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@mblrdr - the raison d'être for most 'portable' software is to sever the application from the Windows registry.
Installed calibre already does that, all of its application settings are in its "configuration folder" - the raison d'être for doing that is to support a range of operating/file system platforms.
As you no doubt know, calibre is open source software, why don't you download the source and change it to fit your expectations.
BR
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