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10.1126/sciadv.abe4724 http://scihub22266oqcxt.onion/10.1126/sciadv.abe4724 33187978!7775747!33187978     free     free     free Deprecated: Implicit conversion from float 227.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 227.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 227.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 227.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 227.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 227.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 261.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 261.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Sci+Adv 2021 ; 7 (1): ä Nephropedia Template TP {{tp|p=33187978|t=2021. JAK inhibition reduces SARS-CoV-2 liver infectivity and modulates inflammatory responses to reduce morbidity and mortality |pdf=|usr=}}{{33187978}} gab.com Text JAK inhibition reduces SARS-CoV-2 liver infectivity and modulates inflammatory responses to reduce morbidity and mortality JO: Sci Adv http://www.kidney.de/pget.php?&tw=1&pmid=33187978 #FOAvip Using AI, we identified baricitinib as having antiviral and anticytokine efficacy. We now show a 71% (95% CI 0.15 to 0.58) mortality benefit in 83 patients with moderate-severe SARS-CoV-2 pneumonia with few drug-induced adverse events, including a large elderly cohort (median age, 81 years). An additional 48 cases with mild-moderate pneumonia recovered uneventfully. Using organotypic 3D cultures of primary human liver cells, we demonstrate that interferon-alpha2 increases ACE2 expression and SARS-CoV-2 infectivity in parenchymal cells by greater than fivefold. RNA-seq reveals gene response signatures associated with platelet activation, fully inhibited by baricitinib. Using viral load quantifications and superresolution microscopy, we found that baricitinib exerts activity rapidly through the inhibition of host proteins (numb-associated kinases), uniquely among antivirals. This reveals mechanistic actions of a Janus kinase-1/2 inhibitor targeting viral entry, replication, and the cytokine storm and is associated with beneficial outcomes including in severely ill elderly patients, data that incentivize further randomized controlled trials. Twit Text FOAVip JAK inhibition reduces SARS-CoV-2 liver infectivity and modulates inflammatory responses to reduce morbidity and mortality ????Sci Adv http://www.kidney.de/pget.php?&tw=1&pmid=33187978 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=33187978 #FOAvip English Wikipedia <ref>{{Cite pmid|33187978}}</ref> JAK inhibition reduces SARS-CoV-2 liver infectivity and modulates inflammatory responses to reduce morbidity and mortality #MMPMID33187978 Stebbing J; Sanchez Nievas G; Falcone M; Youhanna S; Richardson P; Ottaviani S; Shen JX; Sommerauer C; Tiseo G; Ghiadoni L; Virdis A; Monzani F; Rizos LR; Forfori F; Avendano Cespedes A; De Marco S; Carrozzi L; Lena F; Sanchez-Jurado PM; Lacerenza LG; Cesira N; Caldevilla Bernardo D; Perrella A; Niccoli L; Mendez LS; Matarrese D; Goletti D; Tan YJ; Monteil V; Dranitsaris G; Cantini F; Farcomeni A; Dutta S; Burley SK; Zhang H; Pistello M; Li W; Romero MM; Andres Pretel F; Simon-Talero RS; Garcia-Molina R; Kutter C; Felce JH; Nizami ZF; Miklosi AG; Penninger JM; Menichetti F; Mirazimi A; Abizanda P; Lauschke VM Sci Adv 2021[Jan]; 7 (1): ä PMID33187978show ga Using AI, we identified baricitinib as having antiviral and anticytokine efficacy. We now show a 71% (95% CI 0.15 to 0.58) mortality benefit in 83 patients with moderate-severe SARS-CoV-2 pneumonia with few drug-induced adverse events, including a large elderly cohort (median age, 81 years). An additional 48 cases with mild-moderate pneumonia recovered uneventfully. Using organotypic 3D cultures of primary human liver cells, we demonstrate that interferon-alpha2 increases ACE2 expression and SARS-CoV-2 infectivity in parenchymal cells by greater than fivefold. RNA-seq reveals gene response signatures associated with platelet activation, fully inhibited by baricitinib. Using viral load quantifications and superresolution microscopy, we found that baricitinib exerts activity rapidly through the inhibition of host proteins (numb-associated kinases), uniquely among antivirals. This reveals mechanistic actions of a Janus kinase-1/2 inhibitor targeting viral entry, replication, and the cytokine storm and is associated with beneficial outcomes including in severely ill elderly patients, data that incentivize further randomized controlled trials. |Adult[MESH] |Aged[MESH] |Aged, 80 and over[MESH] |Antiviral Agents/*pharmacology[MESH] |Azetidines/*pharmacology[MESH] |COVID-19 Drug Treatment[MESH] |COVID-19/metabolism/*mortality/virology[MESH] |Cytokine Release Syndrome[MESH] |Cytokines/metabolism[MESH] |Drug Evaluation, Preclinical[MESH] |Enzyme Inhibitors/*pharmacology[MESH] |Female[MESH] |Gene Expression Profiling[MESH] |Humans[MESH] |Interferon alpha-2/metabolism[MESH] |Italy[MESH] |Janus Kinases/*antagonists & inhibitors/metabolism[MESH] |Liver/drug effects/*virology[MESH] |Male[MESH] |Middle Aged[MESH] |Patient Safety[MESH] |Platelet Activation[MESH] |Proportional Hazards Models[MESH] |Purines/*pharmacology[MESH] |Pyrazoles/*pharmacology[MESH] |RNA-Seq[MESH] |SARS-CoV-2/*pathogenicity[MESH] |Spain[MESH] |Sulfonamides/*pharmacology[MESH]JAK inhibition reduces SARS-CoV-2 liver infectivity and modulates infl(epmc).pdf DeepDyve Pubget Overpricing