99 research outputs found
An evaluation between confidence judgments and differences in monitoring ability
- Author
- Publication venue
- Digital Scholarship@UNLV
- Publication date
- 01/01/2001
- Field of study
Metacognition is the awareness of a person\u27s thinking and the ability to regulate that thinKing This study examines how confident a person is at monitoring progress during two cognitive tasks. The fast task was the feeling-of-knowing paradigm, when participants judge how accurately they can retrieve an answer in a recognition task, when they cannot retrieve the answer in free recall. The second task was a paired-associate interference paradigm. Participants were presented with a list of noun-noun pairs twice and then a new list was presented for recall. Participants were placed into three groups (high, medium, low) based on responses to the Metacognitive Awareness Inventory. Results showed no significant differences between groups in either task. The results are discussed in terms of measuring strategy knowledge instead of monitoring
Heterotopic gray matter in white matter in a 62 year old
- Publication venue
- Publication date
- 01/01/2013
- Field of study
"Heterotopia" describes normal cells in an abnormal location, and in the context of neurobiology, usually refers to neurons or gray matter in the leptomeninges or in periventricular or subcortical white matter, ("Gray Matter Heterotopia"). While once thought to be quite rare, the widespread MRI availability allowed increased recognition of these malformations. Clinically, gray matter heterotopias usually manifest as seizures in the first and second decades of life and may have associated motor and cognitive developmental disturbances. We report a patient with no known prior neurologic history, who developed seizures at the age of 62, which were subsequently determined to be from a subcortical gray matter heterotopia. The patient presented to an outside hospital with episodic confusion thought to represent partial seizures, and also numbness in her left foot, leg, and arm. MRI revealed a thickened corpus callosum and abnormal signal extending into the right cingulate gyrus white matter with an infiltrative appearance suggestive of a glioma or gliomatosis. Stereotactic biopsy demonstrated white matter containing irregular islands of synaptophysin-immunopositive gray matter within which there were large dysplastic neurons. This established a diagnosis of ectopic gray matter in the subcortical white matter. To our knowledge, this is the oldest age at which a person with this congenital condition has experienced onset of related symptoms
Lymphocytic Choriomeningitis Virus in Employees and Mice at Multipremises Feeder-Rodent Operation, United States, 2012
- Author
- Albariño
- Amman
- Arcavi
- Aridth Gibbons
- Barbara Knust
- Barton
- Becker
- Biggar
- Bonthius
- Bonthius
- Bowen
- Bret Marsh
- Brett Petersen
- Centers for Disease Control and Prevention
- Centers for Disease Control and Prevention
- Centers for Disease Control and Prevention
- Childs
- Clayton Horton
- Craig Manning
- César G. Albariño
- Deborah Cannon
- Deibel
- Denise Cory
- Douglas Metcalf
- Dykewicz
- Edison
- Emilian Armeanu
- Fischer
- Foster
- Gregg
- Hinman
- Jennifer House
- Jessica Austin
- Jodi Lovejoy
- John Poe
- Kang
- Kathy L. Fowler
- Kraig E. Humbaugh
- Laura Edison
- Lisa Guerrero
- Macneil
- Morita
- Nicklas
- Palacios
- Pierre E. Rollin
- Shelley Campbell
- Skinner
- Stuart T. Nichol
- Ute Ströher
- Vanzee
- Zachary Reed
- Publication venue
- 'Centers for Disease Control and Prevention (CDC)'
- Publication date
- Field of study
Politics, 1641-1660
- Author
- Aalen
- Abbott
- Adair
- Adair
- Adamson
- Addison
- Adelman
- Ainsworth
- Ainsworth
- Ainsworth
- Akagi
- Akenson
- Anderson
- Andrews
- Andrews
- Andrews
- Andrews
- Annesley
- Anon
- Anon
- Archdekin
- Archer
- Armstrong
- Armstrong
- Armstrong
- Armstrong
- Armstrong
- Armstrong
- Armstrong
- Armstrong
- Arnold
- Ashford
- Athar Ali
- Atkinson
- Bagwell
- Bagwell
- Baillie
- Bailyn
- Bale
- Bard
- Barnard
- Barnard
- Barnard
- Barnard
- Barnard
- Barnard
- Barnard
- Barnard
- Barnard
- Barnard
- Barnard
- Barnard
- Barnard
- Barnard
- Barnard
- Barnard
- Barnard
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- Barry
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- Bartlett
- Basill
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- Boate
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- Bradshaw
- Bradshaw
- Bradshaw
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- Brady
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- Bramhall
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- Brown
- Brunicardi
- Bryskett
- Burke
- Burnell
- Burns
- Butler
- Byrne
- C[aulfield]
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- Caball
- Caball
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- Ó Tuama
- Publication venue
- 'Cambridge University Press (CUP)'
- Publication date
- 01/01/2018
- Field of study
SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues
- Author
- Aarno Palotie
- Abdolmajid Hosseini
- Abdulaziz AlMalik
- Abdulraheem Alshareef
- Achille Iolascon
- Adam S. Butterworth
- Afshar Etemadi Aleagha
- Agnese Verzuri
- Agostino Ognibene
- Agostino Riva
- Ahmadreza Niavarani
- Ahna Girshick
- Aida Fiz-Lopez
- Alba Parra Martınez
- Albandary M. Alowayn
- Albert Tenesa
- Albert V. Smith
- Alessandra Guarnaccia
- Alessandra Renieri
- Alessandra Stella
- Alessandra Vergori
- Alessandro Pancrazzi
- Alessia Giorli
- Alex Serra-Llovich
- Alex Soriano
- Alex Stuckey
- Alexander Labkowsky
- Alexander T. Williams
- Alexander W. Charney
- Alexandra Aksentijevich
- Alexandre Belisle
- Ali Amirsavadkouhi
- Ali Sobh
- Alice Donati
- Alicia de Felipe Mimbrera
- Alicia R. Martin
- Alireza Adamsara
- Altaf Ali
- Amal Al Mutairi
- Amin K. Khattab
- Amr M. Yassen
- Amr Samir
- Amy Trankiem
- Anastasia Lucas
- Andre G. Uitterlinden
- Andrea Antinori
- Andrea Cossarizza
- Andrea Ganna
- Andrea Ganna
- Andrea Martın-Nalda
- Andrea Tommasi
- Andres Metspalu
- Andrew Beck
- Andrew P. Boughton
- Anil P. S. Ori
- Ann E. Woolley
- Anna Canaccini
- Anna Carreras
- Anna Dominguez-Mayoral
- Anna L. Guyatt
- Anna M. Planas
- Anna Maria Pinto
- Annarita Giliberti
- Anne E. Justice
- Anne Kallaste
- Anne Marie O’Connell
- Anne Richmond
- Anne Richmond
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- Matthew Solomonson
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- Shang-Kuan Lin
- Shannon McCurdy
- Shawn N. Murphy
- Shawneequa Callier
- Shea J. Andrews
- Shea J. Andrews
- Shea J. Andrews
- Shefali S. Verma
- Shona M. Kerr
- Silvia Baroni
- Silvia Cappelli
- Silvia Rojo
- Simona Dei
- Simona Marcantonio
- Simona Sarzi-Braga
- Simone Furini
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- Sophie Venturelli
- Souad Rahmouni
- Spencer Knight
- Stefania Mantovani
- Stefano Baratti
- Stefano Busani
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- Ste´ phanie Gofflot
- Stuart C. Sealfon
- Susan Walker
- Susanna Croci
- Susanna Guerrini
- Tala Abdullah
- Tamer A. Elhadidy
- Tess Levy
- Thanyawee Puthanakit
- Thitima B. Suttichet
- Tim D. Spector
- Tiziana Bachetti
- Tom Fowler
- Tomas Segura
- Tomislav Maricic
- Tomoko Nakanishi
- Tomoko Nakanishi
- Tonu Esko
- Tooraj Mirshahi
- Tormod Rogne
- Triin Laisk
- Tullio Trotta
- Valentina Anemoli
- Vasilios Polymeropoulos
- Veronica Rico
- Veronica Robles
- Ve´ronique Erard
- Victor Moreno
- Vincent Mooser
- Vincenzo Forgetta
- Vincenzo Forgetta
- Voraphoj Nilaratanakul
- Vorasuk Shotelersuk
- Walaa A. Felemban
- Walaa M. El-Lawaty
- Walid T. Khafaga
- Wanna Chetruengchai
- Watsamon Jantarabenjakul
- Wei Zhou
- Wei Zhou
- Wenhan Lu
- Werner Albrich
- Xavier Farre
- Xiao Chang
- Xiao Chang
- Xiaoqing Xue
- Xueyang Wang
- Yan V. Sun
- Yaseen M. Arabi
- Yasmine Belhaj
- Yasser M. El-Sherbiny
- Yen-Chen Anne Feng
- Yuk-Lam Ho
- Yuki Bradford
- Yunsung Lee
- Yuval Itan
- Yves Beguin
- Zaman Afrasiabi
- Zeinab Naderpour
- Zhu Wanying
- Ziab Z. Alahmadey
- Øyvind Helgeland
- Publication venue
- 'Elsevier BV'
- Publication date
- 01/01/2022
- Field of study
Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to
genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility
and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component.
Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci
(eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene),
including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform
genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer
SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the
diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types
Mitochondrial physiology
- Author
- Aasander Frostner Eleonor
- Abdel-Rahman Engy Ali
- Abdul Karim Norwahidah
- Abumrad Nada A
- Acuna-Castroviejo Dario
- Adiele Reginald C
- Ahn Bumsoo
- Alencar Mayke Bezerra
- Ali Sameh S
- Almeida Angeles
- Alton Lesley
- Alves Marco G
- Amati Francesca
- Amoedo Nivea Dias
- Amorim Ricardo
- Anderson Ethan J
- Andreadou Ioanna
- Antunes Diana
- Arago Marc
- Aral Cenk
- Arandarcikaite Odeta
- Arias-Reyes Christian
- Armand Anne-Sophie
- Arnould Thierry
- Avram Vlad F
- Axelrod Christopher L
- Bailey Damian M
- Bairam Aida
- Bajpeyi Sudip
- Bajzikova Martina
- Bakker Barbara M
- Banni Aml
- Bardal Tora
- Barlow J
- Bastos Sant'Anna Silva Ana Carolina
- Batterson Philip M
- Battino Maurizio
- Bazil Jason N
- Beard Daniel A
- Bednarczyk Piotr
- Beleza Jorge
- Bello Fiona
- Ben-Shachar Dorit
- Bento Guida Jose Freitas
- Bergdahl Andreas
- Berge Rolf K
- Bergmeister Lisa
- Bernardi Paolo
- Berridge Michael V
- Bettinazzi Stefano
- Bishop David J
- Blier Pierre U
- Blindheim Dan Filip
- Boardman Neoma T
- Boersheim Elisabet
- Boetker Hans Erik
- Borchard Sabine
- Boros Mihaly
- Borras Consuelo
- Borutaite Vilma
- Botella Javier
- Bouillaud Frederic
- Bouitbir Jamal
- Boushel Robert C
- Bovard Josh
- Bravo-Sagua Roberto
- Breton Sophie
- Brown David A
- Brown Guy C
- Brown Robert Andrew
- Brozinick Joseph T
- Buettner Garry R
- Burtscher Johannes
- Bustos Matilde
- Calabria Elisa
- Calbet Jose AL
- Calzia Enrico
- Cannon Daniel T
- Cano Sanchez Maria Consolacion
- Canto Alvarez Carles
- Cardinale Daniele A
- Cardoso Luiza HD
- Carvalho Eugenia
- Casado Pinna Marta
- Cassar Samantha
- Castelo Rueda Maria Paulina
- Castilho Roger F
- Cavalcanti-de-Albuquerque Joao Paulo
- Cecatto Cristiane
- Celen Murat C
- Cervinkova Zuzana
- Chabi Beatrice
- Chakrabarti Lisa
- Chakrabarti Sasanka
- Chaurasia Bhagirath
- Chen Quan
- Chicco Adam J
- Chinopoulos Christos
- Chowdhury Subir Kumar
- Cizmarova Beata
- Clementi Emilio
- Coen Paul M
- Cohen Bruce H
- Coker Robert H
- Collin-Chenot Anne
- Coughlan Melinda T
- Coxito Pedro
- Crisostomo Luis
- Crispim Marcell
- Crossland Hannah
- Dahdah Norma Ramon
- Dalgaard Louise T
- Dambrova Maija
- Danhelovska Tereza
- Darveau Charles-A
- Darwin Paula M
- Das Anibh Martin
- Dash Ranjan K
- Davidova Eliska
- Davis Michael S
- Dayanidhi Sudarshan
- De Bem Andreza Fabro
- De Goede Paul
- De Palma Clara
- De Pinto Vito
- Dela Flemming
- Dembinska-Kiec Aldona
- Detraux Damian
- Devaux Yvan
- Di Marcello Marco
- Di Paola Floriana Jessica
- Dias Candida
- Dias Tania R
- Diederich Marc
- Distefano Giovanna
- Djafarzadeh Siamak
- Doermann Niklas
- Doerrier Carolina
- Dong Lan-Feng
- Donnelly Chris
- Drahota Zdenek
- Duarte Filipe Valente
- Dubouchaud Herve
- Duchen Michael R
- Dumas Jean-Francois
- Durham William J
- Dymkowska Dorota
- Dyrstad Sissel E
- Dyson Alex
- Dzialowski Edward M
- Eaton Simon
- Ehinger Johannes K
- Elmer Eskil
- Endlicher Rene
- Engin Ayse Basak
- Escames Germaine
- Evinova Andrea
- Ezrova Zuzana
- Falk Marni J
- Fell David A
- Ferdinandy Peter
- Ferko Miroslav
- Fernandez-Ortiz Marisol
- Fernandez-Vizarra Erika
- Ferreira Julio Cesar B
- Ferreira Rita Maria P
- Ferri Alessandra
- Fessel Joshua Patrick
- Festuccia William T
- Filipovska Aleksandra
- Fisar Zdenek
- Fischer Christine
- Fischer Michael J
- Fisher Gordon
- Fisher Joshua J
- Fontanesi Flavia
- Forbes-Hernandez Tamara Y
- Ford Ellen
- Fornaro Mara
- Fuertes Agudo Marina
- Fulton Montana
- Galina Antonio
- Galkin Alexander
- Gallee Leon
- Galli Gina L J
- Gama Perez Pau
- Gan Zhenji
- Ganetzky Rebecca
- Gao Yun
- Garcia Geovana S
- Garcia-Rivas Gerardo
- Garcia-Roves Pablo Miguel
- Garcia-Souza Luiz F
- Garlid Keith D
- Garrabou Gloria
- Garten Antje
- Gastaldelli Amalia
- Gayen Jiaur
- Genders Amanda J
- Genova Maria Luisa
- Giampieri Francesca
- Giovarelli Matteo
- Glatz Jan FC
- Gnaiger Erich
- Goikoetxea Usandizaga Naroa
- Goncalo Teixeira da Silva Rui
- Goncalves Debora Farina
- Gonzalez- Armenta Jenny L
- Gonzalez-Franquesa Alba
- Gonzalez-Freire Marta
- Gonzalo Hugo
- Goodpaster Bret H
- Gorr Thomas A
- Gourlay Campbell W
- Grams Bente
- Granata Cesare
- Grefte Sander
- Grilo Luis
- Guarch Meritxell Espino
- Gueguen Naig
- Gumeni Sentiljana
- Haas Clarissa
- Haavik Jan
- Hachmo Yafit
- Haendeler Judith
- Haider Markus
- Hajrulahovic Anesa
- Hamann Andrea
- Han Jin
- Han Woo Hyun
- Hancock Chad R
- Hand Steven C
- Handl Jiri
- Hansikova Hana
- Hardee Justin P
- Hargreaves Iain P
- Harper Mary- Ellen
- Harrison David K
- Hassan Hazirah
- Hatokova Zuzana
- Hausenloy Derek J
- Heales Simon JR
- Hecker Matthias
- Heiestad Christina
- Hellgren Kim T
- Henrique Alexandrino
- Hepple Russell T
- Hernansanz- Agustin Pablo
- Hewakapuge Sudinna
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- Teodoro Joao Soeiro
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- Vaupel Peter
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- Vercesi Anibal E
- Verdaguer Ignasi Bofill
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- Victor Victor Manuel
- Vidimce Josif
- Vieira Ligo Teixeira Camila
- Viel Christian
- Vieyra Adalberto
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- Vinogradov Andrey D
- Viscomi Carlo
- Vitorino Rui Miguel Pinheiro
- Vlachaki Walker Julia
- Vogt Sebastian
- Volani Chiara
- Volska Kristine
- Votion Dominique-Marie
- Vujacic-Mirski Ksenija
- Wagner Brett A
- Ward Marie Louise
- Warnsmann Verena
- Wasserman David H
- Watala Cezary
- Wei Yau-Huei
- Weinberger Klaus M
- Weissig Volkmar
- White Sarah Haverty
- Whitfield Jamie
- Wickert Anika
- Wieckowski Mariusz R
- Wiesner Rudolf J
- Williams Caroline M
- Winwood-Smith Hugh
- Wohlgemuth Stephanie E
- Wohlwend Martin
- Wolff Jonci Nikolai
- Wrutniak-Cabello Chantal
- Wuest Rob CI
- Yokota Takashi
- Zablocki Krzysztof
- Zanon Alessandra
- Zanou Nadege
- Zaugg Kathrin
- Zaugg Michael
- Zdrazilova Lucie
- Zhang Yizhu
- Zhang Yong
- Zikova Alena
- Zischka Hans
- Zorzano Antonio
- Zujovic Tijana
- Zurmanova Jitka
- Zvejniece Liga
- Publication venue
- Publication date
- 01/01/2020
- Field of study
As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery
Genetic mechanisms of critical illness in COVID-19.
- Author
- A A Roger Thompson
- A Abraheem
- A Agasou
- A Ahmed
- A Ali
- A Allan
- A Altabaibeh
- A Alvaro
- A Aspinwall
- A Ayers
- A Bamford
- A Barron
- A Bashyal
- A Bellini
- A Bociek
- A Botello
- A Bowes
- A Brady
- A Brayne
- A Brown
- A Brown
- A Butler
- A Campbell
- A Carter
- A Collins
- A Cowley
- A Cowton
- A Cowton
- A Cox
- A Crew
- A Dance
- A Daniel
- A Daniels
- A Dela Rosa
- A Drummond
- A Durie
- A E Heron
- A Easthope
- A Easthope
- A Evans
- A Fofano
- A Gales
- A Ganesan
- A Gardner
- A Garg
- A Gherman
- A Gordon
- A Gratrix
- A Gulati
- A Gupta
- A Haigh
- A Haldeos
- A Harrison
- A Harvey
- A Hayes
- A Higham
- A Higham
- A Hilldrith
- A Holden
- A Hormis
- A Hutcheon
- A Javaid
- A Joseph
- A Kaliappan
- A Katary
- A Kay
- A Kayani
- A Kent
- A Kirkby
- A Knight
- A Kubisz-Pudelko
- A Kuravi
- A Lewis
- A Loveridge
- A Lyle
- A Mayer
- A McAlpine
- A McCarthy
- A McGregor
- A McGregor
- A Meikle
- A Mitchell
- A Mitra
- A Morris
- A Morrison
- A Naranjo
- A Nicholson
- A Nicholson
- A Nilsson
- A Noakes
- A Patel
- A Pickard
- A Poole
- A Price
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- A Quinn
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- A Rattray
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- A Reed
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- A Rose
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- A Salberg
- A Sanderson
- A Serrano-Ruiz
- A Solesbury
- A Sukha
- A Swain
- A Tariq
- A Thomas
- A Thomas
- A Todd
- A Tomas
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- A Tucci
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- A Waite
- A Walden
- A Whileman
- A Wilkinson
- A Williams
- A Williams
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- A Zak
- A Zaki
- Achille Iolascon
- Adam Auton
- Adam Brown
- Agnese Verzuri
- Agostino Ognibene
- Agostino Riva
- Ailsa Golightly
- Alan Maclean
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- Alessandra Stella
- Alessandra Vergori
- Alessia Giorli
- Alexander J Mentzer
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- Alistair Nichol
- Ana da Silva Filipe
- Andrea Antinori
- Andrea Cossarizza
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- Andy Law
- Anjali J Shastri
- Anna Canaccini
- Anna Maria Pinto
- Annarita Giliberti
- Annemarie B Docherty
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- Antonio Di Biagio
- Antony Symons
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- Stephanie Roberts
- Stephen R Knight
- Summers Charlotte
- Susanna Croci
- Susanna Guerrini
- T Anderson
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- Tammy Gilchrist
- Tenesa Albert
- Teresa Filshtein-Sonmez
- Thomas M Drake
- Thushan de Silva
- Tim Walsh
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- Tony Wackett
- Trevor Paterson
- Tullio Trotta
- Turtle Lance
- U Poultney
- V Amin
- V Anumakonda
- V Bastion
- V Cannons
- V Crickmore
- V Gopal
- V Irvine
- V Kasipandian
- V Krishnamurthy
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- V Waugh
- Valentina Anemoli
- Vanessa Sancho-Shimizu
- Victoria Shaw
- Vitart Veronique
- W Harrison
- W Khaliq
- W Khaliq
- W McCormick
- W Woodyatt
- Walker Susan
- Walsh Timothy
- Wang Bo
- Wei Shen Lim
- Wendy S Barclay
- William A Paxton
- William Greenhalf
- Wilson James F
- Wrobel Nicola
- Wu Yang
- X Qiu
- Y Baird
- Y Choudhury
- Y Hussain
- Y Jackson
- Y Thirlwall
- Yang Jian
- Yang Zhijian
- Z Alldis
- Z Belagodu
- Z Bradshaw
- Z Coton
- Z Daly
- Z Farzad
- Z Fernandez
- Z Garland
- Z Maqsood
- Z Omar
- Z Prime
- Z Scott
- Zechner Marie
- Zhai Ranran
- Zheng Chenqing
- Publication venue
- Nature
- Publication date
- 01/01/2020
- Field of study
Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice
Whole-genome sequencing reveals host factors underlying critical COVID-19
- Author
- Abd Elghafar M. S.
- Abdel-Aziz M.
- Abdelrazik M.
- Abdollahi H.
- Abdullah T.
- Abecasis G. R.
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- Abel L.
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- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- 01/01/2022
- Field of study
Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2–4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease
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