About the binding(s?) and missing folios

[ReneZ]

The answer to (2) is "not always" because the Zodiac bifolios were clearly not meant to be nested.

That is correct. A similar argument can be made for the three sheets with pharma illustrations, if one looks at the evolving shapes of the containers. This works best if they are consecutive, and not nested.

The presence of quire numbers on one out of every four sheets with herbal illustrations clearly means that these were meant at that time to be nested in stacks of four. Even with alternating A and B sheets.