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Abstract Background The efficacy of anti‐CTLA‐4 antibody (ipilimumab) plus anti‐programmed cell death 1 antibody (nivolumab) in treating advanced non‐small cell lung cancer (NSCLC) is impeded by an elevated risk of severe immune‐related adverse events. However, our understanding of associations among pre‐existing fibrosis, emphysematous changes, and objective indicators as predictive factors is limited for severe pneumonitis in NSCLC patients receiving this combination therapy. Thus, we retrospectively investigated these associations, including overall tumor burden, before treatment initiation in the Japanese population. Methods We focused on patients (n = 76) with pre‐existing interstitial lung disease (ILD) to identify predictors of severe pneumonitis. Variables included age, sex, smoking status, programmed cell death ligand 1 expression, overall tumor burden, chest computed tomography‐confirmed fibrosis, serum markers, and respiratory function test results. Results Severe pneumonitis was more frequent in patients with squamous cell carcinoma, fibrosis, low diffusing capacity for carbon monoxide (%DLCO), and high surfactant protein D (SP‐D) level. Notably, squamous cell carcinoma, baseline %DLCO, and SP‐D level were significant risk factors. Our findings revealed the nonsignificance of tumor burden (≥85 mm) in predicting severe pneumonitis, emphasizing the importance of pre‐existing ILD. Conversely, in cases without pre‐existing fibrosis, severe pneumonitis was not associated with %DLCO or SP‐D level (93.2% vs. 91.9%, and 63.3 vs. 40.9 ng/mL, respectively) and was more common in patients with a large overall tumor burden (97.5 vs. 70.0 mm). Conclusion Vigilant monitoring and early intervention are crucial for patients with squamous cell carcinoma, high SP‐D level, or low %DLCO undergoing ipilimumab plus nivolumab therapy.

Background The impact of high‐risk coronary artery plaques identified using optical coherence tomography on late luminal narrowing and clinical events remains poorly understood. Methods and Results This multicenter prospective study included 176 patients who underwent percutaneous coronary intervention and serial optical coherence tomography at baseline and 1‐year follow‐up to investigate nontarget regions with angiographically intermediate stenosis. At 1 year after percutaneous coronary intervention, the coronary artery lumen area decreased significantly from 6.06 (95% CI, 5.60–6.53) mm2 to 5.88 (95% CI, 5.41–6.35) mm2 (difference, −0.18; 95% CI, −0.22 to −0.14 mm2; P

With the ongoing spread and functional improvement of hearables, we may soon find ourselves in a society where users are wearing hearables at all times. In a hearable environment of this kind, the constant presentation of aural information to users may impede their ability to hear external noises that require their attention. For example, suppose the constant presentation of information in a particular frequency band causes a reduction in the subjective perception of sound pressure (loudness) of the corresponding frequency band. In such a case, the response to environmental sounds that indicate danger (e.g., the sound of an approaching car or an emergency alarm) may be delayed, leading to potential disaster. In this study, we investigated 1) how the presentation of a sound of a specific frequency through a hearable affects the loudness; and 2) which stimulus sound is most effective for recovering the decrease in loudness. In the first investigation, a loudspeaker presented the sound of a specific frequency that imitates environmental sound, and a hearable gave a stimulus sound of a particular frequency based on the frequency of the loudspeaker sound. The results showed that the loudness decreased by more than 10.0% in all stimulus sounds listened to with hearables, and the amount of the decrease tended to be larger the closer the frequency of the loudspeaker sound was to that of the hearable sound. In the second investigation, we hypothesized that the presence of specific recovery stimulus sounds would be effective in quickly restoring any loudness that had decreased, and the results showed that the amount of recovery was greater for all the recovery stimulus sounds we used compared to when the stimulus sounds were not presented.

Inner ear malformations are predominantly attributed to developmental arrest during the embryonic stage of membranous labyrinth development. Due to the inherent difficulty in clinically assessing the status of the membranous labyrinth, these malformations are diagnosed with radiographic imaging, based on the morphological characteristics of the bony labyrinth. While extensive research has elucidated the intricacies of membranous labyrinth development in mouse models, comprehensive investigations into the developmental trajectory of the bony labyrinth, especially about its calcification process, have been notably lacking. One of the most prominent types of inner ear malformations is known as incomplete partition (IP), characterized by nearly normal external cochlear appearance but pronounced irregularities in the morphology of the modiolus and inter-scalar septa. IP type II (IP-II), also known as Mondini dysplasia, is generally accompanied by an enlargement of the vestibular aqueduct and is primarily attributed to mutations in the SLC26A4 gene. In the case of IP-II, the modiolus and inter-scalar septa of the cochlear apex are underdeveloped or missing, resulting in the manifestation of a cystic structure on radiographic imaging. In this overview, we not only explore the normal development of the bony labyrinth in mice but also present our observations on otolith mineralization. Furthermore, we investigated the specifics of bony labyrinth and otolith mineralization in Slc26a4-deficient mice, which served as an animal model for IP-II. We ensured that these findings promise to provide valuable insights for the establishment of therapeutic interventions, optimal timing, targeted sites, and preventive measures when considering the management of this condition.

Abstract Objective We aimed to elucidate the ossification process of the otic capsule in postnatal C57BL/6 mice and depict the three‐dimensional (3D) process of otoconial mineralization in vivo. Methods The otic capsules of C57BL/6 mice were stained with alizarin red and imaged/compared using micro‐computed tomography on postnatal day (P) between P0 and P8, P10, P15, and P30 and 3–4 months old (P3–4Mo). We reconstructed 3D images of the otic capsule and otoconia and measured the bone mineral density using x‐ray absorptiometry on each age. Results The 3D reconstructed otic capsule images revealed two ossification centers of the otic capsule at P0. One was observed around the ampulla of the superior semicircular canal and utricle, and the other was observed around the ampulla of the posterior semicircular canal. The cross‐sectional views demonstrated that modiolar ossification developed from the base to the apex from P4 to P8. The inter‐scalar septum ossified bidirectionally from the modiolus and bony otic capsule from P8 to P15. The mineralized otoconia were first detected in the utricle at P3 and saccular otoconia at P6. The density of the utricle and saccular otoconia showed different growth trends. Conclusion To the best of our knowledge, this is the first study to demonstrate the 3D appearance of the otic capsule and otoconia in different developmental stages of mice. We also revealed that modiolar and inter‐scalar septal calcification is the final event in the cochlea and that it can be susceptible to pathological conditions (cochlear congenital malformations and hereditary vestibular diseases). The unique features of the ossification process and duration may explain these pathological conditions observed in humans. Level of Evidence 3

Abstract Background Although cases of respiratory bacterial infections associated with coronavirus disease 2019 (COVID-19) have often been reported, their impact on the clinical course remains unclear. Herein, we evaluated and analyzed the complication rates of bacterial infections, causative organisms, patient backgrounds, and clinical outcome in Japanese patients with COVID-19. Methods We performed a retrospective cohort study that included inpatients with COVID-19 from multiple centers participating in the Japan COVID-19 Taskforce (April 2020 to May 2021) and obtained demographic, epidemiological, and microbiological results and the clinical course and analyzed the cases of COVID-19 complicated by respiratory bacterial infections. Results Of the 1,863 patients with COVID-19 included in the analysis, 140 (7.5%) had respiratory bacterial infections. Community-acquired co-infection at COVID-19 diagnosis was uncommon (55/1,863, 3.0%) and was mainly caused by Staphylococcus aureus, Klebsiella pneumoniae and Streptococcus pneumoniae. Hospital-acquired bacterial secondary infections, mostly caused by Staphylococcus aureus, Pseudomonas aeruginosa, and Stenotrophomonas maltophilia, were diagnosed in 86 patients (4.6%). Severity-associated comorbidities were frequently observed in hospital-acquired secondary infection cases, including hypertension, diabetes, and chronic kidney disease. The study results suggest that the neutrophil–lymphocyte ratio (> 5.28) may be useful in diagnosing complications of respiratory bacterial infections. COVID-19 patients with community-acquired or hospital-acquired secondary infections had significantly increased mortality. Conclusions Respiratory bacterial co-infections and secondary infections are uncommon in patients with COVID-19 but may worsen outcomes. Assessment of bacterial complications is important in hospitalized patients with COVID-19, and the study findings are meaningful for the appropriate use of antimicrobial agents and management strategies.

IntroductionThe wearable cyborg Hybrid Assistive Limb (HAL) is the world’s first cyborg-type wearable robotic device, and it assists the user’s voluntary movements and facilitates muscle activities. However, since the minimum height required for using the HAL is 150 cm, a smaller HAL (2S size) has been newly developed for pediatric use. This study aimed to (1) examine the feasibility and safety of a protocol for treatments with HAL (2S size) in pediatric patients and (2) explore the optimal method for assessing the efficacy of HAL.MethodsThis clinical study included seven pediatric patients with postural and motor function disorders, who received 8–12 sessions of smaller HAL (2S size) treatment. The primary outcome was the Gross Motor Function Measure-88 (GMFM-88). The secondary outcomes were GMFM-66, 10-m walk test, 2- and 6-min walking distances, Canadian Occupational Performance Measure (COPM), a post-treatment questionnaire, adverse events, and device failures. Statistical analyses were performed using the paired samples t-test or Wilcoxon signed-rank test.ResultsAll participants completed the study protocol with no serious adverse events. GMFM-88 improved from 65.51 ± 21.97 to 66.72 ± 22.28 (p = 0.07). The improvements in the secondary outcomes were as follows: GMFM-66, 53.63 ± 11.94 to 54.96 ± 12.31, p = 0.04; step length, 0.32 ± 0.16 to 0.34 ± 0.16, p = 0.25; 2-MWD, 59.1 ± 57.0 to 62.8 ± 63.3, p = 0.54; COPM performance score, 3.7 ± 2.0 to 5.3 ± 1.9, p = 0.06; COPM satisfaction score, 3.3 ± 2.1 to 5.1 ± 2.1, p = 0.04.DiscussionIn this exploratory study, we applied a new size of wearable cyborg HAL (2S size), to children with central nervous system disorders. We evaluated its safety, feasibility, and identified an optimal assessment method for multiple treatments. All participants completed the protocol with no serious adverse events. This study suggested that the GMFM would be an optimal assessment tool for validation trials of HAL (2S size) treatment in pediatric patients with posture and motor function disorders.

Many earphone-type wearable devices (hearables) with noise-canceling features can capture external sound and present it to the user (transparency mode). This function helps the user avoid being cut off from the outside while wearing the earphones. However, because the built-in microphone/speaker has a frequency response, the presented sound differs from the sound acquired by the user’s original auditory system. Since humans use a head-related transfer function (HRTF) to identify the direction of sound sources, changes in the user’s HRTF caused by transparency mode may adversely affect their sound localization ability. Therefore, this study investigated the changes in sound localization ability when using the transparency mode of commercially available hearables. A sound localization experiment was conducted on 10 participants using three hearables to identify 12 sound sources separated by 30° around each participant. The results show that the accuracy of sound localization decreases from 91.5% to 68.9% when using transparency mode. Moreover, a method was proposed to cancel the device’s microphone/speaker frequency characteristics. Evaluation results confirmed that the proposed method increased the accuracy of sound localization from 62.7% to 72.0%.

Abstract While information enriches daily life, it can also sometimes have a negative impact, depending on an individual’s mental state. We recorded electroencephalogram (EEG) signals from depressed and non-depressed individuals classified based on the Beck Depression Inventory-II score while they listened to news to clarify differences in their attention to affective information and the impact of attentional bias on language processing. Results showed that depressed individuals are characterized by delayed attention to positive news and require a more increased load on language processing. The feasibility of detecting a depressed state using these EEG characteristics was evaluated by classifying individuals as depressed and non-depressed individuals. The area under the curve in the models trained by the EEG features used was 0.73. This result shows that individuals’ mental states may be assessed based on EEG measured during daily activities like listening to news.

Silverfish are known as one of the major pests which feed on paper and starch-based materials and can cause serious problems in museums, libraries and archives.Ctenolepisma calvum (Ritter, 1910) was first recorded from Ceylon (now Sri Lanka) and has also been known from Central American countries including Guyana and Cuba. Recently, its rapid spread to European countries, including Austria, Czech, Germany and Norway, has been reported. In addition, there are unverified records of C. calvum from 17 more countries in the on-line citizen-science platforms iNaturalist.We report C. calvum in Japan for the first time, from Hokkaido, Miyagi, Tokyo, Fukuoka and Nagasaki Prefectures. The specimens in Japan were observed in detail by stereomicroscope, optical microscope and scanning electron microscope. The occurrence of this species is a serious problem from the viewpoint of protection of cultural properties. We also registered their mitochondrial cytochrome oxidase I (COI) gene in EMBL/GenBank/DDBJ.

Patients with SLC26A4 mutations exhibit highly variable hearing loss and vestibular dysfunction. Although Slc26a4 mutant mice similarly exhibit vestibular deficits, including circling behavior, head tilting, and torticollis, the underlying pathogenesis of the vestibular symptoms remains unclear, hindering its effective management for patients with SLC26A4 mutations. In this study, we evaluated the equilibrium function using the inspection equipment, which can record eye movements against rotational, gravitational, and thermal stimulations. Moreover, we correlated the degree of functional impairment with the morphological alterations observed in Slc26a4Δ/Δ mice. The rotational stimulus and ice water caloric tests revealed considerable impairment of the semicircular canal, while the tilted gravitational stimulus test showed a severe functional decline of the otolithic system in Slc26a4Δ/Δ mice. Generally, the degree of impairment was more severe in circling Slc26a4Δ/Δ mice than in non-circling Slc26a4Δ/Δ mice. In non-circling Slc26a4Δ/Δ mice, the semicircular canal function was normal. Micro-computed tomography results showed enlargement of the vestibular aqueduct and bony semicircular canals but no correlative relationship between the severity of the caloric response and the size of bony labyrinths. Giant otoconia and a significant decrease in total otolith volume in the saccule and utricle were observed in Slc26a4Δ/Δ mice. However, the giant otoconia were not overly dislocated in the bony otolithic system and ectopic otoconia were absent in the semicircular canal. The number and morphology of the utricular hair cells in Slc26a4Δ/Δ mice were not significantly reduced compared to those in Slc26a4Δ/+ mice. Collectively, we can conclude that vestibular impairments are mainly associated with otoconia formation and morphology rather than hair cell degeneration. In addition, severe disturbances of semicircular canals cause circling behavior in Slc26a4Δ/Δ mice. Our comprehensive morphological and functional assessments apply to mouse models of other genetic diseases with vestibular impairment.

BackgroundSpinal and bulbar muscular atrophy (SBMA) is a progressive neuromuscular degenerative disease characterized by the degeneration of lower motor neurons in the spinal cord and brainstem and neurogenic atrophy of the skeletal muscle. Although the short-term effectiveness of gait treatment using a wearable cyborg hybrid assistive limb (HAL) has been demonstrated for the rehabilitation of patients with SBMA, the long-term effects of this treatment are unclear. Thus, this study aimed to investigate the long-term effects of the continued gait treatment with HAL in a patient with SBMA.ResultsA 68-year-old man with SBMA had lower limb muscle weakness and atrophy, gait asymmetry, and decreased walking endurance. The patient performed nine courses of HAL gait treatment (as one course three times per week for 3 weeks, totaling nine times) for ~5 years. The patient performed HAL gait treatment to improve gait symmetry and endurance. A physical therapist adjusted HAL based on the gait analysis and physical function of the patient. Outcome measurements, such as 2-min walking distance (2MWD), 10-meter walking test (maximal walking speed, step length, cadence, and gait symmetry), muscle strength, Revised Amyotrophic Lateral Sclerosis Functional Assessment Scale (ALSFRS-R), and patient-reported outcomes, were evaluated immediately before and after gait treatment with HAL for each course. 2MWD improved from 94 m to 101.8 m, and the ALSFRS-R gait items remained unchanged (score 3) for approximately 5 years. The patient could maintain walking ability in terms of gait symmetry, walking endurance, and independence walking despite disease progression during HAL treatment.ConclusionThe long-term gait treatment with HAL in a patient with SBMA may contribute to the maintenance and improvement of the gait endurance and ability to perform activities of daily living. The cybernics treatment using HAL may enable patients to relearn correct gait movements. The gait analysis and physical function assessment by a physical therapist might be important to maximize the benefits of HAL treatment.

Background: The second demonstration experiment of supporting elderly people going out with the Choisoko system was conducted. The first study showed that for women, friends, shopping, convenience, and events are factors that have the potential to be effective motivational factors for encouraging these women to go out. On the other hand, these factors did not lead to any behavioral change in men. Since there are approximately 15 million men over the age of 65 in Japan, behavioral changes in the entire elderly population will not occur without guidance for elderly men to go out. Methods: Sixteen elderly men and forty-seven elderly women participated. Interestingly, men are far more passionate about games than women. Therefore, we hypothesized that a preference for games could be a hint as to how we might encourage older men to go out. Then, a second demonstration experiment was conducted, and we analyzed the relationship between six game preferences and the frequency of going out. Results: Among gaming preferences, men with gaming preferences such as Philanthropists, Achievers, and Free Spirits showed a tendency to go out. Conclusions: These stimuli may have the potential to be factors that may encourage elderly men to go out.

Malignant pleural mesothelioma (MPM) develops primarily from asbestos exposures and has a poor prognosis. In this study, The Cancer Genome Atlas was used to perform a comprehensive survival analysis, which identified the CHST4 gene as a potential predictor of favorable overall survival for patients with MPM. An enrichment analysis of favorable prognostic genes, including CHST4, showed immune-related ontological terms, whereas an analysis of unfavorable prognostic genes indicated cell-cycle-related terms. CHST4 mRNA expression in MPM was significantly correlated with Bindea immune-gene signatures. To validate the relationship between CHST4 expression and prognosis, we performed an immunohistochemical analysis of CHST4 protein expression in 23 surgical specimens from surgically treated patients with MPM who achieved macroscopic complete resection. The score calculated from the proportion and intensity staining was used to compare the intensity of CHST4 gene expression, which showed that CHST4 expression was stronger in patients with a better postoperative prognosis. The median overall postoperative survival was 107.8 months in the high-expression-score group and 38.0 months in the low-score group (p = 0.044, log-rank test). Survival after recurrence was also significantly improved by CHST4 expression. These results suggest that CHST4 is useful as a prognostic biomarker in MPM.

Genetic mechanisms influencing COVID-19 susceptibility are not well understood. Here, the authors analyzed whole blood RNA-seq data of 465 Japanese individuals with COVID-19, highlighting thousands of fine-mapped variants affecting expression and splicing of genes, as well as the presence of COVID-19 severity-interaction eQTLs.

Key message Perinatal cardiomyopathy presents similarly to dilated cardiomyopathy and should be suspected in perinatal women presenting with dyspnoea, even with no previous history of heart disease.

Mountain observatories at high altitudes, far from local anthropogenic emission sources, are considered ideal for monitoring temporal variations of tropospheric air pollutants. During August 17–21 in 2013, we measured sulfur dioxide and nitric acid concentrations in the free troposphere at the top (3776 m a.s.l.) of Mt. Fuji, Japan. A parallel plate wet denuder-ion chromatographic system was used for the online measurement with 15 min temporal resolution. The continuous observations were successfully achieved without any problems. Of the samples collected, 97.8% of sulfur dioxide and 75.7% of nitric acid were above the limits of quantification. The average gas concentrations ± standard deviation (n = 408) were 0.106 ± 0.377 ppbv for sulfur dioxide and 0.015 ± 0.014 ppbv for nitric acid, respectively. Episodic elevations of sulfur dioxide concentration were recorded from August 20 to 21. Backward trajectory analyses indicated that the high-temporal resolution monitor detected the volcanic sulfur dioxide from Mt. Sakurajima, located 857 km from the sampling point. High-time-resolved observations in the free troposphere proved useful for source identification of air pollutants.

A technique to establish electrical contact and perform multi-probe electrical measurements (e.g., four-probe measurements), even at low temperatures, is presented in this work. The natural adhesion contact (NAC) is applicable to the wide range of dimensions of organic crystals. Furthermore, the precise electrode patterns required to carry out multi-probe measurements are guaranteed, in contrast to fine conductive paste painting methods. We demonstrate four-probe electrical measurements of α-(BEDT-TTF)2I3 (where BEDT-TTF = bis(ethylenedithio) tetrathiafulvalene) at temperatures down to 100 K. The obtained temperature dependence showed a steep meta l–insulator transition and exhibited zero hysteresis throughout several measurement sequences.

Abstract Background Biologics dramatically improve symptoms of severe asthma; however, various exacerbating factors may induce flare-up. Pneumocystis spp. have not been reported as a cause of asthma exacerbation during biologic use, although patients with severe asthma have high levels of antibodies against Pneumocystis spp. Case presentation An 87-year-old female with severe asthma that was well-controlled with mepolizumab, who developed a steroid-resistant refractory flare-up. Chest computed tomography showed bilateral ground glass opacities, and results of polymerase chain reaction tests on induced sputum were positive for Pneumocystis DNA. Therefore, a diagnosis of Pneumocystis pneumonia was made. The clinical symptoms improved after treatment with sulfamethoxazole–trimethoprim. Conclusion Clinicians should be aware of Pneumocystis pneumonia as a cause of refractory exacerbation of bronchial asthma during use of interleukin-5 inhibitors.

Echolocation has been shown to improve the independence of visually impaired people, and utilizing ultrasound in echolocation offers additional advantages, such as a higher resolution of object sensing and ease of extraction from background sounds. However, humans cannot innately make and hear ultrasound. A wearable device that enables ultrasonic echolocation, i.e., that transmits ultrasound through an ultrasonic speaker and converts the reflected ultrasound into audible sound, has therefore been attracting interest. Such a system can be utilized with machine learning (ML) to help visually impaired users recognize objects. We have therefore been developing a cooperative echolocation system that combines human recognition with ML recognition. As the first step toward cooperative echolocation, this paper presents the effectiveness of ML in echolocation. We implemented a prototype device and evaluated the performance of object detection with/without ML and found that the mental workload on the user was significantly decreased when ML was used. Based on the findings from the evaluation, we discussed the design of cooperative echolocation.

Abstract Power devices are operated under harsh conditions, such as high currents and voltages, and so degradation of these devices is an important issue. Our group previously found significant increases in reverse leakage current after applying continuous forward current stress to GaN p–n junctions. In the present study, we identified the type of threading dislocations that provide pathways for this reverse leakage current. GaN p–n diodes were grown by metalorganic vapor phase epitaxy on freestanding GaN(0001) substrates with threading dislocation densities of approximately 3 × 105 cm−2. These diodes exhibited a breakdown voltage on the order of 200 V and avalanche capability. The leakage current in some diodes in response to a reverse bias was found to rapidly increase with continuous forward current injection, and leakage sites were identified by optical emission microscopy. Closed-core threading screw dislocations (TSDs) were found at five emission spots based on cross-sectional transmission electron microscopy analyses using two-beam diffraction conditions. The Burgers vectors of these dislocations were identified as [0001] using large-angle convergent-beam electron diffraction. Thus, TSDs for which b = 1c are believed to provide current leakage paths in response to forward current stress.

Abstract Anhydrobiosis, one of the most extensively studied forms of cryptobiosis, is induced in certain organisms as a response to desiccation. Anhydrobiotic species has been hypothesized to produce substances that can protect their biological components and/or cell membranes without water. In extremotolerant tardigrades, highly hydrophilic and heat-soluble protein families, cytosolic abundant heat-soluble (CAHS) proteins, have been identified, which are postulated to be integral parts of the tardigrades’ response to desiccation. In this study, to elucidate these protein functions, we performed in vitro and in vivo characterizations of the reversible self-assembling property of CAHS1 protein, a major isoform of CAHS proteins from Ramazzottius varieornatus, using a series of spectroscopic and microscopic techniques. We found that CAHS1 proteins homo-oligomerized via the C-terminal α-helical region and formed a hydrogel as their concentration increased. We also demonstrated that the overexpressed CAHS1 proteins formed condensates under desiccation-mimicking conditions. These data strongly suggested that, upon drying, the CAHS1 proteins form oligomers and eventually underwent sol–gel transition in tardigrade cytosols. Thus, it is proposed that the CAHS1 proteins form the cytosolic fibrous condensates, which presumably have variable mechanisms for the desiccation tolerance of tardigrades. These findings provide insights into molecular strategies of organisms to adapt to extreme environments.

The challenge level of goal achievement affects intrinsic motivation. Thus, the goal score learners are required to achieve is an important element in gamified educational applications to foster users' intrinsic motivation. However, determining optimal goal scores that enhance the intrinsic motivation of each learner is not easy because individual competence and preferences for the challenge level (e.g., preference for difficult-to-achieve challenges) vary. One approach is to determine the goal score using physiological measurements to estimate when an individual's intrinsic motivation is reinforced. Measurement of event-related potentials (ERPs) is considered useful for this purpose. ERPs time-locked to feedback onset, such as feedback-related negativity and P300, reflect intrinsic motivation. However, it remains unclear whether these ERPs can serve as indicators of optimal goal scores for gamified educational applications in terms of intrinsic motivation. The present study aimed to examine whether ERP measures vary with the challenge levels of the goal score determined by participants' competence (too-easy, moderate and too-hard levels) and/or with their preference for these levels when using a gamified mental arithmetic application. Thirty-three participants solved 64 addition problems in one session in this application and received auditory feedback immediately after each answer entry. Scores were then calculated based on their task performance. Before each session, participants were informed of the goal score and instructed to exceed it as much as possible. Sessions were repeated six times at easy, moderate, and hard levels of goal scores, with two sessions per level. Goal score preferences were quantified based on subjective ratings of the motivation to achieve each level of goal score using a 7-point Likert scale. The mean amplitudes of ERPs were obtained for each participant. Results showed that P300 was significantly related to subjective ratings but not to levels of goal scores, indicating that P300 could be an indicator of participant preference for goal score levels. This study suggests that measurement of P300 may serve as a neural indicator providing an optimal goal score for individual learners that maximizes their intrinsic motivation in gamified learning applications.

Key message There are more complications in transbronchial lung cryobiopsy than in a conventional transbronchial lung biopsy. Respiratory endoscopists should be aware of the potential complications, including rare complications such as hemothorax.

Key message Negligence of health safety is common cause for occupational hazards such as charcoal maker's pneumoconiosis. This case report highlights such a case where the condition developed because of not wearing a dust mask due to the heat during production. As the condition is mostly asymptomatic, preventive measures must be encouraged.

Key message Transesophageal ultrasound‐guided bronchoscopic aspiration (EUS‐B‐FNA) allowed for minimally invasive and simultaneous diagnosis and evaluation of the degree of invasion by echocardiography. EUS‐B‐FNA may be useful for the evaluation and diagnosis of tumours with cardiac invasion.

Multidomain proteins can exhibit sophisticated functions based on cooperative interactions and allosteric regulation through spatial rearrangements of the multiple domains. This study explored the potential of using multidomain proteins as a basis for Förster resonance energy transfer (FRET) biosensors, focusing on protein disulfide isomerase (PDI) as a representative example. PDI, a well-studied multidomain protein, undergoes redox-dependent conformational changes, enabling the exposure of a hydrophobic surface extending across the b’ and a’ domains that serves as the primary binding site for substrates. Taking advantage of the dynamic domain rearrangements of PDI, we developed FRET-based biosensors by fusing the b’ and a’ domains of thermophilic fungal PDI with fluorescent proteins as the FRET acceptor and donor, respectively. Both experimental and computational approaches were used to characterize FRET efficiency in different redox states. In vitro and in vivo evaluations demonstrated higher FRET efficiency of this biosensor in the oxidized form, reflecting the domain rearrangement and its responsiveness to intracellular redox environments. This novel approach of exploiting redox-dependent domain dynamics in multidomain proteins offers promising opportunities for designing innovative FRET-based biosensors with potential applications in studying cellular redox regulation and beyond.

Background and Objectives: Although postoperative C5 palsy is a frequent complication of cervical spine surgery, no effective therapeutic rehabilitation approach has been established for postoperative C5 palsy. The purpose of this study was to find evidence confirming the effectiveness and feasibility of robotic Hybrid Assistive Limb (HAL) shoulder exercises for C5 palsy. Materials and Methods: In this before-after, uncontrolled case series clinical study, we performed a mean of 11.7 shoulder training sessions using a shoulder HAL immediately after the onset of C5 palsy in seven shoulders of six patients who developed postoperative C5 palsy and had difficulty raising their shoulder during the acute postoperative phase of cervical spine surgery. Shoulder HAL training was introduced as early as possible after evaluating the general condition of all inpatients who developed C5 palsy. Patients underwent shoulder abduction training using shoulder HAL on an inpatient and outpatient basis at 2-week or 1-month intervals. Adverse events associated with shoulder HAL training were investigated. The shoulder abduction angle and power without the shoulder HAL were evaluated before shoulder HAL usage, at every subsequent session, and upon completion of all sessions. Results: Severe adverse events due to shoulder HAL training were not reported. After completion of all shoulder HAL sessions, all patients showed improved shoulder elevation, while shoulder abduction angle and power improved over time. Conclusions: Shoulder elevation training with HAL in patients in the acute stage of postoperative C5 palsy has the potential to demonstrate improvement in shoulder joint function with a low risk of developing severe adverse events.

In myoelectrical pattern recognition (PR), the feature extraction methods for stroke-oriented applications are challenging and remain discordant due to a lack of hemiplegic data and limited knowledge of skeletomuscular function. Additionally, technical and clinical barriers create the need for robust, subject-independent feature generation while using supervised learning (SL). To the best of our knowledge, we are the first study to investigate the brute-force analysis of individual and combinational feature vectors for acute stroke gesture recognition using surface electromyography (EMG) of 19 patients. Moreover, post-brute-force singular vectors were concatenated via a Fibonacci-like spiral net ranking as a novel, broadly applicable concept for feature selection. This semi-brute-force navigated amalgamation in linkage (SNAiL) of EMG features revealed an explicit classification rate performance advantage of 10–17% compared to canonical feature sets, which can drastically extend PR capabilities in biosignal processing.

Ctenolepisma calvum (Ritter, 1910) (Zygentoma: Lepismatidae) is a primitive wingless insect that causes damage to paper, and it is regarded as a pest of collections in museums, archives, and libraries. This species was recently discovered in Japan for the first time and may have already spread over large areas of Japan, but, currently, no information is available on the biological characteristics of C. calvum in Japan. In this study, we observed the processes of development and reproduction of C. calvum found in Japan at room temperature. Oviposition was observed from April to November, with a peak in early June. The average egg period was 56.9 days at average temperatures above 24.0 °C, and was 72.4 days at average temperatures below 24.0 °C. The 1st, 2nd, and 3rd instars lasted 4.7 days, 13.2 days, and 26.1 days on average, respectively, at average temperatures above 22.0 °C. Average instar periods were 23–28 days in 4th–7th instars and tended to increase in later instars. Instar periods also increased when the average temperature was 22.0 °C or lower. In individual rearing, the longest-living individual lived for approximately two years, up to the 15th instar. The head width grew at an approximate ratio of 1.1 per molt. First oviposition occurred at the 10th or 11th instar. Individually observed females oviposited once or twice a year, laying 6–16 eggs at one time, but females at least two years old laid 78.2 eggs per year on average in a mass-culture cage. Through this study, only females were found, and the mature females produced their progenies parthenogenetically.

Introduction: Staphylococci is the most commonly isolated bacteria in blood cultures (BC), and is mostly regarded as contamination. However, the clinical relevance and characteristics of CNS other than Staphylococcus epidermidis (Non-SE-CNS) is still unknown. Methods: For the purpose of clarifying the epidemiology and clinical significance of Non-Se-CNS infections, we retrospectively evaluated BC isolates of Non-Se-CNS at our institute from May 2013 to March 2017.Infections were defined as true bacteremia if (1) two or more positive BCs of the same species were present (or detection of the same species in another clinically relevant sample), (2) the patient had clinical symptoms as outlined in the Centers for Disease Control and Prevention's definition of primary blood stream infection8 and the symptoms or markers of inflammation (e.g., fever, symptoms, white cell counts, C-reactive protein, or procalcitonin) were improved after pathogen-directed therapy (e.g. either antibiotic therapy and/or removal of the foreign body in the case of catheter-related blood stream infections suspected) and (3) without any other infection. Results: During the period, 279 patients with BC positive for Non Se–CNS were identified. 44 patients were excluded, either due to missing data or multiple pathogens in the same BC. Among the remaining 235 patients, 67 (29%) were categorized as true bacteremia (n = 43) or possible infections (n = 24). Resistance rate to methicillin among Non-SE-CNS is about 60%, which is lower than those among S. epidermidis of 78%. Conclusion: About 30% of Non-Se-CNS isolates were clinically relevant in our study. Antibiotic susceptibility of Non-SE-CNS is quite different than those of S. epidermidis.

Eye-fixation-related potential (EFRP)—an event-related potential that is time-locked to the saccade offset (SO)—can be measured without synchronizing with time when external stimuli occur. Such an advantage in measurement enables the mean amplitude of the EFRP to be used to estimate the cognitive workload, which is known to change the amplitude, under real-world conditions. However, to observe EFRPs reliably, the SO timing must be correctly and consistently determined in milliseconds owing to the high temporal resolution of the electroencephalogram (EEG). As the electrooculogram (EOG) is commonly measured simultaneously with the EEG and the SO timing is reflected as a steep change in the waveforms, attempts have been made to determine the SO timing from EOG signals visually (the VD method). However, the SO timing detected by the VD method may be inconsistent across trials. We propose a gated recurrent unit—a recurrent neural network model—to detect the SO timing from EOGs consistently and automatically. We used EOG data from a task that mimics visual inspections, in which participants periodically traversed their eyes from left to right, for the model training. As a result, the amplitudes of the EFRPs based on the proposed method were significantly larger than those based on the VD method and the previous automatic method. This suggests that the proposed method can prevent the decrease in EFRP amplitudes owing to the inconsistent determination of the SO timing and increase the applicability of cognitive workload estimation using the EFRP in real-world environments.

Abstract Background Candidemia has emerged as an important nosocomial infection, with a mortality rate of 30–50%. It is the fourth most common nosocomial bloodstream infection (BSI) in the United States and the seventh most common nosocomial BSI in Europe and Japan. The aim of this study was to assess the performance of the Sequential Organ Failure Assessment (SOFA) score for determining the severity and prognosis of candidemia. Methods We performed a retrospective study of patients admitted to hospital with candidemia between September 2014 and May 2018. The severity of candidemia was evaluated using the SOFA score and the Acute Physiology, Age, Chronic Health Evaluation II (APACHE II) score. Patients’ underlying diseases were assessed by the Charlson Comorbidity Index (CCI). Results Of 70 patients enrolled, 41 (59%) were males, and 29 (41%) were females. Their median age was 73 years (range: 36–93 years). The most common infection site was catheter-related bloodstream infection (n=36, 51%).The 30-day, and in-hospital mortality rates were 36 and 43%, respectively. Univariate analysis showed that SOFA score ≥5, APACHE II score ≥13, initial antifungal treatment with echinocandin, albumin 6, disturbance of consciousness, and CCI ≥3 were related with 30-day mortality. Of these 7, multivariate analysis showed that the combination of SOFA score ≥5 and CCI ≥3 was the best independent prognostic indicator for 30-day and in-hospital mortality. Conclusions The combined SOFA score and CCI was a better predictor of the 30-day mortality and in-hospital mortality than the APACHE II score alone.

Abstract Background Since the ToGA trial, trastuzumab-based chemotherapy is the standard treatment for HER2 positive stage IV gastric cancer. However, it is not yet clear whether surgical resection after trastuzumab-based chemotherapy (conversion surgery) can improve survival of HER2 positive stage IV gastric cancer. The purpose of this study is to evaluate the prognostic benefit of conversion surgery in HER2 positive stage IV gastric cancer patients. Case presentation We retrospectively investigated the medical records of the patients with HER2 positive (IHC3(+) or IHC2(+)/FISH(+)) stage IV gastric cancer treated with trastuzumab-based chemotherapy as the first line treatment. Overall survival (OS) was compared between patients with conversion surgery and without. Eleven HER2 positive stage IV gastric cancer patients treated with trastuzumab-based chemotherapy as the first line treatment were evaluated. Response rate was 63.6%, and 6 of 11 patients could receive conversion surgery. R0 resection was achieved in four patients. In Kaplan–Meier analysis, patients who received conversion surgery showed significantly better OS than those without surgery (3-year survival rate, 66.7% vs. 20%, P = 0.03). The median OS of patients who achieved R0 resection is 51.8 months. Conclusions Conversion surgery might have a survival benefit for HER2 positive stage IV gastric cancer patients. If curative surgery is technically possible, conversion surgery could be a treatment option for HER2 positive stage IV gastric cancer.

Introduction As most patients with epidermal growth factor receptor (EGFR)‐mutant non‐small cell lung cancer (NSCLC) develop progressive disease after treatment with osimertinib, it is important to develop more effective treatment options. Afatinib has been shown to be more effective in in vitro studies than osimertinib when used in cancer cell lines containing some specific EGFR mutations. Therefore, afatinib may be an effective solution, especially when used in combination with an anti‐VEGF agent such as bevacizumab. Methods A phase II multicenter, open‐label, single‐arm trial has been initiated to evaluate the efficacy and safety of afatinib and bevacizumab combination as salvage therapy for EGFR‐mutated lung cancer in patients previously treated with osimertinib. The primary endpoint will be the objective response rate (ORR) and secondary endpoints are progression‐free survival (PFS), overall survival (OS), disease control rate (DCR), and adverse events (AEs). Discussion A previous study indicated that afatinib inhibits lung cancer cells with specific EGFR mutations more effectively than other EGFR‐TKIs such as osimertinib. Therefore, we expect that combination therapy using afatinib and bevacizumab will be effective in patients previously treated with osimertinib (registration no. jRCTs031190077).

Abstract In this study, X-ray computed tomography (CT) and acoustic emission (AE) monitoring were used to nondestructively analyze the oviposition behavior of the bamboo powderpost beetle, Dinoderus minutus, which takes place inside bamboo culms. Newly mated adult females of D. minutus were singly exposed to a bamboo piece, obtained from culms of madake (Phyllostachys bambusoides), and were kept at a temperature of 28 °C and a relative humidity of 65% with a photoperiod of L12:D12. The bamboo pieces were subjected to X-ray CT scanning every 2–5 days, and they were also monitored continuously using AE. The behavior of males after mating was also analyzed in a similar manner. Oviposition tunnels bored across the bamboo vascular bundles and eggs deposited in the metaxylem vessels were visualized in the CT images. The females lived for 75 ± 17 days (mean ± SD) after mating, and they created tunnels that were 116.4 ± 52.1 mm in length and 177.2 ± 78.9 mm3 in volume and laid 253.1 ± 125.3 eggs in total. Using AE monitoring, the tunneling activity of the females was detected. The AE data indicated that continuous tunneling activity of the females was separated by regular short pauses, lasting approximately 1 h, occurring at intervals of around 2 days. The tunneling activity of the females did not exhibit clear circadian rhythms, suggesting that it was unaffected by external photoperiod. The males tunneled more slowly than the females and had no preference to the boring direction, and their activities were in synchronization with the photoperiod.

Abstract Background Presepsin (soluble CD14 subtype) is a novel biomarker of sepsis used for early diagnosis. Originally, CD14 is known as the pattern recognition receptor for the lipopolysaccharide (LPS)/LBP complexes, and the diagnostic value of this molecule for gram-positive bacteria, which contain less amount of LPS, is uncertain. To confirm its effectiveness in the diagnosis of bacteremia caused by gram positive bacteria, and to evaluate the interspecies difference of presepsin production against various bacterial strains, we conducted an in vitro assay to evaluate presepsin levels in response to five Gram negative and four Gram positive bacteria. Results Whole blood was yielded from five healthy volunteers and co-cultured with bacterial strains at 37 °C for 4 h. Twenty seven clinical isolates of nine species (E. coli, K. pneumoniae, E. cloacae, P. aeruginosa, S. maltophilia, S. aureus, S. pyogenes, B. cereus, and C. striatum) derived from blood cultures of non-neutropenic bacteremia patients were used. Culture supernatants were harvested and presepsin levels were measured. The presepsin level in the gram-negative bacteria 273 (218–352) pg/mL was significantly higher than in the gram-positive bacteria 200 (143–275) pg/mL (p = 0.0002). The presepsin levels were significantly lower in C. striatum, in comparison to other bacteria, and S. pyogenes showed similar results. And the presepsin levels in P. aeruginosa were significantly lower compared to E. cloacae, K. pneumoniae, and S. aureus. Conclusions Presepsin production can also be evoked by gram-positive bacteria, and interspecies differences of presepsin response may exist, which should be considered in the diagnosis of sepsis, especially in certain gram-positive bacteremia such as S. pyogenes or C. striatum.

HPC is an ashless coal obtained via the thermal extraction of coal and is soluble in organic solvents. In this study, carbon powder was prepared from the HPC/pyridine solution via precipitation using water as a poor solvent and was subsequently carbonized via heat treatment at 900°C. The evaluation of the pore characteristics of the obtained carbon powder revealed that the carbon powders mainly contained micropores. The average pore diameter (Dave) of the micropores was 0.75 nm, suggesting that they are super-micropores or ultra-micropores. The applicability of the carbon powder was verified by examining the EDLC characteristics. The capacitance of the EDLC containing the aqueous solution of H2SO4 as the electrolyte was 170 F cm−3 (200–210 F g−1) at a current density of 50 mA g−1, denoting a capacitance similar to that of the activated carbon powder (YP-50F). The capacitance was 140 F cm−3 (170 F g−1) even when the current density increased from 50 to 5000 mA g−1, indicating a high retention rate of approximately 80%. Subsequently, the capacitance became 210 F cm−3 (260 F g−1) when the CO2 activation treatment was conducted for 60 or 90 min. Therefore, a high yield of carbon powders with extremely fine pores can be easily obtained via precipitation using HPC as the raw material.

AimsThere is a scarcity of studies comparing percutaneous coronary intervention (PCI) using new-generation drug-eluting stents (DES) with coronary artery bypass grafting (CABG) in patients with multi-vessel coronary artery disease.Methods and resultsThe CREDO-Kyoto PCI/CABG registry Cohort-3 enrolled 14927 consecutive patients who underwent first coronary revascularization with PCI or isolated CABG between January 2011 and December 2013. The current study population consisted of 2464 patients who underwent multi-vessel coronary revascularization including revascularization of left anterior descending coronary artery (LAD) either with PCI using new-generation DES (N = 1565), or with CABG (N = 899). Patients in the PCI group were older and more often had severe frailty, but had less complex coronary anatomy, and less complete revascularization than those in the CABG group. Cumulative 5-year incidence of a composite of all-cause death, myocardial infarction or stroke was not significantly different between the 2 groups (25.0% versus 21.5%, P = 0.15). However, after adjusting confounders, the excess risk of PCI relative to CABG turned to be significant for the composite endpoint (HR 1.27, 95%CI 1.04-1.55, P = 0.02). PCI as compared with CABG was associated with comparable adjusted risk for all-cause death (HR 1.22, 95%CI 0.96-1.55, P = 0.11), and stroke (HR 1.17, 95%CI 0.79-1.73, P = 0.44), but with excess adjusted risk for myocardial infarction (HR 1.58, 95%CI 1.05-2.39, P = 0.03), and any coronary revascularization (HR 2.66, 95%CI 2.06-3.43, PConclusionsIn this observational study, PCI with new-generation DES as compared with CABG was associated with excess long-term risk for major cardiovascular events in patients who underwent multi-vessel coronary revascularization including LAD.

ATAD2 AAA+ ATPases are a family of histone chaperones that regulate nucleosome density and chromatin dynamics. Here, authors find that the fission yeast ATAD2 homolog Abo1 deposits histone H3–H4 onto DNA in an ATP-hydrolysis-dependent manner, and present the cryo-EM structure of an ATAD2 family ATPase to reveal the structural basis of nucleosome assembly by Abo1.

Background/purpose: Acinetobacter is an aerobic, gram-negative coccobacillus, which causes nosocomial infections including bacteremia. Recent development of molecular techniques has made classification of the Acinetobacter genomospecies possible, but there are still only a few studies comparing clinical features of the subspecies. We investigated bacteremia caused by Acinetobacter, isolated subspecies, and compared clinical features for each group. Methods: A retrospective analysis of Acinetobacter bacteremia cases was made in a 900-bed hospital in Japan. In addition to conventional procedures, subspecies identification based on rpoB sequence was made, and comparison of clinical characteristics between each subspecies were analyzed. Results: We collected 35 cases (Acinetobacter baumannii 14, A. nosocomialis 12, Acinetobacter ursingii 6, and A. seifertii 3). All of the A. seifertii bacteremia cases were blood stream infection occurring in cerebrovascular disease patients, showing particularly higher incidence of shock (100%) and high Pitt bacteremia score (PBS) (6.33 ± 2.52) in comparison to A. baumannii (43% and 2.86 ± 2.25, respectively). Sequential Organ Failure Assessment (SOFA) score and the PBS were slightly higher in A. nosocomialis in comparison to A. baumannii, and the 7 day mortality rate was higher in A. nosocomialis (25%) than in A. baumannii (7%), though this difference was not found to be significant. Conclusions: A.seifertii, the recently defined novel species, showed distinctive clinical features of bacteremia. And, in contrast to previous studies, the severity of A. nosocomialis infection was not lower than that of A. baumannii, which might suggest the influence of local epidemiology. Further characterization of these subspecies should be continued. Keywords: Acinetobacter seifertii, Acinetobacter nosocomialis, Acinetobacter baumanii, Bacteremia, rpoB, Genomospecies

A touch interface is an important technology used in many devices, including touch panels in smartphones. Many touch panels only detect the contact position. If devices can detect shear force in addition to the contact position, various touch interactions are possible. We propose a two-step recognition method for recognizing the pressing position and shear force using active acoustic sensing, which transmits acoustic signals to an object and recognizes the state of the object by analyzing its response. Specifically, we attach a contact speaker transmitting an ultrasonic sweep signal and a contact microphone receiving ultrasonic waves to a plate of gel. The propagation characteristics of ultrasonic waves differ due to changes in the shape of the gel caused by the user’s actions on the gel. This system recognizes the pressing position and shear force on the basis of the difference in acoustic characteristics. An evaluation of our method involving a user-independent model confirmed that four pressing positions were recognized with an F1 score of 85.4%, and four shear-force directions were recognized with an F1 score of 69.4%.

C5 palsy is a serious complication that may occur after cervical spine surgery; however, standard procedures for shoulder rehabilitation for patients with postoperative C5 palsy have not yet been established. We used a wearable robot suit Hybrid Assistive Limb (HAL) in a patient with delayed recovery after postoperative C5 palsy and conducted shoulder abduction training with the HAL. A 62-year-old man presented with weakness in his left deltoid muscle 2 days after cervical spine surgery. He experienced great difficulty in elevating his left arm and was diagnosed with postoperative C5 palsy. Seven months after surgery, shoulder abduction training with a HAL was initiated. In total, 23 sessions of shoulder HAL rehabilitation were conducted until 26 months after surgery. His shoulder abduction angle and power improved at every HAL session, and he was able to fully elevate his arm without any compensatory movement after the 23rd session, suggesting that the HAL is a useful tool for shoulder rehabilitation in patients with postoperative C5 palsy. We employed shoulder HAL training for a patient with delayed recovery from postoperative C5 palsy and achieved complete restoration of shoulder function. We believe that the HAL-based training corrected the erroneous motion pattern of his paralyzed shoulder and promoted errorless motor learning for recovery. Our collective experience suggests that shoulder HAL training could be an effective therapeutic tool for patients with postoperative C5 palsy.

In clinical practice, acute post-stroke paresis of the extremities fundamentally complicates timely rehabilitation of motor functions; however, recently, residual and distorted musculoskeletal signals have been used to initiate feedback-driven solutions for establishing motor rehabilitation. Here, we investigate the possibilities of basic hand gesture recognition in acute stroke patients with hand paresis using a novel, acute stroke, four-component multidomain feature set (ASF-4) with feature vector weight additions (ASF-14NP, ASF-24P) and supervised learning algorithms trained only by surface electromyography (sEMG). A total of 19 (65.9 ± 12.4 years old; 12 men, seven women) acute stroke survivors (12.4 ± 6.3 days since onset) with hand paresis (Brunnstrom stage 4 ± 1/4 ± 1, SIAS 3 ± 1/3 ± 2, FMA-UE 40 ± 20) performed 10 repetitive hand movements reflecting basic activities of daily living (ADLs): rest, fist, pinch, wrist flexion, wrist extension, finger spread, and thumb up. Signals were recorded using an eight-channel, portable sEMG device with electrode placement on the forearms and thenar areas of both limbs (four sensors on each extremity). Using data preprocessing, semi-automatic segmentation, and a set of extracted feature vectors, support vector machine (SVM), linear discriminant analysis (LDA), and k-nearest neighbors (k-NN) classifiers for statistical comparison and validity (paired t-tests, p-value < 0.05), we were able to discriminate myoelectrical patterns for each gesture on both paretic and non-paretic sides. Despite any post-stroke conditions, the evaluated total accuracy rate by the 10-fold cross-validation using SVM among four-, five-, six-, and seven-gesture models were 96.62%, 94.20%, 94.45%, and 95.57% for non-paretic and 90.37%, 88.48%, 88.60%, and 89.75% for paretic limbs, respectively. LDA had competitive results using PCA whereas k-NN was a less efficient classifier in gesture prediction. Thus, we demonstrate partial efficacy of the combination of sEMG and supervised learning for upper-limb rehabilitation procedures for early acute stroke motor recovery and various treatment applications.

The mechanical parameters of keyboard switches affect the psychological sense of pressing. The effects of different mechanical parameters on psychological sense have been quantified using questionnaires, but these subjective evaluations are unable to fully clarify the modulation of information processing in the brain due to these differences. This study aimed to elucidate the ability of electroencephalography (EEG) measurements to detect the modulation of subconscious information processing according to mechanical parameter values. To this end, we prepared five mechanical switches with linearly increasing values of pretravel (PT: the distance from the free position until the operating position). We hypothesized that the differences in PTs would subconsciously affect the motor preparation prior to pressing switches because switches with PTs that deviated from those commonly used were predicted to increase the users' attention level when pressing. Differences in motor preparation were quantified using the mean amplitudes of the late contingent negative variation (CNV). We recorded EEGs of 25 gamers during a reaction task for fast switch pressing after a response cue preceded by a pre-cue for response preparation; we also measured the reaction time feedback on each switch pressing trial. Participants performed five sessions (60 trials per session) in total. For the analysis, trials were divided into first (session 1, 2, and 3) and second half sessions (session 4 and 5). In the latter session, CNV amplitudes were significantly higher for the switch with the highest PT than for that with a medium PT, which is closest to that commonly used in commercial mechanical switches. On the other hand, the questionnaire did not detect any significant differences between PTs in their subjective rankings of the psychological effects of switch pressing. These results suggest that differences in PTs modulate motor preparation to press switches, and that EEG measurements may provide a novel objective evaluation of the mechanical parameters of keyboard switches.

We hypothesized that gait treatment with a wearable cyborg Hybrid Assistive Limb (HAL) would improve the walking ability of patients with hemiparesis after stroke. This study aims to evaluate the efficacy and safety of gait treatment using HAL versus conventional gait training (CGT) in hemiplegic patients with acute stroke and establish a protocol for doctor-initiated clinical trials for acute stroke. We will enroll patients with acute stroke at the University of Tsukuba Hospital. This study is a single-center, randomized, parallel-group, controlled trial (HAL group, n = 20; control group, n = 20) that will include three phases: (1) pre-observation phase (patient enrollment, baseline assessment, and randomization); (2) treatment phase (nine sessions, twice or thrice per week over 3−4 weeks; the HAL and control groups will perform gait treatment using HAL or CGT, respectively, and finally (3) post-treatment evaluation phase. The Functional Ambulation Category score will be the primary outcome measure, and the following secondary outcome measures will be assessed: Mini-Mental State Examination, Brunnstrom recovery stage of lower limbs, Fugl–Meyer assessment of lower limbs, 6-min walking distance, comfortable gait speed, step length, cadence, Barthel Index, Functional Independence Measure, gait posture, motion analysis (muscle activity), amount of activity (evaluated using an activity meter), stroke-specific QOL, and modified Rankin Scale score. The baseline assessment, post-treatment evaluation, and follow-up assessment will evaluate the overall outcome measures; for other evaluations, physical function evaluation centered on walking will be performed exclusively, excluding ADL and QOL scores. This study is a randomized controlled trial that aims to clarify the efficacy and safety of gait treatment using HAL compared with CGT in hemiplegic patients with acute stroke. In addition, we aim to establish a protocol for doctor-initiated clinical trials for acute stroke based on the study results. If our results demonstrate the effectiveness of the proposed treatment regarding outcomes of patients with hemiplegic acute stroke, this study will promote the treatment of these patients using the HAL system as an effective tool in future stroke rehabilitation programs. The study protocol was registered with the Japan Registry of Clinical Trials on October 14, 2020 (jRCTs032200151).

This study had two goals: to clarify the relationship between electroencephalographic (EEG) features estimated while non-native speakers listened to a second language (L2) and their proficiency in L2 determined by a conventional paper test and to provide a predictive model for L2 proficiency based on EEG features. We measured EEG signals from 205 native Japanese speakers, who varied widely in English proficiency while they listened to natural speech in English. Following the EEG measurement, they completed a conventional English listening test for Japanese speakers. We estimated multivariate temporal response functions separately for word class, speech rate, word position, and parts of speech. We found significant negative correlations between listening score and 17 EEG features, which included peak latency of early components (corresponding to N1 and P2) for both open and closed class words and peak latency and amplitude of a late component (corresponding to N400) for open class words. On the basis of the EEG features, we generated a predictive model for Japanese speakers’ English listening proficiency. The correlation coefficient between the true and predicted listening scores was 0.51. Our results suggest that L2 or foreign language ability can be assessed using neural signatures measured while listening to natural speech, without the need of a conventional paper test.

We quantified the electroencephalogram signals associated with the selective attention processing of experienced simultaneous interpreters and calculated the phase-locked responses evoked by a 40-Hz auditory steady-state response (40-Hz ASSR) and the values of robust inter-trial coherence (ITC) for environmental changes. Since we assumed that an interpreter's attention ability improves with an increase in the number of years of experience of simultaneous interpretation, we divided the participants into two groups based on their simultaneous interpretation experience: experts with more than 15 years of experience (E group; n = 7) and beginners with

Background: The Japanese Respiratory Society recently updated its prognostic guidelines for pneumonia, recommending that pneumonia severity be evaluated using the sequential organ failure assessment (SOFA) and quick SOFA (qSOFA) scoring systems in a therapeutic strategy flowchart. However, the efficacy and accuracy of these tools are still unknown. Methods: All patients with community-acquired pneumonia (CAP) and healthcare-associated pneumonia (HCAP) who were admitted to the study institution between 2014 and 2017 were enrolled in this study. Pneumonia severity on admission was evaluated by A-DROP, CURB-65, PSI, I-ROAD, qSOFA, and SOFA scoring systems. Prognostic factors for 30-day mortality were also analyzed. Results: This study included 406 patients, 257 male (63%) and 149 female (37%). The median age was 79 years (range 19–103 years). The 30-day and in-hospital mortality rates were both 5%. With respect to the diagnostic value of the predictive assessments for 30-day mortality, the area under the receiver operating characteristic curve (AUROC) value for the SOFA score was 0.769 for CAP patients and 0.774 for HCAP patients. Further, the AUROC values for the SOFA score in CAP and HCAP patients with a qSOFA score ≥2 were 0.829 and 0.784, respectively, for 30-day mortality. Conclusions: qSOFA and SOFA scores were able to correctly evaluate the severity of CAP and HCAP. Keyword: qSOFA, SOFA score, Community-acquired pneumonia, Healthcare-associated pneumonia

Abstract Background Brevibacteria are obligate aerobic gram-positive rods that are associated with milk products and are also found on human skin. Brevibacterium has been reported as a rare cause of catheter related blood steam infection mainly in immunocompromised hosts such as malignancies or AIDS patients. Case presentation A 94-year old woman, which had a past history of diabetes mellitus and chronic heart failure, presented with high fever associated with decreased oral intake and appetite loss and was admitted to our institute. A physical examination at the time of presentation was unremarkable. On day 2, both blood cultures collected on admission became positive with coryneform organism within 24 h without Staphylococci and Brevibacterium species were identified by Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Subsequently, genetic investigation by 16S ribosomal RNA analysis was performed in order to identify the organism. Finally, the result identified this pathogen as Brevibacterium paucivorans with 99.5% homology on the Ez taxon database. The patient was started empirically on meropenem and teicoplanin for broad-spectrum antibiotic coverage. The patient’s fever finally abated and labs were also improved. On day 14, the antibiotic therapy was discontinued. The site of infections was unknown. We hereby report a case of Brevibacterium paicivorans bacteremia in an immunocompetent patient and review cases of Brevibacterium specises bacteremia previously reported. This is the first case of B. paucivorans bacteremia as far as we could search. Conclusion Physicians and microbiologists should be aware that Brevibacteria are uncommon but important agents which could cause opportunistic infections in immunocompetent.