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Osteoporosis in postmenopausal women is one of the causes of femoral fractures and is prevented by the administration of bisphosphonates. Individual morphologies are considered to increase the risk of atypical fractures associated with long‐term administration. To evaluate cortical bone morphology quantitatively, we established a method to measure the distance from the center point of a cross‐section to the external and internal borders based on CT images. Using this method, 44 sides of a female femoral skeleton specimen were examined and areas of protrusion and thickening in the medial anterior and lateral posterior regions just below the lesser trochanter were identified. These positions strongly correlated with the anteversion angle, suggesting the involvement of the distribution of the load received from body weight defined by the angle. The finite element method was used to examine the relationships between the positions of these areas with compressive and tensile stress distribution areas in the one‐legged standing condition. The medial anterior region and lateral posterior region protruded and thickened in response to compressive and tensile stress, respectively. In addition, a hierarchical relationship was observed between the anteversion angle, tensile stress distribution, protrusion, and thickening in femurs with thinning of cortical bone, indicating that morphogenesis occurs adaptively to loading. The present results demonstrate the usefulness of this method in considering the formation mechanism and function of the femoral diaphysis and suggest that bone remodeling is necessary to maintain adaptability. [ABSTRACT FROM AUTHOR]

BACKGROUND: Strawberry is a rich source of antioxidants, including ascorbic acid (ASA) and polyphenols, which have numerous health benefits. Antioxidant content and activity are often determined manually using laboratory equipment, which is destructive and time‐consuming. This study constructs a prediction model for antioxidant compounds utilizing machine learning (ML) and multiple linear regression based on environmental, plant growth and agronomic fruit quality‐related parameters as well as antioxidant levels. These were studied in three farms at two‐week intervals during two years of cultivation. RESULTS: During the ML model screening, artificial neural network (ANN)‐boosted models displayed a moderate coefficient of determination (R2) at 0.68–0.78 and relative root mean square error (RRMSE) at 3.8–4.8% in polyphenols and total ASA levels, as well as a high R2 of 0.96 and low RRMSE at <3.0% in antioxidant activity. Additionally, we developed variable selection models regarding the antioxidant activity, and variables two and five (environmental parameters and leaf length, respectively) with high accuracy were selected. The linear regression analysis between the actual and predicted data of antioxidants in the ANN‐boosted models revealed high fitness with all parameters in almost all training, validation and test sets. Furthermore, environmental parameters are essential in developing such reliable models. CONCLUSION: We conclude that ANN‐boosted, stepwise and double‐Lasso regression models can predict antioxidant compounds with enhanced accuracy, and the relevant parameters can be easily acquired on‐site without the need for any specific equipment. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

We successfully produced a dopant‐free oxygen‐defective HfO2−x film that exhibit room‐temperature ferromagnetism via a heat treatment of metallic Hf foil at 1673 K for 10 h under an oxygen partial pressure of 1.0 × 10−4 atm. The sample, which exhibits ∼50% transmission of visible light, demonstrates room‐temperature ferromagnetism, with saturation and residual magnetizations of ∼0.05 emu/g and ∼0.005 emu/g, respectively. The HfO2−x film comprises columnar grains several hundred nanometers wide and several micrometers long. High‐angle annular dark‐field scanning electron microscopy observations indicated that the tetragonal HfO2 structure was distributed in nanodomains within the monoclinic HfO2 grains; that is, the films exhibited a hybridized microstructure. The tetragonal HfO2 structure would be mainly due to the introduction of oxygen deficiencies, which led to the room‐temperature ferromagnetism. [ABSTRACT FROM AUTHOR]

Bovine spongiform encephalopathy (BSE) is a prion disease in cattle caused by classical‐type (C‐), L‐type (L‐), or H‐type (H‐) BSE prions. While C‐BSE prions are zoonotic agents responsible for variant Creutzfeldt–Jakob disease, L‐ and H‐BSE prions are believed not to be connected to human prion diseases. However, L‐BSE prions have been shown to transmit to cynomolgus monkeys (Macaca fascicularis), suggesting they may have zoonotic potential. In the present study, we examined whether H‐BSE prions are transmissible to cynomolgus monkeys. The monkeys were injected intracranially (n = 2) or given orally (n = 2) with brain homogenates from a cow infected with H‐BSE prions. After asymptomatic observation periods of 4–6 years, the monkeys were euthanized for autopsy. Histological examination of the brain did not reveal any pathological changes. Immunohistochemical and Western blot analyses did not detect disease‐associated forms of prion protein (PrPSc) in the brain, peripheral neurons, or lymphatic tissues. The unsuccessful transmission indicates an effective barrier against the transmission of cattle H‐BSE prions to cynomolgus monkeys. Based on the results obtained in this nonhuman primate model, we estimated that the potential transmission of H‐BSE prions to humans is substantially lower than C‐ and L‐BSE prions. [ABSTRACT FROM AUTHOR]

Purpose: The safety and long‐term durability of minimally invasive mitral valvuloplasty (MIMVP) remain controversial. This study aimed to compare the perioperative and long‐term outcomes of minimally invasive mitral valve surgery (MIMVS) and conventional sternotomy. Methods: This study included 476 patients who underwent mitral valve surgeries at our institution between January 2011 and December 2023. Patients were classified according to whether they underwent sternotomy: the nonsternotomy (NS: 271 cases) and sternotomy (S: 205 cases) groups. Perioperative and long‐term outcomes were compared between the two groups. Results: The NS group had a lower preoperative age and EuroScore II. In the S group, the left ventricular ejection fraction was lower, while the left ventricular end‐systolic diameter and left atrial diameter were larger. Operative time, cardiopulmonary bypass time, and aortic cross‐clamp time were longer in the NS group. Postoperative atrial fibrillation, more transfusion, and increased length of hospital stay were more frequent in the S group. The 10‐year freedom from reoperation and 10‐year survival rates in the NS and S groups were 98.1% vs. 93.6% (p = 0.07) and 94.8% vs. 86.9%, respectively (p = 0.08), with no significant differences. Conclusion: MIMVP demonstrates noninferior perioperative and long‐term outcomes compared with conventional sternotomy. [ABSTRACT FROM AUTHOR]

Active colloids are modular assemblies of distinct micro‐ and nanoscale components that can perform complex robotic tasks. While recent advances in templated assembly methods enable high‐throughput fabrication of multi‐material active colloids, their limitations reduce the ability to construct flexibly linked colloidal systems, restricting their complexity, agility, and functionality. Here, templated assembly by selective removal (TASR) is leveraged to construct multicomponent colloidal microstructures that are connected with compliant DNA nanotube linkages. Polycarbonate heat (PCH) molding is employed to create high‐surface‐energy templates for improved polystyrene microsphere assembly via TASR. This increase in template surface energy improves microsphere assembly by more than 100‐fold for two‐sphere microstructures. An inverse relationship between microstructure complexity (i.e., the number of microspheres) and assembly yields is observed. PCH‐assisted TASR is leveraged to construct larger colloidal structures containing up to 26 microspheres, multi‐sphere microrotors, and structurally homogeneous populations of flexibly linked, two‐sphere microswimmers that locomote in fluid environments. Real‐time modification of a microswimmer is also demonstrated through nuclease‐mediated degradation of the DNA linkages, highlighting the DNA‐enabled reconfiguration and responsiveness capabilities of these microswimmers. These results establish PCH‐assisted TASR as a versatile method for constructing flexibly linked, modular microrobots with controlled geometry, enhanced agility, and dynamic response. [ABSTRACT FROM AUTHOR]

Aim: Although immune checkpoint inhibitors (ICPi) for salivary gland cancer (SGC) have been investigated in clinical trials, details of the tumor immune microenvironment (TIME) remain unclear. This research aimed to elucidate the TIME of SGC and its relationship with tumor mutation burden (TMB) and to explore the rationale for the applicability of ICPi. Materials and methods: We selected five pathological types, namely adenoid cystic carcinoma (ACC); adenocarcinoma, not otherwise specified (ANOS); salivary duct carcinoma (SDC); and low/high‐grade mucoepidermoid carcinoma (MEClow/high). We investigated the TIME and TMB of each pathological type. TIME was evaluated by multiplexed fluorescent immunohistochemistry. TMB was measured by next‐generation sequencing. Results: ACC and MEChigh showed the lowest and highest infiltration of immune effector and suppressor cells in both tumor and stroma. ANOS, SDC, and MEClow showed modest infiltration of immune effector cells in tumors. Correlation analysis showed a positive correlation between CD3+CD8+ T cells in tumor and TMB (r = 0.647). CD3+CD8+ T cells in tumors showed a positive correlation with programmed cell death‐ligand 1 expression in tumor cells (r = 0.513) and a weak positive correlation with CD3+CD4+Foxp3+ cells in tumors (r = 0.399). However, no correlation was observed between CD3+CD8+ T cells and CD204+ cells in tumors (r = ‐0.049). Conclusion: The TIME of ACC was the so‐called immune desert type, which may explain the mechanisms of the poor response to ICPi in previous clinical trials. On the other hand, MEChigh was the immune‐inflamed type, and this may support the rationale of ICPi for this pathological subtype. [ABSTRACT FROM AUTHOR]

Aims: Knowing the upper time limit for successful weaning from temporary mechanical circulatory support in cardiogenic shock will help with decision‐making regarding advanced heart failure (HF) therapy or considering withdrawal of care. The aim of this study was to investigate the association between the support duration and successful weaning from veno‐arterial extracorporeal membrane oxygenation (VA‐ECMO) in patients with cardiogenic shock. Methods and results: A retrospective single‐centre cohort study was conducted between January 2013 and June 2023. It included 100 consecutive patients with cardiogenic shock who were treated with VA‐ECMO. Patients with out‐of‐hospital cardiac arrest were excluded. The primary outcome was successful weaning from VA‐ECMO (i.e., VA‐ECMO decannulation and survival to discharge). The association between the length of support duration and the weaning success rate was analysed. Patients were divided into three groups according to ECMO support duration: Group A (≤7 days), Group B (8–14 days), and Group C (≥15 days). Multivariable logistic regression analysis was used to evaluate the impact of the length of support duration on successful weaning of VA‐ECMO. The median age was 67 years, and 73% of study participants were male. The underlying aetiologies of cardiogenic shock were as follows: acute myocardial infarction, 50; fulminant myocarditis, 19; cardiomyopathy, 15; valvular heart disease, 8; and other, 8. Seventy‐five patients (75%) were attempted to wean VA‐ECMO, and 67 moved on to decannulation. In total, 43 (43%) patients were successfully weaned from VA‐ECMO. The median length of ECMO support duration was 8 [3–15] days. Compared with those who underwent successful ECMO decannulation, those who did not had a significantly longer support duration of VA‐ECMO (5 [3–9] days vs. 12 [3–22] days, P = 0.004). The weaning success rate was significantly higher in patients with short support duration; 58% (29/50), 40% (10/25), 16% (4/25) in Groups A, B, and C, respectively (P = 0.002). Overall, none of the patients supported for over 24 days (0/11) were successfully weaned from VA‐ECMO. On multivariable logistic regression analysis, the length of support duration was independently associated with successful weaning after adjusting for age, sex, underlying aetiology, and left ventricular ejection fraction (odds ratio, 0.813 [per 3 days]; 95% confidence interval, 0.679–0.914; P = 0.025). Conclusions: Long support duration of VA‐ECMO was significantly associated with a low rate of successful weaning in patients with cardiogenic shock. Patients who require VA‐ECMO for over 1 week should start considering advanced HF therapy or withdrawal of care. [ABSTRACT FROM AUTHOR]

Objective: We evaluated the effect of CHA2DS2‐VASc score and prior use of oral anticoagulants (OACs) on endovascular treatment (EVT) in patients with acute ischemic stroke and atrial fibrillation (AF). Methods: Patients with AF who received EVT in 353 centers in Japan (2018–2020) were included. The outcomes were symptomatic intracerebral hemorrhage (sICH), in‐hospital mortality, functional independence, and successful and complete reperfusion. The effects of CHA2DS2‐VASc score, its components, and prior use of OACs were assessed via a multiple logistic regression model. Results: Of the 6984 patients, 780 (11.2%) used warfarin and 1168 (16.7%) used direct oral anticoagulants (DOACs) before EVT. Based on the CHA2DS2‐VASc score, 6046 (86.6%) presented a high risk (≥2 for males and ≥3 for females) while 938 (13.4%) had intermediate to low risks. Higher CHA2DS2‐VASc scores were associated with increased sICH, in‐hospital mortality, and decreased functional independence, regardless of prior OACs. For patients with a high‐risk category, prior DOACs increased the odds of successful and complete reperfusion (adjusted odds ratio [95% confidence interval (CI)], 1.27 [1.00–1.61] and 1.30 [1.10–1.53]). For those with integrated intermediate to low risks, neither prior warfarin nor DOAC affected the outcomes. Regardless of total CHA2DS2‐VASc scores, patients with congestive heart failure or left ventricular dysfunction, hypertension, age >75 years, or female benefited similarly from prior DOAC use. Interpretation: Prior DOAC use for patients with high‐ and selected intermediate‐risk CHA2DS2‐VASc scores increased prevalence of successful and complete reperfusion. These findings may provide supplemental evidence to introduce preventive DOAC for patients with AF. [ABSTRACT FROM AUTHOR]

Introduction: Functional decline occurs during dialysis initiation, particularly in unplanned cases. To prevent unplanned hemodialysis, we aimed to identify associated factors from the first referral to the nephrology department to hemodialysis initiation and assess patient prognosis post‐unplanned hemodialysis initiation. Methods: This retrospective study involved 257 Japanese patients initiating hemodialysis and compared patient characteristics based on whether hemodialysis was planned or unplanned at a single center. Patient outcomes were evaluated in collaboration with maintenance hemodialysis centers. Results: Unplanned hemodialysis initiation correlated with heart failure history (p < 0.05) and infections like pneumonia (p < 0.001). Patients with unplanned hemodialysis initiation had a worse prognosis than those with planned initiation (p < 0.001), and multivariable Cox regression showed it as an independent risk factor for death (p < 0.05). Conclusions: Hygiene and careful attention to heart failure may reduce unplanned hemodialysis and improve patient well‐being and healthcare efficiency. This retrospective analysis highlights crucial considerations for optimizing the initiation of hemodialysis. [ABSTRACT FROM AUTHOR]

An insulator‐based spin‐thermoelectric (STE) generator is composed of a thin paramagnetic metal (PM: Pt) layer for generating the STE voltage VSTE via the inverse spin Hall effect and a ferrimagnetic insulator (FMI) film or slab used for producing spin‐wave spin currents due to a temperature gradient ∇T$$ \nabla T $$. Yttrium iron garnet (YIG) is a key material used for the FMI of STE generators. We examined in detail the ferromagnetic resonance (FMR) properties of YIG (Y3Fe5O12), Bi‐substituted YIG (Y3‐xBixFe5O12) and Bi‐ and Al‐substituted YIG (Y3‐xBixFe5‐yAlyO12) films grown by liquid phase epitaxy (LPE). Bi‐substituted YIG films exhibited the large FMR damping and high STE voltage when the films were incorporated in the STE generator. The LPE‐grown Y2.35Bi0.65Fe5O12 film exhibited the FMR linewidth ΔH of 30 mT and the VSTE of 70 μV for the ∇T of 90×10−3°C/μm$$ 90\times {10}^{-3{}^{\circ}}C/\upmu \mathrm{m} $$. This paper comprehensively presents the origin of the STE generation in the insulator‐based generators on the basis of the results of FMR and STE measurements. To clarify the origin of STE generation in the generators fabricated from single crystal YIG (YIG, Bi‐substituted YIG and Bi‐ and Al‐substituted YIG) films grown by LPE, three principal factors are explained: (a) thermal energy transfer from the phonon system to the spin system, which strengthens the heat excitation of spin precession, through the spin–orbit coupling enhanced by the growth‐induced magnetic anisotropy of LPE‐grown YIG films, (b) in the YIG films incorporated in the STE generators, the generation of spin‐wave spin currents owing its origin to the ferromagnetic spin exchange interaction acting between neighboring spins due to ∇T$$ \nabla T $$, and (c) how the spin currents pumped into the Pt layer from the YIG film at the Pt/YIG bilayer interface are affected by the magnetization processes of single crystal YIG films. It is concluded that the STE generation of insulator‐based STE generators can be explained from a viewpoint of the spin dynamics under the effect of ∇T$$ \nabla T $$ in the Pt/YIG bilayer structure. © 2024 Institute of Electrical Engineers of Japan and Wiley Periodicals LLC. [ABSTRACT FROM AUTHOR]

SPring‐8‐II is a major upgrade project of SPring‐8 that was inaugurated in October 1997 as a third‐generation synchrotron radiation light source. This upgrade project aims to achieve three goals simultaneously: achievement of excellent light source performance, refurbishment of aged systems, and significant reduction in power consumption for the entire facility. A small emittance of 50 pm rad will be achieved by (1) replacing the existing double‐bend lattice structure with a five‐bend achromat one, (2) lowering the stored beam energy from 8 to 6 GeV, (3) increasing the horizontal damping partition number from 1 to 1.3, and (4) enhancing horizontal radiation damping by installing damping wigglers in long straight sections. The use of short‐period in‐vacuum undulators allows ultrabrilliant X‐rays to be provided while keeping a high‐energy spectral range even at the reduced electron‐beam energy of 6 GeV. To reduce power consumption, the dedicated, aged injector system has been shut down and the high‐performance linear accelerator of SACLA, a compact X‐ray free‐electron laser (XFEL) facility, is used as the injector of the ring in a time‐shared manner. This allows the simultaneous operation of XFEL experiments at SACLA and full/top‐up injection of the electron beam into the ring. This paper overviews the concept of the SPring‐8‐II project, the system design of the light source and the details of the accelerator component design. [ABSTRACT FROM AUTHOR]

Recent evidence suggests an association between age‐related osteoporosis and cellular senescence in the bone; however, the specific bone cells that play a critical role in age‐related osteoporosis and the mechanism remain unknown. Results revealed that age‐related osteoporosis is characterized by the loss of osteoblast Men1. Osteoblast‐specific inducible knockout of Men1 caused structural changes in the mice bones, matching the phenotypes in patients with age‐related osteoporosis. Histomorphometrically, Men1‐knockout mice femurs decreased osteoblastic activity and increased osteoclastic activity, hallmarks of age‐related osteoporosis. Loss of Men1 induces cellular senescence via mTORC1 activation and AMPK suppression, rescued by metformin treatment. In bone morphogenetic protein‐indued bone model, loss of Men1 leads to accumulation of senescent cells and osteoporotic bone formation, which are ameliorated by metformin. Our results indicate that cellular senescence in osteoblasts plays a critical role in age‐related osteoporosis and that osteoblast‐specific inducible Men1‐knockout mice offer a promising model for developing therapeutics for age‐related osteoporosis. [ABSTRACT FROM AUTHOR]

Evidence indicates that combinations of anti‐EGFR antibodies and KRAS p.G12C (c.34G>T) inhibitors can be an effective treatment strategy for advanced colorectal cancer. We hypothesized that KRAS c.34G>T (p.G12C)‐mutated colorectal carcinoma might be a distinct tumor subtype. We utilized a prospective cohort incident tumor biobank (including 1347 colorectal carcinomas) and detected KRAS c.34G>T (p.G12C) mutation in 43 cases (3.2%) and other KRAS mutations (in codon 12, 13, 61, or 146) in 467 cases (35%). The CpG island methylator phenotype (CIMP)‐low prevalence was similarly higher in KRAS c.34G>T mutants (52%) and other KRAS mutants (49%) than in KRAS‐wild‐type tumors (31%). KRAS c.34G>T mutants showed higher CIMP‐high prevalence (14%) and lower CIMP‐negative prevalence (33%) compared with other KRAS mutants (6% and 45%, respectively; p = 0.0036). Similar to other KRAS mutants, KRAS c.34G>T‐mutated tumors were associated with cecal location, non‐microsatellite instability (MSI)‐high status, BRAF wild type, and PIK3CA mutation when compared with KRAS‐wild‐type tumors. Compared with BRAF‐mutated tumors, KRAS c.34G>T mutants showed more frequent LINE‐1 hypomethylation, a biomarker for early‐onset colorectal carcinoma. KRAS c.34G>T mutants were not associated with other features, including the tumor tissue abundance of Fusobacterium nucleatum (F. animalis), pks+Escherichia coli, Bifidobacterium, or (enterotoxigenic) Bacteroides fragilis. Among 1122 BRAF‐wild‐type colorectal carcinomas, compared with KRAS‐wild‐type tumors, multivariable‐adjusted colorectal cancer‐specific mortality hazard ratios (95% confidence interval) were 1.82 (1.05–3.17) in KRAS c.34G>T (p.G12C)‐mutated tumors (p = 0.035) and 1.57 (1.22–2.02) in other KRAS‐mutated tumors (p = 0.0004). Our study provides novel evidence for clinical and tumor characteristics of KRAS c.34G>T (p.G12C)‐mutated colorectal carcinoma. [ABSTRACT FROM AUTHOR]

Background: In a randomized phase II/III trial (JCOG1008), weekly cisplatin (40 mg/m2) was non‐inferior to 3‐weekly cisplatin (100 mg/m2) for postoperative high‐risk head and neck cancer. We investigated how acute kidney injury (AKI), a major dose‐limiting toxicity effect of cisplatin, affects overall survival (OS). Methods: We analyzed 251 patients from JCOG1008 receiving chemoradiotherapy. AKI was defined based on AKI Network criteria (serum creatinine increase of ≥0.3 mg/dL or ≥1.5‐fold [≥ stage I]) within 30 days after completing chemoradiotherapy. OS in the two arms was compared according to AKI development using the log‐rank test. Results: The total incidence of AKI was lower in the weekly arm than in the 3‐weekly arm (38/122 [31.1%] vs. 56/129 [43.4%]). Additionally, stage II/III AKI occurred less frequently in the weekly arm than in the 3‐weekly arm (8/122 [6.6%] vs. 19/129 [14.7%]). Cisplatin doses were similar in the weekly arm for patients with and without AKI (median, 238.6 mg/m2 vs. 239.2 mg/m2; p = 0.94), but lower in the 3‐weekly arm for those who developed AKI (median, 276.3 mg/m2 vs. 297.4 mg/m2; p = 0.007). In the weekly arm, there was no difference in OS between patients with and without AKI (hazard ratio [HR], 1.06; 95% confidence interval [CI], 0.53 to 2.10). However, in the 3‐weekly arm, patients with AKI had poorer OS than those without AKI (HR, 1.83; 95% CI, 1.04 to 3.21). Conclusions: In this supplementary analysis of JCOG1008 data, AKI impacted the OS of patients with head and neck cancer undergoing postoperative chemoradiotherapy in the 3‐weekly arm but not in the weekly arm. Our results further endorse the utilization of weekly cisplatin at 40 mg/m2 in this setting. [ABSTRACT FROM AUTHOR]

Introduction: This study aimed to evaluate the efficacy and safety of atezolizumab combined with bevacizumab (Atez/Bev) compared to lenvatinib (LEN) as first‐line systemic therapy for patients with Barcelona Clinic Liver Cancer (BCLC) stage B hepatocellular carcinoma (HCC) exceeding the up‐to‐seven criteria threshold, who are typically unsuitable for transarterial chemoembolization (TACE). Methods: A retrospective analysis was conducted on 49 consecutive patients with HCC treated at Tokyo Metropolitan Komagome Hospital between May 2018 and October 2023. The patients were divided into two groups: the Atez/Bev group (21 patients) and the LEN group (28 patients). Eligibility criteria included Child‐Pugh A classification, no prior systemic therapy, and ineligibility for resection, ablation, or transplantation. Treatment outcomes were assessed through periodic imaging and laboratory tests, evaluating OS, PFS, ORR, and disease control rate (DCR). Results: Both groups demonstrated comparable baseline characteristics, with a median follow‐up of 15.4 months. No significant difference was observed in OS between the Atez/Bev and LEN groups (median OS: 19.80 vs. 22.20 months, p = 0.763). The median PFS was 10.23 months for Atez/Bev and 7.20 months for LEN (p = 0.343). There were no statistically significant differences in ORR or DCR between the two groups. Common adverse events included elevated AST and ALT levels, with no significant difference in the overall rate of adverse events between the groups. Conclusions: Atez/Bev and LEN demonstrated comparable efficacy and safety as first‐line systemic treatments for patients with BCLC stage B HCC exceeding the up‐to‐seven criteria. Both therapeutic options are viable for this population, though further large‐scale prospective studies are required to confirm these findings. [ABSTRACT FROM AUTHOR]

In‐vacuum undulators (IVUs), which have become an essential tool in synchrotron radiation facilities, have two technical challenges toward further advancement: one is a strong attractive force between top and bottom magnetic arrays, and the other is a stringent requirement on magnetic materials to avoid demagnetization. The former imposes a complicated design on mechanical and vacuum structures, while the latter limits the possibility of using high‐performance permanent magnets. To solve these issues, a number of technical developments have been made, such as force cancellation and modularization of magnetic arrays, and enhancement of resistance against demagnetization by means of a special magnetic circuit. The performance of a new IVU built upon these technologies has revealed their effectiveness for constructing high‐performance IVUs in a cost‐effective manner. [ABSTRACT FROM AUTHOR]

Aim: The Japanese Society for Respiratory Care and Rehabilitation, Japanese Association on Sarcopenia and Frailty, Japanese Society of Respiratory Physical Therapy, and Japanese Association of Rehabilitation Nutrition proposed the definition and diagnosis of respiratory sarcopenia using low respiratory muscle strength and appendicular skeletal muscle mass (ASM; ASM/height2) instead of respiratory muscle mass; however, these parameters have not been validated. This study aimed to confirm the validity of the respiratory sarcopenia definition proposed by these four professional organizations. Methods: Participants of our cohort study in 2015 of 468 community‐dwelling older people who were evaluated for sarcopenia and underwent spirometry were included in this analysis. We determined two respiratory sarcopenia models based on low skeletal muscle mass and respiratory muscle strength. Low skeletal muscle mass was defined by low ASM/height2, and low respiratory muscle strength was defined by peak expiratory flow rate (PEFR) or percentage of predicted PEFR (%PEFR). Survival status was assessed 5 years after baseline assessment (in 2020). To evaluate the validity of the cut‐off values for PEFR and %PEFR, we determined different respiratory sarcopenia models by sequentially varying the cut‐off values for each parameter, including ASM/height2, from high to low. We subsequently calculated the hazard ratio (HR) for mortality for each respiratory sarcopenia model using the Cox proportional hazards model. Additionally, we plotted the HR for each combination of cut‐off values for ASM/height2 and PEFR or %PEFR on a three‐dimensional chart to observe the relationship between the different cut‐off values and HR. Results: A total of 31 people died during the 5‐year observation period. With ASM/height2 cut‐off values of approximately 7.0 kg/m2 for men and 5.7 kg/m2 for women and %PEFR cut‐off values of 66–75%, respiratory sarcopenia was associated with mortality risk (HR, 2.36–3.27, point estimation range). Conclusions: The definition of respiratory sarcopenia by the four professional organizations is related to future health outcomes, and this definition is valid. Geriatr Gerontol Int 2024; 24: 948–953. [ABSTRACT FROM AUTHOR]

Background and Objective: The identification of factors associated with long‐term prognosis after community‐onset pneumonia in elderly patients should be considered when initiating advance care planning (ACP). We aimed to identify these factors and develop a prediction score model. Methods: Patients aged 65 years and older, who were hospitalized for pneumonia at nine collaborating institutions, were included. The prognosis of patients 180 days after the completion of antimicrobial treatment for pneumonia was prospectively collected. Results: The total number of analysable cases was 399, excluding 7 outliers and 42 cases with missing data or unknown prognosis. These cases were randomly divided in an 8:2 ratio for score development and testing. The median age was 82 years, and there were 68 (17%) deaths. A multivariate analysis showed that significant factors were performance status (PS) ≥2 (Odds ratio [OR], 11.78), hypoalbuminemia ≤2.5 g/dL (OR, 5.28) and dementia (OR, 3.15), while age and detection of antimicrobial‐resistant bacteria were not associated with prognosis. A scoring model was then developed with PS ≥2, Alb ≤2.5, and dementia providing scores of 2, 1 and 1 each, respectively, for a total of 4. The area under the curve was 0.8504, and the sensitivity and specificity were 94.6% and 61.7% at the cutoff of 2, respectively. In the test cases, the sensitivity and specificity were 91.7% and 63.1%, respectively, at a cutoff value of 2. Conclusion: Patients meeting this score should be considered near the end of life, and the initiation of ACP practices should be considered. We aimed to identify factors influencing the long‐term prognosis of elderly patients with pneumonia and to develop a prediction score model for the effective initiation of advance care planning. Performance status (PS) ≥2, hypoalbuminemia ≤2.5 g/dL and dementia were significant factors. The scoring model demonstrated 94.6% sensitivity and 61.7% specificity. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the effectiveness of yokukansan, a traditional Japanese medicine, as treatment for nocturia due to sleep disorders. Methods: In this study, we included patients diagnosed with nocturia due to sleep disorders, evaluated using the Pittsburgh Sleep Quality Index (PSQI). Participants received 2.5 g of yokukansan, three times daily, for 12 weeks. We evaluated the changes in the overactive bladder (OAB) symptom score (OABSS), hours of undisturbed sleep (HUS), and PSQI score. In addition, patients were categorized based on the severity of their sleep disorders, and we divided patients into two groups according to whether the severity of the disorder was downgraded after treatment: the improved and unchanged groups. Results: Among 35 patients with a mean ± standard deviation age of 73.2 ± 10.5 years, yokukansan administration was associated with significant improvements in nighttime urinary frequency (from 3.8 ± 2.1 to 2.1 ± 1.9), total OABSS score (from 4.9 ± 1.8 to 2.9 ± 1.9), OABSS urgency score (from 1.3 ± 1.0 to 0.7 ± 0.9), HUS (from 2.2 ± 0.6 to 3.5 ± 1.1 h), and global PSQI score (from 11.9 ± 3.1 to 10.0 ± 1.4; all p < 0.001). In addition, significant improvements were noted in both the improved and unchanged groups in terms of the total OABSS, nocturia, and urgency scores. Furthermore, yokukansan treatment was related to improved global PSQI scores in both groups (improved group: from 10.8 ± 0.7 to 8.6 ± 0.5, p = 0.001; unchanged group: from 12.3 ± 3.4 to 10.4 ± 1.3, p = 0.004). Conclusion: Yokukansan may effectively ameliorate nocturia due to sleep disorders. [ABSTRACT FROM AUTHOR]

This study investigates the potential impact of Solar Energetic Particles (SEPs) on the V0 layer of the Venus ionosphere. Electron density profiles obtained from radio occultation experiments conducted by the Venus Express (VEX) and Akatsuki missions were utilized for this purpose. Background data from the Analyzer of Space Plasma and EneRgetic Atoms (ASPERA‐4) aboard VEX were used to detect SEP events. Additionally, observations from the Space Environment Monitor (SEM) suite onboard the Geostationary Operational Environmental Satellite (GOES) during alignments of Venus, Earth, and the Sun were also considered. Our findings indicate that while SEPs may contribute to the formation of the V0 layer, they are not the main driving force in the Venusian ionosphere. Plain Language Summary: The Venusian ionosphere shows sporadic enhancements in electron density around 110 km altitude. Despite extensive investigation, the exact cause of its sporadic presence remains elusive. Previous studies have explored various theories, including meteoric influences, gravity waves, and the impact of minor atmospheric constituents such as NO, O2, C, Ar, H2, and H. However, none have conclusively explained its formation mechanism. In this study, we have investigated the potential influence of Solar Energetic Particles (SEPs) on the V0 layer. By analyzing electron density profiles obtained from VEX/Akatsuki missions, hot plasma measurements by ASPERA‐4 onboard VEX, and SEM suite onboard GOES to identify SEP events, we surmise that while SEPs may contribute to the formation of the V0 layer, they are not the primary driving force in the Venusian ionosphere. Key Points: The Impact of solar energetic particle (SEP) events on the formation of V0 layers in the Venusian ionosphere has been exploredEnhanced ionization is seen above the V2 layer peak whenever a V0 layer seen in the Venus ionosphereSEPs and enhanced ionization at 110 km altitudes, however, are not correlated [ABSTRACT FROM AUTHOR]

Biomolecules containing adenosine di‐ or triphosphate (ADP or ATP) are crucial for diverse biological processes. Synthesis of these biomolecules and development of their chemical probes are important to elucidate their functions. Enabling reproducible and high‐yielding access to these ADP‐ and ATP‐containing molecules via conventional P(III)‐P(V) and P(V)‐P(V) coupling reactions is challenging owing to water content in highly polar phosphate‐containing substrates. Herein, we report an efficient and reliable method for protecting‐group‐free P(V)‐P(V) coupling reaction through in situ activation of phosphates using hydrolysis‐stable 2‐[N‐(2‐methylimidazoyl)]‐1,3‐dimethylimidazolinium chloride (2‐MeImIm‐Cl), providing the corresponding electrophilic P(V) intermediates for subsequent nucleophilic attack using their coupling partners. This P(V)‐P(V) coupling reaction proceeded even in a wet reaction medium and showed a broad substrate scope, accommodating protecting‐group‐free synthesis of ADP‐ribose and nicotinamide adenine diphosphate analogs, ATP‐containing biomolecules, and ADP‐ribosyl peptides. [ABSTRACT FROM AUTHOR]

Introduction: This study evaluates surgical outcomes of minimally invasive Ivor Lewis esophagectomy (ILE) for esophageal and esophagogastric cancer, with the comparison of the robotic approach (RA) and the conventional minimally invasive approach (CA). Methods: Selected patients who underwent minimally invasive ILE for esophageal cancer were included between January 2017 and December 2023. We retrospectively investigated the patients' background characteristics and the short‐term surgical outcomes. Results: In this period, among a total of 840 esophagectomies, 81 patients (9.6%) underwent minimally invasive ILE, consisting of 24 cases with RA and 57 with CA. The major indications for ILE were adenocarcinoma of the distal esophagus or esophagogastric junction and patients with prior head and neck cancer treatment. Among these thoracic approaches, there were no significant differences in the patients' indications and characteristics, including age, histology, tumor location, clinical TNM stage, and preoperative therapy. Compared with the CA group, no anastomotic leakage was observed in the RA group (17.5% vs. 0, p =.035). Rates of total postoperative complications and length of hospital stay also tended to be reduced in the RA group but did not reach significance. Conclusion: In the Ivor Lewis esophagectomy with a side‐to‐side linear‐stapled anastomosis, the fully robotic approach has the potential to powerfully reduce anastomotic leakage compared to the conventional minimally invasive approach. [ABSTRACT FROM AUTHOR]

Background: Although surgical resection is the only curative treatment for biliary tract cancer, in some cases, the disease is diagnosed as unresectable at initial presentation. There are few reports of conversion surgery after the initial treatment for unresectable locally advanced biliary tract cancer. This study aimed to evaluate the efficacy and safety of conversion surgery in patients with initially unresectable locally advanced biliary tract cancer. Methods: We retrospectively collected clinical data from groups of patients in multiple centers belonging to the Japanese Society of Hepato‐Biliary‐Pancreatic Surgery and Korean Association of Hepato‐Biliary‐Pancreatic Surgery. We analyzed two groups of prognostic factors (pretreatment and surgical factors) and their relation to the treatment outcomes. Results: A total of 56 patients with initially unresectable locally advanced biliary tract cancer were enrolled in this study of which 55 (98.2%) patients received chemotherapy, and 16 (28.6%) patients received additional radiation therapy. The median time from the start of the initial treatment to resection was 6.4 months. Severe postoperative complications of Clavien‐Dindo grade III or higher occurred in 34 patients (60.7%), and postoperative mortality occurred in five patients (8.9%). Postoperative histological results revealed CR in eight patients (14.3%). The median survival time from the start of the initial treatment in all 56 patients who underwent conversion surgery was 37.7 months, the 3‐year survival rate was 53.9%, and the 5‐year survival rate was 39.1%. Conclusions: Conversion surgery for initially unresectable locally advanced biliary tract cancer may lead to longer survival in selected patients. However, more precise preoperative safety evaluation and careful postoperative management are required. [ABSTRACT FROM AUTHOR]

L‐type amino acid transporter 1 (LAT1) is specifically expressed in many malignancies, contributes to the transport of essential amino acids, such as leucine, and regulates the mammalian target of rapamycin (mTOR) signaling pathway. We investigated the expression profile and functional role of LAT1 in prostate cancer using JPH203, a specific inhibitor of LAT1. LAT1 was highly expressed in castration‐resistant prostate cancer (CRPC) cells, including C4‐2 and PC‐3 cells, but its expression level was low in castration‐sensitive LNCaP cells. JPH203 significantly inhibited [14C] leucine uptake in CRPC cells but had no effect in LNCaP cells. JPH203 inhibited the proliferation, migration, and invasion of CRPC cells but not of LNCaP cells. In C4‐2 cells, Cluster of differentiation (CD) 24 was identified by RNA sequencing as a novel downstream target of JPH203. CD24 was downregulated in a JPH203 concentration‐dependent manner and suppressed activation of the Wnt/β‐catenin signaling pathway. Furthermore, an in vivo study showed that JPH203 inhibited the proliferation of C4‐2 cells in a castration environment. The results of this study indicate that JPH203 may exert its antitumor effect in CRPC cells via mTOR and CD24. [ABSTRACT FROM AUTHOR]

INTRODUCTION: To detect early cognitive impairment in community‐dwelling older adults, this study explored the viability of artificial intelligence (AI)‐assisted linear acceleration and angular velocity analysis during walking. METHODS: This cross‐sectional study included 879 participants without dementia (female, 60.6%; mean age, 73.5 years) from the 2011 Comprehensive Gerontology Survey. Sensors attached to the pelvis and left ankle recorded the triaxial linear acceleration and angular velocity while the participants walked at a comfortable speed. Cognitive impairment was determined using Mini‐Mental State Examination scores. Deep learning models were used to discern the linear acceleration and angular velocity data of 12,302 walking strides. RESULTS: The models' average sensitivity, specificity, and area under the curve were 0.961, 0.643, and 0.833, respectively, across 30 testing datasets. DISCUSSION: AI‐enabled gait analysis can be used to detect signs of cognitive impairment. Integrating this AI model into smartphones may help detect dementia early, facilitating better prevention. Highlights: Artificial intelligence (AI)‐enabled gait analysis can be used to detect the early signs of cognitive decline.This AI model was constructed using data from a community‐dwelling cohort.AI‐assisted linear acceleration and angular velocity analysis during gait was used.The model may help in early detection of dementia. [ABSTRACT FROM AUTHOR]

Exploring the nature of human intelligence and behavior is a longstanding pursuit in cognitive neuroscience, driven by the accumulation of knowledge, information, and data across various studies. However, achieving a unified and transparent interpretation of findings presents formidable challenges. In response, an explainable brain computing framework is proposed that employs the never‐ending learning paradigm, integrating evidence combination and fusion computing within a Knowledge‐Information‐Data (KID) architecture. The framework supports continuous brain cognition investigation, utilizing joint knowledge‐driven forward inference and data‐driven reverse inference, bolstered by the pre‐trained language modeling techniques and the human‐in‐the‐loop mechanisms. In particular, it incorporates internal evidence learning through multi‐task functional neuroimaging analyses and external evidence learning via topic modeling of published neuroimaging studies, all of which involve human interactions at different stages. Based on two case studies, the intricate uncertainty surrounding brain localization in human reasoning is revealed. The present study also highlights the potential of systematization to advance explainable brain computing, offering a finer‐grained understanding of brain activity patterns related to human intelligence. [ABSTRACT FROM AUTHOR]

Background: Asparaginase is essential for treating T‐cell acute lymphoblastic leukemia (T‐ALL). Despite the ongoing debate on whether T‐ALL and T‐cell lymphoblastic lymphoma (T‐LBL) are the same disease entity or two distinct diseases, patients with T‐LBL often receive the same or similar treatment protocols as those with T‐ALL. Methods: The outcomes of patients with or without L‐asparaginase discontinuation were retrospectively analyzed among four national protocols: Japan Association of Childhood Leukemia Study (JACLS) ALL‐02 and ALL‐97 for T‐ALL and Japanese Pediatric Leukemia/Lymphoma Study Group ALB‐NHL03 and JACLS NHL‐98 for T‐LBL. The hazard ratio (HR) was calculated with the Cox regression model by considering L‐asparaginase discontinuation as a time‐dependent variable. Results: In total, 199 patients with T‐ALL, and 133 patients with T‐LBL were included. L‐asparaginase discontinuation compromised event‐free survival (EFS) of T‐ALL patients (ALL‐02: HR 3.32, 95% confidence interval [CI] 1.40–7.90; ALL‐97: HR 3.39, 95%CI 1.19–9.67). Conversely, EFS compromise was not detected among T‐LBL patients (ALB‐NHL03: HR 1.39, 95%CI 0.41–4.68; NHL‐98: HR 0.92, 95%CI 0.11–7.60). Conclusion: The effects of L‐asparaginase discontinuation differed between T‐ALL and T‐LBL. We assume that the differential impact results from (1) the inherent differential response to L‐asparaginase between them and/or (2) a less stringent assessment of early treatment response in T‐LBL than in T‐ALL. Given the poor salvage rate of refractory or relapsed T‐ALL and T‐LBL, optimization of the frontline therapy is critical, and the current study provides a new suggestion for further treatment modifications. However, larger studies in contemporary intensified treatment protocols are required. [ABSTRACT FROM AUTHOR]

Adenine diphosphate (ADP)‐ribosylation catalyzed by bacterial toxins is the addition of an ADP‐ribose moiety to specific amino acid residues in target proteins such as arginine, asparagine, glutamine, and histidine through 1,2‐cis(α)‐glycosidic bond formation. ADP‐ribosylation modifies host cell functions, altering normal cellular processes to facilitate their survival, and replication. Despite the development of click chemistry and solid‐phase peptide synthesis‐based approaches, the synthesis of structurally well‐defined naturally occurring N‐linked ADP‐ribosyl molecules remains challenging. Herein, we report a direct and α‐selective N‐ADP‐ribosylation using unprotected β‐ADP‐ribosyl azide and triphenylphosphine esters through traceless Staudinger ligation. The stereoselectivity of this protecting‐group‐free N‐ADP‐ribosylation was validated by enzymatic degradation experiment and high‐performance liquid chromatography, referencing synthetic standards. This method facilitated the facile and rapid synthesis of N‐ADP‐ribosyl acetamide, biotin, fluorescent dye, amino acids, and tripeptide with complete α‐selectivity and moderate yields (37–55 %). [ABSTRACT FROM AUTHOR]

Aims: The application of indices in the context of metabolic dysfunction‐associated steatotic liver disease (MASLD) remains unexplored. We aimed to validate the ability of alanine aminotransferase (ALT), fatty liver index (FLI), and hepatic steatosis index (HSI) to identify MASLD during health checkups. Methods: We recruited 627 participants and utilized their health checkup data and ultrasound to assess the potential of using ALT, FLI, and HSI as indices for MASLD; this was indicated by the area under the curve (AUC) and restricted cubic spline (RCS) model. The optimal, rule‐out (sensitivity ≥90%), and rule‐in (specificity ≥90%) cutoff values of each index for identifying MASLD were reported. Results: Among participants with a median age of 46 years, the prevalence of MASLD was 28% in total (38% in males and 18% in females). RCS models confirmed a linear association between indices and MASLD. ROC analyses indicated that the AUC of ALT in identifying MASLD was 0.79 for the total cohort, 0.81 for males, and 0.69 for females. The optimal, rule‐out, and rule‐in cutoff values for ALT were 21, 13, and 29, respectively. Similarly, the AUC of FLI/HSI in identifying MASLD was 0.90/0.88 for the total cohort, 0.86/0.85 for males, and 0.93/0.90 for females. Considering the reference cutoff values, distinct cutoff values were observed between the sexes for FLI, while HSI had similar cutoff values. Conclusion: This study demonstrated that ALT > 30 IU/L is a reasonable cutoff value to rule‐in MASLD. ALT, FLI, and HSI are reliable indices for identifying MASLD during health checkups. [ABSTRACT FROM AUTHOR]

Background: With the entire papilla preservation (EPP) technique, it is possible to perform regenerative therapy without incisions in the interdental papilla and to reduce the risk of papillary rupture. However, one limitation of the EPP is the sole access from the buccal side. Here, we present a case of periodontitis treated by the combination regenerative therapy employing the Double‐sided (buccal‐palatal) EPP (DEPP) technique, which adds a palatal vertical incision to the EPP. Methods: A patient with 1–2 wall intrabony defects received the regenerative therapy using recombinant human fibroblast growth factor (rhFGF)‐2 and carbonate apatite (CO3Ap). Using the DEPP technique, vertical incisions at buccal and palatal aspects were placed to gain adequate access to the 1–2 wall intrabony defects between #11 and #12 without incision in the interdental papilla. After debridement, rhFGF‐2 and CO3Ap were applied to the defect. Periodontal clinical parameters and radiographic images were evaluated at the first visit, following initial periodontal therapy (baseline), 6, 9, and 12 months postoperatively. Results: Wound healing was uneventful. Scarring of the incision lines was minimal. At 12 months postoperatively, probing depth reduction was 4 mm, clinical attachment gain was 4 mm, and gingival recession was not observed. An improvement in radiopacity in the previous bone defect was observed. Conclusion: The DEPP is an innovative technique that allows approaching from both the buccal and palatal sides while ensuring flap extensibility without compromising the interdental papilla. This report suggests that the combination of regenerative therapy with the DEPP may be promising in the treatment of intrabony defects. Key points: Why is this case new information?The DEPP allows a direct visual approach to a 1–2 wall intrabony defect extending from the buccal to palatal sides, and increases flap extensibility, without compromising the papilla. What are the keys to the successful management of this case?Assessment of three‐dimensional bone defect morphology is required. Computed tomography images are very useful. The flap elevation just under the interdental papilla should be carefully performed with a small excavator to avoid damage to the interdental papilla. What are the primary limitations to success in this case?Despite the addition of a palatal incision, it was not possible to obtain complete flexibility of the palatal gingiva. Caution must be taken in a case in which the distance between the interdental papilla is narrow. Even if the interdental papilla is ruptured during the operation, recovery is possible by continuing the operation and suturing the rupture at the end. [ABSTRACT FROM AUTHOR]

Background: This phase 2b/3, randomized, placebo‐controlled trial explored the efficacy and evaluated the safety of ensitrelvir. This trial involved individuals with asymptomatic infection with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) and patients with mild symptoms of coronavirus disease 2019 (COVID‐19). Methods: The trial was conducted at 57 medical institutions in Japan, South Korea, and Vietnam (study period: January 6–August 14, 2022). Eligible participants were randomized (1:1:1) to the ensitrelvir 125‐mg, ensitrelvir 250‐mg, or placebo group, received the allocated intervention orally, and were followed up until Day 28. Participants self‐rated the severity of 14 typical COVID‐19 symptoms and recorded the data in an electronic diary. Results: In total, 572 participants (194, 189, and 189 in the ensitrelvir 125‐mg, ensitrelvir 250‐mg, and placebo groups, respectively) were included in the intention‐to‐treat population. Ensitrelvir 125‐mg group observed a 77% reduction in the risk of developing any of the 14 COVID‐19 symptoms or fever and a 29% reduction in the risk of worsening of such symptoms or fever versus placebo (statistically nonsignificant). The viral RNA, viral titer, and time to infectious viral clearance observed a statistically significant decrease versus placebo. Most treatment‐related adverse events (TEAEs) were mild to moderate in severity, and the most common TEAE observed across groups was a decrease in high‐density lipoprotein. Conclusions: Our exploratory results suggest a potential reduction in the risk of development or worsening of COVID‐19 symptoms with ensitrelvir. Ensitrelvir showed antiviral efficacy and was well tolerated. Trial Registration: Japan Registry of Clinical Trials identifier: jRCT2031210350. [ABSTRACT FROM AUTHOR]

Aims: Remote dielectric sensing (ReDS) represents a contemporary non‐invasive technique reliant on electromagnetic energy to quantify pulmonary congestion. Its prognostic significance within the context of heart failure (HF) patients remains elusive. This study aimed to assess the prognostic implications of residual pulmonary congestion, as gauged by the ReDS system, among patients admitted due to congestive HF. Methods and results: We enrolled hospitalized HF patients who underwent ReDS assessments upon admission and discharge in a blinded manner, independent of attending physicians. We evaluated the prognostic impact of the ReDS ratio between admission and discharge on the primary outcome, which encompassed all‐cause mortality and HF‐related re‐hospitalizations. A cohort of 133 patients (median age 78 [72, 84] years, 78 male [59%]) was included. Over a median observation period of 363 days post‐index discharge, an escalated ReDS group (ReDS ratio > 100%), determined through statistical calculation, emerged as an independent predictor of the primary outcome, exhibiting an adjusted hazard ratio of 4.37 (95% confidence interval 1.13–16.81, P = 0.032). The cumulative incidence of the primary outcome was notably higher in the increased ReDS group compared with the decreased ReDS group (50.1% vs. 8.5%, P = 0.034). Conclusions: Elevated ReDS ratios detected during the index hospitalization could serve as a promising prognostic indicator in HF patients admitted for treatment. The clinical ramifications of ReDS‐guided HF management warrant validation in subsequent studies. [ABSTRACT FROM AUTHOR]

Background: A decrease in the regenerative capacity of age‐damaged liver tissue has been reported. Liver progenitor cells may play an important role in the regeneration of injured livers. In the present study we aimed to investigate improvements in the regenerative capacity of age‐damaged livers using chemically induced liver progenitors (CLiPs) derived from mature hepatocytes. Methods: Old (>90 weeks) and young (<20 weeks) mice underwent 70% hepatectomy, with or without trans‐splenic CLiP administration. The residual liver/bodyweight (LW/BW) ratio was measured on postoperative days 1 and 7, and changes in liver regeneration and histology were evaluated. Results: At 7 days post‐hepatectomy, LW/BW ratios were significantly better in CLiP‐treated old mice than in untreated old mice (p =.02). By contrast, no effect of CLiP transplantation was observed in young mice (p =.62). Immunofluorescence staining of liver tissue after CLiP administration showed an increase in Ki67‐positive cells (p <.01). Flow cytometry analysis of green fluorescent protein‐labeled CLiPs indicated that transplanted CLiPs differentiated into mature hepatocytes and were present in the recipient liver. Conclusions: CLiP transplantation appears to ameliorate the age‐related decline in liver regeneration in mice. [ABSTRACT FROM AUTHOR]

The Royal Prince Alfred Hospital Mpox Vaccination Clinic opened in response to the 2022 multicountry mpox outbreak. A total of 9500 vaccinations were administered intradermally and subcutaneously during the first 16 weeks of clinic operation. The rate of adverse events was 0.1%. Compared to people who received the vaccine intradermally, those who received it subcutaneously were more likely to be aged 30–39 years (P = 0.047), sexual partners of gay and bisexual men (P < 0.001), eligible for Medicare (P < 0.001) and born in the Philippines (P = 0.01) or Malaysia (P = 0.04). [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to investigate the impact of memory function and social capital on depressive symptoms during the COVID‐19 pandemic among older adults in rural Japan. Methods: A retrospective study with longitudinal data was conducted during COVID‐19 from May 2021 to November 2021 (T2) in Kurogawa, Japan. The candidate population for this study was 145 with the following requirements: (1) older individuals aged 65 years or above who were registered in the Kurogawa study, and (2) those with previous data (from November 2016 to February 2020; T1 as pre‐pandemic). Memory function was assessed using the Wechsler Memory Scale‐Revised Logical Memory II delayed recall part A (LM II‐DR). Depressive symptoms were assessed using the Japanese version of the 15‐item Geriatric Depression Scale (GDS‐15). Social capital was evaluated through civic participation, social cohesion, and reciprocity. Fear of the COVID‐19 infection (FCV‐19S) was evaluated. Results: The final analysis included 96 participants (mean age = 81.0 years, SD = 4.8) Multivariate analysis for GDS‐15 score by Mixed Model Repeated Measures (MMRM) revealed significant associations between LM II‐DR (β = −0.13, 95% CI: −0.21–0.05, p = 0.002) and FCV‐19S during COVID‐19 (β = 0.08, 95% CI: 0.01–0.15, p = 0.02) with GDS‐15 score. However, civic participation, social cohesion and reciprocity were not associated with GDS‐15 score. Conclusions: Among older adults in rural Japan, memory function and fear of the COVID‐19 infection were significantly associated with depressive symptoms in MMRM analysis. However, social capital was not associated with depressive symptoms. This highlights the need to address memory function and fear of the COVID‐19 infection in interventions for older adults during crises like the COVID‐19 pandemic. Key points: This study examined the impact of memory function and social capital on depressive symptoms during the COVID‐19 pandemic among older adults in rural Japan.LM II‐DR and FCV‐19S were significantly associated with GDS‐15 scores, under considering within‐individual correlation and time points (before and during COVID‐19) in Mixed Model Repeated Measures (MMRM) analysis.However, civic participation, social cohesion and reciprocity were not associated with depressive symptoms in MMRM analysis.This highlights the need to address memory function and fear of the COVID‐19 infection in interventions for older adults during crises such as the COVID‐19 pandemic. [ABSTRACT FROM AUTHOR]

Successful treatment of pediatric cancers often results in long‐term health complications, including potential effects on fertility. Therefore, assessing the male reproductive toxicity of anti‐cancer drug treatments and the potential for recovery is of paramount importance. However, in vivo evaluations are time‐intensive and require large numbers of animals. To overcome these constraints, we utilized an innovative organ culture system that supports long‐term spermatogenesis by placing the testis tissue between a base agarose gel and a polydimethylsiloxane ceiling, effectively mirroring the in vivo testicular environment. The present study aimed to determine the efficacy of this organ culture system for accurately assessing testicular toxicity induced by cisplatin, using acrosin‐green fluorescent protein (GFP) transgenic neonatal mouse testes. The testis fragments were treated with different concentrations of cisplatin‐containing medium for 24 h and incubated in fresh medium for up to 70 days. The changes in tissue volume and GFP fluorescence over time were evaluated to monitor the progression of spermatogenesis, in addition to the corresponding histopathology. Cisplatin treatment caused tissue volume shrinkage and reduced GFP fluorescence in a concentration‐dependent manner. Recovery from testicular toxicity was also dependent on the concentration of cisplatin received. The results demonstrated that this novel in vitro system can be a faithful replacement for animal experiments to assess the testicular toxicity of anti‐cancer drugs and their reversibility, providing a useful method for drug development. Assessing the male reproductive toxicity of anti‐cancer drugs and the potential for recovery is of paramount importance; however, in vivo evaluations are time‐intensive and require large numbers of animals. We utilized an innovative organ culture system that mirrors the in vivo testicular environment to determine its efficacy in accurately assessing testicular toxicity induced by cisplatin. The results demonstrate that this system can be a faithful replacement for animal experiments to assess the testicular toxicity of anti‐cancer drugs and their reversibility. [ABSTRACT FROM AUTHOR]

Objective: Adrenocortical carcinoma is a rare condition, with limited comprehensive reports from Japan. This study aimed to review Japan's data on adrenocortical carcinoma by assessing information from 46 patients—with adrenocortical carcinoma across 10 Japanese university hospitals. Methods: We conducted a retrospective multi‐institutional analysis of the clinical characteristics of adrenocortical carcinoma in Japan. We evaluated data from 46 patients across 10 university hospitals over 10 years and analyzed the relationship between clinicopathological characteristics and overall survival. Results: Five‐ and 10‐year overall survival rates were 59% and 53%, respectively. Overall survival was significantly different among the tumor–node–metastasis system for adrenocortical carcinoma of the American Joint Committee on Cancer/International Union Against Cancer, with the worst prognosis in stage IV (p = 0.0044). In our cohort, neither the Weiss score nor the Ki‐67 proliferation index correlated with overall survival. Adjuvant treatment did not yield improved overall survival, whereas resection of the primary tumor in stage IV disease was significantly associated with improved overall survival (p = 0.0262). Out of the cases evaluated for plasma hormones, plasma cortisol, aldosterone, testosterone, and DHEA‐S levels were measured at 23%, 42%, 29%, and 62%, respectively, demonstrating higher levels than the upper normal limits. Conclusion: Patients with stage IV adrenocortical carcinoma had a poor prognosis; however, resection of the primary tumor in stage IV disease was associated with prolonged survival. The results of this study are expected to contribute to future treatment of adrenocortical carcinoma in Japan. [ABSTRACT FROM AUTHOR]

Genome‐wide association studies (GWAS) have facilitated a substantial and rapid increase in the number of confirmed genetic susceptibility variants for complex diseases. Approximately 700 variants predisposing individuals to the risk for type 2 diabetes have been identified through GWAS until 2023. From 2018 to 2022, hundreds of type 2 diabetes susceptibility loci with smaller effect sizes were identified through large‐scale GWAS with sample sizes of 200,000 to >1 million. The clinical translation of genetic information for type 2 diabetes includes the development of novel therapeutics and risk predictions. Although drug discovery based on loci identified in GWAS remains challenging owing to the difficulty of functional annotation, global efforts have been made to identify novel biological mechanisms and therapeutic targets by applying multi‐omics approaches or searching for disease‐associated coding variants in isolated founder populations. Polygenic risk scores (PRSs), comprising up to millions of associated variants, can identify individuals with higher disease risk than those in the general population. In populations of European descent, PRSs constructed from base GWAS data with a sample size of approximately 450,000 have predicted the onset of diseases well. However, European GWAS‐derived PRSs have limited predictive performance in non‐European populations. The predictive accuracy of a PRS largely depends on the sample size of the base GWAS data. The results of GWAS meta‐analyses for multi‐ethnic groups as base GWAS data and cross‐population polygenic prediction methodology have been applied to establish a universal PRS applicable to small isolated ethnic populations. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Sturge–Weber syndrome (SWS) is a neurocutaneous syndrome characterized by angiomas. This report presents airway management using submental intubation in sagittal split ramus osteotomy under general anesthesia and aimed to explore better anesthetic management for avoiding the rupture of angiomas in a patient with SWS. [ABSTRACT FROM AUTHOR]