In "When Carl Met George," we learn that the Brain has an uncle who has Asperger's Syndrome and is also a Noble Prize winner.
During Francine's nightmare. Mrs. MacGrady was originally suppose to be walking towards a white light, but the film crew thought that it would be too much for a kids show, so they added a green wall over the lighting effects.
In this episode, we learn that Francine's grandfather died of cancer.
Francine reads the title display. It's the one in which Arthur falls behind in a race, so he hops on the back of D.W.'s tricycle to try to catch up.
And Now A Word From Us Kids: The kids talk about their school principal Mr. Springer, who has cancer and they talk about how they dealt with it. Notably, this segment was broadcast following the episode, rather than in the middle, splitting into two-parts as had been done with past double-length stories.
In "No Acting, Please", Fern said all she ever played was a tree in the Arbor Day Extravaganza. However, she did appear in school plays in "Francine Frensky, Superstar" and "Elwood City Turns 100".
Of course, those were school plays. Not really independent productions.