The different brain areas occupied for integrating information of hierarchical linguistic units: a study based on EEG and TMS.

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.

Information transmission velocity-based dynamic hierarchical brain networks.

The brain functions as an accurate circuit that regulates information to be sequentially propagated and processed in a hierarchical manner. However, it is still unknown how the brain is hierarchically organized and how information is dynamically propagated during high-level cognition. In this study, we developed a new scheme for quantifying the information transmission velocity (ITV) by combining electroencephalogram (EEG) and diffusion tensor imaging (DTI), and then mapped the cortical ITV network (ITVN) to explore the information transmission mechanism of the human brain. The application in MRI-EEG data of P300 revealed bottom-up and top-down ITVN interactions subserving P300 generation, which was comprised of four hierarchical modules. Among these four modules, information exchange between visual- and attention-activated regions occurred at a high velocity, related cognitive processes could thus be efficiently accomplished due to the heavy myelination of these regions. Moreover, inter-individual variability in P300 was probed to be attributed to the difference in information transmission efficiency of the brain, which may provide new insight into the cognitive degenerations in clinical neurodegenerative disorders, such as Alzheimer's disease, from the transmission velocity perspective. Together, these findings confirm the capacity of ITV to effectively determine the efficiency of information propagation in the brain.

Deep learning derived automated ASPECTS on non-contrast CT scans of acute ischemic stroke patients.

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.

Reliability of EEG microstate analysis at different electrode densities during propofol-induced transitions of brain states.

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.

Recycling diagnostic MRI for empowering brain morphometric research - Critical & practical assessment on learning-based image super-resolution.

Preliminary studies have shown the feasibility of deep learning (DL)-based super-resolution (SR) technique for reconstructing thick-slice/gap diagnostic MR images into high-resolution isotropic data, which would be of great significance for brain research field if the vast amount of diagnostic MRI data could be successively put into brain morphometric study. However, less evidence has addressed the practicability of the strategy, because lack of a large-sample available real data for constructing DL model. In this work, we employed a large cohort (n = 2052) of peculiar data with both low through-plane resolution diagnostic and high-resolution isotropic brain MR images from identical subjects. By leveraging a series of SR approaches, including a proposed novel DL algorithm of Structure Constrained Super Resolution Network (SCSRN), the diagnostic images were transformed to high-resolution isotropic data to meet the criteria of brain research in voxel-based and surface-based morphometric analyses. We comprehensively assessed image quality and the practicability of the reconstructed data in a variety of morphometric analysis scenarios. We further compared the performance of SR approaches to the ground truth high-resolution isotropic data. The results showed (i) DL-based SR algorithms generally improve the quality of diagnostic images and render morphometric analysis more accurate, especially, with the most superior performance of the novel approach of SCSRN. (ii) Accuracies vary across brain structures and methods, and (iii) performance increases were higher for voxel than for surface based approaches. This study supports that DL-based image super-resolution potentially recycle huge amount of routine diagnostic brain MRI deposited in sleeping state, and turning them into useful data for neurometric research.

Predicting individual decision-making responses based on single-trial EEG.

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 ±â€¯0.09 for the first dataset, and 0.90 ±â€¯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.

Peroxidasin contributes to lung host defense by direct binding and killing of gram-negative bacteria.

Innate immune recognition is classically mediated by the interaction of host pattern-recognition receptors and pathogen-associated molecular patterns; this triggers a series of downstream signaling events that facilitate killing and elimination of invading pathogens. In this report, we provide the first evidence that peroxidasin (PXDN; also known as vascular peroxidase-1) directly binds to gram-negative bacteria and mediates bactericidal activity, thus, contributing to lung host defense. PXDN contains five leucine-rich repeats and four immunoglobulin domains, which allows for its interaction with lipopolysaccharide, a membrane component of gram-negative bacteria. Bactericidal activity of PXDN is mediated via its capacity to generate hypohalous acids. Deficiency of PXDN results in a failure to eradicate Pseudomonas aeruginosa and increased mortality in a murine model of Pseudomonas lung infection. These observations indicate that PXDN mediates previously unrecognized host defense functions against gram-negative bacterial pathogens.

Exploring resting-state EEG complexity before migraine attacks.

Objective Entropy-based approaches to understanding the temporal dynamics of complexity have revealed novel insights into various brain activities. Herein, electroencephalogram complexity before migraine attacks was examined using an inherent fuzzy entropy approach, allowing the development of an electroencephalogram-based classification model to recognize the difference between interictal and preictal phases. Methods Forty patients with migraine without aura and 40 age-matched normal control subjects were recruited, and the resting-state electroencephalogram signals of their prefrontal and occipital areas were prospectively collected. The migraine phases were defined based on the headache diary, and the preictal phase was defined as within 72 hours before a migraine attack. Results The electroencephalogram complexity of patients in the preictal phase, which resembled that of normal control subjects, was significantly higher than that of patients in the interictal phase in the prefrontal area (FDR-adjusted p < 0.05) but not in the occipital area. The measurement of test-retest reliability (n = 8) using the intra-class correlation coefficient was good with r1 = 0.73 ( p = 0.01). Furthermore, the classification model, support vector machine, showed the highest accuracy (76 ± 4%) for classifying interictal and preictal phases using the prefrontal electroencephalogram complexity. Conclusion Entropy-based analytical methods identified enhancement or "normalization" of frontal electroencephalogram complexity during the preictal phase compared with the interictal phase. This classification model, using this complexity feature, may have the potential to provide a preictal alert to migraine without aura patients.

Resting-state EEG power and coherence vary between migraine phases.

BACKGROUND: Migraine is characterized by a series of phases (inter-ictal, pre-ictal, ictal, and post-ictal). It is of great interest whether resting-state electroencephalography (EEG) is differentiable between these phases. METHODS: We compared resting-state EEG energy intensity and effective connectivity in different migraine phases using EEG power and coherence analyses in patients with migraine without aura as compared with healthy controls (HCs). EEG power and isolated effective coherence of delta (1-3.5 Hz), theta (4-7.5 Hz), alpha (8-12.5 Hz), and beta (13-30 Hz) bands were calculated in the frontal, central, temporal, parietal, and occipital regions. RESULTS: Fifty patients with episodic migraine (1-5 headache days/month) and 20 HCs completed the study. Patients were classified into inter-ictal, pre-ictal, ictal, and post-ictal phases (n = 22, 12, 8, 8, respectively), using 36-h criteria. Compared to HCs, inter-ictal and ictal patients, but not pre- or post-ictal patients, had lower EEG power and coherence, except for a higher effective connectivity in fronto-occipital network in inter-ictal patients (p < .05). Compared to data obtained from the inter-ictal group, EEG power and coherence were increased in the pre-ictal group, with the exception of a lower effective connectivity in fronto-occipital network (p < .05). Inter-ictal and ictal patients had decreased EEG power and coherence relative to HCs, which were "normalized" in the pre-ictal or post-ictal groups. CONCLUSION: Resting-state EEG power density and effective connectivity differ between migraine phases and provide an insight into the complex neurophysiology of migraine.

Ultrashort echo time (UTE) imaging of receptor targeted magnetic iron oxide nanoparticles in mouse tumor models.

PURPOSE: The purpose of this study was to investigate an ultrashort echo time (UTE) imaging approach for improving the detection of receptor targeted magnetic nanoparticles in cancer xenograft models using positive contrast. MATERIALS AND METHODS: Iron oxide nanoparticle (IONP) conjugated with tumor targeting ligands were prepared. A 3D UTE gradient echo sequence with the shortest TE of 0.07 msec was evaluated on a 3T magnetic resonance imaging (MRI) scanner using IONP solution, cancer cells bound with targeted IONPs and orthotopic human pancreatic, and breast cancer mouse models administered tumor targeting IONPs. A simulation was performed to analyze contrast-to-noise ratios (CNR) of UTE images and subtraction of the images obtained UTE and longer TE (SubUTE). T2-weighted imaging and T2 relaxometry mapping were applied for comparison and validation. RESULTS: UTE and SubUTE images showed positive contrast in pancreatic tumors accumulated with EGFR targeted ScFvEGFR-IONPs and mammary tumors accumulated with uPAR targeted ATF-IONPs. The positive contrast observed in UTE images was consistent with the negative contrast observed in the T2-weighted images. A flip angle of 10° and a maximal possible TE for the second echo are suitable for SubUTE imaging. CONCLUSION: UTE imaging is capable of detecting tumor targeted IONPs in vivo with positive contrast in molecular MRI applications.

SATF: A Scalable Attentive Transfer Framework for Efficient Multiagent Reinforcement Learning.

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.

Unified Model for Children's Brain Image Segmentation with Co-Registration Framework Guided by Longitudinal MRI.

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.

High-contrast NIR fluorescent probes for selective detection of NQO1 in breast cancer.

NAD(P)H:quinone oxidoreductase 1 (NQO1) is a potential biomarker for breast cancer (BC) diagnosis and prognosis. However, existing fluorescent probes for NQO1 detection have limitations such as short emission wavelength, weak fluorescence response, or large background interference. Here, we developed two novel near-infrared (NIR) fluorescent probes, DCl-Q and DCl2-Q, that selectively detect NQO1 activity in BC cells and tissues. They consist of a trimethyl-locked quinone as the recognition group and a donor-π-acceptor structure with halogen atoms as the reporter group. They exhibit strong fluorescence emission at around 660 nm upon binding to NQO1. We demonstrated that they can distinguish BC cells with different NQO1 expression levels and image endogenous NQO1 in tumor-bearing mice. Our probes provide a convenient and highly sensitive tool for BC diagnosis and prognosis based on NQO1 detection.

Nonparametric Dynamic Granger Causality based on Multi-Space Spectrum Fusion for Time-varying Directed Brain Network Construction.

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.

NQO1 Triggers Neutrophil Recruitment and NET formation to Drive Lung Metastasis of Invasive Breast Cancer.

Metastasis to the lungs is a leading cause of death for breast cancer patients. Therefore, effective therapies are urgently needed to prevent and treat breast cancer 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 breast cancer patients.

An Efficient Graph Learning System for Emotion Recognition Inspired by the Cognitive Prior Graph of EEG Brain Network.

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.

Hunting imaging biomarkers in pulmonary fibrosis: Benchmarks of the AIIB23 challenge.

Airway-related quantitative imaging biomarkers are crucial for examination, diagnosis, and prognosis in pulmonary diseases. However, the manual delineation of airway structures remains prohibitively time-consuming. While significant efforts have been made towards enhancing automatic airway modelling, current public-available datasets predominantly concentrate on lung diseases with moderate morphological variations. The intricate honeycombing patterns present in the lung tissues of fibrotic lung disease patients exacerbate the challenges, often leading to various prediction errors. To address this issue, the 'Airway-Informed Quantitative CT Imaging Biomarker for Fibrotic Lung Disease 2023' (AIIB23) competition was organized in conjunction with the official 2023 International Conference on Medical Image Computing and Computer Assisted Intervention (MICCAI). The airway structures were meticulously annotated by three experienced radiologists. Competitors were encouraged to develop automatic airway segmentation models with high robustness and generalization abilities, followed by exploring the most correlated QIB of mortality prediction. A training set of 120 high-resolution computerised tomography (HRCT) scans were publicly released with expert annotations and mortality status. The online validation set incorporated 52 HRCT scans from patients with fibrotic lung disease and the offline test set included 140 cases from fibrosis and COVID-19 patients. The results have shown that the capacity of extracting airway trees from patients with fibrotic lung disease could be enhanced by introducing voxel-wise weighted general union loss and continuity loss. In addition to the competitive image biomarkers for mortality prediction, a strong airway-derived biomarker (Hazard ratio>1.5, p < 0.0001) was revealed for survival prognostication compared with existing clinical measurements, clinician assessment and AI-based biomarkers.

Targeted delivery of siRNA-generating DNA nanocassettes using multifunctional nanoparticles.

Molecular therapy using a small interfering RNA (siRNA) has shown promise in the development of novel therapeutics. Various formulations have been used for in vivo delivery of siRNAs. However, the stability of short double-stranded RNA molecules in the blood and efficiency of siRNA delivery into target organs or tissues following systemic administration have been the major issues that limit applications of siRNA in human patients. In this study, multifunctional siRNA delivery nanoparticles are developed that combine imaging capability of nanoparticles with urokinase plasminogen activator receptor-targeted delivery of siRNA expressing DNA nanocassettes. This theranostic nanoparticle platform consists of a nanoparticle conjugated with targeting ligands and double-stranded DNA nanocassettes containing a U6 promoter and a shRNA gene for in vivo siRNA expression. Targeted delivery and gene silencing efficiency of firefly luciferase siRNA nanogenerators are demonstrated in tumor cells and in animal tumor models. Delivery of survivin siRNA expressing nanocassettes into tumor cells induces apoptotic cell death and sensitizes cells to chemotherapy drugs. The ability of expression of siRNAs from multiple nanocassettes conjugated to a single nanoparticle following receptor-mediated internalization should enhance the therapeutic effect of the siRNA-mediated cancer therapy.

DOT corrected fluorescence molecular tomography using targeted contrast agents for small animal tumor imaging.

PURPOSE: To demonstrate diffuse optical tomography (DOT) corrected fluorescence molecular tomography (FMT) for quantitatively imaging tumor-targeted contrast agents in a 4T1 mouse mammary tumor model. PROCEDURES: In the first set of experiments, we validated our DOT corrected FMT method using subcutaneously injected 4T1 cells pre-labeled with a near-infrared (NIR) Cy 5.5 dye labeled recombinant amino-terminal fragment (ATF) of the receptor binding domain of urokinase plasminogen activator (uPA), which binds to uPA receptor (uPAR) that is highly expressed in breast cancer tissues. Next, we apply the DOT corrected FMT method to quantitatively evaluate the ability of sensitive tumor imaging after systemic delivery of new uPAR-targeted optical imaging probes in the mice bearing 4T1 mammary tumors. These uPAR-targeted optical imaging probes are ATF peptides labeled with a newly developed NIR-830 dye being conjugated to magnetic iron oxide nanoparticles (IONPs). RESULTS: Our results have shown that DOT corrected FMT can accurately quantify and localize the injected imaging probe labeled 4T1 cells. Following systemic delivery of the targeted imaging nanoprobes into the mice bearing orthotopic mammary tumors, specific accumulation of the imaging probes in the orthotopic mammary tumors was detected in the mice that received uPAR targeted NIR-830-ATF-IONP probes but not in the mice injected with non-targeted NIR-830-mouse serum albumin (MSA)-IONPs. Additionally, DOT corrected FMT also enables the detection of both locally recurrent tumor and lung metastasis in the mammary tumor model 72 hrs after systemic administration of the uPAR-targeted NIR-830-labeled ATF peptide imaging probes. CONCLUSIONS: DOT corrected FMT and uPAR-targeted optical imaging probes have great potential for detection of breast cancer, recurrent tumor and metastasis in small animals.

Reinforcement Learning From Hierarchical Critics.

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.