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Abstract Intervention for social cognition could be key to improving social functioning in patients with schizophrenia. A first step towards its clinical implementation involves interviewing patients about their subjective difficulties with social cognition as they experience them in the real world. The present study focused on the clinical subtypes classified by the discrepancies between the subjective difficulties in social cognition and actual cognitive impairment. A total of 131 outpatients with schizophrenia and 68 healthy controls were included. Objective measurement of social cognition was performed using a test battery covering four representative domains, and subjective difficulties were determined by a questionnaire covering the same domains. A two-step cluster analysis explored the potential classification of social cognition in patients with schizophrenia. There was little correlation between the objective performance on social cognition tasks and subjective difficulties in social cognition. The analysis yielded three clusters: the low-impact group (low objective impairment and low subjective difficulties), the unaware group (high objective impairment but low subjective difficulties), and the perceptive group (moderate objective impairment and high subjective difficulties). Positive, negative, and general symptoms were more severe in the two groups that showed impaired performance on the social cognition tasks (i.e., the unaware and perceptive groups) than those in the low-impact group. Neurocognition and functional capacity were the lowest in the unaware group, and social functioning was the lowest in the perceptive group. Awareness about the clinical subtypes of social cognition could serve as a guidepost for providing individualized, targeted interventions.

Introduction: Oligometastasis and oligoprogression (OP) has not been adequately defined in extensive-stage SCLC (ES-SCLC) and may be a good indication for adding local treatment. Therefore, this multicenter study aimed to investigate the prognostic impact of oligometastasis and OP in ES-SCLC. Methods: We enrolled patients who received chemoimmunotherapy between September 2019 and June 2022. Patients were classified into oligometastasis and non-oligometastasis groups by determining the number of original tumor lesions and distant metastases (worsening or newly appearing lesions) at the time of initial diagnosis and disease progression after first-line treatment. Results: We retrospectively analyzed 265 consecutive patients with ES-SCLC. Synchronous oligometastasis (SOM) and OP was defined as less than or equal to five lesions in less than or equal to two organs, including lungs; 21.0% and 53.2% of patients had SOM and OP, respectively. Median progression-free survival was 5.8 months and 4.9 months in patients with and without SOM, respectively (hazard ratio [HR] = 0.72, 95% confidence interval [CI]: 0.51–1.02, p = 0.065). Median overall survival was 20.5 months and 15.0 months in patients with and without SOM (HR = 0.58, 95% CI: 0.37–0.95, p = 0.027) from the initiation of first-line treatment. The OP group revealed a better progression-free survival of 5.2 months (versus 3.2 mo, HR = 0.69, 95% CI: 0.50–0.96, p = 0.026) and overall survival of 15.1 months (versus 7.5 mo, HR = 0.44, 95% CI: 0.29–0.66, p = 0.027) from the initiation of second-line treatment compared with the non-OP group. The Lung Immune Prognostic Index score was significantly lower in the SOM and OP group. Conclusions: ES-SCLC in patients with SOM and OP may be more indolent than that of the nonoligometastasis group, therefore, new treatment strategies, including the addition of local treatment, should be explored. Clinical trial registration: This study was registered at UMIN-CTR (UMIN000053402).

Background: Enterovirus D68 (EV-D68) is an important reemerging pathogen that causes severe acute respiratory infection and acute flaccid paralysis, mainly in children. Since 2014, EV-D68 outbreaks have been reported in the United States, Europe, and east Asia; however, no outbreaks have been reported in southeast Asian countries, including Myanmar, during the previous 10 years. Methods: EV-D68 was detected in nasopharyngeal swabs from children with acute lower respiratory infections in Myanmar. The samples were previously collected from children aged 1 month to 12 years who had been admitted to the Yankin Children Hospital in Yangon, Myanmar, between May 2017 and January 2019. EV-D68 was detected with a newly developed EV-D68–specific real-time PCR assay. The clade was identified by using a phylogenetic tree created with the Bayesian Markov chain Monte Carlo method. Results: During the study period, nasopharyngeal samples were collected from 570 patients. EV-D68 was detected in 42 samples (7.4 %)—11 samples from 2017 to 31 samples from 2018. The phylogenetic tree revealed that all strains belonged to clade B3, which has been the dominant clade worldwide since 2014. We estimate that ancestors of currently circulating genotypes emerged during the period 1980–2004. Conclusions: To our knowledge, this is the first report of EV-D68 detection in children with acute lower respiratory infections in Yangon, Myanmar, in 2017–2018. Detection and detailed virologic analyses of EV-D68 in southeast Asia is an important aspect of worldwide surveillance and will likely be useful in better understanding the worldwide epidemiologic profile of EV-D68 infection.

Lymphocytes are generally non-adherent. This makes it challenging to fabricate three-dimensional (3D) structures mimicking the three-dimensional lymphoma microenvironment in vivo. This study presents the fabrication of a hemispherical 3D lymphoma model using the on-chip Cell Dome system with a hemispherical cavity (1 mm in diameter and almost 300 µm in height). Both the human brain lymphoma cell line (TK) and human B cell lymphoma cell line (KML-1) proliferated and filled the cavities. Hypoxic regions were observed in the center of the hemispherical structures. CD19 expression did not change in either cell line, while CD20 expression was slightly upregulated in TK cells and downregulated in KML-1 cells cultured in the Cell Dome compared to those cultured in two-dimensional (2D) flasks. In addition, both TK and KML-1 cells in the hemispherical structures exhibited higher resistance to doxorubicin than those in 2D flasks. These results demonstrate the effectiveness of the on-chip Cell Dome for fabricating 3D lymphoma models and provide valuable insights into the study of lymphoma behavior and the development of new drugs for lymphoma treatment.

The drug floxuridine (5-fluorodeoxyuridine, FUdR) is an active metabolite of 5-Fluorouracil (5-FU). It converts to 5-fluorodeoxyuridine monophosphate (FdUMP) and 5-fluorodeoxyuridine triphosphate (FdUTP), which on incorporation into the genome inhibits DNA replication. Additionally, it inhibits thymidylate synthase, causing dTMP shortage while increasing dUMP availability, which induces uracil incorporation into the genome. However, the mechanisms underlying cellular tolerance to FUdR are yet to be fully elucidated. In this study, we explored the mechanisms underlying cellular resistance to FUdR by screening for FUdR hypersensitive mutants from a collection of DT40 mutants deficient in each genomic maintenance system. We identified REV3, which is involved in translesion DNA synthesis (TLS), to be a critical factor in FUdR tolerance. Replication using a FUdR-damaged template was attenuated in REV3-/- cells, indicating that the TLS function of REV3 is required to maintain replication on the FUdR-damaged template. Notably, FUdR-exposed REV3-/- cells exhibited defective cell cycle arrest in the early S phase, suggesting that REV3 is involved in intra-S checkpoint activation. Furthermore, REV3-/- cells showed defects in Chk1 phosphorylation, which is required for checkpoint activation, but the survival of FUdR-exposed REV3-/- cells was further reduced by the inhibition of Chk1 or ATR. These data indicate that REV3 mediates DNA checkpoint activation at least through Chk1 phosphorylation, but this signal acts in parallel with ATR-Chk1 DNA damage checkpoint pathway. Collectively, we reveal a previously unappreciated role of REV3 in FUdR tolerance.

Abstract Background For chronic pain after thoracic surgery, optimal timing of its diagnosis and effective treatment remains unresolved, although several treatment options are currently available. We examined the efficacy and safety of mirogabalin, in combination with conventional pain therapy (nonsteroidal anti-inflammatory drugs and/or acetaminophen), for treating peripheral neuropathic pain (NeP) after thoracic surgery. Methods In this multicenter, randomized, open-label, parallel-group study, patients with peripheral NeP were randomly assigned 1:1 to mirogabalin as add-on to conventional therapy or conventional treatment alone. Results Of 131 patients of consent obtained, 128 were randomized (mirogabalin add-on group, 63 patients; conventional treatment group, 65 patients). The least squares mean changes (95% confidence interval [CI]) in Visual Analogue Scale (VAS) score for pain intensity at rest from baseline to Week 8 (primary endpoint) were − 51.3 (− 54.9, − 47.7) mm in the mirogabalin add-on group and − 47.7 (− 51.2, − 44.2) mm in the conventional group (between-group difference: − 3.6 [95% CI: − 8.7, 1.5], P = 0.161). However, in patients with Self-administered Leeds Assessment of Neuropathic Symptoms and Signs (S-LANSS) score (used for the screening of NeP) ≥ 12 at baseline, the greater the S-LANSS score at baseline, the greater the decrease in VAS score in the mirogabalin add-on group, while no such trend was observed in the conventional treatment group (post hoc analysis). This between-group difference in trends was statistically significant (interaction P value = 0.014). Chronic pain was recorded in 7.9% vs. 16.9% of patients (P = 0.171) at Week 12 in the mirogabalin add-on vs. conventional treatment groups, respectively. Regarding activities of daily living (ADL) and quality of life (QOL), changes in Pain Disability Assessment Scale score and the EQ-5D-5L index value from baseline to Week 8 showed significant improvement in the mirogabalin add-on group vs. conventional treatment group (P

Abstract Background Intrathoracic neurogenic tumors arise from sympathetic nerve trunks and intercostal nerves; more than 90% are benign. Schwannomas are the most common histological variety, but fatalities due to giant schwannomas are rare. Case presentation We report a case of a 65-year-old woman who presented with chest pain and cough. Computed tomography (CT) revealed a large left chest wall mass of 130-mm in size, and the patient was referred to our department. Tumor biopsy was performed under local anesthesia, and a diagnosis of schwannoma was made. Ten years previously, a 30-mm tumor had been noted in the left third intercostal space by a previous doctor, but follow-up had been interrupted owing to depressive disorder. Although we planned to perform intercostal artery embolization followed by chest wall tumor resection, the patient did not consent to surgery due to uncontrolled depression. After four months, she developed respiratory failure caused by compression due to an enlarged tumor and died. Autopsy also revealed a benign schwannoma with no malignant findings. Conclusions Although schwannomas are benign tumors, there are some very rare cases in which they can become huge and life-threatening. Therefore, a benign tumor should not be neglected, and if surgery is not possible at the time of diagnosis, a regular follow up is necessary, in order not to miss the right timing for surgery.

The interaction between bubbles and tissues (bone and fat) in ultrasound and the mechanism of drug transport accompanied by bubble collapse were investigated numerically by using the ghost fluid methods with zonal grids. A parameter defined by the ratio of t0 to ts which is proportional to the ratio of bubble radius to wavelength, where t0 is the bubble collapse time and ts is the period of an incident pressure wave, was used to characterize the relationship between the incident pressure waveform and the bubble collapse. It was found that the bubble collapse near a tissue surface was classified into three types by considering the penetration of liquid jet and bubble blobs into the tissues. The transport process of matter (imaginary drug) distributed around the bubble surface was calculated with the bubble collapse. The results showed that the mechanism of matter transport due to bubble collapse was summarized as follows. First, both the shock wave by the liquid jet impact on the bubble surface and the rebound shock wave lead to the depression of the tissue wall, and the matter is transported with the vortex flow due to liquid jet formation. Then, the bubble penetrates into the depression, increasing the amount of matter transported into the tissue. The bubble collapse and the matter transport in the bone wall case were compared with those in the fat wall case. Although the maximum wall pressure was higher in the bone case, the amount of matter transported inside the tissue was higher in the fat case. This was caused by the difference in the acoustic impedance between both tissues: the large acoustic impedance of bone induced the reflection of the incident wave, leading to the superposition of the incident wave and the reflection wave that contributed to the acceleration of bubble collapse. Since the stiffer property of bone suppressed the development of the vortex flow and the bubble growth inside the tissue, a larger circulation existed inside the fat, which contributed to the advection of the matter, resulting in a higher concentration of matter inside the fat than inside the bone.

Mass timber construction has recently gained popularity due to its outstanding environmental benefits and building performance, which hold revolutionary potential for the construction industry. However, its impacts from the perspective of occupants have not been thoroughly explored. This study introduces an innovative empirical approach that explores the potential benefits of mass timber construction for individuals and organizations, with an emphasis on the workplace. We review the conceptual framework regarding how visual and physical exposure to timber construction materials and finishes have a positive effect on individuals and organizations at a broad level. We propose a more holistic mixed-method behavioral approach to studying occupant behavior and well-being by integrating self-reported questionnaires, objective biomarkers (heart rate variability and hair cortisol), and indoor environmental quality (IEQ) measures. Our study offers a novel research primer on the exploration of mass timber construction impacts and benefits for both office workers and construction workers. Participants from different office settings completed pre- and post-occupancy evaluation surveys to assess their experiences, including IEQ satisfaction, productivity, and health. Office workers were located in three different offices: a controlled laboratory environment, an open-plan office, and an open-plan space with a timber interior. The construction workers worked in a timber space for three months and then moved to work in a building with a concrete structure. The analysis included descriptive statistics, t-tests, ANOVA, and linear regression to compare differences between office settings and assess the relationship between environmental variables and overall satisfaction in IEQ, comfort, productivity, and health. In office workers, in terms of building image, thermal comfort, and artificial lighting, the data analysis revealed significant differences in occupants’ satisfaction levels between office settings. However, the low number of participants affected the results, and some factors were not found significant in relation to the office setting. Among tradespeople, there was no relationship between the building environment and productivity, health, or comfort. However, the results of hair cortisol testing indicated that working in a timber space can decrease the level of cortisol (stress) and have an impact on the productivity of workers. Such occupant’s perspective research is pivotal to informing policy makers, developers, business owners, construction professionals, timber industry stakeholders, environmentalists, and researchers in their decision-making processes. Fostering the future widespread adoption and advancement of mass timber construction.

BackgroundCognitive impairment, a core feature of schizophrenia, is associated with poor outcomes. Pharmacotherapy and psychosocial treatment, when used alone, have inadequate effect sizes for cognitive impairment, leading to recent interest in combination interventions. A previous study examined the additive effect of cognitive remediation on lurasidone in patients with schizophrenia, which was negative. Although improvement in cognitive function was suggested for lurasidone, it was inconclusive because there was no antipsychotic control in the study. To clarify whether lurasidone has a meaningful impact on cognitive function in combination with cognitive remediation, we use paliperidone as a control antipsychotic in this study. We hypothesize that combination with lurasidone will improve cognitive and social function to a greater extent than paliperidone.MethodsThe valuable interaction with cognitive remediation and optimal antipsychotics for recovery in schizophrenia study is a multicenter, interventional, open-label, rater-blind, randomized comparison study, comparing the effect of lurasidone plus cognitive remediation with that of paliperidone plus cognitive remediation in patients with schizophrenia. The Neuropsychological Educational Approach to Remediation (NEAR) is used for cognitive remediation. Eligible patients will be randomized 1:1 to receive lurasidone or paliperidone combined with NEAR (6 weeks antipsychotic alone followed by 24 weeks combination antipsychotic plus NEAR). The primary endpoint is the change from baseline in the tablet-based Brief Assessment of Cognition in Schizophrenia composite T-score at the end of the NEAR combination treatment period. Secondary endpoints will include change from baseline in social function, schizophrenia symptoms, and quality of life at the end of the NEAR combination treatment period. Furthermore, change from baseline to the end of the pharmacotherapy period and change from the end of the pharmacotherapy period to the end of the NEAR combination treatment period will be assessed for all endpoints. Safety will also be evaluated.DiscussionAchievement of adequate cognitive function is central to supporting social function, which is a key treatment goal for patients with schizophrenia. We think this study will fill in the gaps of the previous study and provide useful information regarding treatment decisions for patients with schizophrenia.Clinical trial registrationJapan Registry of Clinical Trials ID, jRCTs031200338.

Abstract Deep ocean water (DOW) exerts positive effects on the growth of marine organisms, suggesting the presence of unknown component(s) that facilitate their aquaculture. We observed that DOW suppressed plasma cortisol (i.e., a stress marker) concentration in Japanese flounder (Paralichthys olivaceus) reared under high-density condition. RNA-sequencing analysis of flounder brains showed that when compared to surface seawater (SSW)-reared fish, DOW-reared fish had lower expression of hypothalamic (i.e., corticotropin-releasing hormone) and pituitary (i.e., proopiomelanocortin, including adrenocorticotropic hormone) hormone-encoding genes. Moreover, DOW-mediated regulation of gene expression was linked to decreased blood cortisol concentration in DOW-reared fish. Our results indicate that DOW activated osteoblasts in fish scales and facilitated the production of Calcitonin, a hypocalcemic hormone that acts as an analgesic. We then provide evidence that the Calcitonin produced is involved in the regulatory network of genes controlling cortisol secretion. In addition, the indole component kynurenine was identified as the component responsible for osteoblast activation in DOW. Furthermore, kynurenine increased plasma Calcitonin concentrations in flounders reared under high-density condition, while it decreased plasma cortisol concentration. Taken together, we propose that kynurenine in DOW exerts a cortisol-reducing effect in flounders by facilitating Calcitonin production by osteoblasts in the scales.

Molecular chaperones are indispensable proteins that assist the folding of aggregation‐prone proteins into their functional native states, thereby maintaining organized cellular systems. Two of the best‐characterized chaperones are the Escherichia coli chaperonins GroEL and GroES (GroE), for which in vivo obligate substrates have been identified by proteome‐wide experiments. These substrates comprise various proteins but exhibit remarkable structural features. They include a number of α/β proteins, particularly those adopting the TIM β/α barrel fold. This observation led us to speculate that GroE obligate substrates share a structural motif. Based on this hypothesis, we exhaustively compared substrate structures with the MICAN alignment tool, which detects common structural patterns while ignoring the connectivity or orientation of secondary structural elements. We selected four (or five) substructures with hydrophobic indices that were mostly included in substrates and excluded in others, and developed a GroE obligate substrate discriminator. The substructures are structurally similar and superimposable on the 2‐layer 2α4β sandwich, the most popular protein substructure, implying that targeting this structural pattern is a useful strategy for GroE to assist numerous proteins. Seventeen false positives predicted by our methods were experimentally examined using GroE‐depleted cells, and 9 proteins were confirmed to be novel GroE obligate substrates. Together, these results demonstrate the utility of our common substructure hypothesis and prediction method.

Abstract Artificial phase-separating (PS) peptides can be used in various applications such as microreactors and drug delivery; however, the design of artificial PS peptides remains a challenge. This can be attributed to the limitation of PS-relevant residues that drive phase separation by interactions of their pairs in short peptides and the difficulty in the design involving interaction with target PS proteins. In this study, we propose a rational method to design artificial PS peptides that satisfy the requirements of liquid droplet formation and co-phase separation with target PS proteins based on the target PS protein sequence. As a proof of concept, we designed five artificial peptides from the model PS protein p53 using this method and confirmed their PS properties using differential interference contrast and fluorescence microscopy. Single-molecule fluorescent tracking demonstrated rapid diffusion of the designed peptides in their droplets compared to that of p53 in p53 droplets. In addition, size-dependent uptake of p53 oligomers was observed in the designed peptide droplets. Large oligomers were excluded from the droplet voids and localized on the droplet surface. The uptake of high-order p53 oligomers into the droplets was enhanced by the elongated linker of the designed peptides. Furthermore, we found that the designed peptide droplets recruited p53 to suppress gel-like aggregate formation. Finally, we discuss aspects that were crucial in the successful design of the artificial PS peptides.

IntroductionSotorasib is a crucial therapeutic agent for patients with non-small cell lung cancer (NSCLC) harboring the KRAS p.G12C mutation. Despite its efficacy, the relationship between blood sotorasib concentrations and side effects remains largely unexplored.MethodsThis study enrolled five patients with KRAS p.G12C-positive NSCLC treated with sotorasib (LUMAKRAS® Tablets, Amgen, Japan) between July 2022 and February 2023 at Asahikawa Medical University Hospital. Blood sotorasib levels were monitored, and their association with adverse events was examined, with no adjustments made to drug dosages based on these levels.ResultsVariable blood sotorasib levels were observed among the participants. Notably, one patient developed interstitial pneumonitis, although a definitive attribution to sotorasib was uncertain due to prior pembrolizumab treatment. The study revealed no consistent association between blood sotorasib levels and adverse events or therapeutic outcomes, with some patients experiencing severe side effects at higher concentrations, while others did not.ConclusionPreliminary findings suggested that monitoring blood sotorasib levels may aid in anticipating adverse events in this small cohort. However, future studies with larger sample sizes and extended follow-up periods are required to validate these initial observations. Such studies could potentially offer insights into personalized dosing strategies, thereby mitigating adverse effects and enhance patient care for individuals with KRAS p.G12C-positive NSCLC.

Abstract This study aimed to determine effects of cooling on contraction‐induced peroxisome proliferator‐activated receptor γ coactivator‐1α (PGC‐1α) and vascular endothelial growth factor (VEGF) gene expression, phosphorylations of its related protein kinases, and metabolic responses. Male rats were separated into two groups; room temperature (RT) or ice‐treated (COLD) on the right tibialis anterior (TA). The TA was contracted isometrically using nerve electrical stimulation (1‐s stimulation × 30 contractions, with 1‐s intervals, for 10 sets with 1‐min intervals). The TA was treated before the contraction and during 1‐min intervals with an ice pack for the COLD group and a water pack at RT for the RT group. The muscle temperature of the COLD group decreased to 19.42 ± 0.44°C (p

Commuter carpooling is a practical transportation demand management that promotes employees picking up and dropping off co-workers during their daily work commute. The benefits include reducing carbon footprint, traffic congestion, parking needs, and transportation-related costs in urban and suburban areas since lessening the number of cars and kilometers traveled. Numerous conventional studies have highlighted the social importance and efficacy of carpooling across different countries. Nevertheless, carpooling with co-workers still requires to be developed in Japan. This paper reports on proof of concept (PoC) to verify a carpooling model’s feasibility and highlight challenges to successfully adapting carpooling to Japanese customs and regulations in practical implementation. Under two companies’ cooperation in Hiroshima, Japan, twenty employees commuted via carpooling for two weeks using a developed mobile application. We validated the need and identified five realistic challenges by analyzing the questionnaire survey and the driver’s plan-actual route reproduced from the GPS data. These challenges are to reduce waiting times, provide incentives for the driver, provide navigation with easy-to-drive route guidance and traffic avoidance, operate flexibly, and drop in on the way.

Abstract Predicting geomagnetic conditions based on in-situ solar wind observations allows us to evade disasters caused by large electromagnetic disturbances originating from the Sun to save lives and protect economic activity. In this study, we aimed to examine the relationship between the K p index, representing global magnetospheric activity level, and solar wind conditions using an interpretable neural network known as potential learning (PL). Data analyses based on neural networks are often difficult to interpret; however, PL learns by focusing on the “potentiality of input neurons” and can identify which inputs are significantly utilized by the network. Using the full advantage of PL, we extracted the influential solar wind parameters that disturb the magnetosphere under southward Interplanetary magnetic field (IMF) conditions. The input parameters of PL were the three components of the IMF (Bx, By, Bz), solar wind flow speed (Vx), and proton number density (Np) in geocentric solar magnetospheric (GSM) coordinates obtained from the OMNI solar wind database between 1998 and 2019. Furthermore, we classified these input parameters into two groups (targets), depending on the K p level: K p = 6–9 (positive target) and K p = 0 to 1 + (negative target). Negative target samples were randomly selected to ensure that numbers of positive and negative targets were equal. The PL results revealed that solar wind flow speed is an influential parameter for increasing K p under southward IMF conditions, which was in good agreement with previous reports on the statistical relationship between the K p index and solar wind velocity, and the K p formulation based on the IMF and solar wind plasma parameters. Based on this new neural network, we aim to construct a more correct and parameter-dependent space weather forecasting model. Graphical Abstract

Deep ocean water (DOW) is the water obtained from depth of >200 m below the surface of Earth's oceans and is characterized by rich nutrients and cleanliness [1,2]. We have recently reported that DOW suppresses the high-density-induced increase of plasma cortisol levels (i.e., a stress marker) in Japanese flounder (Paralichthys olivaceus) [1]. The current study aimed to examine whether the cortisol-reducing effect of DOW was observed in other marine organisms as well by comparing the plasma cortisol levels of nibbler fish Girella punctata reared under high-density conditions between surface seawater (SSW) and DOW. The nibbler fish were caught from Tsukumo Bay of Noto Peninsula (Ishikawa Prefecture, Japan). The DOW was obtained from seawater 320 m below the Noto Bay surface at a facility (Aquas Noto, Ishikawa Prefecture, Japan), whereas SSW was obtained from Tsukumo Bay (Noto Peninsula, Ishikawa Prefecture). The dissolved oxygen was maintained at approximately 7 mg/L in DOW as well as in SSW. Before they were transferred to the high-density condition, nibbler fish were acclimated in SSW at 20°C for 1 week at a mean density of 100 g/62.5 L. To expose them to the high-density stress, each of fish was kept at a density of 10 kg/m3 in a single aquarium (60 × 25 × 30 cm) containing either SSW or DOW (n = 8). Subsequently, the fish were reared with SSW or DOW for 10 days at 20°C ± 1°C under a 12:12-h light–dark cycle. A heparin containing syringe was used to obtain the blood samples from the caudal vessels of the fish anesthetized with a 0.04% 2-phenoxyethanol (FUJIFILM Wako Pure Chemical Corporation). The blood sampling was performed on days 0, 5, and 10 after rearing in the small aquaria. The plasma samples were prepared from the collected blood by centrifuging it at 5200 × g for 5 min and the cortisol concentrations were determined using an enzyme-linked immunosorbent assay (ELISA) kit (Cosmo Bio Co. Ltd., Tokyo, Japan) from those samples. The plasma cortisol concentration of nibbler fish reared in SSW on day 10 was significantly higher than that on day 0, whereas those reared in DOW did not show significant difference on the respective days. The current data contributes to the generalization of the cortisol-reducing effect of DOW on fish, which has been proposed in Japanese flounder [1]. These data could be used for developing and designing experiments to analyze the mechanisms underlying the cortisol-reducing effects by using small fish such as zebrafish, a well-established animal model.

Nattokinase (NK) intake may improve blood flow; however, its effects on skin temperature, which is predominantly controlled by skin surface blood flow, are unknown. The purpose of this study was to determine the effects of a single dose of NK on changes in skin temperature after cold water immersion. A double-blinded, placebo-controlled, crossover intervention study was performed on nine healthy men. The participants were randomised to receive either a single dose of 2,000 fibrinolytic units (FU) of NK or a placebo with subsequent crossover. Two hours after supplementation, the participants immersed both hands in a water bath maintained at 10 °C for 1 min. Skin temperature, perceived coldness, cardiac output, and sympathetic nervous activity were measured before, during, and after water immersion. Two-way analysis of variance showed a significant effect of treatment interaction on the skin temperature of the middle finger, palm, and back of the right hand (p

Abstract Background Duodenal gastrointestinal stromal tumors are rare. If tumor growth is extraluminal and involves the head of the pancreas, the diagnosis of a duodenal gastrointestinal stromal tumor is difficult. Case presentation A 44-year-old Japanese woman was referred to our hospital with anemia. An enhanced computed tomography scan showed a hypervascular mass 30 mm in diameter, but the origin of the tumor, either the duodenum or the head of the pancreas, was unclear. Upper gastrointestinal endoscopy revealed bulging accompanied by erosion and redness in part of the duodenal bulb. Mucosal biopsy was not diagnostic. Endoscopic ultrasound fine-needle aspiration was difficult to perform because a pulsating blood vessel was present in the region to be punctured. These findings led to a diagnosis of pancreatic neuroendocrine tumor invasion to the duodenum. The patient underwent pancreaticoduodenectomy. Histologically, the tumor was made up of spindle-shaped cells immunohistochemically positive for c-Kit and CD34. The tumor was ultimately diagnosed as a duodenal gastrointestinal stromal tumor. Conclusion Extraluminal duodenal gastrointestinal stromal tumors are rare and mimic pancreatic neuroendocrine tumors. Endoscopic ultrasound fine-needle aspiration is useful for preoperative diagnosis, but it is not possible in some cases. Intraoperative diagnosis based on a completely resected specimen of the tumor may be useful for modifying the surgical technique.

Abstract Background and Objective The importance of brown adipose tissue (BAT) is well recognized in healthy infants and children. However, information regarding age‐related changes in BAT vascular density (BAT‐d) and the impact of BAT‐d on body adiposity are lacking. This study aimed to evaluate the normal values of BAT‐d, factors influencing BAT‐d, and the impact of BAT‐d on body adiposity in healthy infants and children. Methods This study included 240 participants (127 girls and 113 boys) aged 1 month to 5 years. The tissue total hemoglobin concentration in the supraclavicular region adjusted according to the subcutaneous adipose tissue thickness (SAT) ([total‐Hb‐Adj]sup) as BAT‐d. SAT in the deltoid and interscapular regions (SATdel+int), the Kaup index (body weight [g]/height or length [cm]/height or length [cm] × 10) as body adiposity, and fertilization season were also measured. Results The [total‐Hb‐Adj]sup of boys was higher than that of girls (r = 0.277, p = 0.009). Younger children had a significantly higher Kaup index (r = 0.495, p

The current study explored the effects of low root-zone temperature (LT) and UV radiation (UV) alone and combined on changes in growth, transcription, and gene expression related to secondary metabolite production. Nicotiana benthamiana plants were grown in a controlled environment (25/20°C, 16/8 h [light/dark], 70% relative humidity, 1,000 µmol·mol−1 CO2 with photosynthetic photon flux densities of 100 and 200 µmol·m−2·s−1 for 10 and 18 d, respectively). Twenty-eight days after sowing, these plants were treated with LT (15°C), 0.3 W·m−2 of UV radiation, and a combined treatment with LT and UV (LT*UV) for 3 d. Results found that the treatment with UV alone decreased the quantum efficiency of photosystem II by approximately 1.5 times, and most growth characteristics decreased under the UV (approximately 1.5 times) and LT*UV (approximately 2 times) treatments. Treatment with LT*UV significantly inhibited the growth characteristics and photosynthetic rates compared to those under the single LT and UV treatments. Changes in the transcriptome of plants in response to different environmental conditions were determined based on the expression levels of genes related to secondary metabolites and microarrays. In particular, the transcriptome levels of phenylpropanoid and flavonoid biosynthesis were the most significantly affected by LT*UV. This suggests the potential of using LT treatment in hydroponic systems and UV radiation to control the synthesis of health-promoting compounds of secondary metabolites in greenhouses and controlled-environment agricultural facilities.

Abstract Background The purpose of this study was to determine the prevalence of Segond fractures and to compare knee stability between patients undergoing primary anterior cruciate ligament (ACL) reconstruction with and without Segond fractures pre- and postoperatively. Methods A total of 712 patients who underwent primary ACL reconstruction between 2014 and 2019. Exclusion criteria included patients with multi-ligament knee injuries, skeletally immature patients, osteoarthritis in the knee, combined surgery of high tibial osteotomy, lack of data, and loss to follow-up for at least 2 years. Segond fractures were confirmed using plain radiography, computed tomography (CT), and magnetic resonance imaging (MRI). Patients with Segond fractures were classified into Group S and without Segond fractures into Group N. Pre- and postoperative Lachman grades, pivot-shift grades, and assessment of side-to-side differences in anterior stability were evaluated. Results Five hundred and forty patients included in this study. There were 22 patients with Segond fractures. Of these, all 22 cases (4.1%) were identified on CT, but only 20 cases (3.7%) were identified on MRI and 18 cases (3.3%) on plain radiographs. There was no significant difference in preoperative Lachman grade or pivot-shift grade between Groups S and N (p = 0.662, p = 0.677, respectively). There was no significant difference in postoperative Lachman grade or pivot-shift grade between Groups S and N (p = 0.685, p = 0.390, respectively). There were no significant differences in preoperative (p = 0.398) or postoperative (p = 0.546) side-to-side differences of anterior stability between Groups S and N. Conclusions Segond fractures were confirmed in 4.1% of the cases on CT scans among patients undergoing primary ACL reconstruction. Segond fractures did not affect preoperative or 2-year follow-up evaluations of knee stability. From these results, we concluded that Segond fractures did not affect the clinical outcomes of the primary ACL reconstruction and that it may not be necessary to treat Segond fractures.

Abstract The composite films of polydimethylsiloxane (PDMS) and cyanoethylsucrose (CR‐U) were prepared and investigated as an electroactive silicone actuator in the air. CR‐U is highly viscose and soluble in tetrahydrofuran (THF) and acetone (ACT). The composites showed a phase‐separation structure, in which the spherical CR‐U dispersed in the PDMS domain. The films from THF had an asymmetric cross‐sectional view, in which CR‐U large sphere dispersed with a thin skin layer of PDMS on one side. On the other hand, the films from ACT had a symmetric cross‐sectional structure, in which CR‐U small sphere dispersed uniformly without a PDMS thin skin layer. By applying DC electric field, the films from THF deformed by expanding the thin skin layer regardless of the electric field polarity. The films from ACT showed almost no deformation. The space‐charge distribution explained deformation behavior.

The combination of high-temperature fermentation and membrane separation has the potential to realize a simple on-site process to produce concentrated bioethanol. The performance of dehydration membranes in separating bioethanol was investigated in this study. Three types of zeolite membranes, LTA, MFI, and MOR, were synthesized. Their dehydration ability was compared using a bioethanol solution produced by high-temperature fermentation followed by vacuum distillation. The LTA zeolite membranes deformed and became amorphous while treating the distillate. On the contrary, no significant changes were observed in the MFI and MOR zeolite membranes analyzed by X-ray diffraction after treating the distillate. However, the flux declined when the membranes were in contact with the distillate (pH = 3.8). Neutralizing the distillate to pH 6.6 with sodium hydroxide did not prevent the flux decline. Even though flux decreased by about 20–30%, the MOR membrane showed quite high water-selectivity, with a water concentration of over 99.9% in the permeate, suggesting the feasibility of its application to concentrate bioethanol.

Dang Ngoc Anh Suong et al find that vertical mixing generates iPSC-derived brain organoids displaying an inverted structure with neurons localising at the centre and neural progenitors at the outside. This study illustrates the influence of fluid mechanics relevant to the direction of primary cilia on stem cell differentiation.

BackgroundSocial cognitive impairments adversely affect social functioning (e.g., employment status) in patients with schizophrenia. Although pharmacological interventions have been suggested to provide some benefits on social cognition, little information is available on the comparative efficacy of pharmacotherapy. Thus, the aim of this planned systematic review and network meta-analysis is to perform a quantitative comparison of the effects of various psychotropic drugs, including supplements, on social cognition disturbances of schizophrenia.MethodsThe literature search will be carried out using the PubMed, Embase, Cochrane Central Register of Controlled Trials, PsycINFO, ClinicalTrials.gov, and International Clinical Trials Registry Platform databases from inception onward. Randomized controlled trials that examined the efficacy of drugs in social cognitive disturbances will be included, based on the most recent studies and the broader literature than previously searched. This protocol defines a priori the methods that will be used for study selection, data collection, quality assessment, and statistical syntheses.DiscussionThe findings this work are expected to help promote the development of better therapeutics of social cognitive impairments in schizophrenia and related psychiatric conditions.Systematic Review Registration[www.crd.york.ac.uk/prospero], identifier [CRD42021293224].

Abstract Background Lymphovascular invasion (LVI), which includes vascular or lymphatic invasions, is a representative prognostic factor even in patients with resected stage IA non-small cell lung cancer (NSCLC). Because tegafur-uracil is effective on cancers with LVI, we conducted a multi-center single-arm phase II study to estimate the efficacy of adjuvant tegafur-uracil in patients with LVI-positive stage IA NSCLC. Methods Patients with completely resected LVI-positive stage IA NSCLC were registered. LVI was diagnosed by consensus of two of three pathologists. Adjuvant chemotherapy consisted of 2 years of oral tegafur-uracil at 250 mg/m2/day. Fifty-five patients from 7 institutions were enrolled from June 2007 to September 2012. Results Among the 52 eligible patients, 36 (69.2%) completed the treatment course. There were 39 male and 13 female patients. The observation period was calculated as 562 to 3107 days using the reverse Kaplan-Meier method. The 5-year overall and relapse free survival rates were 94.2 and 88.5% respectively, which were significantly better than that of any other studies conducted on patients with LVI-positive stage IA NSCLC. Notably, the overall survival rate was 15% better than that of our prior retrospective study. The retrospective analysis of stage IA NSCLC patients who had received an operation in the same period revealed that the 5-year overall survival rate of the LVI positive group was 73.6% when adjuvant chemotherapy was not applied. Among 55 safety analysis sets, 4 cases of grade 3 hepatic function disorder (9.1%) and 5 cases of grade 2 anorexia (10.9%) were most frequently observed. No grade 4 adverse effects were encountered. Conclusion A 2-year course of oral tegafur-uracil administration is feasible and might have a significant benefit in the adjuvant treatment of LVI-positive stage IA NSCLC. Trial registration UMIN identifier: UMIN000005921 ; Date of enrolment of the first participant to the trial: 19 June 2007; Date of registration: 5 July 2011 (retrospectively registered).

BackgroundBoth impairment and sex differences in social cognition and neurocognition have been documented in schizophrenia. However, whether sex differences exist in the association between social cognition and neurocognition are not known. We aimed to investigate the contribution of areas of neurocognition to theory of mind (ToM) and hostility bias, representing social cognition, according to sex in early course schizophrenia.MethodsIn this cross-sectional study, we assessed neurocognition using the Japanese version of the Brief Assessment of Cognition in Schizophrenia (BACS) and assessed the ToM and hostility bias subdomains of social cognition using the Social Cognition Screening Questionnaire (SCSQ) in 131 participants (65 female, 66 male) diagnosed with schizophrenia within 5 years of onset. Sex differences were analyzed using t-tests. The associations of neurocognitive subdomains with ToM and hostility bias according to sex were analyzed using multiple regression analysis. Results were adjusted by age, estimated premorbid intelligence quotient, and symptomatology.ResultsNo sex differences were found in ToM (p = 0.071) or hostility bias (p = 0.057). Higher verbal fluency was significantly associated with higher ToM in females (p < 0.01), whereas higher executive function was significantly associated with higher ToM in males (p < 0.05). Higher verbal fluency was significantly associated with lower hostility bias in females (p < 0.05), whereas neurocognition and hostility bias were not significantly associated in males.ConclusionThe results suggest that neurocognition associated with social cognition differ according to sex. These differences should be considered for more effective treatment of social cognition.

Amyloid fibrillation is provoked by the conformational rearrangement of its source. In our previous study, we claimed that the conformational rearrangement of hen egg white lysozyme requires intermolecular aggregation/packing induced. Our proposed causality of the aggregation and amyloid formation was demonstrated by the quantitative dependence of amyloid fibrillation on pH difference from its isoelectric point (pI) and on the square root of ionic strength in order to reduce the intermolecular repulsion due to the shielding effect of electrolytes (DLVO effect). When Congo red has dianionic form at the pH higher than its pKa, it forms ribbon-like micelle colloids under lower ionic strength, while it loses electrostatic repulsion and aggregates to be emulsified in the octanolic phase under the higher ionic strength. These behaviors of Congo red were resembling to molecular assembly of surfactants. In contrast, the amyloid formation of insulin was proportional to the square root of ionic strength at the pH lower than its isoelectric point. Therefore, the trigger for conformational rearrangement of amyloid fibrillation is predominantly gripped by hydrophobic hydration and an electrostatic shielding effect. We concluded that the both behaviors of Congo red and insulin were derived from a driving force related to the hydrophobic hydration.

Abstract A patient with late phase of COVID‐19 pneumonia presented peripheral cystic features on chest computed tomography, which were spontaneously resolved with no antibiotic therapy or surgery. Physicians should pay attention to follow up the late phase of COVID‐19 pneumonia for better understanding its progression and clinical course.

Osteochondral lesions of the tarsal navicular bone are rare. The pathogenesis of osteochondral lesions of the tarsal navicular involves direct trauma to the tarsal navicular joint and repetitive trauma caused by excessive shear force, including a stress fracture. Osteochondral autograft transplantation (OAT) has emerged as a surgical treatment option for osteochondral lesions of the knee, ankle, and elbow joints. This report discusses the surgical treatment of an osteochondral lesion in the tarsal navicular bone of a 16-year-old track and field jumper. The patient was surgically treated with curettage of the osteochondral lesion at the center of the tarsal navicular and OAT. Computed tomography images 3 months postoperatively revealed adequate bone-to-bone healing of the graft and tarsal navicular joint surface. He returned to track and field competition without experiencing foot pain for 10 postoperative months. No symptom recurrence was observed during the 4-year follow-up. Based on the results of this case, we recommend OAT as a viable treatment option for patients with isolated cartilage lesion of the navicular bone (without fracture line) that does not respond to conservative treatment.

The western conifer seed bug (WCSB, Leptoglossus occidentalis) is a pest of many pine species and is invasive worldwide. WCSB directly and indirectly deteriorates pine nut production by sucking seeds from cones. Currently, researchers think that WCSBs search for food by a combination of cues from visible light, infrared radiation, and chemicals such as monoterpenes. Some research revealed that WCSBs prefer larger cones, and it was thought that WCSBs suck seeds from and obtain more heat on larger cones. However, in early spring, we observed that most WCSBs gathered on male cones rather than on female cones and young cones. We hypothesized that male pine cones were warmer than female cones and needles, and WCSBs sucking male cones may receive more heat. To test these hypotheses, we measured spectral reflectance with a hyperspectral sensor and temperature of pine organs with tiny thermocouples, and the data were analyzed by a heat budget model. Our results revealed that male cones were significantly warmer and more reflective than female cones and needles, which may attract WCSBs. These results supported our hypothesis that WCSBs on male cones were warmer than those on other organs. This study will help further understanding of WCSBs and the adaptive value of pine cone colors.

Human-hepatoblastoma-derived cell line, HepG2, has been widely used in liver and liver cancer studies. HepG2 spheroids produced in a three-dimensional (3D) culture system provide a better biological model than cells cultured in a two-dimensional (2D) culture system. Since cells at the center of spheroids exhibit specific behaviors attributed to hypoxic conditions, a 3D cell culture system that allows the observation of such cells using conventional optical or fluorescence microscopes would be useful. In this study, HepG2 cells were cultured in “Cell Dome”, a micro-dome in which cells are enclosed in a cavity consisting of a hemispherical hydrogel shell. HepG2 cells formed hemispherical cell aggregates which filled the cavity of Cell Domes on 18 days of culture and the cells could continue to be cultured for 29 days. The cells at the center of hemispherical cell aggregates were observed using a fluorescence microscope. The cells grew in Cell Domes for 18 days exhibited higher Pi-class Glutathione S-Transferase enzymatic activity, hypoxia inducible factor-1α gene expression, and higher tolerance to mitomycin C than those cultured in 2D on tissue culture dishes (* p < 0.05). These results indicate that the center of the glass adhesive surface of hemispherical cell aggregates which is expected to have the similar environment as the center of the spheroids can be directly observed through glass plates. In conclusion, Cell Dome would be useful as an evaluation platform for organized HepG2 cells.

The thermal grill illusion induces a pain sensation under a spatial display of warmth and coolness of approximately 40 °C; and 20 °C. To realize virtual pain display more universally during the virtual reality experience, we proposed a spatiotemporal control method to realize a variable thermal grill illusion and evaluated the effect of the method. First, we examined whether there was a change in the period until pain occurred due to the spatial temperature distribution of pre-warming and pre-cooling and verified whether the period until pain occurred became shorter as the temperature difference between pre-warming and pre-cooling increased. Next, we examined the effect of the number of grids on the illusion and verified the following facts. In terms of the pain area, the larger the thermal area, the larger the pain area. In terms of the magnitude of the pain, the larger the thermal area, the greater the magnitude of the sensation of pain.

Hormone-secreting pituitary adenomas show unregulated hormonal hypersecretion and cause hyperpituitarism. However, the mechanism of the unregulated hormone production and secretion has not yet been fully elucidated. Solid tumors show reduced extracellular pH, partly due to lactate secretion from anaerobic glycolysis. It is known that extracellular acidification affects hormone secretion. However, whether and how the extracellular acidification influences the unregulated hormone production and secretion remain unknown. In the present study, we found that GPR4, a proton-sensing G protein-coupled receptor, was highly expressed in MtT/S cells, a growth hormone-producing and prolactin-producing pituitary tumor cell line. When we reduced the extracellular pH, growth hormone and prolactin mRNA expressions increased in the cells. Both increased expressions were partially suppressed by a GPR4 antagonist. We also found that extracellular acidification enhanced growth hormone-releasing factor-induced growth hormone secretion from MtT/S cells. These results suggest that GPR4 may play a role in hypersecretion of the hormone from hormone-producing pituitary tumors. A GPR4 antagonist will be a useful tool for preventing the hypersecretion.

The present paper aims to propose a new type of information-theoretic method to interpret the inference mechanism of neural networks. We interpret the internal inference mechanism for itself without any external methods such as symbolic or fuzzy rules. In addition, we make interpretation processes as stable as possible. This means that we interpret the inference mechanism, considering all internal representations, created by those different conditions and patterns. To make the internal interpretation possible, we try to compress multi-layered neural networks into the simplest ones without hidden layers. Then, the natural information loss in the process of compression is complemented by the introduction of a mutual information augmentation component. The method was applied to two data sets, namely, the glass data set and the pregnancy data set. In both data sets, information augmentation and compression methods could improve generalization performance. In addition, compressed or collective weights from the multi-layered networks tended to produce weights, ironically, similar to the linear correlation coefficients between inputs and targets, while the conventional methods such as the logistic regression analysis failed to do so.

We study the dynamics of dark energy in the presence of a 2-form field coupled to a canonical scalar field ϕ. We consider the coupling proportional to e−μϕ/MplHαβγHαβγ and the scalar potential V(ϕ)∝e−λϕ/Mpl, where Hαβγ is the 2-form field strength, μ,λ are constants, and Mpl is the reduced Planck mass. We show the existence of an anisotropic matter-dominated scaling solution followed by a stable accelerated fixed point with a non-vanishing shear. Even if λ≥O(1), it is possible to realize the dark energy equation of state wDE close to −1 at low redshifts for μ≫λ. The existence of anisotropic hair and the oscillating behavior of wDE are key features for distinguishing our scenario from other dark energy models like quintessence.

Cyclic adenosine monophosphate (cAMP) plays a pivotal role in gonadotrope responses in the pituitary. Gonadotropin-releasing hormone (GnRH) mediated synthesis and secretion of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) are regulated by both the Gs/cAMP and Gq/Ca2+ signaling pathways. Pituitary adenylate cyclase-activating polypeptide (PACAP) also regulates GnRH responsiveness in gonadotropes through the PACAP receptor, which activates the Gs/cAMP signaling pathway. Therefore, measuring intracellular cAMP levels is important for elucidating the molecular mechanisms of FSH and LH synthesis and secretion in gonadotropes. The GloSensor cAMP assay is useful for detecting cAMP levels in intact, living cells. In this study, we found that increased GloSensor luminescence intensity did not correlate with cAMP accumulation in LβT2 cells under low pH conditions. This result indicates that cell type and condition must be considered when using GloSensor cAMP.

In quadratic-order degenerate higher-order scalar–tensor (DHOST) theories compatible with gravitational-wave constraints, we derive the most general Lagrangian allowing for tracker solutions characterized by ϕ˙/Hp=constant, where ϕ˙ is the time derivative of a scalar field ϕ, H is the Hubble expansion rate, and p is a constant. While the tracker is present up to the cubic-order Horndeski Lagrangian L=c2X−c3X(p−1)/(2p)□ϕ, where c2,c3 are constants and X is the kinetic energy of ϕ, the DHOST interaction breaks this structure for p≠1. Even in the latter case, however, there exists an approximate tracker solution in the early cosmological epoch with the nearly constant field equation of state wϕ=−1−2pH˙/(3H2). The scaling solution, which corresponds to p=1, is the unique case in which all the terms in the field density ρϕ and the pressure Pϕ obey the scaling relation ρϕ∝Pϕ∝H2. Extending the analysis to the coupled DHOST theories with the field-dependent coupling Q(ϕ) between the scalar field and matter, we show that the scaling solution exists for Q(ϕ)=1/(μ1ϕ+μ2), where μ1 and μ2 are constants. For the constant Q, i.e., μ1=0, we derive fixed points of the dynamical system by using the general Lagrangian with scaling solutions. This result can be applied to the model construction of late-time cosmic acceleration preceded by the scaling ϕ-matter-dominated epoch.

An increase in resting blood lactate (La−) concentration due to metabolic conditions has been reported. However, it is not clear whether resting La− changes with training cycles in athletes. The purpose of this study was to test the hypotheses that (1) the morning resting La− levels are lower in periods of high training compared to periods of low training and (2) these changes in La− concentration are related to athletes’ metabolic capacity during exercise in male college-aged rugby players. Resting La− and blood glucose concentrations were measured in the morning in eight league rugby players during the summer pre-season period (Pre-period), the training and competition season period (TC-period), and the winter post-season period (Post-period). In each period, anaerobic power, La− concentration, and respiratory responses were measured during the 40 s maximal Wingate anaerobic test (WT). The resting La− concentration in the morning was significantly lower in the TC-Period (1.9 ± 0.6 mmol/L) than in the Post-Period (2.3 ± 0.9 mmol/L). The rate of decrease in La− level immediately after the 40 s WT was significantly higher in the TC-Period than in the Post-Period. The resting La− concentration was significantly correlated with the peak oxygen uptake and the carbon dioxide output during the WT. These results support the hypothesis that an athlete’s training cycle (i.e., in season and off season) influences the resting La− levels as well as the metabolic capacity during high-intensity exercise. The monitoring of resting La− fluctuations may provide a convenient indication of the training cycle-dependent metabolic capacity in athletes.

Recent studies on the Buddhist threefold wisdom model and its suggested potentialities have warranted a rediscovery of the model in different historical and cultural contexts. Saichō (最澄, 766/7–822), founder of Japanese Tendai Buddhism, references the three wisdoms in his documents outlining the Tendai monastic education curriculum. Through modification of translation and analysis of related original texts by Saichō, and an interview with the current dean of the Tendai monastic education institution, this paper aims to (1) uncover Sino-Japanese history of expressions of threefold wisdom and Buddhist education, (2) clarify the content of Saichō’s curriculum, and (3) examine the role of compassion in said curriculum. This paper argues that the threefold wisdom served as a foundational framework of Saichō’s education; he envisioned that his graduates would develop into religious leaders of the nation who would benefit all sentient beings through their own training, preaching the Dharma, and contributing to social work. At the same time, it became clear that compassionate attitudes were considered to be fundamental to all practices of the three wisdoms at Mount Hiei, which makes Saichō’s curriculum a captivating case of a theological application of the threefold wisdom.

Abstract Purpose The purpose of this study was to examine the effect of simple core muscle training (CMT) program on trunk muscle strength and neuromuscular control among pediatric athletes. Methods Forty‐nine male soccer players (mean age, 10.8 years) participated. The CMT program had three components (bench, side bench, and Nordic hamstrings) and was performed at least three times weekly for a year. Trunk flexion/extension muscle strength and the K/H ratio (determined by dividing knee separation distance by hip separation distance during drop‐jump test and used as an index of lower limb valgus alignment) were measured, and the Y balance test (YBT) was performed before and after intervention. This study did not include the pure control group among the same team. To consider the effect of CMT on trunk muscle strength due to physical growth, we used the data of trunk muscle strength from the local cohort study previously conducted in our institution. One hundred participants who matched the age, height, body weight, and body mass index of the training group was designated as a control group. Results In the training group, the trunk flexion/extension strength significantly increased at 6 months (p

Summary: Heterogeneity of gene expression and rarity of replication hamper molecular analysis of β-cell mass restoration in adult pancreas. Here, we show transcriptional dynamics in β-cell replication process by single-cell RNA sequencing of murine pancreas with or without partial pancreatectomy. We observed heterogeneity of Ins1-expressing β-cells and identified the one cluster as replicating β-cells with high expression of cell proliferation markers Pcna and Mki67. We also recapitulated cell cycle transition accompanied with switching expression of cyclins and E2F transcription factors. Both transient activation of endoplasmic reticulum stress responders like Atf6 and Hspa5 and elevated expression of tumor suppressors like Trp53, Rb1, and Brca1 and DNA damage responders like Atm, Atr, Rad51, Chek1, and Chek2 during the transition to replication associated fine balance of cell cycle progression and protection from DNA damage. Taken together, these results provide a high-resolution map depicting a sophisticated genetic circuit for replication of the β-cells.

Cerebral ischemia induces neuronal cell death and causes various kinds of brain dysfunction. Therefore, prevention of neuronal cell death is most essential for protection of the brain. On the other hand, it has been reported that epigenetics including DNA methylation plays a pivotal role in pathogenesis of some diseases such as cancer. Accumulating evidences indicate that aberrant DNA methylation is related to cell death. However, DNA methylation after cerebral ischemia has not been fully understood yet. The aim of this present study was to investigate the relationships between DNA methylation and neuronal cell death after cerebral ischemia. We examined DNA methylation under the ischemic condition by using transient middle cerebral artery occlusion and reperfusion (MCAO/R) model rats and N-methyl-D-aspartate (NMDA)–treated cortical neurons in primary culture. In this study, we demonstrated that DNA methylation increased in these neurons 24 h after MCAO/R and that DNA methylation, possibly through activation of DNA methyltransferases (DNMT) 3a, increased in such neurons immediately after NMDA treatment. Furthermore, NMDA-treated neurons were protected by treatment with a DNMT inhibitor that were accompanied by inhibition of DNA methylation. Our results showed that DNA methylation would be an initiation factor of neuronal cell death and that inhibition of such methylation could become an effective therapeutic strategy for stroke.

Summary: Ureteric bud (UB) is the embryonic kidney progenitor tissue that gives rise to the collecting duct and lower urinary tract. UB-like structures generated from human pluripotent stem cells by previously reported methods show limited developmental ability and limited branching. Here we report a method to generate UB organoids that possess epithelial polarity and tubular lumen and repeat branching morphogenesis. We also succeed in monitoring UB tip cells by utilizing the ability of tip cells to uptake very-low-density lipoprotein, cryopreserving UB progenitor cells, and expanding UB tip cells that can reconstitute the organoids and differentiate into collecting duct progenitors. Moreover, we successfully reproduce some phenotypes of multicystic dysplastic kidney (MCDK) using the UB organoids. These methods will help elucidate the developmental mechanisms of UB branching and develop a selective differentiation method for collecting duct cells, contributing to the creation of disease models for congenital renal abnormalities.

Brown adipose tissue (BAT) mediates adaptive thermogenesis upon food intake and cold exposure, thus potentially contributing to the prevention of lifestyle-related diseases. 18F-fluorodeoxyglucose (FDG)–positron emission tomography (PET) with computed tomography (CT) (18FDG–PET/CT) is a standard method for assessing BAT activity and volume in humans. 18FDG–PET/CT has several limitations, including high device cost and ionizing radiation and acute cold exposure necessary to maximally stimulate BAT activity. In contrast, near-infrared spectroscopy (NIRS) has been used for measuring changes in O2-dependent light absorption in the tissue in a non-invasive manner, without using radiation. Among NIRS, time-resolved NIRS (NIRTRS) can quantify the concentrations of oxygenated and deoxygenated hemoglobin ([oxy-Hb] and [deoxy-Hb], respectively) by emitting ultrashort (100 ps) light pulses and counts photons, which are scattered and absorbed in the tissue. The basis for assessing BAT density (BAT-d) using NIRTRS is that the vascular density in the supraclavicular region, as estimated using Hb concentration, is higher in BAT than in white adipose tissue. In contrast, relatively low-cost continuous wavelength NIRS (NIRCWS) is employed for measuring relative changes in oxygenation in tissues. In this review, we provide evidence for the validity of NIRTRS and NIRCWS in estimating human BAT characteristics. The indicators (IndNIRS) examined were [oxy-Hb]sup, [deoxy-Hb]sup, total hemoglobin [total-Hb]sup, Hb O2 saturation (StO2sup), and reduced scattering coefficient (μs sup′) in the supraclavicular region, as determined by NIRTRS, and relative changes in corresponding parameters, as determined by NIRCWS. The evidence comprises the relationships between the IndNIRS investigated and those determined by 18FDG–PET/CT; the correlation between the IndNIRS and cold-induced thermogenesis; the relationship of the IndNIRS to parameters measured by 18FDG–PET/CT, which responded to seasonal temperature fluctuations; the relationship of the IndNIRS and plasma lipid metabolites; the analogy of the IndNIRS to chronological and anthropometric data; and changes in the IndNIRS following thermogenic food supplementation. The [total-Hb]sup and [oxy-Hb]sup determined by NIRTRS, but not parameters determined by NIRCWS, exhibited significant correlations with cold-induced thermogenesis parameters and plasma androgens in men in winter or analogies to 18FDG–PET. We conclude that NIRTRS can provide useful information for assessing BAT-d in a simple, rapid, non-invasive way, although further validation study is still needed.

We investigate a dark energy scenario in which a canonical scalar field ϕ is coupled to the four velocity ucμ of cold dark matter (CDM) through a derivative interaction ucμ∂μϕ. The coupling is described by an interacting Lagrangian f(X,Z), where f depends on X=−∂μϕ∂μϕ/2 and Z=ucμ∂μϕ. We derive stability conditions of linear scalar perturbations for the wavelength deep inside the Hubble radius and show that the effective CDM sound speed is close to 0 as in the standard uncoupled case, while the scalar-field propagation speed is affected by the interacting term f. Under a quasi-static approximation, we also obtain a general expression of the effective gravitational coupling felt by the CDM perturbation. We study the late-time cosmological dynamics for the coupling f∝X(2−m)/2Zm and show that the gravitational coupling weaker than the Newton constant can be naturally realized for m>0 on scales relevant to the growth of large-scale structures. This allows the possibility for alleviating the tension of σ8 between low- and high-redshift measurements.

Abstract This paper presents the LogDrive framework for mitigating the following problems of storage forensics in Infrastructure-as-a-Service (IaaS) cloud environments: volatility, increasing volume of forensic data, and anti-forensic attacks that hide traces of incidents in virtual machines. The proposed proactive data collection function of virtual block devices mitigates the problem of volatility within the cloud environments and enables a time-traveling investigation to reveal overwritten or deleted evidence files. We employ a sector-hash-based file detection method with random sampling to search for an evidence file in the record of the write logs of the virtual storage. The problem formulation, the investigation context, and the design with five algorithms are presented. We explore the performance of LogDrive through a detailed evaluation. Finally, security analysis of LogDrive is presented based on the STRIDE (Spoofing, Tampering, Repudiation, Information disclosure, Denial of service, and Elevation of privilege) threats model and related work. We posted the source code of LogDrive on GitHub.

AND-1, the vertebrate orthologue of Ctf4, is a critical player during DNA replication and for maintenance of genome integrity. Here the authors use a conditional AND-1 depletion system in avian DT40 cells to reveal the consequences of the lack of AND-1 on cell proliferation and DNA replication.