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The Argentine midfielder scored one goal and set up the other two to send Napoli up to joint fifth in Italy's Serie A, two points behind AC Milan who are fourth after leapfrogging Parma thanks to Marco Borriello's double in a 2-0 home win.
Juve, second in the table, came into the game on a high after Wednesday's 5-1 thrashing of Sampdoria but left the pitch completely stunned having appeared to have the match wrapped up.
"When a coach makes a change, it's so the players will respond and Datolo has done really well," Napoli boss Walter Mazzarri, who has won three out of four games since replacing Roberto Donadoni at the start of the month, told Sky television.