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Secretary of State John Kerry condemned the killing of scores of Arab Brotherhood supporters during a sit-in at a Cairo mosque, calling for its Arab ally to respect freedom of expression.
The United States has urged Egypt to pull "back from the brink" after security forces killed dozens of supporters of deposed Islamist president Mohamed Morsi.
Egyptian security forces reportedly opened fire on crowds gathered before dawn Saturday for a sit-in near at Rabaa al-Adawiya mosque in north-east Cairo.
A report in the Independent cited the Muslim Brotherhood as saying 66 people had been killed, and another 61 were "brain dead" on life-support machines.
Egypt's department of health, meantime, put the official figure at 65 dead, with another 4,000 being treated for gunshot wounds and the effects of tear gas.
The New York-based Human Rights Watch put the number at 74 pro-Morsy protesters, many of them shot in the head or chest.
A Muslim Brotherhood spokesman Gehad el-Haddad told the BBC that those responsible for the shootings could be grouped into three — "badly dressed thugs, police in three types of uniform and plain-clothed police."
The sit-in came after a day of huge rival rallies in the Egyptian capital, pitting pro- and anti-Morsi supporters — the latter called by Egypt's interim military leader Egyptian army chief General Abdel Fattah al-Sisi who led the July 3 ouster.
HRW said the killings suggested a "shocking willingness" by police and some politicians to ratchet up violence against their foes.
US Secretary of State John Kerry, meantime, condemned the violence and called on its most important Arab ally to respect the right of peaceful assembly and freedom of expression
According to Reuters he spoke with two senior members of Egypt’s army-installed interim cabinet and released a statement that said:
"This is a pivotal moment for Egypt. The United States ... calls on all of Egypt’s leaders across the political spectrum to act immediately to help their country take a step back from the brink."
Defence secretary Chuck Hagel, meantime, spoke by telephone with Gen. Sisi himself.
Egypt receives over $1 billion in military aid from the US.
Last week, a Washington Post article complained that Egypt’s generals had "ignored" the US and its political advice for the past two years, terming it a "collapse of US prestige and influence in Cairo."
The article was also critical of the Obama administration for not using the "leverage" of US military aid to quell the violence.
President Barack Obama and the Pentagon have responded to by delaying the shipment of F-16 fighter jets to Egypt.
Meanwhile, despite the bloodshed and a threat by the interior minister that they will "soon" be dispersed, Brotherhood supporters vowed to hold their ground on Sunday.