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The ray emission originating from in-flight annihilation (IA) of positrons is a powerful observable for constraining high-energy positron production from exotic sources. By comparing diffuse ray observations of INTEGRAL, COMPTEL and EGRET to theoretical predictions, we set the most stringent constraints on electrophilic feebly interacting particles (FIPs), thereby proving IA as a valuable probe of new physics. In particular, we extensively discuss the case of MeV-scale sterile neutrinos, where IA sets the most stringent constraints, excluding |U₄|^2 10^-13 and |U₄|^2 2 10^-13 for sterile neutrinos mixed with and neutrinos respectively. These constraints improve existing limits by more than an order of magnitude. We briefly discuss the application of these results to a host of exotic positron sources such as dark photons, axion-like particles, primordial black holes (PBHs) and sub-GeV dark matter (DM).
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