Really want information about if there is a left-handed software setting for the new side-oriented buttons

Yes, I also was curious about left-handed users watching the demo, it seems very right-hand oriented at this time. Maybe there will be a toggle in Settings to switch some of the UI around, kind of like how Apple Watch asks which wrist it's wrapped around.

Right handed women (which is a giant market) are going to love this thing.

They do it for the watch, so it should be on their radar.