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The accident at the Fukushima Daiichi Nuclear Power Plant (FDNPP) caused a radioactive contamination in seabed sediment. The 137Cs supply from rivers could be an important process for the long-term behavior of 137Cs in seabed sediment. In this study, a ten-year simulation of the 137Cs behavior in seabed sediment was conducted using an oceanic dispersion model combined with a prediction model of 137Cs behavior in land and river. In the waters north of FDNPP, the simulation results suggested that the 137Cs supply from rivers had a great impact on the concentrations in coastal sediment due to the initial low concentrations in seabed sediment and the large supply of 137Cs from rivers. In the waters near FDNPP and south of FDNPP, the simulation results suggested that the impact of the 137Cs supply on the temporal variation of 137Cs concentration in coastal sediment was relatively small due to the large initial adsorption from seawater. Overall, these results indicated that 137Cs supply from rivers had an impact on the spatiotemporal distribution of 137Cs concentrations in seabed sediment on a decadal time scale and the impact was especially great in the waters north of FDNPP.

Background: In aging societies, the prevalence of chronic kidney disease (CKD) is expected to increase but may be underestimated because many asymptomatic patients remain undiagnosed. This study aimed to estimate the CKD prevalence among the general older population in Japan., Methods: This cross-sectional study used health screening data from the Japan Health Insurance Association collected between April 2014 and March 2023. Data from older people aged 65-90 years who underwent renal function screening for estimated glomerular filtration rate (eGFR) and urine protein tests were analyzed. CKD was defined as eGFR < 60 mL/min/1.73 m 2 or proteinuria ≥ 1 + . Inverse probability weighting was used to account for the selection bias. The variables used for weighting were age, sex, insurance status, and the number of previous screenings., Results: Among 2.98 million older individuals, 588,809 (19.7%) had undergone screening (median [IQR] age, 69.9 [67.9-76.2] years, 337,862 women [57.4%]). Regarding the weighted CKD prevalence, 25.3% of the individuals aged 65-90 years had CKD; 11.8% of those aged 65-75 years and 34.6% of those aged 75 years and over showed an increase in prevalence with age. Among the patients with CKD, over half exhibited mild renal dysfunction without proteinuria. Hypertension and diabetes were common comorbidities in older patients with CKD., Conclusions: This cross-sectional study revealed that the weighted prevalence of CKD in the older population aged 65-90 years was high (one in four individuals), indicating that it increases with age. Further studies are required to examine the clinical significance of these findings., (© 2024. The Author(s).)

This study analyzed the association of romosozumab, a human monoclonal antibody with bone-forming and bone resorption-inhibiting effects, and bisphosphonates with the development of cardiovascular disease among patients with osteoporosis. A new-user design was employed to address selection bias, and instrumental variable analysis was used to address confounding by indication. Japanese patients aged ≥40 years, diagnosed with osteoporosis or experienced a fragility fracture, were admitted to medical facilities covered by a commercial administrative claims database, and newly prescribed romosozumab or bisphosphonates after the commercialization of romosozumab in Japan (March 4, 2019) were included based on verification of a 180-day washout period. Cardiovascular disease (myocardial infarction or stroke) was identified based on information regarding diagnosis, medical procedures, and drug codes. Facility-level prescription preference for romosozumab was used as an instrumental variable, defined as the proportion of romosozumab prescribed at the patient's facility within 90 days prior to the index date. Of the 59 694 included prescriptions, 8808 were for romosozumab and 50 886 were for bisphosphonates. The mean age in the romosozumab group was higher than that in the bisphosphonates group (80.5 vs. 78.2 years, respectively), and most patients were females (85.3 vs. 80.2%, respectively). The incidence of cardiovascular disease within 1 year of prescription was 12.3 per 100 person-years for romosozumab versus 11.4 for bisphosphonates (unadjusted incidence rate ratio: 1.08, 95% confidence interval: 1.00-1.18). An instrumental variable analysis using the two-stage residual inclusion method yielded a hazard ratio of 1.30 (95% confidence interval: 0.88-1.90) for romosozumab compared with bisphosphonates over 1 year. Although possibly underpowered, this study showed that no definitive evidence of increased cardiovascular risk associated with romosozumab use compared with bisphosphonates was observed in patients with osteoporosis. These findings should be further validated by larger pharmacoepidemiological studies to alleviate clinicians' concerns about romosozumab's safety., (© The Author(s) 2025. Published by Oxford University Press on behalf of the American Society for Bone and Mineral Research.)

Objectives: To explore practice variations in the rate and timing of tracheostomy and gastrostomy for adolescent with severe traumatic brain injury (TBI) across trauma center types., Design: Retrospective cohort study., Setting: Trauma centers participating in the American College of Surgeons Trauma Quality Improvement Program (2017-2021) included adult (ATC), mixed (MTC), and pediatric trauma centers (PTC)., Patients: Adolescent 14-18 years old with severe TBI (Head Abbreviated Injury Scale: 3-5 and Glasgow Coma Scale: 3-8) requiring mechanical ventilation., Interventions: None., Measurements and Main Results: A multilevel mixed-effect Poisson regression model assessed the association between trauma center type and tracheostomy/gastrostomy rates. Effect sizes for fixed effects were reported as adjusted incidence rate ratio (IRR) with 95% CI. Secondary analyses were performed to assess the association between trauma center types and ventilator-associated pneumonia (VAP). Of 6978 patients, tracheostomy and gastrostomy were performed in 22.5% and 21.3% at ATC, 20.8% and 21.3% at MTC, and 6.9% and 11.1% at PTC, respectively. The median time to tracheostomy was 10 days (interquartile range [IQR], 7-13 d) at ATC, 11 days (IQR, 7-15 d) at MTC, and 15 days (IQR, 11-23 d) at PTC, demonstrating a significantly later timing of tracheostomy at PTC. In the regression model adjusting for potential confounders, treatment at PTC was significantly associated with a decreased likelihood of tracheostomy and gastrostomy placement compared with ATC (adjusted IRR, 0.38; 95% CI, 0.28-0.52; p < 0.001 and adjusted IRR, 0.58; 95% CI, 0.44-0.75; p < 0.001, respectively). There was no significant difference in the occurrence rate of VAP between ATC, MTC, and PTC., Conclusions: Our results offer insights into the existing current practice variations between ATC, MTC, and PTC in tracheostomy and gastrostomy placement for adolescent with severe TBI. Further research is warranted to examine the impact of these observed disparities on short- and long-term outcomes and to standardize the care process for adolescent patients., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2025 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Background: The optimal surgical management of penetrating carotid artery injuries (PCAIs) remains controversial. This study aimed to examine the association between operative techniques for PCAI and the incidence of stroke., Study Design: This retrospective cohort study used the American College of Surgeons TQIP (2016 to 2021) database. We included patients (age 16 years or older) with severe penetrating injuries to the common or internal carotid arteries (CCA/ICA) who underwent one of the following operative procedures: primary suture repair, ligation, and arterial reconstruction with a graft. Multivariate logistic regression analysis with cluster-adjusted-robust SEs was performed to estimate the adjusted odds ratio (AOR) for postoperative stroke stratified by the initial Glasgow Coma Scale (GCS)., Results: A total of 492 patients were included (329 underwent primary suture repair, 82 underwent ligation, and 81 underwent arterial reconstruction with a graft). The median age was 31 years (interquartile range 24 to 43) and median GCS on arrival was 11 (interquartile range 3 to 15). On multivariate analysis after adjusting for potential confounders, ligation of CCA/ICA was significantly associated with increased odds of stroke in patients with initial GCS ≥9 (AOR: 4.40, 95% CI 1.16 to 16.58, p = 0.029), whereas there was no significant association in patients with GCS <9 (AOR 0.77, 95% CI 0.28 to 2.11, p = 0.37). No significant association was identified between arterial reconstruction with a graft and stroke, irrespective of the initial GCS., Conclusions: The study findings suggest that the preoperative level of consciousness may help in planning operative strategies for PCAI. In patients with an initial GCS ≥9, definitive repair of the CCA/ICA, including arterial reconstruction with a graft, should be pursued instead of ligation., (Copyright © 2024 by the American College of Surgeons. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Pseudomyxoma peritonei (PMP) is a rare disease caused by mucin-producing tumors that develop most frequently from the appendix. The disease is characterized by the accumulation of mucin in the abdominal cavity. Although frequent mutations in the KRAS and GNAS genes have been reported in PMP, gene expression profiles of the tumors remain to be fully clarified because of its rarity and the difficulties in collecting pure cancerous cells scattered within the mucin. To disclose the molecular features of PMP cells, we performed RNA-seq analysis of ten PMPs and their matched non-tumorous colonic epithelium in combination with laser-microdissection. As a result, we identified a total of 32 differently expressed genes (DEGs) between the tumors and non-tumorous colonic epithelium. A cell-of-origin subtype analysis with the nearest template prediction algorithm corroborated that PMP tumor cells belonged to the goblet cell subtype, and tumorous cells of PMP appear to arise from goblet cells. Interestingly, over representation analysis (ORA) uncovered that the tumors were significantly associated with three ontology terms, namely epithelial mesenchymal transition (EMT), angiogenesis, and inflammatory response. Comparison of gene expression profiles between disseminated peritoneal adenomucinosis (DPAM) and peritoneal mucinous adenocarcinomas (PMCA) identified a total of 687 DEGs. Additional gene set enrichment analysis (GSEA) revealed that ontology terms "G2M checkpoint" and "E2F targets" were significantly enriched in PMCA supporting the view that PMCA has more aggressive properties than DPAM. These data may be useful to further understand the molecular characteristics of PMP., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Background: Despite the increasing use of minimally invasive surgeries, the outcome benefits of adopting minimally invasive surgery for colostomy reversal remain unclear. We aimed to analyze nationwide trends in the use of minimally invasive surgery for colostomy reversal and compare patient outcomes between different surgical approaches., Methods: The National Inpatient Sample was queried for patients who underwent colostomy reversal for benign disease from 2015 to 2021. National trends in the use of minimally invasive surgery for colostomy reversal were analyzed by Cochran-Armitage tests. Multivariable linear and logistic regressions accounting for hospital sample weights were developed to examine the association between operative approach (open, laparoscopic, and robotic) and patient outcomes, including hospital complications, length of stay, and hospital charges., Results: A total of 23,260 patients underwent colostomy reversal: 18,880 (81.2%) open, 3,245 (14.0%) laparoscopic, and 1,135 (4.9%) robotic surgery. From 2015 to 2021, the proportion of robotic approaches increased >5-fold (range 2.1-12.5%; P trend < .001), whereas the increase in laparoscopic approaches was not significant (range 11.5-16.2%; P trend  = .34). Multivariable analysis showed that the laparoscopic approach was associated with a lower incidence of pulmonary complications (adjusted odds ratio, 0.49; 95% confidence interval, 0.28-0.87), surgical-site infection (odds ratio, 0.37; 95% CI, 0.19-0.72), peritonitis/abdominal abscess (odds ratio, 0.45; 95% confidence interval, 0.26-0.78), and paralytic ileus (odds ratio, 0.67; 95% confidence interval, 0.48-0.92). The robotic approach was associated with a lower incidence of paralytic ileus (odds ratio, 0.58; 95% confidence interval, 0.33-0.99). Laparoscopic and robotic approaches were associated with 22.9% and 29.9% shorter length of stay, respectively. The robotic approach was associated with 33.0% greater hospital charge., Conclusions: This study observed a significant trend toward the increased use of robotics in colostomy reversal and potential clinical benefits with minimally invasive surgery. Robotic colostomy reversal, along with laparoscopic approach, may provide better postoperative recovery compared with the open approach; however, the utility of robotic surgeries needs to be reevaluated in the future, given the limited clinical benefits despite greater hospital charges., Competing Interests: Conflicts of Interest/Disclosure All authors report no potential conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The influx of microplastics (MPs) into the Arctic Ocean poses a collective risk, particularly with pronounced sea ice depletion due to global warming. A total of 73 replicate sediment samples were collected at different depths (38 to 79 m) from Chukchi and the Beaufort Seas at 8 stations in the Arctic region during the R/V Mirai cruise (MR22-06C) from August to September 2022. The average concentration of MPs is 79.25 ± 31.08 items/kg d.w. Fibrous MPs of 0-1 mm size range are predominant, with blue being the most prevalent colour. Polymer characterization identified polyethylene (PE) as the predominant polymer. Arctic Ocean regions face heightened health risks from the coexistence of MPs and harmful additives, amplifying concerns over plastic pollution. The alarming surge in MPs within Arctic sediment underscores the urgent need for a proactive, collaborative approach to mitigate this environmental threat and its far-reaching impacts., 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.)

The Kuroshio Extension recirculation gyre in the western North Pacific is an accumulation site of plastic litter transported by the Kuroshio Current. A sediment trap was moored at a depth of 4900 m at Station KEO within the Kuroshio Extension recirculation gyre, and the vertical flux of microplastics in sinking particles of size <1 mm was observed. Forty-one sediment-trap samples collected from July 1, 2014, to October 2, 2016, were analyzed with a micro-Fourier transform infrared spectrometer and microplastics were detected in all samples. Seventeen polymer types were identified, and 90% of the microplastics were less than 100 μm in size. Microplastic sinking was driven by the action of the biological pump, which was in turn driven by seasonal variations in solar radiation and increased surface primary production typical of the spring season. Microplastic mass flux varied from 4.5 × 10 -3 to 0.38 mg m -2 day -1 during the sampling period, with a mean and standard deviation of 0.054 ± 0.075 mg m -2 day -1 . Extrapolating the annual microplastic mass flux at Station KEO to the entire Kuroshio Extension recirculation gyre, it is estimated that 0.028 million metric tons of microplastics are transported annually to 4900 m depth in this area.

Early detection of cognitive decline is essential for timely intervention and effective management of age-related impairments. We monitored repetitive reaction times to a simple task on senior-friendly tablet computers among 72 functionally independent older adults, with a mean age of 82, ranging up to 100 years, within natural settings over two years. Functional principal component analyses revealed a consistent decrease in reaction time in line with their task experience among those without subjective cognitive decline. Conversely, individuals reporting subjective cognitive decline showed no consistent trend and exhibited wide variability over time. These distinctive reaction time trajectories in very old adults suggest the potential for monitoring as a non-invasive, convenient method for early detection of cognitive impairment., (© 2024. The Author(s).)

Although community-acquired acute kidney injury (CA-AKI) represents a significant subset of all AKI incidence, evidence is limited due to the lack of comprehensive data prior to diagnosis. Here, we examined the risk of drug use for CA-AKI by using exhaustive pre-diagnostic prescription data. We included 78,754 working-age healthy individuals who underwent an annual health checkup program. We conducted a cohort study to assess the association between prevalent drug use and subsequent CA-AKI incidence using the Cox proportional hazard model. Subsequently, we conducted a case-crossover study to compare the new drug use in the case period directly before the CA-AKI incidence (- 3 to 0 months) with that in the control period far before the CA-AKI incidence (- 15 to - 12 months and - 9 to - 6 months) using the conditional Poisson regression model. The prevalent use of renin-angiotensin-aldosterone system (RAAS) inhibitors was associated with an increased CA-AKI incidence, but the new use was not. The new use of diuretics, anti-infectious drugs, and contrast medium was also associated with an increased CA-AKI incidence. These results suggest we need to pay attention for the incidence of AKI among the general population taking those common drugs., (© 2024. The Author(s).)

Background and Aim: The diagnostic accuracy for cholangiocarcinoma (CCA) is inadequate, necessitating the exploration of novel diagnostic approaches. Protoporphyrin IX (Pp IX), a metabolic product of 5-aminolevulinic acid (5-ALA), emits red fluorescence upon blue light exposure. Because it accumulates selectively in cancer cells, photodynamic diagnosis using 5-ALA (5-ALA-PDD) has been integrated into clinical practice for diverse cancer types. Nevertheless, there is currently no device capable of capturing Pp IX-derived fluorescence for real-time 5-ALA-PDD within the biliary tract, largely due to challenges in device miniaturization., Methods: To investigate the feasibility of real-time 5ALA-PDD in CCA, we developed two essential components of the cholangioscopy system: a small-diameter flexible camera and a light guide for emitting blue light. We evaluated the detectability of Pp IX fluorescence using these devices in experimental gels and animal models., Results: Our camera and light guide were smoothly inserted into the lumen of existing cholangioscopes. Incorporating a long-pass filter at the camera tip enabled efficient detection of red fluorescence without significantly impacting white-light observation. The integration of these devices facilitated clear visualization of red fluorescence from gels containing Pp IX at concentrations of 5 μM or higher. Additionally, when observing subcutaneous human CCA tumor models in nude mice treated with 5-ALA, we successfully demonstrated distinct red fluorescence from Pp IX accumulation in tumors compared to peritumoral subcutaneous areas., Conclusion: The integration of our device combination holds promise for real-time 5-ALA-PDD in human CCA, potentially enhancing the diagnostic accuracy for this complex condition., Competing Interests: Declaration of competing interest Shiho Furudate and Yuki Kodama are employees of Japan Lifeline Co., Ltd., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: The optimal management of pediatric patients with high-grade blunt pancreatic injury (BPI) involving the main pancreatic duct remains controversial. This study aimed to assess the nationwide trends in the management of pediatric high-grade BPI at pediatric (PTC), mixed (MTC), and adult trauma centers (ATC)., Study Design: This is a retrospective observational study of the National Trauma Data Bank. We included pediatric patients (age 16 years or less) sustaining high-grade BPI (Abbreviated Injury Scale 3 or more) from 2011 to 2021. Patients who did not undergo pancreatic operation were categorized into the nonoperative management (NOM) group. Trauma centers were defined as PTC (level I/II pediatric only), MTC (level I/II adult and pediatric), and ATC (level I/II adult only). Primary outcome was the proportion of patients undergoing NOM, and secondary outcomes included the use of ERCP and in-hospital mortality. A Cochran-Armitage test was used to analyze the trend., Results: A total of 811 patients were analyzed. The median age was 9 years (interquartile range 6 to 13), 64% were male patients, and the median injury severity score was 17 (interquartile range 10 to 25). During the study period, there was a significant upward linear trend in the use of NOM and ERCP among the overall cohort (range 48% to 66%; p trend = 0.033, range 6.1% to 19%; p trend = 0.030, respectively). The significant upward trend for NOM was maintained in the subgroup of patients at PTC and MTC (p trend = 0.037), whereas no significant trend was observed at ATC (p trend = 0.61). There was no significant trend in in-hospital mortality (p trend = 0.38)., Conclusions: For the management of pediatric patients with high-grade BPI, this study found a significant trend toward increasing use of NOM and ERCP without mortality deterioration, especially at PTC and MTC., (Copyright © 2024 by the American College of Surgeons. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Deregulation of the Wnt/β-catenin pathway is associated with the development of human cancer including colorectal and liver cancer. Although we previously showed that histidine ammonia lyase (HAL) was transcriptionally reduced by the β-catenin/TCF complex in liver cancer cells, the mechanism(s) of its down-regulation by the complex remain to be clarified. In this study, we search for the transcription factor(s) regulating HAL, and identify CEBPA and FOXA1, two factors whose expression is suppressed by the knockdown of β-catenin or TCF7L2. In addition, RNA-seq analysis coupled with genome-wide mapping of CEBPA- and FOXA1-binding regions reveals that these two factors also increase the expression of arginase 1 (ARG1) that catalyzes the hydrolysis of arginine. Metabolome analysis discloses that activated Wnt signaling augments intracellular concentrations of histidine and arginine, and that the signal also increases the level of lactic acid suggesting the induction of the Warburg effect in liver cancer cells. Further analysis reveals that the levels of metabolites of the urea cycle and genes coding its related enzymes are also modulated by the Wnt signaling. These findings shed light on the altered cellular metabolism in the liver by the Wnt/β-catenin pathway through the suppression of liver-enriched transcription factors including CEBPA and FOXA1., (© 2024. The Author(s).)

PVRL4 (or nectin‑4) is a promising therapeutic target since its upregulated expression is found in a wide range of human cancer types. Enfortumab vedotin, an antibody‑drug conjugate targeting PVRL4, is clinically used for the treatment of urothelial bladder cancer. In addition, rMV‑SLAMblind, a genetically engineered oncolytic measles virus, can infect cancer cells and induce apoptosis through interaction with PVRL4. Although PVRL4 transcript levels are elevated in breast, lung and ovarian cancer, the mechanisms of its upregulation have not yet been uncovered. To clarify the regulatory mechanisms of elevated PVRL4 expression in breast cancer cells, Assay for Transposase‑Accessible Chromatin‑sequencing and chromatin immunoprecipitation‑sequencing (ChIP‑seq) data were used to search for its regulatory regions. Using breast cancer cells, an enhancer region was ultimately identified. Additional analyses, including ChIP and reporter assays, demonstrated that FOS interacted with the PVRL4 enhancer region, and that alterations of the FOS‑binding motifs in the enhancer region decreased reporter activity. Consistent with these data, exogenous expression of FOS enhanced the reporter activity and PVRL4 expression in breast cancer cells. Furthermore, RNA‑seq analysis using breast cancer cells treated with PVRL4 small interfering RNA revealed its possible involvement in the cytokine response and immune system. These data suggested that FOS was involved, at least partly, in the regulation of PVRL4 expression in breast cancer cells, and that elevated PVRL4 expression may regulate the response of cancer cells to cytokines and the immune system.

Introduction: Pseudomyxoma peritonei (PMP) is a disease characterized by progressive accumulation of intraperitoneal mucinous ascites produced by neoplasms in the abdominal cavity. Since the prognosis of patients with PMP remains unsatisfactory, the development of effective therapeutic drug(s) is a matter of pressing concern. Genetic analyses of PMP have clarified the frequent activation of GNAS and/or KRAS. However, the involvement of global epigenetic alterations in PMPs has not been reported., Methods: To clarify the genetic background of the 15 PMP tumors, we performed genetic analysis using AmpliSeq Cancer HotSpot Panel v2. We further investigated global DNA methylation in the 15 tumors and eight noncancerous colonic epithelial tissues using MethylationEPIC array BeadChip (Infinium 850k) containing a total of 865,918 probes., Results: This is the first report of comprehensive DNA methylation profiles of PMPs in the world. We clarified that the 15 PMPs could be classified into at least two epigenotypes, unique methylation epigenotype (UME) and normal-like methylation epigenotype (NLME), and that genes associated with neuronal development and synaptic signaling may be involved in the development of PMPs. In addition, we identified a set of hypermethylation marker genes such as HOXD1 and TSPYL5 in the 15 PMPs., Conclusions: These findings may help the understanding of the molecular mechanism(s) of PMP and contribute to the development of therapeutic strategies for this life-threatening disease., (© 2024 S. Karger AG, Basel.)

Objectives: To assess whether acoustic stimulations relieve venipuncture pain and determine which stimulation is the most effective type., Design: Systematic review and network meta-analysis., Data Sources: PubMed, Cochrane Central Register of Controlled Trials, Excerpta Medica dataBASE, Cumulative Index to Nursing and Allied Health Literature, ClinicalTrials.gov and the International Clinical Trials Registry Platform databases were systematically searched in September 2023., Study Selection: Randomised controlled trials evaluating the efficacy of acoustic stimulations on patients undergoing venipuncture were eligible. Acoustic stimulations were classified into seven categories: five types of acoustic stimulations (music medicine (researcher selected), music medicine (patient selected), music therapy, sounds with linguistic meaning and sounds without linguistic meaning) and two controls (only wearing headphones and no treatment)., Primary and Secondary Outcome Measures: Primary outcomes included self-reported pain intensity assessed during venipuncture and treatment cost, and secondary outcomes were self-reported mental distress and adverse events., Results: Of 6406 citations, this network meta-analysis included 27 studies including 3416 participants; the mean age was 31.5 years, and 57% were men. Among the five types of acoustic stimulations, only musical interventions, such as music medicine (patient selected) (standardised mean difference (SMD) -0.44 (95% CI: -0.84 to -0.03); low confidence), music medicine (researcher selected) (SMD -0.76 (95% CI: -1.10 to -0.42); low confidence) and music therapy (SMD -0.79 (95% CI: -1.44 to -0.14); low confidence), were associated with improved pain relief during venipuncture compared with no treatment. No significant differences existed between the types of acoustic stimulations. Free-of-charge acoustic stimulations were provided to patients, and no specific adverse events were reported. In many studies, the risk of bias was rated high because of the difficulty of blinding the intervention to the participants and the self-reported pain outcome., Conclusions: Music interventions were associated with reduced venipuncture pain. Comparisons between types of acoustic stimulations revealed no significant differences. Therefore, music intervention could be a safe and inexpensive pain relief method for venipuncture., Prospero Registration Number: CRD42022303852., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Immune thrombocytopenia (ITP) is a thrombocytopenic condition induced by autoimmune mechanisms and includes secondary ITP with underlying diseases such as connective tissue diseases (CTD). In recent years, it has been elucidated that the subsets of the ITP are associated with complement abnormalities but much remains unclear. To perform a literature review and identify the characteristics of complement abnormalities in ITP. PUBMED was used to collect the literature published up to June 2022 related to ITP and complement abnormalities. Primary and secondary ITP (CTD-related) were examined. Out of the collected articles, 17 were extracted. Eight articles were related to primary ITP (pITP) and 9 to CTD-related ITP. Analysis of the literature revealed that the ITP severity was inversely correlated with serum C3, C4 levels in both ITP subgroups. In pITP, a wide range of complement abnormalities was reported, including abnormalities of initial proteins, complement regulatory proteins, or the end products. In CTD-related ITP, reported complement abnormalities were limited to the initial proteins. Activation of the early complement system, mainly through activation of C3 and its precursor protein C4, was reported for both ITPs. On the other hand, more extensive complement activation has been reported in pITP.

Background: Endometrial cancer (EC) is one of the leading causes of cancer death among women and early detection is crucial for its successful treatment. We previously showed that cytological examination combined with genetic analysis using liquid-based cytology (LBC) samples improved the diagnostic sensitivity of EC., Methods: Among 218 individuals who underwent endometrial screening by LBC, 208 samples were analysed by cancer-panel sequencing. Excluding 13 samples with low sequence coverage, we further analysed 195 samples., Results: Among the 195 women analysed, 39 and 15 were eventually shown to suffer from malignant endometrial and non-endometrial neoplasms, respectively. Driver mutation(s) were found in nine of the 15 cytology-negative patients with endometrial malignancy, corroborating that combination of cytological and genetic analyses should increase the sensitivity of the diagnosis of malignant endometrial neoplasms. Importantly, driver alterations were found in 32 of 125 women without malignant or premalignant diseases, which raises caution for the interpretation of genetic alterations detected in the endometrial samples. Comparison between the driver mutations in the 32 subjects and those in the 29 endometrial malignancies unveiled that the number of mutations and mutations in PTEN, CTNNB1, and TP53 may be applied for the assessment and prediction of development of EC., Conclusions: The genetic analysis combined with liquid-based cytology is useful to improve the diagnostic sensitivity of endometrial neoplasms. However, caution must be taken when cancer-associated mutation(s) are detected in the genetic analysis. Further investigation may clarify the risk of malignant endometrial neoplasms in women with driver mutation(s)., (© 2023. The Author(s).)

We aimed to evaluate the renoprotective effects of remote ischemic preconditioning (RIPC) in patients undergoing robot-assisted laparoscopic partial nephrectomy (RAPN). Data from 59 patients with solitary renal tumors who underwent RAPN with RIPC comprising three cycles of 5-min inflation to 200 mmHg of a blood pressure cuff applied to one lower limb followed by 5-min reperfusion by cuff deflation, from 2018 to 2020 were analyzed. Patients who underwent RAPN for solitary renal tumors without RIPC between 2018 and 2020 were selected as controls. The postoperative estimated glomerular filtration rate (eGFR) at the nadir during hospitalization and the percentage change from baseline were compared using propensity score matching analysis. We performed a sensitivity analysis with imputations for missing postoperative renal function data weighted by the inverse probability of the data being observed. Of the 59 patients with RIPC and 482 patients without RIPC, 53 each were matched based on propensity scores. No significant differences in the postoperative eGFR in mL/min/1.73 m 2 at nadir (mean difference 3.8; 95% confidence interval [CI] - 2.8 to 10.4) and its percentage change from baseline (mean difference 4.7; 95% CI - 1.6 to 11.1) were observed between the two groups. Sensitivity analysis also indicated no significant differences. No complications were associated with the RIPC. In conclusion, we found no significant evidence of the protective effect of RIPC against renal dysfunction after RAPN. Further research is required to determine whether specific patient subgroups benefit from RIPC.Trial registration number: UMIN000030305 (December 8, 2017)., (© 2023. The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature.)

Background and Objectives: Pain during cannulation for vascular access is a considerable problem for patients with kidney disease who are undergoing hemodialysis. We examined whether listening to music can reduce cannulation pain in these patients., Design, Setting, Participants, & Measurements: We conducted a multicenter, single-blind, crossover, randomized trial of 121 patients who reported pain during cannulation for hemodialysis. We compared participants listening to "Sonata for Two Pianos in D Major, K.448" or white noise as control while undergoing the cannulation procedure. The cannulation operator was blinded to the intervention, and the hypothesized superiority of music over white noise was concealed during explanations to the participants. The primary end point was the visual analog scale score for cannulation pain independently evaluated by participants., Results: The primary analysis was on the basis of the modified intention-to-treat principle. The median baseline visual analog scale pain score was 24.7 mm (interquartile range, 16.5-42.3). Median change of the visual analog scale pain score from the "no sound" to the music period was -2.7 mm (interquartile range, -9.2 to 3.6), whereas it was -0.3 mm (interquartile range, -5.8 to 4.5) from "no sound" to white noise. The visual analog scale pain score decreased when listening to music compared with white noise. (Adjusted difference of visual analog scale pain score: -12%; 95% confidence interval, -21 to -2; P =0.02.) There were no significant differences in the secondary outcomes of anxiety, BP, or stress assessed by salivary amylase (adjusted difference of visual analog scale anxiety score -8%, 95% confidence interval, -18 to 4; P =0.17). No intervention-related adverse events were reported., Conclusions: Listening to music reduced cannulation pain in patients on hemodialysis, although there was no significant effect on anxiety, BP, or stress markers., (Copyright © 2022 by the American Society of Nephrology.)

Aims: The aim of this study is to investigate whether consumption of sturgeon fillets reduces the oxidative stress marker urinary 8-hydroxy-2'-deoxyguanosine (8OHdG) in top-ranked Japanese female long-distance runners., Methods: In a before-and-after study, nine professional long-distance female athletes ate 100 g/day of sturgeon fillets for 2 weeks. Urinalysis (8OHdG, an oxidative stress marker, and creatinine), blood tests (fatty acids and 25-hydroxyvitamin D [25OHD]), exercise intensity, subjective fatigue, muscle elasticity, muscle mass, body fat mass, and nutritional intake using image-based dietary assessment (IBDA) were compared before, immediately after, and 1 month after the intervention., Results: Consumption of sturgeon fillets suppressed 8OHdG (p < 0.05) in the increased exercise intensity female athletes. Eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and 25OHD levels in blood increased from before to immediately after and 1 month after the intervention (p < 0.05). IBDA showed that intake of n-3 fatty acid increased after and one month after the intervention, whereas DHA, imidazole dipeptide and vitamin D intake increased after the intervention (p < 0.05) and then decreased after 1 month (p < 0.05). There were no significant changes in subjective fatigue, muscle elasticity, muscle mass, and body fat., Conclusions: The results suggest that eating sturgeon fillets during intense training may increase blood levels of EPA, DHA, and 25OHD, which may suppress urinary oxidative stress (8OHdG) in top-ranked Japanese long-distance runners., (© 2023 Japan Society of Obstetrics and Gynecology.)

There is considerable interest in drug discovery targeting the aggregation of α-synuclein (αSyn) since this molecular process is closely associated with Parkinson's disease. However, inhibiting αSyn aggregation remains a major challenge because of its highly dynamic nature which makes it difficult to form a stable binding complex with a drug molecule. Here, by exploiting Random non-standard Peptides Integrated Discovery (RaPID) system, we identified a macrocyclic peptide, BD1, that could interact with immobilized αSyn and inhibit the formation of fibrils. Furthermore, improving the solubility of BD1 suppresses the co-aggregation with αSyn fibrils while it kinetically inhibits more effectively without change in their morphology. We also revealed the molecular mechanism of kinetic inhibition, where peptides bind to fibril ends of αSyn, thereby preventing further growth of fibrils. These results suggest that our approach for generating non-standard macrocyclic peptides is a promising approach for developing potential therapeutics against neurodegeneration., (© 2023 The Authors. ChemBioChem published by Wiley-VCH GmbH.)

The Fukushima Daiichi Nuclear Power Plant accident caused a radioactive contamination of deposited radionuclides, including 137 Cs, on the land surface. Cesium-137 deposited on the land surface was strongly adsorbed on soil particles and was then washed off through soil erosion. Trends of temporal variation of 137 Cs wash-off varied greatly depending on land use. Therefore, it is important to reflect the characteristics of 137 Cs migration processes in each land use to clarify the long-term fate of 137 Cs. In this study, a 30-year simulation of environmental fate of 137 Cs was conducted using a distributed radiocesium prediction model, taking into account the characteristics of the 137 Cs behavior in each land use. Overall, in the Abukuma River basin, the 137 Cs transported into the ocean for 30 years was estimated to correspond to 4.6 % of the initial deposition in the basin, and the effective half-life of 137 Cs deposited in the basin was estimated to be 3.7 years shorter (by 11.6 %) than its physical half-life. These results suggested that 137 Cs deposited from the accident could still remain for decades. Based on the analysis of the 137 Cs behavior in land use, in 2011, the contribution of 137 Cs export to the ocean from urban lands was estimated to correspond to 70 % of the total 137 Cs export. Meanwhile, from 2012 to 2040, the contribution of 137 Cs export from agricultural lands was estimated to correspond to 75 % of the total 137 Cs export. The reduction ratios excluding radioactive decay of 137 Cs remained in areas with and without human activities for 30 years after the accident, defined as the ratios of the total outflow to the initial deposition, were estimated to be 11.5 %-17.7 % and 0.4 %-1.4 %, respectively. These results suggested that human activities enhance the reduction of 137 Cs remaining in land in the past and future., 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 © 2023 Elsevier B.V. All rights reserved.)

Background: Abnormal activation of Wnt/β-catenin signaling is associated with various aspects of cancer development. This study explored the roles of novel target genes of the Wnt/β-catenin signaling pathway in cancer cells., Methods: Using the haploid chronic myelogenous leukemia cell line HAP1, RNA sequencing (RNA-seq) was performed to identify genes whose expression was increased by APC disruption and reversed by β-catenin knockdown (KD). The regulatory mechanism and function of one of the candidate genes was investigated in colorectal cancer (CRC) cells., Results: In total, 64 candidate genes whose expression was regulated by Wnt/β-catenin signaling were identified. Of these candidate genes, the expression levels of six were reduced by β-catenin KD in HCT116 CRC cells in our previous microarray. One of these genes was Visinin-like 1 (VSNL1), which belongs to the neuronal calcium-sensor gene family. The expression of VSNL1 was regulated by the β-catenin/TCF7L2 complex via two TCF7L2-binding elements in intron 1. VSNL1 KD-induced apoptosis in VSNL1-positive CRC cells. Additionally, forced expression of wild-type VSNL1, but not a myristoylation, Ca 2+ -binding, or dimerization-defective mutant, suppressed the apoptosis induced by camptothecin and doxorubicin in VSNL1-negative CRC cells., Conclusion: Our findings suggest that VSNL1, a novel target gene of the Wnt/β-catenin signaling pathway, is associated with apoptosis resistance in CRC cells., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Bicyclic peptides have great therapeutic potential since they can bridge the gap between small molecules and antibodies by combining a low molecular weight of about 2 kDa with an antibody-like binding specificity. Here we apply a recently developed in silico rational design strategy to produce a bicyclic peptide to target the C-terminal region (residues 31-42) of the 42-residue form of the amyloid β peptide (Aβ42), a protein fragment whose aggregation into amyloid plaques is linked with Alzheimer's disease. We show that this bicyclic peptide is able to remodel the aggregation process of Aβ42 in vitro and to reduce its associated toxicity in vivo in a C. elegans worm model expressing Aβ42. These results provide an initial example of a computational approach to design bicyclic peptides to target specific epitopes on disordered proteins.

Bromodomain-containing protein 8 (BRD8) is a subunit of the NuA4/TIP60-histone acetyltransferase complex. Although BRD8 has been considered to act as a co-activator of the complex, its biological role remains to be elucidated. Here, we uncovered that BRD8 accumulates in colorectal cancer cells through the inhibition of ubiquitin-dependent protein degradation by the interaction with MRG domain binding protein. Transcriptome analysis coupled with genome-wide mapping of BRD8-binding sites disclosed that BRD8 transactivates a set of genes independently of TIP60, and that BRD8 regulates the expression of multiple subunits of the pre-replicative complex in concert with the activator protein-1. Depletion of BRD8 induced cell-cycle arrest at the G1 phase and suppressed cell proliferation. We have also shown that the bromodomain of BRD8 is indispensable for not only the interaction with histone H4 or transcriptional regulation but also its own protein stability. These findings highlight the importance of bromodomain as a therapeutic target., Competing Interests: The authors declare no competing interests., (© 2023 The Author(s).)

Objectives: Social distancing due to the coronavirus disease 2019 crisis can exacerbate inactivity in older adults. Novel approaches for older adults must be designed to improve their activity and maintain their health. This study examined the effect of nudge-based behavioral interventions on health-promoting activities in older adults in Japan., Design: Two-arm, participant-blinded randomized controlled trial., Setting and Participants: Japanese continuing care retirement community residents (n = 99, median age 82 years, 73% women) INTERVENTION: Two-step nudge-based behavioral intervention promoting tablet usage., Methods: We enrolled participants from an ongoing Internet of Things project in a retirement community in Japan. For the health promotion program, tablet computers were installed in a common area for participants to receive information about their health. The intervention group received a 1-time loss-emphasized nudge (first step), followed by asking questions about when they planned to use it again (second step). The control group used the tablet computers without being asked those questions. The main outcome was the participants' mean daily tablet activity every 4 weeks for the next 16 weeks., Results: Ninety-nine individuals were randomly assigned to the intervention or control group. The rate ratios for tablet use were significantly higher in the intervention group in the second and third periods. The subgroup analysis showed that these effects were largely attributable to men., Conclusions and Implications: Nudge-based interventions can be effective in promoting activities for older adults, especially older men. The finding of this study indicates a possible intervention to engage people who are socially isolated., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

The Wnt/β-catenin signaling pathway plays a key role in development and carcinogenesis. Although some target genes of this signaling have been identified in various tissues and neoplasms, the comprehensive understanding of the target genes and their roles in the development of human cancer, including hepatoma and colorectal cancer remain to be fully elucidated. In this study, we searched for genes regulated by the Wnt signaling in liver cancer using HuH-7 hepatoma cells. A comparison of the expression profiles between cells expressing an active form of mutant β-catenin and cells expressing enhanced green fluorescent protein (EGFP) identified seven genes upregulated by the mutant β-catenin gene (CTNNB1). Among the seven genes, we focused in this study on ODAM, odontogenic, ameloblast associated, as a novel target gene. Interestingly, its expression was frequently upregulated in hepatocellular carcinoma, colorectal adenocarcinoma, and hepatoblastoma. We additionally identified a distant enhancer region that was associated with the β-catenin/TCF7L2 complex. Further analyses revealed that ODAM plays an important role in the regulation of the cell cycle, DNA synthesis, and cell proliferation. These data may be useful for clarification of the main molecular mechanism(s) underlying these cancers., (© 2022 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

The recent influx of microplastics into the Arctic Ocean may increase environmental stress on the western Arctic marine ecosystem, which is experiencing significant sea-ice loss due to global warming. Quantitative data on microplastics in the western Arctic Ocean are very limited, and the microplastic budget of the water column is completely unknown. To fill in gaps in our knowledge of Arctic microplastics, we observed surface concentrations (number of particles per unit volume of seawater) of meso- and microplastics using a neuston net, and we observed wind speeds and significant wave heights in the Chukchi Sea, Bering Strait, and Bering Sea. From these observations, we estimated the total number (particle inventory) and mass (mass inventory) of microplastics in the entire water column by taking into account the effect of vertical mixing. The particle inventory of microplastics in the Chukchi Sea ranged from 0 to 18,815 pieces km -2 with a mean and standard deviation of 5236 ± 6127 pieces km -2 . The mass inventory ranged from 0 to 445 g km -2 with a mean and standard deviation of 124 ± 145 g km -2 . Mean particle inventories for the Chukchi Sea were one-thirtieth of those for the Arctic Ocean on the Atlantic side and less than one-tenth of the average for the global ocean, suggesting that the Chukchi Sea is less polluted. However, the annual flux of microplastics from the Pacific Ocean into the Chukchi Sea, estimated from microplastic concentrations in the Bering Strait, was about 5.5 times greater than the total amount of microplastic in the entire Chukchi Sea water. This suggests that microplastic inflows from the Pacific Ocean are accumulating in large amounts in reservoirs other than the Chukchi Sea water (e.g., sea ice and seafloor sediments) or in the downstream regions of the Pacific-origin water., 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 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: Computed tomography (CT) can accurately measure muscle mass, which is necessary for diagnosing sarcopenia, even in dialysis patients. However, CT-based screening for such patients is challenging, especially considering the availability of equipment within dialysis facilities. We therefore aimed to develop a bedside prediction model for low muscle mass, defined by the psoas muscle mass index (PMI) from CT measurement., Methods: Hemodialysis patients (n = 619) who had undergone abdominal CT screening were divided into the development (n = 441) and validation (n = 178) groups. PMI was manually measured using abdominal CT images to diagnose low muscle mass by two independent investigators. The development group's data were used to create a logistic regression model using 42 items extracted from clinical information as predictive variables; variables were selected using the stepwise method. External validity was examined using the validation group's data, and the area under the curve (AUC), sensitivity, and specificity were calculated., Results: Of all subjects, 226 (37%) were diagnosed with low muscle mass using PMI. A predictive model for low muscle mass was calculated using ten variables: each grip strength, sex, height, dry weight, primary cause of end-stage renal disease, diastolic blood pressure at start of session, pre-dialysis potassium and albumin level, and dialysis water removal in a session. The development group's adjusted AUC, sensitivity, and specificity were 0.81, 60%, and 87%, respectively. The validation group's adjusted AUC, sensitivity, and specificity were 0.73, 64%, and 82%, respectively., Discussion/conclusion: Our results facilitate skeletal muscle screening in hemodialysis patients, assisting in sarcopenia prophylaxis and intervention decisions., (© 2022 The Author(s). Published by S. Karger AG, Basel.)

Lynch syndrome is a hereditary disease characterized by an increased risk of colorectal and other cancers. Germline variants in the mismatch repair (MMR) genes are responsible for this disease. Previously, we screened the MMR genes in colorectal cancer patients who fulfilled modified Amsterdam II criteria, and multiplex ligation-dependent probe amplification (MPLA) identified 11 structural variants (SVs) of MLH1 and MSH2 in 17 patients. In this study, we have tested the efficacy of long read-sequencing coupled with target enrichment for the determination of SVs and their breakpoints. DNA was captured by array probes designed to hybridize with target regions including four MMR genes and then sequenced using MinION, a nanopore sequencing platform. Approximately, 1000-fold coverage was obtained in the target regions compared with other regions. Application of this system to four test cases among the 17 patients correctly mapped the breakpoints. In addition, we newly found a deletion across an 84 kb region of MSH2 in a case without the pathogenic single nucleotide variants. These data suggest that long read-sequencing combined with hybridization-based enrichment is an efficient method to identify both SVs and their breakpoints. This strategy might replace MLPA for the screening of SVs in hereditary diseases., (© 2021. The Author(s), under exclusive licence to The Japan Society of Human Genetics.)

We measured the concentrations of cesium isotopes ( 133 Cs, 134 Cs, and 137 Cs) in zooplankton samples collected in waters off the east coast of Japan from May 2015 to June 2020. By combining these data with those obtained previously from May 2012 to February 2015, we evaluated the long-term impacts of the Fukushima Dai-ichi Nuclear Power Plant accident on marine zooplankton. Relatively high 137 Cs concentrations in zooplankton, exceeding 10 Bq/kg-dry weight, were sporadically observed until June 2016, regardless of year or station. After May-June 2017, 137 Cs concentrations decreased to below 1 Bq/kg-dry at most stations, and by May 2020, concentrations were below 0.5 Bq/kg-dry except those off Fukushima Prefecture. Since the accident, the 137 Cs/ 133 Cs atom ratios of zooplankton samples were higher than those of ambient seawater until 2019, but in May-June 2020 the ratios matched those of seawater except off Fukushima Prefecture. Highly radioactive particles were not detected in zooplankton samples by autoradiography using imaging plates after May-June 2017, although they were before. Therefore, the persistence of elevated 137 Cs/ 133 Cs ratios in zooplankton relative to seawater for nine years after the accident was probably due to the incorporation of highly radioactive particles (cesium-bearing particles or clay-mineral aggregates with highly adsorbed radiocesium) onto/into zooplankton for several years after the accident. However, since at least May-June 2017, these elevated ratios have likely been caused by small highly radioactive particles (or larger particles disaggregated into small pieces) entering the ocean from land via rivers or directly discharged from the Fukushima Nuclear Power Plant. Microplastics enriched with radiocesium with higher 137 Cs/ 133 Cs ratios than seawater may have also contributed 137 Cs to the zooplankton., 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 Ltd. All rights reserved.)

Introduction: In Japan, patients with coronavirus disease 2019 (COVID-19) who do not require medical intervention are provided care in recovery accommodation facilities (RAFs). However, some patients may require hospitalization if their symptoms become more severe during their stay. We conducted an observational study using epidemiological data of patients with COVID-19 admitted to RAFs in Tokyo., Methods: This was an observational cohort study using data from COVID-19 patients admitted to one of the RAFs in Tokyo from December 2020 to November 2021. Admissions to the facilities were limited to patients with asymptomatic or mild COVID-19 with no underlying disease or at least stable underlying disease at the time of admission. Patients were hospitalized when they required oxygen administration or when they had, or persistent fever, or severe respiratory symptoms. We evaluated the association between hospitalization and the risk factors for hospitalization using a Cox regression model., Results: The number of patients with COVID-19 admitted to the RAF was 6176. The number of hospitalized patients was 393 (6.4%), and the median length of stay was 5.50 days (IQR: 4.50, 6.50). In the Cox regression analysis, the hazard ratio increased with age and was significantly higher among patients aged >60 years (HR = 10.23, 95% CI: 6.72-15.57) than those in other age groups. This trend is similar to that observed in the sensitivity analysis., Conclusion: Patients with diabetes, the elderly, obesity, and medications for gout and psychiatric diseases may be at a high risk of hospitalization. In particular, an age over 60 years was strongly associated with hospitalization., (Copyright © 2022 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)