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I looked at the log, it's the updating of the SQLite database that chewing up the time, the metadata.opf activity is diddlysquat. What appears to be temporary file I/O in the root of the config directory surprised me… calibre normally does such things in its cache directory.
Re Process Explorer. Nothing leapt off the page, just a couple of "I wonder what that is, and why is he running that. "
Can you try without running calibre when Firefox is not running. I recently discovered Firefox was making my system unstable… such as unwanted reboots… disabling DuckDuckGo Privacy Essentials seems to have fixed it.
Seeing as how the problem manifests in Windows Safe Mode, could you run calibre under it again and capture another ProcExplorer list.
BR
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