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When converting from an e-book source, I leave "Disable font rescalling" check on, unless the book in question has, to my opinion, poor font size choices.
Deciding on whether I'll fix those manually, or by letting Calibre scale the fonts, is on a case by case basis.
If using Calibre font scalling, I find calibre shrinks smaller font sizes *way* too much, so I use this font size key instead of the default:
10.5, 11.0, 11.5, 12.0, 13.5, 17.0, 20.0, 22.0, 24.0
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