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Got a clue.
Most of the time, I connect my laptop to an USB-C docking station, hooking up a wireless keyboard/mouse and two screen.
If I detach the docking, Calibre starts. If I re-connect the docking, it keeps running. If I exit Calibre while still docked and re-start it, it doesn't work.
So, nothing to do with safe mode, AV or conflicting processes, it's the docking.
Maybe this has to do with the last message before exiting "Turning on automatic hidpi scaling"?
Note that I work this way since many years and Calibre used to work OK. Maybe something has changed in the drivers.
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