Thanks for the detailed writeup, all of this checked out when I dug in.
Fusion was the big one. The core drip was getting multiplied by your entire production multiplier stack, which it was never meant to do, so by late game it out-earned the whole real chain. It's flat now (and halved). Still a nice shortcut early on, but it won't carry runs anymore.
Patents were the other half. The payout curve past the softcap was too generous, which is how 2 publishes bought you everything. A run like yours pays about 190 now instead of ~450, so full mastery should take the 8-12 publishes it was meant to. The publish/patent achievements should actually take a while now too.
Challenge goals now scale off what you're actually earning per prestige instead of just patents, and lock in when you start the run. The exhibitions with number goals scale the same way. So no more solving themselves, in theory. Your save carries over fine and anything you've already completed stays completed.
Fair warning that I'm not sure the challenge tuning is right on the first pass. If goals feel brutal at your patent count, or still free, say so and I'll adjust.