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• In the baseline and moderate sedation conditions, the microstate topography and parameters in the 91-, 64-, and 32-channel configurations were consistent. • The microstate characteristics of propofol induction remained stable in the 91-, 64-, and 32-channel configurations, but not at the 19- or 8-channel resolutions. • These findings imply that microstate analysis is not reliable at low electrode densities, such as fewer than 20 channels. Electroencephalogram (EEG) microstate analysis is a promising and effective spatio-temporal method that can segment signals into several quasi-stable classes, providing a great opportunity to investigate short-range and long-range neural dynamics. However, there are still many controversies in terms of reproducibility and reliability when selecting different parameters or datatypes. In this study, five electrode configurations (91, 64, 32, 19, and 8 channels) were used to measure the reliability of microstate analysis at different electrode densities during propofol-induced sedation. First, the microstate topography and parameters at five different electrode densities were compared in the baseline (BS) condition and the moderate sedation (MD) condition, respectively. The intraclass correlation coefficient (ICC) and coefficient of variation (CV) were introduced to quantify the consistency of the microstate parameters. Second, statistical analysis and classification between BS and MD were performed to determine whether the microstate differences between different conditions remained stable at different electrode densities, and ICC was also calculated between the different conditions to measure the consistency of the results in a single condition. The results showed that in both the BS or MD condition, respectively, there were few significant differences in the microstate parameters among the 91-, 64-, and 32-channel configurations, with most of the differences observed between the 19- or 8-channel configurations and the other configurations. The ICC and CV data also showed that the consistency among the 91-, 64-, and 32-channel configurations was better than that among all five electrode configurations after including the 19- and 8-channel configurations. Furthermore, the significant differences between the conditions in the 91-channel configuration remained stable at the 64- and 32-channel resolutions, but disappeared at the 19- and 8-channel resolutions. In addition, the classification and ICC results showed that the microstate analysis became unreliable with fewer than 20 electrodes. The findings of this study support the hypothesis that microstate analysis of different brain states is more reliable with higher electrode densities; the use of a small number of channels is not recommended. [ABSTRACT FROM AUTHOR]

Decision-making plays an essential role in the interpersonal interactions and cognitive processing of individuals. There has been increasing interest in being able to predict an individual's decision-making response (i.e., acceptance or rejection). We proposed an electroencephalogram (EEG)-based computational intelligence framework to predict individual responses. Specifically, the discriminative spatial network pattern (DSNP), a supervised learning approach, was applied to single-trial EEG data to extract the DSNP feature from the single-trial brain network. A linear discriminate analysis (LDA) trained on the DSNP features was then used to predict the individual response trial-by-trial. To verify the performance of the proposed DSNP, we recruited two independent subject groups, and recorded the EEGs using two types of EEG systems. The performances of the trial-by-trial predictors achieved an accuracy of 0.88 ± 0.09 for the first dataset, and 0.90 ± 0.10 for the second dataset. These trial-by-trial prediction performances suggested that individual responses could be predicted trial-by-trial by using the specific pattern of single-trial EEG networks, and our proposed method has the potential to establish the biologically inspired artificial intelligence decision system. • A single-trial EEG based approach is developed to predict individual decision-making response. • A supervised learning approach is developed to extract the discriminative spatial network pattern. • The proposed approach achieves the high prediction performances (over 0.88) for two independent EEG datasets. [ABSTRACT FROM AUTHOR]

Metastasis to the lungs is a leading cause of death for patients with breast cancer. Therefore, effective therapies are urgently needed to prevent and treat lung metastasis. In this study, we uncovered a mechanism by which NAD(P)H:quinone oxidoreductase 1 (NQO1) orchestrates lung metastasis. NQO1 stabilized and upregulated peptidyl-prolyl cis-trans isomerase A (PPIA), a chaperone that regulates protein conformation and activity, by preventing its oxidation at a critical cysteine residue C161. PPIA subsequently activated CD147, a membrane protein that facilitates cell invasion. Moreover, NQO1-induced secretion of PPIA modulated the immune landscape of both primary and lung metastatic sites. Secreted PPIA engaged CD147 on neutrophils and triggered the release of neutrophil extracellular traps (NET) and neutrophil elastase, which enhanced tumor progression, invasiveness, and lung colonization. Pharmacological targeting of PPIA effectively inhibited NQO1-mediated breast cancer lung metastasis. These findings reveal a previously unrecognized NQO1-PPIA-CD147-NET axis that drives breast cancer lung metastasis. Inhibiting this axis is a potential therapeutic strategy to limit lung metastasis in patients with breast cancer.  Significance: NQO1 stabilizes and promotes the secretion of PPIA to activate CD147 in neutrophils and stimulate NET formation, promoting breast cancer lung metastasis and providing therapeutic targets for this fatal condition., (©2024 American Association for Cancer Research.)

Granger causality-based effective brain connectivity provides a powerful tool to probe the neural mechanism for information processing and the potential features for brain computer interfaces. However, in real applications, traditional Granger causality is prone to the influence of outliers, such as inevitable ocular artifacts, resulting in unreasonable brain linkages and the failure to decipher inherent cognition states. In this work, motivated by constructing the sparse causality brain networks under the strong physiological outlier noise conditions, we proposed a dual Laplacian Granger causality analysis (DLap-GCA) by imposing Laplacian distributions on both model parameters and residuals. In essence, the first Laplacian assumption on residuals will resist the influence of outliers in electroencephalogram (EEG) on causality inference, and the second Laplacian assumption on model parameters will sparsely characterize the intrinsic interactions among multiple brain regions. Through simulation study, we quantitatively verified its effectiveness in suppressing the influence of complex outliers, the stable capacity for model estimation, and sparse network inference. The application to motor-imagery (MI) EEG further reveals that our method can effectively capture the inherent hemispheric lateralization of MI tasks with sparse patterns even under strong noise conditions. The MI classification based on the network features derived from the proposed approach shows higher accuracy than other existing traditional approaches, which is attributed to the discriminative network structures being captured in a timely manner by DLap-GCA even under the single-trial online condition. Basically, these results consistently show its robustness to the influence of complex outliers and the capability of characterizing representative brain networks for cognition information processing, which has the potential to offer reliable network structures for both cognitive studies and future brain-computer interface (BCI) realization.

Nonparametric estimation of time-varying directed networks can unveil the intricate transient organization of directed brain communication while circumventing constraints imposed by prescribed model-driven methods. A robust time-frequency representation - the foundation of its causality inference - is critical for enhancing its reliability. This study proposed a novel method, i.e., nonparametric dynamic Granger causality based on Multi-space Spectrum Fusion (ndGCMSF), which integrates complementary spectrum information from different spaces to generate reliable spectral representations to estimate dynamic causalities across brain regions. Systematic simulations and validations demonstrate that ndGCMSF exhibits superior noise resistance and a powerful ability to capture subtle dynamic changes in directed brain networks. Particularly, ndGCMSF revealed that during instruction response movements, the laterality in the hemisphere ipsilateral to the hemiplegic limb emerges upon instruction onset and diminishes upon task accomplishment. These intrinsic variations further provide reliable features for distinguishing two types of hemiplegia (left vs. right) and assessing motor functions. The ndGCMSF offers powerful functional patterns to derive effective brain networks in dynamically changing operational settings and contributes to extensive areas involving dynamical and directed communications.

Multichannel electroencephalogram (EEG) is an array signal that represents brain neural networks and can be applied to characterize information propagation patterns for different emotional states. To reveal these inherent spatial graph features and increase the stability of emotion recognition, we propose an effective emotion recognition model that performs multicategory emotion recognition with multiple emotion-related spatial network topology patterns (MESNPs) by learning discriminative graph topologies in EEG brain networks. To evaluate the performance of our proposed MESNP model, we conducted single-subject and multisubject four-class classification experiments on two public datasets, MAHNOB-HCI and DEAP. Compared with existing feature extraction methods, the MESNP model significantly enhances the multiclass emotional classification performance in the single-subject and multisubject conditions. To evaluate the online version of the proposed MESNP model, we designed an online emotion monitoring system. We recruited 14 participants to conduct the online emotion decoding experiments. The average online experimental accuracy of the 14 participants was 84.56%, indicating that our model can be applied in affective brain-computer interface (aBCI) systems. The offline and online experimental results demonstrate that the proposed MESNP model effectively captures discriminative graph topology patterns and significantly improves emotion classification performance. Moreover, the proposed MESNP model provides a new scheme for extracting features from strongly coupled array signals.

Benefiting from the high-temporal resolution of electroencephalogram (EEG), EEG-based emotion recognition has become one of the hotspots of affective computing. For EEG-based emotion recognition systems, it is crucial to utilize state-of-the-art learning strategies to automatically learn emotion-related brain cognitive patterns from emotional EEG signals, and the learned stable cognitive patterns effectively ensure the robustness of the emotion recognition system. In this work, to realize the efficient decoding of emotional EEG, we propose a graph learning system Graph Convolutional Network framework with Brain network initial inspiration and Fused attention mechanism (BF-GCN) inspired by the brain cognitive mechanism to automatically learn graph patterns from emotional EEG and improve the performance of EEG emotion recognition. In the proposed BF-GCN, three graph branches, i.e., cognition-inspired functional graph branch, data-driven graph branch, and fused common graph branch, are first elaborately designed to automatically learn emotional cognitive graph patterns from emotional EEG signals. And then, the attention mechanism is adopted to further capture the brain activation graph patterns that are related to emotion cognition to achieve an efficient representation of emotional EEG signals. Essentially, the proposed BF-CGN model is a cognition-inspired graph learning neural network model, which utilizes the spectral graph filtering theory in the automatic learning and extracting of emotional EEG graph patterns. To evaluate the performance of the BF-GCN graph learning system, we conducted subject-dependent and subject-independent experiments on two public datasets, i.e., SEED and SEED-IV. The proposed BF-GCN graph learning system has achieved 97.44% (SEED) and 89.55% (SEED-IV) in subject-dependent experiments, and the results in subject-independent experiments have achieved 92.72% (SEED) and 82.03% (SEED-IV), respectively. The state-of-the-art performance indicates that the proposed BF-GCN graph learning system has a robust performance in EEG-based emotion recognition, which provides a promising direction for affective computing.

Accurate segmentation of brain structures is crucial for analyzing longitudinal changes in children's brains. However, existing methods are mostly based on models established at a single time-point due to difficulty in obtaining annotated data and dynamic variation of tissue intensity. The main problem with such approaches is that, when conducting longitudinal analysis, images from different time points are segmented by different models, leading to significant variation in estimating development trends. In this paper, we propose a novel unified model with co-registration framework to segment children's brain images covering neonates to preschoolers, which is formulated as two stages. First, to overcome the shortage of annotated data, we propose building gold-standard segmentation with co-registration framework guided by longitudinal data. Second, we construct a unified segmentation model tailored to brain images at 0-6 years old through the introduction of a convolutional network (named SE-VB-Net), which combines our previously proposed VB-Net with Squeeze-and-Excitation (SE) block. Moreover, different from existing methods that only require both T1- and T2-weighted MR images as inputs, our designed model also allows a single T1-weighted MR image as input. The proposed method is evaluated on the main dataset (320 longitudinal subjects with average 2 time-points) and two external datasets (10 cases with 6-month-old and 40 cases with 20-45 weeks, respectively). Results demonstrate that our proposed method achieves a high performance (>92%), even over a single time-point. This means that it is suitable for brain image analysis with large appearance variation, and largely broadens the application scenarios.

It is challenging to train an efficient learning procedure with multiagent reinforcement learning (MARL) when the number of agents increases as the observation space exponentially expands, especially in large-scale multiagent systems. In this article, we proposed a scalable attentive transfer framework (SATF) for efficient MARL, which achieved goals faster and more accurately in homogeneous and heterogeneous combat tasks by transferring learned knowledge from a small number of agents (4) to a large number of agents (up to 64). To reduce and align the dimensionality of the observed state variations caused by increasing numbers of agents, the proposed SATF deployed a novel state representation network with a self-attention mechanism, known as dynamic observation representation network (DorNet), to extract the dominant observed information with excellent cost-effectiveness. The experiments on the MAgent platform showed that the SATF outperformed the distributed MARL (independent Q-learning (IQL) and A2C) in task sequences from 8 to 64 agents. The experiments on StarCraft II showed that the SATF demonstrated superior performance relative to the centralized training with decentralized execution MARL (QMIX) by presenting shorter training steps, achieving a desired win rate of up to approximately 90% when increasing the number of agents from 4 to 32. The findings of our study showed the great potential for enhancing the efficiency of MARL training in large-scale agent combat missions.

Information can be quantified and expressed by uncertainty, and improving the decision level of uncertain information is vital in modeling and processing uncertain information. Dempster-Shafer evidence theory can model and process uncertain information effectively. However, the Dempster combination rule may provide counter-intuitive results when dealing with highly conflicting information, leading to a decline in decision level. Thus, measuring conflict is significant in the improvement of decision level. Motivated by this issue, this paper proposes a novel method to measure the discrepancy between bodies of evidence. First, the model of dynamic fractal probability transformation is proposed to effectively obtain more information about the non-specificity of basic belief assignments (BBAs). Then, we propose the higher-order fractal belief Rényi divergence (HOFBReD). HOFBReD can effectively measure the discrepancy between BBAs. Moreover, it is the first belief Rényi divergence that can measure the discrepancy between BBAs with dynamic fractal probability transformation. HoFBReD has several properties in terms of probability transformation as well as measurement. When the dynamic fractal probability transformation ends, HoFBReD is equivalent to measuring the Rényi divergence between the pignistic probability transformations of BBAs. When the BBAs degenerate to the probability distributions, HoFBReD will also degenerate to or be related to several well-known divergences. In addition, based on HoFBReD, a novel multisource information fusion algorithm is proposed. A pattern classification experiment with real-world datasets is presented to compare the proposed algorithm with other methods. The experiment results indicate that the proposed algorithm has a higher average pattern recognition accuracy with all datasets than other methods. The proposed discrepancy measurement method and multisource information algorithm contribute to the improvement of decision level.

Accurate pathological classification and grading of gliomas is crucial in clinical diagnosis and treatment. The application of deep learning techniques holds promise for automated histological pathology diagnosis. In this study, we collected 733 whole slide images from four medical centers, of which 456 were used for model training, 150 for internal validation, and 127 for multi-center testing. The study includes 5 types of common gliomas. A subtask-guided multi-instance learning image-to-label training pipeline was employed. The pipeline leveraged "patch prompting" for the model to converge with reasonable computational cost. Experiments showed that an overall accuracy of 0.79 in the internal validation dataset. The performance on the multi-center testing dataset showed an overall accuracy to 0.73. The findings suggest a minor yet acceptable performance decrease in multi-center data, demonstrating the model's strong generalizability and establishing a robust foundation for future clinical applications., Competing Interests: T.S., Z.C., F.S., and D.S. are employees in United Imaging Intelligence. Y.Z. and J.Z. are employees in Zhongji Biotechnology. These two companies have no role in designing and performing the surveillances and analyzing and interpreting the data. All other authors report no competing interest relevant to this article., (© 2023 The Author(s).)

Human language units are hierarchical, and reading acquisition involves integrating multisensory information (typically from auditory and visual modalities) to access meaning. However, it is unclear how the brain processes and integrates language information at different linguistic units (words, phrases, and sentences) provided simultaneously in auditory and visual modalities. To address the issue, we presented participants with sequences of short Chinese sentences through auditory, visual, or combined audio-visual modalities while electroencephalographic responses were recorded. With a frequency tagging approach, we analyzed the neural representations of basic linguistic units (i.e. characters/monosyllabic words) and higher-level linguistic structures (i.e. phrases and sentences) across the 3 modalities separately. We found that audio-visual integration occurs in all linguistic units, and the brain areas involved in the integration varied across different linguistic levels. In particular, the integration of sentences activated the local left prefrontal area. Therefore, we used continuous theta-burst stimulation to verify that the left prefrontal cortex plays a vital role in the audio-visual integration of sentence information. Our findings suggest the advantage of bimodal language comprehension at hierarchical stages in language-related information processing and provide evidence for the causal role of the left prefrontal regions in processing information of audio-visual sentences., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Identifying individuals at risk for severe mental illness (SMI) is crucial for prevention and early intervention strategies. While MRI shows potential for case identification even before illness onset, no practical model for mental health risk monitoring has been developed. This study aims to develop an initial version of an efficient and practical model for mental health screening among at-risk populations., Methods: A deep learning model known as Multiple Instance Learning (MIL) was adopted to train and test a SMI detection model with clinical MRI scans of 14,915 patients with SMI (age 32.98 ± 12.01 years, 9102 women) and 4538 healthy controls (age 40.60 ± 10.95 years, 2424 women) in the primary dataset. Validation analysis was conducted in an independent dataset with 290 patients (age 28.08 ± 10.95 years, 169 women) and 310 healthy participants (age 33.55 ± 11.09 years, 165 women). Another three machine learning models of ResNet, DenseNet and EfficientNet were used for comparison. We also recruited 148 individuals receiving high-stress medical school education to characterize the potential real-world utility of the MIL model in detecting risk of mental illness., Findings: Similar performance of successful differentiation of individuals with SMI and healthy controls was observed for the MIL model (AUC: 0.82) and other models (ResNet, DenseNet, EfficientNet, 0.83, 0.81, and 0.80 respectively). MIL had better generalization in the validation test than other models (AUC: 0.82 vs 0.59, 0.66 and 0.59), and less drop-off in performance from 3.0T to 1.5T scanners. The MIL model did better in predicting clinician ratings of distress than self-ratings with questionnaires (84% vs 22%) in the medical student sample. Brain regions that contributed to SMI identification were mainly neocortical, including right precuneus, bilateral temporal regions, left precentral/postcentral gyrus, bilateral medial prefrontal cortex and right cerebellum., Interpretation: Our digital model based on brief clinical MRI protocols identified individual SMI patients with good accuracy and high sensitivity, suggesting that with incremental improvements the approach may offer potentially useful aid for early identification and intervention to prevent illness onset in vulnerable at-risk populations., Funding: This study was supported by the National Natural Science Foundation of China, National Key Technologies R&D Program of China, and Sichuan Science and Technology Program., Competing Interests: Declaration of interests Wenjing Zhang and John A. Sweeney consult to VeraSci. Zehong Cao, Yichu He, Qing Zhou and Feng Shi are employees of Shanghai United Imaging Intelligence Co., Ltd. The company has no role in designing and performing the study or analyzing and interpreting the data. The remaining authors have no competing interests or financial support to disclose., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

In this study, we investigate the use of global information to speed up the learning process and increase the cumulative rewards of reinforcement learning (RL) in competition tasks. Within the framework of actor-critic RL, we introduce multiple cooperative critics from two levels of a hierarchy and propose an RL from the hierarchical critics (RLHC) algorithm. In our approach, each agent receives value information from local and global critics regarding a competition task and accesses multiple cooperative critics in a top-down hierarchy. Thus, each agent not only receives low-level details, but also considers coordination from higher levels, thereby obtaining global information to improve the training performance. Then, we test the proposed RLHC algorithm against a benchmark algorithm, that is, proximal policy optimization (PPO), under four experimental scenarios consisting of tennis, soccer, banana collection, and crawler competitions within the Unity environment. The results show that RLHC outperforms the benchmark on these four competitive tasks.

Ischemic stroke is the most common type of stroke, ranked as the second leading cause of death worldwide. The Alberta Stroke Program Early CT Score (ASPECTS) is considered as a systematic method of assessing ischemic change on non-contrast CT scans (NCCT) of acute ischemic stroke (AIS) patients, while still suffering from the requirement of experts' experience and also the inconsistent results between readers. In this study, we proposed an automated ASPECTS method to utilize the powerful learning ability of neural networks for objectively scoring CT scans of AIS patients. First, we proposed to use the CT perfusion (CTP) from one-stop stroke imaging to provide the golden standard of ischemic regions for ASPECTS scoring. Second, we designed an asymmetry network to capture features when comparing the left and right sides for each ASPECTS region to estimate its ischemic status. Third, we performed experiments in a large main dataset of 870 patients, as well as an independent testing dataset consisting of 207 patients with radiologists' scorings. Experimental results show that our network achieved remarkable performance, as sensitivity and accuracy of 93.7 and 92.4% in the main dataset, and 95.5 and 91.3% in the independent testing dataset, respectively. In the latter dataset, our analysis revealed a high positive correlation between the ASPECTS score and the prognosis of patients in 90DmRs. Also, we found ASPECTS score is a good indicator of the size of CTP core volume of an infraction. The proposed method shows its potential for automated ASPECTS scoring on NCCT images., (© 2022 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Objective . Electroencephalogram (EEG)-based motor imagery (MI) brain-computer interface offers a promising way to improve the efficiency of motor rehabilitation and motor skill learning. In recent years, the power of dynamic network analysis for MI classification has been proved. In fact, its usability mainly depends on the accurate estimation of brain connection. However, traditional dynamic network estimation strategies such as adaptive directed transfer function (ADTF) are designed in the L2-norm. Usually, they estimate a series of pseudo connections caused by outliers, which results in biased features and further limits its online application. Thus, how to accurately infer dynamic causal relationship under outlier influence is urgent. Approach . In this work, we proposed a novel ADTF, which solves the dynamic system in the L1-norm space (L1-ADTF), so as to restrict the outlier influence. To enhance its convergence, we designed an iteration strategy with the alternating direction method of multipliers, which could be used for the solution of the dynamic state-space model restricted in the L1-norm space. Furthermore, we compared L1-ADTF to traditional ADTF and its dual extension across both simulation and real EEG experiments. Main results . A quantitative comparison between L1-ADTF and other ADTFs in simulation studies demonstrates that fewer bias errors and more desirable dynamic state transformation patterns can be captured by the L1-ADTF. Application to real MI EEG datasets seriously noised by ocular artifacts also reveals the efficiency of the proposed L1-ADTF approach to extract the time-varying brain neural network patterns, even when more complex noises are involved. Significance . The L1-ADTF may not only be capable of tracking time-varying brain network state drifts robustly but may also be useful in solving a wide range of dynamic systems such as trajectory tracking problems and dynamic neural networks., (© 2022 IOP Publishing Ltd.)

Heme-containing peroxidases are widely distributed in the animal and plant kingdoms and play an important role in host defense by generating potent oxidants. Myeloperoxidase (MPO), the prototype of heme-containing peroxidases, exists in neutrophils and monocytes. MPO has a broad spectrum of microbial killing. The difficulty of producing MPO at a large scale hinders its study and utilization. This study aimed to overexpress recombinant human MPO and characterize its microbicidal activities in vitro and in vivo . A human HEK293 cell line stably expressing recombinant MPO (rMPO) was established as a component of this study. rMPO was overexpressed and purified for studies on its biochemical and enzymatic properties, as well as its microbicidal activities. In this study, rMPO was secreted into culture medium as a monomer. rMPO revealed enzymatic activity similar to that of native MPO. rMPO, like native MPO, was capable of killing a broad spectrum of microorganisms, including Gram-negative and -positive bacteria and fungi, at low nM levels. Interestingly, rMPO could kill antibiotic-resistant bacteria, making it very useful for treatment of nosocomial infections and mixed infections. The administration of rMPO significantly reduced the morbidity and mortality of murine lung infections induced by Pseudomonas aeruginosa or methicillin-resistant Staphylococcus aureus. In animal safety tests, the administration of 100 nM rMPO via tail vein did not result in any sign of toxic effects. Taken together, the data suggest that rMPO purified from a stably expressing human cell line is a new class of antimicrobial agents with the ability to kill a broad spectrum of pathogens, including bacteria and fungi with or without drug resistance. IMPORTANCE Over the past 2 decades, more than 20 new infectious diseases have emerged. Unfortunately, novel antimicrobial therapeutics are discovered at much lower rates. Infections caused by resistant microorganisms often fail to respond to conventional treatment, resulting in prolonged illness, greater risk of death, and high health care costs. Currently, this is best seen with the lack of a cure for coronavirus disease 2019 (COVID-19). To combat such untreatable microorganisms, there is an urgent need to discover new classes of antimicrobial agents. Myeloperoxidase (MPO) plays an important role in host defense. The difficulty of producing MPO on a large scale hinders its study and utilization. We have produced recombinant MPO at a large scale and have characterized its antimicrobial activities. Most importantly, recombinant MPO significantly reduced the morbidity and mortality of murine pneumonia induced by Pseudomonas aeruginosa or methicillin-resistant Staphylococcus aureus. Our data suggest that recombinant MPO from human cells is a new class of antimicrobials with a broad spectrum of activity.

In the above article [1], to track the loss of consciousness (LOC) induced by general anesthesia (GA), we first developed the multi-channel cross fuzzy entropy method to construct the time- varying networks, whose temporal fluctuations were then explored and quantitatively evaluated. Since time-varying network topologies were found to fluctuate from long-range frontal-occipital to short-range prefrontal-frontal connectivity during the LOC period, a new parameter, i.e., the long-range connectivity (LRC) that measured the number of frontal-occipital connectivity, was accordingly calculated and then investigated between the coherence (COH) and cross fuzzy entropy (C-FuzzyEn) approaches, as displayed in Fig. 1. The distinct time-varying fluctuations of both approaches were indeed found within this period, where only C-FuzzyEn effectively captured the consciousness fluctuation induced by the GA.

The current reward learning from human preferences could be used to resolve complex reinforcement learning (RL) tasks without access to a reward function by defining a single fixed preference between pairs of trajectory segments. However, the judgment of preferences between trajectories is not dynamic and still requires human input over thousands of iterations. In this study, we proposed a weak human preference supervision framework, for which we developed a human preference scaling model that naturally reflects the human perception of the degree of weak choices between trajectories and established a human-demonstration estimator through supervised learning to generate the predicted preferences for reducing the number of human inputs. The proposed weak human preference supervision framework can effectively solve complex RL tasks and achieve higher cumulative rewards in simulated robot locomotion-MuJoCo games-relative to the single fixed human preferences. Furthermore, our established human-demonstration estimator requires human feedback only for less than 0.01% of the agent's interactions with the environment and significantly reduces the cost of human inputs by up to 30% compared with the existing approaches. To present the flexibility of our approach, we released a video (https://youtu.be/jQPe1OILT0M) showing comparisons of the behaviors of agents trained on different types of human input. We believe that our naturally inspired human preferences with weakly supervised learning are beneficial for precise reward learning and can be applied to state-of-the-art RL systems, such as human-autonomy teaming systems.

The vehicle platoon will be the most dominant driving mode on future roads. To the best of our knowledge, few reinforcement learning (RL) algorithms have been applied in vehicle platoon control, which has large-scale action and state spaces. Some RL-based methods were applied to solve single-agent problems. If we need to tackle multiagent problems, we will use multiagent RL algorithms since the parameters space grows exponentially with the increasing number of agents involved. Previous multiagent RL algorithms generally may provide redundant information to agents, indicating a large amount of useless or unrelated information, which may cause to be difficult for convergence training and pattern extractions from shared information. Also, random actions usually contribute to crashes, especially at the beginning of training. In this study, a communication proximal policy optimization (CommPPO) algorithm was proposed to tackle the above issues. In specific, the CommPPO model adopts a parameter-sharing structure to allow the dynamic variation of agent numbers, which can well handle various platoon dynamics, including splitting and merging. The communication protocol of the CommPPO consists of two parts. In the state part, the widely used predecessor-leader follower typology in the platoon is adopted to transmit global and local state information to agents. In the reward part, a new reward communication channel is proposed to solve the spurious reward and "lazy agent" problems in some existing multiagent RLs. Moreover, a curriculum learning approach is adopted to reduce crashes and speed up training. To validate the proposed strategy for platoon control, two existing multiagent RLs and a traditional platoon control strategy were applied in the same scenarios for comparison. Results showed that the CommPPO algorithm gained more rewards and achieved the largest fuel consumption reduction (11.6%).

Complete removal of tumors by surgery is the most important prognostic factor for cancer patients with the early stage cancers. The ability to identify invasive tumor edges of the primary tumor, locally invaded small tumor lesions, and drug resistant residual tumors following neoadjuvant therapy during surgery should significantly reduce the incidence of local tumor recurrence and improve survival of cancer patients. In this study, we report that urokinase plasminogen activator (uPA) and its receptor (uPAR) are the ligand/cell surface target pair for the development of targeted optical imaging probes for enhancing imaging contrasts in the tumor border. Recombinant peptides of the amino terminal fragment (ATF) of the receptor binding domain of uPA were labeled with near infrared fluorescence (NIR) dye molecules either as peptide-imaging or peptide-conjugated nanoparticle imaging probes. Systemic delivery of the uPAR-targeted imaging probes in mice bearing orthotopic human breast or pancreatic tumor xenografts or mouse mammary tumors led to the accumulation of the probes in the tumor and stromal cells, resulting in strong signals for optical imaging of tumors and identification of tumor margins. Histological analysis showed that a high level of uPAR-targeted nanoparticles was present in the tumor edge or active tumor stroma immediately adjacent to the tumor cells. Furthermore, following targeted therapy using uPAR-targeted theranostic nanoparticles, residual tumors were detectable by optical imaging through the imaging contrasts produced by NIR-dye-labeled theranostic nanoparticles in drug resistant tumor cells. Therefore, results of our study support the potential of the development of uPAR-targeted imaging and theranostic agents for image-guided surgery.

It is well known that dysfunction of the apoptotic pathway confers apoptosis resistance and results in a low sensitivity of human cancer cells to therapeutic agents. A novel strategy to overcome the resistance is to target the apoptotic pathway directly. To identify molecular targets in the apoptotic pathway that are differentially regulated in cancer and normal cells, we have examined the levels of apoptotic effectors and inhibitors in human tumor and normal cell lines as well as in cancer and normal tissues. These include three pancreatic cancer lines (BXPC-3, MIA PaCa-2, and Panc-1), four breast cancer cell lines (MDA-MB-231, MDA-MB-435, MDA-MB-361, and MCF-7), and colon carcinoma line (SW620). Additionally, breast carcinoma tissue specimens were examined. Compared with normal human fibroblast and mammary epithelial cell lines, we detected high basal levels of caspase-3 and caspase-8 activities and active caspase-3 fragments in the tumor cell lines and cancer tissues in the absence of apoptotic stimuli. Furthermore, the tumor cells expressed high levels of survivin and XIAP, two members of the inhibitor of apoptosis (IAP) protein family. When the activity of these IAPs was blocked by expression of dominant-negative mutant survivin (survivinT34A) and XIAP-associated factor 1, respectively, apoptosis was induced in tumor but not normal cell lines. Moreover, down-regulation of both survivin and XIAP significantly enhanced tumor-cell apoptosis as compared with inhibition of either survivin or XIAP alone. These results suggest that up-regulated IAP expression counteracts the high basal caspase-3 activity observed in these tumor cells and that apoptosis in tumor cells but not normal cells can be induced by blocking IAP activity. Therefore, IAPs are important molecular targets for the development of cancer-specific therapeutic approaches.