258 research outputs found
Targeted mutagenesis in a human-parasitic nematode.
- Author
- Publication venue
- eScholarship, University of California
- Publication date
- 01/10/2017
- Field of study
Parasitic nematodes infect over 1 billion people worldwide and cause some of the most common neglected tropical diseases. Despite their prevalence, our understanding of the biology of parasitic nematodes has been limited by the lack of tools for genetic intervention. In particular, it has not yet been possible to generate targeted gene disruptions and mutant phenotypes in any parasitic nematode. Here, we report the development of a method for introducing CRISPR-Cas9-mediated gene disruptions in the human-parasitic threadworm Strongyloides stercoralis. We disrupted the S. stercoralis twitchin gene unc-22, resulting in nematodes with severe motility defects. Ss-unc-22 mutations were resolved by homology-directed repair when a repair template was provided. Omission of a repair template resulted in deletions at the target locus. Ss-unc-22 mutations were heritable; we passed Ss-unc-22 mutants through a host and successfully recovered mutant progeny. Using a similar approach, we also disrupted the unc-22 gene of the rat-parasitic nematode Strongyloides ratti. Our results demonstrate the applicability of CRISPR-Cas9 to parasitic nematodes, and thereby enable future studies of gene function in these medically relevant but previously genetically intractable parasites
Genome sequence of Acetomicrobium hydrogeniformans OS1
- Author
- Publication venue
- Digital Commons@Becker
- Publication date
- 01/01/2018
- Field of study
Acetomicrobium hydrogeniformans, an obligate anaerobe of the phylum Synergistetes, was isolated from oil production water. It has the unusual ability to produce almost 4 molecules H2/molecule glucose. The draft genome of A. hydrogeniformans OS1 (DSM 22491T) is 2,123,925 bp, with 2,068 coding sequences and 60 RNA genes
Macrophage-derived human resistin is induced in multiple helminth infections and promotes inflammatory monocytes and increased parasite burden.
- Author
- A Tarkowski
- AL Moncayo
- AM Gan
- B Min
- Cathy Steel
- CH Kuo
- CM Steppan
- D Artis
- D Voehringer
- DD Taub
- DR Herbert
- DR Herbert
- DR Neill
- Edward J. Pearce
- F Chen
- Gang Chen
- GD Thomas
- Graham Le Gros
- H Helmby
- HK Park
- HS Jung
- J Bethony
- J Urban
- J Wang
- JA Jackson
- Jessica C. Jang
- JF Urban Jr
- JI Odegaard
- JJ Reece
- Josiah I. Chung
- JT Pesce
- K Migita
- KT Cuenco
- L Boring
- L Le Goff
- L Patel
- LC Osborne
- M Lehrke
- M Lehrke
- M Qatanani
- Mali Camberis
- Mark A. Barnes
- Meera G. Nair
- MG Nair
- MG Nair
- MG Nair
- Mitchell A. Lazar
- MM Pirvulescu
- MP Reilly
- N Silswal
- P Loke
- PF Weller
- Philip J. Cooper
- PJ George
- PJ Hotez
- R Anuradha
- RM Anthony
- RT Semnani
- RZ Yang
- S Babu
- S Babu
- S Babu
- S Babu
- S Jiang
- S Lee
- Spencer H. Wang
- Thomas B. Nutman
- TT MacDonald
- W He
- Y Benomar
- YY Hsieh
- Publication venue
- 'Public Library of Science (PLoS)'
- Publication date
- 01/01/2015
- Field of study
Parasitic helminth infections can be associated with lifelong morbidity such as immune-mediated organ failure. A better understanding of the host immune response to helminths could provide new avenues to promote parasite clearance and/or alleviate infection-associated morbidity. Murine resistin-like molecules (RELM) exhibit pleiotropic functions following helminth infection including modulating the host immune response; however, the relevance of human RELM proteins in helminth infection is unknown. To examine the function of human resistin (hResistin), we utilized transgenic mice expressing the human resistin gene (hRetnTg+). Following infection with the helminth Nippostrongylus brasiliensis (Nb), hResistin expression was significantly upregulated in infected tissue. Compared to control hRetnTg- mice, hRetnTg+ mice suffered from exacerbated Nb-induced inflammation characterized by weight loss and increased infiltration of inflammatory monocytes in the lung, along with elevated Nb egg burdens and delayed parasite expulsion. Genome-wide transcriptional profiling of the infected tissue revealed that hResistin promoted expression of proinflammatory cytokines and genes downstream of toll-like receptor signaling. Moreover, hResistin preferentially bound lung monocytes, and exogenous treatment of mice with recombinant hResistin promoted monocyte recruitment and proinflammatory cytokine expression. In human studies, increased serum resistin was associated with higher parasite load in individuals infected with soil-transmitted helminths or filarial nematode Wuchereria bancrofti, and was positively correlated with proinflammatory cytokines. Together, these studies identify human resistin as a detrimental factor induced by multiple helminth infections, where it promotes proinflammatory cytokines and impedes parasite clearance. Targeting the resistin/proinflammatory cytokine immune axis may provide new diagnostic or treatment strategies for helminth infection and associated immune-mediated pathology
New genetic loci link adipose and insulin biology to body fat distribution.
- Author
- Aalto Ville
- Aasarød Knut
- Abecasis Goncalo R
- Abecasis Gonçalo
- Absher Devin
- Adair Linda S
- Adam Martin
- Adeyemo Adebowale
- Ahlqvist Emma
- Ahmadi Kourosh R
- Ahola Aila
- Ainali Chrysanthi
- Akylbekova Ermeg
- Ala-Korpela Mika
- Alavere Helen
- Albagha Omar M E
- Albrecht Eva
- Alen Markku
- Alexander Myriam
- Alhenc-Gelas François
- Alizadeh Behrooz Z
- Allison Matthew A
- Alonso Nerea
- Altshuler David
- Ambite Jose Luis
- Amin Najaf
- Amouyel Philippe
- An Ping
- Anderson Carl A
- Anderson Denise
- Anderson Garnet
- Andrews Jeanette S
- Antonella Mulas
- Antti Jula
- Aragaki Aaron K
- Arking Dan E
- Arnold Alice
- Arnold Alice M
- Arora Pankaj
- Arscott Gillian M
- Artigas Maria Soler
- Arveiler Dominique
- Asiki Gershim
- Aspelund Thor
- Assimes Themistocles L
- Atalay Mustafa
- Atkinson Elizabeth J
- Aulchenko Yurii
- Avery Christy
- Bain Stephen C
- Bakker Stephan J L
- Balcells Susana
- Balkau Beverley
- Ballantyne Christie M
- Balmforth Anthony J
- Bandinelli Stefania
- Barbalic Maja
- Barrett Amy
- Barroso Ines
- Barroso Inês
- Basart Hanneke
- Basart Hanneke V
- Bataille Veronique
- Baumert Jens
- Beckmann Jacques S
- Beekman Marian
- Been Latonya F
- Beilby John
- Beilby John P
- Bell Jordana T
- Bellis Claire
- Bennett Amanda J
- Bennett Franklyn
- Berenson Gerald S
- Bergman Richard N
- Bergmann Sven
- Berndt Sonja I
- Berne Christian
- Bidulescu Aurelian
- Bielak Lawrence F
- Bierut Laura J
- Biffar Reiner
- Bis Joshua C
- Blackburn Hannah
- Blangero John
- Blankenberg Stefan S
- Blüher Matthias
- Boban Mladen
- Bochud Murielle
- Boehm Bernhard O
- Boehnke Michael
- Boerwinkle Eric
- Boezen H Marike
- Bolton Jennifer L
- Bolton Judith A Hoffman
- Bonnet Fabrice
- Bonnycastle Lori L
- Boomsma Dorret I
- Borecki Ingrid
- Boright Andrew P
- Borja Judith B
- Bornstein Stefan R
- Boston Jonathan
- Bots Michiel L
- Bouatia-Naji Nabila
- Bouchard Claude
- Bovet Pascal
- Boyd Heather A
- Bragg-Gresham Jennifer L
- Brambilla Paolo
- Brand Eva
- Brand Stefan-Martin
- Brandi Maria Luisa
- Braund Peter S
- Brennan Eoin P
- Brismar Kerstin
- Brody Jennifer
- Broekmans Frank J
- Broer Linda
- Brown Matthew A
- Brown Morris J
- Brown-Gentry Kristin
- Bruinenberg Marcel
- Buchkovich Martin L
- Buckley Brendan M
- Buil Alfonso
- Bull Shelley B
- Burgdorf Christof
- Buring Julie E
- Burnett Mary S
- Burnier Michel
- Burri Andrea
- Burton Paul R
- Bush William S
- Busonero Fabio
- Buxbaum Sarah G
- Buyske Steve
- Buzkova Petra
- Byrne Enda M
- Böger Carsten A
- Böhringer Stefan
- Böttcher Yvonne
- Cambien Francois
- Campbell Harry
- Campbell Susan
- Carba Delia B
- Carlson Chris
- Carlson Olga D
- Carty Cara
- Casas Juan P
- Caspersen Ida H
- Castano-Betancourt Martha
- Cauchi Stéphane
- Cauley Jane A
- Caulfield Mark
- Cavalieri Margherita
- Cazier Jean-Baptiste
- Center Jacqueline R
- Cesana Giancarlo
- Chakravarti Aravinda
- Chambers John
- Chandak Giriraj R
- Chang Hsing-Yi
- Chang Yen-Pei C
- Chanock Stephen J
- Charchar Fadi J
- Chasman Dan
- Chaturvedi Nish
- Chen Constance
- Chen Han
- Chen Ida
- Chen Jin
- Chen Ming-Huei
- Chen Wei
- Chen Yii-Der Ida
- Cheng Iona
- Cheng Sulin
- Chines Peter S
- Cho Yoon Shin
- Choi Murim
- Chouraki Vincent
- Christiansen Claus
- Chu Audrey Y
- Cimponeriu Dan
- Ciullo Marina
- Clark Graeme R
- Clarke Robert
- Claudi-Boehm Simone
- Coassin Stefan
- Cochran Barbara
- Cole Shelley
- Colhoun Helen
- Colhoun Helen M
- Collins Francis S
- Collins Rory
- Connell John M
- Cooper Cyrus
- Cooper Jackie A
- Cooper Matthew N
- Cooper Richard S
- Coresh Josef
- Cornelis Marilyn C
- Corre Tanguy
- Corsi Anna Maria
- Couper David
- Cousminer Diana L
- Coviello Andrea D
- Cox David
- Crawford Dana
- Crisponi Laura
- Croteau-Chonka Damien C
- Cucca Francesco
- Cummings Steven R
- Cupples Adrienne L
- Cupples L Adrienne
- Curhan Gary
- d'Adamo Pio
- Dahgam Santosh
- Dailiana Zoe
- Danesh John
- Danoy Patrick
- Dastani Zari
- Davies Gail
- Daw E Warwick
- Day Felix R
- Day Ian N M
- de Andrade Mariza
- de Boer Ian H
- de Boer Rudolf A
- de Faire Ulf
- de Geus Eco J C
- Deary Ian J
- Dedoussis George
- Dedoussis George V
- Dedoussis George V Z
- Deelen Joris
- Deelman Ewa
- Dehghan Abbas
- Delgado Graciela
- Deloukas Panagiotis
- Deloukas Panos
- Demerath Ellen W
- Demirkan Ayse
- Demirkan Ayşe
- Den Hertog Heleen M
- Denniff Matthew
- Dennison Elaine M
- Dermitzakis Emmanouil T
- Deshmukh Harshal
- Deshmukh Harshal A
- Devuyst Olivier
- di Meglio Paola
- Diemert Patrick
- Dimas Antigone S
- Dimitriou Maria
- Ding Jingzhong
- Do Ron
- Dominiczak Anna F
- Doney Alex
- Dong Yanbin
- Donnelly Louise A
- Doumatey Ayo
- Dreisbach Albert W
- Drong Alexander W
- Duggan David
- Dumitrescu Logan
- Duncan Bruce B
- Duncan Emma L
- Dupuis Josee
- Dupuis Josée
- Durbin Richard
- Durda Peter
- Döring Angela
- Dörr Marcus
- Eastell Richard
- Easton Douglas F
- Ebrahim Shah
- Econs Michael J
- Edkins Sarah
- Egan Josephine
- Ehret Georg
- Eiriksdottir Gudny
- Eisman John A
- Eklund Niina
- El Mokhtari NourEddine
- Elks Cathy E
- Ellinghaus David
- Elliott Paul
- Elosua Roberto
- Emilsson Valur
- Endlich Karlhans
- Epstein Stephen E
- Erbel Raimund
- Erdmann Jeanette
- Erdos Michael R
- Eriksson Joel
- Eriksson Johan
- Eriksson Niclas
- Eriksson Per
- Ernst Florian
- Esko Tonu
- Esko Tõnu
- Esko Tönu
- Estrada Karol
- Eury Elodie
- Evangelou Evangelos
- Evans Alun
- Evans David M
- Eyheramendy Susana
- Eyjolfsson Gudmundur Ingi
- Fagerholm Emma
- Falhammar Henrik
- Fall Tove
- Farrall Martin
- Fauser Bart C J M
- Fava Cristiano
- Feenstra Bjarke
- Fehrmann Rudolf
- Feitosa Mary
- Feranil Alan B
- Ferrannini Ele
- Ferrario Marco M
- Ferreira Teresa
- Ferreli Liana
- Ferrières Jean
- Ferrucci Luigi
- Fischer Krista
- Florez Jose C
- Folkersen Lasse
- Folsom Aaron R
- Fontanillas Pierre
- Ford Ian
- Fornage Myriam
- Foroud Tatiana
- Forouhi Nita G
- Forrester Terrence
- Forsblom Carol
- Foster Meredith C
- Fowke Jay
- Fowkes F Gerald R
- Fowkes Gerard R
- Fox Caroline S
- Fox Ervin R
- Franceschini Nora
- Franco Oscar H
- Franco-Cereceda Anders
- Franke Andre
- Franke Lude
- Franks Paul W
- Frants Rune
- Fraser Ross M
- Frayling Timothy M
- Freedman Barry I
- Freimer Nelson B
- Freitag Daniel F
- Friedrich Nele
- Froguel Philippe
- Frost Morten
- Fuchsberger Christian
- Galan Pilar
- Ganesh Santhi K
- Ganna Andrea
- Gansevoort Ron T
- Gao Xiaoyi
- Garcia Melissa
- Garcia-Giralt Natàlia
- Garnaas Maija
- Gasparini Paolo
- Gauguier Dominique
- Gaunt Tom R
- Gautvik Kaare M
- Geller Frank
- Gharavi Ali G
- Giedraitis Vilmantas
- Gieger Christian
- Gierman Hinco J
- Gigante Bruna
- Gill Geoffrey V
- Giroux Sylvie
- Giulianini Franco
- Glass Daniel
- Glazer Nicole
- Glazer Nicole L
- Glenn Kim
- Glorioso Nicola
- Go Alan S
- Go Min Jin
- Godson Catherine
- Goel Anuj
- Goessling Wolfram
- Golay Alain
- Goldstein Benjamin A
- Goltzman David
- Gong Jian
- González-Macías Jesús
- Goodall Alison H
- Goodarzi Mark O
- Goodloe Robert
- Gordin Daniel
- Gordon Scott D
- Gorski Mathias
- Grabe Hans-Jörgen
- Graff Misa
- Grallert Harald
- Grammer Tanja B
- Gravito Martha L
- Greenwood Celia M T
- Grewal Jagvir
- Grimsby Jonna
- Grobbee Diederick E
- Groop Leif
- Groop Per-Henrik
- Gross Myron
- Groves Christopher J
- Grundberg Elin
- Grässler Jürgen
- Gräßler Jürgen
- Gu Harvest F
- Gu Tianwei
- Guarrera Simonetta
- Gudbjartsson Daniel F
- Gudnason Villi
- Gudnason Vilmundur
- Guiducci Candace
- Guo Qun
- Guo Xiuqing
- Gurdasani Deepti
- Gustafsson Stefan
- Gyllensten Ulf
- Gyllensten Ulf B
- Hadjadj Samy
- Hadley David
- Haessler Jeff
- Hager Jörg
- Haiman Christopher
- Haines Jonathan
- Hall Alistair S
- Hall Per
- Hallan Stein
- Haller Toomas
- Hallmans Goran
- Hallmans Göran
- Hamsten Anders
- Han Bok-Ghee
- Hankinson Susan E
- Hanson Robert L
- Hardy Rebecca
- Haritunians Talin
- Harjutsalo Valma
- Harris Tamara
- Hartikainen Anna-Liisa
- Hartman Catharina A
- Hass Merli
- Hassanali Neelam
- Hassinen Maija
- Hastie Nicholas D
- Hastie Nick
- Hattersley Andrew T
- Haun Margot
- Havulinna Aki S
- Hayward Caroline
- Hazen Stanley L
- He Bing
- He Chunyan
- Heard-Costa Nancy L
- Heath Andrew C
- Heath Simon
- Heckbert Susan R
- Hedblad Bo
- Hedman Åsa K
- Heid Iris M
- Heikkilä Kauko
- Heikkilä Outi
- Heiss Gerardo
- Heliövaara Markku
- Helmer Catherine
- Helmer Quinta
- Henders Anjali K
- Henderson Brian
- Hengstenberg Christian
- Henneman Peter
- Hercberg Serge
- Herder Christian
- Hernandez Dena
- Hernandez Dena G
- Herrera Lizbeth
- Herzig Karl-Heinz
- Hicks Andrew A
- Hietala Kustaa
- Higashio Julia
- Hillege Hans L
- Hilton Gina
- Hindorff Lucia
- Hingorani Aroon
- Hirschhorn Joel N
- Hivert Marie-France
- Ho Weang K
- Hocking Lynne J
- Hoffmann Wolfgang
- Hofman Albert
- Holliday Elizabeth G
- Holm Hilma
- Holmen Oddgeir
- Homuth Georg
- Hopewell Jemma C
- Horikoshi Momoko
- Hosseini Mohsen
- Hottenga Jouke-Jan
- Hovingh G Kees
- Howard Philip
- Hsiung Chao Agnes
- Hsu Yi-Hsiang
- Hu Frank B
- Huang Huateng
- Huang Jinyan
- Hui Jennie
- Humphries Steve E
- Hundertmark Claudia
- Hung Yi-Jen
- Hunt Sarah E
- Hunt Steven C
- Hunter David J
- Husted Lise Bjerre
- Hveem Kristian
- Hwang Shih-Jen
- Hyppönen Elina
- Igl Wilmar
- Ikram M Arfan
- Illig Thomas
- Imboden Medea
- Ingelsson Erik
- Ingle Catherine
- Ingvarsson Thorvaldur
- Ioannidis John P A
- Iribarren Carlos
- Isaacs Aaron
- Isakova Tamara
- Islam Muhammad
- Ittermann Till
- Iwai Naoharu
- Jackson Anne U
- Jackson Rebecca
- Jacobs Gunnar
- Jafar Tazeen H
- James Alan L
- Jameson Karen A
- Jang Yangsoo
- Janipalli Charles S
- Jansen Hanneke
- Janssens A Cecile J W
- Jarvelin Marjo-Riitta
- Jeff Janina
- Jenny Nancy
- Johannsdottir Hrefna
- Johansen Berit
- Johansson Ingegerd
- Johansson Åsa
- Johnson Andrew
- Johnson Louise
- Johnson Paul C D
- Johnson Toby
- Jones Graeme
- Jones Michelle R
- Jousilahti Pekka
- Ju Sung Yun
- Jukema J Wouter
- Jula Antti
- Juliusdottir Thorhildur
- Justice Anne E
- Järvelin Marjo-Riitta
- Jöckel Karl-Heinz
- Kaakinen Marika
- Kahali Bratati
- Kalafati Ioanna-Panagiota
- Kaleebu Pontiano
- Kammerer Candace M
- Kanaya Alka
- Kang Hyun M
- Kang Hyun Min
- Kangas Antti J
- Kanoni Stavroula
- Kao Linda
- Kao W H L
- Kao Wen Hong Linda
- Kaplan Robert C
- Kaprio Jaakko
- Kaptoge Stephen K
- Kapur Karen A
- Karasik David
- Kardia Sharon L
- Karjalainen Juha
- Karlsson Magnus
- Karpe Fredrik
- Kastelein John J P
- Kathiresan Sekar
- Katsareli Efi
- Kedenko Lyudmyla
- Kee Frank
- Keildson Sarah
- Keinanen-Kiukaanniemi Sirkka M
- Keller Benjamin J
- Kemp John P
- Kennedy Stephen H
- Kessler Thorsten
- Kestenbaum Bryan
- Kesäniemi Antero
- Ketkar Shamika
- Kettunen Johannes
- Keyzer Jules
- Khaw Kay-Tee
- Khusainova Rita
- Khusnutdinova Elza
- Kiel Douglas P
- Kiess Wieland
- Kilpeläinen Tuomas O
- Kim Eric
- Kim Ghi Su
- Kim Hyo-Soo
- Kim Hyung-Lae
- Kim Stuart K
- Kinnunen Leena
- Kinra Sanjay
- Kiryluk Krzysztof
- Kita Yoshikuni
- Kivimaki Mika
- Kizer Jorge R
- Klaric Irena Martinovic
- Kleber Marcus E
- Klopp Norman
- Kloppenburg Margreet
- Knowles David
- Knowles Joshua W
- Kocarnik Jonathan
- Koenig Wolfgang
- Koh Jung-Min
- Kolcic Ivana
- Koller Daniel L
- Kollerits Barbara
- Kollia Panagoula
- Kolonel Laurence
- Kolovou Genovefa
- Komulainen Pirjo
- Kong Augustine
- Kooner Ishminder K
- Kooner Jaspal
- Kooperberg Charles
- Koromila Theodora
- Koudstaal Peter J
- Kovacs Peter
- Kraft Peter
- Kraja Aldi T
- Kramer Holly
- Kratzer Wolfgang
- Krauss Ronald M
- Krestyaninova Maria
- Kretzler Matthias
- Kristiansson Kati
- Kroemer Heyo K
- Kronenberg Florian
- Kruk Marcin
- Krämer Bernhard K
- Kuh Diana
- Kulkarni Smita R
- Kuller Lew
- Kumar M J Kranthi
- Kumari Meena
- Kung Annie Wai Chee
- Kutalik Zoltan
- Kutalik Zoltán
- Kuulasmaa Kari
- Kuusisto Johanna
- Kuznetsova Tatiana
- Kwan Tony
- Kytö Janne
- Kyvik Kirsten O
- Kähönen Mika
- König Inke R
- Körner Antje
- Köttgen Anna
- Laakso Markku
- Laaksonen Marika
- Laaksonen Reijo
- Laan Maris
- LaCroix Andrea
- Lacroix Andrea Z
- Ladenvall Claes
- Ladouceur Martin
- Lagou Vasiliki
- Lahermo Päivi
- Lahti Jari
- Lai Sandra
- Laisk Triin
- Laitinen Jaana
- Lajer Maria
- Lakatta Edward G
- Lakka Timo A
- Lambert Ann
- Lamina Claudia
- Langdahl Bente Lomholt
- Langefeld Carl D
- Langenberg Claudia
- Langford Cordelia
- Larson Martin
- Larson Martin G
- Lathrop Mark
- Lauc Lovorka Barac
- Launer Lenore
- Laven Joop S E
- Lawlor Debbie A
- Lawrence Robert W
- Le Marchand Loic
- Le Marchand Loïc
- Leak Tennille S
- Leander Karin
- Lecoeur Cecile
- Lee Ji-Young
- Lee Jong-Young
- Lee Nanette R
- Lee Sang Hong
- Lee Seung Hun
- Lefebvre Pierre
- Lehtimäki Terho
- Lehto Markku
- Leo Paul J
- Leslie William D
- Leung Ping C
- Levy Daniel
- Lewis Joshua R
- Li Guo
- Li Man
- Li Rui
- Li Shengxu
- Li Xiaohui
- Li Yali
- Liang Liming
- Lichtner Peter
- Lifton Richard P
- Lim Unhee
- Lin Danyu
- Lin Peng
- Lin Shih-Yi
- Lin Yi
- Lind Lars
- Lindgren Cecilia M
- Lindström Jaana
- Lips Paul
- Liu Ching-Ti
- Liu Jianjun
- Liu Yongmei
- Ljunggren Östen
- Lobbens Stéphane
- Locke Adam E
- Lohman Kurt
- Lohman Kurt K
- Lokki Marja-Liisa
- Longstreth W T
- Loo Britt-Marie
- Loos Ruth J F
- Lopez Lorna M
- Lorenc Roman S
- Lorentzon Mattias
- Louwers Yvonne V
- Lowe Christopher E
- Lu Xiaoning
- Luan Jian'an
- Luben Robert
- Lucas Gavin
- Ludwig Barbara
- Lumley Thomas
- Lundmark Anders
- Lundmark Per
- Lunetta Kathryn L
- Lyssenko Valeriya
- Lyytikainen Leo-Pekka
- Lyytikäinen Leo-Pekka
- Ma Baoshan
- MacCluer Jean
- Macgregor Stuart
- Mach François
- Maerz Winfried
- Maestroni Anna
- Maestroni Silvia
- Magnusson Patrik K E
- Mahajan Anubha
- Malinowski Jennifer
- Mangino Massimo
- Mani K Radha
- Manning Alisa K
- Manolio Teri
- Maouche Seraya
- Marc Janja
- Marette André
- Marmot Michael G
- Marongiu Mara
- Marre Michel
- Martin Finian
- Martin Nicholas G
- Marullo Letizia
- Masciullo Corrado
- Masi Laura
- Mateo Leach Irene
- Matise Tara
- Mattace-Raso Francesco U S
- Matullo Giuseppe
- Maxwell Alexander P
- McArdle Patick F
- McArdle Patrick F
- McArdle Wendy L
- McCarthy Mark I
- McCloskey Eugene
- McKay Gareth J
- McKenzie Colin A
- McKnight Amy J
- McKnight Amy Jayne
- McKnight Barbara
- McPherson Ruth
- Medina-Gomez Carolina
- Medina-Gómez Carolina
- Medland Sarah E
- Meduri Eshwar
- Meigs James B
- Meisinger Christa
- Meitinger Thomas
- Melander Olle
- Melbye Mads
- Mellström Dan
- Melzer David
- Mencej-Bedrac Simona
- Meneton Pierre
- Menni Cristina
- Merger Sigrun
- Meschia James F
- Metspalu Andres
- Metzger Marie
- Meulenbelt Ingrid
- Mihai Ioana
- Mihailov Evelin
- Miki Tetsuro
- Milaneschi Yuri
- Milani Lili
- Miljkovic Iva
- Mills Rebecca
- Min Josine L
- Minelli Cosetta
- Minster Ryan L
- Mirel Daniel B
- Missmer Stacey A
- Mitchell Braxton D
- Mitchell Paul
- Mitchell Sabrina L
- Moayyeri Alireza
- Moffatt Miriam F
- Mohlke Karen L
- Moilanen Leena
- Monda Keri L
- Monroe Kristine
- Montasser May E
- Montgomery Grant W
- Montgomery Stephen B
- Mooijaart Simon P
- Mooser Vincent
- Mora Samia
- Morken Mario A
- Morris Andrew D
- Morris Andrew P
- Morris Richard W
- Morrison Alanna C
- Mosley Thomas H
- Mota Eugen
- Mota Maria
- Mulas Antonella
- Munroe Patricia
- Murabito Joanne M
- Murdock Deborah
- Murgia Federico
- Murray Anna
- Murray Jeffrey C
- Murray Sarah S
- Musani Solomon
- Musk Arthur W
- Mychaleckyj Josyf C
- Mägi Reedik
- Mäkinen Ville-Petteri
- Männistö Satu
- März Winfried
- Möhlenkamp Stefan
- Möllsten Anna
- Mühleisen Thomas W
- Müller Gabriele
- Müller Gabrielle
- Müller-Nurasyid Martina
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- Wong Tien Y
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- Workalemahu Tsegaselassie
- Wright Alan F
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- Wu Joseph M W
- Wu Ying
- Würtz Peter
- Xiao Su-Mei
- Yajnik Chittaranjan S
- Yang Jian
- Yang Qiong
- Yang Tsun-Po
- Yao Jie
- Yengo Loïc
- Yerges-Armstrong Laura M
- Young Alicia
- Young Elizabeth H
- Young J H
- Young Lauren
- Yuan Xin
- Zaboli Ghazal
- Zalloua Pierre A
- Zarrabeitia María T
- Zelenika Diana
- Zemunik Tatijana
- Zerbini Gianpaolo
- Zgaga Lina
- Zhai Guangju
- Zhang Feng
- Zhang Qunyuan
- Zhang Weihua
- Zhao Jing Hua
- Zhao Wei
- Zheng Hou-Feng
- Zheng Wei
- Zhou Yanhua
- Zhu Haidong
- Zhu Kun
- Zhu Xiaofeng
- Zhuang Wei V
- Zhuang Wei Vivian
- Ziegler Andreas
- Zillikens M Carola
- Zimmermann Martina E
- Zitting Paavo
- Zondervan Krina T
- Zukowska-Szczechowska Ewa
- Zygmunt Marek
- Ärnlöv Johan
- Österholm Anne-May
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- 01/01/2015
- Field of study
Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms
Finishing the euchromatic sequence of the human genome
- Author
- . Haifeng
- . Magner
- . Yin
- Abbott Scott
- Abbott-Ozersky Amanda
- Abdellah Zahra
- Abouelleil Amr
- Abrajano Anne
- Adachi Tamami
- Adam Catherine
- Adams Charles Q.
- Adamson Aaron
- Adekoya Emmanuel
- Adio-Oduola Babajide
- Aerts Andrea
- Aggarwal Arun
- Ahmadi Alireza
- Ahmed Shahana
- Aimable Matthew
- Ainscough Rachael
- Ait-Zahra Mostafa
- Aizu Tomoyuki
- Alcivare Dana
- Alegria Michelle
- Ali Alla
- Ali Johar
- Allegria-hartmann Michelle
- Alleman Jennifer
- Allen Carlana C.
- Allen Heather
- Allen Nicole R.
- Allen Susan
- Allen Thaddeus
- Almeida Jeff
- Almond Claire
- Alsbrooks Stephen L.
- Altherr Michael R.
- Amaratunge Harshinie C.
- Ambler Andrew
- Ambrose Karen
- Ambrose Kerrie
- Amemiya Chris
- Amico-Keller Gina
- Amin Amita G.
- Anderson Mechele
- Anderson Scott
- Anderson Scott
- Andora Janice
- Andredesz Carol
- Andrew Robert
- Andrews Dan
- Andrews Daniel
- Andrews Neil
- Andrews Stephanie
- Andriese Tim
- Anthouard Véronique
- Antonarakis Stylianos E.
- Anyalebechi Vivian
- Aoki Norie
- Apostolou Sinoula
- Apweiler Eva
- Arachchi Harindra
- Arai Rie
- Arbery Hazel
- Arcaina Marlon
- Arcaina Terisita
- Archer Beth
- Arellano Andre
- Arellano-Jones Perry
- Armbruster Jeff
- Armstrong Jon
- Arredondo Dilrukshi P.
- Arredondo Heather Hope
- Artiguenave François
- Asakawa Shuichi
- Asakawa Teruyo
- Ash Gareth
- Ashcroft Kevin
- Ashurst Jennifer
- Ashwell Robert
- Ashworth Linda K.
- Aslanidis Cara
- Asomugha Chinwe O.
- Asuncion Lawreen
- Atkin Deborah
- Atkinson Andrea
- Atkinson Barry
- Attix Cristina
- Attwood John
- Aubin Keith
- Auger Katherine
- Austin Shannon Michelle
- Avila Aaron
- Avis Terry
- Ayele Mulu
- Babayan Primo
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- Bach Phil
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- Badri Hummy
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- Bateman Alex
- Bates Karen
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- Batzer Mark
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- Baynes Caroline
- Bayul Tashi
- Beall Keith
- Beard Lisa
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- Beare David
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- Bituin Aleksandr
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- Chen Hsiu-Chuan
- Chen Jianlong
- Chen Jie
- Chen Jin
- Chen Junbao
- Chen Lihong
- Chen Lixia
- Chen Ray
- Chen Shu
- Chen Tong
- Chen Xiaoyun
- Chen Xinyi
- Chen Yanjiong
- Chen Yiyu
- Chen Zhu
- Chen Zhu
- Chen Zhu
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- Cheng Zhihua
- Chertkov Olga
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- Clee Chris
- Clegg Shelia
- Clerc Blankenburg Kerstin Petra
- Cleveland David
- Clifford Karen
- Clifton Sandra W.
- Coates Julia
- Cobley Victoria
- Cockrell Raynard
- Coffey Alison
- Cofield Jackie
- Coggill Penelope
- Cohn Judith D.
- Colayco Rick
- Cole Lotte
- Collier Rachael
- Collings Simon
- Collins Francis S.
- Collins John
- Collins Philip
- Collymore Al
- Colman Louise
- Combs Jessie
- Comstock Robin
- Cong Bin
- Conner Richard
- Connolly Anthony
- Connolly Karen
- Conquer Jennie
- Conrad Ansgar
- Conroy Donald
- Considine Tony
- Constance Doug
- Cook April
- Cook Leanna
- Cooke Patrick
- Cooper Jonathan
- Cooper Rachel
- Cooper Robert
- Copeland Alex
- Coppola Maria
- Copsey Teresa
- Corby Nicole
- Cordes Matt
- Cordray Rebecca
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- Cornell Ruth
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- Crawley Matt
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- Crespeau Hervé
- Crew Victor
- Critchlow Terrance
- Critz Paul
- Cruaud Corinne
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- Dawson Elisabeth
- De Anda Claudia
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- Dearden Frances
- DeArellano Kurt
- Deaven Larry I.
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- Zhang Haiqing
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- Zhang Xianglin
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- Zhang Xiuqing
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- Zhang Yi
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- Zhang Yilin
- Zhang Ying
- Zhang Yuansen
- Zhang Yuzhi
- Zhang Zhengdong
- Zhao Hongmei
- Zhao Lijian
- Zhao Shenru
- Zhao Zhijing
- Zhen Zhicheng
- Zheng Haibo
- Zhong Ming
- Zhou Carol
- Zhou Haixia
- Zhou Jianling
- Zhou Nannan
- Zhou Xinfeng
- Zhou Yan
- Zhou Yang
- Zhou Yi
- Zhu Bingying
- Zhu Bofeng
- Zhu Fenghua
- Zhu Genfeng
- Zhu Genfeng
- Zhu Miao
- Zhu Ning
- Zhu Yongge
- Zhu Zhen
- Zhuang Shitao
- Zierten Deborah
- Zimmer Andrew
- Zody Michael C.
- Zollo Massimo
- Zorrilla Sara E.
- Zuo Lin
- Publication venue
- LSU Digital Commons
- Publication date
- 21/10/2004
- Field of study
The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead
Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease
- Author
- Aaltonen M
- Abdur Rahman M
- Abell T
- Abide W. Jr
- Acheatel R
- Achiri P
- Acon J
- Adams T
- Affinito S
- Agarwal S
- Aggarwal K
- Aggarwal R
- Ahlström P
- Ahmad A
- Ahmed M
- Aillon C
- Airaksinen A
- Ait-sadi R
- Akers J
- Al-jumaily J
- Albers C
- Albert M
- Alberti A
- Alexander T
- Alford C
- Algotsson L
- Allen T
- Allworth M
- Almond E
- Aloisi A
- Alternburg C
- Alton M
- Amin J
- Amundson A
- Andersen K
- Andersen M
- Anderson E
- Anderson G
- Anderson R
- Anderson T
- Andersson H
- Andersson L
- Andreo J
- Andres C
- Andresen D
- Andrews G
- Andrews L
- Andrews R
- Andrioli V
- Angermann Ce
- Annas T
- Ansell V
- Antonio-drabek C
- Antonishen D
- Antonishen M
- Anuschek V
- Appel Kf
- Appel S
- Appleyard D
- Archer A
- Armitage J
- Armstrong L
- Armstrong M
- Arnesson K
- Arnold M
- Arora P
- Arp H
- Asbill B
- Ashbrook-raby C
- Ashton L
- Assarsson E
- Audet K
- Augenbraun C
- Aung HNIN THANDA
- Auscher S
- Ausner J
- Aviles R
- Awasty V
- Axelsson U
- Ayers S
- Ayub H
- Babar G
- Babington G
- Backlund M
- Badal B
- Baggiore C
- Baghiana S
- Bai H
- Bai J
- Baigent C
- Baillargeon G
- Bakbak A
- Baker S
- Baldin Mg
- Baldini E
- Baldwin E
- Ballantyne C
- Baltic A
- Banerjee S
- Bang Hansen M
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- Zhao L
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- Zlatewa R
- Zoghbi J
- Zong C
- Zong D
- Zong X
- Zuchelkowski A
- Zulauf N
- Ågårdh A
- Öner A
- Publication venue
- 'Massachusetts Medical Society'
- Publication date
- 01/01/2017
- Field of study
BACKGROUND:
Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes.
METHODS:
We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization.
RESULTS:
During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events.
CONCLUSIONS:
Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .)
Comparative analysis of the transcriptome across distant species
- Author
- Adam Frankish
- Alex Dobin
- Alexandre Reymond
- Ali Mortazavi
- Anastasia Samsonova
- Andrea Tanzer
- Ann Hammonds
- Anurag Sethi
- Arif O. Harmanci
- AT Kalinka
- Baikang Pei
- Benjamin W. Booth
- BR Graveley
- Brent Ewing
- Brenton R. Graveley
- Brian Oliver
- Burak H. Alver
- Carrie A. Davis
- Chao Cheng
- Chao Di
- Chau Huynh
- Chenghai Xue
- Chris Zaleski
- Cristina Sisu
- Cédric Howald
- D Brawand
- Daifeng Wang
- David M. Miller
- DF Simola
- Dionna Kasper
- Dmitri Pervouchine
- Elise A. Feingold
- Eric Lai
- Erik Ladewig
- Felix Schlesinger
- Frank J. Slack
- Gang Fang
- Garrett Robinson
- Gary I. Saunders
- Gemma May
- Gennifer Merrihew
- Guanjun Gao
- Guilin Wang
- Haiyan Huang
- Henry Zheng
- Huaien Wang
- J Merkin
- J Reichardt
- James B. Brown
- Jen Harrow
- Jiayu Wen
- Jing Leng
- Jingyi Jessica Li
- JJ Li
- JM Stuart
- Joel Rozowsky
- Jorg Drenkow
- Julien Lagarde
- Kathie L. Watkins
- Kejia Wen
- Kenneth H. Wan
- Kevin Yip
- Kimberly Bell
- KK Yan
- Koon-Kiu Yan
- LaDeana Hillier
- Li Yang
- Long Hu
- Lucy Cherbas
- M Levin
- M Talerico
- Marcus H. Stoiber
- Mark B. Gerstein
- Masaomi Kato
- Max E. Boeck
- MB Gerstein
- Megan Fastuca
- Michael J. Pazin
- Michael MacCoss
- Michael O. Duff
- modENCODE Consortium
- Nathan P. Boley
- NL Barbosa-Morais
- Norbert Perrimon
- Owen A. Thompson
- Peter Cherbas
- Peter J. Bickel
- Peter J. Good
- Peter J. Park
- Pnina Strasbourger
- R Karlić
- Rabi Murad
- Raymond Auerbach
- Rebecca McWhirter
- Robert R. Kitchen
- Robert Waterston
- Roderic Guigó
- Roger A. Hoskins
- Roger P. Alexander
- S Djebali
- S Kirkpatrick
- Sara Olson
- Sarah Djebali
- Sonali Jha
- Steven E. Brenner
- Susan E. Celniker
- T Domazet-Lošo
- Thomas C. Kaufman
- Thomas R. Gingeras
- Tim J. P. Hubbard
- Valerie Reinke
- William C. Spencer
- Yan Zhang
- Zhi Lu
- ZJ Lu
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- 01/01/2014
- Field of study
The transcriptome is the readout of the genome. Identifying common features in it across distant species can reveal fundamental principles. To this end, the ENCODE and modENCODE consortia have generated large amounts of matched RNA-sequencing data for human, worm and fly. Uniform processing and comprehensive annotation of these data allow comparison across metazoan phyla, extending beyond earlier within-phylum transcriptome comparisons and revealing ancient, conserved features. Specifically, we discover co-expression modules shared across animals, many of which are enriched in developmental genes. Moreover, we use expression patterns to align the stages in worm and fly development and find a novel pairing between worm embryo and fly pupae, in addition to the embryo-to-embryo and larvae-to-larvae pairings. Furthermore, we find that the extent of non-canonical, non-coding transcription is similar in each organism, per base pair. Finally, we find in all three organisms that the gene-expression levels, both coding and non-coding, can be quantitatively predicted from chromatin features at the promoter using a 'universal model' based on a single set of organism-independent parameters
31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two
- Author
- Abassi Yama
- Abelin Jennifer G
- Abolhalaj Milad
- Abraham Tara S
- Adam Ammar
- Adams David
- Adams Homer
- Adams Sarah F
- Adamus Tomasz
- Addepalli Murali
- Addepalli Murali
- Adjei Alex A
- Agapova Larissa
- Agarwala Sanjiv
- Ager Casey
- Aggarwal Charu
- Agnello Giulia
- Agudo Judith
- Aguilar Ethan G
- Aguilera Todd
- Ahamadi Malidi
- Ahn Yong-Oon
- Ahrens Eric T
- Aizer Ayal
- Ajina Reham
- Akerley Wallace
- Al-Muftah Mariam
- Albershardt Tina C
- Albershardt Tina C
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- Fantini Massimo
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- Faustman Denise
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- Franklin Wilbur
- Frascaro Federica
- Fraser Kathryn
- Frederix Kim
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- Yao Shiyin
- Ye Yun-bin
- Yin Catherine
- Ylösmäki Erkko
- Ylösmäki Erkko
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- Young Kristina
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- Young Steve W
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- Yu Huakui
- Yu Ling
- Yu Naichen
- Zafar Sadia
- Zalevsky Jonathan
- Zalevsky Jonathan
- Zalevsky Jonathan
- Zalevsky Jonathan
- Zappasodi Roberta
- Zappasodi Roberta
- Zauderer Maurice
- Zeh Herbert
- Zelenetz Andrew D
- Zeng Weiping
- Zeng Xue
- Zha Yuanyuan
- Zhang Danhui
- Zhang Jing
- Zhang Ping
- Zhang Qifang
- Zhang Shannon S
- Zhang Theresa
- Zhang Winter
- Zhang Yanping
- Zhao Fei
- Zhao Leyna
- Zhao Xingli
- Zheng Lianxing
- Zheng Wenxin
- Zheng Xianxian
- Zheng Yi
- Zhong Hong
- Zhou Li
- Zhou Xiangjun
- Zippelius Alfred
- Zloza Andrew
- Zloza Andrew
- Zloza Andrew
- Zloza Andrew
- Zloza Andrew
- Zou Jun
- Zuba-Surma Ewa
- Zubkova Olga
- Zureikat Amer
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- 01/01/2016
- Field of study
Background
The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd.
Methods
We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background.
Results
First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001).
Conclusions
In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival
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- Aali Amirali
- Ababneh Hazim S
- Abate Yohannes Habtegiorgis
- Abbafati Cristiana
- Abbasgholizadeh Rouzbeh
- Abbasi-Kangevari Mohsen
- Abbasian Mohammadreza
- Abbastabar Hedayat
- Abd ElHafeez Samar
- Abd-Elsalam Sherief
- Abdelmasseh Michael
- Abdelwahab Ahmed
- Abdollahi Mohammad
- Abdollahifar Mohammad-Amin
- Abdoun Meriem
- Abdulah Deldar Morad
- Abdullahi Auwal
- Abebe Mesfin
- Abebe Samrawit Shawel
- Abedi Aidin
- Abegaz Kedir Hussein
- Abhilash E S
- Abidi Hassan
- Abiodun Olumide
- Aboagye Richard Gyan
- Abolhassani Hassan
- Abolmaali Meysam
- Abouzid Mohamed
- Aboye Girma Beressa
- Abreu Lucas Guimarães
- Abrha Woldu Aberhe
- Abtahi Dariush
- Abu Rumeileh Samir
- Abu-Gharbieh Eman
- Abu-Rmeileh Niveen ME
- Abu-Zaid Ahmed
- Abualruz Hasan
- Abubakar Bilyaminu
- Aburuz Salahdein
- Accrombessi Manfred Mario Kokou
- Adal Tadele Girum
- Adamu Abdu A
- Addo Isaac Yeboah
- Addolorato Giovanni
- Adebiyi Akindele Olupelumi
- Adekanmbi Victor
- Adepoju Abiola Victor
- Adetunji Charles Oluwaseun
- Adetunji Juliana Bunmi
- Adeyeoluwa Temitayo Esther
- Adeyinka Daniel Adedayo
- Adeyomoye Olorunsola Israel
- Admass Biruk Adie Adie
- Adnani Qorinah Estiningtyas Sakilah
- Adra Saryia
- Afolabi Aanuoluwapo Adeyimika
- Afzal Muhammad Sohail
- Afzal Saira
- Agampodi Suneth Buddhika
- Agasthi Pradyumna
- Aggarwal Manik
- Aghamiri Shahin
- Agide Feleke Doyore
- Agodi Antonella
- Agrawal Anurag
- Agyemang-Duah Williams
- Ahinkorah Bright Opoku
- Ahmad Aqeel
- Ahmad Danish
- Ahmad Firdos
- Ahmad Muayyad M
- Ahmad Sajjad
- Ahmad Shahzaib
- Ahmad Tauseef
- Ahmadi Keivan
- Ahmadzade Amir Mahmoud
- Ahmed Ali
- Ahmed Ayman
- Ahmed Haroon
- Ahmed Luai A
- Ahmed Mehrunnisha Sharif
- Ahmed Meqdad Saleh
- Ahmed Muktar Beshir
- Ahmed Syed Anees
- Ajami Marjan
- Aji Budi
- Akara Essona Matatom
- Akbarialiabad Hossein
- Akinosoglou Karolina
- Akinyemiju Tomi
- Akkaif Mohammed Ahmed
- Akyirem Samuel
- Al Hamad Hanadi
- Al Hasan Syed Mahfuz
- Al-Aly Ziyad
- Al-amer Rasmieh Mustafa
- Al-Azzam Sayer
- Al-Gheethi Adel Ali Saeed
- Al-Hanawi Mohammed Khaled
- Al-Marwani Sabah
- Al-Maweri Sadeq Ali Ali
- Al-Mekhlafi Hesham M
- Al-Omari Basem
- Al-Sabah Salman Khalifah
- Al-Tawfiq Jaffar A
- Al-Worafi Yaser Mohammed
- Alahdab Fares
- Alalalmeh Samer O
- Alalwan Tariq A
- Alam Khurshid
- Alam Manjurul
- Alam Noore
- Alanezi Fahad Mashhour
- Alanzi Turki M
- Albakri Almaza
- Albashtawy Mohammed
- AlBataineh Mohammad T
- Alcalde-Rabanal Jacqueline Elizabeth
- Aldawsari Khalifah A
- Aldhaleei Wafa A
- Aldridge Robert W
- Alema Haileselasie Berhane
- Alemayohu Mulubirhan Assefa
- Alemi Sharifullah
- Alemu Yihun Mulugeta
- Alhabib Khalid F
- Alhalaiqa Fadwa Alhalaiqa Naji
- Ali Abid
- Ali Amjad
- Ali Liaqat
- Ali Mohammed Usman
- Ali Rafat
- Ali Shahid
- Ali Syed Shujait Shujait
- Alicandro Gianfranco
- Alif Sheikh Mohammad
- Alikhani Reyhaneh
- Alimohamadi Yousef
- Aliyi Ahmednur Adem
- Aljasir Mohammad A M
- Aljunid Syed Mohamed
- Alla François
- Allebeck Peter
- Almazan Joseph Uy
- Almidani Louay
- Almidani Omar
- Alomari Mahmoud A
- Alonso Jordi
- Alqahtani Jaber S
- Alqalyoobi Shehabaldin
- Alqutaibi Ahmed Yaseen
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- Aluh Deborah Oyine
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- Amani Reza
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- Amegbor Prince M
- Ameyaw Edward Kwabena
- Amin Tarek Tawfik
- Amindarolzarbi Alireza
- Amiri Sohrab
- Amirzade-Iranaq Mohammad Hosein
- Amu Hubert
- Amugsi Dickson A
- Amusa Ganiyu Adeniyi
- Ancuceanu Robert
- Anderlini Deanna
- Anderson David B
- Andrade Pedro Prata
- Andrei Catalina Liliana
- Andrei Tudorel
- Angus Colin
- Anil Abhishek
- Anil Sneha
- Anoushiravani Amir
- Ansari Hossein
- Ansari-Moghaddam Alireza
- Ansariadi Ansariadi
- Antony Catherine M
- Antriyandarti Ernoiz
- Anvari Davood
- Anvari Saeid
- Anwar Saleha
- Anwar Sumadi Lukman
- Anwer Razique
- Anyasodor Anayochukwu Edward
- Aqeel Muhammad
- Arab Juan Pablo
- Arabloo Jalal
- Arafat Mosab
- Aravkin Aleksandr Y
- Areda Demelash
- Aremu Abdulfatai
- Aremu Olatunde
- Ariffin Hany
- Arkew Mesay
- Armocida Benedetta
- Arndt Michael Benjamin
- Arooj Mahwish
- Artamonov Anton A
- Arulappan Judie
- Aruleba Raphael Taiwo
- Arumugam Ashokan
- Asaad Malke
- Asadi-Lari Mohsen
- Asgedom Akeza Awealom
- Asghari-Jafarabadi Mohammad
- Asghariahmadabad Mona
- Ashraf Muhammad
- Aslani Armin
- Astell-Burt Thomas
- Athar Mohammad
- Athari Seyyed Shamsadin
- Atinafu Bantalem Tilaye Tilaye
- Atlaw Habtamu Wondmagegn
- Atorkey Prince
- Atout Maha Moh'd Wahbi
- Atreya Alok
- Aujayeb Avinash
- Ausloos Marcel
- Avan Abolfazl
- Awedew Atalel Fentahun
- Aweke Amlaku Mulat
- Ayala Quintanilla Beatriz Paulina
- Ayatollahi Haleh
- Ayuso-Mateos Jose L
- Ayyoubzadeh Seyed Mohammad
- Azadnajafabad Sina
- Azevedo Rui M S
- Azzam Ahmed Y
- B Darshan B
- Babu Abraham Samuel
- Badar Muhammad
- Badiye Ashish D
- Baghdadi Soroush
- Bagheri Nasser
- Bagherieh Sara
- Bah Sulaiman
- Bahadorikhalili Saeed
- Bahmanziari Najmeh
- Bai Ruhai
- Baig Atif Amin
- Baker Jennifer L
- Bako Abdulaziz T
- Bakshi Ravleen Kaur
- Balakrishnan Senthilkumar
- Balasubramanian Madhan
- Baltatu Ovidiu Constantin
- Bam Kiran
- Banach Maciej
- Bandyopadhyay Soham
- Banik Palash Chandra
- Bansal Hansi
- Bansal Kannu
- Barbic Franca
- Barchitta Martina
- Bardhan Mainak
- Bardideh Erfan
- Barker-Collo Suzanne Lyn
- Barone-Adesi Francesco
- Barqawi Hiba Jawdat
- Barrero Lope H
- Barrow Amadou
- Barteit Sandra
- Barua Lingkan
- Basharat Zarrin
- Bashiri Azadeh
- Basiru Afisu
- Baskaran Pritish
- Basnyat Buddha
- Bassat Quique
- Basso João Diogo
- Basting Ann V L
- Basu Sanjay
- Batra Kavita
- Baune Bernhard T
- Bayati Mohsen
- Bayileyegn Nebiyou Simegnew
- Beaney Thomas
- Bedi Neeraj
- Beghi Massimiliano
- Behboudi Emad
- Behera Priyamadhaba
- Behnoush Amir Hossein
- Behzadifar Masoud
- Beiranvand Maryam
- Bejarano Ramirez Diana Fernanda
- Belay Sefealem Assefa
- Belete Chalie Mulu
- Bell Michelle L
- Bello Muhammad Bashir
- Bello Olorunjuwon Omolaja
- Belo Luis
- Beloukas Apostolos
- Bender Rose Grace
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- Xu Xiaoyue
- Xu Yvonne Yiru
- Yadollahpour Ali
- Yamagishi Kazumasa
- Yang Danting
- Yang Lin
- Yano Yuichiro
- Yao Yao
- Yaribeygi Habib
- Ye Pengpeng
- Yehualashet Sisay Shewasinad
- Yesiltepe Metin
- Yesuf Subah Abderehim
- Yezli Saber
- Yi Siyan
- Yigezu Amanuel
- Yip Paul
- Yismaw Malede Berihun
- Yismaw Yazachew
- Yiğit Arzu
- Yiğit Vahit
- Yon Dong Keon
- Yonemoto Naohiro
- Yoon Seok-Jun
- You Yuyi
- Younis Mustafa Z
- Yousefi Zabihollah
- Yu Chuanhua
- Yu Yong
- Yuh Faith H
- Zadey Siddhesh
- Zadnik Vesna
- Zafari Nima
- Zakham Fathiah
- Zaki Nazar
- Zaman Sojib Bin
- Zamora Nelson
- Zand Ramin
- Zangiabadian Moein
- Zar Heather J
- Zare Iman
- Zarrintan Armin
- Zeariya Mohammed G M
- Zeinali Zahra
- Zhang Haijun
- Zhang Jianrong
- Zhang Jingya
- Zhang Liqun
- Zhang Yunquan
- Zhang Zhi-Jiang
- Zhao Hanqing
- Zhong Chenwen
- Zhou Juexiao
- Zhu Bin
- Zhu Lei
- Ziafati Makan
- Zielińska Magdalena
- Zitoun Osama A
- Zoladl Mohammad
- Zou Zhiyong
- Zuhlke Liesl J
- Zumla Alimuddin
- Zweck Elric
- Zyoud Samer H
- Ärnlöv Johan
- Šekerija Mario
- Publication venue
- Elsevier
- Publication date
- 03/04/2024
- Field of study
BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation
Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study
- Author
- A. Mohammed Kalakwa
- A. Nemer Ayoub
- Abantanga Francis A.
- Abatli Safa' Jamal
- Abbas Wisam
- Abbo Olivier
- Abdelbaqi Reem
- Abdelhady Dina Sobhy
- Abdelhafez Mohammad Omar Mohammad
- Abdelhamid Sultan S.
- Abdelmaksoud Sherif
- Abdelmoumen Roua
- Abdelmutalib Fakereldeen
- Abdul-Mumin Alhassan
- Abduljawad Fatima Mousa
- Abdullah Fizan
- Abdullah Mohd Yusof bin
- Abdulraheem Nurudeen
- Abdulrahman Alaa
- Abdulsalam Moruf Adekunle
- Abdunomonovich Dekhkonboev Avazjon
- Aboelela Ahmed
- Abouheba Mohamed
- Abrahamsson Kate
- Abrunhosa Matias Marcia
- Abu-Nejmah Fawzi
- Abuajaila Abdulsalam
- Abuattaya Adham Ashraf
- Abubakar Auwal M
- Abueideh Ahmad
- Abuhayyeh Husam Aldean
- Abuhlega Ma'aly A.
- Abukhalaf Sadi
- Abumunshar Ali Abdelhay
- Acuna Gaston
- Adams Stephen
- Adamu Sani
- Adanan Mohd Fitri Shukri bin Mohamed
- Adawi Ihda
- Adawi Samer
- Adawy Ahmad
- Ade-Ajayi Niyi
- Adegboyega Rilwan
- Ademuyiwa Adesoji
- Adesanya Opeoluwa
- Adhiwidjaja Cathline Freya
- Adofo-Ansong Nana
- Agboola Titiloye Hannah
- Agelebe Efeturi
- Aguilar Aguilar Faye
- Aguilar Gargurevich Prince Pamela
- Aguirre-Lopez Pastor
- Agulham Miguel Angelo
- Ahmad Hira
- Ahmad Zahidah Adlynee Haji
- Ahmed Hazem
- Ahmed Mahmoud Abdelfattah
- Ajai Olalekan Temitope
- Ajao Emmanuel Akinlabi
- Ajiboye Olalekan S.
- Ajrami Yara
- Ajwa Ahmad Elian Abu
- Akan M. Eren
- Akhbari Melika
- Akhter Nadeem
- Akova Fatih
- Al-Attar Hala M.
- Al-Halbouni Layana
- Al-Mamun Abdullah
- Al-Mayoof Ali Farooq
- Al-Momani Hashem M.
- Al-Mouakeh Ahmad
- Al-Rayyes Maisara
- Al-saleem Hasan Subhi Hasan Abu
- Al-Salhi Ashraf Ayman
- Al-Shwaikh Samar H.
- Al-Slaibi Ibrahim
- Al-Taher Raed Nael
- Al-Taher Raed Nael
- Al-Tammam Hiba
- Alakaloko Felix
- Alamrain Abdulwhhab Ayman Abu
- Alanguia Chipana Cathy Lee
- Alattas Khalid
- Alberto Carlos
- Albozidi Aya
- Alcántara Elvyn
- ALDIRAWI MOHAMMED A. M.
- Alebbini Mohanad Mutasem
- Alfoghi Mabroka
- Algabri Hayder Nadhim Obaid
- Alglaib Mohammed Meftah
- Alhamid Ahmad
- Alhamid Aos
- Alhassan Priscilla
- Ali Hassan
- Ali Karim Osamy
- Ali Liza
- Ali Mansour
- Alijla Sharif
- Alijla Sharif S.
- Aliwisat Ahmad Hasan
- Aljaboo Hajir
- Aljadidi Wesal Omar F. Saied
- Aljarad Ziad
- Alkareem Raghad mohammad abdu
- Almada Suad Ahmed
- Almadhoun Walaa
- Almasri Murad
- Almeida Aguiar Arthur
- Almeida Giovana
- Almengar Inas
- Almohamady Hisham
- Almosaibli Mohammad
- Almusleh Tasneem Fathi Hasan
- Alnaeri Ali
- Alnahhal Khaled
- Alonso Verónica
- Alosta Hasan Mustafa
- Alqarajeh Firas
- Alqor Mohammad Omar Ibrahim
- Alsaadi Nijmeh Nasser
- Alsaggaf Ameen
- Alsaied Amer
- Alser Mohammed
- Alser Osaid H.
- Alshaikhkhalil Haya Abdulnasser Ali
- Alshehri Abdullah
- Altaweel Ahmed
- Altın Merve
- Altokhais Tariq
- Altomi Mohamed
- Alturki Fahad
- Alvarado Zelada Jackelyne
- Alves Dutra da Silva Érika
- Alwadia Soha Marwan Salem
- Alwaggaa Nouriyah Ali
- Alzamari Ainaa Ata Mohammad
- Alzate Gallego Edgar
- Alzeer Asmahan Mohammad Suliman
- Alzerei Sulaiman T.
- Alzraikat Sayel H.
- Alzubair Afnan
- Alzughayyar Tareq Z.
- Amad Mohamed
- Amado Fernando
- Amaechi Chukwubinyelum
- Amah Christopher Chim
- Amarin Justin Z.
- Amarin Marzouq
- Ambriz-González Gabriela
- Ameh Emmanuel
- Amjad Muhammad Bin
- Amoabin Afua Amoabin
- Anatole Nzanzu
- Anatole Nzanzu Kipata
- Anaya Dominguez Marlene
- Anaya Firas
- Andrade Jerhy
- Andreussi Lorna
- Anicama Elias Rocio
- Annajjar Mohammad hasan
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- Arancibia Gutiérrez Elsa
- Aranda Sánchez Cristian Irela
- Arar Ahmad Samih
- Arauco Jenny
- Arbab Hana
- Arboleda Jenny
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- Arnaud Alexis P
- Arnold Marion
- Arnoletto Lucia Beatriz
- Arrmali Saddam
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- Darwish Ahmed S
- Darwish Ammar
- Dass Anthony
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- de Assis Silva Murilo
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- dos Santos Dias André Iván Bradley
- Dosselman Luke J.
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- Løfberg Katrine
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- Martinez-Leo Bruno
- Martins Bianca M. R.
- Martínez Hernández Magro Nestor
- Mary Koshy Roshine
- Massry Nasrallah Ashraf Al
- Matour Bashar M.
- Mayaleh Abdelrazzaq Abu
- Mbonicura Jean Claude
- Mbonisweni Akhona
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- Wong Marilyn
- Wright Naomi Jane
- Wu Guowei
- Wyrzykowski Dariusz
- Xiaodong Guo
- Xie Hua
- Yacoub Mina A.
- Yaghi Bashar
- Yaghi Dua Hasan
- Yalcinkaya Ali
- Yang Hee-Beom
- Yanis Ahmad H.
- Yanowsky Reyes Guillermo
- Yao Yang
- Yapo Benjamin
- Yarza Fernández Jessica
- Yeniay Aslı Öztürk
- Yola Mariya Mukhtar
- Yong Feng
- Youn Joong Kee
- Yousuf Hina
- Yu Mengnan
- Yu Raisa
- Yuen Quah Soong
- Yuldashev Rustam Z.
- Yunus Aayenah
- Za'nouneh Faris J. Abu
- Zaghlol Louay Y.
- Zahari Dato' Dr Zakaria bin
- Zain Mostafa
- Zaman Azrina SK
- Zanellato Josiane Bernartt
- Zarwawi Ahmad Zulhisyam bin
- Zea-Salazar Luis Enrique
- Zeinelabdeen Ali
- Zhao Xiaoxia
- Zhu Jianming
- Zhu Libin
- Zidan Mazen
- Zivanovic Dragoljub
- Zottis Barcelos Fabricio
- Zreeg Dafer abdulhakim . S.
- Zurikat Rajai O.
- Zvizdic Nada
- Zvizdic Zlatan
- Çekiç Bahanur
- Çelik Müge
- Özçelik Zerrin
- Şeref Kıvanç
- Šafus Antonín
- Škvařil Jan
- Štichhauer Radek
- Publication venue
- 'Elsevier BV'
- Publication date
- 01/01/2021
- Field of study
Summary
Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally.
Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies
have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of
the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income
countries globally, and identified factors associated with mortality.
Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to
hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis,
exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a
minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical
status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary
intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause,
in-hospital mortality for all conditions combined and each condition individually, stratified by country income status.
We did a complete case analysis.
Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital
diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal
malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome
countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male.
Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3).
Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income
countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups).
Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome
countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries;
p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients
combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11],
p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20
[1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention
(ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety
checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed
(ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of
parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65
[0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality.
Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome,
middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will
be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger
than 5 years by 2030
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