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Modelling the spatiotemporal dynamics in the activity of neural populations while also enabling their flexible inference is hindered by the complexity and noisiness of neural observations. Here we show that the lower-dimensional nonlinear latent factors and latent structures can be computationally modelled in a manner that allows for flexible inference causally, non-causally and in the presence of missing neural observations. To enable flexible inference, we developed a neural network that separates the model into jointly trained manifold and dynamic latent factors such that nonlinearity is captured through the manifold factors and the dynamics can be modelled in tractable linear form on this nonlinear manifold. We show that the model, which we named 'DFINE' (for 'dynamical flexible inference for nonlinear embeddings') achieves flexible inference in simulations of nonlinear dynamics and across neural datasets representing a diversity of brain regions and behaviours. Compared with earlier neural-network models, DFINE enables flexible inference, better predicts neural activity and behaviour, and better captures the latent neural manifold structure. DFINE may advance the development of neurotechnology and investigations in neuroscience., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Synthetic chemistry has traditionally relied on reactions between reactants of high chemical potential and transformations that proceed energetically downhill to either a global or local minimum (thermodynamic or kinetic control). Catalysts can be used to manipulate kinetic control, lowering activation energies to influence reaction outcomes. However, such chemistry is still constrained by the shape of one-dimensional reaction coordinates. Coupling synthesis to an orthogonal energy input can allow ratcheting of chemical reaction outcomes, reminiscent of the ways that molecular machines ratchet random thermal motion to bias conformational dynamics. This fundamentally distinct approach to synthesis allows multi-dimensional potential energy surfaces to be navigated, enabling reaction outcomes that cannot be achieved under conventional kinetic or thermodynamic control. In this Review, we discuss how ratcheted synthesis is ubiquitous throughout biology and consider how chemists might harness ratchet mechanisms to accelerate catalysis, drive chemical reactions uphill and programme complex reaction sequences., (© 2023. Springer Nature Limited.)

Purpose: Bibliometric analyses have gained popularity for studying scientific literature, but their application to evaluate technological literature (patents) remains unexplored. We conducted a bibliometric analysis on the top 100 most-cited patents in scoliosis surgery., Methods: Multiple databases were queried using The Lens to identify the top 100 scoliosis surgery patents, which were selected based on forward patent citations. These patents were then categorized into 8 groups based on technological descriptors and assessed based on various factors including earliest priority date, year issued, and expiration status., Results: The top 100 most-cited patents included technology underlying anterolateral tethering and distraction systems (n = 11), posterior tethering and distraction systems (n = 23), posterior segmental bone anchor and rod engagement systems (n = 29), interbody devices (n = 10), biological and electrophysiological agents for scoliosis treatment and/or improved arthrodesis (n = 8), intraoperative arthroplasty devices (n = 5), orthotic devices (n = 12), and implantable devices for non-invasive, postoperative alterations of skeletal alignment (n = 2). Seventy-five patents were expired, 21 are still active, and 4 were listed as inactive. The late 1970s and early 2000s saw increased numbers of patent filings. Demonstrated trends showed no meaningful correlation between patent rank and earliest priority date (linear trendline y = 0.2648x - 477.27; R 2  = 0.0114), while a very strong correlation was found between patent rank and citations per year (power trendline y = 118.82x --0.83 ; R 2  = 0.8983)., Conclusion: Patent bibliometric analyses in the field of spinal deformity surgery provide a means to assess past advancements, better understand what it takes to make a difference in the field, and to potentially facilitate the development of innovative technologies in the future. The method described is a reliable and reproducible technique for evaluating technological literature in our field., (© 2023. The Author(s), under exclusive licence to Scoliosis Research Society.)