Questionnaire survey on the prevention and development of cervical cancer in patients with systemic lupus erythematosus in Japan.

OBJECTIVES: The aim is to evaluate the prevention and development of cervical cancer in systemic lupus erythematosus (SLE) patients in Japan and its background based on a questionnaire survey. METHODS: The questionnaire was handed to 460 adult female SLE patients at 12 medical institutions. The participants were grouped by age, and data related to their human papillomavirus vaccination status, age at first coitus, cervical cancer screening, and diagnosis of cervical cancer were analysed. RESULTS: A total of 320 responses were received. Patients aged 35-54 years included a higher proportion of patients whose age at first coitus was <20 years. This group also showed a higher rate of cervical cancer/dysplasia. Only nine patients had a human papillomavirus vaccination history. Adequate frequency of cervical cancer screening was slightly higher (52.1%) among SLE patients than in the Japanese general population. However, 23% of the patients had never undergone examination, primarily because of a feeling of troublesome. The incidence of cervical cancer was significantly higher among SLE patients. One reason for this may be associated with the use of immunosuppressants, although the difference was not significant. CONCLUSIONS: SLE patients are at a higher risk of cervical cancer and dysplasia. Rheumatologists should proactively recommend vaccination and screening examinations for SLE female patients.

Eosinophilic granulomatous with polyangiitis complicated by swelling of the oral cavity floor and cervical soft tissue as initial manifestation mimicking IgG4-related disease: A case report.

Eosinophilic granulomatous polyangiitis is a systemic vasculitis associated with bronchial asthma and eosinophilic sinusitis. Here, we describe an unusual presentation of eosinophilic granulomatous polyangiitis that initially manifested as swelling of the oral cavity floor and cervical soft tissue. A 58 year-old Japanese man was diagnosed with bronchial asthma during childhood but did not receive regular medication. Prior to this presentation, he had a persistent cough for over 1 month, and a local physician diagnosed him with bronchial asthma. However, 6 months later, his cough worsened, and a blood test revealed elevated eosinophil levels. Immediately afterward, swelling of the floor of the oral cavity and cervical soft tissue developed. Cellulitis was suspected and antimicrobial treatment was initiated; however, the symptoms persisted and abdominal pain developed. An endoscopic examination revealed duodenitis and a duodenal ulcer. The patient was diagnosed with eosinophilic granulomatous polyangiitis based on three items of the 2022 American College of Rheumatology/European College of Rheumatology classification criteria: obstructive airway disease, blood eosinophil count ≥1 × 109 cells/L, and extravascular eosinophilic infiltration with a score of 10. Oral prednisolone (70 mg/day), intravenous cyclophosphamide (500 mg/m2), and subcutaneous mepolizumab (300 mg every 4 weeks) were administered. The patient's symptoms improved after these treatments, and the eosinophil count and inflammatory marker levels declined. When swelling of the oral cavity floor and cervical soft tissue following an increase in eosinophilia and allergic symptoms occurs, it is crucial to consider the likelihood of eosinophilic granulomatous polyangiitis and collaborate with otolaryngologists and dentists to ensure its prompt identification.

Simulating developmental diversity: Impact of neural stochasticity on atypical flexibility and hierarchy.

Introduction: Investigating the pathological mechanisms of developmental disorders is a challenge because the symptoms are a result of complex and dynamic factors such as neural networks, cognitive behavior, environment, and developmental learning. Recently, computational methods have started to provide a unified framework for understanding developmental disorders, enabling us to describe the interactions among those multiple factors underlying symptoms. However, this approach is still limited because most studies to date have focused on cross-sectional task performance and lacked the perspectives of developmental learning. Here, we proposed a new research method for understanding the mechanisms of the acquisition and its failures in hierarchical Bayesian representations using a state-of-the-art computational model, referred to as in silico neurodevelopment framework for atypical representation learning. Methods: Simple simulation experiments were conducted using the proposed framework to examine whether manipulating the neural stochasticity and noise levels in external environments during the learning process can lead to the altered acquisition of hierarchical Bayesian representation and reduced flexibility. Results: Networks with normal neural stochasticity acquired hierarchical representations that reflected the underlying probabilistic structures in the environment, including higher-order representation, and exhibited good behavioral and cognitive flexibility. When the neural stochasticity was high during learning, top-down generation using higher-order representation became atypical, although the flexibility did not differ from that of the normal stochasticity settings. However, when the neural stochasticity was low in the learning process, the networks demonstrated reduced flexibility and altered hierarchical representation. Notably, this altered acquisition of higher-order representation and flexibility was ameliorated by increasing the level of noises in external stimuli. Discussion: These results demonstrated that the proposed method assists in modeling developmental disorders by bridging between multiple factors, such as the inherent characteristics of neural dynamics, acquisitions of hierarchical representation, flexible behavior, and external environment.

Positive effect of inaudible high-frequency components of sounds on glucose tolerance: a quasi-experimental crossover study.

Although stress significantly impacts on various metabolic syndromes, including diabetes mellitus, most stress management techniques are based on psychological and subjective approaches. This study examined how the presence or absence of the inaudible high-frequency component (HFC) of sounds, which activates deep-brain structures, affects glucose tolerance in healthy participants using the oral glucose tolerance test (OGTT). Sounds containing HFC suppressed the increase in glucose levels measured by incremental area under the curve in the OGTT compared with the otherwise same sounds without HFC. The suppression effect of HFC was more prominent in the older age group and the group with high HbA1c. This suggests that sounds with HFC are more effective in improving glucose tolerance in individuals at a higher risk of glucose intolerance.

Basal ganglia-cortical connectivity underlies self-regulation of brain oscillations in humans.

Brain-computer interfaces provide an artificial link by which the brain can directly interact with the environment. To achieve fine brain-computer interface control, participants must modulate the patterns of the cortical oscillations generated from the motor and somatosensory cortices. However, it remains unclear how humans regulate cortical oscillations, the controllability of which substantially varies across individuals. Here, we performed simultaneous electroencephalography (to assess brain-computer interface control) and functional magnetic resonance imaging (to measure brain activity) in healthy participants. Self-regulation of cortical oscillations induced activity in the basal ganglia-cortical network and the neurofeedback control network. Successful self-regulation correlated with striatal activity in the basal ganglia-cortical network, through which patterns of cortical oscillations were likely modulated. Moreover, basal ganglia-cortical network and neurofeedback control network connectivity correlated with strong and weak self-regulation, respectively. The findings indicate that the basal ganglia-cortical network is important for self-regulation, the understanding of which should help advance brain-computer interface technology.

Deep Feature Extraction for Resting-State Functional MRI by Self-Supervised Learning and Application to Schizophrenia Diagnosis.

In this study, we propose a deep-learning technique for functional MRI analysis. We introduced a novel self-supervised learning scheme that is particularly useful for functional MRI wherein the subject identity is used as the teacher signal of a neural network. The neural network is trained solely based on functional MRI-scans, and the training does not require any explicit labels. The proposed method demonstrated that each temporal volume of resting state functional MRI contains enough information to identify the subject. The network learned a feature space in which the features were clustered per subject for the test data as well as for the training data; this is unlike the features extracted by conventional methods including region of interests (ROIs) pooling signals and principal component analysis. In addition, applying a simple linear classifier to the per-subject mean of the features (namely "identity feature"), we demonstrated that the extracted features could contribute to schizophrenia diagnosis. The classification accuracy of our identity features was comparable to that of the conventional functional connectivity. Our results suggested that our proposed training scheme of the neural network captured brain functioning related to the diagnosis of psychiatric disorders as well as the identity of the subject. Our results together highlight the validity of our proposed technique as a design for self-supervised learning.

Bilateral Optic Disc Swelling with Preserved Visual Function Associated with Giant Cell Arteritis.

A 68-year-old Japanese man was introduced to our hospital for optic disc swelling (ODS) in his both eyes (OU). Other than floaters in his right eye, he did not report any symptoms including blurred vision, visual field defect, and ocular pain. Light reflex was prompt and complete OU, and critical flicker frequency was within the normal range OU. By fluorescein angiography, hyperfluorescence was detected on optic discs OU; however, no fluorescein leakage or filling defect was observed. By Goldmann perimetry, enlargement of the Mariotte blind spot was revealed OU, while no central scotoma or remarkable visual field defects were detected. By neuroimaging and lumbar puncture, papilledema due to intracranial pressure elevation was denied. Based on the reassessment of fundus findings, narrowing and segmental whitening/sheathing of peripapillary vessels predominantly to arterioles were realized, and systemic arteritis was suspected. Based on the subject age, elevation of erythrocyte sedimentation rate, positron emission tomography findings in the aorta, and MRI findings in temporal arteries, underlying giant cell arteritis (GCA) was diagnosed. After the start of systemic and local steroid therapies, ODS improved OU. Although rare, bilateral ODS with no visual disturbance can occur in patients with GCA. This case emphasizes the importance of careful assessment of ocular findings to reach the correct diagnosis of even a rare cause of ODS.

Three-Dimensional Convolutional Autoencoder Extracts Features of Structural Brain Images With a "Diagnostic Label-Free" Approach: Application to Schizophrenia Datasets.

There has been increasing interest in performing psychiatric brain imaging studies using deep learning. However, most studies in this field disregard three-dimensional (3D) spatial information and targeted disease discrimination, without considering the genetic and clinical heterogeneity of psychiatric disorders. The purpose of this study was to investigate the efficacy of a 3D convolutional autoencoder (3D-CAE) for extracting features related to psychiatric disorders without diagnostic labels. The network was trained using a Kyoto University dataset including 82 patients with schizophrenia (SZ) and 90 healthy subjects (HS) and was evaluated using Center for Biomedical Research Excellence (COBRE) datasets, including 71 SZ patients and 71 HS. We created 16 3D-CAE models with different channels and convolutions to explore the effective range of hyperparameters for psychiatric brain imaging. The number of blocks containing two convolutional layers and one pooling layer was set, ranging from 1 block to 4 blocks. The number of channels in the extraction layer varied from 1, 4, 16, and 32 channels. The proposed 3D-CAEs were successfully reproduced into 3D structural magnetic resonance imaging (MRI) scans with sufficiently low errors. In addition, the features extracted using 3D-CAE retained the relation to clinical information. We explored the appropriate hyperparameter range of 3D-CAE, and it was suggested that a model with 3 blocks may be related to extracting features for predicting the dose of medication and symptom severity in schizophrenia.

Conjunctival Chemosis and Annular Ciliochoroidal Detachments Detected by Anterior-Segment Optical Coherence Tomography in a Case of Systemic Lupus Erythematosus.

A 61-year-old Japanese woman presented to our hospital for treatment of systemic serositis associated with systemic lupus erythematosus (SLE). At the initial ophthalmologic examination, her best-corrected visual acuity was 1.2 and 0.6 in her right and left eyes, respectively. Slit-lamp examination showed marked chemosis in both eyes (OU). Swept source-based, anterior-segment optical coherence tomography (AS-OCT) clearly showed conjunctival elevations corresponding to the chemosis in all scan directions OU. In some scans, hyporeflective spaces with luminal structures corresponding to dilated lymphatic channels and nonluminal structures corresponding to interstitial fluid accumulation were seen clearly under the conjunctival epithelium and/or in the parenchyma. In all scan directions, the supraciliary space was seen clearly, suggesting the presence of an annular ciliochoroidal detachment. Fundus examinations showed retinal edema temporal to the optic nerve head and subfoveal serous retinal detachments OU. Ocular effusions resolved by 2 weeks after the start of steroid pulse therapy, and pleural effusions and ascites resolved and pericardial effusion decreased by 2 months. AS-OCT can be useful for understanding the mechanism(s) of the less common anterior-segment ocular manifestations of SLE.

Distinct decrease in peripheral lymphocytes in EBER-positive cases of MTX-LPD.

OBJECTIVES: To determine the clinical characteristics of methotrexate-associated lymphoproliferative disorder (MTX-LPD). METHODS: In this study, 12 RA patients who developed MTX-LPD were assessed. The peripheral blood lymphocyte (PBL) count at the onset of MTX-LPD was compared to that 6 months before the onset, in Epstein-Barr virus-encoded RNA (EBER)-positive and -negative subgroups. We examined the change in the PBL count after MTX withdrawal. In patients with relapsed LPD, changes in the PBL count before relapse were also examined. RESULTS: Regression of LPD after MTX withdrawal was noted in eight patients. In these patients, the PBL count was decreased at the onset of MTX-LPD compared to 6 months before the onset; the decrease was significantly more prominent in EBER-positive patients. In cases of spontaneous regression of LPD, the PBL count recovered quickly after MTX withdrawal. Four of eight patients showed a recurrence of LPD after they improved following MTX withdrawal. These patients also exhibited a decreased PBL count at recurrence compared to 6 months before recurrence. CONCLUSION: A decrease in the PBL count might be involved in the pathogenesis of MTX-LPD, especially in EBER-positive cases and in patients with LPD relapse after MTX withdrawal following initial improvement.

A case of rheumatoid arthritis with multiple lung rheumatoid nodules successfully treated with tofacitinib.

Sporadic cases of rheumatoid nodules (RNs) in the lung during treatment with tumour necrosis factor (TNF) inhibitors have been reported, but no treatment has been established. Here, we report a case of symptomatic lung RNs refractory to abatacept (ABT) and intravenous cyclophosphamide (IVCY) that improved with tofacitinib (TOF) treatment. A 75-year-old Japanese woman with a 10-year history of rheumatoid arthritis (RA) presented with a cough and haemoptysis during treatment with etanercept (ETN). Radiographic examinations revealed multiple nodules that were diagnosed as lung RNs via biopsy. The ETN was discontinued and ABT followed by IVCY was introduced; however, neither was sufficiently effective against the lung RNs. Thereafter, TOF was started and the lung RNs improved rapidly. The precise mechanisms that induce RNs during treatment with TNF inhibitors are unknown. Cytokines (IL-23 and IL-6) are suspected to be involved. TOF may be a reasonable strategy for treating symptomatic lung RNs.

[Neural Basis of "Breath of Aun"].

Many musical expressions exist in various cultures of the world, where multiple performers autonomously synchronize without a conductor or a metronome, and achieve an undisturbed musical performance by "breath of Aun". As a typical example, we considered the ritual performing art of Kecak in Bali, Indonesia, and performed simultaneous electroencephalogram (EEG) measurements on multiple participants during a Kecak performance. The study revealed that the inter-individual synchronization of the EEG during and after the performance was enhanced as compared to that before the performance. The author will also discuss the relation between synchronization of brain function and society and the culture of Bali.

Electrophysiological Effects of Transcranial Direct Current Stimulation on Neural Activity in the Rat Motor Cortex.

Transcranial direct current stimulation (tDCS) is a non-invasive technique that modulates the neuronal membrane potential. We have previously documented a sustainable increase in extracellular dopamine levels in the rat striatum of cathodal tDCS, suggesting that cathodal tDCS enhances the neuronal excitability of the cortex. In the present study, we investigated changes in neuronal activity in the cerebral cortex induced by tDCS at the point beneath the stimulus electrode in anesthetized rats in vivo. Multiunit recordings were performed to examine changes in neuronal activity before and after the application of tDCS. In the cathodal tDCS group, multiunit activity (indicating the collective firing rate of recorded neuronal populations) increased in the cerebral cortex. Both anodal and cathodal tDCS increased the firing rate of isolated single units in the cerebral cortex. Significant differences in activity were observed immediately following stimulation and persisted for more than an hour after stimulation. The primary finding of this study was that both anodal and cathodal tDCS increased in vivo neuronal activity in the rat cerebral cortex underneath the stimulus electrode.

Plastic frontal pole cortex structure related to individual persistence for goal achievement.

Persistent goal-directed behaviours result in achievements in many fields. However, the underlying neural mechanisms of persistence and the methods that enhance the neuroplasticity underlying persistence, remain unclear. We here demonstrate that the structural properties of the frontal pole cortex (FPC) before tasks contain information that can classify Achievers and Non-achievers (goal-directed persistence) participating in three tasks that differ in time scale (hours to months) and task domains (cognitive, language, and motor learning). We also found that most Achievers exhibit experience-dependent neuroplastic changes in the FPC after completing language and motor learning tasks. Moreover, we confirmed that a coaching strategy that used subgoals modified goal-directed persistence and increased the likelihood of becoming an Achiever. Notably, we discovered that neuroplastic changes in the FPC were facilitated by the subgoal strategy, suggesting that goal-striving, using effective coaching, optimizes the FPC for goal persistence.

Inaudible components of the human infant cry influence haemodynamic responses in the breast region of mothers.

Distress vocalizations are fundamental for survival, and both sonic and ultrasonic components of such vocalizations are preserved phylogenetically among many mammals. On this basis, we hypothesized that ultrasonic inaudible components of the acoustic signal might play a heretofore hidden role in humans as well. By investigating the human distress vocalization (infant cry), here we show that, similar to other species, the human infant cry contains ultrasonic components that modulate haemodynamic responses in mothers, without the mother being consciously aware of those modulations. In two studies, we measured the haemodynamic activity in the breasts of mothers while they were exposed to the ultrasonic components of infant cries. Although mothers were not aware of ultrasounds, the presence of the ultrasounds in combination with the audible components increased oxygenated haemoglobin concentration in the mothers' breast region. This modulation was observed only when the body surface was exposed to the ultrasonic components. These findings provide the first evidence indicating that the ultrasonic components of the acoustic signal play a role in human mother-infant interaction.

Augmentation of Positive Valence System-Focused Cognitive Behavioral Therapy by Inaudible High-Frequency Sounds for Anhedonia: A Trial Protocol for a Pilot Study.

Importance: Recent conceptualizations in Research Domain Criteria have indicated that anhedonia, 1 of 2 core symptoms of depression, which can be treatment resistant, is associated with deficits in the positive valence system, and inaudible high-frequency sound therapy has been shown to enhance reward-related brain circuitry. Hence, cognitive behavioral therapy focusing on the positive valence system enhanced with sound therapy could have a synergistic effect on anhedonia. Objective: To test the augmentation effect of inaudible high-frequency sounds on the efficacy of positive valence system-focused cognitive behavioral therapy to treat anhedonia. Design, Setting, and Participants: In this individual-level allocation, exploratory, single-center randomized superiority pilot trial, patients, therapists, and evaluators will be masked to intervention or placebo assignment. The trial will take place at a national psychiatric referral hospital in Tokyo, Japan, among 44 adult patients with clinically significant anhedonia and moderate to severe depression. Outcomes will be analyzed following the intent-to-treat principle using a repeated-measures mixed model. Intervention: The intervention group will participate in 8 weekly sessions of positive valence system-focused cognitive behavioral therapy with in-session exposure to an inaudible high-frequency sound; the comparison group will undergo cognitive behavioral therapy with in-session exposure to a placebo sound. Main Outcomes and Measures: The primary outcome is anhedonia assessed using the self-reported Snaith-Hamilton Pleasure Scale. The secondary outcome is anhedonia assessed using the clinician-administered version of the Snaith-Hamilton Pleasure Scale. Discussion: Recruitment for this study began in May 2018, and the projected date of final allocation is January 2020. A total of 21 eligible patients were registered for participation as of May 30, 2019. To date, treatments for depression do not guarantee clinically successful outcomes. This pilot trial will provide preliminary evidence of the augmentation effect of high-frequency inaudible sounds on cognitive behavioral therapy for anhedonia. Overall, exposure to an inaudible high-frequency sounds does not require attentional or cognitive effort from either patients or therapists; therefore, results from a future confirmative trial could indicate that cognitive behavioral therapy can be augmented in an effortless manner. Trial Registration: umin.ac.jp/ctr Identifier: UMIN000031948.

Reciprocal cortical activation patterns during incisal and molar biting correlated with bite force levels: an fMRI study.

In humans, the incisors and molars have distinct functions during mastication, analogous to the two main types of handgrip, the precision and power grips. In the present study, we investigated cortical activation and masticatory muscle activity during incisal and molar biting via simultaneous functional magnetic resonance imaging and electromyogram (EMG) recordings. We conducted recordings in 15 healthy adult participants while they performed incisal and molar biting tasks at three step-wise force levels using two custom-made splints. Regarding the results of the ROI analysis, we found a significantly stronger positive linear correlation between the blood oxygenation level dependent signal and EMG activity during molar biting than incisal biting, which was particularly prominent in the primary sensorimotor cortex and the cerebellum. We also found a significantly stronger negative linear correlation during incisal biting than molar biting, which was particularly prominent in the rostral cingulate motor area, superior frontal gyrus, and caudate nucleus. These findings indicate that molar biting enables powerful chewing: brain activity in several brain areas related to motor function was increased with increasing bite force levels, while incisal biting enables fine motor control: brain activity in several brain areas related to motor control was increased with reduced bite force levels.

Effective Augmentation of Creativity-Involving Productivity Consequent to Spontaneous Selectivity in Knowledge Acquisition.

The results of many studies have suggested that we actively select information from the environment. However, the functional consequences of such selectivity in knowledge acquisition remain unclear, even though it is a vital factor in determining the characteristics of our future knowledge and cognition. We hypothesized that spontaneous selectivity in knowledge acquisition results in effective augmentation of productivity, especially in creativity-demanding task. To test this, we conducted experiments in which subjects acquired novel compositional words during their rapid presentation, evaluated memory confidence rates for the acquired words, and then produced essays based on these words. First, in experiment 1, we showed that the level of confidence in the recognition memory for the words positively related with the length of the essays (a measure of creativity-involving productivity in quantity). Additionally, we found that the semantic distance from the essay to the components of the compositional word (a measure of creative-productivity in quality) was farther for the word with higher memory confidence than for the word with lower memory confidence, suggesting creative leaps when writing the former. While this result supported our hypothesis, it might also reflect better memory that was independent of spontaneous selection. Thus, in a different subject group, we conducted a similar experiment (experiment 2) in which two of the 20 compositional words were presented more often (five times per block) to force memorization. Again, consistent with our hypothesis, essays based on spontaneously memorized words (presented once per block) were significantly longer than those produced using the forcedly memorized words. Therefore, better memory per se did not explain the higher productivity. Instead, these results suggested that the higher creativity-involving productivity was consequent to spontaneous selectivity in the knowledge acquisition. Additionally, we propose a possible mechanism for the observed results based on the results of a neural network simulation. In this simulation, we found that novel information that was assigned to locations more easily accessible to the entire network was better assimilated and therefore selectively acquired. Based on this simulation, we moderately suggest that spontaneously acquired knowledge effectively confers productivity because it effectively activates large parts of the neural networks.