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Introduction: Platelet-rich plasma obtained by centrifuging peripheral blood can promote osteogenesis owing to its abundant growth factors but has drawbacks, including rapid growth factor loss and inconsistent effects depending on donor factors. To overcome these issues, we were the first in the world to use freeze-dried human induced pluripotent stem cell-derived megakaryocytes and platelets (S-FD-iMPs) and found that they have osteogenesis-promoting effects. Since turbulence was found to activate platelet biogenesis and iPS cell-derived platelets can now be produced on a clinical scale by a device called VerMES, this study examined the osteogenesis-promoting effect and safety of clinical-scale FD-iMP (V-FD-iMPs) for future human clinical application., Method: We administered either S-FD-iMPs, V-FD-iMPs, or saline along with artificial bone to the lumbar spine of 8-week-old male Sprague-Dawley rats (n = 4 each) and evaluated bone formation by computed tomography (CT) and pathology. Next, we administered V-FD-iMPs or saline along with artificial bone to the lumber spines of 5-week-old male New Zealand White rabbits (n = 4 each) and evaluated the bone formation by CT and pathology. Rats (n = 10) and rabbits (n = 6) that received artificial bone and V-FD-iMPs in the lumbar spine were also observed for 6 months for adverse events, including infection, tumor formation, and death., Results: Both V-FD-iMPs and S-FD-iMPs significantly enhanced osteogenesis in the lumber spines of rats in comparison with the controls 8 weeks postoperatively, with no significant differences between them. Furthermore, V-FD-iMPs vigorously promoted osteogenesis in the lumber spines of rabbits 8 weeks postoperatively. In rats and rabbits, V-FD-iMPs showed no adverse effects, including infection, tumor formation, and death, over 6 months., Conclusion: These results suggest that V-FD-iMPs promote safe osteogenesis., Competing Interests: Y.S., M.M., N.T., K.K., K.E. and S.Ohtori hold stock of Kineplat Co.Ltd. that has a related patent of this research., (© 2024 Japanese Society of Regenerative Medicine. Published by Elsevier B.V.)

Objective: People with hearing loss often encounter difficulties in hearing under adverse conditions, such as listening in the presence of noise. Listening effort is an indicator used to assess listening difficulties in daily life. Although many studies on listening effort have been conducted in recent years, there is a notable gap in the exploration of how task load influences listening effort in young adults. This study compared the effects of background noise and memory load on task performance and subjective listening effort in young adults with and without hearing loss., Methods: The study included a group of 8 adults with hearing loss (mean age: 24.1 ± 6.0 years) and a group of 16 individuals with normal hearing (mean age: 27.9 ± 4.9 years). A number memorizing task was conducted, involving two types of auditory digits (either three or seven digits) presented under multi-talker babble noise conditions of signal-to-noise ratio of -5 dB [SN -5 dB] or SN +5 dB. Participants determined whether the number presented in the encoding interval matched the one presented in the retrieval interval. Subsequently, they were asked to complete a questionnaire using a Visual Analog Scale (VAS) to assess their subjective listening effort. Percentage of correct responses, reaction times, and VAS ratings were compared between adults with and without hearing loss., Results: Our results showed significant differences between the two groups in the percentage of correct responses and the reaction time under the SN -5 dB conditions, regardless of the memory load. Under the SN +5 dB conditions, a significant difference was found only in the percentage of correct responses for seven digits. In the normal hearing group, the percentage of correct responses and VAS ratings tended to decrease as the memory load increased, even under the same noise condition. Conversely, in the hearing loss group, a consistent trend could not be identified in the effects of noise and memory load on the percentage of correct responses and VAS ratings., Conclusion: These results suggest that in conditions of high noise load, young adults with hearing loss show a higher tendency for listening effort to be affected by other loads. We confirmed that for some participants with hearing loss, the task exceeded a certain level of difficulty in the SN -5 dB and seven digits condition, leading to a change in their motivation and strategy used. Future research should examine ways to control for participants' motivations., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2024. Published by Elsevier B.V.)

Purpose: To elucidate the relationship between in-hospital mortality and the institutional factors of intensive care units (ICUs), with a focus on the intensivist-to-bed ratio. Methods: A retrospective cohort study was conducted using a Japanese ICU database, including adult patients admitted between April 1, 2020 and March 31, 2021. We used a multilevel logistic regression model to investigate the associations between in-hospital mortality and the following institutional factors: the intensivist-to-bed ratios on weekdays or over weekends/holidays, different work shifts, hospital-to-ICU-bed ratio, annual-ICU-admission-to-bed ratio, type of hospital, and the presence of other medical staff. Results: The study population comprised 46 503 patients admitted to 65 ICUs. The in-hospital mortality rate was 8.1%. The median numbers of ICU beds and intensivists were 12 (interquartile range [IQR] 8-14) and 4 (IQR 2-9), respectively. In-hospital mortality decreased significantly as the intensivist-to-bed ratio at 10 am on weekdays increased: the average contrast indicated a 20% (95% confidence interval [CI]: 1%-38%) reduction when the ratio increased from 0 to 0.5, and a 38% (95% CI: 9%-67%) reduction when the ratio increased from 0 to 1. The other institutional factors did not present a significant effect. Conclusions: The intensivist-to-bed ratio at 10 am on weekdays had a significant effect on in-hospital mortality. Further investigation is needed to understand the processes leading to improved outcomes., Competing Interests: Declaration of Conflicting InterestsHE and HM are affiliated with the Department of Healthcare Quality Assessment at the University of Tokyo, a social collaboration department supported by grants from the National Clinical Database, Johnson & Johnson K.K., Nipro Corporation, and Intuitive Surgical Sàrl. The other authors do not have any competing interests.

Previous studies have emphasized the necessity of surveillance and control measures for hepatitis E virus (HEV) infection in wild boars, an important reservoir of HEV. To assess the current situation of HEV infection in wild boars in Japan, this study investigated the prevalence and genetic diversity of HEV among wild boars captured in 16 prefectures of Japan during 2018-2023. Serum samples from 968 wild boars were examined for anti-HEV IgG antibodies and HEV RNA. The prevalence of anti-HEV IgG varied geographically from 0 % to 35.0 %. HEV RNA was detected in 3.6 % of boars, with prevalence varying by prefecture from 0 % to 22.2 %. Genotype 3 was the most prevalent genotype (91.9 %), followed by genotype 4 (5.4 %), with one strain closely related to genotype 6. The prevalence of HEV infection among wild boars decreased from 2018/2019 to 2022/2023 with significant declines in levels of anti-HEV IgG antibodies (14.5 % vs. 6.2 %, P < 0.0001) and HEV RNA (7.6 % vs. 1.5 %, P < 0.0001). Regional analysis showed varying trends, with no HEV RNA-positive boars found in several regions in recent years. A plausible factor contributing to the decline in HEV infection is the application of countermeasures, including installing fences to prevent intrusion into pig farms, implemented in response to the emergence of classical swine fever virus (CSFV) infection in wild boars and domestic pigs, with incidents reported annually since 2018. Further investigation is warranted to explore the association between countermeasures to CSFV infection and the decrease in HEV infection among wild boars., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background & Aims: The benefits of physical activity, including exercise and daily and household chores, on the bioimpedance phase angle remain unclear. We aimed to examine the longitudinal association between objectively measured physical activity and bioimpedance phase angle among community-dwelling older adults., Methods: This community-based cohort study enrolled individuals aged 65 years or older without any disability in the basic activities of daily living. The exposure was physical activity level measured objectively using a tri-axial accelerometer at baseline. The outcome was a whole body phase angle at 50 kHz obtained from a bioelectrical impedance analyzer at a one-year follow-up. The linear regression model was fitted to estimate the continuous associations of physical activity level and phase angle with adjustment of confounders, including age, sex, body mass index, physical performance, and phase angle at baseline., Results: The primary analysis included 229 individuals (mean age = 72.6 years [standard deviation = 4.9], 62.9% females). In the multivariable linear regression model, physical activity level at baseline is associated with a greater phase angle at follow-up (mean difference per 1 increase, 0.53° [95%CI, 0.23-0.83]). Subgroup analysis by sex showed similar trends. Restricted cubic spline analysis indicated a linear association between phase angle at follow-up and physical activity level at baseline (p = 0.66 for non-linearity)., Conclusions: Higher physical activity level was associated with greater phase angle at one-year follow-up in a linear dose-response manner, independent of demographics, physical performance, and phase angle at baseline, in community-dwelling older adults., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest., (Copyright © 2024 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

Objective: Adenomyosis-related infertility is increasingly being diagnosed, and surgical intervention has been suggested to improve fertility. Elastography, a noninvasive ultrasound technique, is promising for diagnosing and guiding the resection of adenomyosis. This report presents the first case of successful delivery after twin pregnancies achieved with IVF following intraoperative elastography-guided laparoscopic adenomyomectomy., Case Report: A 35-year-old Japanese woman with uterine adenomyosis received a gonadotropin analog before surgery. Preoperative MRI revealed a 5.0 × 7.0 cm adenomyoma, leading to scheduled laparoscopic adenomyomectomy with intraoperative elastography. During surgery, elastography ensured the complete resection of the adenomyotic tissue while preserving the endometrium. Postoperative MRI confirmed the absence of residual adenomyosis. The patient underwent in vitro fertilization and embryo transfer, leading to a successful twin pregnancy after double blastocyst transfer. Despite a stable perinatal course, she required hospitalization to prevent preterm labor. At 32 weeks, an elective cesarean section delivered healthy twins. The intra- and post-operation was uncomplicated, and the patient and infants had an optimal health., Conclusion: This is the first reported case of a twin pregnancy resulting from vitrified-warmed embryo transfer after elastography-guided laparoscopic adenomyomectomy, culminating in a successful delivery via cesarean section. This technique allows precise resection and mitigates the risks of uterine rupture and placenta accreta spectrum disorders. Although promising, further studies are required to validate the safety and efficacy of this innovative surgical approach., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Ota, Ota, Takahashi, Horikawa, Kuroda, Okamoto, Tanaka, Kusumoto, Oda, Matsuyama, Miyake, Honda and Shimoya.)

Inspired by the previous machine-learning study that the number of hydrogen-bonding acceptor (N HBA ) is important index for the hole mobility of organic semiconductors, seven dithienobenzothiazole (DBT) derivatives 1 a-g (N HBA =5) were designed and synthesized by one-step functionalization from a common precursor. X-ray single-crystal structural analyses confirmed that the molecular arrangements of 1b (the diethyl and ethylthienyl derivative) and 1c (the di(n-propyl) and n-propylthienyl derivative) in the crystal are classified into brickwork structures with multidirectional intermolecular charge-transfer integrals, as a result of incorporation of multiple hydrogen-bond acceptors. The solution-processed top-gate bottom-contact devices of 1b and 1c had hole mobilities of 0.16 and 0.029 cm 2  V -1 s -1 , respectively., (© 2024 Wiley-VCH GmbH.)

The present study aimed to summarize and report data on errors related to treatment planning, which were collected by medical physicists. The following analyses were performed based on the 10-year error report data: (1) listing of high-risk errors that occurred and (2) the relationship between the number of treatments and error rates, (3) usefulness of the Automated Plan Checking System (APCS) with the Eclipse Scripting Application Programming Interface and (4) the relationship between human factors and error rates. Differences in error rates were observed before and after the use of APCS. APCS reduced the error rate by ~1% for high-risk errors and 3% for low-risk errors. The number of treatments was negatively correlated with error rates. Therefore, we examined the relationship between the workload of medical physicists and error occurrence and revealed that a very large workload may contribute to overlooking errors. Meanwhile, an increase in the number of medical physicists may lead to the detection of more errors. The number of errors was correlated with the number of physicians with less clinical experience; the error rates were higher when there were more physicians with less experience. This is likely due to the lack of training among clinically inexperienced physicians. An environment to provide adequate training is important, as inexperience in clinical practice can easily and directly lead to the occurrence of errors. In any environment, the need for additional plan checkers is an essential factor for eliminating errors., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology.)

Virtual reality (VR) has emerged as a powerful tool for investigating neural mechanisms of decision-making, spatial cognition, and navigation. In many head-fixed VRs for rodents, animals locomote on spherical treadmills that provide rotation information in two axes to calculate two-dimensional (2D) movement. On the other hand, zebrafish in a submerged head-fixed VR can move their tail to enable movement in 2D VR environment. This motivated us to create a VR system for adult zebrafish to enable 2D movement consisting of forward translation and rotations calculated from tail movement. Besides presenting the VR system, we show that zebrafish can learn a virtual Morris water maze-like (VMWM) task in which finding an invisible safe zone was necessary for the zebrafish to avoid an aversive periodic mild electric shock. Results show high potential for our VR system to be combined with optical imaging for future studies to investigate spatial learning and navigation., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Proprotein convertase subtilisin/kexin type 9 inhibitors stabilize vulnerable plaque, reducing cardiovascular events. However, manual optical coherence tomography (OCT) analysis of drug efficacy is challenging because of signal attenuation within lipid plaques., Methods and Results: Twenty-four patients with thin-cap fibroatheroma were prospectively enrolled and randomized to receive alirocumab (75 mg every 2 weeks) plus rosuvastatin (10 mg/day) or rosuvastatin (10 mg/day) alone. OCT images at baseline and 36 weeks were analyzed manually and with artificial intelligence (AI)-aided software. AI-aided OCT analysis showed significantly greater percentage changes in the alirocumab+rosuvastatin vs. rosuvastatin-alone group in fibrous cap thickness (FCT; median [interquartile range] 212.3% [140.5-253.5%] vs. 88.6% [63.0-119.6%]; P=0.006) and lipid volume (median [interquartile range] -30.8% [-51.8%, -16.6%] vs. -2.1% [-21.6%, 4.3%]; P=0.015). Interobserver reproducibility for changes in minimum FCT and lipid index was relatively low for manual analysis (interobserver intraclass correlation coefficient [ICC] 0.780 and 0.499, respectively), but high for AI-aided analysis (interobserver ICC 0.999 and 1.000, respectively). Agreements between manual and AI-aided OCT analyses of FCT and the lipid index were acceptable (concordance correlation coefficients 0.859 and 0.833, respectively)., Conclusions: AI-aided OCT analysis objectively showed greater plaque stabilization of adding alirocumab to rosuvastatin. Our results highlight the benefits of a fully automated AI-assisted approach for assessing drug efficacy, offering greater objectivity in evaluating serial changes in plaque stability vs. conventional OCT assessment.

Acute respiratory distress syndrome (ARDS) is a life-threatening lung injury that induces cytokine hypersecretion. Receptor activity-modifying protein (RAMP) 1, a subunit of the calcitonin gene-related peptide (CGRP) receptor, regulates the production of cytokines. This study examined the role of RAMP1 signaling during lipopolysaccharide (LPS)-induced acute lung injury (ALI). LPS administration to wild-type (WT) mice depleted alveolar macrophages (AMs) and recruited monocyte-derived macrophages (MDMs) and neutrophils. RAMP1-deficient (RAMP1 -/- ) mice exhibited higher lung injury scores, cytokine levels, and cytokine-producing neutrophil infiltration. RAMP1-deficient AMs produced more cytokines in response to LPS than WT AMs. Adoptive transfer of RAMP1-deficient AMs to RAMP1 -/- mice increased cytokine levels and neutrophil accumulation compared to the transfer of WT AMs. RAMP1 -/- mice had reduced MDM recruitment and lower pro-inflammatory and reparative macrophage profiles. Cultured bone marrow (BM)-derived RAMP1-deficient macrophages stimulated with LPS showed decreased expression of pro-inflammatory and pro-repairing genes. CGRP administration to WT mice reduced cytokine production and neutrophil accumulation. These findings indicate that RAMP1 signaling mitigates LPS-induced ALI by inactivating AMs and promoting inflammatory and repair activities of MDMs. Targeting RAMP1 signaling presents a potential therapeutic approach for the treatment of ARDS.

Follicular lymphoma is a common hematologic malignancy; however, it is less common among all malignant diseases and is difficult to suspect in advance due to the lack of specific clinical findings. Here, we report a case in which a late recurrence of corpus cancer was first suspected and finally diagnosed as follicular lymphoma. A 67-year-old female presented to our department with enlarged pelvic lymph nodes. She was diagnosed with breast cancer (HER2-posiotive with lymph node metastasis) and corpus cancer (endometrioid carcinoma grade 2, stage IA) 16 years prior, received definitive therapy and was followed up. A positron emission tomography scan was performed, and an accumulation of 18F-fluorodeoxyglucose (FDG) was detected in multiple lymph nodes, including the lymph nodes with no change in size or enlargement. We performed laparoscopic resection of the enlarged and FDG-accumulated lymph nodes and a pathological examination. The patient was diagnosed with follicular lymphoma (FL) grade 1 and is currently under observation at the Department of Hematology. FL can be considered when there is a discrepancy between the change in lymph node size and the degree of FDG accumulation. A pathological examination is useful for accurate diagnosis. Therefore, it is important to consider tissue collection; however, care must be taken to minimize the invasiveness of the procedure for the patient., Competing Interests: Conflict of interestThere are no conflicts of interest to be disclosed in this case report., (© The Author(s) under exclusive licence to The Japan Society of Clinical Oncology 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

The 15th Japan Bioanalysis Forum (JBF) Symposium was held in Kyoto, Japan, between 5 and 7 February 2024. The conference theme, 'Toward the new world - Science as a universal endeavor' indicated that universal discussion based on science is making a basis of regulatory and analytical sciences, now internationally harmonized. The symposium discussed a wide range of topics, including ICH M10, quantitative PCR, immunogenicity, peptide LC-MS, e-notebooks, artificial intelligence, reliability standards, carrier development, inviting domestic and overseas experts. Approximately 360 attendees from various fields, including pharmaceutical companies, contract research organizations, academia and regulators, gathered in person or online.

Background:  In the treatment of peripheral nerve injuries with nerve defects, second-generation collagen-based conduits, such as Renerve® (Nipro, Osaka, Japan), have shown the potential for promoting nerve regeneration. However, there is concern related to the weak material properties. No previous studies have addressed the strength of the bridging model using collagen conduits. This study aimed to investigate the tensile strength and failure patterns in nerve defect models bridged with Renerve® conduits through biomechanical research., Methods:  Using fresh chicken sciatic nerves, we examined the maximum failure load of four groups: bridging models using Renerve® with one suture (group A), with two sutures (group B), with three sutures (group C), and end-to-end neurorrhaphy models with two sutures (group N). Each group had eight specimens. We also evaluated failure patterns of the specimens., Results:  Group N showed a significantly higher maximum failure load (0.96 ± 0.13 N) compared to groups A (0.23 ± 0.06 N, p  < 0.0001), B (0.29 ± 0.05 N, p  < 0.0001), and C (0.40 ± 0.10 N, p  < 0.0001). Regarding failure patterns, all specimens in group A showed nerve-end dislocation from the conduit. Two specimens in group B and three specimens in group C failed due to circumferential cracks in the conduit. Six specimens in group B and five specimens in group C exhibited cutting out of sutures from the conduit., Conclusion:  This study suggests that the number of sutures in synthetic collagen nerve conduits has little effect on the maximum failure load. To take advantage of its biomaterial benefits, a period of postoperative range of motion restriction may be required., Competing Interests: The authors declare the existence of a financial competing interest from NIPRO Corporation., (Thieme. All rights reserved.)

Background: Robotic simple hysterectomy (RSH) is the most common robotic gynecologic surgery in the United States. Uterine manipulators are commonly used to handle the uterus during laparoscopic surgery, but few studies have examined their necessity in RSH. This study retrospectively compares RSH cases with and without the use of manipulators, and identifies predictors for their intraoperative use., Materials and Methods: This retrospective cohort study included patients undergoing RSH for benign pathologies at Kawasaki Medical School from October 2020 to December 2022. Patients with malignancies were excluded. The robotic surgeries were performed by three skilled surgeons using the four-arm da Vinci Xi surgical system. Data on perioperative and operative parameters were collected, including age, body mass index (BMI), history of abdominal surgery, disease type, presence of ovarian cysts, and operative time. Statistical analyses were performed using EZR software, with multivariate logistic regression to identify predictive factors for uterine manipulator use., Results: The study included 113 patients who underwent RSH without a uterine manipulator and 58 with one. Patients without a manipulator were older, while those with a manipulator had higher BMIs and a higher prevalence of ovarian chocolate cysts and Douglas obliteration. Operating time was shorter without a manipulator. Independent predictors for manipulator use were higher BMI, presence of ovarian endometrioid cysts, and Douglas obliteration., Conclusion: RSH without a uterine manipulator is feasible and can reduce the need for surgical assistants. Predictors for manipulator use include higher BMI, ovarian cysts, and Douglas obliteration. The use of a fourth robotic arm can enhance surgical independence and resource efficiency. Further research is needed to assess the long-term cost-effectiveness and outcomes of this approach., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Kawamura, Ota, Ota, Takahashi, Fujiwara, Tasaka, Okamoto, Morimoto, Saito, Sugihara, Matsuyama, Koike, Shiota and Shimoya.)

Mammalian genome research has conventionally involved mice and rats as model organisms for humans. Given the recent advances in life science research, to understand complex and higher-order biological phenomena and to elucidate pathologies and develop therapies to promote human health and overcome diseases, it is necessary to utilize not only mice and rats but also other bioresources such as standardized genetic materials and appropriate cell lines in order to gain deeper molecular and cellular insights. The Japanese bioresource infrastructure program called the National BioResource Project (NBRP) systematically collects, preserves, controls the quality, and provides bioresources for use in life science research worldwide. In this review, based on information from a database of papers related to NBRP bioresources, we present the bioresources that have proved useful for mammalian genome research, including mice, rats, other animal resources; DNA-related materials; and human/animal cells and microbes., (© 2024. The Author(s).)

A 46-year-old Japanese man was referred to our hospital because of a marked increase in his eosinophil count (22,870/μL) and elevated liver enzyme levels. Computed tomography (CT) showed thrombi measuring approximately 8 cm in both femoral veins. A liver biopsy revealed eosinophilic infiltration, hepatocyte necrosis, fibrosis, and multiple thrombi. We suspected acute liver injury and deep vein thrombosis associated with hypereosinophilic syndrome and initiated steroids and heparin treatment. Four days after starting treatment, the patient experienced sudden chest pain and cardiopulmonary arrest. CT revealed bilateral pulmonary artery thrombosis, and despite administration of a tissue plasminogen activator, the patient died.

Previous plan competitions have largely focused on dose metric assessments. However, whether the submitted plans were realistic and reasonable from a quality assurance (QA) perspective remains unclear. This study aimed to investigate the relationship between aperture-based plan complexity metrics (PCM) in volumetric modulated arc therapy (VMAT) competition plans and clinical treatment plans verified through patient-specific QA (PSQA). In addition, the association of PCMs with plan quality was examined. A head and neck (HN) plan competition was held for Japanese institutions from June 2019 to July 2019, in which 210 competition plans were submitted. Dose distribution quality was quantified based on dose-volume histogram (DVH) metrics by calculating the dose distribution plan score (DDPS). Differences in PCMs between the two VMAT treatment plan groups (HN plan competitions held in Japan and clinically accepted HN VMAT plans through PSQA) were investigated. The mean (± standard deviation) DDPS for the 98 HN competition plans was 158.5 ± 20.6 (maximum DDPS: 200). DDPS showed a weak correlation with PCMs with a maximum r of 0.45 for monitor unit (MU); its correlation with some PCMs was "very weak." Significant differences were found in some PCMs between plans with the highest 20% DDPSs and the remaining plans. The clinical VMAT and competition plans revealed similar distributions for some PCMs. Deviations in PCMs for the two groups were comparable, indicating considerable variability among planners regarding planning skills. The plan complexity for HN VMAT competition plans increased for high-quality plans, as shown by the dose distribution. Direct comparison of PCMs between competition plans and clinically accepted plans showed that the submitted HN VMAT competition plans were realistic and reasonable from the QA perspective. This evaluation may provide a set of criteria for evaluating plan quality in plan competitions., Competing Interests: Conflict of Interest There are no ethical issues concerning this manuscript. Mr. Akihisa Wakita received a research grant from the Japanese Society for Radiation Oncology (JASTRO); Dr. Hiroshi Igaki received a research grant from HekaBio K.K. honoraria for lectures from Itochu corporation and AstraZeneca, and personal fee from Hekabio., (Copyright © 2024 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.)

Introduction: Ballet dancers have a special morphology, such as a large muscle thickness that affects passive torque. Ballet dancers also possess specialized mechanical, and neural properties of muscles and tendons. These characteristics may produce different static stretching effects than non-dancers. Therefore, this study aimed to determine the differences in the effects of static stretching on joint range of motion, passive torque, and muscle strength between ballet dancers and non-dancers. Methods: This study included 13 ballet dancers and 13 college students. The muscle and tendon thicknesses were assessed using ultrasonography. In the right lower extremity, torque-angle data and muscle-tendon junction displacement measurements were obtained during isokinetic passive dorsiflexion before and after a 5-minute static stretch against the right plantar flexors. The relative stretching intensity was calculated by dividing the stretching angle by the maximal dorsiflexion angle pre-stretch. Additionally, the isometric maximal voluntary plantar flexion torque on the left ankle was measured before and after 5 minutes of static stretching against the left plantar flexors. Results: Ballet dancers had significantly greater muscle thickness than non-dancers (22.4 ± 2.2 vs 18.1 ± 1.7 mm), whereas no significant difference was observed in the Achilles tendon thickness. No significant difference was observed in the stretching angle; however, the relative stretching intensity was higher in the control group (65.9 ± 19.8 vs 127.5 ± 63.8%). Static stretching increased the maximal dorsiflexion angle (dancer: 30.4° ± 9.6° to 33.9° ± 9.5°, non-dancer: 18.4° ± 8.6° to 20.5° ± 9.5°) and maximal passive torque in both groups, whereas the maximal isometric plantar flexion torque and submaximal passive torque decreased. However, no significant differences were observed in the changes between the groups. Conclusion: These results indicate that despite having a lower relative stretching intensity, ballet dancers experienced similar changes as non-dancers after 5 minutes of static stretching., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: To protect the rectum and bladder from high dose exposure, the Japanese guidelines for managing uterine cervical carcinoma recommend pelvic irradiation with central shielding (CS). Conversely, the European Society for Radiotherapy and Oncology (ESTRO) and the American Brachytherapy Society (ABS) guidelines recommend delivering ≥85 Gy to high-risk clinical target volume D 90 (CTV HR D 90% ). In this study, we investigated whether a gel spacer can enable the safe delivery of the ESTRO/ABS-recommended doses to the target while observing dose constraints for the OARs without using CS in external beam radiation therapy (EBRT)., Materials and Methods: Twenty patients who received definitive radiation therapy without CS and were treated by brachytherapy with a gel spacer between 2017 and 2022 were retrospectively reviewed. The cumulative doses of EBRT and brachytherapy treatment outcomes and incidence of adverse events were also examined., Results: The median cumulative CTV HR D 90% , rectum D 2cm3 , and bladder D 2cm3 were 86.6 Gy, 62.9 Gy, and 72.0 Gy, respectively. The 2-year local control rate was 95%. There were no CTCAE ≥Grade 3 late gastrointestinal or genitourinary adverse events., Conclusions: The use of gel spacer can enable ESTRO/ABS-recommended dose constraints even without using CS in EBRT, with favorable outcomes and low adverse event rates., (Copyright © 2024 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Purpose: This study aimed to clarify the dosimetric impact of the respiratory motion of the liver on stereotactic body radiation therapy (SBRT) for spine metastasis and examine the utility of introducing beam avoidance (beam-off at specific gantry angles)., Methods: A total of 112 consecutive patients who underwent SBRT for spine metastasis between 2018 and 2024 were examined. Overall, 15 patients who had lesions near the liver dome were included in this study. Retrospective treatment plans were generated using computed tomography (CT) images acquired during inhalation and exhalation to evaluate the dosimetric impact of respiratory motion of the liver. The dose difference (DD) and relative value (DD%) were evaluated using the dose-volume histogram (DVH) metrics, planning target volume D max , D 95% , spinal cord D 0.035 cc , and esophagus D 2.5 cc . The magnitude of the liver movements was evaluated based on differences of liver size L ave at the isocentric axial plane between the inspiratory and expiratory CT images., Results: The DD in almost all DVH metrics tended to increase when the liver moved away from the target during inhalation: For example, Mean ± $ \pm $ a standard deviation (SD) DD in PTV D 95% for the treatment plan incorporating beam avoidance and those without beam avoidance was 0.5 ± $\pm$ 0.3 and 0.9 ± $ \pm $ 0.6 Gy, respectively. The spinal cord D 0.035 cc for those shows 0.4 ± $ \pm $ 0.2 and 0.7 ± $ \pm $ 0.7 Gy, respectively. The treatment plans without beam avoidance also showed moderate or strong correlations between L ave and DD for almost all DVH metrics. No correlation was seen in the beam avoidance plan. The spinal cord D 0.035 cc revealed approximately 1 Gy or +4% in DD when L ave was < -4 cm., Conclusions: Respiratory motion of the liver dome can cause substantial dosimetric discrepancies in the dose delivered to the spinal cord, although the extent depends on patient variables. Dose assessment should be performed for determining the appropriate means of respiratory management, such as breath-hold. Alternatively, beam avoidance effectively mitigates the impact., (© 2024 The Author(s). Journal of Applied Clinical Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)

Increased brain size and its rostral bias are hallmarks of vertebrate evolution, but the underlying developmental and genetic basis remains poorly understood. To provide clues to understanding vertebrate brain evolution, we investigated the developmental mechanisms of brain enlargement observed in the offspring of a previously unrecognized, spontaneously occurring female variant line of Xenopus that appears to reflect a genetic variation. Brain enlargement in larvae from this line showed a pronounced rostral bias that could be traced back to the neural plate, the primordium of the brain. At the gastrula stage, the Spemann organizer, which is known to induce the neural plate from the adjacent dorsal ectoderm and give it the initial rostrocaudal patterning, was expanded from dorsal to ventral in a large proportion of the offspring of variant females. Consistently, siamois expression, which is required for Spemann organizer formation, was expanded laterally from dorsal to ventral at the blastula stage in variant offspring. This implies that the active region of the Wnt/β-catenin signaling pathway was similarly expanded in advance on the dorsal side, as siamois is a target gene of this pathway. Notably, the earliest detectable change in variant offspring was in fertilized eggs, in which maternal wnt11b mRNA, a candidate dorsalizing factor responsible for activating Wnt/β-catenin signaling in the dorsal embryonic region, had a wider distribution in the vegetal cortical cytoplasm. Since lateral spreading of wnt11b mRNA, and possibly that of other potential maternal dorsalizing factors in these eggs, is expected to facilitate lateral expansion of the active region of the Wnt/β-catenin pathway during subsequent embryonic stages, we concluded that aberrant Wnt/β-catenin signaling could cause rostral-biased brain enlargement via expansion of siamois expression and consequent expansion of the Spemann organizer in Xenopus. Our studies of spontaneously occurring variations in brain development in Xenopus would provide hints for uncovering genetic mutations that drive analogous morphogenetic variations during vertebrate brain evolution., Competing Interests: Declaration of competing interest The authors declare no competing or financial interests., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

In this study, we aimed to conduct a survey on the current clinical practice of, staffing for, commissioning of, and staff training for online adaptive radiotherapy (oART) in the institutions that installed commercial oART systems in Japan, and to share the information with institutions that will implement oART systems in future. A web-based questionnaire, containing 107 questions, was distributed to nine institutions in Japan. Data were collected from November to December 2023. Three institutions each with the MRIdian (ViewRay, Oakwood Village, OH, USA), Unity (Elekta AB, Stockholm, Sweden), and Ethos (Varian Medical Systems, Palo Alto, CA, USA) systems completed the questionnaire. One institution (MRIdian) had not performed oART by the response deadline. Each institution had installed only one oART system. Hypofractionation, and moderate hypofractionation or conventional fractionation were employed in the MRIdian/Unity and Ethos systems, respectively. The elapsed time for the oART process was faster with the Ethos than with the other systems. All institutions added additional staff for oART. Commissioning periods differed among the oART systems owing to provision of beam data from the vendors. Chambers used during commissioning measurements differed among the institutions. Institutional training was provided by all nine institutions. To the best of our knowledge, this was the first survey about oART performed using commercial systems in Japan. We believe that this study will provide useful information to institutions that installed, are installing, or are planning to install oART systems., (© 2024. The Author(s), under exclusive licence to Japanese Society of Radiological Technology and Japan Society of Medical Physics.)

The zoonotic transmission of hepatitis E virus (HEV) genotypes 3 (HEV-3) and 4 (HEV-4), and rabbit HEV (HEV-3ra) has been documented. Vaccination against HEV infection depends on the capsid (open reading frame 2, ORF2) protein, which is highly immunogenic and elicits effective virus-neutralizing antibodies. Escherichia coli ( E. coli ) is utilized as an effective system for producing HEV-like particles (VLPs). However, research on the production of ORF2 proteins from these HEV genotypes in E. coli to form VLPs has been modest. In this study, we constructed 21 recombinant plasmids expressing various N-terminally and C-terminally truncated HEV ORF2 proteins for HEV-3, HEV-3ra, and HEV-4 in E. coli . We successfully obtained nine HEV-3, two HEV-3ra, and ten HEV-4 ORF2 proteins, which were primarily localized in inclusion bodies. These proteins were solubilized in 4 M urea, filtered, and subjected to gel filtration. Results revealed that six HEV-3, one HEV-3ra, and two HEV-4 truncated proteins could assemble into VLPs. The purified VLPs displayed molecular weights ranging from 27.1 to 63.4 kDa and demonstrated high purity (74.7-95.3%), as assessed by bioanalyzer, with yields of 13.9-89.6 mg per 100 mL of TB medium. Immunoelectron microscopy confirmed the origin of these VLPs from HEV ORF2. Antigenicity testing indicated that these VLPs possess characteristic HEV antigenicity. Evaluation of immunogenicity in Balb/cAJcl mice revealed robust anti-HEV IgG responses, highlighting the potential of these VLPs as immunogens. These findings suggest that the generated HEV VLPs of different genotypes could serve as valuable tools for HEV research and vaccine development.

This study explores the impact of royal jelly (RJ) on small intestinal epigenomic changes. RJ, produced by honeybees, is known for its effects on metabolic diseases. The hypothesis is that RJ induces epigenomic modifications in small intestinal epithelial cells, affecting gene expression and contributing to metabolic health. Male db/m and db/db mice were used to examine RJ's effects through mRNA sequencing and CUT&Tag methods. This study focused on histone modifications and gene expression changes, with statistical significance set at p < 0.05. RJ administration improved insulin sensitivity and lipid metabolism without affecting body weight. GO and KEGG pathway analyses showed significant enrichment in metabolic processes, cellular components, and molecular functions. RJ altered histone modifications, increasing H3K27me3 and decreasing H3K23Ac in genes associated with the G2M checkpoint. These genes, including Smc2, Mcm3, Ccnd1, Rasal2, Mcm6, and Mad2l1, are linked to cancer progression and metabolic regulation. RJ induces beneficial epigenomic changes in small intestinal epithelial cells, improving metabolic health and reducing cancer-associated gene expression. These findings highlight RJ's potential as a therapeutic agent for metabolic disorders. Further research is needed to fully understand the mechanisms behind these effects and their implications for human health.

Introduction: In an MRI-guided linear accelerator (MR-LINAC) system, the planned doses for organs at risk and for tumours are assessed by MR imaging and re-contouring at every treatment. This allows treatment to be safer and more precise by ensuring that it is suitable for the state of the patient's organs on that day, as well as by allowing images to be acquired during radiation therapy to prevent radiation while organs are in motion.Here, we will conduct a confirmatory study of two-fractionated stereotactic magnetic resonance-guided adaptive radiation therapy for patients with localised prostate cancer., Methods and Analysis: This will be a single-arm study to demonstrate the safety and efficacy of ultra-hypofractionated radiation (26 Gy/2 Fr) using an MR-LINAC system in patients with very low-intermediate risk prostate cancer.The primary endpoint will be the incidence of grade ≥2 acute urinary tract adverse events occurring within 90 days of the start of radiation therapy.The sample size has been determined to be 58., Ethics and Dissemination: This study is performed in accordance with Ethical Guidelines for Medical and Health Research Involving Human Subjects, published by Japan's Ministry of Education, Science and Technology and the Ministry of Health, Labour and Welfare and the modified act on the Protection of Personal Information as well as the Declaration of Helsinki. This study was approved by the institutional ethics committee of the National Cancer Center on 20 November 2021.The findings of this trial will be submitted to an international peer-reviewed journal and the key findings will be presented at an international scientific conference.Authorship will be ascribed in accordance with the International Committee of Medical Journal Editors guidance., Trial Registration Number: UMIN000049746., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The combination of platinum-based chemotherapy and an antibody to PD-1 or to its ligand PD-L1, with or without an antibody to CTLA-4, has improved the survival of individuals with metastatic non-small-cell lung cancer (NSCLC). However, no randomised controlled trial has evaluated the survival benefit of adding a CTLA-4 inhibitor to platinum-based chemotherapy plus a PD-1 or PD-L1 inhibitor., Methods: This open-label, randomised, phase 3 trial was conducted at 48 hospitals in Japan. Eligible patients were aged 20 years or older with previously untreated advanced NSCLC and an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients with known driver oncogenes were excluded. Participants were randomly assigned (1:1) to receive platinum-based chemotherapy (four cycles) plus pembrolizumab (pembrolizumab group) or platinum-based chemotherapy (two cycles) plus nivolumab-ipilimumab (nivolumab-ipilimumab group). The primary endpoint was overall survival and assessed in all randomly assigned patients on an intention-to-treat basis. The trial is registered in the Japan Registry for Clinical Trials, jRCTs031210013, and is now closed to new enrolment and is ongoing., Findings: Between patient accrual initiation on April 6, 2021, and discontinuation of the trial on March 30, 2023, 11 (7%) of 148 patients in the nivolumab-ipilimumab group had a treatment-related death. Because of the high number of treatment-related deaths, patient accrual was terminated early, resulting in 295 patients (236 [80%] male and 59 [20%] female) enrolled; the primary analysis was done on the basis of 117 deaths (fewer than the required 329 deaths). By May 25, 2023 (data cutoff), overall survival did not differ significantly between the nivolumab-ipilimumab group and the pembrolizumab group (median 23·7 months [95% CI 17·6-not estimable] vs 20·5 months [17·6-not estimable], respectively; hazard ratio 0·98 [90% CI 0·72-1·34]; p=0·46). Non-haematological adverse events of grade 3 or worse occurred in 87 (60%) of 146 patients in the nivolumab-ipilimumab group and 59 (41%) of 144 patients in the pembrolizumab group. The pembrolizumab group tended to have a better quality of life compared with the nivolumab-ipilimumab group., Interpretation: The safety and efficacy data suggest an unfavourable benefit-risk profile for nivolumab-ipilimumab combined with platinum-based chemotherapy relative to pembrolizumab combined with platinum-based chemotherapy as a first-line treatment for patients with advanced NSCLC, although a definitive conclusion awaits an updated analysis of overall survival., Funding: The National Cancer Center Research and Development Fund and Japan Agency for Medical Research and Development., Competing Interests: Declaration of interests YoS has received grants from Chugai Pharmaceutical; and personal fees from Chugai Pharmaceutical, Ono Pharmaceutical, AstraZeneca, Bristol Myers Squibb, Taiho Pharmaceutical, and Kyowa Kirin, all outside of the submitted work. ShN has received grants from AstraZeneca, Chugai Pharmaceutical, and MSD; consulting fees from Asahi Kasei Pharma; and personal fees from AstraZeneca, Bayer, Chugai Pharmaceutical, Asahi Kasei Pharma, Kyowa Hakko Bio, and MSD, all outside of the submitted work. SS has received grants from AnHeart Therapeutics, AstraZeneca, Chugai Pharmaceutical, MSD, Daiichi Sankyo, Bristol Myers Squibb, Nippon Boehringer Ingelheim, Ono Pharmaceutical, AbbVie, Amgen, Taiho Pharmaceutical, Takeda, Accerise, and Parexel International; and personal fees from AstraZeneca, Chugai Pharmaceutical, Ono Pharmaceutical, Bristol Myers Squibb, MSD, Nippon Boehringer Ingelheim, Pfizer, Taiho Pharmaceutical, Eli Lilly, Novartis, Kyowa Kirin, Takeda, Nippon Kayaku, Merck, Amgen, AbbVie, Otsuka, Thermo Fisher Scientific, Towa Pharmaceutical, Sysmex, and Eisai, all outside of the submitted work. HidehH has received research fundings from MSD, AbbVie, AstraZeneca, Bristol Myers Squibb, Ono Pharmaceutical, Daiichi Sankyo, Janssen, Chugai Pharmaceutical, and Roche; personal fees from AstraZeneca, MSD, Eli Lilly, Ono Pharmaceutical, Bristol Myers Squibb, Chugai Pharmaceutical, Roche, Amgen, and Abbvie; and personal fees from AstraZeneca, Chugai Pharmaceutical, Roche, Ono Pharmaceutical, Bristol Myers Squibb, and AbbVie (served on the advisory board), all outside of the submitted work. YaY has received personal fees from Taiho Pharmaceutical and Takeda, all outside of the submitted work. HidetH has received grants from IQVIA Services Japan, Eisai, Syneos Health Clinical, EP-CRSU, EPS, Shionogi, Nippon Kayaku, Otsuka Pharmaceutical, Takeda, GSK, MSD, Sanofi, Amgen, Chugai Pharmaceutical, Taiho Pharmaceutical, Nippon Boehringer Ingelheim, Bristol Myers Squibb, SRL Medisearch, Janssen Pharmaceutical, PRA Health Sciences, CMIC, Astellas Pharma, Pfizer R&D Japan, Ascent Development Services, Labcorp Development Japan, Eisai, Kobayashi Pharmaceutical, Bayer, and Pfizer Japan; royalties or licenses from Sysmex; personal fees from Ono Pharmaceutical, Merck, Daiichi Sankyo, 3H Clinical Trial, AstraZeneca, Novartis Pharma, Chugai Pharmaceutical, Bristol Myers Squibb, Eli Lilly Japan, Amgen, MSD, Sysmex, Pfizer Japan, Takeda, Nippon Boehringer Ingelheim; and personal fees for serving on an advisory board from Daiichi Sankyo, Nippon Boehringer Ingelheim, AstraZeneca, Amgen, Chugai Pharmaceutical, Novocure, Eli Lilly Japan, Gilead Science, and Blueprint Medicine, all outside of the submitted work. KA has received lecture fees from AstraZeneca, Ono Pharmaceutical, Chugai Pharmaceutical, MSD, Bristol Myers Squibb, and Takeda, all outside of the submitted work. SN has received grants from GSK, Chugai Pharmaceutical, Eli Lilly, Taiho Pharmaceutical, Teijin, Kyowa Kirin, Shionogi, Boehringer Ingelheim, Daiichi Sankyo, Kyorin, and Nippon Kayaku; personal fees from AstraZeneca, Pfizer, Chugai Pharmaceutical, Eli Lilly, Daiichi Sankyo, MSD, Ono Pharmaceutical, Eisai, Kyorin, Taiho Pharmaceutical, Takeda, Boehringer Ingelheim, Novartis, Amgen, Merck, Nippon Kayaku, and Kyowa Kirin; and personal fees for serving on advisory boards from AstraZeneca and Daiichi Sankyo, all outside of the submitted work. RM has received personal fees from Daiichi Sankyo, Chugai Pharmaceutical, AstraZeneca, Bristol Myers Squibb, Eli Lilly Japan, MSD, Amgen, and Merck; and personal fees for serving on an advisory board from Daiichi Sankyo, all outside of the submitted work. MY has received grants from Bristol Myers Squibb, Chugai Pharmaceutical, Eli Lilly Japan, MSD, Nippon Kayaku, Taiho Pharmaceutical, and Takeda; and personal fees from AstraZeneca, Bristol Myers Squibb, Chugai Pharmaceutical, Daiichi Sankyo, Eli Lilly Japan, Johnson & Johnson, MSD, Nippon Kayaku, Ono Pharmaceutical, Pfizer Japan, and Taiho Pharmaceutical, all outside of the submitted work. TY has received grants from MSD, Chugai Pharmaceutical, Bristol Myers Squibb, Boehringer Ingelheim Japan, Takeda, Delta-Fly Pharma, Janssen, AbbVie, Daiichi Sankyo, and Parexel International; and personal fees from AstraZeneca, Chugai Pharmaceutical, Eli Lilly Japan, Pfizer Japan, Bristol Myers Squibb, Ono Pharmaceutical, Takeda, Nippon Kayaku, MSD, Novartis, and Merck, all outside of the submitted work. KY has received grants from AbbVie, Amgen, AstraZeneca, Boehringer Ingelheim, Chugai Pharmaceutical, Daiichi Sankyo, Lilly, MSD, Pfizer, Taiho Pharmaceutical, and Takeda; and personal fees from AbbVie, Amgen, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Chugai Pharmaceutical, Daiichi Sankyo, Janssen, Kyowa Kirin, Lilly, Merck Serono, Novartis, Ono Pharmaceutical, Otsuka, Taiho Pharmaceutical, and Takeda, all outside of the submitted work. TakayK has received grants from AstraZeneca, Amgen, MSD, Janssen, Takeda, and Daiichi Sankyo; and personal fees from AstraZeneca, Eli Lilly, Ono Pharmaceutical, Bristol Myers Squibb, Chugai Pharmaceutical, MSD, Pfizer, and Nippon Kayaku, all outside of the submitted work. HO has received grants from Bristol Myers Squibb, MSD, and Taiho Pharmaceutical, all outside of the submitted work. TakasK has received personal fees from MSD, AstraZeneca, Ono Pharmaceutical, Chugai Pharmaceutical, and Bristol Myers Squibb, all outside of the submitted work. KK has received personal fees from AstraZeneca, MSD, Chugai Pharmaceutical, Eli Lilly Japan, and Taiho Pharmaceutical; payment for expert testimony from Eli Lilly Japan; and personal fees for serving on advisory boards from Eli Lilly Japan and AstraZeneca, all outside of the submitted work. YF has received personal fees from AstraZeneca, Amgen, Bristol Myers Squibb, Chugai Pharmaceutical, Daiichi Sankyo, Eli Lilly, Merck, MSD, Novartis, Ono Pharmaceutical, Pfizer, Takeda, and Taiho Pharmaceutical; payment for expert testimony from Chiome Bioscience, Otsuka Pharmaceutical, and Ono Pharmaceutical; and personal fees for serving on advisory boards from AstraZeneca, Daiichi Sankyo, Micron, and Ono Pharmaceutical, all outside of the submitted work. SM has received grants from AstraZeneca, Takeda, Chugai Pharmaceutical, Sanofi, MSD, Daiichi Sankyo, Ono Pharmaceutical, and Janssen; and personal fees from AstraZeneca, Chugai Pharmaceutical, Takeda, Eli Lilly, MSD, Pfizer, Novartis, and Taiho Pharmaceutical, all outside of the submitted work. SK has received personal fees from Boehringer Ingelheim Japan, Taiho Pharmaceutical, Chugai Pharmaceutical, Bristol Myers Squibb, MSD, Ono Pharmaceutical, and Guardant Health Japan, all outside of the submitted work. HA reports grants from Amgen and Chugai Pharmaceutical; personal fees from Amgen, AstraZeneca, Boehringer Ingelheim Japan, Bristol Myers Squibb, Chugai Pharmaceutical, Eli Lilly Japan, MSD, Nippon Kayaku, Novartis, Ono Pharmaceutical, Pfizer, Takeda, and Taiho Pharmaceutical; personal fees for serving on advisory boards from Amgen, MSD, Janssen, and Sandoz; and a role on the WCLC Patient Advocacy Committee, all outside of the submitted work. HK has received grants from Eli Lilly; and personal fees from Chugai Pharmaceutical, AstraZeneca, MSD, Bristol Myers Squibb, Novartis, Eli Lilly Japan, Ono Pharmaceutical, and Takeda, all outside of the submitted work. ToshiK has received grants from Chugai Pharmaceutical, AstraZeneca, Eli Lilly Japan, Taiho Pharmaceutical, Bristol Myers Squibb, Ono Pharmaceutical, MSD, Kyowa Hakko Kirin, Merck, Daiichi Sankyo, Amgen, AbbVie, Sanofi, Eisai, Labcorp Development Japan, IQVIA Services Japan, Gilead Sciences, Pfizer, and Bayer; consulting fees from Chugai Pharmaceutical, AstraZeneca, Ono Pharmaceutical, Pfizer Japan, Daiichi Sankyo, Bayer, and AbbVie; and personal fees from Chugai Pharmaceutical, AstraZeneca, Eli Lilly Japan, Taiho Pharmaceutical, Bristol Myers Squibb, Ono Pharmaceutical, MSD, Pfizer Japan, Kyowa Hakko Kirin, Nippon Boehringer Ingelheim, Merck, Nippon Kayaku, Novartis, Daiichi Sankyo, Takeda, Bayer, Sawai, Amgen, and Eisai, all outside of the submitted work. HF has received grants from the National Cancer Center Research and Development Fund; and lecture fees from Kyowa Kirin, Chugai Pharmaceutical, and CMIC, all outside of the submitted work. YO reports grants from AstraZeneca, Chugai Pharmaceutical, Eli Lilly, LOXO, Kirin, Sumitomo, Pfizer, Taiho Pharmaceutical, Novartis, Takeda, Kissei, Daiichi Sankyo, and Janssen; personal fees from AstraZeneca, Chugai Pharmaceutical, Eli Lilly, Ono Pharmaceutical, Bristol Myers Squibb, Boehringer Ingelheim, Bayer, Pfizer, MSD, Taiho Pharmaceutical, Nippon Kayaku, Kyowa Hakko Kirin, Eisai, and Daiichi Sankyo; payment for expert testimony from AstraZeneca, Chugai Pharmaceutical, Ono Pharmaceutical, Bristol Myers Squibb, Kyorin, Celltrion, Amgen, Nippon Kayaku, Boehringer Ingelheim, AnHeart Therapeutics, and PharmaMar; personal fees for serving on an advisory board from Haihe Biopharma; and roles in the Japanese Society of Medical Oncology, Japan Lung Cancer Society, and Japan Clinical Oncology Group, all outside of the submitted work. IO has received grants from the National Cancer Center Research and Development Fund and Japan Agency for Medical Research and Development during the conduct of the study; grants from AstraZeneca, Taiho Pharmaceutical, Boehringer Ingelheim, Ono Pharmaceutical, MSD, Eli Lilly, Astellas, Bristol Myers Squibb, Novartis, Chugai Pharmaceutical, Pfizer, and AbbVie; consulting fees from AstraZeneca, Bristol Myers Squibb, and AbbVie; and personal fees from AstraZeneca, Taiho Pharmaceutical, Boehringer Ingelheim, Ono Pharmaceutical, MSD, Eli Lilly, Bristol Myers Squibb, Novartis, Chugai Pharmaceutical, and Pfizer, all outside of the submitted work. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Progress toward single-molecule electronics relies on a thorough understanding of local physico-chemical processes and development of synthetic routines for controlled hetero-coupling. We demonstrate a structurally unexpected ring closure process for a homo-coupled 4,4'-bipicenyl, realized in on-surface synthesis. An initial covalent C-C coupling of 4-bromopicene locks at lower temperatures the position and geometrically shields part of 4,4'-bipicenyl. Employing this effect of shielding might offer a path toward controlled stepwise hetero-coupling. At higher temperatures, a thermally activated three-dimensional rotation upon hydrogen dissociation, a dehydrogenative roto-cyclization, lifts the surface-dimensionality restriction, and leads to the formation of a perylene. Thereby, the shielded molecular part becomes accessible again., (© 2024 Wiley-VCH GmbH.)

The serotonergic neurons in the raphe nucleus are implicated in various cognitive functions such as learning and emotion. In vertebrates, the raphe nucleus is divided into the dorsal raphe and the median raphe. In contrast to the abundance of knowledge on the functions of the dorsal raphe, the roles of the serotonergic neurons in the median raphe are relatively unknown. The studies using zebrafish revealed that the median raphe serotonergic neurons receive input from the two distinct pathways from the habenula and the IPN. The use of zebrafish may reveal the function of the Hb-IPN-median raphe pathway. To clarify the functions of the median raphe serotonergic neurons, it is necessary to distinguish them from those in the dorsal raphe. Most median raphe serotonergic neurons originate from rhombomere 2 in mice, and we generated the transgenic zebrafish which can label the serotonergic neurons derived from rhombomere 2. In this study, we found the serotonergic neurons derived from rhombomere 2 are localized in the median raphe and project axons to the rostral dorsal pallium in zebrafish. This study suggests that this transgenic system has the potential to specifically reveal the function and information processing of the Hb-IPN-raphe-telencephalon circuit in learning., Competing Interests: Declaration of competing interest The authors report no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Acute hepatitis E was considered rare until reports emerged affirming the existence of hepatitis E virus (HEV) genotypes 3 and 4 infections in Japan in the early 2000s. Extensive studies by Japanese researchers have highlighted the pivotal role of pigs and wild animals, such as wild boars and deer, as reservoirs for HEV, linking them to zoonotic infections in Japan. Currently, when hepatitis occurs subsequent to the consumption of undercooked or grilled pork, wild boar meat, or offal (including pig liver and intestines), HEV infection should be considered. Following the approval of anti-HEV immunoglobulin A antibody as a diagnostic tool for hepatitis E by Japan's Health Insurance System in 2011, the annual number of diagnosed cases of HEV infection has surged. Notably, the occurrence of post-transfusion hepatitis E promoted nationwide screening of blood products for HEV using nucleic acid amplification tests since 2020. Furthermore, chronic hepatitis E has been observed in immunosuppressed individuals. Considering the significance of hepatitis E, heightened preventive measures are essential. The Japan Agency for Medical Research and Development Hepatitis A and E viruses (HAV and HEV) Study Group, which includes special virologists and hepatologists, held a virtual meeting on February 17, 2024. Discussions encompassed pathogenesis, transmission routes, diagnosis, complications, severity factors, and ongoing and prospective vaccination or treatments for hepatitis E. Rigorous assessment of referenced studies culminated in the formulation of recommendations, which are detailed within this review. This comprehensive review presents recent advancements in HEV research and Japanese clinical practice guidelines for HEV infection., (© 2024 Japan Society of Hepatology.)

[3 2 ](1,4)Naphthalenophanes, bearing carbon-bridge chains (syn- and anti-NPs) and nitrogen-bridge chains (syn- and anti-ANPs), were synthesized, and their X-ray structures and photoreactions were investigated. The intramolecular separation distance between the naphthalene cores for ANPs was shorter than that for NPs, suggesting that intramolecular interactions between the naphthalene rings  were more efficient for ANPs compared to NPs. Upon photoirradiation at 300 nm, anti-NP, syn-ANP and anti-ANP produced the corresponding intramolecular [π4s + π4s] cycloadducts, whereas syn-NP gave an unidentified complex product mixture. Quantum yields for the photo-consumption (Φ PC ) of NPs and ANPs were evaluated to quantitatively compare their photoreactivity. The Φ PC values of ANPs were approximately two-fold higher than those of ANPs.Noteworthily, the Φ PC value of syn-ANP was estimated to be unity. Based on these results we discuss the effects of the alignments of the naphthalene cores (anti vs. syn) and the bridging elements (C-bridge vs. N-bridge) on the photoreaction efficiencies of [3 2 ](1,4)naphthalenophanes., (© 2024. The Author(s).)

Spontaneous reactivation of the Hepatitis B virus (HBV) is rare in individuals with previously resolved infections. This report presents the case of a 71 year-old Japanese woman who experienced HBV reactivation without any prior immunosuppressive therapy or chemotherapy. Before the onset of liver injury, the patient was negative for hepatitis B surface antigen (HBsAg) but positive for hepatitis B surface antibody. She subsequently developed liver injury, with the reappearance of HBsAg and HBV DNA. The patient was successfully treated with tenofovir alafenamide, and prednisolone. Full-genome sequencing of HBV revealed subgenotype B1 without hepatitis B e-negative mutations in the precore and core promoter regions and 12 amino acid alterations in the pre-S1/S, P, and X genes. Notably, the S gene mutations D144A and K160N, which alter the antigenicity of HBsAg and potentially contribute to its reactivation, were identified. This case emphasizes the importance of vigilance for spontaneous reactivation of resolved HBV, highlighting the need for comprehensive genomic analysis to understand the associated virological intricacies., (© 2024. Japanese Society of Gastroenterology.)

Background: Although clinical guidelines recommend self-care assessment for patients with chronic heart failure (CHF), its prognostic significance remains controversial. This study aimed to compare the prognostic significance of self-care behavior on mortality between patients with and without a history of recent hospitalization for heart failure (HF)., Methods: We analyzed consecutive 1907 CHF patients from a Japanese multicenter registry (January 2020-June 2023) using the 9-item European Heart Failure Self-care Behavior Scale (EHFScBS-9) at enrolment. Suboptimal self-care behavior was defined as a score < 70 on the EHFScBS-9. Patients were divided into recent (within 30 days post-discharge, n = 664) and no recent hospitalization for HF groups (n = 1263), respectively. The primary outcome was a composite of all-cause death and rehospitalization for HF., Results: During a median follow-up period of 427 (interquartile range 273-630) days, the primary outcome occurred in 100 patients. Patients with suboptimal self-care behavior exhibited a higher incidence of the primary outcome in the recent hospitalization for HF group (p = 0.020) but not in the no recent hospitalization for HF group (P = 0.16). Multivariable regressions showed suboptimal self-care behavior was independently associated with the primary outcome in the recent hospitalization for HF group with a significant interaction (P = 0.029)., Conclusion: In patients recently hospitalized for HF, but not in those without a recent hospitalization history for HF, suboptimal self-care behavior was associated with adverse events. This indicates the importance of self-care education for these patients., Competing Interests: Declaration of competing interest Dr. Toshiyuki Nagai is an associate editor of “International Journal of Cardiology”. Dr. Toshiyuki Nagai received a research grant from Mitsubishi Tanabe Pharma Corp. and honoraria from Kyowa Kirin Co., Ltd., Bayer Yakuhin, Ltd., Viatris Inc., and Boehringer Ingelheim Japan Co., Ltd. Dr. T.A. received a research grant from Daiichi Sankyo Co., Ltd., scholarship funds from Biotronik Japan Co., Ltd., Medtronic Japan Co., Ltd., Win International Co., Ltd., Medical System Network Co., Ltd., and Hokuyaku Takeyama Holdings, Inc. and honoraria from Daiichi Sankyo Co., Ltd., Ono Pharmaceutical Co., Ltd., Boehringer Ingelheim Japan Co., Ltd., Bayer's Pharmaceuticals Co., Ltd., and Bristol-Myers Squibb Co., Ltd. The remaining authors declare no conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: Despite being a less-invasive procedure, esophagectomy can cause severe infectious complications, such as pneumonia and anastomotic leakage. Herein, we aimed to clarify the inflammatory characteristics of pneumonia/anastomotic leakage after esophagectomy by assessing the difference between the postoperative trends of serum C-reactive protein (CRP) and procalcitonin (PCT) levels in patients with pneumonia/anastomotic leakage using the values on the consecutive postoperative day (POD)., Methods: This study included 439 patients who underwent minimally invasive esophagectomy. Serum CRP and PCT levels were measured on PODs 1-7, 10, and 14. Pneumonia and anastomotic leakage were defined as Clavien-Dindo grades ≥ 2., Results: Pneumonia and anastomotic leakage occurred in 96 and 51 patients, respectively. The CRP and PCT levels peaked on POD 3 (11.6 ± 6.8 mg/dL) and POD 2 (0.69 ± 2.9 ng/mL), respectively. Between PODs 3 and 14, CRP levels were significantly higher in patients with pneumonia and anastomotic leakage than in those without complications (P < 0.001). Between PODs 3 and 14, PCT levels were significantly higher in patients with pneumonia; however, on most PODs, there were no significant differences in PCT levels between patients with and without anastomotic leakage., Conclusion: Inflammatory reactions caused by pneumonia may be more intense than those caused by anastomotic leakage after esophagectomy. Postoperative trends in serum CRP and PCT levels may vary depending on the complication type. Pneumonia and anastomotic leakage after esophagectomy can be potentially distinguished by the postoperative trend of PCT values before detailed examinations, such as computed tomography and endoscopy., (© 2024. The Author(s), under exclusive licence to The Japanese Association for Thoracic Surgery.)

Background Postoperative chylothorax is a rare but life-threatening complication of esophagectomy. However, due to its rarity, researching the risk factors and selecting appropriate treatment options has been limited. Methods This study included 727 patients with esophageal cancer who underwent minimally invasive esophagectomy at our hospital. To detect the risk factors for chylothorax, we divided the patients into two groups, with and without postoperative chylothorax. We then compared patient characteristics, tumor-specific variables, and operative details. Subsequently, we analyzed the peri-treatment characteristics and outcomes for the three distinct treatment options we had chosen: surgery, conversion (the group that finally underwent surgery after unsuccessful conservative treatment), and conservative. Results Of the 727 patients, 18 (2.5%) developed a chylothorax. The mean BMI was lower (20.3 vs. 21.9, p=0.057), and more cases of thoracic duct resection were found in the chylothorax group (33.3% vs. 6.2%, p=0.001), with statistical significance. Multivariate analysis identified thoracic duct resection as a risk factor (adjusted odds ratio, 6.83). The drainage volume two days after chylothorax was higher in the surgery group, although the difference was not statistically significant (surgery group, 1,405 ml vs. conversion group, 260 ml vs. conservative group, 310 ml; p=0.073). The surgery group had the shortest median postoperative hospital days among these groups (21.5 as compared to 102 and 25.0 days in the conversion and conservative groups, respectively; p<0.001). None of the patients died during their hospital stays. Conclusion Thoracic duct resection during the initial minimally invasive esophagectomy was an independent risk factor for chylothorax. If drainage volume does not decrease on the second day, early surgery may lead to earlier discharge., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Ethics Committee of the Graduate School of Medicine, Tohoku University issued approval 2019-1-429. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Tsuchitani et al.)

Background: Compartment syndrome commonly occurs in patients with forearm and lower leg fractures. Compartment syndromes of the gluteal and thigh muscles are less common. It is imperative that compartment syndrome be diagnosed and treated with fasciotomy as soon as possible. However, there are few reports on the diagnosis and treatment strategies for compartment syndromes that occur simultaneously in multiple anatomical regions or in the ipsilateral gluteal region and thigh., Case Presentation: We report on a 76-year-old man who was obliquely crushed under a tree extending from the right forearm to the left groin. He was brought to our emergency room, where he was diagnosed with compartment syndrome of the right forearm and left lower leg and crush syndrome. Emergency fasciotomy was performed. On the day after admission, swelling and tightness of the left gluteal thigh became apparent, and intracompartmental pressures were elevated, which led to an additional diagnosis of these compartment syndromes. A fasciotomy was performed, the gluteal skin incision was made according to the Kocher-Langenbeck approach (one of the posterior approaches for hip fractures), and the thigh was approached by extending the incision laterally. This surgical approach enabled the decompression of the compartments through a single incision and allowed for easier wound treatment and closure., Conclusion: This case highlights the diagnosis and treatment of compartment syndrome in four anatomical regions. Extension of the Kocher-Langenbeck approach to the lateral thigh can be a useful surgical approach for ipsilateral gluteal and thigh compartment syndrome., (© 2024. The Author(s).)

Background: Cold agglutination syndrome is a subtype of autoimmune hemolytic anemia. The condition is referred to as "cold" because the antibodies become active and induce hemolysis at cold temperatures, typically 3-4 °C, which is not always the case in other kinds of autoimmune hemolytic anemia. Whereas primary cold agglutination syndrome may occur in the absence of underlying conditions, secondary cold agglutination syndrome is associated with the presence of underlying infections, including coronavirus disease 2019., Case Presentation: We report the case of a 69-year-old Japanese woman with periodontitis who was referred to our hospital with complaints of brown-colored urine and chest pain. Her hemoglobin level was 6.1 g/dL. Computed tomography revealed multiple lung abscesses. Her direct antibody test results were positive (2+) for anti-complement direct antiglobulin and negative for immunoglobulin G, and her cold agglutinin titer was elevated at 1:4096. Workup for anemia revealed a positive result for cold agglutination syndrome. The patient had received the fourth dose of coronavirus disease 2019 vaccination. Nasopharyngeal swab test for detecting severe acute respiratory syndrome coronavirus 2 using a real-time reverse-transcription polymerase chain reaction gave a cycle threshold value of 42.3, and the level of virus-specific immunoglobulin G was elevated at 7.71 S/C (normal range -1.4 S/C)., Conclusion: A decrease in hemoglobin in patients with coronavirus disease 2019 may be associated with secondary cold agglutination syndrome. The patient was hypothesized to have developed multiple lung abscesses with secondary cold agglutination syndrome following coronavirus disease 2019. Thus, following coronavirus disease 2019, patients can develop secondary cold agglutination syndrome, which could worsen owing to associated bloodstream bacterial infections., (© 2024. The Author(s).)

Background: Approximately 296 million people suffer from chronic hepatitis B (CHB) caused by hepatitis B virus (HBV). Current standard treatment, nucleos(t)ide analogs, are not efficient enough to eradicate HBV from the hepatocytes. Thus, developing new drugs for CHB is desired to achieve complete cure., Methods: Here we established a novel HBV reporter system, HBV-HiBiT-PS2, to screen new drugs for CHB. HBV-HiBiT-PS2 was constructed by introducing a HiBiT-tag at the 5'-end of PreS2 and introduced into HepG2-NTCP cells. Culture supernatant containing HBV-HiBiT-PS2 virions was fractionated by a sucrose density gradient ultracentrifugation to characterize their components. Replication kinetics and reporter function of HBV-HiBiT-PS2 were determined by analyzing the parameters for HBV replication in the presence or absence of HBV inhibitors., Results: HBV-HiBiT-PS2 could be used for monitoring most of the replication cycle of HBV. The effects of well-characterized HBV inhibitors could be evaluated by the HiBiT activity. HBV-HiBiT-PS2 could be specialized for screening secretion inhibitors for hepatitis B surface antigen (HBsAg) because most of the HiBiT activity was derived from subviral particles which are the multimers of HBsAg., Conclusions: We demonstrated that HBV-HiBiT-PS2 would be a robust tool for screening novel drugs, especially HBsAg secretion inhibitors, targeted for CHB., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

The aim of this study was to analyze the population pharmacokinetics of total and unbound concentrations of prophylactic cefazolin (CFZ) in patients with prostatectomy or nephrectomy. We also aimed to calculate a pharmacodynamics target unbound concentration that exceeded the minimum inhibitory concentration (MIC), to design an effective dosing regimen. Briefly, 614 total concentration and 610 unbound concentration samples from 152 individuals were evaluated, using a nonlinear mixed-effects model. The obtained pharmacodynamics index target value reflected the probability of maintaining CFZ unbound trough concentrations exceeding MIC 90 , 0.5 mg/L, and MIC 50 , and 1.0 mg/L, to account for methicillin-susceptible Staphylococcus aureus (MSSA) or Escherichia coli . Population pharmacokinetics were estimated using a two-compartment model with nonlinear protein binding. Unbound systemic clearance (CL) was significantly associated with creatinine clearance, while the maximum protein-binding constant was significantly associated with albumin levels. The probability of achieving an unbound concentration exceeding the MIC 50 for E. coli or MIC 90 for MSSA in a patient with normal renal function following a 1 g CFZ infusion over 15 min was above 90% at 3 h after the initial dose. Our findings indicated that population pharmacokinetic parameters are useful for determining unbound CFZ pharmacokinetics and evaluating intraoperative CFZ redosing intervals., Competing Interests: The authors declare no conflict of interest.

Objective: large-scale multicentre clinical trials conducted by cooperative groups have generated a lot of evidence to establish better standard treatments. The Clinical Trials Act was enforced on 1 April 2018, in Japan, and it has remarkably increased the operational burden on investigators, but its long-term impact on cancer cooperative groups is unknown., Methods: a survey was conducted across the nine major cooperative groups that constitute the Japan Cancer Trials Network to assess the impact of Clinical Trials Act on the number of newly initiated trials from fiscal year (from 1 April to 31 March) 2017 to 2022 and that of ongoing trials on 1 April in each year from 2018 to 2023., Results: the number of newly initiated trials dropped from 38 trials in fiscal year 2017 to 26 trials in fiscal year 2018, surged to 50 trials in fiscal year 2019, but then gradually decreased to 25 trials by fiscal year 2022. Specified clinical trials decreased from 32 trials in fiscal year 2019 to 12 trials in fiscal year 2022. The number of ongoing trials was 220 trials in 2018, peaked at 245 trials in 2020, but then gradually decreased to 219 trials by 2023. The number of specified clinical trials has been in consistent decline. By April 2023, of the 20 ongoing non-specified clinical trials, nine adhered to Clinical Trials Act and 11 followed the Ethical Guidelines for Medical and Health Research Involving Human Subjects., Conclusion: the number of multicentre clinical trials in oncology gradually decreased after the Clinical Trials Act's enforcement, which underscores the need for comprehensive amendment of the Clinical Trials Act to streamline the operational process., (© The Author(s) 2024. Published by Oxford University Press.)

Background: Bevacizumab with platinum doublet therapy including paclitaxel + carboplatin improves the survival of patients with non-squamous non-small cell lung cancer. However, in a previous trial (CA031), paclitaxel + carboplatin led to Grade > 3 neutropenia in a Japanese population. Nanoparticle albumin-bound paclitaxel exhibits an improved toxicity profile. We evaluated the safety, dosage and response rate of the nanoparticle albumin-bound paclitaxel + carboplatin + bevacizumab combination in a Japanese population., Methods: Chemotherapy-naive patients with advanced non-squamous non-small cell lung cancer were included. The dosage schedule was established in the Phase I trial as follows: 4-6 cycles of carboplatin (area under the concentration-time curve = 6 on Day 1) + nanoparticle albumin-bound paclitaxel (100 mg/m2 on Days 1, 8 and 15) + bevacizumab (15 mg/kg on Day 1), followed by maintenance therapy (nanoparticle albumin-bound paclitaxel + bevacizumab). The response rate and presence of adverse effects were evaluated in the Phase II trial., Results: The overall response rate was 56.5% (90% confidence interval: 44.5-68.5), and 93% of patients (43/46) showed tumor shrinkage or maintained a stable disease course. The primary endpoint was achieved. At the median follow-up duration of 42 months, the median overall survival was 18.9 (range: 10.5-32.4) months. The most frequently observed Grade ≥ 3 adverse effects were neutropenia (72%), leukopenia (50%) and anemia (30%)., Conclusions: All adverse effects were manageable and none resulted in patient death. In conclusion, the nanoparticle albumin-bound paclitaxel + carboplatin + bevacizumab combination is favorable and well tolerated in Japanese patients as first-line treatment for advanced non-squamous non-small cell lung cancer., (© The Author(s) 2024. Published by Oxford University Press.)

As a novel conceptual synthesis of a metal-organic framework (MOF)-based proton conductor, UiO-66 based on a pyridinedicarboxylic acid phosphate (PyDC-PA) ion pair linker has been developed, in which the phosphoric acid is fixed to the N donor moiety of pyridine via an ionic bond.

We experimentally clarify the interaction of acoustic pressure and heat release rate fluctuations during a transition to high-frequency combustion instability in a model rocket engine combustor. The dynamical state of acoustic pressure fluctuations undergoes a transition from high-dimensional chaotic oscillations to strongly correlated limit cycle oscillations. The coherent structure in the heat release rate field emerges with the initiation of weakly correlated limit cycle oscillations. The effect of the heat release rate on acoustic pressure fluctuations predominates during high-dimensional chaotic oscillations. In contrast, the effect of acoustic pressure on the heat release rate fluctuations markedly increases during the correlated limit cycle oscillations. These are reasonably shown by an ordinal pattern-based analysis involving the concepts of information theory, synchronization, and complex networks.

Obstructive tract infection caused by urease-producing bacteria can lead to hyperammonemia. We herein report a 73-year-old woman with diabetes and compensated liver cirrhosis who developed obstructive pyelonephritis. Her consciousness level declined on day 3 of hospitalization. Blood tests revealed an elevated ammonia level of 140 μg/dL. Urine and blood cultures identified Proteus mirabilis as a urease-producing bacterium. The treatment included double J (WJ) catheter insertion and administration of antimicrobial agents. On day 7 of hospitalization, the ammonia level gradually decreased, and the patient's consciousness improved. However, despite these interventions, perinephric overflow of urine persisted, necessitating nephrectomy.

Background: The improvement in flowability and adhesion of starch powder (SP) is essential for using starch as an excipient for lactose intolerant patients. In this study, we attempted to evaluate the usefulness of hydroxypropylcellulose with molecular weight 80,000 (HPC-80) in the preparation of the starch granules (SG) as a substitute for excipient lactose., Methods: Hydroxypropylcellulose with molecular weight 30,000 (HPC-30) and HPC-80 were used as binders to prepare the SG, and defined as HPC-30-SG and HPC-80-SG, respectively. Mean particle size (D50) was measured according to the Method, Optical Microscopy of Particle Size Determination in Japanese Pharmacopoeia, Eighteenth Edition, and storage stability were evaluated by measuring of the physical properties after vortexing the granules for 180 s (physical impact). The product loss rate was calculated from the weight change of the various excipients before and after the one dose packaging (ODP)., Results: The D50 of SP (30 µm) was smaller than that of the lactose powder (115 µm). The granulation with 0.75-3% HPC-30 and HPC-80 increased the particle size of SP, and the D50 in 1.5% HPC-30-SG (255 µm) and HPC-80-SG (220 µm) were higher than that of lactose. The excipient was removed from the heat seal of the ODP, and upon visual inspection, a large amount of starchy material was observed to be adhering to the paper in the SP. On the other hand, the low recovery rate in SP was attenuated by the granulation with HPC-30 and HPC-80. In the both HPC-30 and HPC-80, the improvement in recovery rate reached a plateau at 1.5%, and the levels of recovery rate was similar to that of lactose. The recovery rate in the 0.75-3% HPC-30-SG and 0.75% HPC-80-SG were decreased by the physical impact, however, the recovery rate and amount of 1.5% and 3% HPC-80-SG were not affected by the physical impact, and these levels were similar to that of lactose., Conclusions: The use of HPC-80 as a binder of SG was found to produce a higher quality granule product than conventional HPC-based SG. This finding is useful in streamlining the preparation of starch-based powdered medicine in clinical applications., (© 2024. The Author(s).)

In ALK-negative anaplastic large cell lymphoma (ALCL), gene rearrangements of DUSP22 and TP63 are considered mutually exclusive. The former predicts a favorable prognosis, while the latter is generally unfavorable. We report the first case of ALK-negative ALCL in a leukemic phase with small cell pattern transformation, harboring double-hit rearrangements of the DUSP22 gene by inv(6)(p25q21) and TP63 gene by TBL1XR1-TP63 inversion. Despite the resistance to chemotherapies, the patient remained in remission with allogeneic stem cell transplantation over 20 months. Recognizing this pathologically and genetically rare condition is needed for prompt diagnosis and therapeutic decision-making in ALK-negative ALCL., Competing Interests: Shinsuke Mizutani has received honoraria from Amgen, Astellas, Otsuka Pharmaceutical, Nippon Shinyaku, Chugai Pharmaceutical, Ono Pharmaceutical, Sanofi, and BMS. Takahiro Fujino has received honoraria from Janssen Pharmaceutical, Kyowa Kirin, Chugai Pharmaceutical, and Astellas Pharma. Kennosuke Karube has received research grants from Eisai and Takeda Pharmaceutical, honoraria from Chugai Pharmaceutical, Eisai, Takeda Pharmaceutical, Meiji‐Seika Pharma, and Symbio Pharmaceutical. Yasuhito Nannya is a consultant for Otsuka Pharmaceuticals and Bristol Myers Squibb, and has received lecture fees from Otsuka Pharmaceutical, Novartis, Bristol Myers Squibb, Janssen, Astra Zeneca, Astellas, Nippon Shinyaku, Abbvie, and Amgen. Junya Kuroda is a consultant for Janssen Pharmaceutical, Bristol‐Myers Squibb (BMS), Pfizer, BeiGene, and Abbvie, and has received research funding from Kyowa Kirin, Chugai Pharmaceutical, Asahikasei, Taiho Pharmaceutical, Otsuka Pharmaceutical, Sumitomo Pharma, Eisai, Japan Blood Product, Regeneron Pharmaceutical, Takeda Pharmaceutical, and Mochida Pharmaceutical, and has received honoraria from Janssen Pharmaceutical, Kyowa Kirin, Chugai Pharmaceutical, Ono Pharmaceutical, Sanofi, BMS, Abbvie, and Novartis. The remaining authors declare they have no conflicts of interest with this article., (© 2024 The Author(s). eJHaem published by British Society for Haematology and John Wiley & Sons Ltd.)

This randomized pilot trial investigated the feasibility of an active learning physical activity intervention through video conferencing and its preliminary effects. Participants comprised community-dwelling older adults who could use e-mail. The intervention group underwent a 12-week active learning intervention via video conferencing to promote a healthy lifestyle, particularly physical activity. The control group received information via e-mail once per week. The amount of physical activity and sedentary behavior was measured using an accelerometer at baseline, postintervention, and 24-week postintervention (36 weeks). Of the 31 participants, 29 were eligible and randomized into two groups (15 for the intervention and 14 for the control). Adherence to the intervention was 83%-100% (mean, 97%). Compared with the control group, the intervention group showed moderate maintenance effects on total physical activity and sedentary behavior at 36 weeks. Active learning physical activity intervention through video conferencing was found to be feasible and contributed to the prevention of physical activity decline in older adults.

Purpose: Patients with head and neck cancer (HNC) who undergo dental procedures during radiotherapy (RT) face an increased risk of developing osteoradionecrosis (ORN). Accordingly, new tools must be developed to extract critical information regarding the dose delivered to the teeth and mandible. This article proposes a novel approach for visualizing 3-dimensional planned dose distributions on panoramic reconstruction computed tomography (pCT) images., Materials and Methods: Four patients with HNC who underwent volumetric modulated arc therapy were included. One patient experienced ORN and required the extraction of teeth after RT. In the study approach, the dental arch curve (DAC) was defined using an open-source platform. Subsequently, pCT images and dose distributions were generated based on the new coordinate system. All teeth and mandibles were delineated on both the original CT and pCT images. To evaluate the consistency of dose metrics, the Mann-Whitney U test and Student t -test were employed., Results: A total of 61 teeth and 4 mandibles were evaluated. The correlation coefficient between the 2 methods was 0.999, and no statistically significant difference was observed ( P >0.05). This method facilitated a straightforward and intuitive understanding of the delivered dose. In 1 patient, ORN corresponded to the region of the root and the gum receiving a high dosage (approximately 70 Gy)., Conclusion: The proposed method particularly benefits dentists involved in the management of patients with HNC. It enables the visualization of a 3-dimensional dose distribution in the teeth and mandible on pCT, enhancing the understanding of the dose delivered during RT., Competing Interests: Conflicts of Interest: None, (Copyright © 2024 by Korean Academy of Oral and Maxillofacial Radiology.)