7 research outputs found
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Hospital education.
- Publication venue
- ScholarWorks@UMass Amherst
- Publication date
- 01/01/1947
- Field of study
Thesis (M.S.
The specificity of the malarial VAR2CSA protein for chondroitin sulfate depends on 4-O-sulfation and ligand accessibility
- Author
- Publication venue
- 'Elsevier BV'
- Publication date
- 01/01/2021
- Field of study
Placental malaria infection is mediated by the binding of the malarial VAR2CSA protein to the placental glycosaminoglycan, chondroitin sulfate. Recombinant subfragments of VAR2CSA (rVAR2) have also been shown to bind specifically and with high affinity to cancer cells and tissues, suggesting the presence of a shared type of oncofetal chondroitin sulfate (ofCS) in the placenta and in tumors. However, the exact structure of ofCS and what determines the selective tropism of VAR2CSA remains poorly understood. In this study, ofCS was purified by affinity chromatography using rVAR2 and subjected to detailed structural analysis. We found high levels of N-acetylgalactosamine 4-O-sulfation (∼80-85%) in placenta- and tumor-derived ofCS. This level of 4-O-sulfation was also found in other tissues that do not support parasite sequestration, suggesting that VAR2CSA tropism is not exclusively determined by placenta- and tumor-specific sulfation. Here, we show that both placenta and tumors contain significantly more chondroitin sulfate moieties of higher molecular weight than other tissues. In line with this, CHPF and CHPF2, which encode proteins required for chondroitin polymerization, are significantly upregulated in most cancer types. CRISPR/Cas9 targeting of CHPF and CHPF2 in tumor cells reduced the average molecular weight of cell-surface chondroitin sulfate and resulted in a marked reduction of rVAR2 binding. Finally, utilizing a cell-based glycocalyx model, we showed that rVAR2 binding correlates with the length of the chondroitin sulfate chains in the cellular glycocalyx. These data demonstrate that the total amount and cellular accessibility of chondroitin sulfate chains impactrVAR2 binding and thus malaria infection
Depressive comorbidity in personality disorders
- Author
- Abela
- Abrams
- Abreu
- Alnaes
- Alnaes
- Alnaes
- Berlanga
- Bienvenu
- Black
- Block
- Blom
- Boyce
- Boyce
- Boyce
- Brieger
- Bronisch
- Casey
- Charney
- Cheour
- Christensen
- Comtois
- Corruble
- Davidson
- De la Fuente
- De Portugal
- Duberstein
- Duggan
- Farabaugh
- Fava
- Garyfallos
- Gregory
- Grilo
- Gunderson
- Gunderson
- Hayden
- Howland
- Iacoviello
- Ilardi
- Johnson
- Joyce
- Kool
- Kool
- Kronmuller
- Maier
- Marchesi
- Matsudaira
- Morse
- Mulder
- Mulder
- Newman
- Newton-Howes
- Patience
- Pepper
- Peselow
- Petersen
- Pfohl
- Pirkis
- Quilty
- Ramklint
- Reich
- Reich
- Reich
- Rothschild
- Sakado
- Sanderson
- Sato
- Sato
- Sato
- Shea
- Shea
- Shea
- Skodol
- Spijker
- Stankovic
- Viinamaki
- Viinamaki
- Weissman
- Zanarini
- Publication venue
- 'Elsevier BV'
- Publication date
- Field of study
Developments in Mass Spectrometry for Glycosaminoglycan Analysis: A Review
- Author
- Agerbæk
- Agyekum
- Agyekum
- Aichler
- Antia
- Aoki-Kinoshita
- Arungundram
- Auray-Blais
- Bienkowski
- Bodet
- Bohlmann
- Ceroni
- Chi
- Chiu
- Chiu
- Clausen
- Clegg
- Coon
- DeAngelis
- Desaire
- Domon
- Doneanu
- Dreyfuss
- Du
- Duan
- Duan
- Ernest
- Ernst
- Ernst
- Esko
- Fallacara
- Fraser
- Garron
- Gill
- Guerrini
- Guo
- Han
- Heinegård
- Hitchcock
- Hogan
- Huang
- Huang
- Huang
- Huang
- Håkansson
- I. Jonathan Amster
- Igarashi
- Kailemia
- Kailemia
- Kailemia
- Kailemia
- Karst
- Kett
- Khanal
- Klein
- Kovalszky
- Kunzke
- Laremore
- Laremore
- Laremore
- Lauren E. Pepi
- Leach
- Leach
- Leach
- Leach
- Leach
- Leach
- Leach
- Lemmnitzer
- Lemmnitzer
- Lesur
- Li
- Li
- Li
- Li
- Liang
- Lin
- Linhardt
- Liu
- Lu
- Ly
- Ly
- Ly
- Margolis
- Maxwell
- McClellan
- Miller
- Minsky
- Morgan Stickney
- Moure
- Mourier
- Nimptsch
- Ofman
- Oh
- Ouyang
- Patience Sanderson
- Pitt
- Poyer
- Przybylski
- Pudelko
- Rabenstein
- Racaud
- Raia
- Rhomberg
- Rush
- Saad
- Salanti
- Sanderson
- Sasisekharan
- Shao
- Shao
- Shen
- Shi
- Staples
- Stickney
- Sugahara
- Sun
- Sun
- Sun
- Sun
- Szajek
- Thacker
- Tissot
- Turiák
- Vilar
- Vismara
- Volpi
- Volpi
- Volpi
- Wang
- Watanabe
- Weatherly
- Wei
- Wolff
- Wolff
- Wolff
- Wolff
- Wolff
- Wolff
- Wolff
- Wolff
- Wu
- Wu
- Xu
- Yu
- Yu
- Yu
- Zaia
- Zaia
- Zaia
- Zaia
- Zaia
- Zaia
- Zaia
- Zaia
- Zamfir
- Zamfir
- Zhang
- Zhang
- Zhang
- Zhao
- Zhao
- Zhao
- Zhao
- Zhao
- Zhou
- Publication venue
- 'American Society for Biochemistry & Molecular Biology (ASBMB)'
- Publication date
- Field of study
Outcomes after perioperative SARS-CoV-2 infection in patients with proximal femoral fractures: an international cohort study
- Author
- A'Court J
- Aawsaj Y
- Abbadessa F
- Abbas A
- Abbott S
- Abdalaziz H
- Abdalla M
- Abdeh L
- Abdelsaid K
- Abdou H
- Abdul-Jabar H
- Abood A
- Abou-Foul AK
- Abrate A
- Abu-Nayla I
- Abual-Rub Z
- Abuown A
- Adamec A
- Adegbola S
- Ademuyiwa AO
- Advani R
- Aftab R
- Agarwal A
- Agarwal K
- Aggarwal A
- Aghababyan K
- Agilinko J
- Agrawal S
- Ahad S
- Ahmad Y
- Ahmed Elamin H
- Ahmed I
- Ahmeidat A
- Akhtar MA
- Al Ameer E
- Al-mukhtar A
- Al-omishy H
- Al-Samaraee A
- Al-Sukaini A
- Al-Yaseen M
- Aladeojebi A
- Alanbuki A
- Alderson D
- Aldridge K
- Alexander ME
- Alga A
- Ali M
- Ali Mahmoud F
- Ali S
- Allana A
- Allen M
- Almeida AC
- Almond M
- Alotaibi M
- Alqallaf A
- Alsakkaf M
- Alser O
- Alser O
- Altomare DF
- Alves R
- Alwadiya A
- Alzetani A
- Amaral MJ
- Ambler GK
- Ameerally P
- Anania G
- Anazor F
- Anderson C
- Andrade R
- Andreani SM
- Andronic A
- Aneke IA
- Angamuthu N
- Anjarwalla N
- Antar M
- Anthoney J
- Anton-Eguia BT
- Antunes J
- Apampa AA
- Aragon Achig EJ
- Archer JE
- Arigoni M
- Arkani S
- Armao T
- Arminio A
- Arnaud AP
- Arrieta M
- Asaad P
- Ascensao J
- Ashcroft J
- Asher S
- Askari A
- Athayde Nemesio R
- Augestad KM
- Aujayeb A
- Aujayeb A
- Awadallah M
- Ayeni F
- Ayorinde J
- Azevedo P
- Baban C
- Babawale O
- Babu BHB
- Bacarese-Hamilton J
- Bacarese-Hamilton T
- Badran A
- Bagouri E
- Baig M
- Baig MMAS
- Baker M
- Baker OJ
- Balaguer-Castro M
- Balakrishnan A
- Balasubramaniam D
- Balasubramanian SP
- Balau P
- Baldwin AJ
- Ballabio M
- Ballantyne K
- Baltazar G
- Bandyopadhyay S
- Bankhad-Kendall B
- Bankhead-Kendall B
- Bankhead-Kendall B
- Baquedano M
- Barbe Y
- Barbier L
- Barmayehvar B
- Barmpagianni C
- Barret E
- Barry C
- Bartsch A
- Basgaran A
- Basha A
- Bashkirova V
- Baskaran D
- Bateman A
- Bath MF
- Baumber R
- Baxter Z
- Bayer J
- Beak P
- Beamish AJ
- Begona E
- Bekheit M
- Belcher E
- Bellis C
- Beltran-Miranda P
- Ben-Sassi A
- Bence M
- Benitez-Linero I
- Benjamin MW
- Benson RA
- Bernal-Sprekelsen JC
- Bernasconi M
- Bevan K
- Bhalla A
- Bhangu A
- Bhangu A
- Bhangu A
- Bhasin S
- Bhaskar Pala RR
- Bhatia K
- Bhattacharya S
- Bhojwani D
- Bhutiani N
- Bierman W
- Bisagni P
- Blair J
- Blake I
- Blanco J
- Blanco-Colino R
- Blas Laina JL
- Blasco-Moreu J
- Blasco-Torres L
- Bleibleh S
- Blencowe NS
- Bloom O
- Blundell C
- Boal M
- Board T
- Bobak P
- Bodla AS
- Boeckxstaens A
- Boeker C
- Bond-Smith G
- Booth K
- Bordenave M
- Borghi F
- Borgstein ABJ
- Bosanquet D
- Bosch KD
- Bouche PA
- Bourke G
- Bowen D
- Branco C
- Brar A
- Brathwaite CEM
- Bravo A Minaya
- Breda D
- Breen K
- Breen KA
- Breik O
- Brennan C
- Brennan P
- Bretherton C
- Bretherton C
- Brian E
- Britton E
- Brown A
- Brown BC
- Brown O
- Brown O
- Brown S
- Brown SR
- Brown V
- Brunelli A
- Brunt A
- Buarque I Lima
- Burahee A
- Burke JR
- Byrne J
- Byrne MHV
- Cabeleira A
- Cadersa A
- Cagigal Ortega EP
- Caja Vivancos P
- Callahan MP
- Callan R
- Calvo Rey A
- Camacho C
- Camacho-Carrasco P
- Campain N
- Campbell R
- Campuzano-Bitterling B
- Canhoto C
- Cao H
- Capitan-Morales L
- Capitelli-McMahon H
- Caputo M
- Carcoforo P
- Cardoso N
- Cardoso N
- Cardoso P
- Cardoso P
- Carlos W
- Carmichael H
- Carreras-Castaner A
- Carrillo-Rivas M
- Carter J
- Caruana E
- Carvalho L
- Castano-Leon AM
- Castellanos J
- Catala Bauset JC
- Cathala N
- Cathelineau X
- Cato LD
- Catton A
- Cernei C
- Cervera I
- Chakrabortee S
- Chan CD
- Chan CH
- Chan M
- Chase T
- Chatterji S
- Chaudhry D
- Chaudhry D
- Chauhan G
- Chebaro A
- Chek Syed Nong SAH
- Chelva R
- Chen F
- Cheng D
- Chetty G
- Cheung J
- Chia Z
- Chiarpenello R
- Chidambaram S
- Chiozza M
- Choron R
- Choudhry A
- Chowdhury M
- Chowdhury S
- Chrastek D
- Christensen MA
- Christoforidis D
- Chu H
- Chui K
- Chung C
- Chung E
- Cianflocca D
- Cioci A
- Ciriello V
- Cirocchi N
- Clancy H
- Clark J
- Clifford R
- Clough E
- Clynch AL
- Cohnert TU
- Coleman NL
- Colino M
- Collaborative COVIDSurg
- Collera P
- Collier T
- Collis J
- Colombo F
- Colquhoun A
- Colvin HV
- Combellack T
- Connolly H
- Conso C
- Constable J
- Cooper Z
- Cordonnier A
- Cornish J
- Correia S
- Costa M
- Costeira B
- Cotoia A
- Cotsoglou C
- Coughlin P
- Crego-Vita D
- Cresner R
- Crichton A
- Crichton R
- Cros B
- Cross GWV
- Cuming T
- Cumpstey A
- Cunha C
- Cunha MF
- Cunningham Y
- Cuschieri J
- Cuthbert R
- Cymes W
- D'Agruma M
- Daadipour A
- Dalgleish S
- Daliya P
- Dalmasso E
- Daniele A
- Daniels IR
- Das R
- Dasa M
- Dass D
- Dauer MDE
- Davenport D
- Davidson B
- Davidson GH
- Davidson GH
- Davies E
- Davies RJ
- Davies-Jones G
- Davis NF
- Davison S
- Dawe N
- Dawson AC
- Dawson BE
- De Barros J
- de Castro Rubio Garcia E
- De Coster J
- De Gheldere C
- de la Manzanara Cano Lopez CA
- De la Rosa-Estadella M
- de Lacy FB
- De Marchi J
- De Oliveira Lopez AL
- De Vries JPPM
- Dean B
- Dean H
- Deglurkar I
- Dehal A
- del Toro Lopez MD
- Delgado Fernandez J
- Dellonder Frigole J
- Demetriou C
- Denning A
- Denning M
- Desai A
- Desai A
- Dewan V
- Dhaif F
- Di Chiara F
- Di Giuseppe M
- Di Saverio S
- Di Taranto G
- Diaz Del Gobbo R
- Diaz Pena P
- Diaz J
- Diaz J
- Dickson K
- Divecha H
- Dixon J
- Doe M
- Domenech J
- Domingues JC
- Domingues JC
- Doorgakant A
- Dos Santos Carregal L
- Dott C
- Doulias T
- Dovell G
- Drake T
- Drane A
- Duchateau N
- Duck E
- Dudek J
- Duff S
- Duggleby L
- Dunn J
- Dunne N
- Dunning J
- Dunstan M
- Duque M
- Duran-Munoz-Cruzado VM
- Durrani A
- Durst AZED
- Dvorkin LS
- Eardley N
- Eberbach H
- Ebrahim A
- Edmondson R
- Edwards J
- Edwards J
- Egan RJ
- Egglestone A
- Eibinger N
- Eiriz Fernandez C
- El Amrani M
- El Drubi Vega S
- El Hechi M
- El Kafsi J
- El Moheb M
- El-Hasani S
- Elhadi M
- Elhusseini M
- Elkadi H
- Elliott L
- Elmaleh N
- Emerson H
- Emmerson O
- Emslie K
- Enemosah I
- Engel J
- English C
- Enjuto D
- Erdle B
- Eriberto F
- Erridge S
- Escartin J
- Escobar D
- Espino Segura-Illa M
- Estaire Gomez M
- Esteban Sinovas O
- Evans J
- Evans J
- Evans JP
- Evans R
- Exley R
- Farik S
- Farre Font R
- Farrell T
- Fathelbab MSAT
- Faulkner G
- Fawi H
- Fayad A
- Fediuk M
- Fell A
- Ferguson D
- Ferguson H
- Fernandez Bernabe P
- Fernandez Camunas A
- Fernandez-Colorado A
- Fernandez-Marin MR
- Ferrero Herrero E
- Finch JG
- Fine N
- Fiore M
- Fisher A
- Fitzgerald JE
- Flannery O
- Flatman M
- Flindall I
- Flores Clotet R
- Folorunso A
- Ford D
- Ford S
- Ford S
- Forlani S
- Foster L
- Fountain DM
- Fowler GE
- Freedman J
- Freijeiro M
- Freystaetter K
- Fu H
- Fudulu DP
- Fuks D
- Fusai G
- Gabr A
- Gagliano A
- Gainza A
- Gaitanidis A
- Galhoum M
- Galipienso Eri M
- Gallagher B
- Gallagher P
- Gallo G
- Gammeri E
- Ganau M
- Garces Garcia R
- Garcia de Cortazar U
- Garcia Egea J
- Garcia Gutierrez JJ
- Garcia Montesino JD
- Garcia Opere G
- Garcia Perez D
- Garcia Santos EP
- Garcia Villar O
- Garcia-Borda J
- Gardner A
- Garner M
- Garnero A
- Garrido R
- Garrido S
- Garrido-Ondono S
- Gasset-Teixidor A
- Gasulla-Rodriguez A
- Gaujoux S
- Gaunt A
- Gelarda E
- George K
- Georgiades F
- Georgopoulou N
- Gerogiannis I
- Ghanbari A
- Ghattaura H
- Ghobrial M
- Ghosh D
- Ghosh K
- Giblin A
- Gil-Albarova O
- Gilabert Estelles J
- Gill C
- Gill DF
- Gilliland J
- Giraudo G
- Gisbertz SS
- Giuffrida MC
- Glasbey JC
- Gnanachandran C
- Godbole C
- Godinho M
- Gohil K
- Gokcen E
- Gomes GMA
- Gomes H
- Gomez Cruzado Fernandez L
- Gomez Diaz CJ
- Gomez Suarez J
- Gomez P
- Gomez-Rosado J
- Gonzalez De Miguel M
- Gonzalez J
- Gossot D
- Goubran A
- Gowda M
- Goyal A
- Gracia I
- Gradinariu G
- Grainger T
- Granieri S
- Green S
- Greenhalgh MS
- Griffin XL
- Griffiths E
- Griffiths E
- Grigoroiu M
- Grimaldi Di Maria S
- Grimley E
- Groot G
- Guardia N
- Guariglia CA
- Guerreiro P
- Guha S
- Guimaraes A
- Gujjuri RR
- Gusani N
- Habeeb A
- Habeebullah A
- Hadfield JN
- Hagger R
- Hainsworth A
- Hakami I
- Hakmi H
- Halkias C
- Halkias C
- Hall J
- Halliday E
- Hamady Z
- Hamilton E
- Hammond J
- Hampton M
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- Hanna N
- Hannah A
- Hansen L
- Hanson A
- Haq I
- Hardie C
- Hardie J
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- Harris G
- Harrison EM
- Harrison EM
- Hart C
- Hasan MT
- Hasan R
- Hashem M
- Hassan A
- Hassan M
- Hatzantonis C
- Haugstvedt AF
- Hawkin P
- Hazelton J
- Heckburn R
- Heer B
- Henegouwen van Berge MI
- Hennessy EA
- Henriques Marujo D
- Henriques P
- Henriques P
- Henry A
- Henshall DE
- Heritage E
- Hernandez E
- Hernandez I
- Herrera-Merino N
- Hettige R
- Higgs S
- Hill A
- Hill G
- Hilley A
- Hine T
- Hing C
- Hirji SA
- Hirri F
- Hirsch H
- Hitchman L
- HKruijff S
- Ho B
- Ho M
- Holler E
- Holme T
- Holroyd D
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- Hopkins J
- Hormis AP
- Horvath S
- Hosny S
- Hossain F
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- Houston R
- Howden D
- Hudson VE
- Huecas-Martinez M
- Hughes I
- Hughes JL
- Humphreys L
- Hunt I
- Hunt J
- Hussein KMA
- Hutchinson P
- Hutchinson PJ
- Ibrahim Aboelkassem A
- Ibrahim M
- Ikram H
- Ilahi N
- Ip M
- Irune E
- Ishii H
- Isik A
- Ismail M
- Ismail O
- Izquierdo O
- Jackson H
- Jackson K
- Jackson K
- Jaekers J
- Jallad S
- Jambulingam PS
- James A
- James G
- Jamieson NB
- Jamjoom AAB
- Janssen Y
- Jarvis M
- Jauhari Y
- Jayasankar B
- Jeevan D
- Jelley C
- Jenvey C
- Jeong H
- Jeyaretna D
- Jichi T
- Jimenez Higuera E
- Jimenez Jimenez M
- Jimenez-Roldan L
- Jimeno Fraile J
- John J
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- Johnstone J
- Jolissaint JS
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- Jonsson M
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- Joshi P
- Joshi Y
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- Judkins N
- Junca-Marti S
- Kaafarani H
- Kaafarani H
- Kaafarani H
- Kahiu J
- Kahn J
- Kalenderov R
- Kalidindi VK
- Kalson NS
- Kamal M
- Kamarajah SK
- Kamel F
- Kamera BS
- Kang C
- Kanitkar R
- Kanthasamy S
- Kantor E
- Kapoen C
- Karam E
- Karim A
- Karki B
- Kashora F
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- Kaufmann A
- Kauppila JH
- Kaur J
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- Keatley JM
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- Keller Deborah S
- Kelty CJ
- Khajuria A
- Khaleel A
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- Khan J
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- Kim B
- King SD
- Kinnaman G
- Kinross J
- Kisiel A
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- Kouritas V
- Koutentakis M
- Kowal M
- Krishnan E
- Kristinsson S
- Kropf E
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- Kudchadkar S
- Kulkarni R
- Kumar L
- La Regina D
- Labalde Martinez M
- Labib A
- Labib PL
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- Lagares A
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- Lane J
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- Langlands F
- Lara A
- Laurente R
- Lawani I
- Lawday S
- Lawday S
- Layton GR
- Lazaro A
- Lecolle K
- Lecumberri D
- Lederhuber H
- Lee M
- Lefroy R
- Leo CA
- Leotta L
- Leventoglu S
- Lewis SE
- Leyte A
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- Liew I
- Lin DJ
- Linder G
- Lipede C
- Liu H
- Liyanage ASD
- Lizzi V
- Llaquet Bayo H
- Lo T
- Lodhia S
- Loffler MW
- Logishetty K
- Lokman U
- Longhi M
- Lopes C
- Lord J
- Lostis E
- Loubani M
- Lourenco I
- Lourenco S
- Luck J
- Luk ACO
- Luke L
- Lumenta DB
- Lunevicius R
- Luney C
- Luo X
- Lye G
- Lyons O
- Maashi A
- Maccabe T
- MacDonald L
- Macek P
- Machairas N
- Madan S
- Madani R
- Madhvani K
- Madonini M
- Magee C
- Magowan D
- Mahapatra Roy S
- Mahendran V
- Maher M
- Mahmood A
- Mahmoud A
- Mahoney R
- Mahvi DA
- Main B
- Maines J
- Maione F
- Maity A
- Majd Soleymani H
- Majkowski L
- Mak JKC
- Makin-Taylor R
- Malcolm FL
- Maldonado-Sotoca Y
- Mall J
- Mallabiabarrena Ormaechea G
- Manara J
- Mangos E
- Mangwani J
- Manickavasagam J
- Mannan S
- Manning D
- Mannion R
- Manresa-Manresa F
- Manso MI
- Manso MI
- Mansour F
- Mansuri A
- Manu N
- Maqboul F
- Maqsood A
- Marais L
- Marano A
- Marchbank A
- Mariani NM
- Marin H
- Marin H
- Marlow W
- Marqueta De Salas M
- Martin Playa P
- Martin E
- Martin G
- Martin J
- Martin J
- Martin RCG
- Martinez Pascual P
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- Publication venue
- 'BMJ'
- Publication date
- 01/01/2021
- Field of study
Objectives Studies have demonstrated high rates of mortality in people with proximal femoral fracture and SARS-CoV-2, but there is limited published data on the factors that influence mortality for clinicians to make informed treatment decisions. This study aims to report the 30-day mortality associated with perioperative infection of patients undergoing surgery for proximal femoral fractures and to examine the factors that influence mortality in a multivariate analysis. Setting Prospective, international, multicentre, observational cohort study. Participants Patients undergoing any operation for a proximal femoral fracture from 1 February to 30 April 2020 and with perioperative SARS-CoV-2 infection (either 7 days prior or 30-day postoperative). Primary outcome 30-day mortality. Multivariate modelling was performed to identify factors associated with 30-day mortality. Results This study reports included 1063 patients from 174 hospitals in 19 countries. Overall 30-day mortality was 29.4% (313/1063). In an adjusted model, 30-day mortality was associated with male gender (OR 2.29, 95% CI 1.68 to 3.13, p80 years (OR 1.60, 95% CI 1.1 to 2.31, p=0.013), preoperative diagnosis of dementia (OR 1.57, 95% CI 1.15 to 2.16, p=0.005), kidney disease (OR 1.73, 95% CI 1.18 to 2.55, p=0.005) and congestive heart failure (OR 1.62, 95% CI 1.06 to 2.48, p=0.025). Mortality at 30 days was lower in patients with a preoperative diagnosis of SARS-CoV-2 (OR 0.6, 95% CI 0.6 (0.42 to 0.85), p=0.004). There was no difference in mortality in patients with an increase to delay in surgery (p=0.220) or type of anaesthetic given (p=0.787). Conclusions Patients undergoing surgery for a proximal femoral fracture with a perioperative infection of SARS-CoV-2 have a high rate of mortality. This study would support the need for providing these patients with individualised medical and anaesthetic care, including medical optimisation before theatre. Careful preoperative counselling is needed for those with a proximal femoral fracture and SARS-CoV-2, especially those in the highest risk groups. Trial registration number NCT0432364
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- Cienfuegos-Jimenez O
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- Clarey E
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- Íñiguez M
- Publication venue
- Springer Nature
- Publication date
- 17/05/2023
- Field of study
Data availability: Downloadable summary data are available through the GenOMICC data site (https://genomicc.org/data). Summary statistics are available, but without the 23andMe summary statistics, except for the 10,000 most significant hits, for which full summary statistics are available. The full GWAS summary statistics for the 23andMe discovery dataset will be made available through 23andMe to qualified researchers under an agreement with 23andMe that protects the privacy of the 23andMe participants. For further information and to apply for access to the data, see the 23andMe website (https://research.23andMe.com/dataset-access/). All individual-level genotype and whole-genome sequencing data (for both academic and commercial uses) can be accessed through the UKRI/HDR UK Outbreak Data Analysis Platform (https://odap.ac.uk). A restricted dataset for a subset of GenOMICC participants is also available through the Genomics England data service. Monocyte RNA-seq data are available under the title ‘Monocyte gene expression data’ within the Oxford University Research Archives (https://doi.org/10.5287/ora-ko7q2nq66). Sequencing data will be made freely available to organizations and researchers to conduct research in accordance with the UK Policy Framework for Health and Social Care Research through a data access agreement. Sequencing data have been deposited at the European Genome–Phenome Archive (EGA), which is hosted by the EBI and the CRG, under accession number EGAS00001007111.Extended data figures and tables are available online at https://www.nature.com/articles/s41586-023-06034-3#Sec21 .Supplementary information is available online at https://www.nature.com/articles/s41586-023-06034-3#Sec22 .Code availability:
Code to calculate the imputation of P values on the basis of SNPs in linkage disequilibrium is available at GitHub (https://github.com/baillielab/GenOMICC_GWAS).Acknowledgements: We thank the members of the Banco Nacional de ADN and the GRA@CE cohort group; and the research participants and employees of 23andMe for making this work possible. A full list of contributors who have provided data that were collated in the HGI project, including previous iterations, is available online (https://www.covid19hg.org/acknowledgements).Change history: 11 July 2023: A Correction to this paper has been published at: https://doi.org/10.1038/s41586-023-06383-z. -- In the version of this article initially published, the name of Ana Margarita Baldión-Elorza, of the SCOURGE Consortium, appeared incorrectly (as Ana María Baldion) and has now been amended in the HTML and PDF versions of the article.Copyright © The Author(s) 2023, Critical illness in COVID-19 is an extreme and clinically homogeneous disease phenotype that we have previously shown1 to be highly efficient for discovery of genetic associations2. Despite the advanced stage of illness at presentation, we have shown that host genetics in patients who are critically ill with COVID-19 can identify immunomodulatory therapies with strong beneficial effects in this group3. Here we analyse 24,202 cases of COVID-19 with critical illness comprising a combination of microarray genotype and whole-genome sequencing data from cases of critical illness in the international GenOMICC (11,440 cases) study, combined with other studies recruiting hospitalized patients with a strong focus on severe and critical disease: ISARIC4C (676 cases) and the SCOURGE consortium (5,934 cases). To put these results in the context of existing work, we conduct a meta-analysis of the new GenOMICC genome-wide association study (GWAS) results with previously published data. We find 49 genome-wide significant associations, of which 16 have not been reported previously. To investigate the therapeutic implications of these findings, we infer the structural consequences of protein-coding variants, and combine our GWAS results with gene expression data using a monocyte transcriptome-wide association study (TWAS) model, as well as gene and protein expression using Mendelian randomization. We identify potentially druggable targets in multiple systems, including inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).GenOMICC was funded by Sepsis Research (the Fiona Elizabeth Agnew Trust), the Intensive Care Society, a Wellcome Trust Senior Research Fellowship (to J.K.B., 223164/Z/21/Z), the Department of Health and Social Care (DHSC), Illumina, LifeArc, the Medical Research Council, UKRI, a BBSRC Institute Program Support Grant to the Roslin Institute (BBS/E/D/20002172, BBS/E/D/10002070 and BBS/E/D/30002275) and UKRI grants MC_PC_20004, MC_PC_19025, MC_PC_1905 and MRNO2995X/1. A.D.B. acknowledges funding from the Wellcome PhD training fellowship for clinicians (204979/Z/16/Z), the Edinburgh Clinical Academic Track (ECAT) programme. This research is supported in part by the Data and Connectivity National Core Study, led by Health Data Research UK in partnership with the Office for National Statistics and funded by UK Research and Innovation (grant MC_PC_20029). Laboratory work was funded by a Wellcome Intermediate Clinical Fellowship to B.F. (201488/Z/16/Z). We acknowledge the staff at NHS Digital, Public Health England and the Intensive Care National Audit and Research Centre who provided clinical data on the participants; and the National Institute for Healthcare Research Clinical Research Network (NIHR CRN) and the Chief Scientist’s Office (Scotland), who facilitate recruitment into research studies in NHS hospitals, and to the global ISARIC and InFACT consortia. GenOMICC genotype controls were obtained using UK Biobank Resource under project 788 funded by Roslin Institute Strategic Programme Grants from the BBSRC (BBS/E/D/10002070 and BBS/E/D/30002275) and Health Data Research UK (HDR-9004 and HDR-9003). UK Biobank data were used in the GSMR analyses presented here under project 66982. The UK Biobank was established by the Wellcome Trust medical charity, Medical Research Council, Department of Health, Scottish Government and the Northwest Regional Development Agency. It has also had funding from the Welsh Assembly Government, British Heart Foundation and Diabetes UK. The work of L.K. was supported by an RCUK Innovation Fellowship from the National Productivity Investment Fund (MR/R026408/1). J.Y. is supported by the Westlake Education Foundation. SCOURGE is funded by the Instituto de Salud Carlos III (COV20_00622 to A.C., PI20/00876 to C.F.), European Union (ERDF) ‘A way of making Europe’, Fundación Amancio Ortega, Banco de Santander (to A.C.), Cabildo Insular de Tenerife (CGIEU0000219140 ‘Apuestas científicas del ITER para colaborar en la lucha contra la COVID-19’ to C.F.) and Fundación Canaria Instituto de Investigación Sanitaria de Canarias (PIFIISC20/57 to C.F.). We also acknowledge the contribution of the Centro National de Genotipado (CEGEN) and Centro de Supercomputación de Galicia (CESGA) for funding this project by providing supercomputing infrastructures. A.D.L. is a recipient of fellowships from the National Council for Scientific and Technological Development (CNPq)-Brazil (309173/2019-1 and 201527/2020-0)
A second update on mapping the human genetic architecture of COVID-19
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- Akinkugbe O
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- Spinner CD
- Spivey M
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- Sra S
- Sri-Chandana C
- Srikaran S
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- Stacey A
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- Vadla MS
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- Vallerga CL
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- Vandernoot I
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- Vassell K
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- Vehreschild MJGT
- Velasco DG
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- Venkatesh H
- Verdugo RA
- Verdugo RA
- Vergasova E
- Verlander M
- Vertue M
- Verula J
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- Wyllie DH
- Wynter I
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- Xue X
- Yagi K
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- Yamada Y
- Yamagata K
- Yamasaki M
- Yang J
- Yaspan B
- Yassen AM
- Yasui Y
- Yates B
- Yatomi M
- Ye C
- Yermakovich D
- Yeung RSM
- Yi X
- Yonekawa A
- Yoo S
- Yoon K
- Yoshida K
- Yoshida S
- Yoshida S
- Yoshida T
- Yoshihara T
- Yoshiya K
- Yoshiyama T
- Young M
- Yue F
- Yun N
- Yáñez CE
- Yáñez Z
- Zainulabid UA
- Zainy T
- Zak A
- Zaki A
- Zamikula J
- Zamudio IPM
- Zanella A
- Zapata-Contreras D
- Zapatamartinez M
- Zarate R
- Zarei N
- Zavaleta DAF
- Zawadzki P
- Zawati MH
- Zborowski AC
- Zeberg H
- Zechner M
- Zhang Q
- Zhao X
- Zheng C
- Zheng T
- Zhlawi HJ
- Zhlawi MWJ
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- Zhou W
- Zhu W
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- Zoller H
- Zongo O
- Zorloni C
- Zuñiga-Pacheco P
- Zárate RN
- Zúñiga-Ramos J
- Álvarez BG
- Ávila-Arcos MA
- Ávila-Arcos MC
- Özer O
- Überla K
- Þorsteinsdóttir U
- Publication venue
- Nature Research
- Publication date
- 21/06/2023
- Field of study