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This Topical Collection aims to illustrate innovative work and frontier research that explores recent advances, prospects, and challenges in algorithms and mathematical model applications to reduce the chances of either missing, misclassifying, or over-diagnosing suspicious targets on diagnostic systems. It is noteworthy that the keyword “diagnostic” has to be understood in a wide sense, including medical, mechanical systems, civil engineering, and chemical processes. Submissions are invited from both academic researchers and industrial practitioners, and accepted papers will be published continuously in the journal and listed together on the collection website.