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Romosozumab is an anti-sclerostin antibody that increases bone formation and decreases bone resorption. It became available for patients at high risk of osteoporotic fractures in Japan in 2019. The aim of this study was to clarify the clinical effects, safety, and predictors of the effectiveness of 12 months of romosozumab therapy. The study had an observational pre-post design and included 460 patients. Romosozumab was administered at a dose of 210 mg subcutaneously every 4 weeks for 12 months. The incidence of new fractures, safety, and changes in bone mineral density (BMD) and bone turnover markers were recorded. New fractures occurred in 11 cases (3.0 %). Nine patients (2.0 %) experienced cardiovascular events, which were fatal in 3 (0.65 %). Percent changes in BMD at the spine and total hip at 12 months from baseline were +7.7 % and +1.8 %, respectively. Romosozumab had better effects in patients with good renal function, low spine BMD, and high TRACP-5b at baseline and low TRACP-5b or high P1NP after 1 month of treatment. The percent change in spine BMD at 12 months was significantly lower in patients transitioning from denosumab than in those not previously treated with other anti-osteoporosis agents. Romosozumab is considered to be relatively safe in patients with primary osteoporosis compared to those with secondary osteoporosis. Romosozumab resulted in larger increases in spine BMD in patients with primary osteoporosis who were not previously treated with other anti-osteoporosis therapies and those with low spine BMD at the start of treatment., Competing Interests: Declaration of competing interest All authors declare that they have no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objectives　Although physical inactivity is a global concern, quantitative data on its long-term trends in physical activity (PA) are limited. This study aimed to estimate long-term trends in the intensity of occupational PA, constituting the largest portion of PA in Japan.Methods　Data on the number of workers in Japan by occupational category were obtained from the Labour Force Survey. PA intensity (metabolic equivalents [METs]) was assigned to 329 occupations in the Japanese Standard Occupational Classification based on the methods and data of Tudor-Locke et al. (2011), and representative intensity values for 11 occupational categories were calculated. Based on intensity, occupational categories were reclassified into sedentary (≤1.5 METs), light (1.6-2.9 METs), and moderate (≥3 METs). Trends in the prevalence of workers in each category were analyzed, along with the annual mean occupation-related METs from 1953 to 2022. The mean occupation-related METs represented the weighted average of PA intensity, calculated based on the annual worker population for each occupational category. Results　From 1953-2022, the prevalence of moderate-intensity occupations significantly declined, whereas sedentary and light-intensity occupations increased. The mean occupation-related METs decreased continuously for 70 years. During the 48-year period from 1962 to 2010, when there were no major changes in occupational classification methods, there was a decline of 0.25 METs, representing a 9.6% decrease, from 2.60 to 2.35 METs.Conclusion　Over the past 70 years, occupations in Japan have transitioned to ones with lower PA intensity. Consequently, the average PA intensity across all occupations decreased by at least one-tenth. Since this study assumes a constant intensity for each occupation, the actual decline in occupational PA intensity may be even more significant because of societal automation.

Background: Vancomycin regimens are designed to achieve an area under the concentration-time curve/minimum inhibitory concentration (AUC/MIC) ratio ranging between 400 and 600 µg·h/mL in the steady state. However, in cases of critical infections such as bacteremia requiring an early treatment approach, the clinical course may be affected by the AUC/MIC before reaching the steady state, that is, the AUC/MIC values 24 h after the first dose (first 24-h AUC/MIC). This study evaluated the relationship between the first 24-h AUC/MIC and the clinical course of methicillin-resistant Staphylococcus aureus (MRSA) infection., Methods: We retrospectively reviewed the records of patients with MRSA bacteremia in a university hospital between 2015 and 2022. The first 24-h AUC/MIC cutoff was set at 300 µg·h/mL based on the results of early response, and eligible patients were divided into groups with a first 24-h AUC/MIC either < 300 µg·h/mL (< 300 group, n = 32) or ≥ 300 µg·h/mL (≥ 300 group, n = 38). The primary endpoint was the rate of treatment efficacy, and the secondary endpoints were time to clinical and bacteriological improvement and 30-day survival rate., Results: Treatment efficacy and 30-day survival rates were not significantly different between the two groups (78.1% vs. 79.0%, P = 0.933 and 83.9% vs. 87.2%, P = 0.674, respectively). Among patients who showed treatment efficacy, the median time to clinical and bacteriological improvement was 11.5 days and 8.0 days in the < 300 and ≥ 300 groups, respectively; compared to the ≥ 300 group, the < 300 group had a significantly longer time to improvement (P = 0.001)., Conclusions: The first 24-h AUC/MIC had no effect on the treatment efficacy and 30-day survival rates. However, the time to clinical and bacteriological improvement was significantly prolonged in the < 300 group, indicating that the first 24-h AUC/MIC does not affect the rate of therapeutic efficacy but may affect the treatment period., Competing Interests: The authors declare that they have no competing interest., (Copyright 2024, Higashi et al.)

There have been few reports regarding the long-term trends in the genotypes of methicillin-resistant Staphylococcus aureus (MRSA) bloodstream isolates. Therefore, this study was performed to investigate the longitudinal trends in the genotypes of MRSA bloodstream isolates obtained from hospitalized patients during a 12-year study period from 2010 to 2021 at a tertiary care university hospital. Over the 12-year period from 2010 to 2021, we conducted a genetic investigation focusing on 245 MRSA strains isolated from the blood of hospitalized patients. The genotypes of the MRSA bloodstream isolates were determined by Staphylococcal Cassette Chromosome mec (SCC mec ) typing, accessory gene regulator ( agr ) typing, PCR-based ORF typing (POT), and multilocus sequence typing (MLST). Strains with the same POT type detected in two or more isolates were designated as epidemic clones, while strains without a common POT type were classified as sporadic clones. Until 2015, isolates with SCC mec II/ agr II were prevalent, but isolates with SCC mec IV/ agr III increased from 2016. A total of 128 strains (52%) were identified as epidemic clones, while 117 strains (48%) were classified as sporadic clones. The detection rate of sporadic clones increased significantly since 2016 ( p < 0.05). The epidemic clones were classified into three clusters, with MRSA of clonal complex (CC) 1 being prominent after 2016. This study showed that the genotypes of MRSA bloodstream isolates underwent a shift from SCC mec II/ agr II type to SCC mec IV/ agr III type, with a notable increase in MRSA of CC1, after 2016. There was a significant increase in the proportion of sporadic strains among the isolates, suggesting the diversification of genotypes.

Background: Enfortumab vedotin is a novel antibody-drug conjugate used as a third-line therapy for the treatment of urothelial cancer. We aimed to elucidate the effect of enfortumab vedotin-related peripheral neuropathy on its efficacy and whether enfortumab vedotin-induced early electrophysiological changes could be associated with peripheral neuropathy onset., Methods: Our prospective multicenter cohort study enrolled 34 patients with prior platinum-containing chemotherapy and programmed cell death protein 1/ligand 1 inhibitor-resistant advanced urothelial carcinoma and received enfortumab vedotin. The best overall response, progression-free survival, overall survival, and safety were assessed. Nerve conduction studies were also performed in 11 patients., Results: The confirmed overall response rate and disease control rate were 52.9% and 73.5%, respectively. The median overall progression-free survival and overall survival were 6.9 and 13.5 months, respectively, during a median follow-up of 8.6 months. The patients with disease control had significantly longer treatment continuation and overall survival than did those with uncontrolled disease. Peripheral neuropathy occurred in 12.5% of the patients. The overall response and disease control rates were 83.3% and 100%, respectively: higher than those in patients without peripheral neuropathy (p = 0.028 and p = 0.029, respectively). Nerve conduction studies indicated that enfortumab vedotin reduced nerve conduction velocity more markedly in sensory nerves than in motor nerves and the lower limbs than in the upper limbs, with the sural nerve being the most affected in the patients who developed peripheral neuropathy (p = 0.011)., Conclusion: Our results indicated the importance of focusing on enfortumab vedotin-induced neuropathy of the sural nerve to maximize efficacy and improve safety., (© 2024. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

Background: Outpatient cardiac rehabilitation (CR) is a promising tool for improving functional outcome in stroke survivors, however, evidence for improving emotional health is limited. We aimed to clarify the effects of outpatient CR following in-hospital stroke rehabilitation on health-related quality of life (HRQOL) and motor function., Methods: Patients with acute ischemic stroke or transient ischemic attack discharged directly home were recruited, and 128 patients who fulfilled criteria for insurance coverage of CR were divided into the CR (+) group (n = 46) and CR (-) group (n = 82). All patients underwent in-hospital stroke rehabilitation, and within 2 months after stroke onset, patients in the CR (+) group started a 3-month outpatient CR program of supervised sessions. Changes of motor function and HRQOL assessed by the short form-36 version 2 (SF-36) from discharge to 3 months post-discharge were compared between the two groups., Results: Twenty-six patients in the CR (+) group completed the program and 66 patients in the CR (-) group were followed up at a 3-month examination. Least-square mean changes in 6-minute walk distance and isometric knee extension muscle strength were significantly higher in the CR (+) group than the CR (-) group (52.6 vs. 16.3 m; 10.1 vs. 3.50 kgf/kg). Improvement of HRQOL at 3 months was not observed in the CR (+) group., Conclusions: Outpatient CR following in-hospital stroke rehabilitation within 2 months after stroke onset improved exercise tolerance and functional strength but not HRQOL assessed by the SF-36 after completion of CR in the present cohort., 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 Elsevier Ltd. All rights reserved.)

Ivabradine, a hyperpolarization-activated cyclic nucleotide-gated (HCN) channel inhibitor, has been reported to induce photosensitivity-related visual disturbances such as phosphene in humans. Ivabradine-induced visual disturbances are caused by inhibition of HCN channels in the retina, and the mechanisms have been verified using HCN channel knockout mice and electroretinography (ERG). However, in rats, classical ERG using single flash light stimulus with standard analyses of waveform amplitude and latency has not revealed abnormal retinal function after administration of ivabradine. To verify whether retinal dysfunction after ivabradine administration was detectable in rats, we performed ERG using multistep flash light stimulation at the time when plasma concentration of ivabradine was high. Furthermore, the mechanism of the change in the waveform that appeared after the b-wave was investigated. Ivabradine and cilobradine, a selective HCN channel inhibitor, were administered subcutaneously to rats at 4-40 mg/kg as a single dose, and flash or long-duration ERG recordings at each light stimulus luminance were conducted 1.5 h after administration. Plasma and retinal concentrations of both compounds were measured immediately after the ERG recordings. In the flash ERG, prolongation of a- and/or b-wave latencies were detected at each light stimulus, and dose-dependent waveform changes after the b-wave were recorded at the specific light stimulus luminance for both compounds. These ERG changes increased in response to increasing plasma and retinal concentrations for both ivabradine and cilobradine. In the long-duration light stimulus ERG, a change in the waveform of the b-wave trough and attenuation of the c-wave were recorded, suggesting that the feedback control in the photoreceptor cells may be inhibited. This study revealed that the retinal dysfunction by HCN channel inhibitors in rats can be detected by multistep light stimulus ERG. Additionally, we identified that the inhibition of feedback current and the sustained responses in the photoreceptor cells cause the retinal dysfunction of HCN channel inhibitors in rats., Competing Interests: Declaration of competing interest Naohisa Umeya, Yuki Yoshizawa, Kosuke Fukuda, Keigo Ikeda, Mami Kamada, Hiroshi Inada, Toru Usui and Izuru Miyawaki are employees of Sumitomo Pharma Co., Ltd., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: This study aimed to investigate the usefulness of a weight-loss program (WLP) in patients with a high body mass index (BMI) prior to liver resection (Hx) for hepatocellular carcinoma (HCC)., Methods: Among 445 patients with HCC who underwent initial Hx between 2000 and 2020, 19 with a high BMI (≥25.0) were enrolled in our WLP since 2014. For calorie restriction, the amount of energy consumed was calculated as the standard body weight (SBW) kg × 20-25 kcal/day. Protein mass was calculated as SBW kg × 1.0-1.2 g/day to maintain skeletal muscle mass. Patients also performed both aerobic and resistance exercises. The before-and-after changes were compared, and the effect of WLP on the short- and long-term results was investigated., Results: The average length of WLP was 21 days, and weight loss was successfully achieved in all patients. Body fat mass was reduced during the program, while skeletal muscle mass was maintained. WLP led to improvements in liver function and fibrotic markers, without tumor progression. There were no postoperative complications (≥Clavien-Dindo [CD] III). A retrospective comparison between with and without WLP using propensity score-matching analysis revealed that WLP group showed better NLR value, however, there were no significant differences in both short and long-term outcomes after Hx based on participation in the WLP., Conclusions: WLP with multidisciplinary intervention improved immune-nutrition status and liver function of obese patients. WLP had not affected both short and long-term outcomes after Hx., (© 2023. The Author(s) under exclusive licence to Société Internationale de Chirurgie.)

It is important to make an appropriate diagnosis category by evaluating the morphology, blood flow, and hardness of mammary gland disease in breast ultrasound, such as screening and detailed examination. Therefore, understanding the characteristics and effects of B-mode (BM), color Doppler (CD), and elastography (EG) in ultrasonography is considered to lead to improvement in examination accuracy. In this study, we clarified the impact of each function on qualitative diagnosis, with the aim of assisting technologists with high-accuracy breast ultrasound. The subjects were 531 malignant tumor cases. The final evaluation of ultrasonography was classified into 5 levels, BM was classified into 5 levels, CD was classified into 4 levels based on blood flow evaluation, and EG was classified into 9 levels based on the Tsukuba elasticity score. The contribution rates of BM, CD, and EG were 70.4%, 15.0%, and 14.6% in all cases (correlation ratio 0.87). BM was most important at the time of breast ultrasound. No difference was observed between CD and EG. In the evaluation by malignant tumor, each characteristic was seen in the degree of influence. It became clear that comprehensive evaluation is important for benign/malignant evaluation and histological-type estimation.

Background: In cancer genomic medicine, finding driver mutations involved in cancer development and tumor growth is crucial. Machine-learning methods to predict driver missense mutations have been developed because variants are frequently detected by genomic sequencing. However, even though the abnormalities in molecular networks are associated with cancer, many of these methods focus on individual variants and do not consider molecular networks. Here we propose a new network-based method, Net-DMPred, to predict driver missense mutations considering molecular networks. Net-DMPred consists of the graph part and the prediction part. In the graph part, molecular networks are learned by a graph neural network (GNN). The prediction part learns whether variants are driver variants using features of individual variants combined with the graph features learned in the graph part., Results: Net-DMPred, which considers molecular networks, performed better than conventional methods. Furthermore, the prediction performance differed by the molecular network structure used in learning, suggesting that it is important to consider not only the local network related to cancer but also the large-scale network in living organisms., Conclusions: We propose a network-based machine learning method, Net-DMPred, for predicting cancer driver missense mutations. Our method enables us to consider the entire graph architecture representing the molecular network because it uses GNN. Net-DMPred is expected to detect driver mutations from a lot of missense mutations that are not known to be associated with cancer., (© 2023. BioMed Central Ltd., part of Springer Nature.)

The bone morphogenetic protein (BMP) pathway promotes differentiation and induces apoptosis in normal colorectal epithelial cells. However, its role in colorectal cancer (CRC) is controversial, where it can act as context-dependent tumor promoter or tumor suppressor. Here we have found that CRC cells reside in a BMP-rich environment based on curation of two publicly available RNA-sequencing databases. Suppression of BMP using a specific BMP inhibitor, LDN193189, suppresses the growth of select CRC organoids. Colorectal cancer organoids treated with LDN193189 showed a decrease in epidermal growth factor receptor, which was mediated by protein degradation induced by leucine-rich repeats and immunoglobulin-like domains protein 1 (LRIG1) expression. Among 18 molecularly characterized CRC organoids, suppression of growth by BMP inhibition correlated with induction of LRIG1 gene expression. Notably, knockdown of LRIG1 in organoids diminished the growth-suppressive effect of LDN193189. Furthermore, in CRC organoids, which are susceptible to growth suppression by LDN193189, simultaneous treatment with LDN193189 and trametinib, an FDA-approved MEK inhibitor, resulted in cooperative growth inhibition both in vitro and in vivo. Taken together, the simultaneous inhibition of BMP and MEK could be a novel treatment option in CRC cases, and evaluating in vitro growth suppression and LRIG1 induction by BMP inhibition using patient-derived organoids could offer functional biomarkers for predicting potential responders to this regimen., (© 2023 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Background & Aims: This study aimed to investigate the associations of pre-existing sarcopenia with swallowing function, oral intake level, and aspiration pneumonia in patients with acute stroke., Methods: This observational study included patients (≥60 years of age) with acute ischemic stroke or intracerebral hemorrhage within 7 days of onset who were screened for sarcopenia, malnutrition, and swallowing difficulties in a stroke-care unit within 48 h of admission. Sarcopenia was defined by the Asian Working Group on Sarcopenia 2019 as having a low calf circumference, handgrip strength, and appendicular muscle mass index. The primary outcome was impaired oral intake (functional oral intake scale <5 points) at 3, 7, and 14 days after admission, and the secondary outcome was aspiration pneumonia during hospitalization., Results: We enrolled 350 patients (median age of 77 years; 63% males) who underwent the aforementioned screening. Sarcopenia was diagnosed in 34% of patients, and malnutrition was found in 66% of patients with sarcopenia. When compared with the comparison group (defined as patients with either or both normal calf circumference and handgrip strength), the sarcopenia group had significantly lower tongue pressure and a higher prevalence of dysphagia. Sarcopenia was associated with functional oral intake scale <5 at 7 days (adjusted odds ratio [OR], 4.72; 95% confidence interval [CI], 1.91-11.71); p = 0.002) and 14 days (adjusted OR, 3.93; 95% CI, 1.47-10.53; p = 0.006) and with aspiration pneumonia during hospitalization (adjusted OR, 6.12; 95% CI, 1.63-22.94; p = 0.007)., Conclusion: Acute stroke patients with sarcopenia may have weakness of the swallowing-related muscles which may lead to impaired oral intake and aspiration pneumonia., Competing Interests: Conflicts of interest The authors declare no conflict of interest., (Copyright © 2023. Published by Elsevier Ltd.)

Objective: To examine if radiographic ocular lateral deviation (rOLD) could be provoked in stroke patients with mild-to-moderate lateropulsion according to vertical perception., Methods: In this single-center, retrospective study, acute stroke patients with mild-to-moderate lateropulsion assessed by the Scale for Contraversive Pushing were enrolled. Computed tomography or magnetic resonance imaging was performed on all patients on admission and then according to their conditions. The direction and angle of rOLD were compared among three groups according to the responsible lesion: lateral medullary (LM), pontine (P), and hemispheric (H)., Results: Sixty-six patients (male, 47; average age, 67 years) were enrolled and divided into the LM (n = 37), P (n = 8), and H (n = 21) groups. All patients had body tilt. Patients in the LM group showed body tilt to the ipsilesional side during hospitalization, while those in the P and H groups tilted to the contralesional side. All patients had rOLD at the final assessment at an average of 13 days after onset; patients in the P and H groups showed contralateral rOLD, while those in the LM group showed ipsilateral rOLD if they did not have cerebellar or pontine lesions. Significant decreases in the angle and changes in direction of rOLD according to lesion site were observed during hospitalization., Conclusion: Serial changes in rOLD findings after stroke onset are different according to the responsible lesion. The direction of rOLD in most patients is in accordance with vertical perception after the acute stage of stroke., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

This longitudinal study examined the relationship between flexibility-activity and blood-pressure (BP) change among older adults in Japan. Our study included 452 older adults who took part in our survey in both 2012/2013 and 2017/2018. The seated systolic blood pressure (SBP) and diastolic BP (DBP) were measured both at baseline and at the 5 years follow-up. The frequencies of the different physical activities at baseline were assessed using a questionnaire. A generalized linear mixed model was used to estimate the non-standardized coefficient (B) of BP change associated with flexibility activity, after adjustments for sex, age, body mass index, smoking status, alcohol consumption, antihypertensive medication use, history of heart disease, walking time, and muscle-strengthening activity as a fixed-effect, and area of residence as a random-effect. Higher flexibility-activity frequency was significantly associated with reduced SBP (B = -0.77 [95% confidence intervals = -1.36, -0.18], p for linear trend = 0.01, p for quadratic trend = 0.85) and DBP (-0.33 [-0.71, 0.05], p for linear trend = 0.09, p for quadratic trend = 0.04). Engaging in flexibility activity for 3 days per week was significantly associated with a reduction in DBP (B = -4.16, 95% CI [-7.53, -0.79], p = 0.02) compared with that in the reference group (0 days per week). Interaction tests were not significant between basic variables (sex, age, BMI, and antihypertensive medication) and flexibility. In conclusion, higher flexibility activity frequency was associated with a reduction in BP in older adults. Future longitudinal and interventional studies should examine the effects of flexibility activity on cardiovascular disease prevention., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: The causative microorganisms of bloodstream infections (BSIs) in patients with inflammatory bowel disease (IBD) and the clinical characteristics of these patients have not yet been fully identified. Therefore, this study investigated IBD patients who developed BSI to determine their clinical characteristics and identify the BSI-causing bacteria., Methods: The subjects were IBD patients who developed bacteremia between 2015 and 2019 at Fukuoka University Chikushi Hospital. The patients were divided into two groups according to IBD type (Crohn's disease (CD) or ulcerative colitis (UC)). The medical records of the patients were reviewed to determine their clinical backgrounds and identify the BSI-causing bacteria., Results: In total 95 patients, 68 CD and 27 UC patients were included in this study. The detection rates of Pseudomonas aeruginosa ( P. aeruginosa ) and Klebsiella pneumoniae ( K. pneumoniae ) were higher in the UC group than in the CD group (18.5% vs. 2.9%, P = 0.021; 11.1% vs. 0%, P = 0.019, respectively). Immunosuppressive drugs use was higher in the CD group than in the UC group (57.4% vs. 11.1%, P = 0.00003). Hospital stay length was longer in the UC group than in the CD group (15 vs. 9 days; P = 0.045)., Conclusions: The causative bacteria of BSI and clinical backgrounds differed between patients with CD and UC. This study showed that P. aeruginosa and K. pneumoniae had higher abundance in UC patients at the onset of BSI. Furthermore, long-term hospitalized patients with UC required antimicrobial therapy against P. aeruginosa and K. pneumoniae., Competing Interests: The authors declare that they have no competing interests., (Copyright 2023, Kamada et al.)

Objectives: To investigate whether early gait training using Hybrid Assistive Limb (HAL) is feasible and improves walking and independency compared with conventional physical therapy (CPT) in patients with severe walking disability after stroke., Methods: We conducted a single-center, randomized controlled study. Patients with first-ever stroke who had severe walking disability were included. All patients started gait training within 10 days post-stroke onset. Twenty-four patients were randomly assigned into HAL or CPT groups. Outcome measures were collected at three time points, at baseline, completion of 20 sessions of gait training (second assessment), and 3 months after the initiation of gait training. The primary outcomes were changes in motor sub-scores of the Functional Independence Measure or Functional Ambulation Category at the completion of the second assessment from baseline., Results: Twenty-two patients (median age, 68 years; 12 patients in the HAL group and 10 patients in the CPT group) completed the study. There were no significant differences in primary outcomes. Apathy scale, one of the secondary outcomes, showed a decreasing trend in the HAL group (mean change of -3.8, 95% CI -8.14 to 0.475), and a slight increasing trend in the CPT group (mean change of 1.2, 95% CI -2.66 to 5.06) at the second assessment. Patients in the HAL group experienced no adverse events., Conclusions: Early gait training in patients with severe walking disability after stroke using HAL was feasible. Walking ability and independency were not improved at the completion of 20 sessions of gait training., Competing Interests: Declaration of Competing Interest Yoshiyuki Sankai declares conflict of interest using a standard form. The other authors have none of declarations of interest., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: Physical activity is important to improve recovery following surgery. This study investigated the impact of physical activity on the development of pneumonia after radical esophagectomy in patients with thoracic esophageal cancer in the subacute phase from postoperative day 11 to hospital discharge., Methods: This retrospective cohort study included 83 patients who underwent radical esophagectomy for esophageal cancer between 2016 and 2022. Physical activity was measured using an activity tracker, and the average number of steps between postoperative days 8 and 10 was examined. The primary outcome was pneumonia (Clavien-Dindo classification 2 or higher) developing between postoperative day 11 and hospital discharge. We used the receiver operating characteristic (ROC) curve analysis to calculate the optimal cutoff value of physical activity that can predict the development of pneumonia and define low physical activity. We used logistic regression analysis to investigate the impact of low physical activity on postoperative pneumonia., Results: Pneumonia developed in 10 patients (12.0%) during the observation period. The optimal cutoff value of physical activity for predicting pneumonia was 1494 steps per day (sensitivity: 60.0%, specificity: 89.0%, area under the curve: 0.743). In multivariate analysis, low physical activity was an independent predictor of incident pneumonia [odds ratio: 12.10, 95% confidence interval: 2.21-65.90, p = 0.004], with adjustment for age, gastric tube reconstruction route, and postoperative recurrent nerve palsy., Conclusions: Physical activity following radical esophagectomy in patients with thoracic esophageal cancer was an independent predictor of the development of pneumonia in the subacute phase after radical esophagectomy., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Functional relationships between endogenous levels of plant hormones in the growth and development of shoots in etiolated Alaska pea and etiolated Golden Cross Bantam maize seedlings under different gravities were investigated in the "Auxin Transport" experiment aboard the International Space Station (ISS). Comprehensive analyses of 31 species of plant hormones of pea and maize seedlings grown under microgravity (μg) in space and 1 g conditions were conducted. Principal component analysis (PCA) and a multiple regression analysis with the dataset from the plant hormone analysis of the etiolated pea seedlings grown under μg and 1 g conditions in the presence and absence of 2,3,5-triiodobenzoic acid (TIBA) revealed endogenous levels of auxin correlated positively with bending and length of epicotyls. Endogenous cytokinins correlated negatively with them. These results suggest an interaction of auxin and cytokinins in automorphogenesis and growth inhibition of etiolated Alaska pea epicotyls grown under μg conditions in space. Less polar auxin transport with reduced endogenous levels of auxin increased endogenous levels of cytokinins, resulting in changing the growth direction of epicotyls and inhibiting growth. On the other hand, almost no close relationship between endogenous plant hormone levels and growth and development in etiolated maize seedlings grown was observed under μg conditions in space, as per Schulze et al. (1992). However, endogenous levels of IAA in the seedlings grown under μg conditions in space were significantly higher than those grown on Earth, similar to the cases of polar auxin transport already reported., Competing Interests: Declaration of Competing Interest The authors have declared that there are no conflicting interests., (Copyright © 2022 The Committee on Space Research (COSPAR). Published by Elsevier B.V. All rights reserved.)

In the remodeling of axonal arbor, the growth and retraction of branches are differentially regulated within a single axon. Although cell-autonomously generated differences in microtubule (MT) turnover are thought to be involved in selective branch regulation, the cellular system whereby neurons generate differences of MTs between axonal branches has not been clarified. Because MT turnover tends to be slower in longer branches compared with neighboring shorter branches, feedback regulation depending on branch length is thought to be involved. In the present study, we generated a model of MT lifetime in axonal terminal branches by adapting a length-dependent model in which parameters for MT dynamics were constant in the arbor. The model predicted that differences in MT lifetime between neighboring branches could be generated depending on the distance from terminals. In addition, the following points were predicted. Firstly, destabilization of MTs throughout the arbor decreased the differences in MT lifetime between branches. Secondly, differences of MT lifetime existed even before MTs entered the branch point. In axonal MTs in primary neurons, treatment with a low concentration of nocodazole significantly decreased the differences of detyrosination (deTyr) and tyrosination (Tyr) of tubulins, indicators of MT turnover. Expansion microscopy of the axonal shaft before the branch point revealed differences in deTyr/Tyr modification on MTs. Our model recapitulates the differences in MT turnover between branches and provides a feedback mechanism for MT regulation that depends on the axonal arbor geometry., 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 © 2022 Elsevier B.V. All rights reserved.)

Dynamic changes in cell properties lead to intratumor heterogeneity; however, the mechanisms of nongenetic cellular plasticity remain elusive. When the fate of each cell from colorectal cancer organoids was tracked through a clonogenic growth assay, the cells showed a wide range of growth ability even within the clonal organoids, consisting of distinct subpopulations; the cells generating large spheroids and the cells generating small spheroids. The cells from the small spheroids generated only small spheroids (S-pattern), while the cells from the large spheroids generated both small and large spheroids (D-pattern), both of which were tumorigenic. Transition from the S-pattern to the D-pattern occurred by various extrinsic triggers, in which Notch signaling and Musashi-1 played a key role. The S-pattern spheroids were resistant to chemotherapy and transited to the D-pattern upon drug treatment through Notch signaling. As the transition is linked to the drug resistance, it can be a therapeutic target., Competing Interests: J.K., K.O., and M.I. belong to the Department of Clinical Bio-resource Research and Development at Kyoto University, which is sponsored by KBBM, Inc. M.I. is an inventor of the patents related to the CTOS method., (© 2023 The Authors.)

Purpose: Dark band (DB) artifact in head and neck computed tomography (CT) is caused by beam hardening (BH), and decreased CT values in the X-ray target become a problem. Therefore, we investigated whether it is possible to reduce DB artifact in the head and neck with a compensation filter., Methods: We made 2 types of filters with alcohol and water. We set each of these filters in front of the chest phantom's clavicle and evaluated DB artifact. The evaluation method measured CT values in the DB artifact area and background (BG) area by changing each compensation filter thickness and the distance between the chest phantom's surface and each compensation filter. In addition, we measured average standard deviation (SD) in the BG area by the presence of each compensation filter., Results: CT values in the DB artifact area were approximate to those in the BG area by setting the thickness of each compensation filter to more than 30 mm. Furthermore, these CT values were decreased by separating the distance between the chest phantom's surface and each compensation filter. Average SD in the BG area showed no significant difference between no filter and each compensation filter., Conclusion: It was possible to reduce DB artifact by a compensation filter for DB.

Land plants have two types of shoot-supporting systems, root system and rhizoid system, in vascular plants and bryophytes. However, since the evolutionary origin of the systems is different, how much they exploit common systems or distinct systems to architect their structures is largely unknown. To understand the regulatory mechanism of how bryophytes architect the rhizoid system responding to environmental factors, we have developed the methodology to visualize and quantitatively analyze the rhizoid system of the moss, Physcomitrium patens, in 3D. The rhizoids having a diameter of 21.3 µm on the average were visualized by refraction-contrast X-ray micro-computed tomography using coherent X-ray optics available at synchrotron radiation facility SPring-8. Three types of shape (ring-shape, line and black circle) observed in tomographic slices of specimens embedded in paraffin were confirmed to be the rhizoids by optical and electron microscopy. Comprehensive automatic segmentation of the rhizoids, which appeared in three different form types in tomograms, was tested by a method using a Canny edge detector or machine learning. The accuracy of output images was evaluated by comparing with the manually segmented ground truth images using measures such as F1 score and Intersection over Union, revealing that the automatic segmentation using machine learning was more effective than that using the Canny edge detector. Thus, machine learning-based skeletonized 3D model revealed quite dense distribution of rhizoids. We successfully visualized the moss rhizoid system in 3D for the first time., (© The Author(s) 2022. Published by Oxford University Press on behalf of The Japanese Society of Microscopy. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: There is limited understanding of the challenges experienced and supports required to aid effective advocacy of the Global Action Plan on Physical Activity (GAPPA). The purpose of this study was to assess the challenges experienced and supports needed to advocate for the GAPPA across countries of different income levels., Methods: Stakeholders working in an area related to the promotion of physical activity were invited to complete an online survey. The survey assessed current awareness and engagement with the GAPPA, factors related to advocacy, and the perceived challenges and supports related to advocacy for implementation of the GAPPA. Closed questions were analyzed in SPSS, with a Pearson's chi-square test used to assess differences between country income level. Open questions were analyzed using inductive thematic analysis., Results: Participants (n = 518) from 81 countries completed the survey. Significant differences were observed between country income level for awareness of the GAPPA and perceived country engagement with the GAPPA. Challenges related to advocacy included a lack of support and engagement, resources, priority, awareness, advocacy education and training, accessibility, and local application. Supports needed for future advocacy included guidance and support, cooperation and alliance, advocacy education and training, and advocacy resources., Conclusions: Although stakeholders from different country income levels experience similar advocacy challenges and required supports, how countries experience these can be distinct. This research has highlighted some specific ways in which those involved in the promotion of physical activity can be supported to scale up advocacy for the GAPPA. When implementing such supports, consideration of regional, geographic, and cultural barriers and opportunities is important to ensure they are effective and equitable.

Tumors demonstrating deficient mismatch repair (dMMR) account for 12%-15% of colorectal cancers (CRCs), but their characteristics have not been fully elucidated. The aim of this study was to characterize dMMR CRCs in terms of clinicopathological findings and molecular alterations. Immunostaining for mismatch repair (MMR) proteins was performed to determine MMR status, and then MLH1 promoter methylation and genetic variants of 25 genes involved in colorectal carcinogenesis were analyzed by next-generation sequencing in dMMR tumors. Coexistence of precancerous lesions was histologically evaluated to characterize the type of precursors. Immunohistochemistry revealed 34 dMMR tumors in 492 CRCs. Among dMMR CRCs, there were 25 MLH1 methylation-positive, 16 BRAF V600E variant-positive, and 7 KRAS variant-positive tumors. Positive MLH1 methylation was associated with BRAF V600E, older age, and right-side tumor location. MLH1 methylated BRAF/KRAS wild-type tumors were distinct in that all 5 tumors possessed variants in ligand-independent WNT signaling genes including APC, AXIN2, and CTNNB1. Among 10 dMMR CRCs that presented with precancerous lesions, 4 BRAF variant-positive, 1 KRAS variant-positive, and 2 BRAF/KRAS wild-type MLH1 methylated tumors coexisted with serrated lesions, whereas 1 MLH1 methylated BRAF/KRAS wild-type tumor and 2 MLH1 unmethylated tumors accompanied conventional adenomas. The present study characterized distinct subgroups of dMMR CRCs based on molecular alterations including MLH1 methylation and variants in BRAF, KRAS, and ligand-independent WNT signaling genes. The existence of distinct precursor lesions including serrated lesion and conventional adenoma further illustrates the involvement of heterogeneous carcinogenetic pathways in the development of dMMR CRCs., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objectives: Measuring implementation outcomes for digital mental health interventions is essential for examining the effective delivery of these interventions. The "Implementation Outcome Scale of Digital Mental Health" (iOSDMH) has been validated and used in several trials. This study aimed to compare the iOSDMH for participants in six randomized controlled trials (RCTs) involving web-based interventions and to discuss the implications of the iOSDMH for improving the interventions. Additionally, this study examined the associations between iOSDMH scores and program completion rate (adherence)., Methods: Variations in total scores and subscales of the iOSDMH were compared in six RCTs of digital mental health interventions conducted in Japan. The web-based intervention programs were based on cognitive behavioral therapy (2 programs), behavioral activation (1 program), acceptance and commitment (1 program), a combination of mindfulness, behavioral activation, and physical activity (1 program), and government guidelines for suicide prevention (1 program). Participants were full-time employees (2 programs), perinatal women (2 programs), working mothers with children (1 program), and students (1 program). The total score and subscale scores were tested using analysis of variance for between-group differences., Results: Total score and subscale scores of the iOSDMH among six trials showed a significant group difference, reflecting users' perceptions of how each program was implemented, including aspects such as acceptability, appropriateness, feasibility, overall satisfaction, and harm. Subscale scores showed positive associations with completion rate, especially in terms of acceptability and satisfaction (R-squared = 0.93 and 0.89, respectively)., Conclusions: The iOSDMH may be a useful tool for evaluating participants' perceptions of features implemented in web-based interventions, which could contribute to improvements and further development of the intervention.

Low dimensional fermionic quantum systems are exceptionally interesting because they reveal distinctive physical phenomena, including among others, topologically protected excitations, edge states, frustration, and fractionalization. Our aim was to confine 3 He on a suspended carbon nanotube to form 2-dimensional Fermi-system. Here we report our measurements of the mechanical resonance of the nanotube with adsorbed sub-monolayer down to 10 mK. At intermediate coverages we have observed the famous 1/3 commensurate solid. However, at larger monolayer densities we have observed a quantum phase transition from 1/3 solid to an unknown, soft, and mobile solid phase. We interpret this mobile solid phase as a bosonic commensurate crystal consisting of helium dimers with topologically-induced zero-point vacancies which are delocalized at low temperatures. We thus demonstrate that 3 He on a nanotube merges both fermionic and bosonic phenomena, with a quantum phase transition between fermionic solid 1/3 phase and the observed bosonic dimer solid., (© 2022. The Author(s).)

Background: The Olympic Games represent an opportunity to create a 'physical activity legacy' that promotes physical activity at the population level in the host nations and cities. However, previous studies showed little increase in population-level physical activity following the Olympics. The upsurge of public interest in sports and physical activity participation before the Olympics may diminish rapidly following the Games. We examined the pre-Games effects of the Olympics on Japanese population-level physical activity after the announcement of Tokyo's successful bid for the 2020 Olympic and Paralympic Games in September 2013., Methods: We used publicly available data from serial cross-sectional surveys conducted with nationally or regionally representative samples in Japan seven years before and after the announcement (from 2006-2020). The outcomes were 1) daily step counts and 2) exercise habit prevalence (≥ 30 min/day, ≥ 2 days/week, and over a year) from the National Health and Nutrition Surveys Japan (NHNS-J; 14 time points; aggregated data); and 3) sports participation (at least once a week) from the National Sports-Life Survey conducted every two years (NSLS; eight time points; individual-level data of 18,867 adults) and from the Public Opinion Survey on Sports Participation of Tokyo Residents (POSSP; eight time points; aggregated data). Age- and gender-adjusted regression models were used to estimate changes in the outcomes before and after the announcement., Results: There were no significant pre-Games effects of the Olympics on national-level physical activity participation among Japanese adults. Sports participation (56.4% and 57.5%, respectively; P = 0.518), daily steps (6,535 and 6,686 steps/day; P = 0.353), and exercise habit (30.7% and 29.1%, P = 0.309) did not change significantly before and after the announcement. Although an increase in sports participation among Tokyo residents was not found in the NSLS (61.5% and 59.3%, P = 0.227), it was observed in the POSSP (49.1% and 57.7%, P = 0.019). Nonetheless, this increase might not be related to the pre-Games effects since the trend diminished following the announcement., Conclusions: Population-level physical activity did not show significant changes until 2020. Realising the physical activity legacy of an Olympics may require strategic promotion and cross-agency partnership implementation in the pre- and post-event period., (© 2022. The Author(s).)

At our hospital, anti-cancer drug administration is managed using a regimen-ordering system, and orders for the outpatient department and hospital wards have to be placed by 15:00 and 14:00 the day before they are required. On the day of treatment, the doctor examines the patient, confirms the test results, and places the final order for treatment on the patient's electronic medical record. In response, the pharmacist adjusts the anti-cancer drug preparation, and treatment is provided in the outpatient setting or in a ward. Although drug costs have increased due to the widespread use of immunotherapy, there have been cases where a drug was wasted after the required amount was adjusted on the day of treatment or drugs were discarded altogether, which pose serious problems. From April 2016 to March 2021, the total number of cases of drug wastage following placement of the final treatment order and drug disposal were 146 and 84, respectively, and the total associated economic loss was 5.81 million yen. The main causes were pre-confirmation mistakes and patients' physical condition on the day of treatment; some cancellations caused by patient-related factors were unavoidable. The current status of drug disposal is reported to the hospital director every 6 months, and the doctor-in-charge is interviewed regarding the reason for the wastage. In cases involving the disposal of large quantities of drugs(≥100,000 yen), the department manager and medical office manager are contacted, and an incident report is submitted. In 2021, drugs worth 2.03 million yen were discarded between April and September, which is worth serious consideration. It is essential to understand the reasons for drug wastage, pay attention to expensive regimens, and take appropriate measures at each facility.

We report a 25-year-old woman who was diagnosed with atrial septal defect (ASD). An ECG showed only first-degree atrioventricular block and incomplete right bundle branch block. One day after the percutaneous ASD closure, she had a slight fever and an ECG showed a type 1 Brugada pattern. ECG characteristics of ASD are similar to those of a Brugada ECG. This case is rare combination of Brugada syndrome with ASD.

Background: Exercise has been one of the key strategies for preventing frailty. While training programs for preventing frailty have been mainly developed in person, which have now become difficult to perform due to the coronavirus disease pandemic. It would be worthwhile to explore a feasibility of methods for a remote-based training with information and communications technology (ICT) in the pre-frail/robust older adults living at home., Methods: We assessed the feasibility of a remote-based training with ICT device in terms of 1) a measurement accuracy and 2) whether it could be used for remote-based training of different intensities. To evaluate a measurement accuracy of the ICT device, we evaluated an inter-rater reliability between a true score and scores obtaining from the ICT device in 20 participants aged 65 years and older. Intraclass correlation was calculated. To evaluate a feasibility of remote-based training interventions of different intensities, we did a parallel, randomized, active controlled trial. Participants aged 65 years or older were randomly allocated to the two 3-month intervention programs with different intensity of exercise with the ICT (i.e., an Exercise-Intensive program and a Light-load exercise program). The primary outcome was 3-month scores of the 30-s chair-stand test (CS-30), which was compared between two groups using mixed models for repeated measures to account for within-person correlations., Results: The ICT device showed a high intraclass correlation of over 0.99 for all outcomes including CS-30. Between Aug and Oct 2020, 70 participants (36 and 34 in the Exercise-Intensive and Light-load exercise programs, respectively) were randomized. After 3 months of intervention, CS-30 scores and other physical function improved in both groups. Difference in the 3-month CS-30 scores between two programs was found to be 0.08 (95% confidence interval: - 2.64, 2.79; p = 0.955), which was not statistically significant. No harmful incidents, such as falls, occurred in either group., Conclusion: We showed a remote-based training with ICT device in the older adults living at home was feasible. Further studies are warranted to determine what kind of remote exercise intervention programs is more effective for maintaining a physical performance and, beyond that, preventing frailty., Trial Registration Number: UMIN000041616 (05/09/2020) https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&action=brows&recptno=R000047504&type=summary&language=E., (© 2022. The Author(s).)

Background: Food access is an important aspect of health promotion for the elderly. The aim of this study was to investigate the relationship between distance to the nearest food store and diet variety in rural community-dwelling elderly Japanese., Methods: This cross-sectional study analyzed data from 1,103 elderly participants surveyed by mail in rural areas of Japan. Diversity of food intake was assessed using the diet variety score (DVS). Street network distance from home to food store was calculated and categorized by quartile using a geographic information system and analyzed in relation to diet using multivariable regression with the primary outcome as low DVS. Sub-analysis of the association with DVS was conducted for each food store category (convenience store, supermarket, and small food store). The association between intake frequency of each food group and distance was also analyzed., Results: Participants in the fourth quartile of distance to food store had significantly higher prevalence ratio (1.15; 95% CI, 1.01-1.32) for low DVS than those in the first quartile. There was a significant tendency between greater distance to food store and lower DVS (P for trend = 0.033). Supermarkets and convenience stores, in particular, showed significant associations. Greater distance was significantly associated with lower frequency of meat and fruit intake., Conclusion: There was significant association between distance to nearest food store and diet variety in rural Japanese elderly. These findings suggest the importance of interventions for areas at high risk of low diet variety, such as places far away from food stores.

Recent effective therapies enable most rheumatoid arthritis (RA) patients to achieve remission; however, some patients experience relapse. We aimed to predict relapse in RA patients through machine learning (ML) using data on ultrasound (US) examination and blood test. Overall, 210 patients with RA in remission at baseline were dichotomized into remission (n = 150) and relapse (n = 60) based on the disease activity at 2-year follow-up. Three ML classifiers [Logistic Regression, Random Forest, and extreme gradient boosting (XGBoost)] and data on 73 features (14 US examination data, 54 blood test data, and five data on patient information) at baseline were used for predicting relapse. The best performance was obtained using the XGBoost classifier (area under the receiver operator characteristic curve (AUC) = 0.747), compared with Random Forest and Logistic Regression (AUC = 0.719 and 0.701, respectively). In the XGBoost classifier prediction, ten important features, including wrist/metatarsophalangeal superb microvascular imaging scores, were selected using the recursive feature elimination method. The performance was superior to that predicted by researcher-selected features, which are conventional prognostic markers. These results suggest that ML can provide an accurate prediction of relapse in RA patients, and the use of predictive algorithms may facilitate personalized treatment options., (© 2022. The Author(s).)

Despite recent advances in diagnostic procedures for neurological disorders, it is still difficult to definitively diagnose some neurodegenerative diseases without neuropathological examination of autopsied brain tissue. As pathological processes in the brain are frequently reflected in the components of cerebrospinal fluid (CSF), CSF samples are sometimes useful for diagnosis. After CSF is secreted from the choroid plexus epithelial cells in the ventricles, some flows in the brain, some is mixed with intracerebral interstitial fluid, and some is excreted through two major drainage pathways, i.e., the intravascular periarterial drainage pathway and the glymphatic system. Accordingly, substances produced by metabolic and pathological processes in the brain may be detectable in CSF. Many papers have reported changes in the concentration of substances in the CSF of patients with metabolic and neurological disorders, some of which can be useful biomarkers of the disorders. In this paper, we show the significance of glucose- and neurotransmitter-related CSF metabolites, considering their transporters in the choroid plexus; summarize the reported candidates of CSF biomarkers for neurodegenerative diseases, including amyloid-β, tau, α-synuclein, microRNAs, and mitochondrial DNA; and evaluate their potential as efficient diagnostic tools.

Progressive supranuclear palsy (PSP) is a neurodegenerative tauopathy described as a syndrome of postural instability, supranuclear vertical gaze palsy, dysarthria, dystonic rigidity of the neck and trunk, dementia, and pseudobulbar palsy. The clinical diagnosis of PSP is often difficult because there are no established biomarkers, and diagnosis is currently based on clinical and imaging findings. Furthermore, the etiology and pathogenesis of PSP remain unknown. Dysregulation of microRNAs (miRNAs/miRs) has been reported to serve an important role in neurodegenerative diseases. However, the miRNA profiles of patients with PSP are rarely reported. The present study aimed to examine cerebrospinal fluid miRNAs, which are considered to be more sensitive indicators of changes in the brain, to elucidate the pathophysiology of PSP and to establish specific biomarkers for diagnosis. The present study used a microarray chip containing 2,632 miRNAs to examine cerebrospinal fluid miRNA expression levels in 11 patients with PSP aged 68‑82 years. A total of 8 age‑ and sex‑matched controls were also included. A total of 38 miRNAs were significantly upregulated and one miRNA was significantly downregulated in the cerebrospinal fluid of patients with PSP. The patients were divided into two groups based on disease stage (early onset and advanced), and changes in miRNA expression were examined. The miRNAs that were most significantly upregulated or downregulated in the early onset group were miR‑204‑3p, miR‑873‑3p and miR‑6840‑5p. The target genes of these miRNAs were associated with molecules related to the ubiquitin‑proteasome system and autophagy pathway. Furthermore, these miRNAs were found to target genes that have been reported to have epigenetic changes following an epigenome‑wide association study of brain tissues of patients with PSP. This suggested that these miRNAs and genes may have some involvement in the pathogenesis of PSP. However, the sample size of the present study was small; therefore, a greater number of patients with PSP should be examined in future studies.

How microgravity in space influences plant cell growth is an important issue for plant cell biology as well as space biology. We investigated the role of cortical microtubules in the stimulation of elongation growth in Arabidopsis ( Arabidopsis thaliana ) hypocotyls under microgravity conditions with the Resist Tubule space experiment. The epidermal cells in the lower half of the hypocotyls of wild-type Columbia were longer in microgravity than at on-orbit 1 g , which precipitated an increase in the entire hypocotyl length. In the apical region, cortical microtubules adjacent to the outer tangential wall were predominantly transverse to the long axis of the cell, whereas longitudinal microtubules were predominant in the basal region. In the 9th to 12th epidermal cells (1 to 3 mm) from the tip, where the modification of microtubule orientation from transverse to longitudinal directions (reorientation) occurred, cells with transverse microtubules increased, whereas those with longitudinal microtubules decreased in microgravity, and the average angle with respect to the transverse cell axis decreased, indicating that the reorientation was suppressed in microgravity. The expression of tubulin genes was suppressed in microgravity. These results suggest that under microgravity conditions, the expression of genes related to microtubule formation was downregulated, which may cause the suppression of microtubule reorientation from transverse to longitudinal directions, thereby stimulating cell elongation in Arabidopsis hypocotyls.

Background: Sedentary behaviors are prevalent among children and can have a detrimental effect on their health. Little is known about the influence of parental time on children's sedentary behavior. This study examined the association between parental working hours and children's sedentary time., Methods: Cross-sectional data were drawn from the Japanese Study on Stratification, Health, Income, and Neighborhood (J-SHINE) in 2010 and 2011. Participants were 886 children aged 7-18 years and their parents. The primary outcome was self-reported sedentary time after school that comprised screen time and non-screen time. The main explanatory variable was parental working hours. We used multiple regression analysis adjusting for sociodemographic factors., Results: Children's mean sedentary time was 222 (standard deviation [SD], 123) min/day; 144 (SD, 108) min/day screen time and 78 (SD, 65) min/day non-screen time. Children whose mothers worked ≥20 hours/week had 28 (95% CI, 9 to 48) min/day longer sedentary time than children of homemakers (240 min/day vs 214 min/day). The longer maternal working hours, the longer sedentary time (P for trend <0.01). In contrast, children whose fathers worked ≥48 hours/week had 82 (95% CI, -156 to -7) min/day shorter sedentary time than children of non-working fathers (179 min/day vs 264 min/day). When limited to children whose fathers worked, there was no statistically significant association between children's sedentary time and paternal working hours., Conclusions: Children with mothers who work long hours or fathers not working tend to sit more. Supplementing the shortages in resources for childcare may be necessary among those families.

To understand gravity resistance in plants, it is necessary to analyze the changes induced when the magnitude of gravity in a growth environment is modified. Microgravity in space provides appropriate conditions for analyzing gravity resistance mechanisms. Experiments carried out in space involve a large number of constraints and are quite different from ground-based experiments. Here, we describe basic procedures for space-based experiments to study gravity resistance in plants. An appropriate cultivation chamber must be selected according to the growing period of the plants and the purpose of the experiment. After cultivation, the plant material is fixed with suitable fixatives in appropriate sample storage containers such as the Chemical Fixation Bag. The material is then analyzed with a variety of methods, depending on the purpose of the experiment. Plant material fixed with the RNAlater ® solution can be used sequentially to determine the mechanical properties of the cell wall, RNA extraction (which is necessary for gene-expression analysis), estimate the enzyme activity of cell wall proteins, and measure the levels and compositions of cell wall polysaccharides. The plant material can also be used directly for microscopic observation of cellular components such as cortical microtubules., (© 2022. Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: Gamification, the use of game design elements in nongame contexts, in combination with insights from behavioral economics, has been applied increasingly to behavior change interventions. However, little is known about the effectiveness or scalability of this approach, especially in the long term. We tested a large-scale smartphone-based intervention to encourage physical activity among Japanese baseball fans using gamification techniques that leveraged fandom and interteam competition inherent in sports., Methods: A quasi-experimental study was conducted among fans of the Japanese Pacific League. The app, Pa-League Walk, included gamification elements, such as competition between opposing teams' fans based on total daily step counts on game days (>60,000 free downloads since March 2016). We analyzed daily steps of 20,052 app users, supplemented by online survey data of 274 users and 613 matched controls. Difference-in-differences estimators evaluated change in daily steps before and after app installation in users versus matched controls., Results: Users' daily steps increased by 574 (95% confidence interval, 83-1064) steps 3 months after installation, compared with controls. The increase was maintained for up to 9 months (559 (99-1018) more steps per day vs baseline), attenuating over a longer follow-up. Positive effect modification was found by high-frequency of the app use (P < 0.001) but not by other covariables (P ≥ 0.14) such as education or income. Days with 10,000-step achievement increased from 24.4% to 27.5% after the additional introduction of incentives (digital player photographs; P < 0.001)., Conclusions: Using existing fandom and solidarity, the gamification app increased physical activity at scale among baseball fans, including people with lower socioeconomic status underrepresented in traditional health programs., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American College of Sports Medicine.)

Background: Physical inactivity during the coronavirus disease 2019 (COVID-19) pandemic may have hindered the development of fundamental movement skills in preschoolers. This serial cross-sectional study compared fundamental movement skills by age group before and during the COVID-19 pandemic (2019-2020), among Japanese preschoolers aged 3-5 years., Methods: Of the 22 preschools within Unnan City, Shimane Prefecture, Japan, 21 (95.5%) and 17 (77.3%) participated in the 2019 and 2020 surveys, respectively. We analyzed 608 and 517 preschoolers in both surveys. Fundamental movement skills were objectively assessed with a 25 m run, standing long jump, and softball throw, based on the Japanese physical activity guidelines for preschoolers. Mann-Whitney U tests were used to compare the fundamental movement skills data between periods., Results: For the 25 m run, participants aged 5 years were faster before than during the pandemic (p = 0.018), while participants aged 3 and 4 years showed no significant differences. Participants aged 3-5 years showed no significant differences before and during the pandemic for the standing long jump (p ≥ 0.072). For the softball throw, all grades scored higher before than during the pandemic (p < 0.001)., Conclusions: These findings suggest that the COVID-19 pandemic impeded the development of fundamental motor skills, especially for object control skills. This highlights the need for interventions aimed at developing fundamental motor skills in preschoolers during and after the pandemic.

Objectives: Recreational physical activity is an integral part of our society, and the injuries caused by sports activities are a concern for public health. We studied the effect of outdoor ambient temperature on hospital emergency department visits caused by sports injuries in Madrid, Spain, and accounted for its seasonal changes., Methods: We used a time-series design. Data was analysed with quasi-Poisson regression models. We calculated the proportion of emergency visits attributable to seasonal changes before and after adjusting for daily ambient temperature. We modelled the association between emergency visits and temperature using distributed lag non-linear models., Results: The proportion of emergency visits attributable to seasonal changes was 24.1% and decreased to 7.6% after adjusting for temperature. We found a high risk of emergency visits associated with cold and hot temperatures, whereas the risk was higher for heat., Conclusion: Sports and recreational physical activity injuries are not rare events; therefore, appropriate healthcare decisions should consider the impact of outdoor ambient temperature and seasonal changes., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Digital mental health interventions are being used more than ever for the prevention and treatment of psychological problems. Optimizing the implementation aspects of digital mental health is essential to deliver the program to populations in need, but there is a lack of validated implementation outcome measures for digital mental health interventions., Objective: The primary aim of this study is to develop implementation outcome scales of digital mental health for different levels of stakeholders involved in the implementation process: users, providers, and managers or policy makers. The secondary aim is to validate the developed scale for users., Methods: We developed English and Japanese versions of the implementation outcome scales for digital mental health (iOSDMH) based on the literature review and panel discussions with experts in implementation research and web-based psychotherapy. The study developed acceptability, appropriateness, feasibility, satisfaction, and harm as the outcome measures for users, providers, and managers or policy makers. We conducted evidence-based interventions via the internet using UTSMeD, a website for mental health information (N=200). Exploratory factor analysis (EFA) was conducted to assess the structural validity of the iOSDMH for users. Satisfaction, which consisted of a single item, was not included in the EFA., Results: The iOSDMH was developed for users, providers, and managers or policy makers. The iOSDMH contains 19 items for users, 11 items for providers, and 14 items for managers or policy makers. Cronbach α coefficients indicated intermediate internal consistency for acceptability (α=.665) but high consistency for appropriateness (α=.776), feasibility (α=.832), and harm (α=.777) of the iOSDMH for users. EFA revealed 3-factor structures, indicating acceptability and appropriateness as close concepts. Despite the similarity between these 2 concepts, we inferred that acceptability and appropriateness should be used as different factors, following previous studies., Conclusions: We developed iOSDMH for users, providers, and managers. Psychometric assessment of the scales for users demonstrated acceptable reliability and validity. Evaluating the components of digital mental health implementation is a major step forward in implementation science., (©Natsu Sasaki, Erika Obikane, Rajesh Vedanthan, Kotaro Imamura, Pim Cuijpers, Taichi Shimazu, Masamitsu Kamada, Norito Kawakami, Daisuke Nishi. Originally published in JMIR Formative Research (https://formative.jmir.org), 23.11.2021.)

Background: Social participation has been suggested as a means to prevent depressive symptoms. However, it remains unclear whether a one-time boost suffices or whether participation needs to be sustained over time for long-term prevention. We estimated the impacts of alternative hypothetical interventions in social participation on subsequent depressive symptoms among older adults., Methods: Data were from a nationwide prospective cohort study of Japanese older adults ≥65 years of age (n = 32,748). We analyzed social participation (1) as a baseline exposure from 2010 (approximating a one-time boost intervention) and (2) as a time-varying exposure from 2010 and 2013 (approximating a sustained intervention). We defined binary depressive symptoms in 2016 using the Geriatric Depression Scale. We used the doubly robust targeted maximum likelihood estimation to address time-dependent confounding., Results: The magnitude of the association between sustained participation and the lower prevalence of depressive symptoms was larger than the association observed for baseline participation only (e.g., prevalence ratio [PR] for participation in any activity = 0.83 [95% confidence interval = 0.79, 0.88] vs. 0.90 [0.87, 0.94]). For activities with a lower proportion of consistent participation over time (e.g., senior clubs), there was little evidence of an association between baseline participation and subsequent depressive symptoms, while an association for sustained participation was evident (e.g., PR for senior clubs = 0.96 [0.90, 1.02] vs. 0.88 [0.79, 0.97]). Participation at baseline but withholding participation in 2013 was not associated with subsequent depressive symptoms., Conclusions: Sustained social participation may be more strongly associated with fewer depressive symptoms among older adults., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: This cross-sectional study investigated the association between hilliness and walking speed in community-dwelling older adults, and whether it varied according to their car-driving status., Methods: Data were collected from 590 participants aged 65 and older living in Okinoshima Town, Shimane prefecture, Japan, in 2018. Comfortable walking speed (m/s) was objectively assessed. Hilliness was measured by the mean land slope (degree) within a 500-m or 1000-m network buffer around each participant's home using a geographic information system. A multiple linear regression examined whether the land slope was associated with walking speed, adjusted for sex, age, body mass index, smoking habits, alcohol consumption habits, exercise habits, chronic disease, and living arrangements. A stratified analysis by car-driving status was also conducted., Results: After adjusting for all confounders, the land slope within the 500-m or 1000-m network buffer was negatively associated with walking speed (B = -0.007, 95% CI [-0.011, -0.002]; B = -0.007, 95% CI [-0.011, -0.003], respectively). The stratified analysis by car-driving status showed that living in a hilly area was negatively associated with walking speed among non-drivers in the 500-m or 1000-m network buffer (B = -0.011, 95% CI [-0.017, -0.004]; B = -0.012, 95% CI [-0.019, -0.006]), though there were no associations among drivers., Conclusions: A hilly environment is positively associated with slow walking speed in community-dwelling older adults in Japan. Moreover, car-driving status potentially modifies the relationship between living in a hilly environment and slow walking speed., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

The present study aimed to assess spinal tract formation in neurons originating from cervical (C7), brachial (C14), and thoracic (T4) regions, with the lumbar (LS2) region as a reference, in a chick embryo. For the assessment of the spinal tracts, we introduced a vector expressing human placental alkaline phosphatase into progenitor cells generated after neural tube closure and belonging to the above segments, using in ovo electroporation. The ascending axons took primarily similar paths: dorsal commissural, ventral commissural, and dorsal non-commissural paths, with some variance depending on their originating segments. Some populations of non-commissural neurons later extended their axons following a ventral path. The elongation rates of these axons are primarily constant and tended to increase over time; however, some variations depending on the originating segments were also observed. Some of the dorsally ascending axons entered into the developing cerebellum, and spinocerebellar neurons originating from T4 projected their axons into the cortex of the cerebellum differently from those from LS2. These results unveil an overall picture of early ascending spinal tract formation., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Parkinson's disease (PD) is caused by a combination of genetic and environmental factors. Notably, genetic risk factors vary according to ethnicity and geographical regions, and few studies have analyzed the frequency of PD causative genes in Japanese patients. Therefore, we performed genetic analyses of Japanese patients with PD. We recruited 221 participants, including 26 patients with familial PD. Genetic risk factors were evaluated by target sequencing and gene dosage analysis. We detected the genetic risk factors in 58 cases (26.2%) and classified patients into three groups to clarify the differences in genetic risk factors by age at onset (AAO). The early-onset group (AAO < 50 years) included 18 cases (44.7%), who tended to have a larger number of genetic risk factors than the later-onset groups. Regarding the AAO for each causative gene, patients with PRKN variants were significantly younger at onset than those bearing LRRK2 variants. LRRK2 variants showed similar frequency in each AAO group. Of note, we identified two novel variants. Patients with early-onset PD have more genetic risk factors than patients with late-onset PD. In Japanese patients with PD, PRKN, and LRRK2 were the major PD-related genes. Particularly, LRRK2 was a common genetic factor in all age groups because of the presence of the Asian-specific variant such as LRRK2 p.G2385R. Accumulation of genetic and clinical data can contribute to the development of treatments for PD., (© 2021. The Author(s), under exclusive licence to The Japan Society of Human Genetics.)

Low-frequency 1/ f   γ noise is ubiquitous, even in high-end electronic devices. Recently, it was found that adsorbed O 2 molecules provide the dominant contribution to flux noise in superconducting quantum interference devices. To clarify the basic principles of such adsorbate noise, we have investigated low-frequency noise, while the mobility of surface adsorbates is varied by temperature. We measured low-frequency current noise in suspended monolayer graphene Corbino samples under the influence of adsorbed Ne atoms. Owing to the extremely small intrinsic noise of suspended graphene, we could resolve a combination of 1/ f   γ and Lorentzian noise induced by the presence of Ne. We find that the 1/ f   γ noise is caused by surface diffusion of Ne atoms and by temporary formation of few-Ne-atom clusters. Our results support the idea that clustering dynamics of defects is relevant for understanding of 1/ f noise in metallic systems.