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I don't use standalone cores to play (at the moment), so cannot assist in any way with that. But I have interest in near future to try something that is either not available on RetroArch or is strongly limited. But that is something we don't discuss here, as it gets off topic (and often lead to fights amongst passionate users if you know what I mean). But before I hand wave this, have a look at the topic at https://github.com/xenia-project/xenia/issues/1754 , as Xenia seem to support reading ISO files according to the replies. I don't want discuss it here, so just leaving the link for your further investigations (I don't emulate on my Series S).
Before I knew this, I informed myself on the documentation for each core: https://docs.libretro.com/library/mesen-s/ But the description is more informative for quick overview. The description is from the .info files, in example in https://github.com/libretro/libretro-super/blob/master/dist/info/mesen-s_libretro.info on the bottom line that starts with description =