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Looking at it more closely, the problem runs deepers than I originally thought. The loss of precision is not due to a cancelation of terms, but due to Mathematica's evaluation of the 2F1's. This should not normally happen because for Mathematica's...
As an update here are some links reporting similar behaviour sometimes by design, sometimes clearly buggy:...
@ Rui. You are right in the sense that the presence of a second argument does indeed matter. I.e. using Optional[_,something] will allow matching of a Length zero element. However, in terms of matching it doesn't really matter what the second...
You might want to try:Simplify[F,R==(x^2 - y^2 - z^2)]