Cortical theta phase synchronization involved in mismatch-driven perceptual alternation in binocular rivalry.

When two conflicting images are presented to each eye, a phenomenon called binocular rivalry occurs in which we initially perceive one image, and then our perception switches to the other over time. An enhancement of θ-band phase coherence in visual mismatch oscillatory response (vMOR) is reported to be involved in the facilitation of perceptual alternation when the deviant stimulus is presented unconsciously. In this study, we investigated the modulation effect of θ-band transcranial alternating current stimulation (tACS) on perceptual alternation in binocular rivalry, with a focus on its relationship with the θ-band vMOR. The results showed that tACS had no significant effect on the mean proportion of perceptual alternation. Analyzing the differential effects of the modulation, however, we found a positive correlation between the increase in inter-trial phase coherence of the vMOR and the promotion of perceptual alternation under the unconscious deviant condition. Additionally, our findings indicate that the θ-band phase synchrony between frontal and occipital electrode sides, as measured by the phase lag index, is implicated in perceptual alternation, with an increase (decrease) in connection density observed in participants whose perceptual alternation was increased (decreased) by tACS. These results support the hypothesis that deviant visual stimuli evoke θ-band phase synchrony between the frontal and occipital cortices, thereby enhancing perceptual alternation in binocular rivalry.

Accurate deep learning model using semi-supervised learning and Noisy Student for cervical cancer screening in low magnification images.

Deep learning technology has been used in the medical field to produce devices for clinical practice. Deep learning methods in cytology offer the potential to enhance cancer screening while also providing quantitative, objective, and highly reproducible testing. However, constructing high-accuracy deep learning models necessitates a significant amount of manually labeled data, which takes time. To address this issue, we used the Noisy Student Training technique to create a binary classification deep learning model for cervical cytology screening, which reduces the quantity of labeled data necessary. We used 140 whole-slide images from liquid-based cytology specimens, 50 of which were low-grade squamous intraepithelial lesions, 50 were high-grade squamous intraepithelial lesions, and 40 were negative samples. We extracted 56,996 images from the slides and then used them to train and test the model. We trained the EfficientNet using 2,600 manually labeled images to generate additional pseudo labels for the unlabeled data and then self-trained it within a student-teacher framework. Based on the presence or absence of abnormal cells, the created model was used to classify the images as normal or abnormal. The Grad-CAM approach was used to visualize the image components that contributed to the classification. The model achieved an area under the curve of 0.908, accuracy of 0.873, and F1-score of 0.833 with our test data. We also explored the optimal confidence threshold score and optimal augmentation approaches for low-magnification images. Our model efficiently classified normal and abnormal images at low magnification with high reliability, making it a promising screening tool for cervical cytology.

Theta phase coherence in visual mismatch responses involved in access processing to visual awareness.

Introduction: The electroencephalographic brain response to a deviation from the preceding sequential regularity of visual events, called visual mismatch negativity (vMMN), is well known to reflect automatic visual change detection. Our preliminary study showed a significant correlation between the enhancement of the vMMN amplitude and facilitation of perceptual alternation in binocular rivalry when the deviant stimulus was presented unconsciously. This implies that the vMMN is relevant to access processing, in which the unconscious stimulus is consciously perceived. Recent studies have reported that theta band oscillation evoked by a deviant stimulus is involved in evoking vMMN. However, it has not been clarified whether theta band oscillation associated with vMMN is also relevant to access processing. Methods: We analyzed the correlations between event-related spectral perturbation (ERSP) and inter-trial phase coherence (ITPC) in the theta band and the proportion of perceptual alternation from before to after the presentation of deviation in the same experimental paradigm as in our previous study. Results: We found that an increase in ITPC in the theta band tended to correlate with facilitation of perceptual alternation in binocular rivalry when the deviant was presented unconsciously, but there was no significant correlation in ERSP. Discussion: The results suggest that theta phase coherence underlying the visual mismatch process is relevant to the access processing.

Metformin reduces pleural fibroelastosis by inhibition of extracellular matrix production induced by CD90-positive myofibroblasts.

Metformin, an AMP-activated protein kinase activator used to treat diabetes mellitus, has recently attracted attention as a promising anti-fibrotic agent. However, its anti-fibrotic effects on pleural fibroelastosis remain unknown. We induced mouse pleural fibroelastosis by intra-pleural coadministration of bleomycin and carbon and evaluated its validity as a preclinical model for human pleural fibrosis. We assessed the expression of the myofibroblast surface marker CD90 in the fibrotic pleura and the effects of metformin in vivo and in vitro. Finally, we evaluated the effects of metformin on human pleural mesothelial cells stimulated by transforming growth factor ß1 (TGFß1). The fibrotic pleura in mice had collagen and elastin fiber deposition similar to that seen in human fibrotic pleura. Moreover, CD90-positive myofibroblasts were detected in and successfully isolated from the fibrotic pleura. Metformin significantly suppressed the deposition of collagen and elastic fibers in the fibrotic pleura and decreased the expression of extracellular matrix (ECM)-related genes, including Col1a1, Col3a1, Fn1, and Eln, in pleural CD90-positive myofibroblasts. In human pleural mesothelial cells, metformin decreased TGFß1-induced upregulation of ECM-related genes and SNAI1. Overall, metformin suppresses pleural fibroelastosis by inhibition of ECM production by pleural myofibroblasts, suggesting that this drug has therapeutic potential against human pleural fibrosis, including pleuroparenchymal fibroelastosis.

Involvement of Visual Mismatch Negativity in Access Processing to Visual Awareness.

Psychophysiological studies with electroencephalography, focusing on the dynamical aspect of neural correlate of consciousness, reported that visual awareness negativity and P3 enhancement are observed at a latency, 200-300 ms after the visual stimulus onset, when the visual stimulus is consciously perceived. However, access processing to visual awareness (APVA) immediately before conscious perception still remains at the earlier stage of visual sensory processing, though there is little known regarding this subject. The present study hypothesized that visual mismatch negativity (vMMN), which reflects automatic change detection at a latency of 130-250 ms, might be involved in the APVA. In a previous study, vMMN was reported to be evoked by the deviant stimulus that is not consciously perceived in binocular rivalry. To clarify whether the visual change detection affects APVA, we conducted a modified experiment of oddball paradigm on binocular rivalry. The results showed a significant correlation between enhancement of vMMN amplitude and facilitation of perceptual alternation when the unconscious deviant was presented. This implies that vMMN is relevant to the APVA, which is a novel role of vMMN. In early visual processing, the attentional mechanism associated with vMMN is suggested to play an important role in unconscious neural processing at an earlier stage of visual awareness.

O2-Dependent Protein Internalization Underlies Astrocytic Sensing of Acute Hypoxia by Restricting Multimodal TRPA1 Channel Responses.

Hypoxia sensors are essential for regulating local oxygen (O2) homeostasis within the body. This is especially pertinent within the CNS, which is particularly vulnerable to O2 deprivation due to high energetic demand. Here, we reveal hypoxia-monitoring function exerted by astrocytes through an O2-regulated protein trafficking mechanism within the CNS. Strikingly, cultured mouse astrocytes isolated from the parafacial respiratory group (pFRG) and retrotrapezoid nucleus (RTN) region are capable of rapidly responding to moderate hypoxia via the sensor cation channel transient receptor potential (TRP) A1 but, unlike multimodal sensory neurons, are inert to hyperoxia and other TRPA1 activators (carbon dioxide, electrophiles, and oxidants) in normoxia. Mechanistically, O2 suppresses TRPA1 channel activity by protein internalization via O2-dependent proline hydroxylation and subsequent ubiquitination by an E3 ubiquitin ligase, NEDD4-1 (neural precursor cell-expressed developmentally down-regulated protein 4). Hypoxia inhibits this process and instantly accumulates TRPA1 proteins at the plasma membrane, inducing TRPA1-mediated Ca2+ influx that triggers ATP release from pFRG/RTN astrocytes, potentiating respiratory center activity. Furthermore, astrocyte-specific Trpa1 disruption in a mouse brainstem-spinal cord preparation impedes the amplitude augmentation of the central autonomic respiratory output during hypoxia. Thus, reversible coupling of the TRPA1 channels with O2-dependent protein translocation allows astrocytes to act as acute hypoxia sensors in the medullary respiratory center.

Blockade of astrocytic activation delays the occurrence of severe hypoxia-induced seizure and respiratory arrest in mice.

Seizures are induced when subjects are exposed to severe hypoxia. It is followed by ventilatory fall-off and eventual respiratory arrest, which may underlie the pathophysiology of death in patients with epilepsy and severe respiratory disorders. However, the mechanisms of hypoxia-induced seizures have not been fully understood. Because astrocytes are involved in various neurological disorders, we aimed to investigate whether astrocytes are operational in seizure generation and respiratory arrest in a severe hypoxic condition. We examined the effects of astrocytic activation blockade on responses of EEG and ventilation to severe hypoxia. Adult mice were divided into two groups; in one group (n = 24) only vehicle was injected, and in the other group (n = 24) arundic acid, an inhibitory modulator of astrocytic activation, was administered before initiation of recording. After recording EEG and ventilation by whole body plethysmography in room air, the gas in the recording chamber was switched to 5% oxygen (nitrogen balanced) until a seizure and ventilatory depression occurred, followed by prompt switch back to room air. Severe hypoxia initially increased ventilation, followed by a seizure and ventilatory suppression in all mice examined. Fourteen mice without arundic acid showed respiratory arrest during loading of hypoxia. However, 22 mice pretreated with arundic acid did not suffer from respiratory arrest. Time from the onset of hypoxia to the occurrence of seizures was significantly longer in the group with arundic acid than that in the group without arundic acid. We suggest that blockade of astrocytic activation delays the occurrence of seizures and prevents respiratory arrest.

Correlation Between Gait Perception and Autistic Traits in the General Population: A Study on Event-Related Evoked Potentials.

Previous studies have shown that people with autistic traits have difficulties in motion perception, such as human gait as depicted on a point-light display. A recent study reported that adults with autism spectrum disorders showed atypical visual event-related evoked potentials (ERPs) in response to radial optic flow. To determine the correlation between gait perception and autistic traits in the general population, the present study recorded ERPs time-locked to the onset of approaching and receding point-light walkers. ERPs were measured using an 8-channel system in 19 adults and the correlation between the ERP components and the Subthreshold Autism Trait Questionnaire (SATQ) score were assessed to quantitatively measure autistic traits in the general population. The results showed that the higher SATQ score was, the longer the latency of the ERP component for an approaching walker was. In conclusion, people with autistic traits have trouble perceiving the approach of other people.

Discordant HER2 status between primary breast carcinoma and recurrent/metastatic tumors using fluorescence in situ hybridization on cytological samples.

OBJECTIVE: The aim of this study was to show the usefulness of examining HER2 status on fluorescence in situ hybridization using cytological samples taken from recurrent/metastatic tumors. METHODS: One hundred freshly aspirated or scraped cytological samples were obtained from locoregional recurrences or distant metastases. Fluorescence in situ hybridization assay for HER2 amplification was performed on both these samples and the formalin-fixed, paraffin-embedded tissues of the paired primary tumors of breast cancer, and the relationships between various clinico-pathological factors and HER2 amplification of both tumors were examined. RESULTS: A change in HER2 status was observed in nine cases (9%): six cases (6%) underwent a positive-to-negative conversion in HER2 status and three cases (3%) underwent a negative-to-positive conversion in HER2 status. A positive-to-negative conversion of HER2 status was noted in 4 (36%) of 11 'luminal-B' cases. The change in HER2 status in recurrent or metastatic tumor was noted in more cases treated with drug therapy than in those with no drug therapy (P < 0.05; Fisher's exact probability). Although the time to relapse was 3 years or more in three cases showing a negative-to-positive conversion in HER2 status, the time to relapse was less than 3 years in six cases showing a positive-to-negative conversion (P < 0.05; Fisher's exact probability). CONCLUSIONS: HER2 examination on fluorescence in situ hybridization using fine-needle aspiration cytology samples of tumors in recurrent/metastatic sites or disseminated tumor cells in effusion is beneficial, particularly when the primary tumor is not suitable for the testing of HER2 status or negative for HER2 amplification, because aspiration using a needle is technically feasible and not as traumatic as biopsy.

Comparison of evaluations of hormone receptors in breast carcinoma by image-analysis using three automated immunohistochemical stainings.

The aim of this study was to compare the results of immunohistochemistry (IHC) assays evaluated by human examiners with the results evaluated by computerized image analysis, and to compare the computerized image analysis results among three automated IHC assays, namely the BioGenex, Dako and Ventana assays. All slides were semiquantitatively evaluated according to the Allred score and J-score by human examiners. The images were analyzed using MacSCOPE version 2.6 for Macintosh according to the H-score and the percentage of positive-stained nuclei per area of carcinoma cells (PP) irrespective of the intensity of the stained nuclei. The H-score for the estrogen receptor (ER) was significantly correlated with the Allred score (P<0.0001) and the PP for the ER was significantly correlated with the J-score (P<0.0001), suggesting that the image analysis used in the present study is a useful method for the evaluation of ER status. Several discrepancies were identified between the Allred score and H-score and between the PP and J-score due to the positive-stained cytoplasm area of carcinoma cells and/ or the positive-stained nuclei area of non-carcinoma cells, including benign epithelial cells, lymphocytes and stromal cells. Accordingly, advances in the algorithm of the digitized analyzing system is necessary.