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(CNN) —  

Twelve Democratic presidential candidates will take the stage here at Otterbein University on Tuesday during a swirl of news back in Washington and on the other side of the world.

Since Democrats last took the stage in September, House Democrats have opened an impeachment inquiry into President Donald Trump for his attempts to pressure Ukraine into investigating former Vice President Joe Biden’s son, Hunter Biden, and deliver dirt on his possible general election rival. Trump’s former aides and diplomats are being subpoenaed and called to Capitol Hill to talk to Congress about the President.

And Trump’s decision to pull troops from Syria has made way for Turkey to attack the US-allied Kurdish forces, a decision that has been condemned by Democrats and Republicans alike.

The debate represents a number of firsts in the race to take on Trump: It’s the first-time former Biden steps on to the debate stage without being the race’s clear frontrunner, a position he now shares with Massachusetts Sen. Elizabeth Warren; it’s the first time Vermont Sen. Bernie Sanders will return to the campaign trail since suffering a heart attack earlier this month; and the first time a whopping twelve candidates will be on the stage at the same time.

And Tuesday could represent the last time four candidates get this kind of national spotlight: Only eight of the candidates on stage have qualified for the November debate in Georgia, leaving four candidates – Minnesota Sen. Amy Klobuchar, former Rep. Beto O’Rourke, former Housing and Urban Development Secretary Julian Castro and Rep. Tulsi Gabbard – with the real possibility of having Tuesday’s debate be their last.

Here is what to watch for during Tuesday night’s debate:

Warren enters front runner status

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When Democrats gathered in Houston last month for the party’s third debate, Warren had effectively caught Vermont Sen. Bernie Sanders for a share of second place.

And the senator has kept rising from there, catching Biden in a number of national and statewide polls and turning the liberal lawmaker into a co-front runner with the former vice president.

A Quinnipiac poll released earlier this month found Warren in a statistical tie with Biden nationally, with the Massachusetts senator at 29% and the former vice president at 26%. Statewide polls in both Iowa and New Hampshire have also shown a tightening race between the two Democrats, while polls in South Carolina show Biden with a sizable lead.

Warren comes into the debate with an earned confidence, one that has been on display at well-attended rallies across the country.

But, as Biden can attest after the first three debates, the center of the stage is often the focus on the most direct attacks, meaning Warren comes into Tuesday’s debate as the most likely target for candidates looking to make a name for themselves by damaging the race’s new front runner.

And Warren’s opponents have already begun to take aim at her candidacy.

South Bend Mayor Pete Buttigieg suggested her small dollar fundraising strategy that outlaws in-person events – which the mayor described as “pocket change” – won’t defeat Trump. Biden told supporters earlier this month that having plans is “not enough” and that the country won’t support “electing a planner.” And Sanders has faulted Warren for being a “capitalist through her bones.”

“I’m not,” Sanders said.

Biden’s son steps into the spotlight

Joe Biden may be on the stage tonight, but it’s son, who has recently come under withering Republican attacks, who dominated the news on Tuesday morning and could become a topic of the debate during the evening.

Hunter Biden said he used “poor judgment” in serving on the board of a Ukrainian gas company because it has become a political liability for his father.

“I did nothing wrong at all,” he said in an interview with ABC News recorded over the weekend at his home in Los Angeles. “However, was it poor judgment to be in the middle of something that is – it’s a swamp, in many ways? Yeah.”

“Did I do anything improper? No, not in any way. Not in any way whatsoever,” he said.

Biden’s professional involvement with companies in Ukraine and China have led to charges of corruption from President Donald Trump and his allies. There is no evidence of wrongdoing by either Joe or Hunter Biden.

Hunter Biden announced on Sunday that he will resign at the end of the month from his board role in the management company of a private equity fund backed by Chinese state-owned entities, according to a statement released by his attorney. And the former Vice President announced the same day that “no one in my family or associated me will be involved in any foreign operation whatsoever.”

“Period. End of story,” Biden told reporters.

Some Democrats have stepped up to defend Biden during what has become a vitriolic back-and-forth with Trump.

Bernie Sanders returns to the trail

Sanders says it’s been business-as-usual ahead of the debate.

“We are doing what I’m sure every other candidate is doing,” he told CNN on Sunday, “and trying to anticipate the questions that will be asked of them, dealing with complicated answers in 75 seconds or 45 seconds, or whatever it may be.”

But when he steps on the stage at Otterbein University, the 78-year-old will be carrying the added weight of trying to convince voters that, two weeks after his heart attack in Las Vegas, he is physically up for what lies ahead.

This will be Sanders’ first major outing since having two stents inserted to clear a clogged artery. He has spent his time off the trail following up with a cardiologist, doing TV and phone interviews, and – if you go by his social media accounts – taking a lot of batting practice in his backyard up in Burlington, Vermont.

On Tuesday night, though, he will be facing live pitching for the first time in weeks and voters will be keen to see if he can power through three hours on stage, under the lights, without wavering.

The politics will be similarly fraught.

Sanders this weekend made his brightest line contrast with progressive rival Elizabeth Warren this past weekend, noting in an interview with ABC News, “Elizabeth, I think, as you know, has said that she is a capitalist through her bones. I’m not.”

That might not seem like a lot, but Sanders has faithfully held up his end of a nonaggression pact with Warren, even as she climbed up the polls and surpassed him in many. Whether it can hold up as the race heats up remains to be seen.

Impeachment, Ukraine, Syria

Tuesday’s debate takes place as huge, fast-moving national and international news stories continue to develop.

Trump is under threat of impeachment, and Trump’s decision to withdraw troops from Northern Syria has thrown the already chaotic region deeper into bedlam, allowing Turkey to attack U.S.-allied Kurdish forces and threatening to roll back the advancements the United States has made at combating ISIS.

All of this has dominated the news for the last few weeks, largely knocking the Democratic nomination fight out of the headlines and consuming the electorate’s focus.

Candidates are coming to the debate prepared to answer questions on all of these topics. But there is widespread agreement among Democrats on Trump’s handing of Ukraine and Syria, so the candidate that is able to deliver the clearest case against Trump on each issue is likely to leave the debate with some level of confidence.

Buttigieg v. Beto v. Booker

An ongoing fight between South Bend Mayor Pete Buttigieg, O’Rourke and New Jersey Sen. Cory Booker intensified this week.

The three Democrats have publicly sparred over gun control laws for weeks, with Buttigieg and O’Rourke continuing their fight on the issue of ending the tax-exempt status of a religious organization that discriminates against LGBTQ Americans.

The back and forth began earlier this month with the three disagreeing over how far Democrats should go on gun laws. O’Rourke and Booker have pushed for the mandatory buy-backs of assault-style rifles, while Buttigieg has called the focus on that policy a “shiny object” and instead suggested it is smarter to back mandatory background checks, allowing states to adopt “red flag” laws that allow families or police to ask a judge to have a potentially dangerous person’s guns taken away, and banning the sale of additional assault-style rifles.

“I was really offended by those comments,” O’Rourke said of Buttigieg’s comment after a gun control policy forum in Las Vegas on Wednesday. “And I think he represents a kind of politics that is focused on poll-testing and focus-group-driving and triangulating and listening to consultants, before you arrive at a position.”

Buttigieg has not backed down from the fight.

“I get it. He needs to pick a fight in order to stay relevant,” Buttigieg told Snapchat when asked about O’Rourke’s comments.

Buttigieg also called mandatory buy backs “confiscation” in his interview, leading Booker to accuse the Democrats of “doing the NRA’s work for them.”

Booker has also commented on how O’Rourke’s embrace of mandatory buy-backs came after the shooting in El Paso, Texas, his hometown. Booker had already been in favor of the plan by the time O’Rourke supported it.

“He saw the horrors visiting his community,” Booker said of O’Rourke’s reversal on the issue. “Are we going to have to wait until hell’s lottery comes to your community? No, we are a better country.”

O’Rourke and Buttigieg’s sparring continued on the issue of LGBTQ protections in the United States. After O’Rourke argued that religious institutions should lose their tax exempt status if they discriminate against LGBTQ Americans, Buttigieg told CNN that he “wasn’t sure” whether O’Rourke fully “understood the implications of what he was saying.”

“If we want to talk about anti-discrimination law for a school or an organization, absolutely. They should not be able to discriminate,” he told CNN. “But going after the tax-exemption of churches, Islamic centers or other religious facilities in this country, I think that’s just going to deepen the divisions that we’re already experiencing.”

The multi-front fighting leading into the debate makes it likely that the tension could spill out on Tuesday.

Standing out

Tuesday night’s debate stage will be the largest in modern history, presenting candidates with the question of how to stand out when flanked by eleven other candidates.

Businessman Andrew Yang, a candidate who has garnered a devoted following, has made it a point of punctuating each debate performance with a unique moment. Yang opened September’s debate by announcing that he was offering his trademark Freedom Dividend, a $1,000 a year check, to ten people.

And Sen. Kamala Harris has come into each debate with a clear goal to make a moment. Harris, during the June debate, confronted Biden over his history on race and bussing. That moment gave Harris significant momentum, vaulting her all the way to second place in some nationals polls. But that moment proved to be a quick burst and Harris was unable to sustain the momentum.

But Tuesday’s debate could be the last for four Democratic contenders.