripuri, Patricia Martel, Marcelo R. Martins, Jayson S. Marwaha, Aaron J. Masino, Maria Mazzitelli, Diego R. Mazzotti, Arthur Mensch, Marianna Milano, Marcos F. Minicucci, Taha Mohseni Ahooyi, Jason H. Moore, Cinta Moraleda, Jeffrey S. Morris, Karyn L. Moshal, Sajad Mousavi, Douglas A. Murad, Shawn N. Murphy, Thomas P. Naughton, Carlos Tadeu Breda Neto, Jane Newburger, Wanjiku F.M. Njoroge, James B. Norman, Jihad Obeid, Marina P. Okoshi, Karen L. Olson, Nina Orlova, Brian D. Ostasiewski, Nathan P. Palmer, Nicolas Paris, Miguel Pedrera-Jiménez, Ashley C. Pfaff, Emily R. Pfaff, Danielle Pillion, Sara Pizzimenti, Tanu Priya, Hans U. Prokosch, Robson A. Prudente, Andrea Prunotto, Víctor Quirós-González, Rachel B. Ramoni, Maryna Raskin, Siegbert Rieg, Gustavo Roig-Domínguez, Pablo Rojo, Paula Rubio-Mayo, Paolo Sacchi, Carlos Sáez, Elisa Salamanca, L. Nelson Sanchez-Pinto, Arnaud Sandrin, Nandhini Santhanam, Janaina C.C. Santos, Fernando J. Sanz Vidorreta, Maria Savino, Petra Schubert, Juergen Schuettler, Luigia Scudeller, Neil J. Sebire, Pablo Serrano-Balazote, Patricia Serre, Arnaud Serret-Larmande, Mohsin Shah, Zahra Shakeri Hossein Abad, Domenick Silvio, Piotr Sliz, Jiyeon Son, Charles Sonday, Francesca Sperotto, Anastasia Spiridou, Zachary H. Strasser, Suzana E. Tanni, Deanne M. Taylor, Ana I. Terriza-Torres, Emma M.S. Toh, Carlo Torti, Enrico M. Trecarichi, Andrew K. Vallejos, Gael Varoquaux, Margaret E. Vella, Jill-Jênn Vie, Michele Vitacca, Kavishwar B. Wagholikar, Lemuel R. Waitman, Xuan Wang, Demian Wassermann, Martin Wolkewitz, Scott Wong, Xin Xiong, Ye Ye, Nadir Yehya, Joany M. Zachariasse, Janet J. Zahner, Alberto Zambelli, Valentina Zuccaro, and Chiara Zucco
Subjects: COVID-19, Acute kidney injury, SARS-CoV-2, Chronic kidney disease, Electronic health records, Medicine (General), R5-920
Abstract: Summary: Background: While acute kidney injury (AKI) is a common complication in COVID-19, data on post-AKI kidney function recovery and the clinical factors associated with poor kidney function recovery is lacking. Methods: A retrospective multi-centre observational cohort study comprising 12,891 hospitalized patients aged 18 years or older with a diagnosis of SARS-CoV-2 infection confirmed by polymerase chain reaction from 1 January 2020 to 10 September 2020, and with at least one serum creatinine value 1–365 days prior to admission. Mortality and serum creatinine values were obtained up to 10 September 2021. Findings: Advanced age (HR 2.77, 95%CI 2.53–3.04, p
Published: 2023
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7. Epsin-mediated degradation of IP3R1 fuels atherosclerosis

Author: Yunzhou Dong, Yang Lee, Kui Cui, Ming He, Beibei Wang, Sudarshan Bhattacharjee, Bo Zhu, Tadayuki Yago, Kun Zhang, Lin Deng, Kunfu Ouyang, Aiyun Wen, Douglas B. Cowan, Kai Song, Lili Yu, Megan L. Brophy, Xiaolei Liu, Jill Wylie-Sears, Hao Wu, Scott Wong, Guanglin Cui, Yusuke Kawashima, Hiroyuki Matsumoto, Yoshio Kodera, Richard J. H. Wojcikiewicz, Sanjay Srivastava, Joyce Bischoff, Da-Zhi Wang, Klaus Ley, and Hong Chen
Subjects: Science
Abstract: Endothelial cell (EC) dysfunction and inflammation contribute to plaque destabilization in atherosclerosis, increasing the risk of thrombotic events. Here, the authors show that epsin promotes EC inflammation via a mechanism involving IP3R1 degradation, and that deletion of epsin in the endothelium prevents EC dysfunctoin and atherosclerosis in mice.
Published: 2020
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8. Diabetes and Its Cardiovascular Complications: Comprehensive Network and Systematic Analyses

Author: Hao Wu, Vikram Norton, Kui Cui, Bo Zhu, Sudarshan Bhattacharjee, Yao Wei Lu, Beibei Wang, Dan Shan, Scott Wong, Yunzhou Dong, Siu-Lung Chan, Douglas Cowan, Jian Xu, Diane R. Bielenberg, Changcheng Zhou, and Hong Chen
Subjects: diabetes, comprehensive network, system analysis, cardiovascular disease complications, peripheral artery disease, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract: Diabetes mellitus is a worldwide health problem that usually comes with severe complications. There is no cure for diabetes yet and the threat of these complications is what keeps researchers investigating mechanisms and treatments for diabetes mellitus. Due to advancements in genomics, epigenomics, proteomics, and single-cell multiomics research, considerable progress has been made toward understanding the mechanisms of diabetes mellitus. In addition, investigation of the association between diabetes and other physiological systems revealed potentially novel pathways and targets involved in the initiation and progress of diabetes. This review focuses on current advancements in studying the mechanisms of diabetes by using genomic, epigenomic, proteomic, and single-cell multiomic analysis methods. It will also focus on recent findings pertaining to the relationship between diabetes and other biological processes, and new findings on the contribution of diabetes to several pathological conditions.
Published: 2022
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9. Factors associated with high compliance behaviour against COVID-19 in the early phase of pandemic: a cross-sectional study in 12 Asian countries

Author: M Masudur Rahman, Hiroto Miwa, Yinglian Xiao, Yeong Yeh Lee, Tadayuki Oshima, Chun En Chua, Guan Sen Kew, Scott Wong, Hui Xing Lau, Tze Liang Loh, Shien Lung Ooi, Uday C Ghoshal, Ari F Syam, Niandi Tan, Jin-Song Liu, Fang Lu, Chien-Lin Chen, Ruter M Maralit, Yong-Sung Kim, Kewin Tien Ho Siah, Hao Gui, Junxiong Pang, Alla Demutska, Sabrina Quek, Evelyn Xiu Ling Loo, En Xian Sarah Low, Emily C W Hung, Hei Wong, and Cynthia K Y Cheung
Subjects: Medicine
Abstract: Introduction Regardless of having effective vaccines against COVID-19, containment measures such as enhanced physical distancing and good practice of personal hygiene remain the mainstay of controlling the COVID-19 pandemic. Countries across Asia have imposed these containment measures to varying extents. However, residents in different countries would have a differing degree of compliance to these containment measures potentially due to differences in the level of awareness and motivation in the early phase of pandemic.Objectives In our study, we aimed to describe and correlate the level of knowledge and attitude with the level of compliance with personal hygiene and physical distancing practices among Asian countries in the early phase of pandemic.Methods A multinational cross-sectional study was carried out using electronic surveys between May and June 2020 across 14 geographical areas. Subjects aged 21 years and above were invited to participate through social media, word of mouth and electronic mail.Results Among the 2574 responses obtained, 762 (29.6%) participants were from East Asia and 1812 (70.4%) were from Southeast Asia (SEA). A greater proportion of participants from SEA will practise physical distancing as long as it takes (72.8% vs 60.6%). Having safe distancing practices such as standing more than 1 or 2 m apart (AdjOR 5.09 95% CI (1.08 to 24.01)) or more than 3 or 4 m apart (AdjOR 7.05 95% CI (1.32 to 37.67)), wearing a mask when they had influenza-like symptoms before the COVID-19 pandemic, preferring online news channels such as online news websites/applications (AdjOR 1.73 95% CI (1.21 to 2.49)) and social media (AdjOR 1.68 95% CI (1.13 to 2.50) as sources of obtaining information about COVID-19 and high psychological well-being (AdjOR 1.39 95% CI (1.04 to 1.87)) were independent factors associated with high compliance.Conclusions We found factors associated with high compliance behaviour against COVID-19 in the early phase of pandemic and it will be useful to consider them in risk assessment, communication and pandemic preparedness.
Published: 2021
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10. Association between well-being and compliance with COVID-19 preventive measures by healthcare professionals: A cross-sectional study.

Author: Shimoni Urvish Shah, Evelyn Xiu Ling Loo, Chun En Chua, Guan Sen Kew, Alla Demutska, Sabrina Quek, Scott Wong, Hui Xing Lau, En Xian Sarah Low, Tze Liang Loh, Ooi Shien Lung, Emily C W Hung, M Masudur Rahman, Uday C Ghoshal, Sunny H Wong, Cynthia K Y Cheung, Ari F Syam, Niandi Tan, Yinglian Xiao, Jin-Song Liu, Fang Lu, Chien-Lin Chen, Yeong Yeh Lee, Ruter M Maralit, Yong-Sung Kim, Tadayuki Oshima, Hiroto Miwa, Kewin Tien Ho Siah, and Junxiong Pang
Subjects: Medicine, Science
Abstract: ImportanceKnowledge and attitude influence compliance and individuals' practices. The risk and protective factors associated with high compliance to these preventive measures are critical to enhancing pandemic preparedness.ObjectiveThis survey aims to assess differences in mental health, knowledge, attitudes, and practices (KAP) of preventive measures for COVID-19 amongst healthcare professionals (HCP) and non-healthcare professionals.DesignMulti-national cross-sectional study was carried out using electronic surveys between May-June 2020.SettingMulti-national survey was distributed across 36 countries through social media, word-of-mouth, and electronic mail.ParticipantsParticipants ≥21 years working in healthcare and non-healthcare related professions.Main outcomeRisk factors determining the difference in KAP towards personal hygiene and social distancing measures during COVID-19 amongst HCP and non-HCP.ResultsHCP were significantly more knowledgeable on personal hygiene (AdjOR 1.45, 95% CI -1.14 to 1.83) and social distancing (AdjOR 1.31, 95% CI -1.06 to 1.61) compared to non-HCP. They were more likely to have a positive attitude towards personal hygiene and 1.5 times more willing to participate in the contact tracing app. There was high compliance towards personal hygiene and social distancing measures amongst HCP. HCP with high compliance were 1.8 times more likely to flourish and more likely to have a high sense of emotional (AdjOR 1.94, 95% CI (1.44 to 2.61), social (AdjOR 2.07, 95% CI -1.55 to 2.78), and psychological (AdjOR 2.13, 95% CI (1.59-2.85) well-being.Conclusion and relevanceWhile healthcare professionals were more knowledgeable, had more positive attitudes, their higher sense of total well-being was seen to be more critical to enhance compliance. Therefore, focusing on the well-being of the general population would help to enhance their compliance towards the preventive measures for COVID-19.
Published: 2021
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11. The Role of Endothelial-to-Mesenchymal Transition in Cardiovascular Disease

Author: Qianman Peng, Dan Shan, Kui Cui, Kathryn Li, Bo Zhu, Hao Wu, Beibei Wang, Scott Wong, Vikram Norton, Yunzhou Dong, Yao Wei Lu, Changcheng Zhou, and Hong Chen
Subjects: endothelial-to-mesenchymal transition, cell signaling, multidisciplinary and novel approaches, cardiovascular disease, Cytology, QH573-671
Abstract: Endothelial-to-mesenchymal transition (EndoMT) is the process of endothelial cells progressively losing endothelial-specific markers and gaining mesenchymal phenotypes. In the normal physiological condition, EndoMT plays a fundamental role in forming the cardiac valves of the developing heart. However, EndoMT contributes to the development of various cardiovascular diseases (CVD), such as atherosclerosis, valve diseases, fibrosis, and pulmonary arterial hypertension (PAH). Therefore, a deeper understanding of the cellular and molecular mechanisms underlying EndoMT in CVD should provide urgently needed insights into reversing this condition. This review summarizes a 30-year span of relevant literature, delineating the EndoMT process in particular, key signaling pathways, and the underlying regulatory networks involved in CVD.
Published: 2022
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12. Epsins Negatively Regulate Aortic Endothelial Cell Function by Augmenting Inflammatory Signaling

Author: Yunzhou Dong, Beibei Wang, Kui Cui, Xiaofeng Cai, Sudarshan Bhattacharjee, Scott Wong, Douglas B. Cowan, and Hong Chen
Subjects: epsin, adaptor protein, endocytosis, adhesion molecule, selectin, MCP-1, Cytology, QH573-671
Abstract: Background: The endothelial epsin 1 and 2 endocytic adaptor proteins play an important role in atherosclerosis by regulating the degradation of the calcium release channel inositol 1,4,5-trisphosphate receptor type 1 (IP3R1). In this study, we sought to identify additional targets responsible for epsin-mediated atherosclerotic endothelial cell activation and inflammation in vitro and in vivo. Methods: Atherosclerotic ApoE−/− mice and ApoE−/− mice with an endothelial cell-specific deletion of epsin 1 on a global epsin 2 knock-out background (EC-iDKO/ApoE−/−), and aortic endothelial cells isolated from these mice, were used to examine inflammatory signaling in the endothelium. Results: Inflammatory signaling was significantly abrogated by both acute (tumor necrosis factor-α (TNFα) or lipopolysaccharide (LPS)) and chronic (oxidized low-density lipoprotein (oxLDL)) stimuli in EC-iDKO/ApoE−/− mice and murine aortic endothelial cells (MAECs) isolated from epsin-deficient animals when compared to ApoE−/− controls. Mechanistically, the epsin ubiquitin interacting motif (UIM) bound to Toll-like receptors (TLR) 2 and 4 to potentiate inflammatory signaling and deletion of the epsin UIM mitigated this interaction. Conclusions: The epsin endocytic adaptor proteins potentiate endothelial cell activation in acute and chronic models of atherogenesis. These studies further implicate epsins as therapeutic targets for the treatment of inflammation of the endothelium associated with atherosclerosis.
Published: 2021
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13. Pneumothoraces in collagen VI-related dystrophy: a case series and recommendations for management

Author: Kristin L. Fraser, Scott Wong, A. Reghan Foley, Sameer Chhibber, Carsten G. Bönnemann, Daniel J. Lesser, Carla Grosmann, and Anne Rutkowski
Subjects: Medicine
Abstract: Collagen VI-related dystrophy (collagen VI-RD) is a rare neuromuscular condition caused by mutations in the COL6A1, COL6A2 or COL6A3 genes. The phenotypic spectrum includes early-onset Ullrich congenital muscular dystrophy, adult-onset Bethlem myopathy and an intermediate phenotype. The disorder is characterised by distal hyperlaxity and progressive muscle weakness, joint contractures and respiratory insufficiency. Respiratory insufficiency is attributed to chest wall contractures, scoliosis, impaired diaphragmatic function and intercostal muscle weakness. To date, intrinsic parenchymal lung disease has not been implicated in the inevitable respiratory decline of these patients. This series focuses on pneumothorax, an important but previously under-recognised disease manifestation of collagen VI-RD. We describe two distinct clinical presentations within collagen VI-RD patients with pneumothorax. The first cohort consists of neonates and children with a single pneumothorax in the setting of large intrathoracic pressure changes. The second group is made up of adult patients with recurrent pneumothoraces, associated with chest computed tomography scan evidence of parenchymal lung disease. We describe treatment challenges in this unique population with respect to expectant observation, tube thoracostomy and open pleurodesis. Based on this experience, we offer recommendations for early identification of lung disease in collagen VI-RD and definitive intervention.
Published: 2017
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14. International comparisons of laboratory values from the 4CE collaborative to predict COVID-19 mortality.

Author: Griffin M. Weber, Chuan Hong, Zongqi Xia, Nicolas Paris, Miguel Pedrera-Jiménez, Ashley C. Pfaff, Emily R. Pfaff, Danielle Pillion, Sara Pizzimenti, Hans-Ulrich Prokosch, Robson A. Prudente, Andrea Prunotto, Víctor Quirós-González, Maryna Raskin, Siegbert Rieg, Gustavo Roig-Domínguez, Pablo Rojo, Paula Rubio-Mayo, Paolo Sacchi, Carlos Sáez, Elisa Salamanca, Malarkodi Jebathilagam Samayamuthu, L. Nelson Sanchez-Pinto, Arnaud Sandrin, Nandhini Santhanam, Janaina C. C. Santos, Fernando J. Sanz Vidorreta, Maria Savino, Jürgen Schüttler, Luigia Scudeller, Neil J. Sebire, Pablo Serrano-Balazote, Patricia Serre, Arnaud Serret-Larmande, Mohsin Shah, Zahra Shakeri Hossein Abad, Domenick Silvio, Piotr Sliz, Jiyeon Son, Charles Sonday, Andrew M. South, Francesca Sperotto, Zachary H. Strasser, Bryce W. Q. Tan, Suzana E. Tanni, Deanne M. Taylor, Ana I. Terriza-Torres, Patric Tippmann, Emma M. S. Toh, Yi-Ju Tseng, Andrew K. Vallejos, Gaël Varoquaux, Margaret E. Vella, Guillaume Verdy, Jill-Jênn Vie, Michele Vitacca, Kavishwar B. Wagholikar, Lemuel R. Waitman, Demian Wassermann, Martin Wolkewitz, Scott Wong, Xin Xiong, Ye Ye, Nadir Yehya, William Yuan, Alberto Zambelli, Harrison G. Zhang, Daniela Zöller, Valentina Zuccaro, and Chiara Zucco
Published: 2022
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15. International electronic health record-derived post-acute sequelae profiles of COVID-19 patients.

Author: Harrison G. Zhang, Arianna Dagliati, Zahra Shakeri Hossein Abad, Xin Xiong, Clara-Lea Bonzel, Zongqi Xia, Bryce W. Q. Tan, Paul Avillach, Gabriel A. Brat, Chuan Hong, Michele Morris, Shyam Visweswaran, Lav P. Patel, Alba Gutiérrez-Sacristán, David A. Hanauer, John H. Holmes, Malarkodi Jebathilagam Samayamuthu, Florence T. Bourgeois, Sehi L'Yi, Sarah E. Maidlow, Bertrand Moal, Shawn N. Murphy, Zachary H. Strasser, Antoine Neuraz, Kee Yuan Ngiam, Ne-Hooi Will Loh, Gilbert S. Omenn, Andrea Prunotto, Lauren A. Dalvin, Jeffrey G. Klann, Petra Schubert, Fernando J. Sanz Vidorreta, Vincent Benoit, Guillaume Verdy, Ramakanth Kavuluru, Hossein Estiri, Yuan Luo 0001, Alberto Malovini, Valentina Tibollo, Riccardo Bellazzi, Kelly Cho, Yuk-Lam Ho, Amelia L. M. Tan, Byorn W. L. Tan, Nils Gehlenborg, Sara Lozano-Zahonero, Vianney Jouhet, Luca Chiovato, Bruce J. Aronow, Emma M. S. Toh, Wei Gen Scott Wong, Sara Pizzimenti, Kavishwar B. Wagholikar, Mauro Bucalo, Tianxi Cai, Andrew M. South, Isaac S. Kohane, and Griffin M. Weber
Published: 2022
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16. Targeting Epsins to Inhibit Fibroblast Growth Factor Signaling While Potentiating Transforming Growth Factor-β Signaling Constrains Endothelial-to-Mesenchymal Transition in Atherosclerosis

Author: Yunzhou Dong, Beibei Wang, Mulong Du, Bo Zhu, Kui Cui, Kathryn Li, Ke Yuan, Douglas B. Cowan, Sudarshan Bhattacharjee, Scott Wong, Jinjun Shi, Da-Zhi Wang, Kaifu Chen, Joyce Bischoff, MacRae F. Linton, and Hong Chen
Subjects: Physiology (medical), Cardiology and Cardiovascular Medicine
Abstract: Background: Epsin endocytic adaptor proteins are implicated in the progression of atherosclerosis; however, the underlying molecular mechanisms have not yet been fully defined. In this study, we determined how epsins enhance endothelial-to-mesenchymal transition (EndoMT) in atherosclerosis and assessed the efficacy of a therapeutic peptide in a preclinical model of this disease. Methods: Using single-cell RNA sequencing combined with molecular, cellular, and biochemical analyses, we investigated the role of epsins in stimulating EndoMT using knockout in Apoe −/− and lineage tracing/proprotein convertase subtilisin/kexin type 9 serine protease mutant viral-induced atherosclerotic mouse models. The therapeutic efficacy of a synthetic peptide targeting atherosclerotic plaques was then assessed in Apoe −/− mice. Results: Single-cell RNA sequencing and lineage tracing revealed that epsins 1 and 2 promote EndoMT and that the loss of endothelial epsins inhibits EndoMT marker expression and transforming growth factor-β signaling in vitro and in atherosclerotic mice, which is associated with smaller lesions in the Apoe −/− mouse model. Mechanistically, the loss of endothelial cell epsins results in increased fibroblast growth factor receptor-1 expression, which inhibits transforming growth factor-β signaling and EndoMT. Epsins directly bind ubiquitinated fibroblast growth factor receptor-1 through their ubiquitin-interacting motif, which results in endocytosis and degradation of this receptor complex. Consequently, administration of a synthetic ubiquitin-interacting motif–containing peptide atheroma ubiquitin-interacting motif peptide inhibitor significantly attenuates EndoMT and progression of atherosclerosis. Conclusions: We conclude that epsins potentiate EndoMT during atherogenesis by increasing transforming growth factor-β signaling through fibroblast growth factor receptor-1 internalization and degradation. Inhibition of EndoMT by reducing epsin–fibroblast growth factor receptor-1 interaction with a therapeutic peptide may represent a novel treatment strategy for atherosclerosis.
Published: 2023