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Abstract To what extent and how post-transcriptional dysregulation affects aging proteome remains unclear. Here, we provide proteomic data of whole-tissue lysates (WTL) and low-solubility protein-enriched fractions (LSF) of major tissues collected from mice of 6, 15, 24, and 30 months of age. Low-solubility proteins are preferentially affected by age and the analysis of LSF doubles the number of proteins identified to be differentially expressed with age. Simultaneous analysis of proteome and transcriptome using the same tissue homogenates reveals the features of age-related post-transcriptional dysregulation. Post-transcriptional dysregulation becomes evident especially after 24 months of age and age-related post-transcriptional dysregulation leads to accumulation of core matrisome proteins and reduction of mitochondrial membrane proteins in multiple tissues. Based on our in-depth proteomic data and sample-matched transcriptome data of adult, middle-aged, old, and geriatric mice, we construct the Mouse aging proteomic atlas ( https://aging-proteomics.info/ ), which provides a thorough and integrative view of age-related gene expression changes.

Abstract Background Patients with migraine are typically advised to avoid passive smoking because it may aggravate headaches and other health conditions. However, there is insufficient high-quality evidence on the association between passive smoking and migraine, which warrants further investigation using animal models. Therefore, using a mouse model, we examined the effect of passive smoking on susceptibility to cortical spreading depolarization (CSD), the biological basis of migraine with aura. Findings Fifty C57BL/6 mice (25 males and 25 females) were exposed for one hour to cigarette smoke or room air. Subsequently, potassium chloride (KCl) was administered under isoflurane anesthesia to induce CSD, and the CSD threshold, frequency of induction, and propagation velocity were determined. The threshold to induce CSD (median [interquartile range (IQR)]) was significantly lower in female mice (adjusted p = 0.01) in the smoking group (0.05 [0.05, 0.088]) than in the sham group (0.125 [0.1, 0.15]); however, there was no significant difference in the male mice (adjusted p = 0.77). CSD frequency or propagation velocity did not differ significantly between the two groups for either sex. Conclusions Female mice in the smoking group showed lower CSD threshold compared to the sham group, suggesting a potential sex-specific difference in the effect of smoking on the pathogenesis of CSD and migraine with aura. This finding may contribute to the understanding of migraine pathophysiology in association with passive smoking and sex difference.

ABSTRACT Aims/Introduction Chronic kidney disease (CKD) is a very important issue globally because of the risk of its progressing to end‐stage renal disease. We aimed to identify factors contributing to long‐term estimated glomerular filtration rate (eGFR) decline to determine an early diagnosis and prevent CKD progression. Materials and Methods From January 2003 to December 2006, 5,507 individuals underwent health checkups at our hospital's Preventive Medicine Research Center. We ultimately enrolled 2,175 individuals. The eGFR was ≥60 mL/min/1.73 m2 at the start of observation period, which was 20 years. The event onset time was the day that the eGFR became

Abstract Introduction The aim of this prospective and comparative study was to investigate the association of perimetry parameters on visual acuity and contrast sensitivity in primary open-angle glaucoma (POAG) eyes with diffractive extended depth-of-focus (EDoF) and monofocal intraocular lenses (IOLs). Methods In cataract eyes with medicinally controlled POAG with no defects in the central visual field and mean deviation (MD) values of − 10 dB or better, EDoF and monofocal IOLs with the same platform except for echelette optics for EDoF were implanted in 22 and 24 eyes, respectively. Corrected distance visual acuity (CDVA), contrast sensitivity at 3 to 18 cycles per degree (cpd), and automated perimetry using 30-2 and 10-2 Swedish Interactive Threshold Algorithm programs were examined 3 months postoperatively. The influences of perimetry parameters including MD, foveal sensitivity (FS), and the means of the central four points (central MD and central FS) on CDVA and contrast sensitivity were evaluated using linear and multiple regression analyses. Results In POAG eyes with EDoF IOLs, contrast sensitivities at 12 and 18 cpd were associated with 30-2 and 10-2 perimetry parameters. In POAG eyes with monofocal IOLs, associations of 30-2 parameters were found in CDVA and 3-cpd contrast sensitivity. Conclusions The visual function of POAG eyes with EDoF IOLs was associated with perimetry parameters in high spatial frequency contrast sensitivity, which was different from that of POAG eyes with monofocal IOL. Trial Registration Japan Registry for Clinical Research: jRCTs032200218.

Abstract Positive peritoneal washing cytology is an indicator of poor prognosis in patients with pancreatic ductal adenocarcinoma (PDAC); however, its sensitivity is relatively low. This study evaluated the performance of peptide nucleic acid (PNA)-directed PCR clamping as a molecular-based peritoneal washing cytology for sensitive detection of KRAS mutation in PDAC. Intraoperative peritoneal washing fluid (IPWF) obtained from patients with PDAC who underwent surgery was analyzed. PNA-directed PCR clamping was performed on DNA extracted from IPWF. Among 54 patients enrolled, threshold cycle (Ct) was significantly lower in patients with positive peritoneal washing cytology than in those with negative peritoneal washing cytology (P

The soilborne Gram-negative phytopathogenic beta-proteobacterium Ralstonia pseudosolanacearum strain OE1-1 produces methyl 3-hydroxymyristate (3-OH MAME) as the quorum sensing (QS) signal by the methyltransferase PhcB and senses the chemical, activating the LysR family transcriptional regulator PhcA, which regulates the QS-dependent genes responsible for QS-dependent phenotypes including virulence. The sensor histidine kinases PhcS and VsrA are reportedly involved in the regulation of QS-dependent genes. To elucidate the function of PhcS and VsrA in the active QS, we generated the phcS-deletion and vsrA-deletion mutants, which exhibited weak changes to their QS-dependent phenotypes including virulence. The phcS and vsrA-deletion mutant (ΔphcS/vsrA) had significant changes in its QS-dependent phenotypes and was nonvirulent, similar to the phcA-deletion mutant. The mutant (PhcS-H230Q) with a substitution of histidine to glutamine at amino acid position 230 in PhcS but not the mutant (VsrA-H256Q) with a substitution of histidine to glutamine at amino acid position 256 in VsrA exhibited significant changes in QS-dependent phenotypes and lost virulence. The transcriptome analysis with RNA-sequencing revealed significant alterations to the expression of QS-dependent genes in the ΔphcS/vsrA and PhcS-H230Q but not VsrA-H256Q, similar to the phcA-deletion mutant. The exogenous 3-OH MAME application led to a significantly enhanced QS-inducible major exopolysaccharide EPS I production of the strain OE1-1 and phcB-deletion mutant but not ΔphcS/vsrA and PhcS-H230Q. Collectively, results of the present genetic study suggested that PhcS contributes to QS along with VsrA and that histidine at amino acid position 230 of PhcS is required for 3-OH MAME sensing, thereby influencing QS-dependent phenotypes including virulence of the strain OE1-1. [Figure: see text] The author(s) have dedicated the work to the public domain under the Creative Commons CC0 “No Rights Reserved” license by waiving all of his or her rights to the work worldwide under copyright law, including all related and neighboring rights, to the extent allowed by law, 2024.

Pulmonary artery intimal sarcoma has very poor prognosis, for which radical resection may be difficult. A 68-year-old man with pulmonary artery intimal sarcoma underwent bilateral pulmonary artery resection and replacement. At 31 months postoperatively, recurrence occurred at the anastomotic site of the right pulmonary artery. Therefore, he underwent right upper lobectomy and combined resection and reconstruction of the right pulmonary artery. The tumor was removed, while preserving the lungs as much as possible. He is still alive 42 months after the initial surgery.

Abstract Aim The coronavirus disease 2019 (COVID‐19) pandemic greatly impacted medical resources such as cancer screening, diagnosis, and treatment given to people for various diseases. We surveyed the impacts of the pandemic on the incidence of complications and mortality following pancreaticoduodenectomy for pancreatic cancer in Japan. Methods Data on patients who underwent pancreaticoduodenectomy for pancreatic cancer were extracted from the Japanese National Clinical Database (NCD) between 2018 and 2021. The number of the pancreaticoduodenectomy for pancreatic cancer were obtained and then the morbidity and mortality rates were evaluated using a standardized morbidity/mortality ratio (SMR), which is the ratio of the observed number of incidences to the expected number of incidences calculated by the risk calculator previously developed by the NCD. Results This study included 22 255 cases. The number of pancreaticoduodenectomies exhibited an increasing trend even during the COVID‐19 pandemic. The mean observed incidence rates of Grade C pancreatic fistula and Clavien–Dindo grade ≥4 complications, and the 30‐day mortality and surgical mortality rates were 0.8%, 1.8%, 0.8% and 0.9%, respectively. The standardized morbidity ratios did not increase during the COVID‐19 pandemic. The standardized mortality ratios remained within the range of variations observed before the COVID‐19 pandemic. Conclusion The increasing trend in the number of pancreaticoduodenectomies and favorable short‐term outcomes even in the COVID‐19 pandemic suggest the medical care for pancreatic cancer in Japan functioned well during the pandemic.

Abstract Background Due to the coronavirus disease 2019 (COVID‐19) pandemic, cancer screening, diagnosis, and treatment have changed. This study aimed to investigate the impact of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection prior to gastroenterological cancer surgeries on postoperative complications using data from a nationwide database in Japan. Methods Data on patients who underwent surgery for cancer including esophageal, gastric, colon, rectal, liver, and pancreatic cancer between July 1, 2019, and September 300, 2022, from real‐world sources in Japan were analyzed. The association between preoperative SARS‐CoV‐2 infection and short‐term postoperative outcomes was evaluated. A similar analysis stratified according to the interval from SARS‐CoV‐2 infection to surgery (4 weeks) was conducted. Results In total, 60 604 patients were analyzed, and 227 (0.4%) patients were diagnosed with SARS‐CoV‐2 infection preoperatively. The median interval from SARS‐CoV‐2 infection to surgery was 25 days. Patients diagnosed with SARS‐CoV‐2 infection preoperatively had a significantly higher incidence of pneumonia (odds ratio: 2.05; 95% confidence interval: 1.05–3.74; p = 0.036) than those not diagnosed with SARS‐CoV‐2 infection based on the exact logistic regression analysis adjusted for the characteristics of the patients. A similar finding was observed in patients who had SARS‐CoV‐2 infection

Abstract Background Gait ability can be objectively assessed using gait analysis. Three-dimensional gait analysis, the most commonly used analytical method, has limitations, such as a prolonged examination, high system costs, and inconsistently reported gait symmetry in patients with knee osteoarthritis (OA). Therefore, we aimed to evaluate the gait symmetry and changes before and after unilateral total knee arthroplasty (TKA) using the Walkway analyzer, a sheet-type gait analyzer. Methods The healthy group included 38 participants from the Locomotor Frailty and Sarcopenia Registry study with lower limb pain or Kellgren–Lawrence classification grade 3 or 4 OA. The OA group included 34 participants from the registry study who underwent unilateral TKA. The walking speed, step length, step width, cadence, stride time, stance time, swing phase time, double-limb support phase time, stride, step length, and step width were analyzed per side using the Walkway gait analyzer. Results No significant differences between the right and left sides were observed in the healthy group. In the OA group, the time indices and stance phase (p = 0.011) and the double-limb support phase time (p = 0.039) were longer on the contralateral side and the swing phase was longer on the affected side (p = 0.004) pre-operatively. However, these differences disappeared post-operatively. There were no significant differences in the spatial indices. Thus, this study revealed that patients undergoing unilateral TKA had an asymmetric gait pre-operatively, with a time index compensating for the painful side, and an improved symmetric gait post-operatively. Conclusions The Walkway analyzer employs a simple test that requires only walking; hence, it is expected to be used for objective evaluation in actual clinical practice.

Abstract Because hepatic stellate cells (HSCs) play a major role in fibrosis, we focused on HSCs as a potential target for the treatment of liver fibrosis. In this study, we attempted to identify drug candidates to inactivate HSCs and found that several proteasome inhibitors (PIs) reduced HSC viability. Our data showed that a second-generation PI, carfilzomib (CZM), suppressed the expression of fibrotic markers in primary murine HSCs at low concentrations of 5 or 10 nM. Since CZM was not toxic to HSCs up to a concentration of 12.5 nM, we examined its antifibrotic effects further. CZM achieved a clear reduction in liver fibrosis in the carbon tetrachloride (CCl4)-induced mouse model of liver fibrosis without worsening of liver injury. Mechanistically, RNA sequence analysis of primary HSCs revealed that CZM inhibits mitosis in HSCs. In the CCl4-injured liver, amphiregulin, which is known to activate mitogenic signaling pathways and fibrogenic activity and is upregulated in murine and human metabolic dysfunction-associated steatohepatitis (MASH), was downregulated by CZM administration, leading to inhibition of mitosis in HSCs. Thus, CZM and next-generation PIs in development could be potential therapeutic agents for the treatment of liver fibrosis via inactivation of HSCs without liver injury.

Abstract Objective To reveal the clinical features and assess risk factors linked to brain fog and its societal implications, including labor productivity, providing valuable insights for the future care of individuals who have experienced coronavirus disease 2019 (COVID‐19). Methods We analyzed a comprehensive cohort dataset comprising 1,009 patients with COVID‐19 admitted to Japanese hospitals. To assess brain fog, we analyzed patients who responded to a questionnaire indicating symptoms such as memory impairment and poor concentration. Results The prevalence of brain fog symptoms decreased 3 months posthospitalization but remained stable up to 12 months. Neurological symptoms such as taste and smell disorders and numbness at hospitalization correlated with a higher frequency of identifying brain fog as a long COVID manifestation. Our findings indicated that advanced age, female sex, a high body mass index, oxygen required during hospitalization, chronic obstructive pulmonary disease, asthma, and elevated C‐reactive protein and elevated D‐dimer levels were risk factors in patients exhibiting brain fog. Additionally, we demonstrated the negative impact of brain fog on labor productivity by presenteeism scores. Interpretations This study clarified the clinical characteristics of patients experiencing brain fog as a long COVID manifestation, specifically emphasizing neurological symptoms during hospitalization and their correlation with brain fog. Additionally, the study identified associated risk factors for its onset and revealed that the emergence of brain fog was linked to a decline in labor productivity.

Abstract A simple method for determining the anaerobic threshold in patients with heart failure (HF) is needed. This prospective clinical trial (LacS-001) aimed to investigate the safety of a sweat lactate-monitoring sensor and the correlation between lactate threshold in sweat (sLT) and ventilatory threshold (VT). To this end, we recruited 50 patients with HF and New York Heart Association functional classification I–II (mean age: 63.5 years, interquartile range: 58.0–72.0). Incremental exercise tests were conducted while monitoring sweat lactate levels using our sensor. sLT was defined as the first steep increase in lactate levels from baseline. Primary outcome measures were a correlation coefficient of ≥ 0.6 between sLT and VT, similarities as assessed by the Bland–Altman analysis, and standard deviation of the difference within 15 W. A correlation coefficient of 0.651 (95% confidence interval, 0.391–0.815) was achieved in 32/50 cases. The difference between sLT and VT was −4.9 ± 15.0 W. No comparative error was noted in the Bland–Altman plot. No device-related adverse events were reported among the registered patients. Our sweat lactate sensor is safe and accurate for detecting VT in patients with HF in clinical settings, thereby offering valuable additional information for treatment.

The Tsuruoka Metabolomics Cohort Study (TMCS) is an ongoing population-based cohort study being conducted in the rural area of Yamagata Prefecture, Japan. This study aimed to enhance the precision prevention of multi-factorial, complex diseases, including non-communicable and aging-associated diseases, by improving risk stratification and prediction measures. At baseline, 11,002 participants aged 35–74 years were recruited in Tsuruoka City, Yamagata Prefecture, Japan, between 2012 and 2015, with an ongoing follow-up survey. Participants underwent various measurements, examinations, tests, and questionnaires on their health, lifestyle, and social factors. This study uses an integrative approach with deep molecular profiling to identify potential biomarkers linked to phenotypes that underpin disease pathophysiology and provide better mechanistic insights into social health determinants. The TMCS incorporates multi-omics data, including genetic and metabolomic analyses of 10,933 participants, and comprehensive data collection ranging from physical, psychological, behavioral, and social to biological data. The metabolome is used as a phenotypic probe because it is sensitive to changes in physiological and external conditions. The TMCS focuses on collecting outcomes for cardiovascular disease, cancer incidence and mortality, disability and functional decline due to aging and disease sequelae, and the variation in health status within the body represented by omics analysis that lies between exposure and disease. It contains several sub-studies on aging, heated tobacco products, and women’s health. This study is notable for its robust design, high participation rate (89%), and long-term repeated surveys. Moreover, it contributes to precision prevention in Japan and East Asia as a well-established multi-omics platform.

Background: Uremic toxin indoxyl sulfate (IS) induces vascular inflammation, a crucial event in renal failure, and vascular complications in patients with chronic kidney disease (CKD). In endothelial cells, IS increases the production of inflammatory cytokines partially via the activation of the aryl hydrocarbon receptor (AhR), and several food flavonoids have been reported to act as antagonists of AhR. Objective: This study aimed to investigate whether antagonistic flavonoids can attenuate IS-induced inflammatory responses in vascular endothelial cells in vitro and renal failure in vivo. Design: Human umbilical vein endothelial cells (HUVECs) pretreated with the flavones apigenin, chrysin, or luteolin were stimulated with IS. Expression levels of genes involved in AhR signaling, inflammatory cytokine production, and reactive oxygen species (ROS) production were analyzed. Uninephrectomized mice were orally administered chrysin and received daily intraperitoneal injections of IS for 4 weeks. Results: In HUVECs, IS upregulated the mRNA expression of AhR-targeted genes (CYP1A1 and AhRR), and genes involved in inflammation (NOX4, MCP-1, IL-6, and COX2) and monocyte invasion/adhesion (ICAM1). All three flavones attenuated the IS-induced increase in the expression of these mRNAs. They also suppressed the IS-induced nuclear translocation of AhR and intracellular ROS production. Furthermore, IS-induced phosphorylation of the signal transducer and activator of transcription 3 (STAT3) was inhibited by treatment with these flavones. The results of in-vivo experiments showed that administration with chrysin attenuated the elevation of blood urea nitrogen levels and AhR-target gene expression and the pathological impairment of renal tissues in mice, regardless of higher serum levels of IS. Conclusions: Natural food flavones antagonizing AhR exerted protective effects against IS-induced inflammation through the inhibition of the AhR–STAT3 pathway in HUVECs. Moreover, chrysin ameliorated IS-induced renal dysfunction in a mouse model of CKD. These flavonoids could be a therapeutic strategy for vascular inflammation in CKD.

Abstract Possible local influence of an extreme marine heatwave is investigated on unprecedentedly hot summer around northern Japan in 2023. Sea-surface temperatures (SSTs) and subsurface ocean temperatures around northern Japan were also unprecedentedly high in the summer. This was especially the case off the east coast of Japan, where cool Oyashio water was replaced with much warmer water due to a striking poleward meander of the Kuroshio Extension persistent from the spring. Particularly amplified near-surface air temperature anomalies and even stronger warm anomalies in the subsurface ocean suggest that the marine heatwave acted to sustain the atmospheric heatwave. Anomalous upward of latent and sensible heat fluxes from the warmed sea surface are indicative of local oceanic impact. The warm SST anomalies reduced the lower-tropospheric stratification to maintain unfavourable condition for low-level cloud formation, which in turn led to increased surface insolation for further SST warming as positive feedback. The increased moisture in the warmed lower troposphere contributed to the enhanced surface downward longwave radiation. This enhanced greenhouse effect acted not only as positive feedback on the warm SST anomalies that increased evaporation but also as a contributor for the extreme warmth over northern Japan landmass.

Background: Dupilumab has clinical effects in patients with moderate-to-severe asthma. When considering interleukin (IL)-4 and IL-13 signaling, effects of dupilumab on airway mucus hypersecretion and airway remodeling are expected, but they have been reported in only a few short-term studies. Its efficacy for airway hyperresponsiveness (AHR) remains unknown. We comprehensively assessed the efficacy of dupilumab, especially for subjective and objective measures of airway mucus hypersecretion and airway dimensions in moderate-to-severe asthmatic patients. Methods: In 28 adult patients with moderate-to-severe uncontrolled asthma, the comprehensive efficacy of 48-week dupilumab treatment, including the Cough and Sputum Assessment Questionnaire (CASA-Q), radiological mucus scores and airway dimensions on computed tomography (CT), was assessed prospectively. Treatment responsiveness to dupilumab was analyzed. Results: With 48-week dupilumab treatment, all four cough and sputum domain scores of CASA-Q improved significantly. Radiological mucus scores and airway wall thickening on CT were significantly decreased. The decreases in mucus scores were significantly associated with improvements in Asthma Control Questionnaire scores, Asthma Quality of Life Questionnaire (AQLQ) overall scores, airway obstruction, and airway type 2 inflammation. When defined by > 0.5 improvement in AQLQ overall scores, 18 patients (64%) were identified as responders. Conclusions: Dupilumab reversed subjective and objective measures of airway mucus hypersecretion and some aspects of airway remodeling in patients with moderate-to-severe uncontrolled asthma.

Introduction: From the late 1960s to the present, physicians’ dress codes have been actively studied in Western countries. Until the early 21st century, patients tended to prefer a conservative dress style, such as “shirt and tie or skirt” with white coats for physicians. However, as attitudes toward dress codes have changed, knowledge regarding this issue needs to be updated. A variety of colours of scrubs are currently commonly used by medical professionals, but it is not known whether all colours are acceptable to patients. The current study sought to investigate the acceptability of various dress codes for physicians from the patients’ perspective, to inform medical education. Methods: Outpatients and their family members at a university hospital and a small-to-medium-sized hospital were surveyed. We inquired about which of the different styles of white coats and different colours of scrubs were most desirable for male and female physicians. We used Scheffe’s paired comparison method to determine rankings. Results: Patients and their family members expected their physicians to wear white coats rather than scrubs. Furthermore, a more traditional and formal dress code was preferred. The least preferred colour of scrubs was yellow. Conclusion: The current results indicated that patients’ preference for a traditional, conservative appearance has not changed over time. This finding does not match current perspectives on infection prevention. Both patient preferences and infection prevention are important for informing education and gaining patient trust.

Abstract Background Following an acute myocardial infarction (AMI), surgery for left ventricular free wall rupture (LVFWR) and ventricular septal rupture (VSR) has a high in-hospital mortality rate, which has not improved significantly over time. Unloading the LV is critical to preventing excessive stress on the repair site and avoiding problems such as bleeding, leaks, patch dehiscence, and recurrence of LVFWR and VSR because the tissue is so fragile. We present two cases of patients who used Impella 5.5 for LV unloading following emergency surgery for AMI mechanical complications. Case presentation A 76-year-old male STEMI patient underwent fibrinolysis of the distal right coronary artery. Three days later, he passed out and went into shock. Echocardiography revealed a cardiac tamponade. We found an oozing-type LVFWR on the posterolateral wall and treated it with a non-suture technique using TachoSil. Before the patient was taken off CPB, Impella 5.5 was inserted into the LV via a 10 mm synthetic graft connected to the right axillary artery. We kept the flow rate above 4.0 to 4.5 L/min until POD 3 to reduce LV wall tension while minimizing pulsatility. On POD 6, we weaned the patient from Impella 5.5. A postoperative cardiac CT scan showed no contrast leakage from the LV. However, a cerebral hemorrhage on POD 4 during heparin administration complicated his hospitalization. Case 2: A diagnosis of cardiogenic shock caused by STEMI occurred in an 84-year-old male patient, who underwent PCI of the LAD with IABP support. Three days after PCI, echocardiography revealed VSR, and the patient underwent emergency VSR repair with two separate patches and BioGlue applied to the suture line between them. Before weaning from CPB, we implanted Impella 5.5 in the LV and added venoarterial extracorporeal membrane oxygenation (VA-ECMO) support for right heart failure. The postoperative echocardiography revealed no residual shunt. Conclusions Patients undergoing emergency surgery for mechanical complications of AMI may find Impella 5.5 to be an effective tool for LV unloading. The use of VA-ECMO in conjunction with Impella may be an effective strategy for managing VSR associated with concurrent right-sided heart failure.

General circulation models' (GCMs) estimates of the liquid water path adjustment to anthropogenic aerosol emissions differ in sign from other lines of evidence. This reduces confidence in estimates of the effective radiative forcing of the climate by aerosol–cloud interactions (ERFaci). The discrepancy is thought to stem in part from GCMs' inability to represent the turbulence–microphysics interactions in cloud-top entrainment, a mechanism that leads to a reduction in liquid water in response to an anthropogenic increase in aerosols. In the real atmosphere, enhanced cloud-top entrainment is thought to be the dominant adjustment mechanism for liquid water path, weakening the overall ERFaci. We show that the latest generation of GCMs includes models that produce a negative correlation between the present-day cloud droplet number and liquid water path, a key piece of observational evidence supporting liquid water path reduction by anthropogenic aerosols and one that earlier-generation GCMs could not reproduce. However, even in GCMs with this negative correlation, the increase in anthropogenic aerosols from preindustrial to present-day values still leads to an increase in the simulated liquid water path due to the parameterized precipitation suppression mechanism. This adds to the evidence that correlations in the present-day climate are not necessarily causal. We investigate sources of confounding to explain the noncausal correlation between liquid water path and droplet number. These results are a reminder that assessments of climate parameters based on multiple lines of evidence must carefully consider the complementary strengths of different lines when the lines disagree.

Earth system models (ESMs) participating in the latest Coupled Model Intercomparison Project Phase 6 (CMIP6) simulate various components of fine particulate matter (PM2.5) as major climate forcers. Yet the model performance for PM2.5 components remains little evaluated due in part to a lack of observational data. Here, we evaluate near-surface concentrations of PM2.5 and its five main components over China as simulated by 14 CMIP6 models, including organic carbon (OC; available in 14 models), black carbon (BC; 14 models), sulfate (14 models), nitrate (4 models), and ammonium (5 models). For this purpose, we collect observational data between 2000 and 2014 from a satellite-based dataset for total PM2.5 and from 2469 measurement records in the literature for PM2.5 components. Seven models output total PM2.5 concentrations, and they all underestimate the observed total PM2.5 over eastern China, with GFDL-ESM4 (−1.5 %) and MPI-ESM-1-2-HAM (−1.1 %) exhibiting the smallest biases averaged over the whole country. The other seven models, for which we recalculate total PM2.5 from the available component output, underestimate the total PM2.5 concentrations partly because of the missing model representations of nitrate and ammonium. Concentrations of the five individual components are underestimated in almost all models, except that sulfate is overestimated in MPI-ESM-1-2-HAM by 12.6 % and in MRI-ESM2-0 by 24.5 %. The underestimation is the largest for OC (by −71.2 % to −37.8 % across the 14 models) and the smallest for BC (−47.9 % to −12.1 %). The multi-model mean (MMM) reproduces the observed spatial pattern for OC (R = 0.51), sulfate (R = 0.57), nitrate (R = 0.70) and ammonium (R = 0.74) fairly well, yet the agreement is poorer for BC (R = 0.39). The varying performances of ESMs on total PM2.5 and its components have important implications for the modeled magnitude and spatial pattern of aerosol radiative forcing.

Abstract The experimental findings from the Large Helical Device have demonstrated a fast, nondiffusive behavior during the propagation of heat pulses, with an observed increase in speed with reduction in their temporal width. Concurrent propagation of the temperature gradient and turbulence, in a timeframe spanning from a few milliseconds to tens of milliseconds, aligned with the avalanche model. These results indicate that the more spatiotemporally localized the heat and turbulence pulses are, the greater the deviation of the plasma from its equilibrium state, coupled with faster propagation velocity. This insight is pivotal for future fusion reactors, which necessitate the maintenance of a steady-state, non-equilibrium condition.

Abstract Pear pollination is performed by artificial pollination because the pollination rate through insect pollination is not stable. Pollen must be collected to secure sufficient pollen for artificial pollination. However, recently, collecting sufficient amounts of pollen in Japan has become difficult, resulting in increased imports from overseas. To solve this problem, improving the efficiency of pollen collection and strengthening the domestic supply and demand system is necessary. In this study, we proposed an Artificial Intelligence (AI)-based method to estimate the amount of pear pollen. The proposed method used a deep learning-based object detection algorithm, You Only Look Once (YOLO), to classify and detect flower shapes in five stages, from bud to flowering, and to estimate the pollen amount. In this study, the performance of the proposed method was discussed by analyzing the accuracy and error of classification for multiple flower varieties. Although this study only discussed the performance of estimating the amount of pollen collected, in the future, we aim to establish a technique for estimating the time of maximum pollen collection using the method proposed in this study.

Abstract Background Recent studies have indicated the importance of muscle quality in addition to muscle quantity in sarcopenia pathophysiology. Intramuscular adipose tissue (IMAT), which originates from mesenchymal progenitors (MPs) in adult skeletal muscle, is a key factor affecting muscle quality in older adults, suggesting that controlling IMAT formation is a promising therapeutic strategy for sarcopenia. However, the molecular mechanism underlying IMAT formation in older adults has not been clarified. We recently found that the vitamin D receptor (VDR) is highly expressed in MPs in comparison to myotubes (P = 0.028, N = 3), indicating a potential role of vitamin D signalling in MPs. In this study, we aimed to clarify the role of vitamin D signalling in MP kinetics, with a focus on adipogenesis. Methods MPs isolated from mouse skeletal muscles were subjected to adipogenic differentiation conditions with or without vitamin D (1α,25(OH)2D3, 100 nM) for 7 days, and adipogenicity was evaluated based on adipogenic marker expression. For in vivo analysis, tamoxifen‐inducible MP‐specific VDR‐deficient (VdrMPcKO) mice were newly developed to investigate whether lack of vitamin D signalling in MPs is involved in IMAT formation. To induce muscle atrophy, VdrMPcKO male mice were subjected to tenotomy of the gastrocnemius muscle, and then muscle weight, myofibre cross‐sectional area, adipogenic marker expression, and fatty infiltration into the muscle were evaluated at 3 weeks after operation (N = 3–4). In addition, a vitamin D‐deficient diet was provided to wild‐type male mice (3 and 20 months of age, N = 5) for 3 months to investigate whether vitamin D deficiency causes IMAT formation. Results Vitamin D treatment nearly completely inhibited adipogenesis of MPs through Runx1‐mediated transcriptional modifications of early adipogenic factors such as PPARγ (P = 0.0031) and C/EBPα (P = 0.0027), whereas VDR‐deficient MPs derived from VdrMPcKO mice differentiated into adipocytes even in the presence of vitamin D (P = 0.0044, Oil‐Red O+ area). In consistency with in‐vitro findings, VdrMPcKO mice and mice fed a vitamin D‐deficient diet exhibited fat deposition in atrophied (P = 0.0311) and aged (P = 0.0216) skeletal muscle, respectively. Conclusions Vitamin D signalling is important to prevent fate decision of MPs towards the adipogenic lineage. As vitamin D levels decline with age, our data indicate that decreased vitamin D levels may be one of the causes of IMAT formation in older adults, and vitamin D signalling may be a novel therapeutic target for sarcopenia.

Background: Human dental pulp-derived stem cells (hDPSCs) have emerged as a promising source for adult stem cell-based regenerative medicine. Stage-specific embryonic antigen 3 (SSEA3) is a cell surface marker associated with Multilineage-differentiating stress-enduring (Muse) cells, a subpopulation of human bone marrow-derived stem cells (hBMSCs), known for their potent regenerative potential and safety profile. In this study, we investigated the influence of the prolonged culture period and the number of culture passages on the regenerative capacity of hDPSCs and explored the association between SSEA3 expression and their regenerative abilities. Methods: hDPSCs were isolated and cultured for up to 20 passages. Cell proliferation, migration, and osteogenic, adipogenic and neurogenic differentiation potential were assessed at passages 5, 10, and 20. Flow cytometry and immunofluorescence were employed to analyze SSEA3 expression. RNA sequencing (RNA-seq) was performed on SSEA3-positive and SSEA3-negative hDPSCs to identify differentially expressed genes and associated pathways. Results: Our findings demonstrated a progressive decline in hDPSCs proliferation and migration capacity with increasing passage number. Conversely, cell size exhibited a positive correlation with passage number. Early passage hDPSCs displayed superior osteogenic and adipogenic differentiation potential. Notably, SSEA3 expression exhibited a significant negative correlation with passage numbers, reflecting the observed decline in differentiation capacity. RNA-seq analysis revealed distinct transcriptional profiles between SSEA3-positive and SSEA3-negative hDPSCs. SSEA3-positive cells displayed upregulation of genes associated with ectodermal differentiation and downregulation of genes involved in cell adhesion. Conclusions: This study elucidates the impact of passaging on hDPSC behavior and suggests SSEA3 as a valuable biomarker for evaluating stemness and regenerative potential. SSEA3-positive hDPSCs, functionally analogous to Muse cells, represent a promising cell population for developing targeted regenerative therapies with potentially improved clinical outcomes.

Macaques are representative animal models in translational research. However, the distinct shape and location of the brain regions between macaques and humans prevents us from comparing the brain structure directly. Here, we calculated structural connectivity (SC) with multi-scale hierarchical regions of interest (ROIs) to parcel out human and macaque brain into 8 (level 1 ROIs), 28 (level 2 ROIs), or 46 (level 3 ROIs) regions, which consist of anatomically and functionally defined level 4 ROIs (around 100 parcellation of the brain). The SC with the level 1 ROIs showed lower individual and interspecies variation in macaques and humans. SC with level 2 and 3 ROIs shows that the several regions in frontal, temporal and parietal lobe show distinct connectivity between macaques and humans. Lateral frontal cortex, motor cortex and auditory cortex were shown to be important areas for interspecies differences. These results provide insights to use macaques as animal models for translational study.

Abstract Since the 5th Assessment Report of the Intergovernmental Panel on Climate Change (AR5) an extended concept of the energetic analysis of climate change including forcings, feedbacks and adjustment processes has become widely adopted. Adjustments are defined as processes that occur in response to the introduction of a climate forcing agent, but that are independent of global‐mean surface temperature changes. Most considered are the adjustments that impact the Earth energy budget and strengthen or weaken the instantaneous radiative forcing due to the forcing agent. Some adjustment mechanisms also impact other aspects of climate not related to the Earth radiation budget. Since AR5 and a following description by Sherwood et al. (2015, https://doi.org/10.1175/bams‐d‐13‐00167.1), much research on adjustments has been performed and is reviewed here. We classify the adjustment mechanisms into six main categories, and discuss methods of quantifying these adjustments in terms of their potentials, shortcomings and practicality. We furthermore describe aspects of adjustments that act beyond the energetic framework, and we propose new ideas to observe adjustments or to make use of observations to constrain their representation in models. Altogether, the problem of adjustments is now on a robust scientific footing, and better quantification and observational constraint is possible. This allows for improvements in understanding and quantifying climate change.

ABSTRACT Streptococcus pneumoniae is one of the major pathogens responsible for bacterial meningitis and neurological sequelae. The present study was conducted to identify a non-hematogenous route used by S. pneumoniae to gain access to brain tissue without causing bacteremia or pneumonia, as well as bacterial and host factors involved in this process. To investigate the molecular mechanisms and dissemination pathways of pneumococcal infection in brain tissue, mice were intranasally inoculated with S. pneumoniae strain EF3030, a clinical isolate from a patient with otitis media. Pneumococci were isolated from the frontal olfactory bulb, caudal cerebrum, and cerebellum, with neither bacteremia nor pneumonia observed in the present model. Immunostaining imaging revealed the presence of S. pneumoniae organisms in olfactory nerve fibers. Knockout of the ply gene encoding pneumolysin (PLY) markedly compromised the ability of the bacterial organisms to disseminate into brain tissue, whereas the dissemination efficiency of the complemented strain was restored to nearly the same level as the wild type. Notably, distinct upregulation of Gli1 and Snail1, which are involved in the transcriptional repression of junctional proteins, along with downregulation of E-cadherin, was detected in nasal lavage samples from mice infected with the wild-type or complemented strain, but not in those from mice infected with the ply mutant. Taken together, the present findings indicate that PLY induces Gli1-Snail1-dependent dysfunction of the nasal epithelial barrier, thus allowing pneumococcal dissemination to brain tissue that occurs in a non-hematogenous manner.IMPORTANCEBacterial meningitis, considered to be caused by bacteremia, can lead to blood–brain barrier disruption and bacterial dissemination into the central nervous system. Despite the availability of intravenously administered antibiotics with cerebrospinal fluid transferability, bacterial meningitis remains associated with high rates of morbidity and mortality. Here, we utilized Streptococcus pneumoniae strain EF3030, clinically isolated from otitis media, for the construction of a murine infection model to investigate the molecular mechanisms by which nasally colonized pneumococci disseminate into brain tissue. The obtained findings indicate that pneumolysin (PLY) induces Gli1-Snail1-dependent dysfunction of the nasal epithelial barrier, which facilitates pneumococcal dissemination to brain tissue in a non-hematogenous manner. Our results support the existence of an alternative route by which S. pneumoniae can reach the central nervous system and indicate the need for the development of novel therapeutic strategies, which would be an important contribution to the clinical management of bacterial meningitis.

The development of reduced models provide efficient methods that can be used to perform short term experimental data analysis or narrow down the parametric range of more sophisticated numerical approaches. Reduced models are derived by simplifying the physics description with the goal of retaining only the essential ingredients required to reproduce the phenomena under study. This is the role of the gyro-fluid code FAR3d, dedicated to analyze the linear and nonlinear stability of Alfvén Eigenmodes (AE), Energetic Particle Modes (EPM) and magnetic-hydrodynamic modes as pressure gradient driven mode (PGDM) and current driven modes (CDM) in nuclear fusion devices. Such analysis is valuable for improving the plasma heating efficiency and confinement; this can enhance the overall device performance. The present review is dedicated to a description of the most important contributions of the FAR3d code in the field of energetic particles (EP) and AE/EPM stability. FAR3d is used to model and characterize the AE/EPM activity measured in fusion devices as LHD, JET, DIII-D, EAST, TJ-II and Heliotron J. In addition, the computational efficiency of FAR3d facilitates performing massive parametric studies leading to the identification of optimization trends with respect to the AE/EPM stability. This can aid in identifying operational regimes where AE/EPM activity is avoided or minimized. This technique is applied to the analysis of optimized configurations with respect to the thermal plasma parameters, magnetic field configuration, external actuators and the effect of multiple EP populations. In addition, the AE/EPM saturation phase is analyzed, taking into account both steady-state phases and bursting activity observed in LHD and DIII-D devices. The nonlinear calculations provide: the induced EP transport, the generation of zonal structures as well as the energy transfer towards the thermal plasma and between different toroidal/helical families. Finally, FAR3d is used to forecast the AE/EPM stability in operational scenarios of future devices as ITER, CFETR, JT60SA and CFQS as well as possible approaches to optimization with respect to variations in the most important plasma parameters.

The purpose of this study is to discuss epidemic communication for drones to share information in flight and to develop a wireless system for implementation. Various theoretical studies have been conducted on epidemic communication, but their applications are not clear, so a system that assumes practical use is developed. As the main evaluation items, we analyzed the effect of communication interference between drones on the amount of data transmission, and furthermore, proposed an optimal transmission method depending on the flight speed. In these analysis results, we designed functions to be implemented in drones, developed wireless devices, and confirmed their operation through demonstration tests using actual drones. Based on the results of this research, we succeeded in identifying issues to be addressed in order to implement the system on drones and in developing an epidemic communication system based on the results of demonstration experiments, thereby contributing to the realization of inter-drone communication in the future.

Abstract Background Evaluation of the antigen responsible for fibrotic hypersensitivity pneumonitis (HP) is challenging. Serum immunoglobulin (Ig) G testing against HP-associated antigens is performed. Although single-serum IgG testing has been investigated, multiple-serum IgG testing has not yet been studied. Methods This study included patients who underwent histopathological examination and positive inhalation challenge test as well as those with moderate or high HP guideline confidence level. Serum IgG testing against pigeon serum was conducted twice using two methods: enzyme linked-immunosorbent assay (ELISA) and ImmunoCAP. The association between changes in serum IgG antibody titers and changes in forced vital capacity (FVC) and other parameters was investigated. Results In this study, 28 patients (mean age, 64.5 years; mean FVC, 85.3%) with fibrotic avian HP were selected, of whom 20 and 8 underwent surgical lung biopsy and transbronchial lung cryobiopsy, respectively. Of the 28 patients, 19 had been keeping birds for more than 6 months. A correlation was observed between the annual changes in serum IgG antibody titers by ELISA and changes in relative FVC (r = − 0.6221, p

Abstract Background The workload of public health nurses (PHNs) working for local governments has been increasing as health issues become more diverse and complicated. Even amidst the ongoing administrative and fiscal reforms, there is an urgent need to ensure how effectively and efficiently public health nurses can practice in health service development. The objective of this research was to clarify the actual conditions of best practice transfer (BPT) and its related factors. Methods An anonymous postal and self-administered questionnaire survey was conducted among PHNs working at 334 sites, including the local government offices and health centers across Japan, and analysed mainly through logistic regression analysis. Results One hundred eighty-five of the 334 institutions (55.4%) agreed to participate, and of the 966 questionnaire forms distributed, 709 forms (73.4%) were collected, of which 702 responses (72.7%) were valid. Although less than half (43.2%) have experience in BPT in health service development, more than 80% are willing to perform going forward. Significant factors for both the group with experience in BPT and the group with willingness to perform include an organizational culture that promotes BPT, as well as multiple elements of the workplace environment and facilitating factors related to knowledge and learning. The experienced group recognised the needs for criteria to evaluate the adaptability of best practice, while the willing group, to evaluate the quality of practice. Conclusions Through a nationwide survey, this research elucidated for the first time the actual conditions of BPT by PHNs in Japan and related factors. The results indicated the importance of developing a system to promote BPT at the workplace level, also highlighted the importance for practitioners and experts, including researchers, to work together to develop practical guidelines to ensure evidence-based practices. Urgent actions are needed for the national and local governments to develop a system to promote BPT from diverse perspectives, building on the findings of this research.

Abstract Background Muscle and bone are physiologically interconnected, but joint changes of muscle and bone with aging, and whether the muscle‐bone changes are different by sex and by country has been little studied. We examined longitudinal associations of bone mineral density (BMD) and muscle mass or muscle strength in community‐dwelling 65 years or older in the United States and Japan. Methods The present analytic sample included 1129 women and men from the Baltimore Longitudinal Study of Aging (BLSA) (mean age, 74.5 ± 7.5 years; women, 49.8%) and 1998 women and men from the National Institute for Longevity Sciences‐Longitudinal Study of Aging (NILS‐LSA) (mean age, 70.0 ± 4.5 years; women, 51.4%). Median follow‐up was 4.6 (min‐max, 0–15.4) years in the BLSA and 4.0 (min‐max, 0–13.4) years in the NILS‐LSA. We selected visits at which participants had BMD (whole body, pelvic, femoral neck, trochanter, and Ward's triangle BMDs) and muscle mass [appendicular lean mass, (ALM)] measured by DXA scan. In each bone site, we ran cohort‐specific bivariate linear mixed‐effects models adjusted for baseline age, sex, body height, body weight, fat mass, education year, and smoking status. Race was an additional adjustment in the BLSA. Additionally, we performed sex‐specific analyses. Results In the BLSA, the rate of change in ALM positively correlated with the rate of change in the whole body (rho = 0.30, P 0.05). In the NILS‐LSA, ALM positively correlated with the rate of change in all bone sites (rho ranged from 0.20 to 0.71, P

Abstract The association between serum tumor necrosis factor receptor (TNFRs: TNFR1, TNFR2) levels and estimated glomerular filtration rate (eGFR) observed in patients with diabetes has not been comprehensively tested in healthy subjects with normal kidney function. It also remains unclear whether TNFR levels differ by age and sex, and between healthy subjects and diabetics. We measured serum TNFR levels in 413 healthy subjects and 292 patients with type 2 diabetes. In healthy subjects, TNFR levels did not differ between men and women. Additionally, TNFR2, but not TNFR1, levels increased with age. In multivariate analysis, TNFR1 was associated only with cystatin C-based eGFR (eGFR-CysC), whereas TNFR2 was associated with systolic blood pressure in addition to eGFR-CysC. Both TNFRs were associated with lower eGFR (eGFR-Cys

The climate science community aims to improve our understanding of climate change due to anthropogenic influences on atmospheric composition and the Earth's surface. Yet not all climate interactions are fully understood, and uncertainty in climate model results persists, as assessed in the latest Intergovernmental Panel on Climate Change (IPCC) assessment report. We synthesize current challenges and emphasize opportunities for advancing our understanding of the interactions between atmospheric composition, air quality, and climate change, as well as for quantifying model diversity. Our perspective is based on expert views from three multi-model intercomparison projects (MIPs) – the Precipitation Driver Response MIP (PDRMIP), the Aerosol Chemistry MIP (AerChemMIP), and the Radiative Forcing MIP (RFMIP). While there are many shared interests and specializations across the MIPs, they have their own scientific foci and specific approaches. The partial overlap between the MIPs proved useful for advancing the understanding of the perturbation–response paradigm through multi-model ensembles of Earth system models of varying complexity. We discuss the challenges of gaining insights from Earth system models that face computational and process representation limits and provide guidance from our lessons learned. Promising ideas to overcome some long-standing challenges in the near future are kilometer-scale experiments to better simulate circulation-dependent processes where it is possible and machine learning approaches where they are needed, e.g., for faster and better subgrid-scale parameterizations and pattern recognition in big data. New model constraints can arise from augmented observational products that leverage multiple datasets with machine learning approaches. Future MIPs can develop smart experiment protocols that strive towards an optimal trade-off between the resolution, complexity, and number of simulations and their length and, thereby, help to advance the understanding of climate change and its impacts.

Abstract Amidst the global COVID-19 pandemic, telework (remote work) has become a widespread practice adopted by companies worldwide. However, Japan has notably maintained a low rate of telework implementation, suggesting cultural factors hindering its adoption. This study aimed to elucidate the antecedents and consequences of teleworking in Japan. Leveraging the natural experiment created by the COVID-19 pandemic, we addressed two key questions: (1) What socio-psychological factors in Japanese workplaces were important for implementing telework in the first place? and (2) How did the implementation of telework subsequently influence socio-psychological factors in these workplaces? Employees from various Japanese companies completed three waves of an online survey before and during the pandemic. Results showed that telework was more likely to be implemented in organizations characterized by a meritocracy. Results also showed that the implementation of telework demonstrated no measurable negative effects but instead increased levels of independence, organizational commitment, and perceived hierarchy mutability.

Abstract Background Anti-calcitonin gene-related peptide monoclonal antibodies (CGRPmAbs) have greatly changed migraine treatment options. In Japan, although CGRPmAb guidelines (≥ 4 monthly migraine days (MMDs) and ≥ 1 previous preventive failure) are well-acknowledged, the actual use of CGRPmAbs and the circumstances of the related headache care are unknown. Methods We conducted an online survey of Japanese Headache Society members, inquiring about the physicians' experience with CGRPmAbs and how they make decisions related to their use. Results Of the 397 respondents, 320 had prescribed CGRPmAbs. The threshold number of previous preventive failures for recommending a CGRPmAb was two for the majority of the respondents (n = 170, 54.5%), followed by one (n = 64, 20.5%). The MMD threshold was ≥ 4 for 71 respondents (22.8%), ≥ 6 for 68 (21.8%), ≥ 8 for 76 (24.4%), and ≥ 10 for 81 (26.0%). The respondents tended to assess treatment efficacy after 3 months (episodic migraine: n = 217, 69.6%, chronic migraine: n = 188, 60.3%). The cost of CGRPmAbs was described by many respondents in two questions: (i) any request for a CGRPmAb (27.7%), and (ii) the most frequently reported reason for responders to discontinue CGRPmAbs (24.4%). Conclusions Most of the respondents recommended CGRPmAbs to patients with ≥ 2 preventive failures, followed by ≥ 1. The MMD threshold ranged mostly from ≥ 4 to ≥ 10. The concern for costs was raised as a major limiting factor for prescribing CGRPmAbs.

Abstract When someone violates a social norm, others may think that some sanction would be appropriate. We examine how the experience of emotions like anger and disgust relate to the judged appropriateness of sanctions, in a pre-registered analysis of data from a large-scale study in 56 societies. Across the world, we find that individuals who experience anger and disgust over a norm violation are more likely to endorse confrontation, ostracism and, to a smaller extent, gossip. Moreover, we find that the experience of anger is consistently the strongest predictor of judgments of confrontation, compared to other emotions. Although the link between state-based emotions and judgments may seem universal, its strength varies across countries. Aligned with theoretical predictions, this link is stronger in societies, and among individuals, that place higher value on individual autonomy. Thus, autonomy values may increase the role that emotions play in guiding judgments of social sanctions.

Abstract Background At present, there are no consistent findings regarding the association between physical health loss and mental health in older adults. Some studies have shown that physical health loss is a risk factor for worsening of mental health. Other studies revealed that declining physical health does not worsen mental health. This study aimed to clarify whether the relationship between physical health loss and emotional distress varies with age in older inpatients post receiving acute care. Methods Data for this study were collected from 590 hospitalized patients aged ≥ 65 years immediately after their transfer from an acute care ward to a community-based integrated care ward. Emotional distress, post-acute care physical function, and cognitive function were assessed using established questionnaires and observations, whereas preadmission physical function was assessed by the family members of the patients. After conducting a one-way analysis of variance (ANOVA) and correlation analysis by age group for the main variables, a hierarchical multiple regression analysis was conducted with emotional distress as the dependent variable, physical function as the independent variable, age as the moderator variable, and cognitive and preadmission physical function as control variables. Results The mean GDS-15 score was found to be 6.7 ± 3.8. Emotional distress showed a significant negative correlation with physical function in younger age groups (65-79 and 80-84 years); however, no such association was found in older age groups (85-89, and ≥ 90 years). Age moderated the association between physical function and emotional distress. Poor physical function was associated with higher emotional distress in the younger patients; however, no such association was observed in the older patients. Conclusions Age has a moderating effect on the relationship between physical health loss and increased emotional distress in older inpatients after acute care. It was suggested that even with the same degree of physical health loss, mental damage differed depending on age, with older patients experiencing less damage.

Studies employing neural networks to classify emotions from brain waves and other biological signals provide a quantitative perspective on understanding human physiological phenomena. Typically, multimodal networks process combined data without considering the relationships between electrodes, such as in electroencephalograms (EEG) where data are gathered from multiple inputs. However, incorporating electrode relationships when combining data may improve the model accuracy. This study explores EEG data, often treated as a single modality, input into networks of varied structures as a multimodal data stream to evaluate accuracy. Additionally, it investigates the effect of input electrode combination patterns on accuracy. The results underscore the importance of designing appropriate electrode models when integrating EEG data into networks with various structures. Under the conditions of this study, the highest accuracy of 89.08% was obtained by the most appropriate model, significantly surpassing others. Therefore, when incorporating multi-channel EEG data into neural networks, the structure of the model’s specific section receiving the EEG signal must be considered.

BackgroundDuring the COVID-19 pandemic, health care professionals experienced high levels of depression. However, extant research has not highlighted effective internet-based psychological interventions to improve the mental health in this population during the pandemic. It remains unclear whether self-guided, internet-based cognitive behavioral therapy (iCBT) programs are effective in improving the mental health of health care workers during the COVID-19 pandemic. ObjectiveThe aim of this study was to evaluate the effectiveness of a smartphone-based iCBT stress management program for reducing the depression experienced by nurses in Vietnam and Thailand. MethodsFrom March to April 2022, a 2-arm, parallel-group randomized controlled trial was implemented. One arm offered a 7-week self-guided iCBT program, and the other offered treatment as usual as a control arm. Full-time nurses were recruited from 6 hospitals: 2 hospitals in Vietnam and 4 hospitals in Thailand. The primary outcome of this program was the severity of depression measured by the Depression Anxiety Stress Scale-21 items. Follow-up surveys were conducted to measure the change in depression severity at 3 months (July-August 2022) and at 6 months (October-November 2022) after baseline. Mixed modeling for repeated measures was used to test the effects of the intervention compared with the control for the follow-up. ResultsA total of 1203 nurses were included in this study: 602 in the intervention group and 601 in the control group. The follow-up rate at 3 and 6 months ranged from 85.7% (515/601) to 87.5% (527/602). The completion rate for the program was 68.1% (410/602). The group difference in depression was significant at the 3-month follow-up (coefficient=–0.92, 95% CI –1.66 to –0.18; P=.02) and nonsignificant at the 6-month follow-up (coefficient=–0.33, 95% CI –1.11 to 0.45; P=.41). The estimated effect sizes were –0.15 and –0.06 at the 3- and 6-month follow-ups, respectively. ConclusionsOur study shows that the smartphone-based iCBT program was effective in reducing depression at the 3-month follow-up among hospital nurses in Vietnam and Thailand during the COVID-19 pandemic. However, the effect size was small, and therefore, these results may not be clinically meaningful. Trial RegistrationUMIN Clinical Trials Registry UMIN000044145; https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000050128 International Registered Report Identifier (IRRID)RR2-10.20944/preprints202303.0450.v1

Abstract Aim Internationalization at Home (IaH) strategies play an important role in nursing curricula to enhance nursing students' cultural awareness in the globalized world. The Community of Inquiry (CoI) is a theoretical framework for the optimal design of online learning environments to support critical inquiry and discourse among students and teachers. To optimise nursing students' online cultural awareness learning experiences, it was timely to develop online IaH strategies based on a sound theoretical model. This study aimed to examine the effectiveness of CoI‐guided online IaH strategies on enhancing the cultural awareness of nursing undergraduates who enrolled in a community nursing course. Design This was an interventional pre‐test post‐test study. Method One hundred and six nursing undergraduates who enrolled in the course participated in the study. The online IaH strategies were developed focusing on the interactions of teaching presence, cognitive presence and social presence of CoI framework and they were integrated into the course. A previously validated Cultural Awareness Scale was adopted for pre‐post evaluation. Higher scores indicate greater cultural awareness. Results The results showed that there was a significantly higher total score of cultural awareness of participating students at post‐online IaH strategies. To be effective, aligning CoI‐guided online IaH strategies with course content, pedagogy and assessment was shown to be significant. The inclusion of technological elements in related strategies was also critical to engage student learning. The positive change on the total score of cultural awareness suggested the effectiveness of the deployed strategies. In this ever‐changing educational landscape, it may provide insights to educators regarding considering online IaH strategies with theoretical underpinning for curriculum planning and design.

Background: Early postoperative functional recovery is important in older patients with lower-extremity fractures to prevent disuse, and periprosthetic femoral fractures (PFFs) are no exception. This study aimed to compare the postoperative functional recovery in the early phase after revision for PFF with loose stems between cemented and cementless stems. Methods: Eighteen patients with Unified Classification System type B2 PFF were included in this retrospective cohort study with a follow-up period of about 2 years. All patients underwent stem revision and were divided into 2 groups: the cemented stem group (n = 9) and the cementless stem group (n = 9). In postrevision, functional independence measure score, independent walk rate, activities of daily living recovery rate to the original level at 2 weeks postoperatively, the Beals and Tower classification for radiological status, and survival rate for readmission as endpoints were compared between the 2 groups. Results: Patients in the cemented group recovered functional mobility earlier than in the cementless group, with higher postoperative functional independence measure functional subscale values (73 vs 50 points, P = .02), higher independent walk rate (89 vs 11%, P < .01), and more postoperative activities of daily living recovery (100% vs 44%, P = .03) at 2 weeks postoperatively. The Beals and Tower classification and survival rates were similar in both groups. Conclusions: Revision using a cemented stem for PFF in older patients was a useful surgical procedure in terms of early postoperative functional recovery. Cemented stem revision was comparable with cementless in bone union and safety at 2 years postoperatively.

ABSTRACT Background Although transbronchial lung cryobiopsy (TBLC) is widely used in diagnostic algorithms for various interstitial lung diseases (ILDs), its real‐world utility in the therapeutic decision‐making strategy for ILD patients remains unclear, in particular, when judging the time to start antifibrotic agents. Methods We analyzed medical records of 40 consecutive patients with idiopathic or fibrotic hypersensitivity pneumonitis who underwent TBLC. A TBLC‐based usual interstitial pneumonia (UIP) score was used to assess three morphologic descriptors: patchy fibrosis, fibroblastic foci, and honeycombing. Results In our 40 patients with ILD, the most frequent radiological feature was indeterminate for UIP (45.0%). Final diagnosis included idiopathic pulmonary fibrosis (22.5%), fibrotic nonspecific interstitial pneumonia (5.0%), fibrotic hypersensitivity pneumonitis (35.0%), and unclassifiable ILD (37.5%). Linear mixed‐effects analysis showed that declines in the slopes of %FVC and %DLCO in patients with TBLC‐based UIP “Score ≥ 2” were significantly steeper than those of patients with “Score ≤ 1.” During follow‐up of patients with Score ≥ 2 (n = 24), more than half of them (n = 17) received an antifibrotic agent, with most patients (n = 13) receiving early administration of the antifibrotic agent within 6 months after the TBLC procedure. Conclusions TBLC‐based UIP Score ≥ 2 indicated the increased possibility of a progressive fibrosis course that may prove helpful in predicting progressive pulmonary fibrosis/progressive fibrosing ILD even if disease is temporarily stabilized due to anti‐inflammatory agents. Patients may benefit from early introduction of antifibrotic agents by treating clinicians.

ABSTRACT Introduction: Hospital readmission is a common way to assess the quality of care provided in an emergency service. In this context, the aim of this study is to quantify and stratify readmissions in a trauma reference emergency service. Methods: A retrospective longitudinal study was conducted with patients readmitted, twice or more, in the emergency service within a maximum period of 30 days from the initial admission - hospitalized or not. Clinical and demographic data were obtained from electronic medical records. Results: The readmission rate for the service was 4.11% for all readmissions and 2.23% for avoidable readmissions. Within this group, 61.19% were likely avoidable, 19.47% possibly avoidable, and 19.34% eventually avoidable. Regarding time, 48.16% occurred within one week of the initial readmission. Furthermore, no statistically significant association was found in the analysis of biological sex, occupational accident, and comorbidities. A statistically significant association was found in the analysis of age and ambulance transport (OR 1.37; 95% CI 1.17-1.59). Conclusion: The study highlighted that there are still readmissions in the emergency department that could be avoided. A significant relationship was observed between readmissions and patient ages, and ambulance transport.

Abstract Using a reanalysis dataset and large‐ensemble simulation results, this study examines a possible factor of increasing trend in early winter precipitation in recent decades in the Hokuriku region of Japan. Monthly precipitation in December has a significant increasing trend after the early 1990s, which is different from those in January and February. The increasing precipitation in December is related to that in the sea surface upward latent heat flux due to intensified winter monsoon circulation and warming sea surface temperatures (SSTs) over the Sea of Japan. December averaged SSTs show a trend pattern in recent decades that is similar to the negative phase of the interdecadal Pacific oscillation (IPO), accompanied by positive trends from the eastern Indian Ocean to the western tropical Pacific. The enhanced trend of convection over the Bay of Bengal is seen; suggesting a combined effect of climatologically high SSTs and IPO‐related warmed SSTs over the region. Trends in recent decades of an upper‐level wavy pattern from South Asia to near Japan along the subtropical jet associated with enhanced convection near the Bay of Bengal and the related pressure drop from Japan to the north are seen, which contribute to intensified winter monsoon circulation.

Background Multiple prolonged symptoms observed in patients who recovered from COVID-19 are defined as long COVID. Although diverse phenotypic combinations are possible, they remain unclear. This study aimed to perform a cluster analysis of long COVID in Japan and clarify the association between its characteristics and background factors and quality of life (QOL).Methods This multicentre prospective cohort study collected various symptoms and QOL after COVID-19 from January 2020 to February 2021. This study included 935 patients aged ≥18 years with COVID-19 at 26 participating medical facilities. Hierarchical cluster analysis was performed using 24 long COVID symptom at 3 months after diagnosis.Results Participants were divided into the following five clusters: numerous symptoms across multiple organs (cluster 1, n=54); no or minor symptoms (cluster 2, n=546); taste and olfactory disorders (cluster 3, n=76); fatigue, psychoneurotic symptoms and dyspnoea (low prevalence of cough and sputum) (cluster 4, n=207) and fatigue and dyspnoea (high prevalence of cough and sputum) (cluster 5, n=52). Cluster 1 included elderly patients with severe symptoms, while cluster 3 included young female with mild symptoms. No significant differences were observed in the comorbidities. Cluster 1 showed the most impaired QOL, followed by clusters 4 and 5; these changes as well as the composition of symptoms were observed over 1 year.Conclusions We identified patients with long COVID with diverse characteristics into five clusters. Future analysis of these different pathologies could result in individualised treatment of long COVID.Trial registration number The study protocol is registered at UMIN clinical trials registry (UMIN000042299).

Melatonin and dopamine participate in the regulation of reproduction-related hormone/peptide synthesis and secretion at the hypothalamic–pituitary–gonadal axis in fish. Here, we report a unique reproduction-related interaction of melatonin and dopamine in the brain of the sapphire devil Chrysiptera cyanea, a tropical damselfish with a long-day preference. We examined the expression of arylalkylamine N-acetyltransferase 2 (aanat2)—a rate-limiting enzyme of melatonin, dopamine 2b receptor (d2b), gonadotropin-releasing hormone (gnrh1), and β-subunit of follicle-stimulating hormone (fshβ) and luteinizing hormone (lhβ)—in the brain of the sapphire devil. During the reproductive season, mature females were divided into the early vitellogenesis (EV), late vitellogenesis (LV), and post-spawning (PS) stages; a day-low and night-high profile of aanat2 was observed during EV and LV but not during PS. There were nocturnal increases in gnrh1 during EV and LV as well as d2b during LV, suggesting that melatonin has a positive effect on the levels of gnrh1 and d2b transcripts in mature fish. When the brains of females in the non-breeding season were sampled at 4-h intervals, nocturnal increases in the levels of fshβ and lhβ transcripts were observed at 00:00 and 04:00, respectively. The immersion of immature fish in melatonin-containing seawater for 6 h resulted in the upregulation of fshβ and lhβ, as well as downregulation of d2b, in the brain. Additionally, in situ hybridization analysis showed that melatonin treatment lowered the signals of d2b transcripts in the ventral hypothalamus, rostral pars distalis, proximal pars distalis, and pars intermedia, suggesting that melatonin has a negative impact on the levels of d2b transcripts in the hypothalamus and pituitary of immature females; the opposite effect is likely concerning the levels of fshβ and lhβ transcripts in the pituitary. In conclusion, melatonin positively and negatively acted on the hypothalamus and pituitary in the sapphire devil; these opposite effects were related to differences in gonadal development status.

BackgroundRecently, cases of overlapping encephalitis caused by anti-N-methyl-D-aspartate receptor (anti-NMDAR) and anti-myelin oligodendrocyte glycoprotein (MOG) antibodies have been reported, and their clinical characteristics are gradually becoming clear. Acute-phase treatment typically involves the use of steroids, and although some studies have suggested that steroids can be effective, the extent of their efficacy has not yet been fully explored.Case presentationWe present the case of a 25-year-old man with anti-NMDAR and anti-MOG antibody overlapping encephalitis who showed considerable improvement after steroid treatment. To gain a deeper understanding of the efficacy of steroids in managing this condition, we conducted a literature review of cases of anti-NMDAR and anti-MOG antibody double-positive encephalitis that were treated with steroids during the acute phase. Thirteen cases were analyzed, including a new case diagnosed at our hospital. All patients showed improvement after receiving steroid treatment in the acute phase. Ten patients did not have any sequelae, and nine of them showed a rapid or major response during the acute phase. In contrast, three patients experienced sequelae (mild cognitive decline, visual impairment, and memory impairment, respectively), with their response to steroids in the acute phase being slow or limited. Relapses occurred in five patients, in one patient during steroid tapering, and in another two patients after cessation of steroids.ConclusionSteroid therapy can be effective in the acute stage of anti-NMDAR and anti-MOG antibody overlapping encephalitis. A positive prognosis may be expected in patients who experience substantial improvement with steroid therapy during the acute phase.

# Background Secondary anterior cruciate ligament (ACL) injury is a complication of ACL reconstruction (ACLR), which may result from altered neuromuscular control affecting anticipatory postural adjustments (APAs) and compensatory postural adjustments (CPAs) required for maintaining balance during movement. However, it remains unclear how APAs and CPAs differ in single-leg landings post-ACLR compared to healthy subjects. # Purpose The purpose of this study was to clarify the differences in muscle activities of APAs and CPAs, lower limb kinematics, and kinetics between athletes with a history of ACLR and healthy athletes during single-leg landing. # Study design Cross-sectional study. # Methods Eighteen female athletes were recruited and divided into ACLR (n = 9) and control groups (n = 9). The experimental task involved a single-leg landing from a 30 cm box. Joint angles and moments were determined using a 3-dimensional motion analysis system, while muscle activity was assessed using surface electromyography. Analysis intervals were divided into two phases: the APA phase (-150 ms to 50 ms) and the CPA phase (50 ms to 250 ms), with initial contact (0 ms) as the reference point. Muscle activity onset time was defined as the time when the baseline exceeded by the sum of mean values and 2 standard deviations. # Results No significant differences were observed in muscle activity or onset time between the ACLR and control groups. However, an increased hip external rotation moment was observed during the CPA phase in the ACLR group. # Conclusion These findings suggest that APAs and CPAs of athletes who returned to sports more than 1 year post-ACLR may be similar. The increased hip external rotation moment in the ACLR group during the CPA phase could represent a specific compensatory strategy to decrease the hip internal rotation angle post-ACLR. # Level of Evidence III