MELBOURNE, Australia (AP) — Top-ranked Ash Barty built a big lead in the Australian Open quarterfinals before her opponent took a medical timeout and left the court.

More than an hour later, it was Barty heading abruptly for the exit, upset 1-6, 6-3, 6-2 Wednesday by 25th-seeded Karolina Muchova of the Czech Republic.

Muchova earned her first semifinal berth at a Grand Slam tournament and ended Barty’s bid to become the first Australian woman to win the title at home since Chris O’Neil in 1978.

“It’s heartbreaking, of course,” said Barty, who took nearly all of last year off because of the coronavirus pandemic, including opting not to try to defend her 2019 French Open title. “But the sun will come up tomorrow. You’re either winning or you’re learning, and today is a massive learning curve for me.”

No. 2-ranked Rafael Nadal built a big lead in a night-time quarterfinal, but his bid for a men’s-record 21st Grand Slam title ended with an upset five-set loss to Stefanos Tsitsipas of Greece.

It is only the second time in Nadal’s career he has lost a Grand Slam match after taking the opening two

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Now the 22-year-old, fifth-seeded Tsitsipas will try to reach his first major final by beating Daniil Medvedev on Friday.

The women’s semifinals Thursday will be the first matches at Melbourne Park with crowds in nearly a week after the easing of restrictions imposed by the Victoria state government during a five-day lockdown in Australia’s second-largest city to contain the spread of a COVID-19 cluster.

Tournament director Craig Tiley said Wednesday that attendance will be capped at 7,477 — about half the capacity of Rod Laver Arena — for each of the last four days of the tournament.

Muchova’s opponent will be 22nd-seeded Jennifer Brady, who beat fellow American and good friend Jessica Pegula 4-6, 6-2, 6-1. Brady reached her second Grand Slam semifinal, following a run that far at the U.S. Open in September.

“I hope I make it a habit,” Brady said. “Hopefully I have a new habit of making finals.”

She struggled at times and gave her racket an angry toss midway through the second set. But the unseeded Pegula, who advanced beyond the third round at a major for the first time, appeared to tire down the stretch.

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“We’re such good friends,” Brady said. “I’m really happy for her success. I know we’ll be having a lot more tough battles.”

Medvedev beat Andrey Rublev, his friend and teammate on Russia’s ATP Cup-winning squad, by a 7-5, 6-3, 6-2 score and will take a 19-match winning streak into the semifinals.

“It’s never easy,” Medvedev said about playing a pal. “But, I mean, we’re all so competitive. During the match, you can see nothing matters. Just need to win.”

The No. 4-seeded Medvedev hasn’t dropped a set to No. 7-seeded Rublev in four tour-level matches. That includes their meeting in the U.S. Open quarterfinals last year.

Medvedev called for the trainer after the match to massage his left thigh as he sat in a courtside chair before a TV interview.

“I started cramping. I knew he was cramping, also,” Medvedev said. “At the end, I locked completely.”

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Medvedev is into the semifinals of a major for the third time and is one of two Russians into the semifinals at Melbourne Park. He joins 114th-ranked Aslan Karatsev, a qualifier in the main draw of a major for the first time, who plays top-ranked Novak Djokovic for a spot in the final.

Muchova played poorly at the start of her second major quarterfinal, and Barty raced to a 5-0 lead while losing only six points. After nine games, Muchova had one winner and 18 unforced errors.

Early in the second set, she took a medical timeout that lasted nearly 10 minutes, which players are allowed to do if it’s determined they’re having a problem that goes beyond cramps.

Sunny weather, with the temperature in the mid-80s (30 degrees Celsius), was a factor, Muchova said.

“I think it was a bit of the heat,” she said. “It got to me, and I was feeling kind of dizzy, really lost and almost fainting. I just asked for help.”

Medical personnel took her temperature, checked her blood pressure and gave her ice before she left the court. When Muchova returned, she played much better.

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“I tried to play a bit faster rallies so we don’t play long ones as in the first set,” she said, “and it worked well.”

Barty had no complaints about Muchova halting play.

“It’s within the rules,” Barty said. “She’s within her rights to take that time. That shouldn’t be a massive turning point in the match. I’m disappointed I let that be a turning point.”

Comebacks have been a staple in the tournament for Muchova, who rallied in earlier matches to win sets after trailing 5-0 and 4-0.

Against Barty, she began moving into the court to hit her groundstrokes earlier. Barty, pushed behind the baseline, became indecisive and erratic.

During one stretch, Muchova won eight of nine games. Barty finished with 37 unforced errors and lost serve four times in the final two sets.

“I just overplayed,” Barty said. “I just pressed a little bit too much, and gave up too many cheap errors at some pretty critical times.”

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Brady was in a two-week hard lockdown before the Australian Open because she was among the players who shared a charter flight to Australia with someone who later tested positive for COVID-19.

The tradeoff for that initially was some freedom of movement in Australia.

Crowds of up to 30,000 a day, roughly 50% of what’s normally seen at the tournament, were allowed into Melbourne Park — although the daily attendance never topped 22,500 — before the lockdown was imposed.

This was the first Grand Slam tournament since last year’s Australian Open to permit thousands of people to sit in the stands.

Wimbledon was canceled, the U.S. Open barred fans entirely, and the French Open let about 1,000 spectators per day.

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