“…Such effects, fundamentally, cannot be neglected, and they can be detected with appropriate data analysis. , If discovering and quantifying the directionality of the observed dynamics are the objectives, it may also be desirable to estimate entropy production (eq ) directly from raw experimental time series (e.g., the photon sequence in Figure ) rather than after postprocessing the data using, e.g., hidden Markov models. In this regard, histogram entropy estimators and compression algorithm-based estimators appear to be promising, ,, although, to the best of our knowledge, they have not yet been applied to photon sequences. On the theory side, there have been recent developments addressing the question of how measures of irreversibility such as the entropy production can be deduced from partial observations such as some but not all transitions; , application of those ideas to experimental trajectories is a promising new direction.…”