Transient Expression of Tetrameric Recombinant Human Butyrylcholinesterase in Nicotiana benthamiana.

To optimize the expression, extraction and purification of plant-derived tetrameric recombinant human butyrylcholinesterase (prBChE), we describe the development and use of plant viral amplicon-based gene expression system; Tobacco Mosaic Virus (TMV) RNA-based overexpression vector (TRBO) to express enzymatically active FLAG-tagged plant made recombinant butyrylcholinesterase (rBChE) in Nicotiana benthamiana leaves using transient agroinfiltration. Two gene expression cassettes were designed to express the recombinant protein in either the ER or to the apoplastic compartment. Leaf homogenization was used to isolate ER-retained recombinant butyrylcholinesterase (prBChE-ER) while apoplast-targeted rBChE was isolated by either leaf homogenization (prBChE) or vacuum-extraction of apoplastic wash fluid (prBChE-AWF). rBChE from apoplast wash fluid had a higher specific activity but lower enzyme yield than leaf homogenate. To optimize the isolation and purification of total recombinant protein from leaf homogenates, an acidic extraction buffer was used. The acidic extraction buffer yielded >95% enzymatically active tetrameric rBChE as verified by Coomassie stained and native gel electrophoresis. Furthermore, when compared to human butyrylcholinesterase, the prBChE was found to be similar in terms of tetramerization and enzyme kinetics. The N-linked glycan profile of purified prBChE-ER was found to be mostly high mannose structures while the N-linked glycans on prBChE-AWF were primarily complex. The glycan profile of the prBChE leaf homogenates showed a mixture of high mannose, complex and paucimannose type N-glycans. These findings demonstrate the ability of plants to produce rBChE that is enzymatically active and whose oligomeric state is comparable to mammalian butyrylcholinesterase. The process of plant made rBChE tetramerization and strategies for improving its pharmacokinetics properties are also discussed

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p<0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (<1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (<1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

Finishing the euchromatic sequence of the human genome

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

The type II secreted lipase/esterase LesA is a key virulence factor required for Xylella fastidiosa pathogenesis in grapevines

Pierce’s disease (PD) of grapevines is caused by Xylella fastidiosa (Xf), a xylem-limited gamma-proteobacterium that is responsible for several economically important crop diseases. The occlusion of xylem elements and interference with water transport by Xf and its associated biofilm have been posited as the main cause of PD symptom development; however, Xf virulence mechanisms have not been described. Analysis of the Xf secretome revealed a putative lipase/esterase (LesA) that was abundantly secreted in bacterial culture supernatant and was characterized as a protein ortholog of the cell wall-degrading enzyme LipA of Xanthomonas strains. LesA was secreted by Xf and associated with a biofilm filamentous network. Additional proteomic analysis revealed its abundant presence in outer membrane vesicles (OMVs). Accumulation of LesA in leaf regions associated positively with PD symptoms and inversely with bacterial titer. The lipase/esterase also elicited a hypersensitive response in grapevine. Xf lesA mutants were significantly deficient for virulence when mechanically inoculated into grapevines. We propose that Xf pathogenesis is caused by LesA secretion mediated by OMV cargos and that its release and accumulation in leaf margins leads to early stages of observed PD symptoms

Transient Expression of Tetrameric Recombinant Human Butyrylcholinesterase in Nicotiana benthamiana.

To optimize the expression, extraction and purification of plant-derived tetrameric recombinant human butyrylcholinesterase (prBChE), we describe the development and use of plant viral amplicon-based gene expression system; Tobacco Mosaic Virus (TMV) RNA-based overexpression vector (TRBO) to express enzymatically active FLAG-tagged plant made recombinant butyrylcholinesterase (rBChE) in Nicotiana benthamiana leaves using transient agroinfiltration. Two gene expression cassettes were designed to express the recombinant protein in either the ER or to the apoplastic compartment. Leaf homogenization was used to isolate ER-retained recombinant butyrylcholinesterase (prBChE-ER) while apoplast-targeted rBChE was isolated by either leaf homogenization (prBChE) or vacuum-extraction of apoplastic wash fluid (prBChE-AWF). rBChE from apoplast wash fluid had a higher specific activity but lower enzyme yield than leaf homogenate. To optimize the isolation and purification of total recombinant protein from leaf homogenates, an acidic extraction buffer was used. The acidic extraction buffer yielded >95% enzymatically active tetrameric rBChE as verified by Coomassie stained and native gel electrophoresis. Furthermore, when compared to human butyrylcholinesterase, the prBChE was found to be similar in terms of tetramerization and enzyme kinetics. The N-linked glycan profile of purified prBChE-ER was found to be mostly high mannose structures while the N-linked glycans on prBChE-AWF were primarily complex. The glycan profile of the prBChE leaf homogenates showed a mixture of high mannose, complex and paucimannose type N-glycans. These findings demonstrate the ability of plants to produce rBChE that is enzymatically active and whose oligomeric state is comparable to mammalian butyrylcholinesterase. The process of plant made rBChE tetramerization and strategies for improving its pharmacokinetics properties are also discussed

Global multi-stakeholder endorsement of the MAFLD definition

none1055noneMendez-Sanchez N.; Bugianesi E.; Gish R.G.; Lammert F.; Tilg H.; Nguyen M.H.; Sarin S.K.; Fabrellas N.; Zelber-Sagi S.; Fan J.-G.; Shiha G.; Targher G.; Zheng M.-H.; Chan W.-K.; Vinker S.; Kawaguchi T.; Castera L.; Yilmaz Y.; Korenjak M.; Spearman C.W.; Ungan M.; Palmer M.; El-Shabrawi M.; Gruss H.-J.; Dufour J.-F.; Dhawan A.; Wedemeyer H.; George J.; Valenti L.; Fouad Y.; Romero-Gomez M.; Eslam M.; Abate M.L.; Abbas B.; Abbassy A.A.; Abd El Ghany W.; Abd Elkhalek A.; Abd ElMajeed E.; Abdalgaber M.; AbdAllah M.; Abdallah M.; Abdallah N.; Abdelaleem S.; Abdelghani Y.; Abdelghany W.; Abdelhalim S.M.; Abdelhamid W.; Abdelhamid N.; Abdelkader N.A.; Abdelkreem E.; Abdelmohsen A.M.; Abdelrahman A.A.; Abd-elsalam S.M.; Abdeltawab D.; Abduh A.; Abdulhakam N.; Abdulla M.; Abedpoor N.; Abenavoli L.; Aberg F.; Ablack O.; Abo elftouh M.; Abo-Amer Y.E.-E.; Aboubkr A.; Aboud A.; Abouelnaga A.M.; Aboufarrag G.A.; Aboutaleb A.; Abundis L.; Adali G.; Adames E.; Adams L.; Adda D.; Adel N.; Adel N.; Adel Sayed M.; Afaa T.J.; Afredj N.; Aghayeva G.; Aghemo A.; Aguilar-Salinas C.A.; Ahlenstiel G.; Ahmady W.; Ahmed W.; Ahmed A.; Ahmed S.N.; Ahmed H.M.; Ahmed R.; Aigner E.; Akarsu M.; Akroush M.; Akyuz U.; Al Mahtab M.; Al Qadiri T.; Al Rawahi Y.; AL rubaee R.; Al Saffar M.; Alam S.; Al-Ani Z.; Albillos A.; Alboraie M.; Al-Busafi S.; Al-Emam M.; Alharthi J.; Ali K.; Ali B.A.; Ali M.; Ali R.A.R.; Alisi A.; AL-Khafaji A.R.; Alkhatry M.; Aller R.; Almansoury Y.; Al-Naamani K.; Alnakeeb A.; Alonso A.; Alqahtani S.A.; Alrabadi L.; Alswat K.; Altaher M.; Altamimi T.; Altamirano J.; Alvares-da-Silva M.R.; Aly E.A.M.; Alzahaby A.; Alzamzamy A.; Amano K.; Amer M.A.; Amin M.A.; Amin S.A.; Amir A.A.; Ampuero J.; Anas N.; Andreone P.; Andriamandimby S.F.; Anees M.; Angela P.; Antonios M.; Arafat W.; Araya J.M.; Armendariz-Borunda J.; Armstrong M.J.; Ashktorab H.; Aspichueta P.; Assal F.; Atef M.; Attia D.; Atwa H.; Awad R.; Awad M.A.E.; Awny S.; Awolowo O.; Awuku Y.A.; Ayada I.; Aye T.T.; Ayman S.; Ayman H.; Ayoub H.; Azmy H.M.; Babaran R.P.; Badreldin O.; Badry A.; Bahcecioglu I.H.; Bahour A.; Bai J.; Balaban Y.; Balasubramanyam M.; Bamakhrama K.; Banales J.M.; Bangaru B.; Bao J.; Barahona J.S.; Barakat S.; Barbalho S.M.; Barbra B.; Barranco B.; Barrera F.; Baumann U.; Bazeed S.; Bech E.; Benayad A.; Benesic A.; Bernstein D.; Bessone F.; Birney S.; Bisseye C.; Blake M.; Bobat B.; Bonfrate L.; Bordin D.S.; Bosques-Padilla F.; Boursier J.; Boushab B.M.; Bowen D.; Bravo P.M.; Brennan P.N.; Bright B.; Broekaert I.; Buque X.; Burgos-Santamaria D.; Burman J.; Busetto L.; Byrne C.D.; Cabral-Prodigalidad P.A.I.; Cabrera-Alvarez G.; Cai W.; Cainelli F.; Caliskan A.R.; Canbay A.; Cano-Contreras A.; Cao H.-X.; Cao Z.; Carrion A.; Carubbi F.; Casanovas T.; Castellanos Fernandez M.I.; Chai J.; Chan S.P.; Charatcharoenwitthaya P.; Chavez-Tapia N.; Chayama K.; Chen J.; Chen L.; Chen Z.-W.; Chen H.; Chen S.-D.; Chen Q.; Chen Y.; Chen G.; Chen E.-Q.; Chen F.; Chen P.-J.; Cheng R.; Cheng W.; Chieh J.T.W.; Chokr I.; Cholongitas E.; Choudhury A.; Chowdhury A.; Chukwudike E.S.; Ciardullo S.; Clayton M.; Clement K.; Cloa M.M.; Coccia C.; Collazos C.; Colombo M.; Cosar A.M.; Cotrim H.P.; Couillerot J.; Coulibaly A.; Crespo G.; Crespo J.; Cruells M.; Cua I.H.Y.; Dabbous H.K.; Dalekos G.N.; D'Alia P.; Dan L.; Dao V.H.; Darwish M.; Datz C.; Davalos-Moscol M.B.; Dawoud H.; de Careaga B.O.; de Knegt R.; de Ledinghen V.; de Silva J.; Debzi N.; Decraecker M.; Del Pozo E.; Delgado T.C.; Delgado-Blanco M.; Dembinski L.; Depina A.; Derbala M.; Desalegn H.; Desbois-Mouthon C.; Desoky M.; Dev A.; Di Ciaula A.; Diago M.; Diallo I.; Diaz L.A.; Dirchwolf M.; Dongiovanni P.; Dorofeyev A.; Dou X.; Douglas M.W.; Doulberis M.; Dovia C.K.; Doyle A.; Dragojevic I.; Drenth J.P.; Duan X.; Dulskas A.; Dumitrascu D.L.; Duncan O.; Dusabejambo V.; Dwawhi R.S.N.A.; Eiketsu S.; El Amrousy D.; El Deeb A.; El Deriny G.; El Din H.S.; El Kamshishy S.; El Kassas M.; El Raziky M.; Elagamy O.A.; Elakel W.; Elalfy D.; Elaraby H.; ElAwady H.; Elbadawy R.; Eldash H.H.; Eldefrawy M.S.; Elecharri C.L.; Elfaramawy A.; Elfatih M.; Elfiky M.; Elgamsy M.; Elgendy M.; El-Guindi M.A.; Elhussieny N.; Eliwa A.M.; Elkabbany Z.; El-Khayat H.; El-Koofy N.M.; Elmetwalli A.; Elrabat A.; El-Raey F.; Elrashdy F.; Elsahhar M.; Elsaid E.M.; Elsayed S.; Elsayed H.; Elsayed A.; Elsayed A.M.; Elsayed H.; El-Serafy M.; Elsharkawy A.M.; Elsheemy R.Y.; Elshemy E.E.; Elsherbini S.; Eltoukhy N.; Elwakil R.; Emad O.; Emad S.; Embabi M.; Ergenc I.; Ermolova T.; Esmat G.; Esmat D.M.; Estupinan E.C.; Ettair S.; Eugen T.; Ezz-Eldin M.; Falcon L.P.V.; Fan Y.-C.; Fandari S.; Farag M.; Farahat T.M.; Fares E.M.; Fares M.; Fassio E.; Fathy H.; Fathy D.; Fathy W.; Fayed S.; Feng D.; Feng G.; Fernandez-Bermejo M.; Ferreira C.T.; Ferrer J.D.; Forbes A.; Fouad R.; Fouad H.M.; Frisch T.; Fujii H.; Fukunaga S.; Fukunishi S.; Fulya H.; Furuhashi M.; Gaber Y.; Galang A.J.G.; Gallardo J.C.; Galloso R.; Gamal M.; Gamal R.; Gamal H.; Gan J.; Ganbold A.; Gao X.; Garas G.; Garba T.; Garcia-Cortes M.; Garcia-Monzon C.; Garcia-Samaniego J.; Gastaldelli A.; Gatica M.; Gatley E.; Gegeshidze T.; Geng B.; Ghazinyan H.; Ghoneem S.; Giacomelli L.; Giannelli G.; Giannini E.G.; Giefer M.; Gines P.; Girala M.; Giraudi P.J.; Goh G.B.-B.; Gomaa A.A.; Gong B.; Gonzales D.H.C.; Gonzalez H.C.; Gonzalez-Huezo M.S.; Graupera I.; Grgurevic I.; Gronbaek H.; Gu X.; Guan L.; Gueye I.; Guingane A.N.; Gul O.O.; Gul C.B.; Guo Q.; Gupta P.P.; Gurakar A.; Gutierrez J.C.R.; Habib G.; Hafez A.; Hagman E.; Halawa E.; Hamdy O.; Hamed A.E.; Hamed D.H.; Hamid S.; Hamoudi W.; Han Y.; Haridy J.; Haridy H.; Harris D.C.H.H.; Hart M.; Hasan F.; Hashim A.; Hassan I.; Hassan A.; Hassan E.A.; Hassan A.A.; Hassan M.S.; Hassanin F.; Hassnine A.; Haukeland J.W.; Hawal A.I.M.; He J.; He Q.; He Y.; He F.-P.; Hegazy M.; Hegazy A.; Henegil O.; Hernandez N.; Hernandez-Guerra M.; Higuera-de-la-Tijera F.; Hindy I.; Hirota K.; Ho L.C.; Hodge A.; Hosny M.; Hou X.; Huang J.-F.; Huang Y.; Huang Z.; Huang Y.; Huang A.; Huang X.-P.; Hui-ping S.; Hunyady B.; Hussein M.A.; Hussein O.; Hussien S.M.; Ibanez-Samaniego L.; Ibdah J.; Ibrahim L.; Ibrahim M.; Ibrahim I.; Icaza-Chavez M.E.; Idelbi S.; Idilman R.I.; Ikeda M.; Indolfi G.; Invernizzi F.; Irshad I.; Isa H.M.A.; Iskandar N.J.; Ismaiel A.; Ismail M.; Ismail Z.; Ismail F.; Iwamoto H.; Jack K.; Jacob R.; Jafarov F.; Jafri W.; Jahshan H.; Jalal P.K.; Jancoriene L.; Janicko M.; Jayasena H.; Jefferies M.; Jha V.; Ji F.; Ji Y.; Jia J.; Jiang C.; Jiang N.; Jiang Z.-Z.; Jin X.; Jin Y.; Jing X.; Jingyu Q.; Jinjolava M.; Jong F.H.H.; Jucov A.; Julius I.; Kaddah M.; Kamada Y.; kamal A.; Kamal E.M.; Kamel A.S.; Kao J.-H.; Karin M.; Karlas T.; Kashwaa M.; Katsidzira L.; Kaya E.; Kayasseh M.A.; Keenan B.; Keklikkiran C.; Keml W.; Khalaf D.K.; Khalefa R.; Khamis S.; Khater D.; khattab H.; Khavkin A.; Khlynova O.; Khmis N.; Kobyliak N.; Koffas A.; Koike K.; Kok K.Y.Y.; Koller T.; Komas N.P.; Korochanskaya N.V.; Koulla Y.; Koya S.; Kraft C.; Kraja B.; Krawczyk M.; Kuchay M.S.; Kulkarni A.V.; Kumar A.; Kumar M.; Lakoh S.; Lam P.; Lan L.; Lange N.F.; Lankarani K.B.; Lanthier N.; Lapshyna K.; Lashen S.A.; Laure K.N.J.; Lazebnik L.; Lebrec D.; Lee S.S.; Lee W.S.; Lee Y.Y.; Leeming D.J.; Leite N.C.; Leon R.; Lesmana C.R.A.; Li J.; Li Q.; Li J.; Li Y.-Y.; Li Y.; Li L.; Li M.; li Y.; Liang H.; Lijuan T.; Lim S.G.; Lim L.-L.; Lin S.; Lin H.-C.; Lin R.; Lithy R.; Liu Y.; Liu Y.; Liu X.; Liu W.-Y.; Liu S.; Liu K.; Liu T.; Lonardo A.; Lopez M.B.; Lopez-Benages E.; Lopez-Jaramillo P.; Lu H.; Lu L.G.; Lu Y.; Lubel J.; Lui R.; Lupasco I.; Luzina E.; Lv X.-H.; Lynch K.; Ma H.-L.; Machado M.V.; Maduka N.; Madzharova K.; Magdaong R.; Mahadeva S.; Mahfouz A.; Mahmood N.R.K.N.; Mahmoud E.; Mahrous M.; Maiwall R.; Majeed A.; Majumdar A.; Mak L.; Maklouf M.M.; Malekzadeh R.; Mandato C.; Mangia A.; Mann J.; Mansour H.H.; Mansouri A.; Mantovani A.; Mao J.Q.; Maramag F.; Marchesini G.; Marcus C.; Marinho R.A.R.T.; Martinez-Chantar M.L.; Martins A.A.S.; Marwan R.; Mason K.F.; Masoud G.; Massoud M.N.; Matamoros M.A.; Mateos R.M.; Mawed A.; Mbanya J.C.; Mbendi C.; McColaugh L.; McLeod D.; Medina J.F.R.; Megahed A.; Mehrez M.; Memon I.; Merat S.; Mercado R.; Mesbah A.; Meskini T.; Metwally M.; Metwaly R.; Miao L.; Micah E.; Miele L.; Milivojevic V.; Milovanovic T.; Mina Y.L.; Mishkovik M.; Mishriki A.; Mitchell T.; Mohamed A.; Mohamed M.; Mohamed S.; Mohammed S.; Mohammed A.; Mohan V.; Mohie S.; Mokhtar A.; Moniem R.; Montilla M.S.; Morales J.A.O.; Morata M.M.S.; Moreno-Planas J.M.; Morise S.; Mosaad S.; Moselhy M.; Mostafa A.M.; Mostafa E.; Mouane N.; Mousa N.; Moustafa H.M.; Msherif A.; Muller K.; Munoz C.; Munoz-Urribarri A.B.; Murillo O.A.; Mustapha F.I.; Muzurovic E.; Nabil Y.; Nafady S.; Nagamatsu A.; Nakajima A.; Nakano D.; Nan Y.; Nascimbeni F.; Naseef M.S.; Nashat N.; Natalia T.; Negro F.; Nersesov A.V.; Neuman M.; Ng'wanasayi M.; Ni Y.; Nicoll A.; Niizeki T.; Nikolova D.; Ningning W.; Niriella M.; Nogoibaeva K.A.; Nordien R.; O Sullivan C.; O'Beirne J.; Obekpa S.; Ocama P.; Ochwoto M.; Ogolodom M.P.; Ojo O.; Okrostsvaridze N.; Oliveira C.P.; Omana R.C.; Omar O.M.; Omar H.; Omar M.; Omran S.; Omran R.; Osman M.M.; Owise N.; Owusu-Ansah T.; Padilla- Machaca P.M.; Palle S.; Pan Z.; Pan X.-Y.; Pan Q.; Papaefthymiou A.; Paquissi F.C.; Par G.; Parkash A.; Payawal D.; Peltekian K.M.; Peng X.; Peng L.; Peng Y.; Pengoria R.; Perez M.; Perez J.L.; Perez N.M.; Persico M.; Pessoa M.G.; Petta S.; Philip M.; Plaz Torres M.C.; Polavarapu N.; Poniachik J.; Portincasa P.; Pu C.; Purnak T.; Purwanto E.; Qi X.; Qi X.; Qian Z.; Qiang Z.; Qiao Z.; Qiao L.; Queiroz A.; Rabiee A.; Radwan M.; Rahetilahy A.M.; Ramadan Y.; Ramadan D.; Ramli A.S.; Ramm G.A.; Ran A.; Rankovic I.; RAO H.; Raouf S.; Ray S.; Reau N.; Refaat A.; Reiberger T.; Remes-Troche J.M.; Reyes E.C.; Richardson B.; Ridruejo E.; Riestra Jimenez S.; Rizk I.; Roberts S.; Roblero J.P.; Robles J.A.P.; Rockey D.; Rodriguez M.; Rodriguez Hernandez H.; Roman E.; Romeiro F.G.; Romeo S.; Rosales-Zabal J.M.; Roshdi G.R.; Rosso N.; Ruf A.; Ruiz P.C.; Runes N.R.; Ruzzenente A.; Ryan M.; Saad A.; Sabbagh E.B.; Sabbah M.; Saber S.; Sabrey R.; Sabry R.; Saeed M.A.; Said D.; Said E.M.; Sakr M.A.; Salah Y.; Salama R.M.; Salama A.; Saleh H.; Saleh A.; Salem A.; Salem A.T.; Salifou A.; Salih A.F.; Salman A.; Samouda H.; Sanai F.; Sanchez-Avila J.F.; Sanker L.; Sano T.; Sanz M.; Saparbu T.; Sawhney R.; Sayed F.; Sayed S.A.; Sayed A.O.; Sayed M.; Sebastiani G.; Secadas L.; Sediqi K.Q.; Seif S.; Semida N.; Senates E.; Serban E.D.; Serfaty L.; Seto W.-K.; Sghaier I.; Sha M.; Shabaan H.M.; Shalaby L.; Shaltout I.; Sharara A.I.; Sharma V.; Shawa I.T.; Shawkat A.; Shawky N.; Shehata O.; Sheils S.; Shewaye A.B.; Shi G.; Shi J.; Shimose S.; Shirono T.; Shou L.; Shrestha A.; Shui G.; Sievert W.; Sigurdardottir S.; Sira M.M.; Siradj R.; Sison C.; Smyth L.; Soliman R.; Sollano J.D.; Sombie R.; Sonderup M.; Sood S.; Soriano G.; Stedman C.A.M.; Stefanyuk O.; Stimac D.; Strasser S.; Strnad P.; Stuart K.; Su W.; Su M.; Sumida Y.; Sumie S.; Sun D.-Q.; Sun J.; Suzuki H.; Svegliati-Baroni G.; Swar M.O.; TAHARBOUCHT S.; Taher Z.; Takamura S.; Tan L.; Tan S.-S.; Tanwandee T.; Tarek S.; Tatiana G.; Tavaglione F.; Tecson G.Y.; Tee H.-P.; Teschke R.; Tharwat M.; Thong V.D.; Thursz M.; Tine T.; Tiribelli C.; Tolmane I.; Tong J.; Tongo M.; Torkie M.; Torre A.; Torres E.A.; Trajkovska M.; Treeprasertsuk S.; Tsutsumi T.; Tu T.; Tur J.A.; Turan D.; Turcan S.; Turkina S.; Tutar E.; Tzeuton C.; Ugiagbe R.; Uygun A.; Vacca M.; Vajro P.; Van der Poorten D.; Van Kleef L.A.; Vashakidze E.; Velazquez C.M.; Velazquez M.I.; Vento S.; Verhoeven V.; Vespasiani-Gentilucci U.; Vethakkan S.R.; Vilaseca J.; Vitek L.; Volkanovska A.; Wallace M.; Wan W.; Wang Y.; Wang Y.; Wang X.; Wang X.; Wang C.; Wang C.; Wang M.; Wangchuk P.; Weltman M.; White M.; Wiegand J.; Wifi M.-N.; Wigg A.; Wilhelmi M.; William R.; Wittenburg H.; Wu S.; Wubeneh A.M.; Xia H.; Xiao J.; Xiao X.; Xiaofeng W.; Xiong W.; Xu L.; Xu J.; Xu W.; Xu J.-H.; Xu K.; Xu Y.; Xu S.-H.; Xu M.; Xu A.; Xu C.; Yan H.; Yang J.; Yang R.-X.; Yang Y.; Yang Q.; Yang N.; Yao J.; Yara J.; Yaras S.; Yilmaz N.; Younes R.; younes H.; Young S.; Youssef F.; Yu Y.; Yu M.-L.; Yuan J.; Yue Z.; Yuen M.-F.; Yun W.; Yurukova N.; Zakaria S.; Zaky S.; Zaldastanishvili M.; Zapata R.; Zare N.; Zerem E.; Zeriban N.; Zeshuai X.; Zhang H.; Zhang X.; Zhang Y.; Zhang W.-H.; Zhang X.; Zhang Y.-P.; Zhang Y.; Zhang Z.-Q.; Zhao J.; Zhao R.-R.; Zhao H.; Zheng C.; Zheng Y.; Zheng R.; Zheng T.-L.; Zheng K.; Zhou X.Q.; Zhou Y.; Zhou Y.-J.; Zhou H.; Zhou L.; Zhou Y.; Zhu L.D.; Zhu Y.F.; Zhu Y.; Zhu P.-W.; Ziada E.; Ziring D.; Ziyi L.; Zou S.; Zou Z.; Zou H.; Zuart Ruiz R.Mendez-Sanchez, N.; Bugianesi, E.; Gish, R. G.; Lammert, F.; Tilg, H.; Nguyen, M. H.; Sarin, S. K.; Fabrellas, N.; Zelber-Sagi, S.; Fan, J. -G.; Shiha, G.; Targher, G.; Zheng, M. -H.; Chan, W. -K.; Vinker, S.; Kawaguchi, T.; Castera, L.; Yilmaz, Y.; Korenjak, M.; Spearman, C. W.; Ungan, M.; Palmer, M.; El-Shabrawi, M.; Gruss, H. -J.; Dufour, J. -F.; Dhawan, A.; Wedemeyer, H.; George, J.; Valenti, L.; Fouad, Y.; Romero-Gomez, M.; Eslam, M.; Abate, M. L.; Abbas, B.; Abbassy, A. A.; Abd El Ghany, W.; Abd Elkhalek, A.; Abd ElMajeed, E.; Abdalgaber, M.; Abdallah, M.; Abdallah, M.; Abdallah, N.; Abdelaleem, S.; Abdelghani, Y.; Abdelghany, W.; Abdelhalim, S. M.; Abdelhamid, W.; Abdelhamid, N.; Abdelkader, N. A.; Abdelkreem, E.; Abdelmohsen, A. M.; Abdelrahman, A. A.; Abd-elsalam, S. M.; Abdeltawab, D.; Abduh, A.; Abdulhakam, N.; Abdulla, M.; Abedpoor, N.; Abenavoli, L.; Aberg, F.; Ablack, O.; Abo elftouh, M.; Abo-Amer, Y. E. -E.; Aboubkr, A.; Aboud, A.; Abouelnaga, A. M.; Aboufarrag, G. A.; Aboutaleb, A.; Abundis, L.; Adali, G.; Adames, E.; Adams, L.; Adda, D.; Adel, N.; Adel, N.; Adel Sayed, M.; Afaa, T. J.; Afredj, N.; Aghayeva, G.; Aghemo, A.; Aguilar-Salinas, C. A.; Ahlenstiel, G.; Ahmady, W.; Ahmed, W.; Ahmed, A.; Ahmed, S. N.; Ahmed, H. M.; Ahmed, R.; Aigner, E.; Akarsu, M.; Akroush, M.; Akyuz, U.; Al Mahtab, M.; Al Qadiri, T.; Al Rawahi, Y.; AL rubaee, R.; Al Saffar, M.; Alam, S.; Al-Ani, Z.; Albillos, A.; Alboraie, M.; Al-Busafi, S.; Al-Emam, M.; Alharthi, J.; Ali, K.; Ali, B. A.; Ali, M.; Ali, R. A. R.; Alisi, A.; AL-Khafaji, A. R.; Alkhatry, M.; Aller, R.; Almansoury, Y.; Al-Naamani, K.; Alnakeeb, A.; Alonso, A.; Alqahtani, S. A.; Alrabadi, L.; Alswat, K.; Altaher, M.; Altamimi, T.; Altamirano, J.; Alvares-da-Silva, M. R.; Aly, E. A. M.; Alzahaby, A.; Alzamzamy, A.; Amano, K.; Amer, M. A.; Amin, M. A.; Amin, S. A.; Amir, A. A.; Ampuero, J.; Anas, N.; Andreone, P.; Andriamandimby, S. F.; Anees, M.; Angela, P.; Antonios, M.; Arafat, W.; Araya, J. M.; Armendariz-Borunda, J.; Armstrong, M. J.; Ashktorab, H.; Aspichueta, P.; Assal, F.; Atef, M.; Attia, D.; Atwa, H.; Awad, R.; Awad, M. A. E.; Awny, S.; Awolowo, O.; Awuku, Y. A.; Ayada, I.; Aye, T. T.; Ayman, S.; Ayman, H.; Ayoub, H.; Azmy, H. M.; Babaran, R. P.; Badreldin, O.; Badry, A.; Bahcecioglu, I. H.; Bahour, A.; Bai, J.; Balaban, Y.; Balasubramanyam, M.; Bamakhrama, K.; Banales, J. M.; Bangaru, B.; Bao, J.; Barahona, J. S.; Barakat, S.; Barbalho, S. M.; Barbra, B.; Barranco, B.; Barrera, F.; Baumann, U.; Bazeed, S.; Bech, E.; Benayad, A.; Benesic, A.; Bernstein, D.; Bessone, F.; Birney, S.; Bisseye, C.; Blake, M.; Bobat, B.; Bonfrate, L.; Bordin, D. S.; Bosques-Padilla, F.; Boursier, J.; Boushab, B. M.; Bowen, D.; Bravo, P. M.; Brennan, P. N.; Bright, B.; Broekaert, I.; Buque, X.; Burgos-Santamaria, D.; Burman, J.; Busetto, L.; Byrne, C. D.; Cabral-Prodigalidad, P. A. I.; Cabrera-Alvarez, G.; Cai, W.; Cainelli, F.; Caliskan, A. R.; Canbay, A.; Cano-Contreras, A.; Cao, H. -X.; Cao, Z.; Carrion, A.; Carubbi, F.; Casanovas, T.; Castellanos Fernandez, M. I.; Chai, J.; Chan, S. P.; Charatcharoenwitthaya, P.; Chavez-Tapia, N.; Chayama, K.; Chen, J.; Chen, L.; Chen, Z. -W.; Chen, H.; Chen, S. -D.; Chen, Q.; Chen, Y.; Chen, G.; Chen, E. -Q.; Chen, F.; Chen, P. -J.; Cheng, R.; Cheng, W.; Chieh, J. T. W.; Chokr, I.; Cholongitas, E.; Choudhury, A.; Chowdhury, A.; Chukwudike, E. S.; Ciardullo, S.; Clayton, M.; Clement, K.; Cloa, M. M.; Coccia, C.; Collazos, C.; Colombo, M.; Cosar, A. M.; Cotrim, H. P.; Couillerot, J.; Coulibaly, A.; Crespo, G.; Crespo, J.; Cruells, M.; Cua, I. H. Y.; Dabbous, H. K.; Dalekos, G. N.; D'Alia, P.; Dan, L.; Dao, V. H.; Darwish, M.; Datz, C.; Davalos-Moscol, M. B.; Dawoud, H.; de Careaga, B. O.; de Knegt, R.; de Ledinghen, V.; de Silva, J.; Debzi, N.; Decraecker, M.; Del Pozo, E.; Delgado, T. C.; Delgado-Blanco, M.; Dembinski, L.; Depina, A.; Derbala, M.; Desalegn, H.; Desbois-Mouthon, C.; Desoky, M.; Dev, A.; Di Ciaula, A.; Diago, M.; Diallo, I.; Diaz, L. A.; Dirchwolf, M.; Dongiovanni, P.; Dorofeyev, A.; Dou, X.; Douglas, M. W.; Doulberis, M.; Dovia, C. K.; Doyle, A.; Dragojevic, I.; Drenth, J. P.; Duan, X.; Dulskas, A.; Dumitrascu, D. L.; Duncan, O.; Dusabejambo, V.; Dwawhi, R. S. N. A.; Eiketsu, S.; El Amrousy, D.; El Deeb, A.; El Deriny, G.; El Din, H. S.; El Kamshishy, S.; El Kassas, M.; El Raziky, M.; Elagamy, O. A.; Elakel, W.; Elalfy, D.; Elaraby, H.; Elawady, H.; Elbadawy, R.; Eldash, H. H.; Eldefrawy, M. S.; Elecharri, C. L.; Elfaramawy, A.; Elfatih, M.; Elfiky, M.; Elgamsy, M.; Elgendy, M.; El-Guindi, M. A.; Elhussieny, N.; Eliwa, A. M.; Elkabbany, Z.; El-Khayat, H.; El-Koofy, N. M.; Elmetwalli, A.; Elrabat, A.; El-Raey, F.; Elrashdy, F.; Elsahhar, M.; Elsaid, E. M.; Elsayed, S.; Elsayed, H.; Elsayed, A.; Elsayed, A. M.; Elsayed, H.; El-Serafy, M.; Elsharkawy, A. M.; Elsheemy, R. Y.; Elshemy, E. E.; Elsherbini, S.; Eltoukhy, N.; Elwakil, R.; Emad, O.; Emad, S.; Embabi, M.; Ergenc, I.; Ermolova, T.; Esmat, G.; Esmat, D. M.; Estupinan, E. C.; Ettair, S.; Eugen, T.; Ezz-Eldin, M.; Falcon, L. P. V.; Fan, Y. -C.; Fandari, S.; Farag, M.; Farahat, T. M.; Fares, E. M.; Fares, M.; Fassio, E.; Fathy, H.; Fathy, D.; Fathy, W.; Fayed, S.; Feng, D.; Feng, G.; Fernandez-Bermejo, M.; Ferreira, C. T.; Ferrer, J. D.; Forbes, A.; Fouad, R.; Fouad, H. M.; Frisch, T.; Fujii, H.; Fukunaga, S.; Fukunishi, S.; Fulya, H.; Furuhashi, M.; Gaber, Y.; Galang, A. J. G.; Gallardo, J. C.; Galloso, R.; Gamal, M.; Gamal, R.; Gamal, H.; Gan, J.; Ganbold, A.; Gao, X.; Garas, G.; Garba, T.; Garcia-Cortes, M.; Garcia-Monzon, C.; Garcia-Samaniego, J.; Gastaldelli, A.; Gatica, M.; Gatley, E.; Gegeshidze, T.; Geng, B.; Ghazinyan, H.; Ghoneem, S.; Giacomelli, L.; Giannelli, G.; Giannini, E. G.; Giefer, M.; Gines, P.; Girala, M.; Giraudi, P. J.; Goh, G. B. -B.; Gomaa, A. A.; Gong, B.; Gonzales, D. H. C.; Gonzalez, H. C.; Gonzalez-Huezo, M. S.; Graupera, I.; Grgurevic, I.; Gronbaek, H.; Gu, X.; Guan, L.; Gueye, I.; Guingane, A. N.; Gul, O. O.; Gul, C. B.; Guo, Q.; Gupta, P. P.; Gurakar, A.; Gutierrez, J. C. R.; Habib, G.; Hafez, A.; Hagman, E.; Halawa, E.; Hamdy, O.; Hamed, A. E.; Hamed, D. H.; Hamid, S.; Hamoudi, W.; Han, Y.; Haridy, J.; Haridy, H.; Harris, D. C. H. H.; Hart, M.; Hasan, F.; Hashim, A.; Hassan, I.; Hassan, A.; Hassan, E. A.; Hassan, A. A.; Hassan, M. S.; Hassanin, F.; Hassnine, A.; Haukeland, J. W.; Hawal, A. I. M.; He, J.; He, Q.; He, Y.; He, F. -P.; Hegazy, M.; Hegazy, A.; Henegil, O.; Hernandez, N.; Hernandez-Guerra, M.; Higuera-de-la-Tijera, F.; Hindy, I.; Hirota, K.; Ho, L. C.; Hodge, A.; Hosny, M.; Hou, X.; Huang, J. -F.; Huang, Y.; Huang, Z.; Huang, Y.; Huang, A.; Huang, X. -P.; Hui-ping, S.; Hunyady, B.; Hussein, M. A.; Hussein, O.; Hussien, S. M.; Ibanez-Samaniego, L.; Ibdah, J.; Ibrahim, L.; Ibrahim, M.; Ibrahim, I.; Icaza-Chavez, M. E.; Idelbi, S.; Idilman, R. I.; Ikeda, M.; Indolfi, G.; Invernizzi, F.; Irshad, I.; Isa, H. M. A.; Iskandar, N. J.; Ismaiel, A.; Ismail, M.; Ismail, Z.; Ismail, F.; Iwamoto, H.; Jack, K.; Jacob, R.; Jafarov, F.; Jafri, W.; Jahshan, H.; Jalal, P. K.; Jancoriene, L.; Janicko, M.; Jayasena, H.; Jefferies, M.; Jha, V.; Ji, F.; Ji, Y.; Jia, J.; Jiang, C.; Jiang, N.; Jiang, Z. -Z.; Jin, X.; Jin, Y.; Jing, X.; Jingyu, Q.; Jinjolava, M.; Jong, F. H. H.; Jucov, A.; Julius, I.; Kaddah, M.; Kamada, Y.; Kamal, A.; Kamal, E. M.; Kamel, A. S.; Kao, J. -H.; Karin, M.; Karlas, T.; Kashwaa, M.; Katsidzira, L.; Kaya, E.; Kayasseh, M. A.; Keenan, B.; Keklikkiran, C.; Keml, W.; Khalaf, D. K.; Khalefa, R.; Khamis, S.; Khater, D.; Khattab, H.; Khavkin, A.; Khlynova, O.; Khmis, N.; Kobyliak, N.; Koffas, A.; Koike, K.; Kok, K. Y. Y.; Koller, T.; Komas, N. P.; Korochanskaya, N. V.; Koulla, Y.; Koya, S.; Kraft, C.; Kraja, B.; Krawczyk, M.; Kuchay, M. S.; Kulkarni, A. V.; Kumar, A.; Kumar, M.; Lakoh, S.; Lam, P.; Lan, L.; Lange, N. F.; Lankarani, K. B.; Lanthier, N.; Lapshyna, K.; Lashen, S. A.; Laure, K. N. J.; Lazebnik, L.; Lebrec, D.; Lee, S. S.; Lee, W. S.; Lee, Y. Y.; Leeming, D. J.; Leite, N. C.; Leon, R.; Lesmana, C. R. A.; Li, J.; Li, Q.; Li, J.; Li, Y. -Y.; Li, Y.; Li, L.; Li, M.; Li, Y.; Liang, H.; Lijuan, T.; Lim, S. G.; Lim, L. -L.; Lin, S.; Lin, H. -C.; Lin, R.; Lithy, R.; Liu, Y.; Liu, Y.; Liu, X.; Liu, W. -Y.; Liu, S.; Liu, K.; Liu, T.; Lonardo, A.; Lopez, M. B.; Lopez-Benages, E.; Lopez-Jaramillo, P.; Lu, H.; Lu, L. G.; Lu, Y.; Lubel, J.; Lui, R.; Lupasco, I.; Luzina, E.; Lv, X. -H.; Lynch, K.; Ma, H. -L.; Machado, M. V.; Maduka, N.; Madzharova, K.; Magdaong, R.; Mahadeva, S.; Mahfouz, A.; Mahmood, N. R. K. N.; Mahmoud, E.; Mahrous, M.; Maiwall, R.; Majeed, A.; Majumdar, A.; Mak, L.; Maklouf, M. M.; Malekzadeh, R.; Mandato, C.; Mangia, A.; Mann, J.; Mansour, H. H.; Mansouri, A.; Mantovani, A.; Mao, J. Q.; Maramag, F.; Marchesini, G.; Marcus, C.; Marinho, R. A. R. T.; Martinez-Chantar, M. L.; Martins, A. A. S.; Marwan, R.; Mason, K. F.; Masoud, G.; Massoud, M. N.; Matamoros, M. A.; Mateos, R. M.; Mawed, A.; Mbanya, J. C.; Mbendi, C.; Mccolaugh, L.; Mcleod, D.; Medina, J. F. R.; Megahed, A.; Mehrez, M.; Memon, I.; Merat, S.; Mercado, R.; Mesbah,

Global multi-stakeholder endorsement of the MAFLD definition

none1055noneMendez-Sanchez N.; Bugianesi E.; Gish R.G.; Lammert F.; Tilg H.; Nguyen M.H.; Sarin S.K.; Fabrellas N.; Zelber-Sagi S.; Fan J.-G.; Shiha G.; Targher G.; Zheng M.-H.; Chan W.-K.; Vinker S.; Kawaguchi T.; Castera L.; Yilmaz Y.; Korenjak M.; Spearman C.W.; Ungan M.; Palmer M.; El-Shabrawi M.; Gruss H.-J.; Dufour J.-F.; Dhawan A.; Wedemeyer H.; George J.; Valenti L.; Fouad Y.; Romero-Gomez M.; Eslam M.; Abate M.L.; Abbas B.; Abbassy A.A.; Abd El Ghany W.; Abd Elkhalek A.; Abd ElMajeed E.; Abdalgaber M.; AbdAllah M.; Abdallah M.; Abdallah N.; Abdelaleem S.; Abdelghani Y.; Abdelghany W.; Abdelhalim S.M.; Abdelhamid W.; Abdelhamid N.; Abdelkader N.A.; Abdelkreem E.; Abdelmohsen A.M.; Abdelrahman A.A.; Abd-elsalam S.M.; Abdeltawab D.; Abduh A.; Abdulhakam N.; Abdulla M.; Abedpoor N.; Abenavoli L.; Aberg F.; Ablack O.; Abo elftouh M.; Abo-Amer Y.E.-E.; Aboubkr A.; Aboud A.; Abouelnaga A.M.; Aboufarrag G.A.; Aboutaleb A.; Abundis L.; Adali G.; Adames E.; Adams L.; Adda D.; Adel N.; Adel N.; Adel Sayed M.; Afaa T.J.; Afredj N.; Aghayeva G.; Aghemo A.; Aguilar-Salinas C.A.; Ahlenstiel G.; Ahmady W.; Ahmed W.; Ahmed A.; Ahmed S.N.; Ahmed H.M.; Ahmed R.; Aigner E.; Akarsu M.; Akroush M.; Akyuz U.; Al Mahtab M.; Al Qadiri T.; Al Rawahi Y.; AL rubaee R.; Al Saffar M.; Alam S.; Al-Ani Z.; Albillos A.; Alboraie M.; Al-Busafi S.; Al-Emam M.; Alharthi J.; Ali K.; Ali B.A.; Ali M.; Ali R.A.R.; Alisi A.; AL-Khafaji A.R.; Alkhatry M.; Aller R.; Almansoury Y.; Al-Naamani K.; Alnakeeb A.; Alonso A.; Alqahtani S.A.; Alrabadi L.; Alswat K.; Altaher M.; Altamimi T.; Altamirano J.; Alvares-da-Silva M.R.; Aly E.A.M.; Alzahaby A.; Alzamzamy A.; Amano K.; Amer M.A.; Amin M.A.; Amin S.A.; Amir A.A.; Ampuero J.; Anas N.; Andreone P.; Andriamandimby S.F.; Anees M.; Angela P.; Antonios M.; Arafat W.; Araya J.M.; Armendariz-Borunda J.; Armstrong M.J.; Ashktorab H.; Aspichueta P.; Assal F.; Atef M.; Attia D.; Atwa H.; Awad R.; Awad M.A.E.; Awny S.; Awolowo O.; Awuku Y.A.; Ayada I.; Aye T.T.; Ayman S.; Ayman H.; Ayoub H.; Azmy H.M.; Babaran R.P.; Badreldin O.; Badry A.; Bahcecioglu I.H.; Bahour A.; Bai J.; Balaban Y.; Balasubramanyam M.; Bamakhrama K.; Banales J.M.; Bangaru B.; Bao J.; Barahona J.S.; Barakat S.; Barbalho S.M.; Barbra B.; Barranco B.; Barrera F.; Baumann U.; Bazeed S.; Bech E.; Benayad A.; Benesic A.; Bernstein D.; Bessone F.; Birney S.; Bisseye C.; Blake M.; Bobat B.; Bonfrate L.; Bordin D.S.; Bosques-Padilla F.; Boursier J.; Boushab B.M.; Bowen D.; Bravo P.M.; Brennan P.N.; Bright B.; Broekaert I.; Buque X.; Burgos-Santamaria D.; Burman J.; Busetto L.; Byrne C.D.; Cabral-Prodigalidad P.A.I.; Cabrera-Alvarez G.; Cai W.; Cainelli F.; Caliskan A.R.; Canbay A.; Cano-Contreras A.; Cao H.-X.; Cao Z.; Carrion A.; Carubbi F.; Casanovas T.; Castellanos Fernandez M.I.; Chai J.; Chan S.P.; Charatcharoenwitthaya P.; Chavez-Tapia N.; Chayama K.; Chen J.; Chen L.; Chen Z.-W.; Chen H.; Chen S.-D.; Chen Q.; Chen Y.; Chen G.; Chen E.-Q.; Chen F.; Chen P.-J.; Cheng R.; Cheng W.; Chieh J.T.W.; Chokr I.; Cholongitas E.; Choudhury A.; Chowdhury A.; Chukwudike E.S.; Ciardullo S.; Clayton M.; Clement K.; Cloa M.M.; Coccia C.; Collazos C.; Colombo M.; Cosar A.M.; Cotrim H.P.; Couillerot J.; Coulibaly A.; Crespo G.; Crespo J.; Cruells M.; Cua I.H.Y.; Dabbous H.K.; Dalekos G.N.; D'Alia P.; Dan L.; Dao V.H.; Darwish M.; Datz C.; Davalos-Moscol M.B.; Dawoud H.; de Careaga B.O.; de Knegt R.; de Ledinghen V.; de Silva J.; Debzi N.; Decraecker M.; Del Pozo E.; Delgado T.C.; Delgado-Blanco M.; Dembinski L.; Depina A.; Derbala M.; Desalegn H.; Desbois-Mouthon C.; Desoky M.; Dev A.; Di Ciaula A.; Diago M.; Diallo I.; Diaz L.A.; Dirchwolf M.; Dongiovanni P.; Dorofeyev A.; Dou X.; Douglas M.W.; Doulberis M.; Dovia C.K.; Doyle A.; Dragojevic I.; Drenth J.P.; Duan X.; Dulskas A.; Dumitrascu D.L.; Duncan O.; Dusabejambo V.; Dwawhi R.S.N.A.; Eiketsu S.; El Amrousy D.; El Deeb A.; El Deriny G.; El Din H.S.; El Kamshishy S.; El Kassas M.; El Raziky M.; Elagamy O.A.; Elakel W.; Elalfy D.; Elaraby H.; ElAwady H.; Elbadawy R.; Eldash H.H.; Eldefrawy M.S.; Elecharri C.L.; Elfaramawy A.; Elfatih M.; Elfiky M.; Elgamsy M.; Elgendy M.; El-Guindi M.A.; Elhussieny N.; Eliwa A.M.; Elkabbany Z.; El-Khayat H.; El-Koofy N.M.; Elmetwalli A.; Elrabat A.; El-Raey F.; Elrashdy F.; Elsahhar M.; Elsaid E.M.; Elsayed S.; Elsayed H.; Elsayed A.; Elsayed A.M.; Elsayed H.; El-Serafy M.; Elsharkawy A.M.; Elsheemy R.Y.; Elshemy E.E.; Elsherbini S.; Eltoukhy N.; Elwakil R.; Emad O.; Emad S.; Embabi M.; Ergenc I.; Ermolova T.; Esmat G.; Esmat D.M.; Estupinan E.C.; Ettair S.; Eugen T.; Ezz-Eldin M.; Falcon L.P.V.; Fan Y.-C.; Fandari S.; Farag M.; Farahat T.M.; Fares E.M.; Fares M.; Fassio E.; Fathy H.; Fathy D.; Fathy W.; Fayed S.; Feng D.; Feng G.; Fernandez-Bermejo M.; Ferreira C.T.; Ferrer J.D.; Forbes A.; Fouad R.; Fouad H.M.; Frisch T.; Fujii H.; Fukunaga S.; Fukunishi S.; Fulya H.; Furuhashi M.; Gaber Y.; Galang A.J.G.; Gallardo J.C.; Galloso R.; Gamal M.; Gamal R.; Gamal H.; Gan J.; Ganbold A.; Gao X.; Garas G.; Garba T.; Garcia-Cortes M.; Garcia-Monzon C.; Garcia-Samaniego J.; Gastaldelli A.; Gatica M.; Gatley E.; Gegeshidze T.; Geng B.; Ghazinyan H.; Ghoneem S.; Giacomelli L.; Giannelli G.; Giannini E.G.; Giefer M.; Gines P.; Girala M.; Giraudi P.J.; Goh G.B.-B.; Gomaa A.A.; Gong B.; Gonzales D.H.C.; Gonzalez H.C.; Gonzalez-Huezo M.S.; Graupera I.; Grgurevic I.; Gronbaek H.; Gu X.; Guan L.; Gueye I.; Guingane A.N.; Gul O.O.; Gul C.B.; Guo Q.; Gupta P.P.; Gurakar A.; Gutierrez J.C.R.; Habib G.; Hafez A.; Hagman E.; Halawa E.; Hamdy O.; Hamed A.E.; Hamed D.H.; Hamid S.; Hamoudi W.; Han Y.; Haridy J.; Haridy H.; Harris D.C.H.H.; Hart M.; Hasan F.; Hashim A.; Hassan I.; Hassan A.; Hassan E.A.; Hassan A.A.; Hassan M.S.; Hassanin F.; Hassnine A.; Haukeland J.W.; Hawal A.I.M.; He J.; He Q.; He Y.; He F.-P.; Hegazy M.; Hegazy A.; Henegil O.; Hernandez N.; Hernandez-Guerra M.; Higuera-de-la-Tijera F.; Hindy I.; Hirota K.; Ho L.C.; Hodge A.; Hosny M.; Hou X.; Huang J.-F.; Huang Y.; Huang Z.; Huang Y.; Huang A.; Huang X.-P.; Hui-ping S.; Hunyady B.; Hussein M.A.; Hussein O.; Hussien S.M.; Ibanez-Samaniego L.; Ibdah J.; Ibrahim L.; Ibrahim M.; Ibrahim I.; Icaza-Chavez M.E.; Idelbi S.; Idilman R.I.; Ikeda M.; Indolfi G.; Invernizzi F.; Irshad I.; Isa H.M.A.; Iskandar N.J.; Ismaiel A.; Ismail M.; Ismail Z.; Ismail F.; Iwamoto H.; Jack K.; Jacob R.; Jafarov F.; Jafri W.; Jahshan H.; Jalal P.K.; Jancoriene L.; Janicko M.; Jayasena H.; Jefferies M.; Jha V.; Ji F.; Ji Y.; Jia J.; Jiang C.; Jiang N.; Jiang Z.-Z.; Jin X.; Jin Y.; Jing X.; Jingyu Q.; Jinjolava M.; Jong F.H.H.; Jucov A.; Julius I.; Kaddah M.; Kamada Y.; kamal A.; Kamal E.M.; Kamel A.S.; Kao J.-H.; Karin M.; Karlas T.; Kashwaa M.; Katsidzira L.; Kaya E.; Kayasseh M.A.; Keenan B.; Keklikkiran C.; Keml W.; Khalaf D.K.; Khalefa R.; Khamis S.; Khater D.; khattab H.; Khavkin A.; Khlynova O.; Khmis N.; Kobyliak N.; Koffas A.; Koike K.; Kok K.Y.Y.; Koller T.; Komas N.P.; Korochanskaya N.V.; Koulla Y.; Koya S.; Kraft C.; Kraja B.; Krawczyk M.; Kuchay M.S.; Kulkarni A.V.; Kumar A.; Kumar M.; Lakoh S.; Lam P.; Lan L.; Lange N.F.; Lankarani K.B.; Lanthier N.; Lapshyna K.; Lashen S.A.; Laure K.N.J.; Lazebnik L.; Lebrec D.; Lee S.S.; Lee W.S.; Lee Y.Y.; Leeming D.J.; Leite N.C.; Leon R.; Lesmana C.R.A.; Li J.; Li Q.; Li J.; Li Y.-Y.; Li Y.; Li L.; Li M.; li Y.; Liang H.; Lijuan T.; Lim S.G.; Lim L.-L.; Lin S.; Lin H.-C.; Lin R.; Lithy R.; Liu Y.; Liu Y.; Liu X.; Liu W.-Y.; Liu S.; Liu K.; Liu T.; Lonardo A.; Lopez M.B.; Lopez-Benages E.; Lopez-Jaramillo P.; Lu H.; Lu L.G.; Lu Y.; Lubel J.; Lui R.; Lupasco I.; Luzina E.; Lv X.-H.; Lynch K.; Ma H.-L.; Machado M.V.; Maduka N.; Madzharova K.; Magdaong R.; Mahadeva S.; Mahfouz A.; Mahmood N.R.K.N.; Mahmoud E.; Mahrous M.; Maiwall R.; Majeed A.; Majumdar A.; Mak L.; Maklouf M.M.; Malekzadeh R.; Mandato C.; Mangia A.; Mann J.; Mansour H.H.; Mansouri A.; Mantovani A.; Mao J.Q.; Maramag F.; Marchesini G.; Marcus C.; Marinho R.A.R.T.; Martinez-Chantar M.L.; Martins A.A.S.; Marwan R.; Mason K.F.; Masoud G.; Massoud M.N.; Matamoros M.A.; Mateos R.M.; Mawed A.; Mbanya J.C.; Mbendi C.; McColaugh L.; McLeod D.; Medina J.F.R.; Megahed A.; Mehrez M.; Memon I.; Merat S.; Mercado R.; Mesbah A.; Meskini T.; Metwally M.; Metwaly R.; Miao L.; Micah E.; Miele L.; Milivojevic V.; Milovanovic T.; Mina Y.L.; Mishkovik M.; Mishriki A.; Mitchell T.; Mohamed A.; Mohamed M.; Mohamed S.; Mohammed S.; Mohammed A.; Mohan V.; Mohie S.; Mokhtar A.; Moniem R.; Montilla M.S.; Morales J.A.O.; Morata M.M.S.; Moreno-Planas J.M.; Morise S.; Mosaad S.; Moselhy M.; Mostafa A.M.; Mostafa E.; Mouane N.; Mousa N.; Moustafa H.M.; Msherif A.; Muller K.; Munoz C.; Munoz-Urribarri A.B.; Murillo O.A.; Mustapha F.I.; Muzurovic E.; Nabil Y.; Nafady S.; Nagamatsu A.; Nakajima A.; Nakano D.; Nan Y.; Nascimbeni F.; Naseef M.S.; Nashat N.; Natalia T.; Negro F.; Nersesov A.V.; Neuman M.; Ng'wanasayi M.; Ni Y.; Nicoll A.; Niizeki T.; Nikolova D.; Ningning W.; Niriella M.; Nogoibaeva K.A.; Nordien R.; O Sullivan C.; O'Beirne J.; Obekpa S.; Ocama P.; Ochwoto M.; Ogolodom M.P.; Ojo O.; Okrostsvaridze N.; Oliveira C.P.; Omana R.C.; Omar O.M.; Omar H.; Omar M.; Omran S.; Omran R.; Osman M.M.; Owise N.; Owusu-Ansah T.; Padilla- Machaca P.M.; Palle S.; Pan Z.; Pan X.-Y.; Pan Q.; Papaefthymiou A.; Paquissi F.C.; Par G.; Parkash A.; Payawal D.; Peltekian K.M.; Peng X.; Peng L.; Peng Y.; Pengoria R.; Perez M.; Perez J.L.; Perez N.M.; Persico M.; Pessoa M.G.; Petta S.; Philip M.; Plaz Torres M.C.; Polavarapu N.; Poniachik J.; Portincasa P.; Pu C.; Purnak T.; Purwanto E.; Qi X.; Qi X.; Qian Z.; Qiang Z.; Qiao Z.; Qiao L.; Queiroz A.; Rabiee A.; Radwan M.; Rahetilahy A.M.; Ramadan Y.; Ramadan D.; Ramli A.S.; Ramm G.A.; Ran A.; Rankovic I.; RAO H.; Raouf S.; Ray S.; Reau N.; Refaat A.; Reiberger T.; Remes-Troche J.M.; Reyes E.C.; Richardson B.; Ridruejo E.; Riestra Jimenez S.; Rizk I.; Roberts S.; Roblero J.P.; Robles J.A.P.; Rockey D.; Rodriguez M.; Rodriguez Hernandez H.; Roman E.; Romeiro F.G.; Romeo S.; Rosales-Zabal J.M.; Roshdi G.R.; Rosso N.; Ruf A.; Ruiz P.C.; Runes N.R.; Ruzzenente A.; Ryan M.; Saad A.; Sabbagh E.B.; Sabbah M.; Saber S.; Sabrey R.; Sabry R.; Saeed M.A.; Said D.; Said E.M.; Sakr M.A.; Salah Y.; Salama R.M.; Salama A.; Saleh H.; Saleh A.; Salem A.; Salem A.T.; Salifou A.; Salih A.F.; Salman A.; Samouda H.; Sanai F.; Sanchez-Avila J.F.; Sanker L.; Sano T.; Sanz M.; Saparbu T.; Sawhney R.; Sayed F.; Sayed S.A.; Sayed A.O.; Sayed M.; Sebastiani G.; Secadas L.; Sediqi K.Q.; Seif S.; Semida N.; Senates E.; Serban E.D.; Serfaty L.; Seto W.-K.; Sghaier I.; Sha M.; Shabaan H.M.; Shalaby L.; Shaltout I.; Sharara A.I.; Sharma V.; Shawa I.T.; Shawkat A.; Shawky N.; Shehata O.; Sheils S.; Shewaye A.B.; Shi G.; Shi J.; Shimose S.; Shirono T.; Shou L.; Shrestha A.; Shui G.; Sievert W.; Sigurdardottir S.; Sira M.M.; Siradj R.; Sison C.; Smyth L.; Soliman R.; Sollano J.D.; Sombie R.; Sonderup M.; Sood S.; Soriano G.; Stedman C.A.M.; Stefanyuk O.; Stimac D.; Strasser S.; Strnad P.; Stuart K.; Su W.; Su M.; Sumida Y.; Sumie S.; Sun D.-Q.; Sun J.; Suzuki H.; Svegliati-Baroni G.; Swar M.O.; TAHARBOUCHT S.; Taher Z.; Takamura S.; Tan L.; Tan S.-S.; Tanwandee T.; Tarek S.; Tatiana G.; Tavaglione F.; Tecson G.Y.; Tee H.-P.; Teschke R.; Tharwat M.; Thong V.D.; Thursz M.; Tine T.; Tiribelli C.; Tolmane I.; Tong J.; Tongo M.; Torkie M.; Torre A.; Torres E.A.; Trajkovska M.; Treeprasertsuk S.; Tsutsumi T.; Tu T.; Tur J.A.; Turan D.; Turcan S.; Turkina S.; Tutar E.; Tzeuton C.; Ugiagbe R.; Uygun A.; Vacca M.; Vajro P.; Van der Poorten D.; Van Kleef L.A.; Vashakidze E.; Velazquez C.M.; Velazquez M.I.; Vento S.; Verhoeven V.; Vespasiani-Gentilucci U.; Vethakkan S.R.; Vilaseca J.; Vitek L.; Volkanovska A.; Wallace M.; Wan W.; Wang Y.; Wang Y.; Wang X.; Wang X.; Wang C.; Wang C.; Wang M.; Wangchuk P.; Weltman M.; White M.; Wiegand J.; Wifi M.-N.; Wigg A.; Wilhelmi M.; William R.; Wittenburg H.; Wu S.; Wubeneh A.M.; Xia H.; Xiao J.; Xiao X.; Xiaofeng W.; Xiong W.; Xu L.; Xu J.; Xu W.; Xu J.-H.; Xu K.; Xu Y.; Xu S.-H.; Xu M.; Xu A.; Xu C.; Yan H.; Yang J.; Yang R.-X.; Yang Y.; Yang Q.; Yang N.; Yao J.; Yara J.; Yaras S.; Yilmaz N.; Younes R.; younes H.; Young S.; Youssef F.; Yu Y.; Yu M.-L.; Yuan J.; Yue Z.; Yuen M.-F.; Yun W.; Yurukova N.; Zakaria S.; Zaky S.; Zaldastanishvili M.; Zapata R.; Zare N.; Zerem E.; Zeriban N.; Zeshuai X.; Zhang H.; Zhang X.; Zhang Y.; Zhang W.-H.; Zhang X.; Zhang Y.-P.; Zhang Y.; Zhang Z.-Q.; Zhao J.; Zhao R.-R.; Zhao H.; Zheng C.; Zheng Y.; Zheng R.; Zheng T.-L.; Zheng K.; Zhou X.Q.; Zhou Y.; Zhou Y.-J.; Zhou H.; Zhou L.; Zhou Y.; Zhu L.D.; Zhu Y.F.; Zhu Y.; Zhu P.-W.; Ziada E.; Ziring D.; Ziyi L.; Zou S.; Zou Z.; Zou H.; Zuart Ruiz R.Mendez-Sanchez, N.; Bugianesi, E.; Gish, R. G.; Lammert, F.; Tilg, H.; Nguyen, M. H.; Sarin, S. K.; Fabrellas, N.; Zelber-Sagi, S.; Fan, J. -G.; Shiha, G.; Targher, G.; Zheng, M. -H.; Chan, W. -K.; Vinker, S.; Kawaguchi, T.; Castera, L.; Yilmaz, Y.; Korenjak, M.; Spearman, C. W.; Ungan, M.; Palmer, M.; El-Shabrawi, M.; Gruss, H. -J.; Dufour, J. -F.; Dhawan, A.; Wedemeyer, H.; George, J.; Valenti, L.; Fouad, Y.; Romero-Gomez, M.; Eslam, M.; Abate, M. L.; Abbas, B.; Abbassy, A. A.; Abd El Ghany, W.; Abd Elkhalek, A.; Abd ElMajeed, E.; Abdalgaber, M.; Abdallah, M.; Abdallah, M.; Abdallah, N.; Abdelaleem, S.; Abdelghani, Y.; Abdelghany, W.; Abdelhalim, S. M.; Abdelhamid, W.; Abdelhamid, N.; Abdelkader, N. A.; Abdelkreem, E.; Abdelmohsen, A. M.; Abdelrahman, A. A.; Abd-elsalam, S. M.; Abdeltawab, D.; Abduh, A.; Abdulhakam, N.; Abdulla, M.; Abedpoor, N.; Abenavoli, L.; Aberg, F.; Ablack, O.; Abo elftouh, M.; Abo-Amer, Y. E. -E.; Aboubkr, A.; Aboud, A.; Abouelnaga, A. M.; Aboufarrag, G. A.; Aboutaleb, A.; Abundis, L.; Adali, G.; Adames, E.; Adams, L.; Adda, D.; Adel, N.; Adel, N.; Adel Sayed, M.; Afaa, T. J.; Afredj, N.; Aghayeva, G.; Aghemo, A.; Aguilar-Salinas, C. A.; Ahlenstiel, G.; Ahmady, W.; Ahmed, W.; Ahmed, A.; Ahmed, S. N.; Ahmed, H. M.; Ahmed, R.; Aigner, E.; Akarsu, M.; Akroush, M.; Akyuz, U.; Al Mahtab, M.; Al Qadiri, T.; Al Rawahi, Y.; AL rubaee, R.; Al Saffar, M.; Alam, S.; Al-Ani, Z.; Albillos, A.; Alboraie, M.; Al-Busafi, S.; Al-Emam, M.; Alharthi, J.; Ali, K.; Ali, B. A.; Ali, M.; Ali, R. A. R.; Alisi, A.; AL-Khafaji, A. R.; Alkhatry, M.; Aller, R.; Almansoury, Y.; Al-Naamani, K.; Alnakeeb, A.; Alonso, A.; Alqahtani, S. A.; Alrabadi, L.; Alswat, K.; Altaher, M.; Altamimi, T.; Altamirano, J.; Alvares-da-Silva, M. R.; Aly, E. A. M.; Alzahaby, A.; Alzamzamy, A.; Amano, K.; Amer, M. A.; Amin, M. A.; Amin, S. A.; Amir, A. A.; Ampuero, J.; Anas, N.; Andreone, P.; Andriamandimby, S. F.; Anees, M.; Angela, P.; Antonios, M.; Arafat, W.; Araya, J. M.; Armendariz-Borunda, J.; Armstrong, M. J.; Ashktorab, H.; Aspichueta, P.; Assal, F.; Atef, M.; Attia, D.; Atwa, H.; Awad, R.; Awad, M. A. E.; Awny, S.; Awolowo, O.; Awuku, Y. A.; Ayada, I.; Aye, T. T.; Ayman, S.; Ayman, H.; Ayoub, H.; Azmy, H. M.; Babaran, R. P.; Badreldin, O.; Badry, A.; Bahcecioglu, I. H.; Bahour, A.; Bai, J.; Balaban, Y.; Balasubramanyam, M.; Bamakhrama, K.; Banales, J. M.; Bangaru, B.; Bao, J.; Barahona, J. S.; Barakat, S.; Barbalho, S. M.; Barbra, B.; Barranco, B.; Barrera, F.; Baumann, U.; Bazeed, S.; Bech, E.; Benayad, A.; Benesic, A.; Bernstein, D.; Bessone, F.; Birney, S.; Bisseye, C.; Blake, M.; Bobat, B.; Bonfrate, L.; Bordin, D. S.; Bosques-Padilla, F.; Boursier, J.; Boushab, B. M.; Bowen, D.; Bravo, P. M.; Brennan, P. N.; Bright, B.; Broekaert, I.; Buque, X.; Burgos-Santamaria, D.; Burman, J.; Busetto, L.; Byrne, C. D.; Cabral-Prodigalidad, P. A. I.; Cabrera-Alvarez, G.; Cai, W.; Cainelli, F.; Caliskan, A. R.; Canbay, A.; Cano-Contreras, A.; Cao, H. -X.; Cao, Z.; Carrion, A.; Carubbi, F.; Casanovas, T.; Castellanos Fernandez, M. I.; Chai, J.; Chan, S. P.; Charatcharoenwitthaya, P.; Chavez-Tapia, N.; Chayama, K.; Chen, J.; Chen, L.; Chen, Z. -W.; Chen, H.; Chen, S. -D.; Chen, Q.; Chen, Y.; Chen, G.; Chen, E. -Q.; Chen, F.; Chen, P. -J.; Cheng, R.; Cheng, W.; Chieh, J. T. W.; Chokr, I.; Cholongitas, E.; Choudhury, A.; Chowdhury, A.; Chukwudike, E. S.; Ciardullo, S.; Clayton, M.; Clement, K.; Cloa, M. M.; Coccia, C.; Collazos, C.; Colombo, M.; Cosar, A. M.; Cotrim, H. P.; Couillerot, J.; Coulibaly, A.; Crespo, G.; Crespo, J.; Cruells, M.; Cua, I. H. Y.; Dabbous, H. K.; Dalekos, G. N.; D'Alia, P.; Dan, L.; Dao, V. H.; Darwish, M.; Datz, C.; Davalos-Moscol, M. B.; Dawoud, H.; de Careaga, B. O.; de Knegt, R.; de Ledinghen, V.; de Silva, J.; Debzi, N.; Decraecker, M.; Del Pozo, E.; Delgado, T. C.; Delgado-Blanco, M.; Dembinski, L.; Depina, A.; Derbala, M.; Desalegn, H.; Desbois-Mouthon, C.; Desoky, M.; Dev, A.; Di Ciaula, A.; Diago, M.; Diallo, I.; Diaz, L. A.; Dirchwolf, M.; Dongiovanni, P.; Dorofeyev, A.; Dou, X.; Douglas, M. W.; Doulberis, M.; Dovia, C. K.; Doyle, A.; Dragojevic, I.; Drenth, J. P.; Duan, X.; Dulskas, A.; Dumitrascu, D. L.; Duncan, O.; Dusabejambo, V.; Dwawhi, R. S. N. A.; Eiketsu, S.; El Amrousy, D.; El Deeb, A.; El Deriny, G.; El Din, H. S.; El Kamshishy, S.; El Kassas, M.; El Raziky, M.; Elagamy, O. A.; Elakel, W.; Elalfy, D.; Elaraby, H.; Elawady, H.; Elbadawy, R.; Eldash, H. H.; Eldefrawy, M. S.; Elecharri, C. L.; Elfaramawy, A.; Elfatih, M.; Elfiky, M.; Elgamsy, M.; Elgendy, M.; El-Guindi, M. A.; Elhussieny, N.; Eliwa, A. M.; Elkabbany, Z.; El-Khayat, H.; El-Koofy, N. M.; Elmetwalli, A.; Elrabat, A.; El-Raey, F.; Elrashdy, F.; Elsahhar, M.; Elsaid, E. M.; Elsayed, S.; Elsayed, H.; Elsayed, A.; Elsayed, A. M.; Elsayed, H.; El-Serafy, M.; Elsharkawy, A. M.; Elsheemy, R. Y.; Elshemy, E. E.; Elsherbini, S.; Eltoukhy, N.; Elwakil, R.; Emad, O.; Emad, S.; Embabi, M.; Ergenc, I.; Ermolova, T.; Esmat, G.; Esmat, D. M.; Estupinan, E. C.; Ettair, S.; Eugen, T.; Ezz-Eldin, M.; Falcon, L. P. V.; Fan, Y. -C.; Fandari, S.; Farag, M.; Farahat, T. M.; Fares, E. M.; Fares, M.; Fassio, E.; Fathy, H.; Fathy, D.; Fathy, W.; Fayed, S.; Feng, D.; Feng, G.; Fernandez-Bermejo, M.; Ferreira, C. T.; Ferrer, J. D.; Forbes, A.; Fouad, R.; Fouad, H. M.; Frisch, T.; Fujii, H.; Fukunaga, S.; Fukunishi, S.; Fulya, H.; Furuhashi, M.; Gaber, Y.; Galang, A. J. G.; Gallardo, J. C.; Galloso, R.; Gamal, M.; Gamal, R.; Gamal, H.; Gan, J.; Ganbold, A.; Gao, X.; Garas, G.; Garba, T.; Garcia-Cortes, M.; Garcia-Monzon, C.; Garcia-Samaniego, J.; Gastaldelli, A.; Gatica, M.; Gatley, E.; Gegeshidze, T.; Geng, B.; Ghazinyan, H.; Ghoneem, S.; Giacomelli, L.; Giannelli, G.; Giannini, E. G.; Giefer, M.; Gines, P.; Girala, M.; Giraudi, P. J.; Goh, G. B. -B.; Gomaa, A. A.; Gong, B.; Gonzales, D. H. C.; Gonzalez, H. C.; Gonzalez-Huezo, M. S.; Graupera, I.; Grgurevic, I.; Gronbaek, H.; Gu, X.; Guan, L.; Gueye, I.; Guingane, A. N.; Gul, O. O.; Gul, C. B.; Guo, Q.; Gupta, P. P.; Gurakar, A.; Gutierrez, J. C. R.; Habib, G.; Hafez, A.; Hagman, E.; Halawa, E.; Hamdy, O.; Hamed, A. E.; Hamed, D. H.; Hamid, S.; Hamoudi, W.; Han, Y.; Haridy, J.; Haridy, H.; Harris, D. C. H. H.; Hart, M.; Hasan, F.; Hashim, A.; Hassan, I.; Hassan, A.; Hassan, E. A.; Hassan, A. A.; Hassan, M. S.; Hassanin, F.; Hassnine, A.; Haukeland, J. W.; Hawal, A. I. M.; He, J.; He, Q.; He, Y.; He, F. -P.; Hegazy, M.; Hegazy, A.; Henegil, O.; Hernandez, N.; Hernandez-Guerra, M.; Higuera-de-la-Tijera, F.; Hindy, I.; Hirota, K.; Ho, L. C.; Hodge, A.; Hosny, M.; Hou, X.; Huang, J. -F.; Huang, Y.; Huang, Z.; Huang, Y.; Huang, A.; Huang, X. -P.; Hui-ping, S.; Hunyady, B.; Hussein, M. A.; Hussein, O.; Hussien, S. M.; Ibanez-Samaniego, L.; Ibdah, J.; Ibrahim, L.; Ibrahim, M.; Ibrahim, I.; Icaza-Chavez, M. E.; Idelbi, S.; Idilman, R. I.; Ikeda, M.; Indolfi, G.; Invernizzi, F.; Irshad, I.; Isa, H. M. A.; Iskandar, N. J.; Ismaiel, A.; Ismail, M.; Ismail, Z.; Ismail, F.; Iwamoto, H.; Jack, K.; Jacob, R.; Jafarov, F.; Jafri, W.; Jahshan, H.; Jalal, P. K.; Jancoriene, L.; Janicko, M.; Jayasena, H.; Jefferies, M.; Jha, V.; Ji, F.; Ji, Y.; Jia, J.; Jiang, C.; Jiang, N.; Jiang, Z. -Z.; Jin, X.; Jin, Y.; Jing, X.; Jingyu, Q.; Jinjolava, M.; Jong, F. H. H.; Jucov, A.; Julius, I.; Kaddah, M.; Kamada, Y.; Kamal, A.; Kamal, E. M.; Kamel, A. S.; Kao, J. -H.; Karin, M.; Karlas, T.; Kashwaa, M.; Katsidzira, L.; Kaya, E.; Kayasseh, M. A.; Keenan, B.; Keklikkiran, C.; Keml, W.; Khalaf, D. K.; Khalefa, R.; Khamis, S.; Khater, D.; Khattab, H.; Khavkin, A.; Khlynova, O.; Khmis, N.; Kobyliak, N.; Koffas, A.; Koike, K.; Kok, K. Y. Y.; Koller, T.; Komas, N. P.; Korochanskaya, N. V.; Koulla, Y.; Koya, S.; Kraft, C.; Kraja, B.; Krawczyk, M.; Kuchay, M. S.; Kulkarni, A. V.; Kumar, A.; Kumar, M.; Lakoh, S.; Lam, P.; Lan, L.; Lange, N. F.; Lankarani, K. B.; Lanthier, N.; Lapshyna, K.; Lashen, S. A.; Laure, K. N. J.; Lazebnik, L.; Lebrec, D.; Lee, S. S.; Lee, W. S.; Lee, Y. Y.; Leeming, D. J.; Leite, N. C.; Leon, R.; Lesmana, C. R. A.; Li, J.; Li, Q.; Li, J.; Li, Y. -Y.; Li, Y.; Li, L.; Li, M.; Li, Y.; Liang, H.; Lijuan, T.; Lim, S. G.; Lim, L. -L.; Lin, S.; Lin, H. -C.; Lin, R.; Lithy, R.; Liu, Y.; Liu, Y.; Liu, X.; Liu, W. -Y.; Liu, S.; Liu, K.; Liu, T.; Lonardo, A.; Lopez, M. B.; Lopez-Benages, E.; Lopez-Jaramillo, P.; Lu, H.; Lu, L. G.; Lu, Y.; Lubel, J.; Lui, R.; Lupasco, I.; Luzina, E.; Lv, X. -H.; Lynch, K.; Ma, H. -L.; Machado, M. V.; Maduka, N.; Madzharova, K.; Magdaong, R.; Mahadeva, S.; Mahfouz, A.; Mahmood, N. R. K. N.; Mahmoud, E.; Mahrous, M.; Maiwall, R.; Majeed, A.; Majumdar, A.; Mak, L.; Maklouf, M. M.; Malekzadeh, R.; Mandato, C.; Mangia, A.; Mann, J.; Mansour, H. H.; Mansouri, A.; Mantovani, A.; Mao, J. Q.; Maramag, F.; Marchesini, G.; Marcus, C.; Marinho, R. A. R. T.; Martinez-Chantar, M. L.; Martins, A. A. S.; Marwan, R.; Mason, K. F.; Masoud, G.; Massoud, M. N.; Matamoros, M. A.; Mateos, R. M.; Mawed, A.; Mbanya, J. C.; Mbendi, C.; Mccolaugh, L.; Mcleod, D.; Medina, J. F. R.; Megahed, A.; Mehrez, M.; Memon, I.; Merat, S.; Mercado, R.; Mesbah,

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p<0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (<1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (<1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline