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Abstract Background Electronic gambling machines (EGMs) in gambling venues cause gambling-related harm and are a public health concern. This study focused on pachinko parlours as gambling venues and income-generating crimes as gambling-related harm. We aimed to verify whether income-generating crime rates increase in proximity to pachinko parlours and during the opening and post-closing periods of pachinko parlours relative to the pre-opening periods. Methods We used crime records spanning 6.5 years, including data on the opening and closing days of pachinko parlours for 6.5 years. We also sampled the addresses of convenience stores, bowling alleys, and households with official land prices all over Japan. The dependent variable was the daily income-generating crime incidence rate. Areas within 0.5 km, 0.5–1 km, 1–5 km, and 5–10 km radii of the pachinko parlours were the independent variables. The pre-, opening-, and post-closing periods of the pachinko parlours were also independent variables. The covariates included the number of convenience stores and always open pachinko parlours near pachinko parlours. Data were analysed using an analysis of variance (ANOVA) and covariance (ANCOVA). We also used differences-in-differences analysis (DD) to reveal the increase in income-generating crime rates in neighbourhoods exposed to the opening or closing of pachinko parlours. Results The daily income-generating crime incidence rate was significantly higher in areas within 0.5–1 km and 1–5 km radii of pachinko parlours than in those within 0.5 km and 5–10 km radii of them. The daily income-generating crime incidence rate was also significantly higher during the opening and post-closing periods than during the pre-opening period, even when controlling for the number of convenience stores and always open pachinko parlours. In particular, fraud crime rates increased with the opening and closing of pachinko parlours. Conclusions The highest income-generating crime incidence rate was observed within a 0.5–1 km and 1–5 km radius of pachinko parlours. The opening of pachinko parlours also increased income-generating crime incidence rates, which increased after closing. Pachinko parlours are considered to be creating public harm because the corporate activities of these parlours make the youth in their neighbourhood perpetrators of fraud and older adults its victims. Future research should examine the current findings using official crime records.

Abstract Virtual reality self-counseling (VR-SC) is considered an effective approach for addressing mental health problems. Previous studies have shown the effectiveness of VR-SC using Sigmund Freud’s avatar as the counselor. However, considering that virtual reality (VR) enables embodied perspective-taking of another person, VR-SC using the avatar of a person who cares about the participant (an intimate person), such as a family member or friend, is considered effective because it could create warm attitudes toward the participants themselves. In this study, 60 undergraduate and graduate students were split into three conditions: VR-SC with intimate persons, VR-SC with Freud, and a control group. The intervention effects were then compared. The results showed that VR-SC with an intimate person was the most effective in improving anxiety symptoms. These results may be attributed to accepting and affirming oneself from the perspective of the intimate person’s avatar and counseling oneself. This study is significant in that it is the first to conduct VR-SC with the avatar of an intimate person and compare the effects with Freud’s avatar. More importantly, it showed that the same VR-SC method could have different effects depending on the avatar of the counseling partner.

Abstract Background The increasing prevalence of heated tobacco products (HTPs) has heightened concerns regarding their potential health risks. Previous studies have demonstrated the toxicity of cigarette smoke extract (CSE) from traditional tobacco’s mainstream smoke, even after the removal of nicotine and tar. Our study aimed to investigate the cytotoxicity of CSE derived from HTPs and traditional tobacco, with a particular focus on the role of reactive oxygen species (ROS) and intracellular Ca2+. Methods A human oral squamous cell carcinoma (OSCC) cell line, HSC-3 was utilized. To prepare CSE, aerosols from HTPs (IQOS) and traditional tobacco products (1R6F reference cigarette) were collected into cell culture media. A cell viability assay, apoptosis assay, western blotting, and Fluo-4 assay were conducted. Changes in ROS levels were measured using electron spin resonance spectroscopy and the high-sensitivity 2ʹ,7ʹ-dichlorofluorescein diacetate assay. We performed a knockdown of calcium/calmodulin-dependent protein kinase kinase 2 (CaMKK2) by shRNA lentivirus in OSCC cells. Results CSE from both HTPs and traditional tobacco exhibited cytotoxic effects in OSCC cells. Exposure to CSE from both sources led to an increase in intracellular Ca2+ concentration and induced p38 phosphorylation. Additionally, these extracts prompted cell apoptosis and heightened ROS levels. N-acetylcysteine (NAC) mitigated the cytotoxic effects and p38 phosphorylation. Furthermore, the knockdown of CaMKK2 in HSC-3 cells reduced cytotoxicity, ROS production, and p38 phosphorylation in response to CSE. Conclusion Our findings suggest that the CSE from both HTPs and traditional tobacco induce cytotoxicity. This toxicity is mediated by ROS, which are regulated through Ca2+ signaling and CaMKK2 pathways. Graphical Abstract

BackgroundWorsening loneliness and social isolation during the COVID-19 pandemic have become serious public health concerns worldwide. Despite previous research reporting persistent loneliness and social isolation under repeated emergency declarations and prolonged pandemics, long-term studies are needed to identify the actual conditions of loneliness and social isolation, and the factors that explain them. ObjectiveIn this study, 3 web-based surveys were conducted at 1-year intervals during the 2 years after the first state of emergency to examine changes in loneliness and social isolation and the psychosocial factors associated with them in the Japanese population. MethodsThe first survey (phase 1, May 11-12, 2020) was conducted at the end of the first emergency declaration period, the second survey (phase 2, June 14-20, 2021) was conducted at the end of the third emergency declaration period, and the third survey (phase 3, May 13-30, 2022) was conducted when the state of emergency had not been declared but many COVID-19–positive cases occurred during this period. We collected data on 3892 inhabitants (n=1813, 46.58% women; age: mean 50.3, SD 13.4 y) living in the 4 prefectures where emergency declaration measures were applied in phases 1 and 2. A linear mixed model analysis was performed to examine the association between psychosocial variables as explanatory variables and loneliness scores as the dependent variable in each phase. ResultsWhile many psychosocial and physical variables showed improvement for the 2 years, loneliness, social isolation, and the relationship with familiar people deteriorated, and the opportunities for exercise, favorite activities, and web-based interaction with familiar people decreased. Approximately half of those experiencing social isolation in phase 1 remained isolated throughout the 2-year period, and a greater number of people developed social isolation than those who were able to resolve it. The results of the linear mixed model analysis showed that most psychosocial and physical variables were related to loneliness regardless of the phase. Regarding the variables that showed a significant interaction with the phase, increased altruistic preventive behavior and a negative outlook for the future were more strongly associated with severe loneliness in phase 3 (P=.01 to

Abstract To examine changes in individuals’ psychosocial variables (e.g., psychological distress, social isolation, and alcohol use) during the prolonged COVID-19 pandemic, a two-year longitudinal survey was conducted at approximately one-year intervals between May 2020 and May 2022, after the first COVID-19-related state of emergency was announced in Japan. The online survey was conducted on May 11-12, 2020 (Phase 1), June 14–20, 2021 (Phase 2), and May 13–30, 2022 (Phase 3). The survey in Phase 1 was conducted during the first emergency declaration period, the survey in Phase 2 was conducted during the third emergency declaration period, and the survey in Phase 3 was conducted at a time when there was no state of emergency but many COVID-19 positive cases. Notably, 3,892 participants responded to all three surveys. In addition to psychosocial inventories often used worldwide, survey items included lifestyle and stress management indicators related to COVID-19 and various sociodemographic items including occupation (e.g., healthcare workers) or income, history of medical treatment for mental problems, severe physical illnesses, and COVID-19.

Although carnosine (β-Ala-L-His) is one of physiological protectants against in vivo damages caused by reactive oxygen species (ROS), its reactivity against singlet oxygen (1O2), an ROS, is still unclear at the molecular level. Theoretically, the reaction consists of two steps: i) oxygenation of the His side chain to form an electrophilic endoperoxide and ii) nucleophilic addition to the endoperoxide. In this study, the end product of 1O2-mediated carnosine oxidation was evaluated using 2D-NMR and other analytical methods both in the presence and absence of external nucleophiles. Interestingly, as the end product without external nucleophile, a cyclic homodimer was confirmed under our particular conditions. The reaction was also replicated in pork specimens.

Abstract INTRODUCTION The use of anti‐epileptic drugs (AEDs) in degenerative dementia (DD) remains uncertain. We aimed to evaluate the association of early AED administration with subsequent DD occurrence. METHODS Using a large nationwide database, we enrolled patients newly diagnosed with epilepsy from 2014 to 2019 (n = 104,225), and using propensity score matching, we divided them into treatment (those prescribed AEDs in 2014) and control groups. The primary outcome was subsequent DD occurrence in 2019. RESULTS Overall, 4489 pairs of patients (2156 women) were matched. The odds ratio (treatment/control) for DD occurrence was 0.533 (95% confidence interval: 0.459–0.617). The DD proportions significantly differed between the treatment (340/4489 = 0.076) and control (577/4489 = 0.129) groups. DISCUSSION Among patients newly diagnosed with epilepsy, compared to non‐use, early AED use was associated with a lower occurrence of subsequent DD. Further investigations into and optimization of early intervention for epilepsy in DD are warranted. Highlights Anti‐epileptic drug (AED) use before epilepsy diagnosis was linked with a lower subsequent degenerative dementia (DD) occurrence. Identifying the epileptic phenotype was crucial for justifying early AED use in DD. AED use with an epilepsy diagnosis did not pose an additional risk of DD. The potential contribution of combination drug therapy to the strategy was noted.

Background/objective: Arthroscopic lateral ligament repair (ALLR) for chronic lateral ankle instability (CLAI) has been improving with technical innovations. However, there is a lack of information regarding mid- and/or long-term clinical outcomes after the introduction of ALLR. This study aimed to report mid-term clinical outcomes of ALLR with a knotless anchor. Methods: Thirty-two patients (11 men and 21 women; mean age, 28 ± 14 years) who underwent ALLR with a knotless anchor from December 2015 to October 2020 were included. The mean follow-up period was 31 ± 11 months. The Japanese Society for Surgery of the Foot (JSSF) ankle-hindfoot scale and the Self-Administered Foot Evaluation Questionnaire (SAFE-Q) were used for clinical evaluation preoperatively and at the 2-year follow-up. Surgical complications, particularly knot irritation, were also examined. Results: The JSSF scale scores were significantly improved, from 71.3 ± 13.1 preoperatively to 96.6 ± 5.1 postoperatively (P

Abstract Interoception, which pertains to the physiological state of the body, is associated with subjective emotional experiences. In particular, the accuracy of perceiving interoceptive signals (interoceptive accuracy [IAcc]) is linked to the intensity of emotional arousal, known as arousal focus (AF). IAcc is believed to influence the granularity of emotional experiences. Here, we examined the relationship between IAcc and assessment and verbalisation of one's own or others' emotions. Study I demonstrated that individuals with higher IAcc exhibited significantly greater AF when evaluating their own positive emotions. Furthermore, although no correlation between IAcc and AF was found in free descriptions of emotions, a significant positive correlation was found between IAcc and the number of emotion-related words. Study II showed that individuals with higher IAcc displayed significantly higher AF when assessing the positive emotions of characters in videos. Additionally, in free descriptions of these characters, a significant positive correlation was observed between predicted verbal IQ and the number of emotion-related words. These findings support the notion that interoception is associated with AF during assessment of one's own or others' positive emotions as well as the abundance of emotion-related words. This study demonstrates the relationship between bodily sensations and social aspects of human embodiment.

This study proposes to further exploit the potential of the carbon dioxide supercritical anti-solvent precipitation (SAS) process by using liquefied gas as a feed solvent in the SAS process. In this study, liquefied dimethyl ether (DME) is compared to conventional ethyl acetate as the feed solvent for β-carotene. DME is a gas in its standard state, and when it is made into a subcritical liquefied gas, it has a larger self-diffusion coefficient and saturated vapor pressure, and smaller viscosity and surface tension than liquid solvents. Because of these characteristics of liquefied DME, liquefied DME prevents primary particle agglomeration and DME residue. When ethyl acetate was used as the feed solvent, the conditions giving the smallest particles were 60 °C and 12 MPa, and 31 ± 5 nm primary particles of β-carotene were obtained. However, most of these were aggregated into secondary particles of several hundred nanometers. In the case of liquefied DME, the condition giving the smallest particles was 40 °C and 12 MPa, and primary particles of 58 ± 8 nm β-carotene were dispersed without aggregation. Furthermore, FT-IR analysis detected residual ethyl acetate in the aggregated β-carotene particles, whereas DME was not detected in the dispersed particles. Liquefied DME is likely to be a suitable solvent for the micronization of heat-sensitive substances using the SAS method without agglomeration. Combining various liquefied gases, not just DME, with the SAS process may create possibilities for applying the SAS process to target materials that are insoluble in conventional liquid solvents and for synthesizing even finer nanoparticles.

Abstract Liquid-liquid phase separation (LLPS) has been thought to be the biophysical principle governing the assembly of the multiphase structures of nucleoli, the site of ribosomal biogenesis. Condensates assembled through LLPS increase their sizes to minimize the surface energy as far as their components are available. However, multiple microphases, fibrillar centers (FCs), dispersed in a nucleolus are stable and their sizes do not grow unless the transcription of pre-ribosomal RNA (pre-rRNA) is inhibited. To understand the mechanism of the suppression of the FC growth, we here construct a minimal theoretical model by taking into account nascent pre-rRNAs tethered to FC surfaces by RNA polymerase I. The prediction of this theory was supported by our experiments that quantitatively measure the dependence of the size of FCs on the transcription level. This work sheds light on the role of nascent RNAs in controlling the size of nuclear bodies.

Abstract In IDH-mutant astrocytoma, IDH2 mutation is quite rare and biological mechanisms underlying tumor progression in IDH2-mutant astrocytoma remain elusive. Here, we report a unique case of IDH2 mutant astrocytoma, CNS WHO grade 3 that developed tumor progression. We performed a comprehensive genomic and epigenomic analysis for primary and recurrent tumors and found that both tumors harbored recurrent IDH2 R172K and TP53 R248W mutation with CDKN2A/B hemizygous deletion. We also found amplifications of CDK4 and MDM2 with PDGFRA gain in the recurrent tumor and upregulated protein expressions of these genes. We further developed, for the first time, a xenograft mouse model of IDH2 R172K and TP53 R248W mutant astrocytoma from the recurrent tumor, but not from the primary tumor. Consistent with parent recurrent tumor cells, amplifications of CDK4 and MDM2 and PDGFRA gain were found, while CDKN2A/B was identified as homozygous deletion in the xenografts, qualifying for integrated diagnosis of astrocytoma, IDH2-mutant, CNS WHO grade 4. Cell viability assay found that CDK4/6 inhibitor and PDGFR inhibitor potently decreased cell viability in recurrent tumor cells, as compared to primary tumor cells. These findings suggest that gene alterations that activate retinoblastoma (RB) signaling pathways and PDGFR may drive tumor progression and xenograft formation in IDH2-mutant astrocytoma, which is equivalent to progressive IDH1-mutant astrocytoma. Also, our findings suggest that these genomic alterations may represent therapeutic targets in IDH2-mutant astrocytoma.

This study aims to evaluate the academic activities of female neurosurgeons at all branch meetings of the Japan Neurosurgical Society and identify related issues they encountered. The programs of all seven branch meetings of the Japan Neurosurgical Society (Hokkaido, Tohoku, Kanto, Chubu, Kinki, Chugoku/Shikoku, and Kyushu) were used to determine the number of presentations and chairpersons by sex. The covered period was from January 2008 to December 2020, which was available for viewing during the survey. Of note, only the Kinki branch used data from January 2008 to December 2019. The Neurologia Medico-chirurgica (NMC), the journal of the Japan Neurosurgical Society, was also reviewed to identify publication achievements during the same period. In all seven branches, the percentage of presentations given by female physicians increased from 7.9% in 2008 to 9.6% in 2020 (p < 0.05). Conversely, the percentage of female chairpersons in all branch meetings did not change over time and it was significantly lower (1.1%) than that of female presenters (7.9%) for all branch meetings combined in over 13 years (p < 0.01). In the NMC, the number of articles with female physicians as first authors did not increase or decrease over the years. We conclude that efforts to smoothly promote female neurosurgeons as chairpersons and increase the number of female first authors are necessary to facilitate their academic activities.

Abstract Motivated by our recent experiments that demonstrate that the tandemly repeated genes become heterochromatin, here we show a theory of heterochromatin assembly by taking into account the connectivity of these genes along the chromatin in the kinetic equations of small RNA production and histone methylation, which are the key biochemical reactions involved in the heterochromatin assembly. Our theory predicts that the polymeric nature of the tandemly repeated genes ensures the steady production of small RNAs because of the stable binding of nascent RNAs produced from the genes to RDRC/Dicers at the surface of nuclear membrane. This theory also predicts that the compaction of the tandemly repeated genes suppresses the production of small RNAs, consistent with our recent experiments. This theory can be extended to the small RNA-dependent gene silencing in higher organisms.

Common carotid artery (CCA) occlusion (CCAO) is a rare cause of ischemic stroke and bypass surgery is the common treatment approach. However, safer alternatives should be developed to treat CCAO. A 68-year-old male was diagnosed with left-sided CCAO with decreased left visual acuity due to neck radiation therapy for laryngeal cancer. Recanalization therapy using a pull-through technique was initiated because cerebral blood flow progressively decreased during the follow-up period. First, after a short sheath was inserted into the CCA, the occluded CCA was retrogradely penetrated through the sheath. Second, a micro-guidewire was guided to the aorta from the femoral sheath where it was caught using a snare wire guided from the cervical sheath. Subsequently, the micro-guidewire was gently pulled out from the cervical sheath, penetrated the occluded lesion, and was secured to the femoral and cervical sheaths. Finally, the occluded lesion was dilated using a balloon, and the stent was placed. Five days postprocedure, the patient was discharged uneventfully and exhibited improved left visual acuity. In terms of reliable penetration of obstructive lesions and reduction of embolic and hemorrhagic complications, combined endovascular antegrade and direct retrograde carotid artery stenting is a versatile and minimally invasive treatment option for CCAO.

Dural arteriovenous fistula (DAVF) is considered an acquired change in blood flow related to factors such as craniotomy, trauma, and infection. However, several factors related to its development remain unknown. Here, we present a case of a 48-year-old man with Down syndrome and Eisenmenger syndrome. He had a history of craniotomy for multiple brain abscesses, followed by the occurrence of a de novo straight sinus (StS) DAVF within the last 2 years. The patient presented with right putamen hemorrhage due to venous congestion by a StS DAVF. The shunt flow was occluded by transarterial embolization using Onyx. Several studies have reported on DAVF models induced by venous congestion and hypoxemia. In this case, local venous congestion due to craniotomy for multiple brain abscesses was considered as one of the causes of DAVF. Complication of venous thrombosis or chronic hypoxemia due to Eisenmenger syndrome might have led to its progression. Especially in DAVF cases with Down syndrome, concomitant symptoms such as hypoxemia due to congenital heart failure and coagulopathy could worsen the disease state progressively.

Background Perivascular inflammation contributes to the development of atherosclerosis and microcirculatory dysfunction. Pericoronary adipose tissue (PCAT) attenuation, measured by coronary computed tomography angiography, is a potential indicator of coronary inflammation. However, the relationship between PCAT attenuation, microcirculatory dysfunction, and periprocedural myocardial injury (PMI) remains unclear. Methods and Results Patients with chronic coronary syndrome who underwent coronary computed tomography angiography before percutaneous coronary intervention were retrospectively identified. PCAT attenuation and adverse plaque characteristics were assessed using coronary computed tomography angiography. The extent of microcirculatory dysfunction was evaluated using the angio‐based index of microcirculatory resistance before and after percutaneous coronary intervention. Overall, 125 consecutive patients were included, with 50 experiencing PMI (PMI group) and 75 without PMI (non‐PMI group). Multivariable analysis showed that older age, higher angio‐based index of microcirculatory resistance, presence of adverse plaque characteristics, and higher lesion‐based PCAT attenuation were independently associated with PMI occurrence (odds ratio [OR], 1.07 [95% CI, 1.01–1.13]; P=0.02; OR, 1.06 [95% CI, 1.00–1.12]; P=0.04; OR, 6.62 [95% CI, 2.13–20.6]; P=0.001; and OR, 2.89 [95% CI, 1.63–5.11]; P

Objectives. In Japan, caudal block with 1% lidocaine is commonly used for transrectal prostate biopsy. Although 10 mL of 1% lidocaine is commonly used, the appropriate dosage of 1% lidocaine has not been studied. Our hospital routinely uses two different doses (5 or 10 mL) of 1% lidocaine for caudal block for transrectal prostate biopsy. Herein, we retrospectively evaluated the efficacy and safety of both doses of 1% lidocaine. Methods. This retrospective study included 869 patients who underwent transrectal prostate biopsy with caudal block at our hospital. The amount of 1% lidocaine was determined by the day of the week on which the biopsy was performed, and the patient voluntarily chose the day of the biopsy, unaware of the dose of 1% lidocaine used on that day. Pain, anal sphincter tonus, cancer diagnosis rate, and early complications were compared. Results. In total, 466 and 403 patients received 5 and 10 mL of 1% lidocaine for a caudal block, respectively. After propensity-score matching for patient characteristics, each group contained 395 patients. The pain score, anal sphincter tonus score, or prostate cancer diagnosis rate were not significantly different between the two groups. However, rectal bleeding was significantly more frequent and severe in the 10-mL than the 5-mL group (p=0.018 and p=0.0036, respectively). The incidence of other complications was not significantly different between the groups. Conclusions. Our results suggest that 5 mL of 1% lidocaine may be more suitable than 10 mL for caudal block during transrectal prostate biopsy.

This study reveals the crease deviation behavior through the developed forming simulation. A combination resistance model was expanded and applied to simulate the 180° folding process of a creased paperboard, using the shear-yield detaching resistance and the out-of-plane fluffing resistance which were based on the isotropic elastro-plastic model. When varying the misalignment of the creasing rule against the groove, the eccentricity of the crease bulging of a white-coated paperboard was compared through the experiment and simulation of the 180° folding process. Comparing the experimental deformation and the simulation, it was explained that the deviation of e contributed to making the crease deviation cd. At the folding test, the 180° folding was compared with the experiment and simulation. The rolling pass of the folded zone was considered to intensify the deviation state. The 180° folding simulation revealed that the crease deviation of cd ≈ 2e was assessed as an ideal condition when using the rolling pass and non-rolling pass. In the case of some shallow indentation in the experiment, 2e < cd < 4e was observed. The inside folded corners were quite different between the simulation and experiment, especially for a certain shallow indentation model. In the simulation, the local crushing was not performed under the assumption of any isotropic properties. In the simulation, the deviation of the creased position at the 180° folding was sufficiently predictable, when compared with experimental behavior.

Abstract Background Subarachnoid hemorrhage and thyroid storm are similar in their clinical symptomatology, and diagnosis of these conditions, when they occur simultaneously, is difficult. Here, we report a rare case of concurrent subarachnoid hemorrhage and thyroid storm we encountered at our hospital. Case presentation The patient was a 52-year-old woman. While bathing at home, the patient experienced a sudden disturbance of consciousness and was brought to our hospital. The main physical findings upon admittance were Glasgow Coma Scale score of E1V2M4, elevated blood pressure (208/145 mmHg), and tachycardia with atrial fibrillation (180 bpm) along with body temperature of 36.1 °C. Brain computed tomography revealed subarachnoid hemorrhage associated with a ruptured aneurysm of the posterior communicating artery branching from the left internal carotid artery, and aneurysm clipping was performed. Blood tests upon admission revealed high levels of free T3 and free T4 and low levels of thyroid-stimulating hormone. Upon determining that the patient had hyperthyroidism, thiamazole was administered. However, due to continuous impaired consciousness, fever, and persistence of tachycardia, the patient was diagnosed with thyroid storm. Oral potassium iodide and hydrocortisone were added to the treatment. The treatment was successful as the patient’s symptoms improved, and she became lucid. In this case, we believe that in the presence of untreated hyperthyroidism, the onset of subarachnoid hemorrhage induced thyroid storm. Tachycardia of 130 bpm or higher, which is the diagnostic criterion for thyroid storm, rarely occurs with subarachnoid hemorrhage. Therefore, we believe it is an important factor for recognizing the presence of the thyroid storm. In this case, clipping surgery was prioritized which resulted in a favorable outcome. However, it is possible that invasive surgery may have exacerbated thyroid storm, suggesting that treatment should be tailored as per patient’s condition. Conclusion If a pulse rate of 130 bpm or higher is observed alongside subarachnoid hemorrhage, we recommend considering the possibility of concomitant thyroid storm and testing for thyroid hormone. If concomitant thyroid storm is present, we believe that a treatment plan tailored to the patient’s condition is critical, and early diagnosis will lead to a favorable outcome for the patient.

Primary central nervous system lymphoma (PCNSL) is a malignant neoplasm of the central nervous system that is refractory to treatment and has extremely poor prognosis. One factor hindering the development of therapeutic options for PCNSL is its molecular heterogeneity and the extreme difficulty in establishing in vitro cell lines that permit intensive research on this disease. In the present study, we developed a method to propagate PCNSL cells in vitro using a contacting transwell cell culture system involving brain vascular pericytes. The co-culture system was found to recapitulate the tumor microenvironment that is influenced by the biological activity of adjacent pericytes, and to sustain the survival and proliferation of PCNSL cells in vitro. We further delineated the underlying molecular mechanisms and found that the HGF–c-Met axis may be involved in the long-term in vitro culture of PCNSL cells. Moreover, the peptidylprolyl isomerase Pin1 was found to play a key role in PCNSL cell survival and it sustained proliferation through interactions with key transcription factors related to B-cell lymphomagenesis. These results suggest that our in vitro co-culture system is well suited to analyzing the biological and molecular characteristics of PCNSL, and may contribute to the discovery of new therapeutic interventions.

Monodisperse polystyrene particles were first synthesized by soap-free emulsion polymerization to enhance the monodispersity of hollow particles. Thereafter, the polystyrene particles were immersed in an aqueous solution of 2,2′-azobis(2-methylbutyronitrile) (V-59) to allow the particles to absorb V-59 while maintaining their monodispersity. Thermogravimetric measurements using p-styrenesulfonic acid sodium salt revealed that this absorption occurred not through electrostatic interactions but through hydrophobic ones. Subsequently, the TEOS sol-gel reaction was performed on the polystyrene particle surface to create a silica shell with the help of N-vinyl acetoamide. Finally, the synthesized particles were heated to induce the decomposition reaction of V-59 (which emits nitrogen gas) in the particles, thereby creating a hollow structure as the gas stayed in the particle. These procedures enabled the synthesis of monodisperse hollow particles.

In Japanese hospitals, patients undergoing invasive procedures or surgery are screened for anti-HCV antibodies; however, the majority of possible HCV careers are not referred to hepatologists. In addition to the conventional alert email system, a hepatologist extracted monthly lists of anti-HCV-antibody-positive patients who had been tested two months previously and checked medical records to determine whether the doctors who ordered the tests had properly dealt with the positive results. If the doctors had not yet properly followed up, the hepatologist would send emails to both the doctor and a medical clerk to inform them to conduct an HCV-RNA test and to refer HCV-RNA-positive patients to hepatologists. In total, 130 patients managed in the pre-intervention period and 151 patients managed in the post-intervention period were included in this study. The number of anti-HCV-positive patients whose results were not properly handled showed a significant decrease after the introduction of the double alert system (p = 0.034). Among patients undergoing screening anti-HCV antibody testing, a significant number of patients with probable chronic HCV hepatitis were overlooked by the email alert system and their results were not properly handled. The double alert system was useful for reducing the number of positive anti-HCV antibody patients whose results were not properly handled.

The enhanced reaction rate in the epoxidation of cyclohexene with air as an oxidant was discovered without any added catalyst utilizing a continuous flow reactor constructed with readily available stainless steel parts and devices. This continuous-flow process demonstrates a significant improvement in reaction time for highly selective epoxide production over the batch process due to the efficient mass transfer between the liquid phase and air. The flow process discovered was operated continuously with good operational stability, evaluated by a constant high yield of cyclohexene oxide, to obtain the desired product with high productivity.

Sonic hedgehog (Shh) signaling pathways are known to play an important role in the morphological development of the hippocampus in vivo, but their actual roles in humans have not been clarified. Hypothalamic hamartoma (HH) is known to be associated with germline or somatic gene mutations of Shh signaling. We hypothesized that patients with HH and mutations of Shh-related genes also show hippocampal maldevelopment and an abnormal hippocampal infolding angle (HIA). We analyzed 45 patients (age: 1–37 years) with HH who underwent stereotactic radiofrequency thermocoagulation and found Shh-related gene mutations in 20 patients. In addition, 44 pediatric patients without HH (age: 2–25 years) who underwent magnetic resonance imaging (MRI) examinations under the same conditions during the same period were included in this study as a control group. HIA evaluated on MRI was compared between patients with gene mutations and the control group. The median HIA at the cerebral peduncle slice in patients with the gene mutation was 74.36° on the left and 76.11° on the right, and these values were significantly smaller than the corresponding values in the control group (80.46° and 80.56°, respectively, p

Background: Risk-benefit analysis results for the treatment of unruptured aneurysms smaller than 5 mm are controversial. This study aimed to identify the outcomes and complication associated with treating such unruptured aneurysms. Methods: This was a retrospective study of 165 consecutive patients who underwent endovascular procedures for unruptured cerebral aneurysms of a maximum diameter 5 mm between January 2018 and March 2021. Patient background, aneurysm characteristics, adjuvant technique, volume embolization rate (VER), symptomatic complications, and modified Rankin Scale (mRS) scores were examined. Results: Sixty patients with sufficient data were included in the study. The mean age was 62.1 ± 14.6 years, and the median follow-up period was 12 months. The mean maximum diameter was 4.16 ± 0.63 mm, the neck diameter was 2.73 ± 0.82 mm, and 90% of patients had anterior circulation. Complete occlusion was achieved in 34 cases (57.6%). Although there were no intraoperative ruptures, complications were observed in four patients (6.7%), and one patient (1.7%) had worsened mRS score. Only one patient (1.7%) required retreatment. The first coil VER was independently associated with complete occlusion after endovascular treatment. Univariate analysis of complications showed an association between hypertension, hyperlipidaemia, and the estimated glomerular filtration rate. Conclusions: No patient experienced mRS score deterioration, and only one patient developed permanent disability due to ischemic complications; hence, we could safely treat small unruptured aneurysms. Complications are not related to procedural factors such as coiling adjuvant technique. However, lifestyle-related diseases are related to complications, and we suggest that physicians should remain vigilant of the indication for coiling when treating patients with underlying diseases.

Abstract The influence of repeated lockdowns on mental health and social isolation is unknown. We conducted a longitudinal study of the influence of repeated mild lockdowns during two emergency declarations in Japan, in May 2020 and February 2021. The analyses included 7893 people who participated in all online surveys. During repeated mild lockdowns, mental and physical symptoms decreased overall, while loneliness increased and social networks decreased. Subgroup analyses revealed that depression and suicidal ideation did not decrease only in the younger age group (aged 18–29 years) and that younger and middle-aged people (aged 18–49 years), women, people with a history of treatment for mental illness, and people who were socially disadvantaged in terms of income had higher levels of mental and physical symptoms at all survey times. Additionally, comprehensive extraction of the interaction structure between depression, demographic attributes, and psychosocial variables indicated that loneliness and social networks were most closely associated with depression. These results indicate that repeated lockdowns have cumulative negative effects on social isolation and loneliness and that susceptible populations, such as young people and those with high levels of loneliness, require special consideration during repeated lockdown situations.

To enhance the mechanical properties of carbon-fiber-reinforced thermoplastics, it is important to improve the interfacial shear strength (IFSS) between carbon fibers and thermoplastic resins such as poly(methyl methacrylate) (PMMA). In this study, PMMA particles were synthesized through soap-free emulsion polymerization using 2,2′-azobis(2-methylpropionamidine) dihydrochloride. The particles were dispersed in n-butanol, which had a low surface energy and good wettability for carbon fibers. The amount of PMMA particles adsorbed on the carbon fibers increased with the immersion time. In addition, it was considerably larger than the amount of PMMA particles adsorbed on the carbon fibers when water was used as a solvent. The surface of the carbon fibers was coated with PMMA particles to prevent the generation of voids during the hot-press process. Therefore, the IFSS increased with the amount of adsorbed PMMA particles. The results show that it is important to select a dispersion solvent with good wettability for carbon to improve the adsorption of particles on carbon fibers.

Background: Many health care workers around the world tackled with COVID-19, however sadly, the infection of many medical care workers were reported. To reduce the risk of infection, we launched selected team (Team COVID) of non-specialists and brought in active telemedicine method and computed tomography (CT)-first protocol. We describe our actual practice and the health status of medical doctors dealing with COVID-19 patients. Methods: Between April 17, 2020 and May 24, 2020, 10 doctors worked with COVID-19 patients as part of Team COVID. The Team COVID doctors used a CT-first triage protocol for outpatients and telemedicine for inpatients and outpatients. We evaluated paired serum-specific antibodies for SARS-CoV-2 at the initial and end of the study duration and PCR results for SARS-CoV-2 at the end of the study duration. Furthermore, 36-item short-form of the Medical Outcome Study Questionnaire (SF-36) at the beginning and end of the study period were evaluated. Results: Ten doctors worked as Team COVID: seven internal medicine doctors and three surgeons. During the study period, Team COVID treated 165 individuals in the outpatient clinic and isolated hospitalized patients for 315 person-days. There were no positive results of serum-specific antibody testing and PCR testing for SARS-CoV-2 in Team COVID doctors. Furthermore, the SF-36 showed no deterioration in physical and mental QOL status. No in-hospital infection occurred during the study period. Conclusions: The Team COVID fulfilled the treatment using the active telemedicine and CT-first triage protocol without in hospital infection and excess stress. The combination strategy seems acceptable for both the protection and stress relief among the medical staff.

Abstract The primary motor cortex (M1) is crucial for motor learning; however, its interaction with other brain areas during motor learning remains unclear. We hypothesized that the fronto-parietal execution network (FPN) provides learning-related information critical for the flexible cognitive control that is required for practice. We assessed network-level changes during sequential finger tapping learning under speed pressure by combining magnetic resonance spectroscopy and task and resting-state functional magnetic resonance imaging. There was a motor learning-related increase in preparatory activity in the fronto-parietal regions, including the right M1, overlapping the FPN and sensorimotor network (SMN). Learning-related increases in M1-seeded functional connectivity with the FPN, but not the SMN, were associated with decreased GABA/glutamate ratio in the M1, which were more prominent in the parietal than the frontal region. A decrease in the GABA/glutamate ratio in the right M1 was positively correlated with improvements in task performance (p = 0.042). Our findings indicate that motor learning driven by cognitive control is associated with local variations in the GABA/glutamate ratio in the M1 that reflects remote connectivity with the FPN, representing network-level motor sequence learning formations.

AimNumerous reports have demonstrated the key importance of macrophage-elicited metabolic inflammation in insulin resistance (IR). Our previous studies confirmed that hyperuricemia or high uric acid (HUA) treatment induced an IR state in several peripheral tissues to promote the development of type 2 diabetes mellitus (T2DM). However, the effect of HUA on glucose uptake and the insulin sensitivity of macrophages and its mechanism is unclear.MethodsTo assess systemic IR, we generated hyperuricemic mice by urate oxidase knockout (UOX-KO). Then, glucose/insulin tolerance, the tissue uptake of 18F-fluorodeoxyglucose, body composition, and energy balance were assessed. Glucose uptake of circulating infiltrated macrophages in the liver was evaluated by glucose transporter type 4 (GLUT-4) staining. Insulin sensitivity and the insulin signaling pathway of macrophages were demonstrated using the 2-NBDG kit, immunoblotting, and immunofluorescence assays. The immunoprecipitation assay and LC-MS analysis were used to determine insulin receptor substrate 2 (IRS2) levels and its interacting protein enrichment under HUA conditions.ResultsCompared to WT mice (10 weeks old), serum uric acid levels were higher in UOX-KO mice (WT, 182.3 ± 5.091 μM versus KO, 421.9 ± 45.47 μM). Hyperuricemic mice with metabolic disorders and systemic IR showed inflammatory macrophage recruitment and increased levels of circulating proinflammatory cytokines. HUA inhibited the nuclear translocation of GLUT-4 in hepatic macrophages, restrained insulin-induced glucose uptake and glucose tolerance, and blocked insulin IRS2/PI3K/AKT signaling. Meanwhile, HUA mediated the IRS2 protein degradation pathway and activated AMPK/mTOR in macrophages. LC-MS analysis showed that ubiquitination degradation could be involved in IRS2 and its interacting proteins to contribute to IR under HUA conditions.ConclusionThe data suggest that HUA-induced glucose intolerance in hepatic macrophages contributed to insulin resistance and impaired the insulin signaling pathway via IRS2-proteasome degradation

Introduction: Vertebral artery injury (VAI) due to blunt cervical spine injury (BCSI) can cause severe cerebral infarction. This study aimed to evaluate the risks of cerebral infarction and to develop a brain screening algorithm in patients with BCSI. Methods: We examined the characteristics of 37 consecutive patients diagnosed with BCSI at our institute between January 2017 and April 2021 and retrospectively analyzed the risk factors for post-trauma cerebral infarction, such as patient background characteristics, fracture side and level, vertebral artery (VA) status, details of treatment, and complications. Results: A total of 12 patients (32.4%) had VAI, of whom six were treated with intravascular coil embolization to prevent cerebral infarction after cervical spine surgery. Of the five patients (13.5%) with cerebral infarction, four had VAI and one had intact VAs but with a fracture of the intervertebral foramen on the dominant side of the VA (illustrative case). Only the presence of VAI showed a significant difference in the risk of cerebral infarction onset (p = 0.015). Coil embolization did not increase the risk of postoperative cerebral infarction (p = 0.12). Conclusion: VAI was the only risk factor for the development of cerebral infarction in patients with BCSI, suggesting that head magnetic resonance imaging (MRI) screening is recommended for those with VAI. In patients without VAI, vertebral fractures on the dominant side of the VA might be a risk for cerebral infarction, indicating that head MRI screening should also be considered in these patients.

Abstract Background The nasal to temporal amplitudes ratio (N/T) of multifocal electroretinography (mfERG) scans measured within 5° of the macula can be used to detect glaucomatous change. The photopic negative response (PhNR) of mfERG elicited by a circular stimulus centered on the fovea was significantly reduced in eyes with glaucoma. The PhNR to B-wave ratio (PhNR/B) is the optimal measure of the PhNR. However, clinical superiority for evaluating glaucoma patients has not been determined between N/T and PhNR/B yet. Methods For morphological assessments, ganglion cell complex (GCC) in six regions and the average were measured by optical coherence tomography (OCT). For functional assessment, Humphrey visual fields (VF) with mean sensitivities (MT) and mfERG scans with parameters of N/T and the multifocal photopic negative response to B-wave ratio (mfPhNR/B) were measured. Sixty-nine eyes of 44 glaucoma patients were included and correlations between mfERG parameters and OCT or VF parameters were evaluated. Results The mean age of patients was 59.4 years. The mean deviation for all eyes obtained with the VF 30–2 and VF 10–2 was − 7.00 and − 6.31 dB, respectively. Significant correlations between GCC thickness or VF parameter and the N/T were found, especially in the inferior and inforotemporal retinal areas corresponding to superior and superonasal VF sectors (GCC vs N/T; coefficient = − 7.916 and − 7.857, and MT vs N/T; coefficient = − 4.302 and − 4.437, in the inferior and inforotemporal retinal areas, respectively, all p values

Abstract Background Cannabidiol (CBD), the non-psychotropic compound from Cannabis sativa, shows positive results on controlling several health disturbances; however, comparable data regarding additional chemical from C. sativa, such as cannabidiolic acid (CBDA), is scarce due to its instability. To address this limitation, a stable CBDA analogue, CBDA methyl ester (HU-580), was synthetized and showed CBDA-like effects. Recently, we described that HU-580 increased wakefulness and wake-related neurochemicals. Objective To extend the comprehension of HU-580´s properties on waking, the c-Fos and NeuN expression in a wake-linked brain area, the hypothalamus was evaluated. Methods c-Fos and NeuN expression in hypothalamic sections were analyzed after the injections of HU-580 (0.1 or 100 μg/kg, i.p.). Results Systemic administrations of HU-580 increased c-Fos and neuronal nuclei (NeuN) expression in hypothalamic nuclei, including the dorsomedial hypothalamic nucleus dorsal part, dorsomedial hypothalamic nucleus compact part, and dorsomedial hypothalamic nucleus ventral part. Conclusion HU-580 increased c-Fos and NeuN immunoreactivity in hypothalamus nuclei suggesting that this drug might modulate the sleep–wake cycle by engaging the hypothalamus.

Paraspeckles are nuclear bodies scaffolded by RNP complexes of NEAT1_2 RNA transcripts and multiple RNA-binding proteins. The assembly of paraspeckles is coupled with the transcription of NEAT1_2. Paraspeckles form the core-shell structure, where the two terminal regions of NEAT1_2 RNP complexes compose the shell of the paraspeckle and the middle regions of these complexes compose the core. We here construct a theoretical model of paraspeckles by taking into account the transcription of NEAT1_2 in an extension of the theory of block copolymer micelles. This theory predicts that the core-shell structure of a paraspeckle is assembled by the association of the middle region of NEAT1_2 RNP complexes due to the multivalent interactions between RBPs bound to these regions and by the relative affinity of the terminal regions of the complexes to the nucleoplasm. The latter affinity results in the effective repulsive interactions between terminal regions of the RNA complexes and limits the number of complexes composing the paraspeckle. In the wild type, the repulsive interaction between the middle and terminal block dominates the thermal fluctuation. However, the thermal fluctuation can be significant in a mutant, where a part of the terminal regions of NEAT1_2 is deleted, and distributes the shortened terminal regions randomly between the shell and the core, consistent with our recent experiments. With the upregulated transcription, the shortened terminal regions of NEAT1_2 in a deletion mutant is localized to the core to decrease the repulsive interaction between the terminal regions, while the structure does not change with the upregulation in the wild type. The robustness of the structure of paraspeckles in the wild type results from the polymeric nature of NEAT1_2 complexes.

Phase separation is a fundamental mechanism for compartmentalization in cells and leads to the formation of biomolecular condensates, generally containing various RNA molecules. RNAs are biomolecules that can serve as suitable scaffolds for biomolecular condensates and determine their forms and functions. Many studies have focused on biomolecular condensates formed by liquid-liquid phase separation (LLPS), one type of intracellular phase separation mechanism. We recently identified that paraspeckle nuclear bodies use an intracellular phase separation mechanism called micellization of block copolymers in their formation. The paraspeckles are scaffolded by NEAT1_2 long non-coding RNAs (lncRNAs) and their partner RNA-binding proteins (NEAT1_2 RNA-protein complexes [RNPs]). The NEAT1_2 RNPs act as block copolymers and the paraspeckles assemble through micellization. In LLPS, condensates grow without bound as long as components are available and typically have spherical shapes to minimize surface tension. In contrast, the size, shape, and internal morphology of the condensates are more strictly controlled in micellization. Here, we discuss the potential importance and future perspectives of micellization of block copolymers of RNPs in cells, including the construction of designer condensates with optimal internal organization, shape, and size according to design guidelines of block copolymers.

Evidence regarding coronavirus disease 2019 vaccination indicates that some people hesitate to be vaccinated, and previous studies demonstrate the variables that influence hesitancy to vaccinate. However, they have not limited the target population to areas where infection is prominent. This study aimed to clarify the characteristics of people living in these areas who hesitate to be vaccinated and recommend effective approaches to encourage vaccination.The survey was conducted online between February 24 and March 1, 2021, during which the 2nd state of emergency was declared in Japan. The analytic sample comprised 17,582 unvaccinated individuals (mean age ​= ​48.6 ​± ​13.8, range ​= ​18–90 years). The t-test results indicate that current or past treatment for physical illness exerted a strong influence on vaccine hesitancy (ds ​= ​0.30). Similarly, multiple regression analyses revealed that understanding the importance and necessity for preventive behaviors had the greatest influence on the intention to vaccinate (β ​= ​0.48). Regarding recommendations to promote willingness to be vaccinated, our findings indicated that clear explanation of the reasons for the necessity for these behaviors and collaboration between representatives of various communities would effectively encourage vaccination.

Meningioma is the most common primary neoplasm of the central nervous system (CNS). Generally, these tumors are benign and have a good prognosis. However, treatment can be challenging in cases with aggressive variants and poor prognoses. Among various prognostic factors that have been clinically investigated, bone invasion remains controversial owing to a limited number of assessments. Recent study reported that bone invasion was not associated with WHO grades, progression, or recurrence. Whereas, patients with longer-recurrence tended to have a higher incidence of bone invasion. Furthermore, bone invasion may be a primary preoperative predictor of the extent of surgical resection. Increasing such evidence highlights the potential of translational studies to understand bone invasion as a prognostic factor of meningiomas. Therefore, this mini-review summarizes recent advances in pathophysiology and diagnostic modalities and discusses future research directions and therapeutic strategies for meningiomas with bone invasion.

BackgroundLockdowns and stay-at-home orders announced internationally for COVID-19 have led to physical and social distancing, with reports of many individuals experiencing social isolation (SI) and loneliness. Although the emergency declaration in Japan was declared as a “mild” lockdown requested by the government without penalties for violations, the lockdown measures, including SI, had several influences on people’s lives and mental health as in other countries. Furthermore, Japan declared a state of emergency multiple times; thus, it is necessary to examine the influence of the transition of SI caused by repeated emergency declarations and the deterioration of mental health associated with these changes. ObjectiveThis study longitudinally investigated the transition of SI and its related factors during the mild lockdown under 2 declared states of emergency in Japan and analyzed psychosocial characteristics by extracting clusters where people with specific transition patterns of SI predominated. MethodsWe collected data on 7893 inhabitants (3694 [46.8%] women, 49.6 [SD 13.7] years old) living in the 7 prefectures where the initial emergency declaration was applied. The investigations took place online in the final phase of the first and second states of emergency: phase 1 (between May 11 and 12, 2020) and phase 2 (between February 24 and 28, 2021). Nonparametric Bayesian coclustering was used to visualize the exhaustive interaction structure between the transition pattern of SI and the psychosocial variables. ResultsThere were no improvements in social networks and loneliness between the 2 phases, although psychological distress significantly improved and depression slightly decreased. Overall, 3868 (49%) of the 7893 participants remained socially isolated through phases 1 and 2, and 947 (12%) were socially isolated in phase 2, even though they were not socially isolated in phase 1. More participants experienced persistent SI in unmarried, childless, and low-household-income groups. The persistent-SI group had fewer cohabitants than other transition pattern groups. The nonparametric Bayesian coclustering results showed that most clusters, including participants without SI throughout phases 1 and 2, had healthy behaviors, more interactions, good relationships, and less loneliness and psychological stress. Furthermore, the cluster in which relationships deteriorated in phase 1 recovered in phase 2. Comparatively, the clusters with SI throughout phases 1 and 2 were divided into clusters with increased loneliness and psychological stress; clusters were close to participants’ average scores in this study. The clusters with increased loneliness and psychological stress were notable for deteriorating relationships and less online interaction. ConclusionsThis study revealed the actual state of transition of SI and related psychological, social, and behavioral factors under repeated declarations of a state of emergency. These results should help construct intervention methods that fit individual characteristics of people in SI during a pandemic.

Abstract Background Perigraft inflammatory reactions to prosthetic graft materials in vascular surgery have been reported; however, to our knowledge, this is the first report of a perigraft inflammatory reaction to a Viabahn stent-graft used in a superficial femoral artery occlusion lesion. Case presentation A 76-year-old man with right leg claudication was diagnosed with a right superficial femoral artery occlusion via contrast-enhanced computed tomography. Endovascular treatment included intravascular ultrasound for passing through the true lumen. A 25-cm Viabahn stent-graft (diameter 5 mm) was implanted. The patient developed pain and local swelling of the right thigh 5 days after endovascular treatment. Blood analysis revealed elevated inflammatory marker levels. Magnetic resonance imaging revealed extensive soft-tissue edema and a high perivascular T2 signal around the right superficial femoral artery. Clinical symptoms resolved within 7 days after initiating steroid therapy, which was gradually decreased and halted after 3 weeks. Follow-up magnetic resonance imaging demonstrated substantially reduced inflammation over the following months. Conclusions Perigraft inflammatory reaction to a Viabahn stent-graft implant can be immediately diagnosed via magnetic resonance imaging and treated with steroids to reduce the possibility of stent-graft occlusion.

Abstract We present a case of a 14-year old boy with tumor-associated refractory epilepsy. Positron emission tomography imaging demonstrated a region with heterogeneous high 11C-methionine uptake and a region with homogenous low 18F-fluorodeoxyglucose uptake within the tumor. Histopathological and genomic analyses confirmed the tumor as BRAF V600E-mutated polymorphous low-grade neuroepithelial tumor of the young (PLNTY). Within the high-methionine-uptake region, we observed increased protein levels of L-type amino acid transporter 1 (LAT1), a major transporter of methionine; c-Myc; and constituents of the mitogen-activated protein kinase (MAPK) pathway. We also found that LAT1 expression was linked to the BRAF V600E mutation and subsequent activation of MAPK signaling and c-Myc. Pharmacological and genetic inhibition of the MAPK pathway suppressed c-Myc and LAT1 expression in BRAF V600E-mutated PLNTY and glioblastoma cells. The BRAF inhibitor dabrafenib moderately suppressed cell viability in PLNTY. Collectively, our results indicate that BRAF V600E mutation-activated MAPK signaling and downstream c-Myc induces specific metabolic alterations in PLNTY, and may represent an attractive target in the treatment of the disease.

Abstract Background Sex-related differences of plantar pressure distribution during activities should be thoroughly inspected as it can help establish treatment and prevention strategies for foot and ankle problems. In-shoe measurement systems are preferable without space and activity restrictions; however, previously reported systems are still heavy and bulky and induce unnatural movement. Therefore, a slim and light plantar pressure sensor was newly developed to detect the effect of sex difference on plantar pressure during standing and walking. Methods One-hundred healthy adult volunteers (50 women and 50 men) were recruited. Ten plantar pressure sensors were implanted in a 1-mm thick insole, with a total weight of 29 g. Plantar pressure was recorded with 200 Hz during 3 s of standing and while walking 10 steps. The maximum loads during standing and walking were analyzed in each sensor, and the results were compared between different areas of the foot in the antero-posterior direction and the medio-lateral direction and between different time points. The movement of the center of pressure (COP) during walking was also evaluated. Analyses were adjusted for body mass index and gait speed. Results The movement of COP was constant for both sexes. In all cases, the maximum load was observed on the medial of the foot. Women had a significantly higher peak pressure on the hallux, toes, forefoot, and medial aspect of the foot compared to men while standing and walking (p

To date, a neuroscientific investigation of drivers' steering behavior has never been performed because the reaction forces generated by the mechanical characteristics of a steering wheel have been difficult to assess in a magnetic resonance imaging (MRI) environment. In this study, using our previously developed MRI-compatible unit for steering reaction force generation, we investigated changes in human brain activity induced by varying the viscoelastic characteristics associated with manipulating a car steering wheel. Participants performed a simulated driving task with three levels of stiffness and viscosity. An amplitude effect of reaction forces on the measured brain activity due to varying stiffness was found in the primary motor cortex (M1) associated with hand representation. Conversely, the changes in the brain activity induced by varying viscosity were found more dorsally in the premotor cortex and the M1 than in regions associated with hand representation. These results are the first to demonstrate that various viscoelastic characteristics activate different motor regions; more specifically, stiffness and viscosity of the steering wheel mainly affected the motor control of the distal and proximal muscles, respectively.

BackgroundEpidemiological contact tracing is a powerful tool to rapidly detect SARS-CoV-2 infection in persons with a close contact history with COVID-19-affected patients. However, it remains unclear whom and when should be PCR tested among the close contact subjects.MethodsWe retrospectively analyzed 817 close contact subjects, including 144 potentially SARS-CoV-2-infected persons. The patient characteristics and contact type, duration between the date of the close contact and specimen sampling, and PCR test results in PCR positive and negative persons were compared.ResultsWe found that male gender {adjusted odds ratio 1.747 [95% confidence interval (CI) 1.180–2.608]}, age ≥ 60 [1.749 (95% CI 1.07–2.812)], and household contact [2.14 (95% CI 1.388–3.371)] are independent risk factors for close contact SARS-CoV-2 infection. Symptomatic subjects were predicted 6.179 (95% CI 3.985–9.61) times more likely to be infected compared to asymptomatic ones. We could observe PCR test positivity between days 1 and 17 after close contact. However, no subject could be found with a Ct-value

The aim of the current overview was to present the existing literature on the recent phenomenon of eSports. Using a multifaceted approach, we focused on its definitions, historical development, and classification, drawing attention to key disputes that exist between scholars. Furthermore, we investigated the debate on whether eSports should be considered a traditional sport or not, with a particular interest in two processes that have contributed to eSports’ development as a culturally-significant addition to the world of sports, as both a game and an occupation: sportification and professionalization. Lastly, we analysed studies on spectatorship and consumption to understand why people watch and play eSports pointing out data about the recent relationship between practice and the possible development of eSport's addiction, gambling, and the related impact on individual health and wellbeing.

Emotional contagion is a phenomenon by which an individual’s emotions directly trigger similar emotions in others. We explored the possibility that perceiving others’ emotional facial expressions affect mood in people with subthreshold depression (sD). Around 49 participants were divided into the following four groups: participants with no depression (ND) presented with happy faces; ND participants presented with sad faces; sD participants presented with happy faces; and sD participants presented with sad faces. Participants were asked to answer an inventory about their emotional states before and after viewing the emotional faces to investigate the influence of emotional contagion on their mood. Regardless of depressive tendency, the groups presented with happy faces exhibited a slight increase in the happy mood score and a decrease in the sad mood score. The groups presented with sad faces exhibited an increased sad mood score and a decreased happy mood score. These results demonstrate that emotional contagion affects the mood in people with sD, as well as in individuals with ND. These results indicate that emotional contagion could relieve depressive moods in people with sD. It demonstrates the importance of the emotional facial expressions of those around people with sD such as family and friends from the viewpoint of emotional contagion.