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Background: Actigraphy derived measures including amplitude, regularity, and variability of daily rhythm, have been shown to predict incident Alzheimer's dementia. Here we developed an integrated actigraphy biomarker (IAB) for Alzheimer' risk and investigated whether the IAB predicted the conversion from mild cognitive impairment (MCI) to Alzheimer' dementia. Method: We studied 1195 participants (age 80.8±7.2yrs [SD]) from the Rush Memory and Aging Project who had finished baseline actigraphy assessment (∼10 days), were free from Alzheimer's dementia at actigraphy baseline and had been followed for up to 15 years with annual cognitive assessment and clinical diagnoses. Ten sleep/circadian related features were derived from baseline actigraphy recordings and were fed into a random forest survival model for prediction of time and incident Alzheimer's dementia. IAB was derived from the model as the relative risk. Cox proportional hazards and logistic regression models were used to evaluate the performance of IAB in predicting incident Alzheimer's dementia (all 1195 participants) or MCI (858 without MCI at baseline) and predicting the conversion from MCI to Alzheimer's dementia. Demographic variables including age, sex, and education were controlled in all Cox and logistic regression models. Result: Total 287 participants developed Alzheimer's dementia during the follow‐up. The derived IAB was 0.6 SD larger in the participants developed Alzheimer's dementia as compared with the controls. Larger IAB was associated with increased risk of AD with a hazard ratio (HR) = 1.63 (95% CI = 1.46‐1.81, P<0.0001) for 1‐SD increase in IAB. IAB did not predict incident MCI (P = 0.8). Within participants with MCI (337 at baseline and 308 developed), larger IAB was associated with a higher risk for AD, i.e., HR = 1.34 for 1 SD increase (95% CI = 1.18‐1.51, P<0.0001). The logistic model using the cutoff of 3 years for the MCI‐Alzheimer's dementia conversion gives the odd ratio = 1.56 for 1 SD increase of IAB, and results in AUC = 0.68, with a sensitivity = 0.68 and specificity = 0.61. Conclusion: Derived actigraphy biomarker was predictive of Alzheimer's risk at preclinical stages, and the conversion from MCI. Actigraphy provides useful information for early prediction and detection of AD thought its performance needs to be improved. [ABSTRACT FROM AUTHOR]

In this paper, how chitosan hydrogel beads were modified by anionic surfactants (SDS, SDOS, SDBS, AOT, and DTM-12) and then used for the adsorption and removal of an anionic dye (congo red) from aqueous solutions were described. The effect of surfactant concentration, surfactant ionic head-group, and surfactant hydrophobic tail were investigated in detail. The result revealed the modified CS beads all had the obviously higher adsorption capacity than CS beads. Compared to the ionic head-group, the hydrophobic tail of the surfactant plays more important role in the adsorption, and a high adsorption capacity was observed for CS/AOT beads and CS/DTM-12 beads (both with two hydrophobic tails). The Sips isotherm model showed a good fit with the equilibrium experimental data, and the values of the heterogeneity factor (n) indicated heterogeneous adsorption. The adsorption kinetics analysis indicated that the pseudo-second-order rate model could better describe the adsorption process than the pseudo-first-order rate model. The surfactant with double hydrophobic tails (i.e., AOT or DTM-12) impregnated CS beads was the best one among the investigated adsorbents, indicating the hydrophobic tail of the surfactant play an important role in controlling the adsorption capacity of the modified CS beads. [ABSTRACT FROM PUBLISHER]

Current cardiac surgery risk models do not address a substantial fraction of procedures. We sought to create models to predict the risk of operative mortality for an expanded set of cases. Four supervised machine learning models were trained using preoperative variables present in the Society of Thoracic Surgeons (STS) data set of the Massachusetts General Hospital to predict and classify operative mortality in procedures without STS risk scores. A total of 424 (5.5%) mortality events occurred out of 7745 cases. Models included logistic regression with elastic net regularization (LogReg), support vector machine, random forest (RF), and extreme gradient boosted trees (XGBoost). Model discrimination was assessed via area under the receiver operating characteristic curve (AUC), and calibration was assessed via calibration slope and expected-to-observed event ratio. External validation was performed using STS data sets from Brigham and Women's Hospital (BWH) and the Johns Hopkins Hospital (JHH). Models performed comparably with the highest mean AUC of 0.83 (RF) and expected-to-observed event ratio of 1.00. On external validation, the AUC was 0.81 in BWH (RF) and 0.79 in JHH (LogReg/RF). Models trained and applied on the same institution's data achieved AUCs of 0.81 (BWH: LogReg/RF/XGBoost) and 0.82 (JHH: LogReg/RF/XGBoost). Machine learning models trained on preoperative patient data can predict operative mortality at a high level of accuracy for cardiac surgical procedures without established risk scores. Such procedures comprise 23% of all cardiac surgical procedures nationwide. This work also highlights the value of using local institutional data to train new prediction models that account for institution-specific practices. Machine learning models can predict operative mortality at a high level of accuracy for cardiac surgical procedures without established risk scores. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: Based on the complex pathology of AD, a single chemical approach may not be sufficient to deal simultaneously with multiple pathways of amyloid-tau neuroinflammation. A polydrug approach which contains multiple bioactive components targeting multiple pathways in AD would be more appropriate. Here we focused on a Chinese medicine (HLXL), which contains 56 bioactive natural products identified in 11 medicinal plants and displays potent anti-inflammatory and immuno-modulatory activity.Hypothesis/purpose: We investigated the neuroimmune and neuroinflammation mechanisms by which HLXL may attenuate AD neuropathology. Specifically, we investigated the effects of HLXL on the neuropathology of AD using both transgenic mouse models as well as microglial cell-based models.Study Design: The 5XFAD transgenic animals and microglial cell models were respectively treated with HLXL and Aβ42, and/or lipopolysaccharide (LPS), and then analyzed focusing on microglia mediated Aβ uptake and clearance, as well as pathway changes.Methods: We showed that HLXL significantly reduced amyloid neuropathology by upregulation of microglia-mediated phagocytosis of Aβ both in vivo and in vitro. HLXL displayed multi-modal mechanisms regulating pathways of phagocytosis and energy metabolism.Results: Our results may not only open a new avenue to support pharmacologic modulation of neuroinflammation and the neuroimmune system for AD intervention, but also identify HLXL as a promising natural medicine for AD.Conclusion: It is conceivable that the traditional wisdom of natural medicine in combination with modern science and technology would be the best strategy in developing effective therapeutics for AD. [ABSTRACT FROM AUTHOR]

Table of contents A1 Functional advantages of cell-type heterogeneity in neural circuits Tatyana O. Sharpee A2 Mesoscopic modeling of propagating waves in visual cortex Alain Destexhe A3 Dynamics and biomarkers of mental disorders Mitsuo Kawato F1 Precise recruitment of spiking output at theta frequencies requires dendritic h-channels in multi-compartment models of oriens-lacunosum/moleculare hippocampal interneurons Vladislav Sekulić, Frances K. Skinner F2 Kernel methods in reconstruction of current sources from extracellular potentials for single cells and the whole brains Daniel K. Wójcik, Chaitanya Chintaluri, Dorottya Cserpán, Zoltán Somogyvári F3 The synchronized periods depend on intracellular transcriptional repression mechanisms in circadian clocks. Jae Kyoung Kim, Zachary P. Kilpatrick, Matthew R. Bennett, Kresimir Josić O1 Assessing irregularity and coordination of spiking-bursting rhythms in central pattern generators Irene Elices, David Arroyo, Rafael Levi, Francisco B. Rodriguez, Pablo Varona O2 Regulation of top-down processing by cortically-projecting parvalbumin positive neurons in basal forebrain Eunjin Hwang, Bowon Kim, Hio-Been Han, Tae Kim, James T. McKenna, Ritchie E. Brown, Robert W. McCarley, Jee Hyun Choi O3 Modeling auditory stream segregation, build-up and bistability James Rankin, Pamela Osborn Popp, John Rinzel O4 Strong competition between tonotopic neural ensembles explains pitch-related dynamics of auditory cortex evoked fields Alejandro Tabas, André Rupp, Emili Balaguer-Ballester O5 A simple model of retinal response to multi-electrode stimulation Matias I. Maturana, David B. Grayden, Shaun L. Cloherty, Tatiana Kameneva, Michael R. Ibbotson, Hamish Meffin O6 Noise correlations in V4 area correlate with behavioral performance in visual discrimination task Veronika Koren, Timm Lochmann, Valentin Dragoi, Klaus Obermayer O7 Input-location dependent gain modulation in cerebellar nucleus neurons Maria Psarrou, Maria Schilstra, Neil Davey, Benjamin Torben-Nielsen, Volker Steuber O8 Analytic solution of cable energy function for cortical axons and dendrites Huiwen Ju, Jiao Yu, Michael L. Hines, Liang Chen, Yuguo Yu O9 C. elegans interactome: interactive visualization of Caenorhabditis elegans worm neuronal network Jimin Kim, Will Leahy, Eli Shlizerman O10 Is the model any good? Objective criteria for computational neuroscience model selection Justas Birgiolas, Richard C. Gerkin, Sharon M. Crook O11 Cooperation and competition of gamma oscillation mechanisms Atthaphon Viriyopase, Raoul-Martin Memmesheimer, Stan Gielen O12 A discrete structure of the brain waves Yuri Dabaghian, Justin DeVito, Luca Perotti O13 Direction-specific silencing of the Drosophila gaze stabilization system Anmo J. Kim, Lisa M. Fenk, Cheng Lyu, Gaby Maimon O14 What does the fruit fly think about values? A model of olfactory associative learning Chang Zhao, Yves Widmer, Simon Sprecher,Walter Senn O15 Effects of ionic diffusion on power spectra of local field potentials (LFP) Geir Halnes, Tuomo Mäki-Marttunen, Daniel Keller, Klas H. Pettersen,Ole A. Andreassen, Gaute T. Einevoll O16 Large-scale cortical models towards understanding relationship between brain structure abnormalities and cognitive deficits Yasunori Yamada O17 Spatial coarse-graining the brain: origin of minicolumns Moira L. Steyn-Ross, D. Alistair Steyn-Ross O18 Modeling large-scale cortical networks with laminar structure Jorge F. Mejias, John D. Murray, Henry Kennedy, Xiao-Jing Wang O19 Information filtering by partial synchronous spikes in a neural population Alexandra Kruscha, Jan Grewe, Jan Benda, Benjamin Lindner O20 Decoding context-dependent olfactory valence in Drosophila Laurent Badel, Kazumi Ohta, Yoshiko Tsuchimoto, Hokto Kazama P1 Neural network as a scale-free network: the role of a hub B. Kahng P2 Hemodynamic responses to emotions and decisions using near-infrared spectroscopy optical imaging Nicoladie D. Tam P3 Phase space analysis of hemodynamic responses to intentional movement directions using functional near-infrared spectroscopy (fNIRS) optical imaging technique Nicoladie D.Tam, Luca Pollonini, George Zouridakis P4 Modeling jamming avoidance of weakly electric fish Jaehyun Soh, DaeEun Kim P5 Synergy and redundancy of retinal ganglion cells in prediction Minsu Yoo, S. E. Palmer P6 A neural field model with a third dimension representing cortical depth Viviana Culmone, Ingo Bojak P7 Network analysis of a probabilistic connectivity model of the Xenopus tadpole spinal cord Andrea Ferrario, Robert Merrison-Hort, Roman Borisyuk P8 The recognition dynamics in the brain Chang Sub Kim P9 Multivariate spike train analysis using a positive definite kernel Taro Tezuka P10 Synchronization of burst periods may govern slow brain dynamics during general anesthesia Pangyu Joo P11 The ionic basis of heterogeneity affects stochastic synchrony Young-Ah Rho, Shawn D. Burton, G. Bard Ermentrout, Jaeseung Jeong, Nathaniel N. Urban P12 Circular statistics of noise in spike trains with a periodic component Petr Marsalek P14 Representations of directions in EEG-BCI using Gaussian readouts Hoon-Hee Kim, Seok-hyun Moon, Do-won Lee, Sung-beom Lee, Ji-yong Lee, Jaeseung Jeong P15 Action selection and reinforcement learning in basal ganglia during reaching movements Yaroslav I. Molkov, Khaldoun Hamade, Wondimu Teka, William H. Barnett, Taegyo Kim, Sergey Markin, Ilya A. Rybak P17 Axon guidance: modeling axonal growth in T-Junction assay Csaba Forro, Harald Dermutz, László Demkó, János Vörös P19 Transient cell assembly networks encode persistent spatial memories Yuri Dabaghian, Andrey Babichev P20 Theory of population coupling and applications to describe high order correlations in large populations of interacting neurons Haiping Huang P21 Design of biologically-realistic simulations for motor control Sergio Verduzco-Flores P22 Towards understanding the functional impact of the behavioural variability of neurons Filipa Dos Santos, Peter Andras P23 Different oscillatory dynamics underlying gamma entrainment deficits in schizophrenia Christoph Metzner, Achim Schweikard, Bartosz Zurowski P24 Memory recall and spike frequency adaptation James P. Roach, Leonard M. Sander, Michal R. Zochowski P25 Stability of neural networks and memory consolidation preferentially occur near criticality Quinton M. Skilling, Nicolette Ognjanovski, Sara J. Aton, Michal Zochowski P26 Stochastic Oscillation in Self-Organized Critical States of Small Systems: Sensitive Resting State in Neural Systems Sheng-Jun Wang, Guang Ouyang, Jing Guang, Mingsha Zhang, K. Y. Michael Wong, Changsong Zhou P27 Neurofield: a C++ library for fast simulation of 2D neural field models Peter A. Robinson, Paula Sanz-Leon, Peter M. Drysdale, Felix Fung, Romesh G. Abeysuriya, Chris J. Rennie, Xuelong Zhao P28 Action-based grounding: Beyond encoding/decoding in neural code Yoonsuck Choe, Huei-Fang Yang P29 Neural computation in a dynamical system with multiple time scales Yuanyuan Mi, Xiaohan Lin, Si Wu P30 Maximum entropy models for 3D layouts of orientation selectivity Joscha Liedtke, Manuel Schottdorf, Fred Wolf P31 A behavioral assay for probing computations underlying curiosity in rodents Yoriko Yamamura, Jeffery R. Wickens P32 Using statistical sampling to balance error function contributions to optimization of conductance-based models Timothy Rumbell, Julia Ramsey, Amy Reyes, Danel Draguljić, Patrick R. Hof, Jennifer Luebke, Christina M. Weaver P33 Exploration and implementation of a self-growing and self-organizing neuron network building algorithm Hu He, Xu Yang, Hailin Ma, Zhiheng Xu, Yuzhe Wang P34 Disrupted resting state brain network in obese subjects: a data-driven graph theory analysis Kwangyeol Baek, Laurel S. Morris, Prantik Kundu, Valerie Voon P35 Dynamics of cooperative excitatory and inhibitory plasticity Everton J. Agnes, Tim P. Vogels P36 Frequency-dependent oscillatory signal gating in feed-forward networks of integrate-and-fire neurons William F. Podlaski, Tim P. Vogels P37 Phenomenological neural model for adaptation of neurons in area IT Martin Giese, Pradeep Kuravi, Rufin Vogels P38 ICGenealogy: towards a common topology of neuronal ion channel function and genealogy in model and experiment Alexander Seeholzer, William Podlaski, Rajnish Ranjan, Tim Vogels P39 Temporal input discrimination from the interaction between dynamic synapses and neural subthreshold oscillations Joaquin J. Torres, Fabiano Baroni, Roberto Latorre, Pablo Varona P40 Different roles for transient and sustained activity during active visual processing Bart Gips, Eric Lowet, Mark J. Roberts, Peter de Weerd, Ole Jensen, Jan van der Eerden P41 Scale-free functional networks of 2D Ising model are highly robust against structural defects: neuroscience implications Abdorreza Goodarzinick, Mohammad D. Niry, Alireza Valizadeh P42 High frequency neuron can facilitate propagation of signal in neural networks Aref Pariz, Shervin S. Parsi, Alireza Valizadeh P43 Investigating the effect of Alzheimer’s disease related amyloidopathy on gamma oscillations in the CA1 region of the hippocampus Julia M. Warburton, Lucia Marucci, Francesco Tamagnini, Jon Brown, Krasimira Tsaneva-Atanasova P44 Long-tailed distributions of inhibitory and excitatory weights in a balanced network with eSTDP and iSTDP Florence I. Kleberg, Jochen Triesch P45 Simulation of EMG recording from hand muscle due to TMS of motor cortex Bahar Moezzi, Nicolangelo Iannella, Natalie Schaworonkow, Lukas Plogmacher, Mitchell R. Goldsworthy, Brenton Hordacre, Mark D. McDonnell, Michael C. Ridding, Jochen Triesch P46 Structure and dynamics of axon network formed in primary cell culture Martin Zapotocky, Daniel Smit, Coralie Fouquet, Alain Trembleau P47 Efficient signal processing and sampling in random networks that generate variability Sakyasingha Dasgupta, Isao Nishikawa, Kazuyuki Aihara, Taro Toyoizumi P48 Modeling the effect of riluzole on bursting in respiratory neural networks Daniel T. Robb, Nick Mellen, Natalia Toporikova P49 Mapping relaxation training using effective connectivity analysis Rongxiang Tang, Yi-Yuan Tang P50 Modeling neuron oscillation of implicit sequence learning Guangsheng Liang, Seth A. Kiser, James H. Howard, Jr., Yi-Yuan Tang P51 The role of cerebellar short-term synaptic plasticity in the pathology and medication of downbeat nystagmus Julia Goncharenko, Neil Davey, Maria Schilstra, Volker Steuber P52 Nonlinear response of noisy neurons Sergej O. Voronenko, Benjamin Lindner P53 Behavioral embedding suggests multiple chaotic dimensions underlie C. elegans locomotion Tosif Ahamed, Greg Stephens P54 Fast and scalable spike sorting for large and dense multi-electrodes recordings Pierre Yger, Baptiste Lefebvre, Giulia Lia Beatrice Spampinato, Elric Esposito, Marcel Stimberg et Olivier Marre P55 Sufficient sampling rates for fast hand motion tracking Hansol Choi, Min-Ho Song P56 Linear readout of object manifolds SueYeon Chung, Dan D. Lee, Haim Sompolinsky P57 Differentiating models of intrinsic bursting and rhythm generation of the respiratory pre-Bötzinger complex using phase response curves Ryan S. Phillips, Jeffrey Smith P58 The effect of inhibitory cell network interactions during theta rhythms on extracellular field potentials in CA1 hippocampus Alexandra Pierri Chatzikalymniou, Katie Ferguson, Frances K. Skinner P59 Expansion recoding through sparse sampling in the cerebellar input layer speeds learning N. Alex Cayco Gajic, Claudia Clopath, R. Angus Silver P60 A set of curated cortical models at multiple scales on Open Source Brain Padraig Gleeson, Boris Marin, Sadra Sadeh, Adrian Quintana, Matteo Cantarelli, Salvador Dura-Bernal, William W. Lytton, Andrew Davison, R. Angus Silver P61 A synaptic story of dynamical information encoding in neural adaptation Luozheng Li, Wenhao Zhang, Yuanyuan Mi, Dahui Wang, Si Wu P62 Physical modeling of rule-observant rodent behavior Youngjo Song, Sol Park, Ilhwan Choi, Jaeseung Jeong, Hee-sup Shin P64 Predictive coding in area V4 and prefrontal cortex explains dynamic discrimination of partially occluded shapes Hannah Choi, Anitha Pasupathy, Eric Shea-Brown P65 Stability of FORCE learning on spiking and rate-based networks Dongsung Huh, Terrence J. Sejnowski P66 Stabilising STDP in striatal neurons for reliable fast state recognition in noisy environments Simon M. Vogt, Arvind Kumar, Robert Schmidt P67 Electrodiffusion in one- and two-compartment neuron models for characterizing cellular effects of electrical stimulation Stephen Van Wert, Steven J. Schiff P68 STDP improves speech recognition capabilities in spiking recurrent circuits parameterized via differential evolution Markov Chain Monte Carlo Richard Veale, Matthias Scheutz P69 Bidirectional transformation between dominant cortical neural activities and phase difference distributions Sang Wan Lee P70 Maturation of sensory networks through homeostatic structural plasticity Júlia Gallinaro, Stefan Rotter P71 Corticothalamic dynamics: structure, number of solutions and stability of steady-state solutions in the space of synaptic couplings Paula Sanz-Leon, Peter A. Robinson P72 Optogenetic versus electrical stimulation of the parkinsonian basal ganglia. Computational study Leonid L. Rubchinsky, Chung Ching Cheung, Shivakeshavan Ratnadurai-Giridharan P73 Exact spike-timing distribution reveals higher-order interactions of neurons Safura Rashid Shomali, Majid Nili Ahmadabadi, Hideaki Shimazaki, S. Nader Rasuli P74 Neural mechanism of visual perceptual learning using a multi-layered neural network Xiaochen Zhao, Malte J. Rasch P75 Inferring collective spiking dynamics from mostly unobserved systems Jens Wilting, Viola Priesemann P76 How to infer distributions in the brain from subsampled observations Anna Levina, Viola Priesemann P77 Influences of embedding and estimation strategies on the inferred memory of single spiking neurons Lucas Rudelt, Joseph T. Lizier, Viola Priesemann P78 A nearest-neighbours based estimator for transfer entropy between spike trains Joseph T. Lizier, Richard E. Spinney, Mikail Rubinov, Michael Wibral, Viola Priesemann P79 Active learning of psychometric functions with multinomial logistic models Ji Hyun Bak, Jonathan Pillow P81 Inferring low-dimensional network dynamics with variational latent Gaussian process Yuan Zaho, Il Memming Park P82 Computational investigation of energy landscapes in the resting state subcortical brain network Jiyoung Kang, Hae-Jeong Park P83 Local repulsive interaction between retinal ganglion cells can generate a consistent spatial periodicity of orientation map Jaeson Jang, Se-Bum Paik P84 Phase duration of bistable perception reveals intrinsic time scale of perceptual decision under noisy condition Woochul Choi, Se-Bum Paik P85 Feedforward convergence between retina and primary visual cortex can determine the structure of orientation map Changju Lee, Jaeson Jang, Se-Bum Paik P86 Computational method classifying neural network activity patterns for imaging data Min Song, Hyeonsu Lee, Se-Bum Paik P87 Symmetry of spike-timing-dependent-plasticity kernels regulates volatility of memory Youngjin Park, Woochul Choi, Se-Bum Paik P88 Effects of time-periodic coupling strength on the first-spike latency dynamics of a scale-free network of stochastic Hodgkin-Huxley neurons Ergin Yilmaz, Veli Baysal, Mahmut Ozer P89 Spectral properties of spiking responses in V1 and V4 change within the trial and are highly relevant for behavioral performance Veronika Koren, Klaus Obermayer P90 Methods for building accurate models of individual neurons Daniel Saska, Thomas Nowotny P91 A full size mathematical model of the early olfactory system of honeybees Ho Ka Chan, Alan Diamond, Thomas Nowotny P92 Stimulation-induced tuning of ongoing oscillations in spiking neural networks Christoph S. Herrmann, Micah M. Murray, Silvio Ionta, Axel Hutt, Jérémie Lefebvre P93 Decision-specific sequences of neural activity in balanced random networks driven by structured sensory input Philipp Weidel, Renato Duarte, Abigail Morrison P94 Modulation of tuning induced by abrupt reduction of SST cell activity Jung H. Lee, Ramakrishnan Iyer, Stefan Mihalas P95 The functional role of VIP cell activation during locomotion Jung H. Lee, Ramakrishnan Iyer, Christof Koch, Stefan Mihalas P96 Stochastic inference with spiking neural networks Mihai A. Petrovici, Luziwei Leng, Oliver Breitwieser, David Stöckel, Ilja Bytschok, Roman Martel, Johannes Bill, Johannes Schemmel, Karlheinz Meier P97 Modeling orientation-selective electrical stimulation with retinal prostheses Timothy B. Esler, Anthony N. Burkitt, David B. Grayden, Robert R. Kerr, Bahman Tahayori, Hamish Meffin P98 Ion channel noise can explain firing correlation in auditory nerves Bahar Moezzi, Nicolangelo Iannella, Mark D. McDonnell P99 Limits of temporal encoding of thalamocortical inputs in a neocortical microcircuit Max Nolte, Michael W. Reimann, Eilif Muller, Henry Markram P100 On the representation of arm reaching movements: a computational model Antonio Parziale, Rosa Senatore, Angelo Marcelli P101 A computational model for investigating the role of cerebellum in acquisition and retention of motor behavior Rosa Senatore, Antonio Parziale, Angelo Marcelli P102 The emergence of semantic categories from a large-scale brain network of semantic knowledge K. Skiker, M. Maouene P103 Multiscale modeling of M1 multitarget pharmacotherapy for dystonia Samuel A. Neymotin, Salvador Dura-Bernal, Alexandra Seidenstein, Peter Lakatos, Terence D. Sanger, William W. Lytton P104 Effect of network size on computational capacity Salvador Dura-Bernal, Rosemary J. Menzies, Campbell McLauchlan, Sacha J. van Albada, David J. Kedziora, Samuel Neymotin, William W. Lytton, Cliff C. Kerr P105 NetPyNE: a Python package for NEURON to facilitate development and parallel simulation of biological neuronal networks Salvador Dura-Bernal, Benjamin A. Suter, Samuel A. Neymotin, Cliff C. Kerr, Adrian Quintana, Padraig Gleeson, Gordon M. G. Shepherd, William W. Lytton P107 Inter-areal and inter-regional inhomogeneity in co-axial anisotropy of Cortical Point Spread in human visual areas Juhyoung Ryu, Sang-Hun Lee P108 Two bayesian quanta of uncertainty explain the temporal dynamics of cortical activity in the non-sensory areas during bistable perception Joonwon Lee, Sang-Hun Lee P109 Optimal and suboptimal integration of sensory and value information in perceptual decision making Hyang Jung Lee, Sang-Hun Lee P110 A Bayesian algorithm for phoneme Perception and its neural implementation Daeseob Lim, Sang-Hun Lee P111 Complexity of EEG signals is reduced during unconsciousness induced by ketamine and propofol Jisung Wang, Heonsoo Lee P112 Self-organized criticality of neural avalanche in a neural model on complex networks Nam Jung, Le Anh Quang, Seung Eun Maeng, Tae Ho Lee, Jae Woo Lee P113 Dynamic alterations in connection topology of the hippocampal network during ictal-like epileptiform activity in an in vitro rat model Chang-hyun Park, Sora Ahn, Jangsup Moon, Yun Seo Choi, Juhee Kim, Sang Beom Jun, Seungjun Lee, Hyang Woon Lee P114 Computational model to replicate seizure suppression effect by electrical stimulation Sora Ahn, Sumin Jo, Eunji Jun, Suin Yu, Hyang Woon Lee, Sang Beom Jun, Seungjun Lee P115 Identifying excitatory and inhibitory synapses in neuronal networks from spike trains using sorted local transfer entropy Felix Goetze, Pik-Yin Lai P116 Neural network model for obstacle avoidance based on neuromorphic computational model of boundary vector cell and head direction cell Seonghyun Kim, Jeehyun Kwag P117 Dynamic gating of spike pattern propagation by Hebbian and anti-Hebbian spike timing-dependent plasticity in excitatory feedforward network model Hyun Jae Jang, Jeehyun Kwag P118 Inferring characteristics of input correlations of cells exhibiting up-down state transitions in the rat striatum Marko Filipović, Ramon Reig, Ad Aertsen, Gilad Silberberg, Arvind Kumar P119 Graph properties of the functional connected brain under the influence of Alzheimer’s disease Claudia Bachmann, Simone Buttler, Heidi Jacobs, Kim Dillen, Gereon R. Fink, Juraj Kukolja, Abigail Morrison P120 Learning sparse representations in the olfactory bulb Daniel Kepple, Hamza Giaffar, Dima Rinberg, Steven Shea, Alex Koulakov P121 Functional classification of homologous basal-ganglia networks Jyotika Bahuguna,Tom Tetzlaff, Abigail Morrison, Arvind Kumar, Jeanette Hellgren Kotaleski P122 Short term memory based on multistability Tim Kunze, Andre Peterson, Thomas Knösche P123 A physiologically plausible, computationally efficient model and simulation software for mammalian motor units Minjung Kim, Hojeong Kim P125 Decoding laser-induced somatosensory information from EEG Ji Sung Park, Ji Won Yeon, Sung-Phil Kim P126 Phase synchronization of alpha activity for EEG-based personal authentication Jae-Hwan Kang, Chungho Lee, Sung-Phil Kim P129 Investigating phase-lags in sEEG data using spatially distributed time delays in a large-scale brain network model Andreas Spiegler, Spase Petkoski, Matias J. Palva, Viktor K. Jirsa P130 Epileptic seizures in the unfolding of a codimension-3 singularity Maria L. Saggio, Silvan F. Siep, Andreas Spiegler, William C. Stacey, Christophe Bernard, Viktor K. Jirsa P131 Incremental dimensional exploratory reasoning under multi-dimensional environment Oh-hyeon Choung, Yong Jeong P132 A low-cost model of eye movements and memory in personal visual cognition Yong-il Lee, Jaeseung Jeong P133 Complex network analysis of structural connectome of autism spectrum disorder patients Su Hyun Kim, Mir Jeong, Jaeseung Jeong P134 Cognitive motives and the neural correlates underlying human social information transmission, gossip Jeungmin Lee, Jaehyung Kwon, Jerald D. Kralik, Jaeseung Jeong P135 EEG hyperscanning detects neural oscillation for the social interaction during the economic decision-making Jaehwan Jahng, Dong-Uk Hwang, Jaeseung Jeong P136 Detecting purchase decision based on hyperfrontality of the EEG Jae-Hyung Kwon, Sang-Min Park, Jaeseung Jeong P137 Vulnerability-based critical neurons, synapses, and pathways in the Caenorhabditis elegans connectome Seongkyun Kim, Hyoungkyu Kim, Jerald D. Kralik, Jaeseung Jeong P138 Motif analysis reveals functionally asymmetrical neurons in C. elegans Pyeong Soo Kim, Seongkyun Kim, Hyoungkyu Kim, Jaeseung Jeong P139 Computational approach to preference-based serial decision dynamics: do temporal discounting and working memory affect it? Sangsup Yoon, Jaehyung Kwon, Sewoong Lim, Jaeseung Jeong P141 Social stress induced neural network reconfiguration affects decision making and learning in zebrafish Choongseok Park, Thomas Miller, Katie Clements, Sungwoo Ahn, Eoon Hye Ji, Fadi A. Issa P142 Descriptive, generative, and hybrid approaches for neural connectivity inference from neural activity data JeongHun Baek, Shigeyuki Oba, Junichiro Yoshimoto, Kenji Doya, Shin Ishii P145 Divergent-convergent synaptic connectivities accelerate coding in multilayered sensory systems Thiago S. Mosqueiro, Martin F. Strube-Bloss, Brian Smith, Ramon Huerta P146 Swinging networks Michal Hadrava, Jaroslav Hlinka P147 Inferring dynamically relevant motifs from oscillatory stimuli: challenges, pitfalls, and solutions Hannah Bos, Moritz Helias P148 Spatiotemporal mapping of brain network dynamics during cognitive tasks using magnetoencephalography and deep learning Charles M. Welzig, Zachary J. Harper P149 Multiscale complexity analysis for the segmentation of MRI images Won Sup Kim, In-Seob Shin, Hyeon-Man Baek, Seung Kee Han P150 A neuro-computational model of emotional attention René Richter, Julien Vitay, Frederick Beuth, Fred H. Hamker P151 Multi-site delayed feedback stimulation in parkinsonian networks Kelly Toppin, Yixin Guo P152 Bistability in Hodgkin–Huxley-type equations Tatiana Kameneva, Hamish Meffin, Anthony N. Burkitt, David B. Grayden P153 Phase changes in postsynaptic spiking due to synaptic connectivity and short term plasticity: mathematical analysis of frequency dependency Mark D. McDonnell, Bruce P. Graham P154 Quantifying resilience patterns in brain networks: the importance of directionality Penelope J. Kale, Leonardo L. Gollo P155 Dynamics of rate-model networks with separate excitatory and inhibitory populations Merav Stern, L. F. Abbott P156 A model for multi-stable dynamics in action recognition modulated by integration of silhouette and shading cues Leonid A. Fedorov, Martin A. Giese P157 Spiking model for the interaction between action recognition and action execution Mohammad Hovaidi Ardestani, Martin Giese P158 Surprise-modulated belief update: how to learn within changing environments? Mohammad Javad Faraji, Kerstin Preuschoff, Wulfram Gerstner P159 A fast, stochastic and adaptive model of auditory nerve responses to cochlear implant stimulation Margriet J. van Gendt, Jeroen J. Briaire, Randy K. Kalkman, Johan H. M. Frijns P160 Quantitative comparison of graph theoretical measures of simulated and empirical functional brain networks Won Hee Lee, Sophia Frangou P161 Determining discriminative properties of fMRI signals in schizophrenia using highly comparative time-series analysis Ben D. Fulcher, Patricia H. P. Tran, Alex Fornito P162 Emergence of narrowband LFP oscillations from completely asynchronous activity during seizures and high-frequency oscillations Stephen V. Gliske, William C. Stacey, Eugene Lim, Katherine A. Holman, Christian G. Fink P163 Neuronal diversity in structure and function: cross-validation of anatomical and physiological classification of retinal ganglion cells in the mouse Jinseop S. Kim, Shang Mu, Kevin L. Briggman, H. Sebastian Seung, the EyeWirers P164 Analysis and modelling of transient firing rate changes in area MT in response to rapid stimulus feature changes Detlef Wegener, Lisa Bohnenkamp, Udo A. Ernst P165 Step-wise model fitting accounting for high-resolution spatial measurements: construction of a layer V pyramidal cell model with reduced morphology Tuomo Mäki-Marttunen, Geir Halnes, Anna Devor, Christoph Metzner, Anders M. Dale, Ole A. Andreassen, Gaute T. Einevoll P166 Contributions of schizophrenia-associated genes to neuron firing and cardiac pacemaking: a polygenic modeling approach Tuomo Mäki-Marttunen, Glenn T. Lines, Andy Edwards, Aslak Tveito, Anders M. Dale, Gaute T. Einevoll, Ole A. Andreassen P167 Local field potentials in a 4 × 4 mm2 multi-layered network model Espen Hagen, Johanna Senk, Sacha J. van Albada, Markus Diesmann P168 A spiking network model explains multi-scale properties of cortical dynamics Maximilian Schmidt, Rembrandt Bakker, Kelly Shen, Gleb Bezgin, Claus-Christian Hilgetag, Markus Diesmann, Sacha Jennifer van Albada P169 Using joint weight-delay spike-timing dependent plasticity to find polychronous neuronal groups Haoqi Sun, Olga Sourina, Guang-Bin Huang, Felix Klanner, Cornelia Denk P170 Tensor decomposition reveals RSNs in simulated resting state fMRI Katharina Glomb, Adrián Ponce-Alvarez, Matthieu Gilson, Petra Ritter, Gustavo Deco P171 Getting in the groove: testing a new model-based method for comparing task-evoked vs resting-state activity in fMRI data on music listening Matthieu Gilson, Maria AG Witek, Eric F. Clarke, Mads Hansen, Mikkel Wallentin, Gustavo Deco, Morten L. 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A correction to this paper has been published: https://doi.org/10.1007/s11145-021-10171-4 [ABSTRACT FROM AUTHOR]

Background: Medical notes are a rich source of patient data; however, the nature of unstructured text has largely precluded the use of these data for large retrospective analyses. Transforming clinical text into structured data can enable large-scale research studies with electronic health records (EHR) data. Natural language processing (NLP) can be used for text information retrieval, reducing the need for labor-intensive chart review. Here we present an application of NLP to large-scale analysis of medical records at 2 large hospitals for patients hospitalized with COVID-19. Objective: Our study goal was to develop an NLP pipeline to classify the discharge disposition (home, inpatient rehabilitation, skilled nursing inpatient facility [SNIF], and death) of patients hospitalized with COVID-19 based on hospital discharge summary notes. Methods: Text mining and feature engineering were applied to unstructured text from hospital discharge summaries. The study included patients with COVID-19 discharged from 2 hospitals in the Boston, Massachusetts area (Massachusetts General Hospital and Brigham and Women's Hospital) between March 10, 2020, and June 30, 2020. The data were divided into a training set (70%) and hold-out test set (30%). Discharge summaries were represented as bags-of-words consisting of single words (unigrams), bigrams, and trigrams. The number of features was reduced during training by excluding n-grams that occurred in fewer than 10% of discharge summaries, and further reduced using least absolute shrinkage and selection operator (LASSO) regularization while training a multiclass logistic regression model. Model performance was evaluated using the hold-out test set. Results: The study cohort included 1737 adult patients (median age 61 [SD 18] years; 55% men; 45% White and 16% Black; 14% nonsurvivors and 61% discharged home). The model selected 179 from a vocabulary of 1056 engineered features, consisting of combinations of unigrams, bigrams, and trigrams. The top features contributing most to the classification by the model (for each outcome) were the following: "appointments specialty," "home health," and "home care" (home); "intubate" and "ARDS" (inpatient rehabilitation); "service" (SNIF); "brief assessment" and "covid" (death). The model achieved a micro-average area under the receiver operating characteristic curve value of 0.98 (95% CI 0.97-0.98) and average precision of 0.81 (95% CI 0.75-0.84) in the testing set for prediction of discharge disposition. Conclusions: A supervised learning–based NLP approach is able to classify the discharge disposition of patients hospitalized with COVID-19. This approach has the potential to accelerate and increase the scale of research on patients' discharge disposition that is possible with EHR data. JMIR Med Inform 2021;9(2):e25457 doi:10.2196/25457 [ABSTRACT FROM AUTHOR]

Metal nanomaterials have emerged as compelling candidates for ultrafast photonics applications, owing to their outstanding saturable absorption properties induced by surface plasmon resonance effects. In recent years, the exploration of saturable absorbers has encompassed noble to non-noble metals as well as diverse structures such as clusters, nanowires and nanoplates. Herein, we comprehensively elucidate the operational principles of metal nanomaterials in ultrafast lasers, including the surface plasmon resonance effect and their complex optical properties. Furthermore, recent advancements in metal nanomaterials utilized in ultrafast lasers have been systematically summarized and classified according to the dimensional structure that profoundly affects their properties. Moreover, the operating parameters of saturable absorbers based on metal nanomaterials are listed in detail. Finally, we look ahead to further directions of metal nanomaterials in ultrafast photonics, presenting explorations in metasurfaces, potential alternatives, and novel integration methods. [ABSTRACT FROM AUTHOR]

Backgrounds: Sleep disturbances are prevalent among elderly individuals. While polysomnography (PSG) serves as the gold standard for sleep monitoring, its extensive setup and data analysis procedures impose significant costs and time constraints, thereby restricting the long-term application within the general public. Our laboratory introduced an innovative biomarker, utilizing artificial intelligence algorithms applied to PSG data to estimate brain age (BA), a metric validated in cohorts with cognitive impairments. Nevertheless, the potential of exercise, which has been a recognized means of enhancing sleep quality in middle-aged and older adults to reduce BA, remains undetermined. Methods: We conducted an exploratory study to evaluate whether 12 weeks of moderate-intensity exercise can improve cognitive function, sleep quality, and the brain age index (BAI), a biomarker computed from overnight sleep electroencephalogram (EEG), in physically inactive middle-aged and older adults. Home wearable devices were used to monitor heart rate and overnight sleep EEG over this period. The NIH Toolbox Cognition Battery, in-lab overnight polysomnography, cardiopulmonary exercise testing, and a multiplex cytokines assay were employed to compare pre- and post-exercise brain health, exercise capacity, and plasma proteins. Results: In total, 26 participants completed the initial assessment and exercise program, and 24 completed all procedures. Data are presented as mean [lower 95% CI of mean, upper 95% CI of mean]. Participants significantly increased maximal oxygen consumption (Pre: 21.11 [18.98, 23.23], Post 22.39 [20.09, 24.68], mL/kg/min; effect size: −0.33) and decreased resting heart rate (Pre: 66.66 [63.62, 67.38], Post: 65.13 [64.25, 66.93], bpm; effect size: −0.02) and sleeping heart rate (Pre: 64.55 [61.87, 667.23], Post: 62.93 [60.78, 65.09], bpm; effect size: −0.15). Total cognitive performance (Pre: 111.1 [107.6, 114.6], Post: 115.2 [111.9, 118.5]; effect size: 0.49) was significantly improved. No significant differences were seen in BAI or measures of sleep macro- and micro-architecture. Plasma IL-4 (Pre: 0.24 [0.18, 0.3], Post: 0.33 [0.24, 0.42], pg/mL; effect size: 0.49) was elevated, while IL-8 (Pre: 5.5 [4.45, 6.55], Post: 4.3 [3.66, 5], pg/mL; effect size: −0.57) was reduced. Conclusions: Cognitive function was improved by a 12-week moderate-intensity exercise program in physically inactive middle-aged and older adults, as were aerobic fitness (VO2max) and plasma cytokine profiles. However, we found no measurable effects on sleep architecture or BAI. It remains to be seen whether a study with a larger sample size and more intensive or more prolonged exercise exposure can demonstrate a beneficial effect on sleep quality and brain age. [ABSTRACT FROM AUTHOR]

The brain age index (BAI) measures the difference between an individual's apparent "brain age" (BA; estimated by comparing EEG features during sleep from an individual with age norms), and their chronological age (CA); that is BAI = BA–CA. Here, we evaluate whether BAI predicts life expectancy. Brain age was quantified using a previously published machine learning algorithm for a cohort of participants ≥40 years old who underwent an overnight sleep electroencephalogram (EEG) as part of the Sleep Heart Health Study (n = 4877). Excess brain age (BAI >0) was associated with reduced life expectancy (adjusted hazard ratio: 1.12, [1.03, 1.21], p = 0.002). Life expectancy decreased by −0.81 [−1.44, −0.24] years per standard-deviation increase in BAI. Our findings show that BAI, a sleep EEG-based biomarker of the deviation of sleep microstructure from patterns normal for age, is an independent predictor of life expectancy. • Brain age index (BAI), a sleep EEG-based biomarker, is associated with reduced life expectancy. • BAI is the difference between sleep EEG-predicted brain age and chronological age. • Each standard-deviation increase in BAI decreases life expectancy by about one year. [ABSTRACT FROM AUTHOR]

• We developed a deep learning algorithm to detect mesial temporal lobe epileptiform discharges on intracranial EEG. • Convolutional neural networks with simple architectures deliver excellent performance in detecting epileptiform discharges. • Quantification of intracranial epileptiform activity has many research and clinical applications. Develop a high-performing algorithm to detect mesial temporal lobe (mTL) epileptiform discharges on intracranial electrode recordings. An epileptologist annotated 13,959 epileptiform discharges from a dataset of intracranial EEG recordings from 46 epilepsy patients. Using this dataset, we trained a convolutional neural network (CNN) to recognize mTL epileptiform discharges from a single intracranial bipolar channel. The CNN outputs from multiple bipolar channel inputs were averaged to generate the final detector output. Algorithm performance was estimated using a nested 5-fold cross-validation. On the receiver-operating characteristic curve, our algorithm achieved an area under the curve (AUC) of 0.996 and a partial AUC (for specificity > 0.9) of 0.981. AUC on a precision-recall curve was 0.807. A sensitivity of 84% was attained at a false positive rate of 1 per minute. 35.9% of the false positive detections corresponded to epileptiform discharges that were missed during expert annotation. Using deep learning, we developed a high-performing, patient non-specific algorithm for detection of mTL epileptiform discharges on intracranial electrodes. Our algorithm has many potential applications for understanding the impact of mTL epileptiform discharges in epilepsy and on cognition, and for developing therapies to specifically reduce mTL epileptiform activity. [ABSTRACT FROM AUTHOR]

Sleep electroencephalogram (EEG) signals likely encode brain health information that may identify individuals at high risk for age-related brain diseases. Here, we evaluate the correlation of a previously proposed brain age biomarker, the "brain age index" (BAI), with cognitive test scores and use machine learning to develop and validate a series of new sleep EEG-based indices, termed "sleep cognitive indices" (SCIs), that are directly optimized to correlate with specific cognitive scores. Three overarching cognitive processes were examined: total, fluid (a measure of cognitive processes involved in reasoning-based problem solving and susceptible to aging and neuropathology), and crystallized cognition (a measure of cognitive processes involved in applying acquired knowledge toward problem-solving). We show that SCI decoded information about total cognition (Pearson's r = 0.37) and fluid cognition (Pearson's r = 0.56), while BAI correlated only with crystallized cognition (Pearson's r = − 0.25). Overall, these sleep EEG-derived biomarkers may provide accessible and clinically meaningful indicators of neurocognitive health. [ABSTRACT FROM AUTHOR]

Background/objectives: Clinical seizures following acute ischemic stroke (AIS) appear to contribute to worse neurologic outcomes. However, the effect of electrographic epileptiform abnormalities (EAs) more broadly is less clear. Here, we evaluate the impact of EAs, including electrographic seizures and periodic and rhythmic patterns, on outcomes in patients with AIS.Methods: This is a retrospective study of all patients with AIS aged ≥ 18 years who underwent at least 18 h of continuous electroencephalogram (EEG) monitoring at a single center between 2012 and 2017. EAs were classified according to American Clinical Neurophysiology Society (ACNS) nomenclature and included seizures and periodic and rhythmic patterns. EA burden for each 24-h epoch was defined using the following cutoffs: EA presence, maximum daily burden < 10% versus > 10%, maximum daily burden < 50% versus > 50%, and maximum daily burden using categories from ACNS nomenclature ("rare" < 1%; "occasional" 1-9%; "frequent" 10-49%; "abundant" 50-89%; "continuous" > 90%). Maximum EA frequency for each epoch was dichotomized into ≥ 1.5 Hz versus < 1.5 Hz. Poor neurologic outcome was defined as a modified Rankin Scale score of 4-6 (vs. 0-3 as good outcome) at hospital discharge.Results: One hundred and forty-three patients met study inclusion criteria. Sixty-seven patients (46.9%) had EAs. One hundred and twenty-four patients (86.7%) had poor outcome. On univariate analysis, the presence of EAs (OR 3.87 [1.27-11.71], p = 0.024) and maximum daily burden > 10% (OR 12.34 [2.34-210], p = 0.001) and > 50% (OR 8.26 [1.34-122], p = 0.035) were associated with worse outcomes. On multivariate analysis, after adjusting for clinical covariates (age, gender, NIHSS, APACHE II, stroke location, stroke treatment, hemorrhagic transformation, Charlson comorbidity index, history of epilepsy), EA presence (OR 5.78 [1.36-24.56], p = 0.017), maximum daily burden > 10% (OR 23.69 [2.43-230.7], p = 0.006), and maximum daily burden > 50% (OR 9.34 [1.01-86.72], p = 0.049) were associated with worse outcomes. After adjusting for covariates, we also found a dose-dependent association between increasing EA burden and increasing probability of poor outcomes (OR 1.89 [1.18-3.03] p = 0.009). We did not find an independent association between EA frequency and outcomes (OR: 4.43 [.98-20.03] p = 0.053). However, the combined effect of increasing EA burden and frequency ≥ 1.5 Hz (EA burden * frequency) was significantly associated with worse outcomes (OR 1.64 [1.03-2.63] p = 0.039).Conclusions: Electrographic seizures and periodic and rhythmic patterns in patients with AIS are associated with worse outcomes in a dose-dependent manner. Future studies are needed to assess whether treatment of this EEG activity can improve outcomes. [ABSTRACT FROM AUTHOR]

[Display omitted] • Neurologic outcomes are typically extracted by manual chart review of EHR notes. • Chart review is laborious, limiting the scope of EHR based neurologic outcome studies. • The NLP model can automatically extract neurological outcomes from medical notes. • The NLP model has potential to accelerate the scale of research with EHR data. Neurologic disability level at hospital discharge is an important outcome in many clinical research studies. Outside of clinical trials, neurologic outcomes must typically be extracted by labor intensive manual review of clinical notes in the electronic health record (EHR). To overcome this challenge, we set out to develop a natural language processing (NLP) approach that automatically reads clinical notes to determine neurologic outcomes, to make it possible to conduct larger scale neurologic outcomes studies. We obtained 7314 notes from 3632 patients hospitalized at two large Boston hospitals between January 2012 and June 2020, including discharge summaries (3485), occupational therapy (1472) and physical therapy (2357) notes. Fourteen clinical experts reviewed notes to assign scores on the Glasgow Outcome Scale (GOS) with 4 classes, namely 'good recovery', 'moderate disability', 'severe disability', and 'death' and on the Modified Rankin Scale (mRS), with 7 classes, namely 'no symptoms', 'no significant disability', 'slight disability', 'moderate disability', 'moderately severe disability', 'severe disability', and 'death'. For 428 patients' notes, 2 experts scored the cases generating interrater reliability estimates for GOS and mRS. After preprocessing and extracting features from the notes, we trained a multiclass logistic regression model using LASSO regularization and 5-fold cross validation for hyperparameter tuning. The model performed well on the test set, achieving a micro average area under the receiver operating characteristic and F-score of 0.94 (95% CI 0.93–0.95) and 0.77 (0.75–0.80) for GOS, and 0.90 (0.89–0.91) and 0.59 (0.57–0.62) for mRS, respectively. Our work demonstrates that an NLP algorithm can accurately assign neurologic outcomes based on free text clinical notes. This algorithm increases the scale of research on neurological outcomes that is possible with EHR data. [ABSTRACT FROM AUTHOR]

Objective: Although seizures are the cardinal feature, epilepsy is associated with other forms of brain dysfunction including impaired cognition, abnormal sleep, and increased risk of developing dementia. We hypothesized that, given the widespread neurologic dysfunction caused by epilepsy, accelerated brain aging would be seen. We measured the sleep-based brain age index (BAI) in a diverse group of patients with epilepsy. The BAI is a machine learning-based biomarker that measures how much the brain activity of a person during overnight sleep deviates from chronological age-based norms., Methods: This case-control study drew information of age-matched controls without epilepsy from home sleep monitoring volunteers and from non-epilepsy patients with Sleep Lab testing. Patients with epilepsy underwent in-patient monitoring and were classified by epilepsy type and seizure burden. The primary outcomes measured were BAI, processed from electroencephalograms, and epilepsy severity metrics (years with epilepsy, seizure frequency standardized by year, and seizure burden [number of seizures in life]). Subanalyses were conducted on a subset with NIH Toolbox cognitive testing for total, fluid, and crystallized composite cognition., Results: 138 patients with epilepsy (32 exclusively focal and 106 generalizable [focal seizures with secondary generalization]) underwent in-patient monitoring, and age-matched, non-epilepsy controls were analyzed. The mean BAI was higher in epilepsy patients vs controls and differed by epilepsy type: -0.05 years (controls) versus 5.02 years (all epilepsy, p < 0.001), 5.53 years (generalizable, p < 0.001), and 3.34 years (focal, p = 0.03). Sleep architecture was disrupted in epilepsy, especially in generalizable epilepsy. A higher BAI was positively associated with increased lifetime seizure burden in focal and generalizable epilepsies and associated with lower crystallized cognition. Lifetime seizure burden was inversely correlated with fluid, crystallized, and composite cognition., Significance: Epilepsy is associated with accelerated brain aging. Higher brain age indices are associated with poorer cognition and more severe epilepsy, specifically generalizability and higher seizure burden. These findings strengthen the use of the sleep-derived, electroencephalography-based BAI as a biomarker for cognitive dysfunction in epilepsy., Competing Interests: RJT is co-inventor and patent holder of the ECG-derived sleep spectrogram, which may be used to phenotype sleep quality and central/complex sleep apnea. The technology is licensed by Beth Israel Deaconess Medical Center to MyCardio, LLC. He is also co-inventor and patent holder of the Positive Airway Pressure Gas Modulator, being developed for treatment of central/complex sleep apnea. He has consulted for Jazz Pharmaceuticals and consults for Guidepoint Global and GLG Councils. He is co-inventor of a licensed auto-CPAP software to DeVilbiss-Drive. MBW and SC are co-founders of Beacon Biosignals, which is an EEG neurobiomarker platform and acquired Dreem (which provided some of the data in this study). MBW serves as a scientific advisor and consultant to, and has a personal equity interest in, Beacon Biosignals. PA works for Beacon Biosignals. RA has worked on aging and dementia, and has received consulting fees from Signant Health, Biogen, and the Davos Alzheimer’s Collaborative; honoraria from NovoNordisk, support for attending Alzheimer’s Drug Discovery Foundation and American Heart Association meetings; and equipment and materials from Gates Ventures, Davos Alzheimer’s Collaborative, and Linus Health. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be constructed as a potential conflict of interest., (Copyright © 2024 Hadar, Westmeijer, Sun, Meulenbrugge, Jing, Paixao, Tesh, Da Silva Cardoso, Arnal, Au, Shin, Kim, Thomas, Cash and Westover.)

Study Objectives: This study aimed to (1) improve sleep staging accuracy through transfer learning (TL), to achieve or exceed human inter-expert agreement and (2) introduce a scorability model to assess the quality and trustworthiness of automated sleep staging., Methods: A deep neural network (base model) was trained on a large multi-site polysomnography (PSG) dataset from the United States. TL was used to calibrate the model to a reduced montage and limited samples from the Korean Genome and Epidemiology Study (KoGES) dataset. Model performance was compared to inter-expert reliability among three human experts. A scorability assessment was developed to predict the agreement between the model and human experts., Results: Initial sleep staging by the base model showed lower agreement with experts (κ = 0.55) compared to the inter-expert agreement (κ = 0.62). Calibration with 324 randomly sampled training cases matched expert agreement levels. Further targeted sampling improved performance, with models exceeding inter-expert agreement (κ = 0.70). The scorability assessment, combining biosignal quality and model confidence features, predicted model-expert agreement moderately well (R² = 0.42). Recordings with higher scorability scores demonstrated greater model-expert agreement than inter-expert agreement. Even with lower scorability scores, model performance was comparable to inter-expert agreement., Conclusions: Fine-tuning a pretrained neural network through targeted TL significantly enhances sleep staging performance for an atypical montage, achieving and surpassing human expert agreement levels. The introduction of a scorability assessment provides a robust measure of reliability, ensuring quality control and enhancing the practical application of the system before deployment. This approach marks an important advancement in automated sleep analysis, demonstrating the potential for AI to exceed human performance in clinical settings., (© The Author(s) 2024. Published by Oxford University Press on behalf of Sleep Research Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Objectives: Unstructured and structured data in electronic health records (EHR) are a rich source of information for research and quality improvement studies. However, extracting accurate information from EHR is labor-intensive. Here we introduce an automated EHR phenotyping model to identify patients with Alzheimer's Disease, related dementias (ADRD), or mild cognitive impairment (MCI)., Methods: We assembled medical notes and associated International Classification of Diseases (ICD) codes and medication prescriptions from 3,626 outpatient adults from two hospitals seen between February 2015 and June 2022. Ground truth annotations regarding the presence vs. absence of a diagnosis of MCI or ADRD were determined through manual chart review. Indicators extracted from notes included the presence of keywords and phrases in unstructured clinical notes, prescriptions of medications associated with MCI/ADRD, and ICD codes associated with MCI/ADRD. We trained a regularized logistic regression model to predict the ground truth annotations. Model performance was evaluated using area under the receiver operating curve (AUROC), area under the precision-recall curve (AUPRC), accuracy, specificity, precision/positive predictive value, recall/sensitivity, and F1 score (harmonic mean of precision and recall)., Results: Thirty percent of patients in the cohort carried diagnoses of MCI/ADRD based on manual review. When evaluated on a held-out test set, the best model using clinical notes, ICDs, and medications, achieved an AUROC of 0.98, an AUPRC of 0.98, an accuracy of 0.93, a sensitivity (recall) of 0.91, a specificity of 0.96, a precision of 0.96, and an F1 score of 0.93 The estimated overall accuracy for patients randomly selected from EHRs was 99.88%., Conclusion: Automated EHR phenotyping accurately identifies patients with MCI/ADRD based on clinical notes, ICD codes, and medication records. This approach holds potential for large-scale MCI/ADRD research utilizing EHR databases., Competing Interests: Competing Interests The authors declare that there are no competing interests regarding the publication of this paper. Additional Declarations: The authors declare no competing interests.

Background: Postoperative delirium is the most common complication following surgery among older adults, and has been consistently associated with increased mortality and morbidity, cognitive decline, and loss of independence, as well as markedly increased health-care costs. Electroencephalography (EEG) spectral slowing has frequently been observed during episodes of delirium, whereas intraoperative frontal alpha power is associated with postoperative delirium. We sought to identify preoperative predictors that could identify individuals at high risk for postoperative delirium, which could guide clinical decision-making and enable targeted interventions to potentially decrease delirium incidence and postoperative delirium-related complications., Methods: In this prospective observational study, we used machine learning to evaluate whether baseline (preoperative) cognitive function and resting-state EEG could be used to identify patients at risk for postoperative delirium. Preoperative resting-state EEGs and the Montreal Cognitive Assessment were collected from 85 patients (age = 73 ± 6.4 years, 12 cases of delirium) undergoing elective surgery. The model with the highest f1-score was subsequently validated in an independent, prospective cohort of 51 older adults (age = 68 ± 5.2 years, 6 cases of delirium) undergoing elective surgery., Results: Occipital alpha powers have higher f1-score than frontal alpha powers and EEG spectral slowing in the training cohort. Occipital alpha powers were able to predict postoperative delirium with AUC, specificity and accuracy all >90%, and sensitivity >80%, in the validation cohort. Notably, models incorporating transformed alpha powers and cognitive scores outperformed models incorporating occipital alpha powers alone or cognitive scores alone., Conclusions: While requiring prospective validation in larger cohorts, these results suggest that strong prediction of postoperative delirium may be feasible in clinical settings using simple and widely available clinical tools. Additionally, our results suggested that the thalamocortical circuit exhibits different EEG patterns under different stressors, with occipital alpha powers potentially reflecting baseline vulnerabilities., Competing Interests: Dr. E. Santarnecchi serves on the scientific advisory boards for BottNeuro, which has no overlap with present work; and is listed as an inventor on several issued and pending patents on brain stimulation solutions to diagnose or treat neurodegenerative disorders and brain tumors. Dr. A. Pascual-Leone is a co-founder of Linus Health and TI Solutions AG which have no overlap with present work. He serves on the scientific advisory boards for the ACE Foundation and the IT’IS Foundation, Neuroelectrics, TetraNeuron, Skin2Neuron, MedRhythms, and Magstim Inc; and is listed as an inventor on several issued and pending patents on the real-time integration of noninvasive brain stimulation with electroencephalography and magnetic resonance imaging, applications of noninvasive brain stimulation in various neurological disorders, as well as digital biomarkers of cognition and digital assessments for early diagnosis of dementia. Dr. M Berger has received private legal consulting fees related to perioperative neurocognitive disorders. None of the other authors report any conflicts of interest. All the other co-authors fully disclose they have no financial interests, activities, relationships and affiliations. The other co-authors also declare they have no potential conflicts in the three years prior to submission of this manuscript.

Background: Atrial fibrillation (AF) is often asymptomatic and thus under-observed. Given the high risks of stroke and heart failure among patients with AF, early prediction and effective management are crucial. Given the prevalence of obstructive sleep apnea among AF patients, electrocardiogram (ECG) analysis from polysomnography (PSG) offers a unique opportunity for early AF prediction. Our aim is to identify individuals at high risk of AF development from single‑lead ECGs during standard PSG., Methods: We analyzed 18,782 single‑lead ECG recordings from 13,609 subjects undergoing PSG at the Massachusetts General Hospital sleep laboratory. AF presence was identified using ICD-9/10 codes. The dataset included 15,913 recordings without AF history and 2054 recordings from patients diagnosed with AF between one month to fifteen years post-PSG. Data were partitioned into training, validation, and test cohorts ensuring that individual patients remained exclusive to each cohort. The test set was held out during the training process. We employed two different methods for feature extraction to build a final model for AF prediction: Extraction of hand-crafted ECG features and a deep learning method. For extraction of ECG-hand-crafted features, recordings were split into 30-s windows, and those with a signal quality index (SQI) below 0.95 were discarded. From each remaining window, 150 features were extracted from the time, frequency, time-frequency domains, and phase-space reconstructions of the ECG. A compilation of 12 statistical features summarized these window-specific features per recording, resulting in 1800 features (12 × 150). A pre-trained deep neural network from the PhysioNet Challenge 2021 was updated using transfer learning to discriminate recordings with and without AF. The model processed PSG ECGs in 16-s windows to generate AF probabilities, from which 13 statistical features were extracted. Combining 1800 features from feature extraction with 13 from the deep learning model, we performed a feature selection and subsequently trained a shallow neural network to predict future AF and evaluated its performance on the test cohort., Results: On the test set, our model exhibited sensitivity, specificity, and precision of 0.67, 0.81, and 0.3, respectively, for AF prediction. Survival analysis revealed a hazard ratio of 8.36 (p-value: 1.93 × 10 -52 ) for AF outcomes using the log-rank test., Conclusions: Our proposed ECG analysis method, utilizing overnight PSG data, shows promise in AF prediction despite modest precision, suggesting false positives. This approach could enable low-cost screening and proactive treatment for high-risk patients. Refinements, including additional physiological parameters, may reduce false positives, enhancing clinical utility and accuracy., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier Inc.)

The ability to assess sleep at home, capture sleep stages, and detect the occurrence of apnea (without on-body sensors) simply by analyzing the radio waves bouncing off people's bodies while they sleep is quite powerful. Such a capability would allow for longitudinal data collection in patients' homes, informing our understanding of sleep and its interaction with various diseases and their therapeutic responses, both in clinical trials and routine care. In this article, we develop an advanced machine learning algorithm for passively monitoring sleep and nocturnal breathing from radio waves reflected off people while asleep. Validation results in comparison with the gold standard (i.e., polysomnography) (n=880) demonstrate that the model captures the sleep hypnogram (with an accuracy of 80.5% for 30-second epochs categorized into Wake, Light Sleep, Deep Sleep, or REM), detects sleep apnea (AUROC = 0.89), and measures the patient's Apnea-Hypopnea Index (ICC=0.90; 95% CI = [0.88, 0.91]). Notably, the model exhibits equitable performance across race, sex, and age. Moreover, the model uncovers informative interactions between sleep stages and a range of diseases including neurological, psychiatric, cardiovascular, and immunological disorders. These findings not only hold promise for clinical practice and interventional trials but also underscore the significance of sleep as a fundamental component in understanding and managing various diseases., (© The Author(s) 2024. Published by Oxford University Press on behalf of Sleep Research Society.)

Over the past few years, artificial intelligence (AI) has emerged as a powerful tool used to efficiently automate several tasks across multiple domains. Sleep medicine is perfectly positioned to leverage this tool due to the wealth of physiological signals obtained through sleep studies or sleep tracking devices and abundance of accessible clinical data through electronic medical records. However, caution must be applied when utilizing AI, due to intrinsic challenges associated with novel technology. The Artificial Intelligence in Sleep Medicine Committee of the American Academy of Sleep Medicine reviews advancements in AI within the sleep medicine field. In this article, the Artificial Intelligence in Sleep Medicine committee members provide a commentary on the scope of AI technology in sleep medicine. The commentary identifies 3 pivotal areas in sleep medicine that can benefit from AI technologies: clinical care, lifestyle management, and population health management. This article provides a detailed analysis of the strengths, weaknesses, opportunities, and threats associated with using AI-enabled technologies in each pivotal area. Finally, the article broadly reviews barriers and challenges associated with using AI-enabled technologies and offers possible solutions., Citation: Bandyopadhyay A, Oks M, Sun H, et al. Strengths, weaknesses, opportunities, and threats of using AI-enabled technology in sleep medicine: a commentary. J Clin Sleep Med . 2024;20(7):1183-1191., (© 2024 American Academy of Sleep Medicine.)

Background/objectives: Epileptiform activity (EA), including seizures and periodic patterns, worsens outcomes in patients with acute brain injuries (e.g., aneurysmal subarachnoid hemorrhage [aSAH]). Randomized control trials (RCTs) assessing anti-seizure interventions are needed. Due to scant drug efficacy data and ethical reservations with placebo utilization, and complex physiology of acute brain injury, RCTs are lacking or hindered by design constraints. We used a pharmacological model-guided simulator to design and determine the feasibility of RCTs evaluating EA treatment., Methods: In a single-center cohort of adults (age >18) with aSAH and EA, we employed a mechanistic pharmacokinetic-pharmacodynamic framework to model treatment response using observational data. We subsequently simulated RCTs for levetiracetam and propofol, each with three treatment arms mirroring clinical practice and an additional placebo arm. Using our framework, we simulated EA trajectories across treatment arms. We predicted discharge modified Rankin Scale as a function of baseline covariates, EA burden, and drug doses using a double machine learning model learned from observational data. Differences in outcomes across arms were used to estimate the required sample size., Results: Sample sizes ranged from 500 for levetiracetam 7 mg/kg versus placebo, to >4000 for levetiracetam 15 versus 7 mg/kg to achieve 80% power (5% type I error). For propofol 1 mg/kg/h versus placebo, 1200 participants were needed. Simulations comparing propofol at varying doses did not reach 80% power even at samples >1200., Conclusions: Our simulations using drug efficacy show sample sizes are infeasible, even for potentially unethical placebo-control trials. We highlight the strength of simulations with observational data to inform the null hypotheses and propose use of this simulation-based RCT paradigm to assess the feasibility of future trials of anti-seizure treatment in acute brain injury., (© 2024 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Study Objectives: To use relatively noisy routinely collected clinical data (brain magnetic resonance imaging (MRI) data, clinical polysomnography (PSG) recordings, and neuropsychological testing), to investigate hypothesis-driven and data-driven relationships between brain physiology, structure, and cognition., Methods: We analyzed data from patients with clinical PSG, brain MRI, and neuropsychological evaluations. SynthSeg, a neural network-based tool, provided high-quality segmentations despite noise. A priori hypotheses explored associations between brain function (measured by PSG) and brain structure (measured by MRI). Associations with cognitive scores and dementia status were studied. An exploratory data-driven approach investigated age-structure-physiology-cognition links., Results: Six hundred and twenty-three patients with sleep PSG and brain MRI data were included in this study; 160 with cognitive evaluations. Three hundred and forty-two participants (55%) were female, and age interquartile range was 52 to 69 years. Thirty-six individuals were diagnosed with dementia, 71 with mild cognitive impairment, and 326 with major depression. One hundred and fifteen individuals were evaluated for insomnia and 138 participants had an apnea-hypopnea index equal to or greater than 15. Total PSG delta power correlated positively with frontal lobe/thalamic volumes, and sleep spindle density with thalamic volume. rapid eye movement (REM) duration and amygdala volume were positively associated with cognition. Patients with dementia showed significant differences in five brain structure volumes. REM duration, spindle, and slow-oscillation features had strong associations with cognition and brain structure volumes. PSG and MRI features in combination predicted chronological age (R2 = 0.67) and cognition (R2 = 0.40)., Conclusions: Routine clinical data holds extended value in understanding and even clinically using brain-sleep-cognition relationships., (© The Author(s) 2023. Published by Oxford University Press on behalf of Sleep Research Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background and Objectives: Patterns of electrical activity in the brain (EEG) during sleep are sensitive to various health conditions even at subclinical stages. The objective of this study was to estimate sleep EEG-predicted incidence of future neurologic, cardiovascular, psychiatric, and mortality outcomes., Methods: This is a retrospective cohort study with 2 data sets. The Massachusetts General Hospital (MGH) sleep data set is a clinic-based cohort, used for model development. The Sleep Heart Health Study (SHHS) is a community-based cohort, used as the external validation cohort. Exposure is good, average, or poor sleep defined by quartiles of sleep EEG-predicted risk. The outcomes include ischemic stroke, intracranial hemorrhage, mild cognitive impairment, dementia, atrial fibrillation, myocardial infarction, type 2 diabetes, hypertension, bipolar disorder, depression, and mortality. Diagnoses were based on diagnosis codes, brain imaging reports, medications, cognitive scores, and hospital records. We used the Cox survival model with death as the competing risk., Results: There were 8673 participants from MGH and 5650 from SHHS. For all outcomes, the model-predicted 10-year risk was within the 95% confidence interval of the ground truth, indicating good prediction performance. When comparing participants with poor, average, and good sleep, except for atrial fibrillation, all other 10-year risk ratios were significant. The model-predicted 10-year risk ratio closely matched the observed event rate in the external validation cohort., Discussion: The incidence of health outcomes can be predicted by brain activity during sleep. The findings strengthen the concept of sleep as an accessible biological window into unfavorable brain and general health outcomes., Competing Interests: M.B. Westover is the co-founder of Beacon Biosignals and Director for Data Science for the McCance Center for Brain Health. R.J. Thomas discloses (1) patent and license/royalties from MyCardio, LLC, for the ECG-spectrogram; (2) patent and license/royalties from DeVilbiss-Drive for an auto-CPAP algorithm; and (3) consulting for Jazz Pharmaceuticals, Guidepoint Global, and GLG Councils. Other authors declare that they have no conflict of interest. Full disclosure form information provided by the authors is available with the full text of this article at Neurology.org/cp., (© 2023 American Academy of Neurology.)

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition characterized by diverse clinical features. EEG biomarkers such as spectral power and functional connectivity have emerged as potential tools for enhancing early diagnosis and understanding of the neural processes underlying ASD. However, existing studies yield conflicting results, necessitating a comprehensive, data-driven analysis. We conducted a retrospective cross-sectional study involving 246 children with ASD and 42 control children. EEG was collected, and diverse EEG features, including spectral power and spectral coherence were extracted. Statistical inference methods, coupled with machine learning models, were employed to identify differences in EEG features between ASD and control groups and develop classification models for diagnostic purposes. Our analysis revealed statistically significant differences in spectral coherence, particularly in gamma and beta frequency bands, indicating elevated long range functional connectivity between frontal and parietal regions in the ASD group. Machine learning models achieved modest classification performance of ROC-AUC at 0.65. While machine learning approaches offer some discriminative power classifying individuals with ASD from controls, they also indicate the need for further refinement., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Ke, Wu, Sun, Zhou, Liu, Zheng, Liu, Westover, Xu and Kong.)

Background: Fractal motor activity regulation (FMAR), characterized by self-similar temporal patterns in motor activity across timescales, is robust in healthy young humans but degrades with aging and in Alzheimer's disease (AD)., Objective: To determine the timescales where alterations of FMAR can best predict the clinical onset of AD., Methods: FMAR was assessed from actigraphy at baseline in 1,077 participants who had annual follow-up clinical assessments for up to 15 years. Survival analysis combined with deep learning (DeepSurv) was used to examine how baseline FMAR at different timescales from 3 minutes up to 6 hours contributed differently to the risk for incident clinical AD., Results: Clinical AD occurred in 270 participants during the follow-up. DeepSurv identified three potential regions of timescales in which FMAR alterations were significantly linked to the risk for clinical AD: <10, 20-40, and 100-200 minutes. Confirmed by the Cox and random survival forest models, the effect of FMAR alterations in the timescale of <10 minutes was the strongest, after adjusting for covariates., Conclusions: Subtle changes in motor activity fluctuations predicted the clinical onset of AD, with the strongest association observed in activity fluctuations at timescales <10 minutes. These findings suggest that short actigraphy recordings may be used to assess the risk of AD.

Background: Preserving brain health is a critical priority in primary care, yet screening for these risk factors in face-to-face primary care visits is challenging to scale to large populations. We aimed to develop automated brain health risk scores calculated from data in the electronic health record (EHR) enabling population-wide brain health screening in advance of patient care visits., Methods: This retrospective cohort study included patients with visits to an outpatient neurology clinic at Massachusetts General Hospital, between January 2010 and March 2021. Survival analysis with an 11-year follow-up period was performed to predict the risk of intracranial hemorrhage, ischemic stroke, depression, death and composite outcome of dementia, Alzheimer's disease, and mild cognitive impairment. Variables included age, sex, vital signs, laboratory values, employment status and social covariates pertaining to marital, tobacco and alcohol status. Random sampling was performed to create a training (70%) set for hyperparameter tuning in internal 5-fold cross validation and an external hold-out testing (30%) set of patients, both stratified by age. Risk ratios for high and low risk groups were evaluated in the hold-out test set, using 1000 bootstrapping iterations to calculate 95% confidence intervals (CI)., Results: The cohort comprised 17,040 patients with an average age of 49 ± 15.6 years; majority were males (57 %), White (78 %) and non-Hispanic (80 %). The low and high groups average risk ratios [95 % CI] were: intracranial hemorrhage 0.46 [0.45-0.48] and 2.07 [1.95-2.20], ischemic stroke 0.57 [0.57-0.59] and 1.64 [1.52-1.69], depression 0.68 [0.39-0.74] and 1.29 [0.78-1.38], composite of dementia 0.27 [0.26-0.28] and 3.52 [3.18-3.81] and death 0.24 [0.24-0.24] and 3.96 [3.91-4.00]., Conclusions: Simple risk scores derived from routinely collected EHR accurately quantify the risk of developing common neurologic and psychiatric diseases. These scores can be computed automatically, prior to medical care visits, and may thus be useful for large-scale brain health screening., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)