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World number five Simona Halep has confirmed she will miss next week's Pan Pacific Open in Tokyo through injury.
Halep, a quarter-finalist at the last two grand slams, cited a hamstring problem as the reason for her withdrawal.
In a statement posted on the WTA website, the Romanian said: "I am unfortunately not able to play at this year's Toray Pan Pacific Open due to a hamstring injury in my left leg.
"I've always enjoyed playing in front of my fans in Tokyo and hope to be back there very soon."
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Tokyo is currently playing host to the Japan Women's Open and another of the top seeds bowed out on Wednesday.
After the first-round exits of Misaki Doi and reigning champion Yanina Wickmayer 24 hours earlier, fourth seed Johanna Larsson was beaten in three sets by Varvara Lepchenko.
In addition to Lepchenko, who triumphed 6-2 3-6 6-4, Jana Cepelova and Katerina Siniakova progressed to round three with respective victories over Jang Su-jeong and Louisa Chirico. Siniakova needed almost three hours to prevail 6-4 5-7 7-6 (7-3) in an epic encounter.
Third seed Yulia Putintseva, now the highest-ranked player in the field, was one of four players to win first-round matches on Wednesday, together with Magda Linette, Naomi Osaka and Rebecca Peterson.