Mechanistic Rigor [Neurosurgery Wiki]

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===== Mechanistic Rigor =====

**Mechanistic rigor** refers to the depth and quality of experimental evidence supporting the biological mechanism underlying a scientific observation.

==== Key Criteria ====
  * Demonstrates causality, not just correlation
  * Includes mechanistic experiments (e.g., knockouts, inhibitors, pathway analysis)
  * Connects molecular events to phenotypic outcomes
  * Uses appropriate controls and model validation
  * Avoids overreliance on indirect or superficial readouts

==== Lack of Mechanistic Rigor ====
  * Fluorescent cargo delivery without demonstrating biological activity
  * No exploration of endosomal escape or intracellular trafficking
  * Absence of pathway dissection or rescue studies

==== Example ====
A study showing Cas9-loaded EVs editing a gene and rescuing phenotype in a disease model demonstrates mechanistic rigor. A study showing only cargo uptake in cells does not.