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Seiko Miyata,1,* Kunihiro Iwamoto,1,* Ippei Okada,1,* Akihiro Fujimoto,2 Yuki Kogo,2 Daisuke Mori,1,3,4 Manabu Amano,5 Nao Matsuyama,5 Kazuki Nishida,5 Masahiko Ando,5 Toshiaki Taoka,6 Shinji Naganawa,7 Norio Ozaki1,4 1Department of Psychiatry, Nagoya University, Graduate School of Medicine, Nagoya, Japan; 2Medical Headquarters, Eisai Co., Ltd., Tokyo, Japan; 3Brain and Mind Research Center, Nagoya University, Nagoya, Japan; 4Pathophysiology of Mental Disorders, Nagoya University, Graduate School of Medicine, Nagoya, Japan; 5Department of Advanced Medicine, Nagoya University Hospital, Nagoya, Japan; 6Department of Innovative Biomedical Visualization (Ibmv), Nagoya University, Graduate School of Medicine, Nagoya, Japan; 7Department of Radiology, Nagoya University, Graduate School of Medicine, Nagoya, Japan*These authors contributed equally to this workCorrespondence: Seiko Miyata, Department of Psychiatry, Nagoya University, Graduate School of Medicine, 65 Tsurumai, Showa, Nagoya, Aichi, 466-8550, Japan, Tel +81 52 744 2282, Fax +81 52 744 2293, Email miyata.seiko.v4@f.mail.nagoya-u.ac.jpPurpose: Both subjective and objective evaluations are essential for the treatment of insomnia. Lemborexant has been shown to be effective in the long-term based solely on a subjective basis, and no long-term objective measures have been evaluated under natural sleep conditions. Small, lightweight sleep electroencephalogram (EEG) monitor was used, instead of polysomnography, to objectively evaluate sleep at home 4 and 12 weeks after lemborexant treatment.Patients and Methods: Adults and elderly subjects with insomnia disorder, per the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, were enrolled in this open-label, single-arm, single-center trial. Objective and subjective measures of sleep were prospectively assessed. Sleep disturbance, excessive sleepiness, and depressive symptoms were assessed using questionnaires.Results: A total of 45 subjects were screened, of which 33 were enrolled. Paired t-tests were conducted to evaluate changes in sleep variables and compared with the baseline; subjects showed significant improvements in objective sleep efficiency (SE) and subjective sleep parameters at weeks 4 and 12 following treatment with lemborexant. When baseline values were taken into account, a repeated-multivariate analysis of variance (MANOVA) revealed statistically significant changes in the objective measures. Sleep disturbance, excessive sleepiness, and depressive symptoms improved after three months of lemborexant treatment.Conclusion: Furthermore, lemborexant therapy improved nocturnal sleep, when measured objectively using sleep EEG monitoring at home, and improved daytime sleepiness and depressive symptoms in older adults with insomnia disorder.Keywords: insomnia, lemborexant, objective sleep evaluation, portable sleep EEG monitoring, subjective sleep evaluation

The purpose of this study is to clarify the Morphorogical Viewpoint on Movement Observation from phenomenological standpoint. Generally, Movement Observation is interpreted by two viewpoints. First is the Morphological Viewpoint (MOV) which is based on phenomenological morphology. Second is the Mechanistic Viewpoint, which is based on physics. The former corresponds to the core ability of coaches and physical teachers (Meinel, 1981) because the MOV is focused on the generation of movement. However some coaches and physical teachers cannot properly interpret the MOV (Meinel, 1981; Muraki, 1993). In some previous studies, the MOV has been interpreted from applying Gestaltkreis (Weizsäcker, 1940) which is a phenomenological hermeneutic figure for perceiving sound of “Melody of Movement” (Buytendijk, 1958). However, MOV’s Perceptual Phenomenon has not been directly clarified as hermeneutic figure. Because of this, this study deductively analyzes Perceptual Phenomenon of MOV from the relevance of consciousness and perception. On the base of their relevance, this study furthermore conceptualizes “Doppelter Gestaltkreis” which is a hermeneutic figure for directive interpretation of MOV’s Perceptual Phenomenon. This study further discusses the utility of Doppelter Gestaltkreis for enlarging the observation horizon of coaches and physical teachers.

A 9-year-old boy was suspected of having acute myocardial infarction and emergency coronary angiogram was performed. No signs of flow limitation in either coronary artery was detected. We performed intravascular ultrasonography from the ascending aorta, which showed a ridge on the left main trunk acting like a valve, resulting in significant stenosis. Percutaneous coronary intervention with stent deployment was performed with good result., Competing Interests: The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2024 The Authors.)

As the effective use of carbon resources has become a pressing societal issue, the importance of chemical recycling of plastics has increased. The catalytic chemical decomposition for plastics is a promising approach for creating valuable products under efficient and mild conditions. Although several commodity and engineering plastics have been applied, the decompositions of stable resins composed of strong main chains such as polyamides, thermoset resins, and super engineering plastics are underdeveloped. Especially, super engineering plastics that have high heat resistance, chemical resistance, and low solubility are nearly unexplored. In addition, many super engineering plastics are composed of robust aromatic ethers, which are difficult to cleave. Herein, we report the catalytic depolymerization-like chemical decomposition of oxyphenylene-based super engineering plastics such as polyetheretherketone and polysulfone using thiols via selective carbon-oxygen main chain cleavage to form electron-deficient arenes with sulfur functional groups and bisphenols. The catalyst combination of a bulky phosphazene base P 4 -tBu with inorganic bases such as tripotassium phosphate enabled smooth decomposition. This method could be utilized with carbon- or glass fiber-enforced polyetheretherketone materials and a consumer resin. The sulfur functional groups in one product could be transformed to amino and sulfonium groups and fluorine by using suitable catalysts., (© 2024. The Author(s).)

Background: The use of Bio 3D nerve conduits is a promising approach for peripheral nerve reconstruction. This study aimed to assess their safety in three patients with peripheral nerve defects in their hands., Methods: We describe a single institution, non-blinded, non-randomised control trial conducted at Kyoto University Hospital. Eligibility criteria included severed peripheral nerve injuries or a defect in the region distal to the wrist joint not caused by a congenital anomaly; a defect with a length of ≤20 mm in a nerve with a diameter ≤2 mm; failed results of sensory functional tests; ability to register in the protocol within 6 months from the day of injury; refusal of artificial nerve or autologous nerve transplantation; age 20-60 years; and willingness to participate and provide informed written consent. Six weeks before transplantation, skin was harvested, dermal fibroblasts were isolated and expanded, and Bio 3D nerve conduits were created using a Bio 3D printer. Bio 3D nerve conduits were transplanted into the patients' nerve defects. The safety of Bio 3D nerve conduits in patients with a peripheral nerve injury in the distal part of the wrist joint were assessed over a 48-week period after transplantation., Results: No adverse events related to the use of Bio 3D nerve conduits were observed in any patient, and all three patients completed the trial., Conclusions: Bio 3D nerve conduits were successfully used for clinical nerve reconstruction without adverse events and are a possible treatment option for peripheral nerve injuries., (© 2024. The Author(s).)

Background: The aim was to investigate the incidence and clinical predictive factors of de novo overactive bladder (OAB) after robot-assisted radical prostatectomy (RARP), including a Retzius-sparing (RS) approach, in the same period at a single institution., Methods: Of a total of 113 patients with localized prostate cancer, 81 received conventional RARP (CON-RARP) and 32 received RS-RARP at our institution. The basic characteristics data of patients and self-assessment questionnaires, including IPSS and OABSS, were obtained preoperatively and 1, 3, and 6 months after RARP. In addition, a retrospective biomarker analysis was also performed of predictive clinical parameters obtained from cystography that included a postoperative bladder neck to pubic symphysis (BNPS) ratio., Results: Patients' basic characteristics were similar between CON-RARP and RS-RARP groups. With respect to the surgical procedure, anastomosing time was found to be significantly longer for patients in the RS-RARP compared to the CON-RARP group ( p < 0.01). Compared to the CON-RARP group, the RS-RARP group showed a significantly lower postoperative BNPS and aspect ratio ( p < 0.001). The incidence of de novo OAB in patients of the CON-RARP group was greater than for those in the RS-RARP group (40.7% CON-RARP vs. 25.0% RS-RARP), though this was not significant. Regarding the emergence of de novo OAB, the following were revealed in univariate analysis to be independent prognostic factors: age > 64 years (hazards ratio [HR]: 4.32, 95% confidence interval [CI]: 1.51-12.3), postoperative BNPS ratio > 0.44 (HR: 8.7, 95% CI: 6.43-54.5), postoperative aspect ratio > 1.18 (HR: 3.36, 95% CI: 1.49-7.61). Additionally, multivariate analysis identified a sole significant prognostic factor: postoperative BNPS ratio > 0.44 (HR: 13.3, 95% CI: 4.33-41.1)., Conclusion: Our findings indicate that the postoperative BNPS ratio may be a practical predictive indicator of the emergence of de novo OAB after RARP.

A key challenge in haptics is designing human-human communications involving touch to facilitate positive effects on social interactions. An important consideration in designing social touch is understanding the effect of social stimuli on perception, in addition to that of a physical stimulus, because social touch always involves a partner. This study presents an experiment to demonstrate that facial expressions induce haptic perception. We developed a human-agent interaction system on a display in which participants moved the mouse cursor to click the target icon while the agent behaved as if it pulled the cursor back in the opposite direction, showing either a negative or neutral face. The perceived force during the interaction was quantified by the control display ratio using a psychophysical approach. The results show that the negative face induced a significantly greater perceived force than the neutral face. In addition, the perceived force correlated with the individual's evaluation of the facial expression; that is, the more unpleasant or aroused they perceived the facial expression to be, the more force they perceived. This study sheds light on the design of social touch performed by people who have physical or mediated contact with each other in physical space or cyberspace.

Objectives: Ipilimumab and nivolumab treatment against advanced and metastatic renal cell carcinoma (RCC) causes severe and lethal immune-related adverse events (irAEs). Predicting irAEs might improve clinical outcomes, however no practical biomarkers exist. This study examined whether eosinophils could be effective biomarkers for ≥grade 2 irAEs in RCC., Methods: We retrospectively analyzed 75 patients with RCC treated with ipilimumab and nivolumab between August 2018 and March 2021 in a multicenter study. Eosinophils were examined before and 2 weeks after treatment, and immediately after irAEs development. The optimal cut-off value for ≥grade 2 irAEs was determined by a receiver operating characteristic (ROC) curve. Univariate and multivariate analyses were undertaken to identify predictors of ≥grade 2 irAEs., Results: Two weeks after treatment, eosinophils were significantly upregulated in patients who had experienced ≥grade 2 irAEs than in those who had not experienced irAEs (mean, 5.7% vs. 3.2%; p < 0.05). The optimal cut-off value for eosinophils against ≥grade 2 irAEs was 3.0% (area under the curve = 0.69). In multivariate analyses, an eosinophil level ≥ 3.0% was a risk factor for ≥grade 2 irAEs (odds ratio 4.18, 95% confidence interval 1.16-15.1). The eosinophil level 2 weeks after treatment was upregulated by the onset of any type of irAEs including endocrine, gastrointestinal, pulmonary and skin disorders., Conclusions: An increased eosinophil level 2 weeks after treatment might be an effective biomarker for ≥grade 2 irAEs in patients with RCC treated with ipilimumab and nivolumab., (© 2023 The Japanese Urological Association.)

Objective: To identify biomarkers associated with the effectiveness of ipilimumab plus nivolumab against advanced metastatic renal cell carcinoma., Methods: We retrospectively analyzed the data of 75 patients treated with ipilimumab plus nivolumab at seven hospitals between August 2018 and April 2021. Prognostic biomarkers were assessed prior to initiating treatment with ipilimumab plus nivolumab. Median overall survival and progression-free survival were examined using the Kaplan-Meier method. Univariate and multivariate analyses were performed to identify predictors of disease progression. The International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk factors most important for predicting disease progression were determined using classification and regression tree analysis., Results: Median overall survival and progression-free survival were longer in the intermediate IMDC risk group than in the poor IMDC risk group (overall: not reached vs. 18.3 months; progression-free: not reached vs. 13.5 months). The multivariate analysis identified poor IMDC risk as a risk factor for disease progression (hazard ratio 2.61, 95% confidence interval: 1.05-6.51). Based on the results of the classification and regression tree analysis, the cohort was divided into non-anemia, anemia + neutro-Low, and anemia + neutro-High groups. Median overall survival and progression-free survival were longer in the non-anemia and anemia + neutro-Low groups than in the anemia + neutro-High group (overall: not reached vs. 29.3 months vs. 4.3 months: progression-free: not reached vs. 29.0 months vs. 3.9 months)., Conclusion: Hemoglobin and neutrophil levels may represent crucial biomarkers for predicting the effectiveness of ipilimumab plus nivolumab therapy in patients with renal cell carcinoma., (© 2023 The Japanese Urological Association.)

Aims: People living with HIV are at a high risk for cardiovascular disease owing to antiretroviral therapy use and chronic inflammation. There is limited evidence on the evaluation of serum lipid levels through lifestyle modification. This study aims to evaluate the effect of a smartphone application-based diet and exercise improvement program on men living with HIV and dyslipidemia., Methods: This was a randomized controlled trial recruiting Japanese men living with HIV who have dyslipidemia: intervention group (n = 19) and control group (n = 19). The intervention group received a third individual guidance session during the 6-month intervention and was encouraged to record their diet on a smartphone application. An intention-to-treat analysis of the results was conducted., Results: The intervention group showed significantly reduced change in low-density lipoprotein levels compared to the control group (-4.00 ± 20.2 mg/dL vs. 10.11 ± 21.1 mg/dL) (p = .042) from baseline to 6 months post-intervention. No significant differences were found in other serum lipid levels. Abdominal circumference decreased significantly in the intervention group (p = .048) from baseline to 6 months post-intervention. Total energy, protein, carbohydrate, fat, and salt intake, dietary and physical activity behavior change stages and social support, dietary self-efficacy, and loneliness significantly improved in the intervention group (p < .05) from baseline to 6 months post-intervention., Conclusions: A diet and physical activity improvement program using a smartphone application based on Japanese-specific health guidance may reduce low-density lipoprotein cholesterol levels in this population. Further sample expansion and examination of long-term effects are needed., (© 2023 Japan Academy of Nursing Science.)

We report an experimental setup for simultaneously measuring specific heat and thermal conductivity in feedback-controlled pulsed magnetic fields of 50 ms duration at cryogenic temperatures. A stabilized magnetic field pulse obtained by the feedback control, which dramatically improves the thermal stability of the setup and sample, is used in combination with the flash method to obtain absolute values of thermal properties up to 37.2 T in the 22-16 K temperature range. We describe the experimental setup and demonstrate the performance of the present method with measurements on single-crystal samples of the geometrically frustrated quantum spin-dimer system SrCu2(BO3)2. Our proof-of-principle results show excellent agreement with data taken using a standard steady-state method, confirming the validity and convenience of the present approach., (© 2023 Author(s). Published under an exclusive license by AIP Publishing.)

Background Aims: While donor-specific anti-human leukocyte antigen (HLA) antibodies (DSAs) in the recipient before transplantation are associated with graft failure in cord-blood transplantation (CBT), effects of DSAs other than against HLA-A, -B or -DRB1 on transplantation outcomes remained poorly understood., Methods: We retrospectively analyzed 567 single-unit CBT recipients to evaluate impact of DSAs against HLA-DP and -DQ on CBT outcomes., Results: Among 143 recipients (25.2%) who had anti-HLA antibodies, nine harbored DSAs against HLA-DP or -DQ. DSAs against HLA-DP or -DQ were associated with a significantly lower neutrophil engraftment rate (55.6% versus 91.8%, P = 0.032) and with a marginally lower platelet engraftment rate (46.7% versus 75.3%, P = 0.128) at day 100 after transplantation, compared with patients without anti-HLA antibodies. Time to neutrophil and platelet engraftment in patients with DSAs for HLA-DP or -DQ was significantly longer than that in patients without anti-HLA antibodies (median, 25 versus 21 days, P = 0.002 in neutrophil; median 61 versus 46 days, P = 0.014 in platelet). Cumulative incidence of bacterial infection at day 100 was significantly greater (88.9% versus 57.1%, P = 0.024), and re-transplant-free survival was marginally lower (55.6% versus 76.8%, P = 0.132) in patients with DSAs against HLA-DP or -DQ, compared with those without anti-HLA antibodies. These findings suggest that DSAs against HLA-DP or -DQ lead to unfavorable engraftment, which may increase risk of bacterial infection, and reduce survival soon after CBT., Conclusions: Our results suggest the importance of evaluating DSAs against HLA-DP and -DQ in recipients before selecting CB units., Competing Interests: Declaration of Competing Interest The authors have no commercial, proprietary or financial interest in the products or companies described in this article., (Copyright © 2022 International Society for Cell & Gene Therapy. Published by Elsevier Inc. All rights reserved.)

Purpose: This study aimed to analyze a feasible and suitable surgical precautionary preparatory technique. The techniques of double-gloving with hygienic hand wash (DH) and single-gloving with surgical hand wash (SS) were compared for their ability to prevent postoperative infection in robotic and laparoscopic minimally invasive surgeries., Materials and Methods: A prospective, non-randomized, multicenter study was conducted between January 2016 and June 2020. We divided the robotic and laparoscopic cases into two groups: DH and SS. Data on infectious outcomes were collected. Propensity score matching was performed to control for operative characteristics between the two groups. The primary endpoint was the presence of fever and surgical site infections (SSIs) indicating postoperative infection., Results: Among four medical centers, seven surgeons were allocated to either the DH or the SS group. A total of 221 and 251 patients underwent DH and SS, respectively. Propensity score matching, which included 171 cases from each group, showed that the incidence of fever during hospitalization was significantly lower in the DH group than that in the SS group (11.7% vs. 23.4%, p=0.007). Multivariable analysis revealed that DH was associated with a reduced odds ratio for developing postoperative fever during hospitalization (risk ratio: 0.49, p=0.043). No differences were found in SSI before and after hospitalization between the two groups., Conclusion: DH resulted in less postoperative fever and had a comparable effect in preventing SSIs. This procedure could be an alternative to the SS protocol in some minimally invasive surgeries.

Super engineering plastics, high-performance thermoplastic resins such as polyetheretherketone, and polyphenylene sulfide have been utilized in industries, owing to their high thermal stability and mechanical strength. However, their robustness hinders their depolymerization to produce monomers and low-weight molecules. Presently, chemical recycling for most super engineering plastics remains relatively unexplored. Herein, we report the depolymerization of insoluble polyetheretherketone using sulfur nucleophiles via carbon-oxygen bond cleavages to form benzophenone dithiolate and hydroquinone. Treatment with organic halides converted only the former products to afford various dithiofunctionalized benzophenones. The depolymerization proceeded as a solid-liquid reaction in the initial phase. Therefore, this method was not affected by the shape of polyetheretherketone, e.g., pellets or films. Moreover, this depolymerization method was applicable to carbon- or glass fiber-enforced polyetheretherketone material. The depolymerized product, dithiofunctionalized benzophenones, could be converted into diiodobenzophenone, which was applicable to the polymerization., (© 2023. The Author(s).)

Donor-derived platelets are used to treat or prevent hemorrhage in patients with thrombocytopenia. However, ∼5% or more of these patients are complicated with alloimmune platelet transfusion refractoriness (allo-PTR) due to alloantibodies against HLA-I or human platelet antigens (HPA). In these cases, platelets from compatible donors are necessary, but it is difficult to find such donors for patients with rare HLA-I or HPA. To produce platelet products for patients with aplastic anemia with allo-PTR due to rare HPA-1 mismatch in Japan, we developed an ex vivo good manufacturing process (GMP)-based production system for an induced pluripotent stem cell-derived platelet product (iPSC-PLTs). Immortalized megakaryocyte progenitor cell lines (imMKCLs) were established from patient iPSCs, and a competent imMKCL clone was selected for the master cell bank (MCB) and confirmed for safety, including negativity of pathogens. From this MCB, iPSC-PLTs were produced using turbulent flow bioreactors and new drugs. In extensive nonclinical studies, iPSC-PLTs were confirmed for quality, safety, and efficacy, including hemostasis in a rabbit model. This report presents a complete system for the GMP-based production of iPSC-PLTs and the required nonclinical studies and thus supports the iPLAT1 study, the first-in-human clinical trial of iPSC-PLTs in a patient with allo-PTR and no compatible donor using the autologous product. It also serves as a comprehensive reference for the development of widely applicable allogeneic iPSC-PLTs and other cell products that use iPSC-derived progenitor cells as MCB., (© 2022 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Background: Telemonitoring the use of CPAP devices and remote feedback on device data effectively optimizes CPAP adherence in patients with OSA., Research Question: Can expanding the scope of telemonitoring and remote feedback to body weight (BW), BP, and physical activity enhance efforts for BW reduction in Patients with OSA receiving CPAP?, Study Design and Methods: Participants were recruited from patients at 16 sleep centers in Japan with OSA and obesity who were receiving CPAP therapy. Obesity was defined as a BMI of ≥ 25 kg/m 2 , based on Japanese obesity guidelines. Implementation of CPAP telemonitoring was enhanced with electronic scales, BP monitors, and pedometers that could transmit data from devices wirelessly. Participants were randomized to the multimodal telemonitoring group or the usual CPAP telemonitoring group and were followed up for 6 months. Attending physicians provided monthly telephone feedback calls to the usual CPAP telemonitoring group on CPAP data obtained remotely. In the multimodal telemonitoring group, physicians additionally encouraged participants to reduce their BW, after sharing the remotely obtained data on BW, BP, and step count. The primary outcome was set as ≥ 3% BW reduction from baseline., Results: One hundred sixty-eight participants (BMI, 31.7 ± 4.9 kg/m 2 ) completed the study, and ≥ 3% BW reduction occurred in 33 of 84 participants (39.3%) and 21 of 84 participants (25.0%) in the multimodal telemonitoring and usual CPAP telemonitoring groups, respectively (P = .047). Whereas no significant differences were found between the two groups in the change in office and home BP, daily step counts during the study period were significantly higher in the multimodal telemonitoring group than in the usual CPAP telemonitoring group (4,767 steps/d [interquartile range (IQR), 2,864-6,617 steps/d] vs 3,592 steps/d [IQR, 2,117-5,383 steps/d]; P = .02) INTERPRETATION: Multimodal telemonitoring may enhance BW reduction efforts in patients with OSA and obesity., Trial Registry: UMIN Clinical Trials Registry; No.: UMIN000033607; URL: www.umin.ac.jp/ctr/index.htm., (Copyright © 2022 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Introduction: Neonatal hypoxic-ischaemic encephalopathy (HIE) is an important illness associated with death or cerebral palsy. This study aims to assess the safety and tolerability of the allogenic human multilineage-differentiating stress-enduring cell (Muse cell)-based product (CL2020) cells in newborns with HIE. This is the first clinical trial of CL2020 cells in neonates., Methods and Analysis: This is a single-centre, open-label, dose-escalation study enrolling up to 12 patients. Neonates with HIE who receive a course of therapeutic hypothermia therapy, which cools to a body temperature of 33°C-34°C for 72 hours, will be included in this study. A single intravenous injection of CL2020 cells will be administered between 5 and 14 days of age. Subjects in the low-dose and high-dose cohorts will receive 1.5 and 15 million cells per dose, respectively. The primary outcome is the occurrence of any adverse events within 12 weeks after administration. The main secondary outcome is the Bayley Scales of Infant and Toddler Development Third Edition score and the developmental quotient per the Kyoto Scale of Psychological Development 2001 at 78 weeks., Ethics and Dissemination: This study will be conducted in accordance with the Declaration of Helsinki and Good Clinical Practice. The Nagoya University Hospital Institutional Review Board (No. 312005) approved this study on 13 November 2019. The results of this study will be published in peer-reviewed journal and reported in international conferences., Trial Registration Numbers: NCT04261335, jRCT2043190112., Competing Interests: Competing interests: SSh, MM, and YS have collaborative projects with research funding from LSII for perinatal diseases. SSh and AH receive fees based on a consultation contract from LSII. SSh, TS, MM, MH, and YS have a patent for the application of Muse cells in the treatment of HIE and other indications. LSII provided CL2020 for this clinical trial free of charge., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Magnetic skyrmions are topologically stable swirling spin textures with particle-like character, and have been intensively studied as a candidate of high-density information bit. While magnetic skyrmions were originally discovered in noncentrosymmetric systems with Dzyaloshinskii-Moriya interaction, recently a nanometric skyrmion lattice has also been reported for centrosymmetric rare-earth compounds, such as Gd 2 PdSi 3 and GdRu 2 Si 2 . For the latter systems, a distinct skyrmion formation mechanism mediated by itinerant electrons has been proposed, and the search of a simpler model system allowing for a better understanding of their intricate magnetic phase diagram is highly demanded. Here, we report the discovery of square and rhombic lattices of nanometric skyrmions in a centrosymmetric binary compound EuAl 4 , by performing small-angle neutron and resonant elastic X-ray scattering experiments. Unlike previously reported centrosymmetric skyrmion-hosting materials, EuAl 4 shows multiple-step reorientation of the fundamental magnetic modulation vector as a function of magnetic field, probably reflecting a delicate balance of associated itinerant-electron-mediated interactions. The present results demonstrate that a variety of distinctive skyrmion orders can be derived even in a simple centrosymmetric binary compound, which highlights rare-earth intermetallic systems as a promising platform to realize/control the competition of multiple topological magnetic phases in a single material., (© 2022. The Author(s).)

Background and Objectives: Haematopoietic cell transplantation (HCT) therapy tends to be associated with various complications including engraftment failure, regimen-related toxicities, and infectious diseases. In addition, HC infusion itself occasionally elicits adverse events (AEs), one of the most common AEs is an allergic reaction. As appropriate laboratory tests have not yet been established to distinguish allergy-mediated AEs from other complications, clinical responses for HCT-related AEs can only be nonspecific. In this pilot study, using passive immune basophil activation test (pi-BAT), we attempted to distinguish an HC infusion-induced allergic reaction from various HCT-related AEs., Materials and Methods: Using pi-BAT, we examined 34 patients who underwent HCT, that is, 11 with AEs and 23 without AEs as controls., Results: Two of the eleven AE cases were pi-BAT positive and, the rest of nine AE cases were negative, while all non-AE cases were negative. Both of the two positive cases showed erythema, tachycardia, plus cough. Because erythema is one of the representative symptom of allergy, those cases could be classified as allergic reaction cases or anaphylaxis cases if tachycardia and cough were concomitant symptoms of erythema. Among the nine AEs with pi-BAT negative result, four cases showed urticaria, four showed vomiting plus diarrhoea, and one showed cough. Urticaria case was strongly suspected of allergy, however, the AE cases were pi-BAT negative., Conclusion: The pi-BAT may be useful as an auxiliary diagnostic tool to confirm the possible involvement of HC infusion in HCT-related AEs and identify an immunologic mechanism for HCT-related hypersensitivity reactions., (© 2021 International Society of Blood Transfusion.)

Introduction: Bidirectional associations have been reported between sleep disturbance and both cognitive impairment, including Alzheimer's disease and amyloid beta-peptide (Aβ) accumulation. These relationships can be explained by the glymphatic system, which acts as a garbage drainage system in the brain. As interstitial fluid dynamics are suggested to increase during sleep, clearance of Aβ can be influenced by sleep disturbance or deprivation. We hypothesised that using lemborexant, an orexin receptor antagonist, to improve sleep quality would also improve the function of the glymphatic system. We plan to examine the effect of lemborexant on sleep quality and the glymphatic system among patients with insomnia disorder., Methods and Analysis: This pilot study is designed as an open-label, single-arm, single-centre trial. Thirty patients aged 50 years and over with insomnia will be recruited. The participants will take lemborexant (5 mg) at bedtime for 12 weeks and undergo a home-based sleep study at baseline and weeks 4 and 12, as well as MRI examinations to evaluate the glymphatic system at baseline and week 12. The primary outcome will be changes in objective sleep parameters as evaluated using a sleep monitoring system. The secondary outcomes will be changes in subjective sleep parameters. The relationships between changes in sleep parameters and the glymphatic system will be evaluated using diffusion tensor image analysis along the perivascular space, which is called the ALPS-index. Sleep parameters and the ALPS-index will be analysed using a paired t-test or Pearson's correlation coefficient., Ethics and Dissemination: The study protocol was approved by Nagoya University Certified Review Board. The findings from this research will be published in peer-reviewed journals and be presented at local, national and international conferences., Trial Registration Number: jRCTs041210024., Competing Interests: Competing interests: IO, SM, MA and NM have no conflicts of interest to declare. KI has received speakers’ honoraria from Eisai, Kyowa, Meiji Seika Pharma, Otsuka, Sumitomo Dainippon, Taisho, Takeda and Towa. AF and MT are employees of Eisai, Japan. TT has received research funding from Canon Medical Systems Corporation. SN has received speakers’ honoraria from Eisai, Siemens Healthcare Japan, Guerbet, GE Healthcare Pharma, Nihon Medi-Physics, FUJIFILM Toyama Chemical, Bayer and Canon Medical Systems Corporation. NO has received research support or speakers’ honoraria from, or has served as a consultant to, Sumitomo Dainippon, Eisai, Otsuka, KAITEKI, Mitsubishi Tanabe, Shionogi, Eli Lilly, Mochida, DAIICHI SANKYO, Nihon Medi-Physics, Takeda, Meiji Seika Pharma, EA Pharma, Pfizer, MSD, Lundbeck Japan, Taisho Pharma, Janssen, UCB and Shionogi, Nihon Medi-Physics, Tsumura, Novartis and Astellas. Eisai funded this study and participated in the planning of this study. Eisai will also review findings, commission the study report, and review the papers before they are submitted for publication., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The photochemically-induced thrombosis (photothrombosis) method can create focal cerebral infarcts anywhere in the relatively superficial layers of the cerebrum; it is easy to implement and minimally invasive. Taking advantage of this versatility, we aimed to establish a new rat model of urinary frequency with focal cerebral infarction, which was characterized by its simplicity, nonlethal nature, and high reproducibility. The prefrontal cortex and the anterior cingulate cortex, which are involved in lower urinary tract control, were targeted for focal cerebral infarction, and urinary parameters were measured by cystometrogram. Cystometric analysis indicated that micturition intervals significantly shortened in photothrombosis-treated rats compared with those in the sham operative group on Days 1 and 7 (P < 0.01), but prolonged after 14 days, with no difference between the two groups. Immunopathological evaluation showed an accumulation of activated microglia, followed by an increase in reactive astrocytes at the peri-infarct zone after photothrombotic stroke. Throughout this study, all postphotothrombosis rats showed cerebral infarction in the prefrontal cortex and anterior cingulate cortex; there were no cases of rats with fatal cerebral infarction. This model corresponded to the clinical presentation, in that the micturition status changed after stroke. In conclusion, this novel model combining nonlethality and high reproducibility may be a suitable model of urinary frequency after focal cerebral infarction., Competing Interests: The authors have declared that no competing interests exist.

Herein, we disclose the Ni-catalyzed ring-opening C-O functionalization of peri -xanthenoxanthenes using Grignard reagents that forms 8-monofunctionalized binaphthols. 1,2-Bis(dicyclohexylphosphino)ethane was the best ligand for alkylations and ICy for arylation. After mechanistic investigations, we assumed that the reaction proceeds via C-O reduction and subsequent C-O functionalization. To verify the mechanism, the intermediate after reduction was isolated. Moreover, the asymmetric addition, using 8-octylbinaphthol after optical resolution, was studied.

A total of 10-20% of plasma membrane proteins are anchored by glycosylphosphatidylinositol (GPI). GPI is attached to proteins by GPI transamidase (GPI-T), which contains five subunits named PIGK, PIGS, PIGT, PIGU, and GPAA1. We previously reported that PIGT localizes near the nucleus in Drosophila. However, localizations of the other four subunits remain unknown. Here, we show that a catalytic subunit of GPI-T, PIGK, mainly localizes to the endoplasmic reticulum (ER), while the other four subunits localize to the nuclear envelope (NE) and ER. The NE/ER localization ratio of PIGS differs between cell types and developmental stages. Our results suggest that GPI-T catalyzes GPI attachment in the ER and the other four subunits may have other unknown functions in the NE., (© 2021 The Authors. FEBS Letters published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

Purpose: To elucidate factors contributing to early urinary continence recovery after retzius-sparing robot-assisted radical prostatectomy (RS-RARP) by evaluating postoperative pelvic anatomical features between RS-RARP and conventional RARP (CON-RARP). Materials and Methods: We retrospectively examined 50 men who underwent RS-RARP ( n  = 25; the RS-RARP group) and CON-RARP ( n  = 25; the CON-RARP group) between October 2017 and June 2018. Perioperative outcomes and postoperative urinary continence were assessed in both groups. Anatomical features including the bladder neck-to-pubic symphysis ratio (determined from cystograms) and membranous urethral length (MUL) (determined from magnetic resonance imaging) were evaluated. Result: The daily urinary incontinence rate at discharge was significantly lower in the RS-RARP group than in the CON-RARP group (0.046 [range: 0.014-0.160] vs 0.357 [range: 0.139-0.616], p  < 0.001). Postoperative urinary continence at 1, 3, 6, and 12 months was 80%, 92%, 96%, and 96% in the RS-RARP group and 24%, 40%, 68%, and 84% in the CON-RARP group, respectively ( p  < 0.001). The urgency scores in the international prostate symptom score (IPSS) questionnaire at 1 and 3 months were significantly lower in the RS-RARP than in the CON-RARP group ( p  = 0.028 and 0.033, respectively). The quality of life (QOL) indices were more significantly improved in the RS-RARP group than in the CON-RARP group 1 month ( p  = 0.027) and 3 months ( p  = 0.045) postoperatively. Receiver operating characteristic analysis revealed that a postoperative MUL of 12.1 mm (area under the curve: 0.852) was the optimal cutoff value predictive of continence recovery after 1 month. Multivariate analysis demonstrated that RS-RARP (odds ratio [OR]: 23.6; p  < 0.001) and prostate volume (OR: 0.926; p  = 0.049) were the independent factors of a longer MUL. Conclusions: RS-RARP results in an early continence recovery and a better urgency score in the IPSS by suppressing the descent of the bladder and maintaining a long MUL. RS-RARP may contribute to a better QOL recovery after RARP.

This is the case of a 72-year-old man in whom multiple colorectal cancers including rectal and appendiceal cancers and synchronous S3 liver metastases were observed in 2014, and resection was performed in 2 stages. In 2017, a single recurrence was found in the liver S8, and he underwent a liver S8 sub-segmental resection. Implantation of a CV port for postoperative chemotherapy was planned. At the time of insertion, the catheter was punctured from the exterior portion of the left subclavian vein to avoid the pinch-off syndrome wherein the catheter is crushed between the clavicle and the first rib. Subsequently, FOLFOX therapy was started, but it was discontinued because of allergic symptoms, which appeared during the third course. Two years after the CV port was implanted, a catheter fracture was found on a chest X-ray performed during a regular visit. Since the detached catheter did not fall into the vein, it was possible to remove the port under fluoroscopy. When a catheter is implanted, even under ultrasound guidance, it is considered important to always keep in mind the possibility of a catheter fracture and to detect and respond to it early.

We report a case of malignant stenosis due to recurrence of lymph node metastasis treated with laparoscopic gastrojejunal bypass. A 83-year-old man who underwent chemoradiotherapy for esophageal cancer(cT3N2M0). About 3 and half years after chemoradiotherapy, he was referred to hospital for vomiting. As a result of the examination, we diagnosed malignant stenosis of descending part of duodenum due to retroperitoneum lymph node recurrence of esophageal cancer. We performed laparoscopic gastrojejunal bypass operation because we suggested self-expandable metallic stent make easy to migrate into anal side of the duodenum. The postoperative course was good. He was enrolled in oncology department on the 21 days after the operation. Gastroduodenal stenosis is common pathology by malignant tumor. Gastrojejunostomy and placement of self-expandable metallic stent is commonly performed for malignant gastroduodenal obstruction. Endoscopic metallic stent placement is minimally invasive treatment for malignant stenosis of the intestine, however sometime the stent placement will make easy to migrate by extra compression. Gastrojejunostomy mat be more safety than endoscopic stent placement for the malignant gastroduodenal obstruction.

Bone turnover markers (BTMs) are useful parameters for assessing fracture risk and unlike bone mineral density (BMD), can be measured at any institution. However, BTM values have not been established in patients post-allogeneic hematopoietic stem cell transplantation (allo-HSCT). We investigated the practicality of BTMs in patients who underwent allo-HSCT by measuring levels of the serum bone resorption marker, tartrate-resistant acid phosphatase-5b (TRACP-5b), and the bone formation marker, bone-specific alkaline phosphatase (BAP), together with BMD, 1 month before and 6 months after allo-HSCT. Patients were classified into either the alendronate group (n = 14) if alendronate treatment (35 mg orally per week) was administered before allo-HSCT or within 1 month after allo-HSCT, or the control group (n = 16), in which patients did not receive alendronate treatment. Despite the high frequency of corticosteroids users in the alendronate group (71.4 vs. 18.9%; p < 0.01), the mean percentage changes in BMD at the lumbar spine (- 2.9 vs. - 3.1%; p = 0.44) and femoral neck (- 3.2 vs. - 4.1%; p = 1.00), TRACP-5b levels (- 4.8 vs. 9.9%; p = 0.45), and BAP levels (6.9 vs. 1.0%; p = 0.85) during 6 months did not differ significantly between the alendronate and control groups. Additionally, the percentage changes in BMD at the lumbar spine were negatively associated with the TRACP-5b levels 6 months after allo-HSCT (p = 0.03, r = 0.40). Our results indicate the possible effectiveness of alendronate treatment in allo-HSCT patients. BTM levels could be useful to monitor the BMD changes.

A 63-year-old man was admitted for the evaluation of Hb 4.8 g/dL anemia. He underwent colon fiberscopy and was subsequently diagnosed with synchronous cancers of the ascending colon and rectum. He underwent laparoscopic ileocecal resection and low anterior resection with 2 segmental anastomoses. The histopathological diagnosis of A/C and rectal cancer was Stage Ⅱ and Stage Ⅲa, respectively. His treatment was completed after 6months of adjuvant chemotherapy with oral TS-1, which was followed by a subsequent 2 year follow-up study, without disease recurrence. Operations of synchronous cancers with 2 segmental anastomoses usually require longer surgical time and are associated with more postoperative complications compared with a single segmental anastomosis. We report a case of synchronous colorectal cancer successfully treated by laparoscopic surgery with 2 segmental anastomoses.

The patient was an 85-year-old man who received chemotherapy with gemcitabine for 2 years 9 months under the diagnosis of unresectable locally advanced pancreatic body and tail cancer. He visited our hospital because of anorexia, upper abdominal fullness, and vomiting. A CT scan showed severe stenosis in the third portion of the duodenum, which was associated with the direct invasion of the advanced pancreatic cancer. Upper gastrointestinal fiberscopy revealed a severe duodenal obstruction; however, pancreatic cancer exposure within the duodenal mucosa was not observed. As the stenosis of the duodenum was relatively smooth because of the cancer invasion into only the submucosa, deviation of the metallic stent was possible, so we performed laparoscopic gastrojejunostomy. We started the surgery with 5-port settings. A slit was made in the gastric body by using ENDO-GIA®, and bypass surgery with a Roux-en-Y anastomosis was performed. The postoperative course was good, and oral intake resumed on the third postoperative day. Thereafter, he could leave the hospital with good progress and received systemic chemotherapy using gemcitabine. In the present case, an extramural gastrointestinal stenosis without cancer that was not exposed in the gastrointestinal mucosa was poorly fixed with gastrointestinal metallic stents and use of a deviating metallic stent was reported, so we chose laparoscopic gastrojejunostomy. In addition, after undergoing laparoscopic surgery, which is a minimally invasive treatment, he recovered quickly and shifted early to systemic chemotherapy. Herein, the usefulness of laparoscopic gastrojejunostomy for extramural stenosis is reported with a review of related literature.