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Glioblastoma multiforme (GBM) acquires resistance to bevacizumab (Bev) treatment. Bev affects angiogenic factors other than vascular endothelial growth factor (VEGF), which are poorly understood. We investigated changes in angiogenic factors under and after Bev therapy, including angiopoietin-1 (ANGPT1), angiopoietin-2 (ANGPT2), placental growth factor (PLGF), fibroblast growth factor 2, and ephrin A2 (EphA2). Fifty-four GBM tissues, including 28 specimens from 14 cases as paired specimens from the same patient obtained in three settings: initial tumor resection (naïve Bev), tumors resected following Bev therapy (effective Bev), and recurrent tumors after Bev therapy (refractory Bev). Immunohistochemistry assessed their expressions in tumor vessels and its correlation with recurrent MRI patterns. PLGF expression was higher in the effective Bev group than in the naïve Bev group (p = 0.024) and remained high in the refractory Bev group. ANGPT2 and EphA2 expressions were higher in the refractory Bev group than in the naïve Bev group (p = 0.047 and 0.028, respectively). PLGF expression was higher in the refractory Bev group compared with the naïve Bev group for paired specimens (p = 0.036). PLGF was more abundant in T2 diffuse/circumscribe patterns (p = 0.046). This is the first study to evaluate angiogenic factors other than VEGF during effective and refractory Bev therapy in patient-derived specimens., (© 2024. The Author(s).)

Objective . Photoacoustic emitters on the tip of a therapeutic device have been intensively studied for echo-guided intervention purposes. In this study, a novel method for localizing the guidewire tip emitter in the elevation direction using a 1D array probe is proposed to resolve the issue of the tip potentially deviating from the ultrasound-imaged plane. Approach . Our method uses the 'interference split' that appears when the emitter is off-plane. Here, a point source from the emitter splits into two points in images. Based on the split, 'split-based elevation localization (SEL)' is introduced to estimate the absolute elevation position of the emitter. Additionally, 'Signed SEL' incorporates an asymmetric feature into the 1D probe to obtain the sign of the elevation localization. An attenuative coupler is attached to the half side of the probe to control the interference split. In SEL and Signed SEL, we propose a modeled split matching (MSM) algorithm to localize the tip position. MSM performs pattern matching of a measured split waveform with modeled split waveforms corresponding to all emitter positions in a region of interest. The modeled waveforms are precalculated using the spatial impulse response. The proposed method is numerically and experimentally validated. Main results . Numerical simulations for time-domain wave propagation clearly demonstrated the interference split phenomena. In the experimental validation with a vessel-mimicking phantom, the proposed methods successfully estimated the elevation positions,yb.SEL exhibited a root-mean-squared error (RMSE) of 2.0 mm for the range of 0 mm ≤yb≤ 30 mm, while Signed SEL estimated the absolute position with an RMSE of 2.4 mm and the sign with an accuracy of 80.8% for the range of -30 mm ≤yb≤ 30 mm. Significance. These results suggest that the proposed method could provide approximate tip positions and help sonographers track it by fanning the probe., (© 2024 Institute of Physics and Engineering in Medicine.)

Background: To evaluate the clinical usefulness of thin-slice echo-planar imaging (EPI)-based diffusion-weighted imaging (DWI) with an on-console distortion correction technique, termed reverse encoding distortion correction DWI (RDC-DWI), in patients with non-functioning pituitary neuroendocrine tumor (PitNET)/pituitary adenoma., Methods: Patients with non-functioning PitNET/pituitary adenoma who underwent 3-T RDC-DWI between December 2021 and September 2022 were retrospectively enrolled. Image quality was compared among RDC-DWI, DWI with correction for distortion induced by B 0 inhomogeneity alone (B 0 -corrected-DWI), and original EPI-based DWI with anterior-posterior phase-encoding direction (AP-DWI). Susceptibility artifact, anatomical visualization of cranial nerves, overall tumor visualization, and visualization of cavernous sinus invasion were assessed qualitatively. Quantitative assessment of geometric distortion was performed by evaluation of anterior and posterior displacement between each DWI and the corresponding three-dimensional T2-weighted imaging. Signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and apparent diffusion coefficient values were measured., Results: Sixty-four patients (age 70.8 ± 9.9 years [mean ± standard deviation]; 33 females) with non-functioning PitNET/pituitary adenoma were evaluated. In terms of susceptibility artifacts in the frontal and temporal lobes, visualization of left trigeminal nerve, overall tumor visualization, and anterior displacement, RDC-DWI performed the best and B 0 -corrected-DWI performed better than AP-DWI. The right oculomotor and right trigeminal nerves were better visualized by RDC-DWI than by B 0 -corrected-DWI and AP-DWI. Visualization of cavernous sinus invasion and posterior displacement were better by RDC-DWI and B 0 -corrected-DWI than by AP-DWI. SNR and CNR were the highest for RDC-DWI., Conclusions: RDC-DWI achieved excellent image quality regarding susceptibility artifact, geometric distortion, and tumor visualization in patients with non-functioning PitNET/pituitary adenoma., Relevance Statement: RDC-DWI facilitates excellent visualization of the pituitary region and surrounding normal structures, and its on-console distortion correction technique is convenient. RDC-DWI can clearly depict cavernous sinus invasion of PitNET/pituitary adenoma even without contrast medium., Key Points: • RDC-DWI is an EPI-based DWI technique with a novel on-console distortion correction technique. • RDC-DWI corrects distortion due to B 0 field inhomogeneity and eddy current. • We evaluated the usefulness of thin-slice RDC-DWI in non-functioning PitNET/pituitary adenoma. • RDC-DWI exhibited excellent visualization in the pituitary region and surrounding structures. • In addition, the on-console distortion correction of RDC-DWI is clinically convenient., (© 2024. The Author(s).)

Background: Cancer has been identified as a risk factor for severe illness and mortality in coronavirus disease (COVID-19), underscoring the importance of recommending COVID-19 vaccinations to patients with cancer. However, few reports have focused on the vaccination status and the incidence of adverse events among patients with cancer. In this study, we aimed to evaluate the vaccination status, incidence of adverse events, concerns, and anxiety related to COVID-19 vaccination among patients with cancer. In addition, we explored the utilization of information sources by these patients and the ease of use., Methods: A survey was conducted among outpatients undergoing chemotherapy who received medication counseling from a pharmacist at Juntendo University Hospital. Responses were gathered from 60 out of the 143 participants. Of the respondents, 96.7% had received two doses of the COVID-19 vaccine., Results: Common adverse events included pain at the injection site, fever, and fatigue, which were experienced by nearly half of the respondents. Approximately 80% expressed some concern regarding vaccination, with predominant concerns about timing in the context of ongoing cancer treatment and surgery. Among the respondents, 41.7% consulted primary care physicians regarding the vaccine, with only one mentioning consultation with hospital pharmacists. Notably, primary care physicians were considered the most approachable and useful healthcare professionals., Conclusions: These results suggest that patients with cancer can safely receive the vaccine, comparable to patients without cancer. However, they still harbor concerns, even when seeking advice from primary care physicians. Few patients consulted pharmacists about vaccination, highlighting an opportunity for pharmacist intervention. Pharmacists fostering trust with patients with cancer is imperative to explore pharmacist intervention methods to promote the continued administration of COVID-19 vaccines and enhance the quality of life for them., (© 2024. The Author(s).)

Purpose: It is difficult to effectively cure patients with unresectable locally recurrent colorectal cancers (LRCRCs) using conventional chemotherapy or chemoradiation therapy. Furthermore, treatment options vary depending on the patient's history of radiation therapy. Carbon-ion radiation therapy (CIRT) is a potentially curative treatment for these patients. Here, we compare the treatment outcomes of radiation therapy-naïve cases (nRT) and re-irradiation cases (reRT)., Methods and Materials: Patients with LRCRC treated with CIRT at QST Hospital between 2003 and 2019 were eligible. CIRT was administered daily 4 d/wk for 16 fractions. The total irradiated dose was set at 73.6 Gy (relative biologic effectiveness-weighted dose [RBE]) for nRT and 70.4 Gy (RBE) for reRT patients., Results: We included 390 nRT cases and 83 reRT cases. The median follow-up period from the initiation of CIRT was 48 (5-208) months. The 3-year overall survival (OS) rates for nRT and reRT were 73% (95% CI, 68%-77%) and 76% (65%-84%), respectively. The 5-year OS rates were 50% (45%-55%) and 50% (38%-61%), respectively. These rates did not differ significantly (P = .55). The 3-year local control (LC) rates for nRT (73.6 Gy) and reRT (70.4 Gy) cases were 80% (75%-84%) and 80% (68%-88%), respectively. The 5-year LC rates were 72% (67%-78%) and 69% (55%-81%), respectively, without a significant difference (P = .56)., Conclusions: Our results suggest that CIRT for LRCRC is a very effective and promising treatment for both nRT and reRT cases., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: Volatile anesthetics affect the circadian rhythm of mammals, although the effects of different types of anesthetics are unclear. Here, we anesthetized mice using several volatile anesthetics at two different times during the day. Our objective was to compare the effects of these anesthetics on circadian rhythm., Methods: Male adult C57BL/6 J mice were divided into eight groups (n = 8 each) based on the anesthetic (sevoflurane, desflurane, isoflurane, or no anesthesia) and anesthesia time (Zeitgeber time [ZT] 6-12 or ZT18-24). Mice were anesthetized for 6 h using a 0.5 minimum alveolar concentration (MAC) dose under constant dark conditions. The difference between the start of the active phase before and after anesthesia was measured as a phase shift. Clock genes were measured by polymerase chain reaction in suprachiasmatic nucleus (SCN) samples removed from mouse brain after anesthesia (n = 8-9 each)., Results: Phase shift after anesthesia at ZT6-12 using sevoflurane (- 0.49 h) was smaller compared with desflurane (- 1.1 h) and isoflurane (- 1.4 h) (p < 0.05). Clock mRNA (ZT6-12, p < 0.05) and Per2 mRNA (ZT18-24, p < 0.05) expression were different between the groups after anesthesia., Conclusion: 0.5 MAC sevoflurane anesthesia administered during the late inactive to early active phase has less impact on the phase shift of circadian rhythm than desflurane and isoflurane. This may be due to differences in the effects of volatile anesthetics on the expression of clock genes in the SCN, the master clock of the circadian rhythm., (© 2023. The Author(s) under exclusive licence to Japanese Society of Anesthesiologists.)

Purpose: This multi-institutional phase I/II study was conducted to confirm the safety and explore the clinical utility of preoperative Bevacizumab (Bev) for newly diagnosed glioblastoma (GB)., Methods: Patients were enrolled based on magnetic resonance imaging (MRI) findings typically suggestive of GB. Preoperative Bev and temozolomide (TMZ) were administered at doses of 10 mg/kg on day 0 and 150 mg/m 2 on days 1-5, respectively. Surgical resection was performed between days 21 and 30, inclusive. The safety and efficacy were evaluated in a total of 15 cases by progression-free survival (PFS), changes in tumor volume, Karnofsky Performance Scale (KPS) and Mini-Mental State Examination (MMSE) scores after preoperative therapy., Results: Tumor resection was performed on a mean of day 23.7. Pathological diagnosis was GB, isocitrate dehydrogenase (IDH)-wildtype in 14 cases and GB, IDH-mutant in 1 case. Severe adverse events possibly related to preoperative Bev and TMZ were observed in 2 of the 15 patients, as wound infection and postoperative hematoma and thrombocytopenia. KPS and MMSE scores were significantly improved with preoperative therapy. Tumor volume was decreased in all but one case on T1-weighted imaging with contrast-enhancement (T1CE) and in all cases on fluid-attenuated inversion recovery, with mean volume decrease rates of 36.2% and 54.0%, respectively. Median PFS and overall survival were 9.5 months and 16.5 months, respectively., Conclusion: Preoperative Bev and TMZ is safe as long as the instructions are followed. The strategy might be useful for GB in some patients, not only reducing tumor burden, but also improving patient KPS preoperatively., Trial Registration Number: UMIN000025579, jRCT1031180233 https://jrct.niph.go.jp/latest-detail/jRCT1031180233 . Registration Date: Jan. 16, 2017., (© 2024. The Author(s).)

Background: Chronic inflammation is a factor in the pathogenesis of sarcopenia, which is characterized by low muscle mass and reduced strength. Complement C3 is important in the management of the immune network system. This study seeks to determine the relationship between serum C3 levels and body composition and sarcopenia-related status in community-dwelling older adults., Methods: Study participants were 269 older adults living in rural Japan. A bioelectrical impedance analysis device was used to measure body composition parameters including body mass index (BMI), body fat percentage, waist-hip-ratio, and appendicular skeletal muscle mass index (SMI). Muscle function was measured by handgrip strength and 6-m walking speed. The correlation coefficients for C3 level and measurements were calculated using Pearson correlation analysis. Participants were categorized into normal, pre-sarcopenia, dynapenia, or sarcopenia groups. Sarcopenia was defined according to 2019 Asian Working Group for Sarcopenia definition, dynapenia was defined as low muscle function without low muscle mass, and pre-sarcopenia was defined as the presence of low muscle mass only. The C3 threshold score for sarcopenia status was evaluated by receiver operating characteristic curve (ROC) analysis., Results: Significant positive correlations were found between C3 and BMI, body fat percentage, and waist-hip ratio in both sexes, and further positive correlations with SMI were found in women. The relationship with body fat percentage was particularly strong. Body composition measurements (BMI, body fat percentage, and waist- hip ratio) and C3 levels were lowest in the sarcopenia group compared with the others. ROC analysis showed that the significant threshold of C3 for discriminating between the normal and sarcopenia groups was 105 mg/dL. Multiple logistic regression analysis showed that participants with C3 < 105 mg/dL had an odds ratio of 3.27 (95% confidence interval, 1.49-7.18) for sarcopenia adjusted by sex, age and body fat percentage., Conclusion: C3 levels are suggested to be related to body composition and pathophysiological functions of sarcopenia. C3 is expected to become a useful biomarker for sarcopenia, for predicting the onset of the disease and for predicting the effectiveness of interventions., (© 2024. The Author(s).)

Aim: The present study aimed to describe in detail the changes to and assess the risk factors for poor long-term outcomes of psychiatric disorders in families of COVID-19 patients., Methods: A single-center, retrospective study using questionnaires. Family members of patients admitted to the intensive care unit (ICU) with severe COVID-19 participated. Psychiatric disorders refer to the psychological distress such as anxiety, depression, and posttraumatic stress disorder (PTSD) experienced by the patient's family., Results: Forty-six family members completed the survey and were analyzed. Anxiety, depression, and PTSD occurred in 24%, 33%, and 2% of family members, respectively, and psychiatric disorders occurred in 39%. On multivariable analysis, living in the same house with the patient was independently associated with a lower risk of psychiatric disorders in families of COVID-19 patients (OR, 0.180; 95% CI, 0.036-0.908; p  = 0.038). Furthermore, four family members overcame psychiatric disorders, and six family members newly developed psychiatric disorders during the one-year follow-up period., Conclusion: Approximately 40% of family members had long-term psychiatric disorders, and some of them overcame the psychiatric disorders, and some newly developed psychiatric disorders over the one-year follow-up. Living in the same house with the patient was possibly significantly associated with the reduction of long-term symptoms of psychiatric disorders, but this result must be interpreted with care. Further large studies are needed to examine the factors associated with the long-term mental status of family members., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Authors. Acute Medicine & Surgery published by John Wiley & Sons Australia, Ltd on behalf of Japanese Association for Acute Medicine.)

Background: Pulmonary embolism (PE) is a potentially fatal form of venous thromboembolism (VTE). This study compares the mortality, incidence of recurrent VTE, and incidence of major bleeding between non-cancer and cancer-associated PE patients treated with direct oral anticoagulants (DOACs)., Methods and results: This was a retrospective, observational, single-center study involving 130 consecutive patients (87 with active cancer; 43 without cancer) who received DOAC treatment for PE between January 2016 and December 2019. Kaplan-Meier analysis showed significantly higher mortality in cancer-associated PE patients than in non-cancer patients (35/87 [40%] vs. 1/43 [2%], P<0.001, log-rank test, HR 18.6 [95% CI: 2.5-136.0]). In contrast, the cumulative incidences of recurrent VTE and major bleeding were comparable between the 2 groups. Among the cancer-associated PE patients, the incidence for the composite outcome of recurrent VTE or major bleeding was significantly higher in patients undergoing chemotherapy than in those not undergoing chemotherapy (9/37 [24%] vs. 2/50 [4%], P=0.004, log-rank test, HR 6.9 [95% CI: 1.5-32.0])., Conclusions: Although cancer-associated PE patients treated with DOACs showed higher mortality compared with non-cancer patients, presumably because of the presence of cancer, the risk of recurrent VTE or major bleeding was comparable between the 2 groups. Thus, DOAC is an important treatment option for cancer-associated PE, although underlying cancer-related risks (e.g., chemotherapy) remain.

In patients with acute heart failure, early mobilisation is performed according to physical condition, biometric information, and haemodynamic stability. Regional cerebral oxygen saturation (rSO 2 ) is useful in monitoring patients during assisted circulation and cardiac arrest, but the measurement of rSO 2 during early mobilisation is not standardised, and its relationship with percutaneous oxygen saturation (SpO 2 ) has not been investigated. This study aimed to investigate the relationship between rSO 2 and SpO 2 during initial mobilisation in patients with acute heart failure. Patients with acute heart failure who presented to our emergency centre and were referred for physical therapy were included in this study. Data from 21 of the 24 patients who decided to start mobilisation based on the criteria of the Japanese Society of Intensive Care Medicine were analysed. The resting rSO 2 was 58.6%, and it significantly changed (p < 0.001), with a decrease in the first half of sitting on the edge of the bed (SEB) and an increase from the second half to the end of the SEB. The resting SpO 2 was 96.0%, with a trend towards an increase in the latter half of the SEB (p = 0.05608). Changes in rSO 2 during initial mobilisation in patients with acute heart failure differed from those in SpO 2 ., (© 2024. Oxygen Transport to Tissue International.)

Dependency on in vitro culture and regeneration limits the ability to use genome editing on elite wheat (Triticum aestivum L.) varieties. We recently developed an in planta particle bombardment (iPB) technique for gene editing in wheat that utilizes shoot apical meristems (SAMs) as a target tissue. Since the method does not require in vitro culture, it can therefore be used on recalcitrant varieties. In this chapter, we describe in detail the steps used in the iPB method. With this protocol, 3% to 5% of T0 plants grown from bombarded SAMs typically carry mutant alleles and approximately 1% to 2% of the T0 plants inherit mutant alleles in the next generation., (© 2024. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Iron accumulation in vessel walls induces oxidative stress and inflammation, which can cause cerebrovascular damage, vascular wall degeneration, and intracranial aneurysmal formation, growth, and rupture. Subarachnoid hemorrhage from intracranial aneurysm rupture results in significant morbidity and mortality. This study used a mouse model of intracranial aneurysm to evaluate the effect of dietary iron restriction on aneurysm formation and rupture., Methods: Intracranial aneurysms were induced using deoxycorticosterone acetate-salt-induced hypertension and a single injection of elastase into the cerebrospinal fluid of the basal cistern. Mice were fed an iron-restricted diet (n = 23) or a normal diet (n = 25). Aneurysm rupture was detected by neurological symptoms, while the presence of intracranial aneurysm with subarachnoid hemorrhage was confirmed by post-mortem examination., Results: The aneurysmal rupture rate was significantly lower in iron-restricted diet mice (37%) compared with normal diet mice (76%; p &lt; 0.05). Serum oxidative stress, iron accumulation, macrophage infiltration, and 8-hydroxy-2'-deoxyguanosine in the vascular wall were lower in iron-restricted diet mice (p &lt; 0.01). The areas of iron positivity were similar to the areas of CD68 positivity and 8-hydroxy-2'-deoxyguanosine in both normal diet and iron-restricted diet mouse aneurysms., Conclusions: These findings suggest that iron is involved in intracranial aneurysm rupture via vascular inflammation and oxidative stress. Dietary iron restriction may have a promising role in preventing intracranial aneurysm rupture., (© 2023 S. Karger AG, Basel.)

We have developed a simple, compact, and robust eight-channel ultraviolet (UV) absorption detection setup featuring two eight-fiber arrays (an irradiation fiber array and a detection fiber array) whose ends face each other across eight capillaries. UV light of a 220-nm wavelength from a single deuterium lamp is stably and evenly split into eight lights by using a thick homogenizing fiber connected to a fiber bundle with eight thin fibers, which make up the irradiation fiber array. Each capillary is directly irradiated with each UV light emitted from the irradiation fiber array and then each of the UV lights transmitted through the capillaries is collected by each fiber of the detection fiber array without using any other optical devices (e.g., a lens) and is detected by each of the eight photodetectors. This setup achieves simultaneous UV absorption measurement for all eight capillaries with the detection limit of 54 μAU, linear dynamic range of four logs or more, and negligible crosstalk of 0.01% or less. We also implemented an eight-capillary electrophoresis system and simultaneously analyzed eight immunoglobulin G samples, separated by capillary electrophoresis sodium dodecyl sulfate., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Ryo Imai reports a relationship with Hitachi Ltd that includes: employment. Kentaro Osawa reports a relationship with Hitachi Ltd that includes: employment. Takashi Anazawa reports a relationship with Hitachi Ltd that includes: employment. Kentaro Osawa and Takashi Anazawa are inventors of a patent PCT/JP2020/030789 whose rights are owned by Hitachi High-Tech Corp., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objective : Severe pain and other symptoms in complex regional pain syndrome (CRPS), such as allodynia and hyperalgesia, are associated with abnormal resting-state brain network activity. No studies to date have examined resting-state brain networks in CRPS patients using electroencephalography (EEG), which can clarify the temporal dynamics of brain networks. Methods : We conducted microstate analysis using resting-state EEG signals to prospectively reveal direct correlations with pain intensity in CRPS patients (n = 17). Five microstate topographies were fitted back to individual CRPS patients' EEG data, and temporal microstate measures were subsequently calculated. Results : Our results revealed five distinct microstates, termed microstates A to E, from resting EEG data in patients with CRPS. Microstates C, D and E were significantly correlated with pain intensity before pain treatment. Particularly, microstates D and E were significantly improved together with pain alleviation after pain treatment. As microstates D and E in the present study have previously been related to attentional networks and the default mode network, improvement in these networks might be related to pain relief in CRPS patients. Conclusions : The functional alterations of these brain networks affected the pain intensity of CRPS patients. Therefore, EEG microstate analyses may be used to identify surrogate markers for pain intensity., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Serum transthyretin (TTR) level has suggested association with mild cognitive impairment (MCI) and dementia. To clarify its usefulness as a biomarker of change in cognitive function in older individuals with normal cognitive function (NC) as a phenotype, we investigated the relationship between cognitive scores and TTR levels. We also investigated the involvement of TTR in the transition from NC to MCI., Methods: Cognitive function was evaluated using Addenbrooke's Cognitive Examination-Revised (ACE-R). A cross-sectional study was conducted in community-dwelling older people (n = 211) with NC, MCI, or dementia according to ACE-R scores. A 32-month longitudinal study was then conducted (n = 29)., Results: Mean TTR levels did not differ between the NC, MCI and dementia groups. Linear regression analysis showed a significant relationship in people with NC between TTR and ACE-R (β = -0.192; p < 0.001). Multiple regression analysis adjusted for stepwise procedure-selected covariates showed that TTR was significantly associated with ACE-R in people with NC (β = -0.130; p = 0.014). Furthermore, multiple regression analysis showed significant association between TTR level and memory (β = -0.584; p = 0.002) and with language (β = -0.743; p = 0.031) in people with NC. In the longitudinal study, mean TTR level at baseline in women with MCI was significantly higher than that in women with NC (p = 0.044)., Conclusions: Serum TTR level is suggested to be associated with cognitive scores in people with NC and to be an indicator of progression from NC to MCI., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objective: As management for osteoarthritis, clinical practice guidelines (CPGs) have been published worldwide with the aim of attaining optimal treatment and rehabilitation. However, we suspect a lack of knowledge of and/or adherence to osteoarthritis CPGs in physiotherapists' clinical practice. There may be an evidence-to-practice gap in knee osteoarthritis rehabilitation among Japanese physiotherapists. Therefore, we aimed to measure the level of knowledge and adherence to osteoarthritis CPGs within a cohort of Japanese physiotherapists., Methods: An online survey was created based on three appropriate and high-quality CPGs. The first two sections comprised 23 statements, and participants responded via a five-point Likert scale ("completely disagree" to "completely agree"). Consensus was defined as ≥70% agreement with a statement. In the second section, participants read clinical scenarios and selected what they considered to be the most appropriate management and interventions., Results: The survey was completed by 558 Japanese physiotherapists. The mean age of the participants included in the analysis was 34.8 years, 61 participants were female (13.7%). Consensus was attained in just 12 out of 23 items (52%). In the second section, none of the physiotherapists were considered to have good knowledge of CPGs, 85.2% were considered to have only partial knowledge, and 14.8% had no knowledge. Familiarity with the CPGs was therefore poor and there was clearly poor adherence to the recommended rehabilitation guidelines., Conclusions: The level of knowledge and adherence to osteoarthritis CPGs within our cohort was poor, suggesting an evidence-to-practice gap in rehabilitation for knee osteoarthritis among Japanese physiotherapists., (© 2023 John Wiley & Sons Ltd.)

Purpose: To compare image distortion and reproducibility of quantitative values between reverse encoding distortion correction (RDC) diffusion-weighted imaging (DWI) and conventional DWI techniques in a phantom study and in healthy volunteers., Methods: This prospective study was conducted with the approval of our institutional review board. Written informed consent was obtained from each participant. RDC-DWIs were created from images obtained at 3T in three orthogonal directions in a phantom and in 10 participants (mean age, 70.9 years; age range, 63-83 years). Images without distortion correction (noDC-DWI) and those corrected with B0 (B0c-DWI) were also created. To evaluate distortion, coefficients of variation were calculated for each voxel and ROIs were placed at four levels of the brain. To evaluate the reproducibility of apparent diffusion coefficient (ADC) measurements, intra- and inter-scan variability (%CV ADC ) were calculated from repeated scans of the phantom. Analysis was performed using Wilcoxon signed-rank test with Bonferroni correction, and P < 0.05 was considered statistically significant., Results: In the phantom, distortion was less in RDC-DWI than in B0c-DWI (P < 0.006), and was less in B0c-DWI than in noDC-DWI (P < 0.006). Intra-scan %CV ADC was within 1.30%, and inter-scan %CV ADC was within 2.99%. In the volunteers, distortion was less in RDC-DWI than in B0c-DWI in three of four locations (P < 0.006), and was less in B0c-DWI than in noDC-DWI (P < 0.006). At the middle cerebellar peduncle, distortion was less in RDC-DWI than in noDC-DWI (P < 0.006), and was less in noDC-DWI than in B0c-DWI (P < 0.0177)., Conclusion: In both the phantom and in volunteers, distortion was the least in RDC-DWI than in B0c-DWI and noDC-DWI.

The glycoside hydrolase family 55 (GH55) includes inverting exo-β-1,3-glucosidases and endo-β-1,3-glucanases, acting on laminarin, which is a β1-3/1-6-glucan consisting of a β1-3/1-6-linked main chain and β1-6-linked branches. Despite their different modes of action toward laminarin, endo-β-1,3-glucanases share with exo-β-1,3-glucosidases conserved residues that form the dead-end structure of subsite -1. Here, we investigated the mechanism of endo-type action on laminarin by GH55 endo-β-1,3-glucanase MnLam55A, identified from Microdochium nivale. MnLam55A, like other endo-β-1,3-glucanases, degraded internal β-d-glucosidic linkages of laminarin, producing more reducing sugars than the sum of d-glucose and gentiooligosaccharides detected. β1-3-Glucans lacking β1-6-linkages in the main chain were not hydrolyzed. NMR analysis of the initial degradation of laminarin revealed that MnLam55A preferentially cleaved the nonreducing terminal β1-3-linkage of the laminarioligosaccharide moiety at the reducing end side of the main chain β1-6-linkage. MnLam55A liberates d-glucose from laminaritriose and longer laminarioligosaccharides, but k cat /K m values to laminarioligosaccharides (≤4.21 s -1  mM -1 ) were much lower than to laminarin (5920 s -1  mM -1 ). These results indicate that β-glucan binding to the minus subsites of MnLam55A, including exclusive binding of the gentiobiosyl moiety to subsites -1 and -2, is required for high hydrolytic activity. A crystal structure of MnLam55A, determined at 2.4 Å resolution, showed that MnLam55A adopts an overall structure and catalytic site similar to those of exo-β-1,3-glucosidases. However, MnLam55A possesses an extended substrate-binding cleft that is expected to form the minus subsites. Sequence comparison suggested that other endo-type enzymes share the extended cleft. The specific hydrolysis of internal linkages in laminarin is presumably common to GH55 endo-β-1,3-glucanases., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Employment of the elderly is gaining importance in Japan's super-aging society. However, investigating the role of employment on the health of the elderly population during the coronavirus disease 2019 (COVID-19) pandemic, wherein they were susceptible, is necessary. We aimed to investigate whether the presence or absence of employment affected motor and cognitive functions in the elderly during the COVID-19 pandemic. The study involved 144 individuals aged ≥ 65 years who participated in the medical examination project from August to September 2021. The participants were divided into employed and non-employed groups. The motor function was evaluated by determining the walking speed, skeletal muscle mass, 2-step test, and bone density. Cognitive function was evaluated using the Mini Mental State Examination and Trail Making Test-A/B (TMT-A/B). For statistical examination, univariate analysis and logistic regression analysis were performed using significantly differential variables. Out of the 144 participants, 33 (22.9%) and 111 (77.1%) were in the employed and non-employed groups, respectively. TMT-A had an odds ratio of 0.96 (95% confidence interval 0.94-0.99) and was an independent factor in the employed group. In conclusion, the attention function was significantly higher in the employed group., (© 2023. The Author(s).)

RNA vaccines based on lipid nanoparticles (LNPs) with in vitro transcribed mRNA (IVT-mRNA) encapsulated are now a currently successful but still evolving modality of vaccines. One of the advantages of RNA vaccines is their ability to induce CD8 + T-cell-mediated cellular immunity that is indispensable for excluding pathogen-infected cells or cancer cells from the body. In this study, we report on the development of LNPs with an enhanced capability for inducing cellular immunity by using an ionizable lipid with a vitamin E scaffold. An RNA vaccine that contained this ionizable lipid and an IVT-mRNA encoding a model antigen ovalbumin (OVA) induced OVA-specific cytotoxic T cell responses and showed an antitumor effect against an E.G7-OVA tumor model. Vaccination with the LNPs conferred protection against lethal infection by Toxoplasma gondii using its antigen TgPF. The vitamin E scaffold-dependent type I interferon response was important for effector CD8 + T cell differentiation induced by the mRNA-LNPs. Our findings also revealed that conventional dendritic cells (cDCs) were essential for achieving CD8 + T cell responses induced by the mRNA-LNPs, while the XCR1-positive subset of cDCs, cDC1 specialized for antigen cross-presentation, was not required. Consistently, the mRNA-LNPs were found to selectively transfect another subset of cDCs, cDC2 that had migrated from the skin to lymph nodes, where they could make vaccine-antigen-dependent contacts with CD8 + T cells. The findings indicate that the activation of innate immune signaling by the adjuvant activity of the vitamin E scaffold and the expression of antigens in cDC2 are important for subsequent antigen presentation and the establishment of antigen-specific immune responses.

Background: The coexistence of vascular malformations in the conus medullaris and cauda equina has been rarely reported, and the complex angioarchitecture in multiple arteriovenous lesions remains poorly understood., Case Description: A 17-year-old woman presented with a sudden-onset, stepwise worsening of weakness and pain in the bilateral legs. Angiography revealed conus medullaris arteriovenous malformation and cauda equina arteriovenous fistulas. One of the drainers was shared between the coexisting lesions and harboured a varix. Targeted embolisation of a fistulous point in the conus lesion was performed with precaution to prevent occluding the common drainage route, which led to symptom improvement with angiographical diminishment of the varix., Conclusions: Recognising that communications between drainers can be observed in multiple spinal arteriovenous lesions is important in facilitating a safe embolisation. Cautious assessment of angiogram with fusion images of cone-beam computed tomography and volumetric T2 magnetic resonance imaging can help in establishing the diagnosis and treatment strategy.

Low levels of physical activity in individuals with chronic pain can lead to additional functional impairment and disability. This study aims to investigate the predictors of low physical activity levels in individuals with chronic pain, and to determine the accuracy of the artificial neural network used to analyze these predictors. Community-dwelling older adults with chronic pain (n = 103) were surveyed for their physical activity levels and classified into low, moderate, or high physical activity level groups. Chronic pain-related measurements, physical function assessment, and clinical history, which all influence physical activity, were also taken at the same time. Logistic regression analysis and analysis of multilayer perceptron, an artificial neural network algorithm, were performed. Both analyses revealed that history of falls was a predictor of low levels of physical activity in community-dwelling older adults. Multilayer perceptron analysis was shown to have excellent accuracy. Our results emphasize the importance of fall prevention in improving the physical activity levels of community-dwelling older adults with chronic pain. Future cross-sectional studies should compare multiple analysis methods to show results with improved accuracy., (© 2023. Springer Nature Limited.)

Cholesteatoma, which potentially results from tympanic membrane retraction, is characterized by intractable local bone erosion and subsequent hearing loss and brain abscess formation. However, the pathophysiological mechanisms underlying bone destruction remain elusive. Here, we performed a single-cell RNA sequencing analysis on human cholesteatoma samples and identify a pathogenic fibroblast subset characterized by abundant expression of inhibin βA. We demonstrate that activin A, a homodimer of inhibin βA, promotes osteoclast differentiation. Furthermore, the deletion of inhibin βA /activin A in these fibroblasts results in decreased osteoclast differentiation in a murine model of cholesteatoma. Moreover, follistatin, an antagonist of activin A, reduces osteoclastogenesis and resultant bone erosion in cholesteatoma. Collectively, these findings indicate that unique activin A-producing fibroblasts present in human cholesteatoma tissues are accountable for bone destruction via the induction of local osteoclastogenesis, suggesting a potential therapeutic target., (© 2023. The Author(s).)

Purpose: The present study introduced the half-dose method (HDM), which halves the radiation dose for conventional head computed tomography (CT), for postoperative hydrocephalus and follow-up for craniosynostosis at a children's hospital. This study aimed to evaluate the contribution of selective head CT scanning optimization towards the overall reduction of radiation exposure., Materials and Methods: We retrospectively assessed 1227 and 1352 head CT examinations acquired before and after the introduction of the HDM, respectively, in children aged 0-15 years. The radiation exposure was evaluated using the CT dose index volume (CTDI-vol), dose-length product (DLP), rate of HDM introduction, and effect of reducing in-hospital radiation dose before and after the introduction of the HDM. For an objective evaluation of the image quality, head CT scans acquired with HDM and full-dose method (FDM) were randomly selected, and the image noise standard deviation (SD) was measured for each scan. In addition, some HDM images were randomly selected and independently reviewed by two radiologists., Results: The HDM was introduced in 27.9% of all head CTs. The mean CTDI-vol of all head CTs was 21.5 ± 6.9 mGy after the introduction, a 14.9% reduction. The mean DLP was 418.4 ± 152.9 mGy.cm after the introduction, a 17.2% reduction. Compared to the FDM images, the noise SD of the HDM ones worsened by almost 0.9; however, none of the images were difficult or impossible to evaluate., Conclusion: The HDM yielded diagnostically acceptable images. In addition, a change in protocol for only two diseases successfully reduced the patients' overall radiation exposure by approximately 15%. Introducing and optimizing the HDM for frequently performed target diseases will be useful in reducing the exposure dose for the hospital's patient population., (© 2023. The Author(s).)

Background: Patients with breast cancer present with lymphadenopathy involving non-caseating epithelioid cell granulomas in the mediastinum or axilla, referred to as sarcoidosis or sarcoid-like reactions (SLRs). However, sarcoidosis/SLRs prevalence and clinical presentation remain unclear. This study aimed to determine the frequency and clinical presentation of sarcoidosis/SLRs among postoperative patients with breast cancer., Methods: Among all patients who underwent surgery for early-stage breast cancer at St. Luke's International Hospital in Japan between 2010 and 2021, those who subsequently developed enlarged mediastinal lymph nodes and underwent bronchoscopy for suspected breast cancer recurrence were included. Patients were classified into sarcoidosis/SLR or metastatic breast cancer groups, and the clinical characteristics were compared., Results: A total of 9,559 patients underwent breast cancer surgery; bronchoscopy was performed to diagnose enlarged mediastinal lymph nodes in 29 cases. Breast cancer recurrence was observed in 20 patients. Eight women with a median age of 49 years (range 38-75) and a median time from surgery to diagnosis of 4.0 years (range 0.2-10.8) were diagnosed with sarcoidosis/SLRs. Four of the eight patients underwent mammoplasty with silicone breast implants (SBIs), and two experienced postoperative recurrences of breast cancer before or after lymphadenopathy, which was considered inciting factors for SLRs. The remaining two cases could have developed sarcoidosis after breast cancer surgery with no underlying causes for SLR., Conclusions: Postoperative sarcoidosis/SLRs rarely occur in patients with breast cancer. An adjuvant action of SBI likely contributed to the progression of SLRs; few cases exhibited a causal relationship with breast cancer recurrence., Competing Interests: Conflict of Interest The authors have no conflicts of interest to disclose., (Copyright © 2023 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

Introduction: This cross-sectional study aimed to determine the factors related to hallux valgus (HV) and their importance using support vector machine-recursive feature elimination (SVM-RFE)., Methods: A total of 864 participants aged ≥ 18 years were enrolled. The Manchester scale was used to determine the presence of HV (summed scores for both feet ≥ 4). The questionnaire included items such as age, sex, height, weight, and foot measurements. These internal factors were analyzed to determine if they are related to HV using SVM-RFE., Results: The results of tenfold cross-validation using SVM-RFE revealed that the numbers of feature selections were 10, 10, and 9 for age, sex, and body weight, respectively, and these factors were shown to be related to HV. HV was found to be more common in women than in men (women, 24.9%; men, 7.6%), but the sex difference was not significant in older people., Conclusion: Age and sex were found to be important factors associated with HV identified via feature selection using SVM-RFE., (© 2023. The Author(s).)

Glycoside hydrolase family 3 (GH3) β-glucosidase exists in many filamentous fungi. In phytopathogenic fungi, it is involved in fungal growth and pathogenicity. Microdochium nivale is a severe phytopathogenic fungus of grasses and cereals and is the causal agent of pink snow mold, but its β-glucosidase has not been identified. In this study, a GH3 β-glucosidase of M. nivale (MnBG3A) was identified and characterized. Among various p-nitrophenyl β-glycosides, MnBG3A showed activity on d-glucoside (pNP-Glc) and slight activity on d-xyloside. In the pNP-Glc hydrolysis, substrate inhibition occurred (Kis = 1.6 m m), and d-glucose caused competitive inhibition (Ki = 0.5 m m). MnBG3A acted on β-glucobioses with β1-3, -6, -4, and -2 linkages, in descending order of kcat/Km. In contrast, the regioselectivity for newly formed products was limited to β1-6 linkage. MnBG3A has similar features to those of β-glucosidases from Aspergillus spp., but higher sensitivity to inhibitory effects., (© The Author(s) 2023. Published by Oxford University Press on behalf of Japan Society for Bioscience, Biotechnology, and Agrochemistry.)

Despite developing neurosurgical procedures, few treatment options have achieved functional recovery from traumatic brain injury (TBI). Neural stem/progenitor cells (NS/PCs) may produce a long-term effect on neurological recovery. Although induced pluripotent stem cells (iPSCs) can overcome ethical and practical issues of human embryonic or fetal-derived tissues in clinical applications, the tumorigenicity of iPSC-derived populations remains an obstacle to their safe use in regenerative medicine. We herein established a novel treatment strategy for TBI using iPSCs expressing the enzyme-prodrug gene yeast cytosine deaminase-uracil phosphoribosyl transferase (yCD-UPRT). NS/PCs derived from human iPSCs displayed stable and high transgene expression of yCD-UPRT following CRISPR/Cas9-mediated genome editing. In vivo bioluminescent imaging and histopathological analysis demonstrated that NS/PCs concentrated around the damaged cortex of the TBI mouse model. During the subacute phase, performances in both beam walking test and accelerating rotarod test were significantly improved in the treatment group transplanted with genome-edited iPSC-derived NS/PCs compared with the control group. The injury area visualized by extravasation of Evans blue was smaller in the treatment group compared with the control group, suggesting the prevention of secondary brain injury. During the chronic phase, cerebral atrophy and ventricle enlargement were significantly less evident in the treatment group. Furthermore, after 5-fluorocytosine (5-FC) administration, 5-fluorouracil converted from 5-FC selectively eliminated undifferentiated NS/PCs while preserving the adjacent neuronal structures. NS/PCs expressing yCD-UPRT can be applied for safe regenerative medicine without the concern for tumorigenesis., (© The Author(s) 2023. Published by Oxford University Press.)

Background: Posttraumatic stress disorder (PTSD) is a robust risk factor for suicide. Studies have suggested an association between suicide and elevated inflammatory markers, although such evidence in PTSD is scarce. Suicide risk, PTSD, and inflammatory molecules are all shown to be associated with childhood maltreatment and genetic factors., Methods: We examined the association between suicidal ideation/risk and inflammatory markers in 83 civilian women with PTSD, and explored the possible influence of childhood maltreatment and inflammatory genes. Suicidal ideation and risk were assessed using the Beck Depression Inventory-II and the Mini-International Neuropsychiatric Interview. Childhood maltreatment history was assessed with the Childhood Trauma Questionnaire (CTQ). Blood levels of high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6) and high-sensitivity tumor necrosis factor-α were measured. Genetic polymorphisms of CRP rs2794520 and IL6 rs1800796 were genotyped., Results: Suicidal ideation was significantly positively correlated with hsCRP (p = 0.002) and IL-6 (p = 0.015) levels. Suicide risk weighted score was significantly positively correlated with hsCRP (p = 0.016) levels. The risk alleles of CRP rs2794520 and IL6 rs1800796 leading to increased respective protein levels were dose-dependently associated with higher risk of suicide (p = 0.007 and p = 0.029, respectively). The CTQ total score was significantly correlated with suicidal ideation and risk, but not with inflammatory marker levels. Furthermore, a multivariate regression analysis controlling for PTSD severity and potential confounders revealed that rs2794520 and rs1800796, but not hsCRP or IL-6 levels, significantly predicted suicidal ideation (p < 0.001) and risk (p = 0.007), respectively., Conclusion: Genetic variations within inflammatory genes might be useful in detecting PTSD patients at high risk of suicide., Competing Interests: The authors declare that they have no competing interests., (© 2023 The Authors.)

Purpose: Unilateral axillary lymphadenopathy is known to occur after coronavirus disease (COVID-19) vaccination. Post-vaccination lymphadenopathy may mimic the metastatic lymph nodes in breast cancer, and it is challenging to distinguish between them. This study investigated whether the localization of axillary lymphadenopathy on magnetic resonance imaging (MRI) could be used to distinguish reactive lymphadenopathy after COVID-19 vaccines from metastatic nodes., Materials and Methods: We retrospectively examined preoperative MRI images of 684 axillae in 342 patients who underwent breast cancer surgery from June to October 2021. Lymphadenopathy was defined as cortical thickening or short axis ≥ 5 mm. The axilla was divided into ventral and dorsal parts on the axial plane using a perpendicular line extending from the most anterior margin of the muscle group, including the deltoid, latissimus dorsi, or teres major muscles, relative to a line along the lateral chest wall. We recorded the presence or absence of axillary lymphadenopathy in each area and the number of visible lymph nodes., Results: Of 80 axillae, 41 and 39 were included in the vaccine and metastasis groups, respectively. The median time from the last vaccination to MRI was 19 days in the vaccine group. The number of visible axillary lymph nodes was significantly higher in the vaccine group (median, 15 nodes) than in the metastasis group (7 nodes) (P < 0.001). Dorsal lymphadenopathy was observed in 16 (39.0%) and two (5.1%) axillae in the vaccine and metastasis groups, respectively (P < 0.001). If the presence of both ventral and dorsal lymphadenopathy is considered indicative of vaccine-induced reaction, this finding has a sensitivity of 34.1%, specificity of 97.4%, and positive and negative predictive values of 93.3％ and 58.5%, respectively., Conclusion: The presence of deep axillary lymphadenopathy may be an important factor for distinguishing post-vaccination lymphadenopathy from metastasis. The number of axillary lymph nodes may also help., (© 2023. The Author(s).)

We aimed to compare the variables of pain intensity, pain trajectory, and the number of analgesics administered during the acute phase between total and unicompartmental knee arthroplasties. This prospective cohort study recruited 445 patients who planned to undergo knee arthroplasty. Pain intensity was evaluated during hospitalization, and 1 month postoperatively using a numerical rating scale. Pain trajectory (slope and intercept) was calculated using pain intensity data from postoperative days 1 to 4. The number of analgesics administered for worsening pain was monitored during hospitalization. Multiple linear regression analysis with adjustment for potential confounders was conducted to investigate the impact of surgery type on pain variables. Data for 208 and 189 patients who had undergone total and unicompartmental knee arthroplasties, respectively, were included in this study. Pain intensity and pain trajectory were similar between the two surgeries. The number of analgesics administered on postoperative day 3 ( p  = 0.01) and day 4 ( p  = 0.03), as well as total number ( p  = 0.01), were lower for unicompartmental knee arthroplasty than for total knee arthroplasty. Multiple linear regression analysis showed that the type of surgery affected the total number of analgesics administered (β = - 1.24, p  < 0.01, 95% confidence interval: -1.80 to -0.62). This study suggests that pain characteristics observed during the acute phase differ between total and unicompartmental knee arthroplasties. Postoperative pain should be managed, and rehabilitation should be provided at similar levels after the second postoperative day in total and unicompartmental knee arthroplasty patients., Competing Interests: None declared., (Thieme. All rights reserved.)

Background: Under the state of emergency, it has been reported that the amount of physical activity among community-dwelling older adults has decreased significantly due to refraining from going out, and there are strong concerns about the Geriatric Locomotive Function Scale and deterioration of mental health. Therefore, this study aimed to investigate whether the depressive state before the coronavirus disease 2019 (COVID-19) pandemic affected the 25-Geriatric Locomotive (GLFS) score during the COVID-19 pandemic among community-dwelling older adults., Methods: The participants were 194 community-dwelling older adults (45 men, 149 women) with an average age of 75.5 ± 5.5 years who responded to a self-administered survey conducted three times (preliminary, second, and third) from before the 2018 COVID-19 pandemic to March 2021. Individuals with a score of ≥ 10 on the Geriatric Depression Scale 15 (GDS 15) were excluded. The survey items included the 25-question Geriatric Locomotive Function Scale (GLFS25), GDS 15, and other basic attributes. Those with scores of 5 to 9 on the GDS 15 and those with scores of 0 to 4 were assigned to the depressive symptoms (DS) group and the non-DS group, respectively. Statistical analysis was performed using two-way analysis of variance. The Mann-Whitney U test was used for comparisons between the groups., Results: In total, 187 patients were included in the analysis, excluding 7 patients. GLFS 25 showed a significant increase in scores at the second and third time points compared with baseline, and a main effect was confirmed in both groups, with no interaction effect. The second time, the score was 10.0 ± 8.5 and 13.7 ± 10.5 in the non-DS and DS groups, respectively. The third time, the non-DS and DS groups scored 10.8 ± 10.5 and 14.9 ± 10.1 points, respectively, indicating a significant difference., Conclusions: Our results revealed that the increase in the GLFS 25 score in community-dwelling older adults during the COVID-19 pandemic was related to their DS during normal times before the pandemic. Evaluating such individuals and providing social support may effectively reduce the deterioration of the GLFS 25 score., (© 2023. The Author(s).)

Introduction Reports are rare on the usefulness of the FilmArray Respiratory Panel 2.1 (FARP) using lower respiratory tract specimens. This retrospective study assessed its use, as part of a comprehensive infectious disease panel, to detect the viral causes of pneumonia using bronchoalveolar lavage samples from immunosuppressed patients. Methods This study included immunocompromised patients who underwent bronchoalveolar lavage or bronchial washing by bronchoscopy between April 1, 2021, and April 30, 2022. The collected samples were submitted for comprehensive testing, including FARP test; reverse transcription polymerase chain reaction (RT-PCR) for cytomegalovirus, varicella-zoster virus DNA, and herpes simplex virus; PCR for Pneumocystis jirovecii DNA; antigen testing for Aspergillus and Cryptococcus neoformans ; and loop-mediated isothermal amplification method for Legionella . Results Out of 23 patients, 16 (70%) showed bilateral infiltrative shadows on computed tomography and three (13%) were intubated. The most common causes of immunosuppression were anticancer drug use (n=12, 52%) and hematologic tumors (n=11, 48%). Only two (9%) patients tested positive for severe acute respiratory syndrome coronavirus 2 and adenovirus by FARP. Four patients (17%) tested positive for cytomegalovirus by RT-PCR, but no inclusion bodies were identified cytologically. Nine (39%) patients tested positive for Pneumocystis jirovecii by PCR, but cytology confirmed the organism in only one case. Conclusions Comprehensive infectious disease testing, performed using bronchoalveolar lavage samples collected from lung lesions in immunosuppressed patients, showed low positive detection by FARP. The viruses currently detectable by FARP may be less involved in viral pneumonia diagnosed in immunocompromised patients., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Nakamura et al.)

Hallux valgus, a frequently seen foot deformity, requires early detection to prevent it from becoming more severe. It is a medical economic problem, so a means of quickly distinguishing it would be helpful. We designed and investigated the accuracy of an early version of a tool for screening hallux valgus using machine learning. The tool would ascertain whether patients had hallux valgus by analyzing pictures of their feet. In this study, 507 images of feet were used for machine learning. Image preprocessing was conducted using the comparatively simple pattern A (rescaling, angle adjustment, and trimming) and slightly more complicated pattern B (same, plus vertical flip, binary formatting, and edge emphasis). This study used the VGG16 convolutional neural network. Pattern B machine learning was more accurate than pattern A. In our early model, Pattern A achieved 0.62 for accuracy, 0.56 for precision, 0.94 for recall, and 0.71 for F1 score. As for Pattern B, the scores were 0.79, 0.77, 0.96, and 0.86, respectively. Machine learning was sufficiently accurate to distinguish foot images between feet with hallux valgus and normal feet. With further refinement, this tool could be used for the easy screening of hallux valgus.

Background: Intravascular large B-cell lymphoma (IVLBCL) is the proliferation of neoplastic B lymphocytes in the vascular space. Since conventional computed tomography (CT) shows nonspecific findings, differentiation between IVLBCL and other lung diseases, such as diffuse interstitial lung disease, is difficult., Case Presentation: A 73-year-old man presented with dyspnea and hypoxemia. Laboratory findings showed an increased lactate dehydrogenase level of 1690 U/L (normal: 130-235 U/L) and soluble interleukin-2 receptor level of 1140 U/mL (normal: 157-474U/mL). Dual-energy CT iodine mapping showed a significant symmetrical decrease in iodine distribution in the upper lungs, suggesting an unusual distribution of pulmonary hypoperfusion. Therefore, IVLBCL was suspected. A random skin biopsy confirmed the diagnosis of IVLBCL. Due to the severity of the disease, lung biopsy was averted. After admission to the hospital, high-dose methotrexate was administered for central nervous system involvement, due to findings of suspected intracranial infiltration on a brain magnetic resonance imaging and elevated cell counts on lumbar puncture. Subsequently, oxygen demand improved, and rituximab along with cyclophosphamide, doxorubicin, vincristine, and prednisone was added to the patient's regime. Eventually, oxygen administration was terminated, the patient's general condition improved, and the patient was discharged after 47 days of hospitalization., Conclusions: Since the diagnosis of IVLBCL depends on whether it is possible to suspect IVLBCL, the finding of decreased iodine perfusion demonstrated on dual-energy CT is considered important information for diagnosis. An immediate diagnosis of IVLBCL is needed to avoid rapid disease progression and introduce early treatment for a favorable prognosis. In this case, unique pulmonary hypoperfusion demonstrated by dual-energy CT promoted early diagnosis of IVLBCL., (© 2023. The Author(s).)

Surgical treatment of pelvic sarcoma involving the bone is the standard of care but is associated with several sequelae and reduced functional quality of life (QOL). Treatment with photon and proton radiotherapy is associated with relapse. Carbon ion radiotherapy (CIRT) may reduce both relapse rates and treatment sequelae. The PROSPER study is a tricontinental, nonrandomized, prospective, three-arm, pragmatic trial evaluating treatments of pelvic sarcoma involving the bone. Patients aged at least 15 years are eligible for inclusion. Participants must have an Eastern Cooperative Oncology Group Performance Status score of two or less, newly diagnosed disease, and histopathologic confirmation of pelvic chordoma, chondrosarcoma, osteosarcoma, Ewing sarcoma with bone involvement, rhabdomyosarcoma (RMS) with bone involvement, or non-RMS soft tissue sarcoma with bone involvement. Treatment arms include (1) CIRT ( n = 30) delivered in Europe and Asia, (2) surgical treatment with or without adjuvant radiotherapy ( n = 30), and (3) proton therapy ( n = 30). Arms two and three will be conducted at Mayo Clinic campuses in Arizona, Florida, and Minnesota. The primary end point is to compare the 1-year change in functional QOL between CIRT and surgical treatment. Additional comparisons among the three arms will be made between treatment sequelae, local control, and other QOL measures.

Background: Persistent post-surgical pain (PPSP) is associated with upper limb dysfunction and decreased quality of life and causes long-term suffering for breast cancer survivors after surgery. However, the predictors of PPSP remain unclear. The purpose of this study was to examine predictors of PPSP intensity and interference at 1 year postoperatively, focusing on treatment-related factors, pre- and postoperative central sensitization (CS), CS-related symptoms (e.g., muscle stiffness, fatigue, sleep disturbances), and psychological factors., Methods: Eighty-eight women with planned unilateral breast cancer surgery were included in this longitudinal study. CS, CS-related symptoms, and psychological factors were assessed preoperatively, 1 month postoperatively, and 1 year postoperatively. Analysis of covariance was used to compare the groups with and without PPSP, accounting for treatment-related factors. Multiple regression analysis was performed to identify predictors of PPSP intensity and interference at 1 year postoperatively., Results: Even after adjusting for covariates, preoperative and 1-month postoperative Central Sensitization Inventory scores in the PPSP group were significantly higher than scores in the group without PPSP. Multiple regression analysis showed that axillary lymph node dissection (ALND) and 1-month postoperative CS-related symptoms were independent predictors of PPSP intensity and interference at 1 year postoperatively (p < 0.01)., Conclusion: We found that ALND and 1-month postoperative CS-related symptoms were predictors of PPSP intensity and interference at 1 year postoperatively., (© 2022. The Author(s), under exclusive licence to The Japanese Breast Cancer Society.)

Combination therapy for cancer is expected for the synergetic effect of different treatments, and the development of promising carrier materials is demanded for new therapeutics. In this study, nanocomposites including functional nanoparticles (NPs) such as samarium oxide NP for radiotherapy and gadolinium oxide NP as a magnetic resonance imaging agent were synthesized and chemically combined with iron oxide NP-embedded or carbon dot-coating iron oxide NP-embedded carbon nanohorn carriers, where iron oxide NP is a hyperthermia reagent and carbon dot exerts effects on photodynamic/photothermal treatments. These nanocomposites exerted potential for delivery of anticancer drugs (doxorubicin, gemcitabine, and camptothecin) even after being coated with poly(ethylene glycol). The co-delivery of these anticancer drugs played better drug-release efficacy than the independent drug delivery, and the thermal and photothermal procedures enlarged the drug release. Thus, the prepared nanocomposites can be expected as materials to develop advanced medication for combination treatment.

Type 1 recombinant enterovirus G (EV-G), which carries the papain-like cysteine protease (PLCP) gene of torovirus between its 2C/3A regions, and type 2 recombinant EV-G, which carries the torovirus PLCP gene with its flanking regions having non-EV-G sequences in place of the viral structural genes, have been detected in pig farms in several countries. In a previous study, we collected 222 fecal samples from 77 pig farms from 2104 to 2016 and detected one type 2 recombinant EV-G genome by metagenomics sequencing. In this study, we reanalyzed the metagenomic data and detected 11 type 2 recombinant EV-G genomes. In addition, we discovered new type 2 recombinant EV-G genomes of the two strains from two pig farms samples in 2018 and 2019. Thus, we identified the genomes of 13 novel type 2 recombinant EV-Gs isolated from several pig farms in Japan. Type 2 recombinant EV-G has previously been detected only in neonatal piglets. The present findings suggest that type 2 recombinant EV-G replicates in weaning piglets and sows. The detection of type 1 recombinant EV-Gs and type 2 recombinant EV-Gs at 3-year and 2-year intervals, respectively, from the same pig farm suggests that the viruses were persistently infecting or circulating in these farms.

Purpose: Postoperative delirium is one of the most common complications after cardiovascular surgery in older adults. Benzodiazepines are a reported risk factor for delirium; however, there are no studies investigating remimazolam, a novel anesthetic agent. Therefore, we prospectively investigated the effect of remimazolam on postoperative delirium., Methods: We included elective cardiovascular surgery patients aged ≥ 65 years at Hamamatsu University Hospital between August 2020 and February 2022. Patients who received general anesthesia with remimazolam were compared with those who received other anesthetics (control group). The primary outcome was delirium within 5 days after surgery. Secondary outcomes were delirium during intensive care unit stay and hospitalization, total duration of delirium, subsyndromal delirium, and differences in the Mini-Mental State Examination scores from preoperative to postoperative days 2 and 5. To adjust for differences in the groups' baseline covariates, we used stabilized inverse probability weighting as the primary analysis and propensity score matching as the sensitivity analysis., Results: We enrolled 200 patients; 78 in the remimazolam group and 122 in the control group. After stabilized inverse probability weighting, 30.3% of the remimazolam group patients and 26.6% of the control group patients developed delirium within 5 days (risk difference, 3.8%; 95% confidence interval -11.5% to 19.1%; p = 0.63). The secondary outcomes did not differ significantly between the groups, and the sensitivity analysis results were similar to those for the primary analysis., Conclusion: Remimazolam was not significantly associated with postoperative delirium when compared with other anesthetic agents., (© 2022. The Author(s) under exclusive licence to Japanese Society of Anesthesiologists.)

Aim: This study aimed to describe the characteristics of cases of out-of-hospital cardiac arrest (OHCA) with an initial asystole rhythm in which extracorporeal cardiopulmonary resuscitation (ECPR) was introduced and discuss the clinical indications for ECPR in such patients., Methods: This was a secondary analysis of the SAVE-J II study, a retrospective, multicentre, registry study involving 36 participating institutions in Japan. Patients with an initial asystole rhythm were selected. Favourable neurological outcomes (cerebral performance categories 1-2) constituted the primary outcome., Results: In total, 202 patients met the inclusion criteria, with favourable neurological outcomes at hospital discharge in 12 patients (5.9%). Causes of cardiac arrest with favourable neurological outcomes were hypothermia (7 cases), acute coronary syndrome (2 cases), arrhythmia (2 cases), and pulmonary embolism (1 case). Among patients with non-hypothermia (temperature ≥32 °C) on hospital arrival with the cardiac rhythm of asystole or pulseless electrical activity (PEA) on arrival, all 107 patients (66 asystole, 41 PEA) who lacked one or more of the requirements (witness; bystander CPR; signs of life or pupil < 5 mm) had unfavourable neurological outcomes. All 5 cases with favourable neurological outcomes, except for 1 case with a short duration of no-flow time that was highly suspected based on the patient's history, met all the requirements on hospital arrival., Conclusions: A total of 202 ECPR cases with an initial asystole rhythm, including 12 patients with favourable neurological outcomes, were described. Even if the initial cardiac rhythm is asystole, ECPR could be considered if certain conditions are met., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The prevalence of chronic lower back pain (CLBP) among baseball players is high. CLBP is associated with reduced participation in practice and games. This pilot study examined the factors associated with CLBP among high school baseball players in Fukui, Japan. The participants underwent two health examinations in high school: (1) as first-grade baseball players (baseline) and (2) as second-grade baseball players (follow-up); a total of 59 players who could be followed-up a year later were included in the study. Players were divided into three groups based on whether they had no lower back pain (LBP) (n = 30), improved LBP (n = 17), or CLBP (n = 12) after 1 year of follow-up. Players were evaluated on the physical and cognitive aspects of pain. The Number Rating System, Pain Catastrophizing Scale (PCS), Tampa Scale for Kinesiophobia (TSK), Central Sensitization Inventory (CSI), body characteristics (age, height, weight, body mass index, and skeletal mass index), and a medical history questionnaire regarding spondylolysis and baseball loads were used to evaluate the players. Inventory scores were highest in the CLBP group, which indicated that this group had significant pain that affected their willingness to engage in baseball-related activities. The TSK scores in the CLBP group were worse on follow-up. High school baseball players with CLBP were more likely to have lumbar spondylolysis and kinesiophobia, which are also factors related to pain chronicity. Kinesiophobia and the presence of lumbar spondylolysis should be considered when creating an exercise program for high school baseball players with CLBP., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Nakao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Accumulated evidence shows that psychological trauma and posttraumatic stress disorder (PTSD) are associated with dysfunction in the hypothalamic-pituitary-adrenal (HPA) axis. Besides the HPA axis hormones, recent evidence suggests that the renin-angiotensin-aldosterone (RAA) system and genetic factors may be involved in trauma/PTSD as well as in HPA axis regulation. This study attempted to better understand the HPA axis function in relation to PTSD and childhood maltreatment by simultaneously examining RAA system and genetic polymorphisms of candidate genes. Here we studied 69 civilian women with PTSD and 107 healthy control women without DSM-IV-based traumatic experience. Childhood maltreatment history was assessed with the Childhood Trauma Questionnaire. PTSD severity was assessed with the Posttraumatic Diagnostic Scale. Functional disability was assessed with the Sheehan Disability Scale. HPA axis was examined by measuring blood levels of cortisol, adrenocorticotropic hormone, and dehydroepiandrosterone-sulphate (DHEA-S). RAA system was examined by measuring blood renin and aldosterone levels. The FKBP5 rs1360780 and CACNA1C rs1006737 polymorphisms were genotyped. No significant differences were seen between patients and controls in any of the five hormone levels. DHEA-S levels were significantly negatively correlated with overall PTSD severity ( p = 0.003) and functional disability ( p = 0.008). A two-way analysis of variance with diagnostic groups and genotypes as fixed factors revealed that patients with the rs1006737 A-allele had significantly lower DHEA-S levels than patients with the GG genotype ( p = 0.002) and controls with the A-allele ( p = 0.006). Childhood maltreatment history was not significantly correlated with any of the five hormone levels. These results were generally unchanged after controlling for the potentially confounding effect of age, depression, and anxiety. Our findings suggest that lower DHEA-S levels could indicate more severe subtype of PTSD, the association of which might be partly modified by the CACNA1C polymorphism., 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 © 2023 Kakehi, Hori, Yoshida, Itoh, Lin, Niwa, Narita, Ino, Imai, Sasayama, Kamo, Kunugi and Kim.)

Overwintering plants acquire substantial levels of freezing tolerance through cold acclimation or winter hardening. This process is essential for the plants survival to harsh winter conditions. In the areas where persistent snow cover lasts several months, plants are protected from freezing but are, however, exposed to other harsh conditions, such as dark, cold, and high humidity. These conditions facilitate the infection of psychrophilic pathogens, which are termed "snow molds." To fight against infection of snow molds, overwintering plants develop disease resistance via the process of cold acclimation. Compared with pathogen-induced disease resistance, the molecular mechanisms of cold-induced disease resistance have yet to be fully elucidated. In this review, we outline the recent progress in our understanding of disease resistance acquired through cold acclimation., (© 2022 Scandinavian Plant Physiology Society.)

For many producers, introduction of improved animal welfare systems is a turning point in their future production strategies as it increases production costs. The increase in egg retail prices is of growing concern not only for producers, but also for retailers and consumers. However, no report has calculated the estimated production costs or retail prices associated with introducing practices that support improved animal welfare in poultry farms in Japan. Therefore, this study aimed to estimate the production costs and table egg prices of 6 types of laying hen systems: conventional cage (CC): 8- and 12-tiers (CC8, CC12), enriched cage (EC): 8- and 12-tiers (EC8, EC12), aviary (AV), and barn systems (BR). Production costs include land purchases, construction costs of facilities, equipment and machinery, quantity of feed provided, farming materials invested, and wages. As a result, farm gate prices were estimated as CC8 = 12.19, CC12 = 12.19, EC8 = 14.52, EC12 = 14.52, AV = 21.14, and BR = 28.74 [yen/egg], and the production cost, including building the new farm, increased by EC8 = 19.1%, EC12 = 19.1%, AV = 73.4%, and BR = 135.7%, respectively, referring to the value of CC. The results show that the prices increase in systems between CC and BN. The retail price or table egg price was estimated to be CC8 = 24.68, CC12 = 24.68, EC8 = 28.07, EC12 = 28.07, AV = 37.27, and BR = 48.53 [yen/egg]. The retail price of BR is approximately twice that of CC. In addition, assuming that all of Japan's eggs were produced in the BR system, the soaring cost of eggs would likely affect the prices of factory eggs, such as liquid eggs and other products, thus affecting the prices of various food products. Understanding the significant management costs that affect the retail price of eggs would facilitate improved policies and practical approaches to support poultry farms and sustainable farming activities while addressing public concerns., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background and Purpose: The correlation between dose-averaged linear energy transfer (LETd) and its therapeutic or adverse effects, especially in carbon-ion radiotherapy (CIRT), remains controversial. This study aimed to investigate the effects of LETd and dose on pelvic insufficiency fractures after CIRT., Material and Methods: Among patients who underwent CIRT for uterine carcinoma, 101 who were followed up for > 6 months without any other therapy were retrospectively analyzed. The sacrum insufficiency fractures (SIFs) were graded according to the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer toxicity criteria. The correlations between the relative biological effectiveness (RBE)-weighted dose, LETd, physical dose, clinical factors, and SIFs were evaluated. In addition, we analyzed the association of SIF with LETd, physical dose, and clinical factors in cases where the sacrum D50% RBE-weighted dose was above the median dose., Results: At the last follow-up, 19 patients developed SIFs. Receiver operating characteristic curve analysis revealed that the sacrum D50% RBE-weighted dose was a valuable predictor of SIF. Univariate analyses suggested that LETd V10 keV/µm, physical dose V5 Gy, and smoking status were associated with SIF. Cox regression analysis in patients over 50 years of age validated that current smoking habit was the sole risk factor for SIF. Therefore, LETd or physical dose parameters were not associated with SIF prediction., Conclusion: The sacrum D50% RBE-weighted dose was identified as a risk factor for SIF. Additionally, neither LETd nor physical dose parameters were associated with SIF prediction., Competing Interests: Declaration of interest Nobuyuki Kanematsu reports relationships with the Japan Society of Medical Physics (which includes board membership and travel reimbursement), Japan Radiology Congress (which includes board membership and travel reimbursement), Kanagawa Cancer Center (which includes consulting or advisory), Osaka International Cancer Treatment Foundation (which includes travel reimbursement), and the Association for Nuclear Technology in Medicine (which includes speaking and lecture fees). In addition, Nobuyuki Kanematsu has patents: #JP2020-044286A (pending), #JP6383429 (issued), #JP5954705 (with royalties paid), #JP5521225 (with royalties paid), and #JP4456045 (with royalties paid), all to the National Institutes for Quantum Science and Technology., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

It has been reported that marked decreases in physical activity including social activities, deterioration in eating habits and mental health, and an increase in frailty have occurred during the COVID-19 pandemic. This study aimed to devise a method to prevent the onset and progression of frailty during the COVID-19 pandemic and to verify its effect. The subjects were 111 community-dwelling older people who answered questionnaires before and after the intervention. A calendar incorporating 31 different tasks, one for each day, was created as an intervention tool with the aim of improving motor, oral, and cognitive functions. The intervention group ( n = 49) participants performed these tasks every day for 3 months. The primary outcome was the Kihon checklist (KCL) score. When the amount of change in the KCL score before and after 3 months was compared between the two groups, no difference in the total score was observed between the two groups; however, the intervention group showed significantly improved cognitive function in the KCL sub-domain. In the intervention group, the number of pre-frailty and frailty patients decreased significantly after the intervention compared to before the intervention. These results suggest that the use of the calendar created in this study during the COVID-19 pandemic could prevent decreased cognitive function in the KCL sub-domain and could help prevent the onset and progression of pre-frailty and frailty.