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Does the book have embedded fonts, and are these fonts being stripped by Calibre?
It is not too common, but there are some (badly constructed) books that have embedded fonts, but which become unreadable if the fonts are stripped. For example if the book loads an embedded italic font as a seperate font-family and doesn't set the font-style to itallic, then a normal instead of italic font will be used if the font is stripped.
If that is the case then the best solution is to edit the CSS and fix the mistakes (and complain to the publisher too), but it is hard to describe exactly what changes to make without seeing the book. The other solution is to avoid stripping the embedded font and just read the book with the "Document Default" font setting, if the embedded fonts are not too awful.
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