IE, if your subbed to notifications on an issue, a...
# random
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IE, if your subbed to notifications on an issue, and somebody leaves a comment on it, you get an email with an address like
<mailto:reply-i-1234ABCD@github.com|reply-i-1234ABCD@github.com>
, if you reply to that email, your reply shows up as a comment on the issue.