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The Gunners now head into their final game of the Premier League season in fifth place, two points behind fourth-placed Tottenham.
Champions League qualification is no longer in Mikel Arteta's hands following back-to-back defeats to Spurs and Newcastle.
Antonio Conte's team smashed Arsenal 3-0 on Thursday, with Arteta's side failing to move above their cross-town after defeat at St James' Park.
Ben White's own goal and a late Bruno Guimaraes strike in the second half condemned Arsenal to yet another crushing defeat.
"A DAGGER TO THE HEART OF ARSENAL, A HUGE BOOST FOR TOTTENHAM HOTSPUR"— Sky Sports Premier League (@SkySportsPL) May 16, 2022
Newcastle take the lead at St James' Park!! 👊💥 pic.twitter.com/u89X4weTPM
TWO!!— Sky Sports Premier League (@SkySportsPL) May 16, 2022
Bruno Guimarães doubles Newcastle's lead! Arsenal's top four hopes are up in smoke 😮 pic.twitter.com/s457bEUvlS
The visitors weren't at the races, with the hosts dominating the game.
As for Newcastle, they continue their remarkable mid-season turnaround and move above Crystal Palace to 12th place.
Spurs, meanwhile, travel to Norwich City while Arsenal host Everton in the final round of league games on Sunday.
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