Search Results (66,601)

A revised two-stage model of preeclampsia is proposed, centering on an autophagy-dependent requirement for extravillous trophoblast entry into the proximal one-third of the myometrium. The One-Third Myometrium Enigma, introduced here, denotes the unresolved physiological rule that early placentation requires trophoblasts to traverse decidua and reach the proximal one-third of myometrium under hypoxia and nutrient scarcity. The hypothesis posits a timed rise in basal autophagy to sustain trophoblast energy homeostasis and invasion, accompanied by TFEB-driven lysosomal programs that enable villous cytotrophoblast syncytialization. Autophagic dysfunction could contribute to shallow invasion, chronic placental hypoxia, fetal growth restriction, and release of placental injury signals preceding maternal syndrome. Potential failure modes include reduced autophagic flux due to inhibition of autophagosome to lysosome fusion or mistimed persistence of hypoxia signaling, such as prolonged HIF-1α activity. Collectively, this evidence suggests that impaired autophagy is a testable contributor to preeclampsia pathogenesis. Predictions include early risk stratification with circulating autophagy markers and extracellular vesicle microRNAs, and therapeutic benefit from autophagy modulation that targets AMPK or mTOR or activates TFEB with safety constraints. This framework reframes preeclampsia as a disorder of placental quality control and specifies where and when autophagy may be required. Full article

In this paper, we investigate the inter-event times of frequent words observed in 17 academic books, where the inter-event time is defined as the number of sentences between two successive appearances of a given word. Our results show that the distributions of inter-event times for frequent words can be classified into three types: the exponential distribution, the q-exponential distribution, and the power-law distribution. To examine the generative mechanisms underlying these three types, we conducted text generation simulations and found that combining two mechanisms for word selection—priority-based selection and randomized selection—is sufficient to reproduce the observed three distribution types. In particular, the priority-based selection mechanism, in which words for a constructed sentence are chosen mechanically according to predefined priorities assigned to each word, is identified as the underlying mechanism of the power-law distribution of inter-event times. We also discuss in detail the relationship between the priority-based selection mechanism and the multivariate Hawkes process, which effectively captures mutual correlations among occurrences of important words. Full article

Aesthetic patients in East Asia are commonly concerned about small apparent eye size. Simultaneous treatment of the glabellar and lateral canthal areas with botulinum neurotoxin has potential to provide improvements. This case series evaluated changes in eye size following treatment of these two areas using standard on-label doses of onabotulinumtoxinA in patients from Japan or China. Outcomes were assessed based on standardised frontal photographs taken before and after treatment (at rest, maximum smile, and maximum frowning). Changes in eye size were examined using a 4-point Likert scale, as evaluated by three independent groups: six injectors; six non-injecting observers; and treated patients. Furthermore, improvements in overall facial impression were analysed using two established tools: ‘emotional attributes’ and ‘social attributes’. Twenty East Asian subjects were included (n = 17 women; mean age: 37.5 ± 6.4 years). The majority of evaluators in all three groups rated patients’ eye size as ‘significantly’ or ‘mildly’ improved post-treatment, whether assessed at rest, when smiling, or during frowning. Furthermore, almost all evaluators noted improvements in one or more emotional and social attributes. This approach has significant potential as a culturally adapted aesthetic technique for improving eye size in East Asian patients. Larger multicentre studies are warranted. Full article

Total hip arthroplasty (THA) reliably restores function, yet instability remains a clinically relevant complication. Increasing evidence indicates that postoperative stability is strongly influenced by the dynamic spine–pelvis–hip interaction, which modulates functional acetabular orientation across postures. This narrative review summarizes current evidence on postoperative spinopelvic alignment changes after THA with emphasis on temporal patterns, underlying mechanisms, and predictive factors. Early after THA, restoration of hip motion can partially normalize hip-driven compensatory patterns, however substantial interindividual variability persists. Mid- to long-term follow-up shows that pelvic orientation continues to evolve, particularly progressive posterior pelvic tilt in standing, largely driven by aging and spinal degeneration, with acceleration in older patients and those with spinal pathology. Prediction of postoperative pelvic behavior requires integrated assessment of pelvic orientation, spinal alignment and mobility, contralateral hip status, and whether imbalance is hip-driven versus spine-driven. Although classification- and model-based approaches can estimate postoperative pelvic tilt, clinically meaningful prediction uncertainty remains, supporting a strategy focused on risk stratification and adaptive preoperative planning. Full article

The threat of antimicrobial resistance in aquatic environments, particularly riverine systems, is escalating, in part due to effluents discharged from healthcare facilities. This issue has been recognized not only in Japan but also in other Asian countries such as Indonesia and Nepal. Nevertheless, existing research remains limited, prompting an investigation into the prevalence of antimicrobial-resistant bacteria in the upstream and downstream sites of environmental rivers. In 2024, six samples were collected from three rivers in Hyogo Prefecture, Japan; five samples from five river sites in Indonesia; and three samples from downstream sites of rivers in Kathmandu, Nepal. These samples were subjected to selective culture–based Next Generation Sequencing and resistome analyses, based exclusively on the selective culture of bacteria propagated on CHROMagar ESBL plates. In Japan and Indonesia, Pseudomonas, Stenotrophomonas and Acinetobacter were frequently detected, whereas Klebsiella was overwhelmingly predominant in Nepal. Significant differences in the similarity of bacterial community composition among sampling sites across the three countries were observed (p < 0.001). Notably, Nepal exhibited the highest abundance level of antimicrobial resistance genes among the three countries, largely consisting of β-lactam resistance genes. In conclusion, these analyses elucidated substantial differences in bacterial community composition and degrees of environmental contamination. Full article

Accurate numerical reproduction of contact line dynamics on three-dimensional curved solid surfaces remains a challenging issue in multiphase flow simulations. In this study, a wetting boundary condition applicable to curved surfaces is developed within a three-dimensional phase-field lattice Boltzmann framework. The proposed method extends an existing curved-surface wetting model and focuses on improving the evaluation of interface normals and order-parameter gradients on Cartesian lattices, while preserving the compact computational stencils and efficiency inherent to the lattice Boltzmann method. Three-dimensional simulations of liquid spreading on a concave spherical surface and droplet spreading on a convex solid sphere are performed over a wide range of prescribed contact angles. The results show that the proposed method eliminates nonphysical behaviors observed with conventional staircase-based boundary conditions, such as droplet sliding along the solid surface and droplet detachment into the surrounding gas phase. In the convex spherical surface cases, the droplet height converges stably to equilibrium through damped oscillations, and the equilibrium droplet shapes show good agreement with theoretical predictions derived from geometric considerations under zero-gravity conditions over a broad range of contact angles. These results demonstrate that the proposed wetting boundary condition can accurately reproduce wetting phenomena on three-dimensional curved solid surfaces. Full article

Background/Objectives: Foot impairments are common in older adults, but the independent associations of specific foot indices with locomotive syndrome (LS) severity remain unclear. We examined hallux valgus angle (HV), navicular height (NH), and passive ankle dorsiflexion (ADF). Methods: This cross-sectional study included 119 community-dwelling older adults classified into LS stages 0–3. Bilateral measures were summarized as maximum HV and minimum NH/ADF, reflecting the worst-affected side. Proportional-odds ordinal logistic regression modeled LS stage (0–3) with foot indices and covariates (age, sex, body mass index [BMI]). Extended models additionally adjusted for Timed Up and Go (TUG), gait speed, or single-leg stance (SLS). Sensitivity analysis used binary logistic regression (LS ≥ 2 vs. <2). Results: Greater ADF was independently associated with lower LS severity (OR per 1°, 0.91; 95% CI, 0.85–0.98; p < 0.01), whereas higher BMI was associated with greater LS severity (OR per 1 kg/m², 1.15; 95% CI, 1.01–1.30; p < 0.05). HV and NH were not significant. After adjustment for TUG, gait speed, or SLS, ADF remained inversely associated with LS severity (ORs, 0.92–0.93; p < 0.05), while the BMI association was attenuated. In binary logistic regression, greater ADF was associated with lower odds of LS ≥ 2 (OR per 1°, 0.85; 95% CI, 0.76–0.94; p < 0.005). Conclusions: Reduced passive ankle dorsiflexion is independently associated with greater LS severity, robust after accounting for key mobility and balance measures. Interventions targeting ankle mobility may represent a potentially modifiable factor and warrants confirmation in longitudinal and interventional studies. Full article

Wind-tunnel experiments were conducted on Trionda, the official match ball of the 2026 FIFA World Cup. Aerodynamic force coefficients derived from these measurements were incorporated into numerical trajectory simulations of kicked balls. The resulting aerodynamic characteristics and simulated flight behavior were compared with those of the four previous World Cup match balls: Al Rihla (2022), Telstar 18 (2018), Brazuca (2014), and Jabulani (2010). Relative to its predecessors, Trionda exhibits a drag crisis at lower flow speeds, consistent with an apparently rougher surface. Although its turbulent-regime drag coefficient is more stable than those of earlier designs, its magnitude is modestly larger. Trajectory simulations therefore indicate the potential for small but perceptible reductions in range for long kicks. This study therefore provides the first aerodynamic characterization of the 2026 FIFA World Cup match ball (Trionda) and places its drag-crisis behavior and flight characteristics in direct quantitative comparison with those of recent World Cup balls examined under identical experimental conditions. Full article

We report a versatile, CMOS-compatible fabrication module for sub-100 nm TiN and TaN pillar electrodes, a key building block for sandwich-type test structures. As a demonstration, the electrodes were integrated into carbon nanotube-based nonvolatile random-access memory (CRAM) test structures. High-resolution hydrogen silsesquioxane (HSQ) masks defined by electron beam lithography were transferred into TiN films using optimized Ar/Cl₂ inductively coupled plasma reactive ion etching. Optical emission spectroscopy was used for real-time endpoint detection, ensuring precise etch control. The process achieved a TiN-to-HSQ selectivity of ~1.6 and reproducible nanoscale features with smooth sidewalls and an average taper angle of ~77°. Buffered hydrogen fluoride treatment effectively removed residual HSQ, revealing sharp TiN features and preserving pillar geometry. Atomic force microscopy (AFM) confirmed pillar height and profile fidelity, while conductive AFM verified electrical conductivity after planarization. The module was further demonstrated through the fabrication of TiN pillar arrays, TaN pillars, and sub-100 nm TiN line arrays. A CRAM test structure incorporating TiN pillars exhibited preliminary switching, indicating that both the test structure and fabrication process are feasible. This fabrication module provides a reproducible platform for nanoscale TiN and TaN electrodes, supporting laboratory-scale research and providing a pathway toward future integration of emerging memory and nanoelectronic technologies. Full article

Lumbar oblique radiography plays a crucial role in diagnosing spinal disorders, particularly spondylolysis and spondylolisthesis. Achieving optimal projection angles remains challenging due to variability in positioning techniques and subjective quality assessment. This study presents a deep learning framework for automatic angle estimation in lumbar oblique X-ray images using a two-stage object detection approach. Training data consisted of synthetic X-ray images generated from CT datasets with known projection angles (20° to 60°), annotated with three classes: L2–L4 vertebral levels, vertebral bodies, and pedicles. Two detection models were compared: Model1, a three-class whole-image detector, and Model2, a single-class pedicle detector applied to vertebral body crops from Model1. The Vertebral–Pedicle Ratio (VPR) was used to estimate projection angle via separate linear regression for negative-angle (n-group) and positive-angle (p-group) projections. Five-fold cross-validation showed Model2 achieved higher detection performance (macro mean AP@0.5 = 0.913, mean DSC = 0.825) than Model1 (macro mean AP@0.5 = 0.762, mean DSC = 0.791). Pooled regression yielded R²_n = 0.832 and R²_p = 0.870. Angle estimation with Model2 achieved MAE = 5.42° (SD 1.08°), substantially lower than Model1 (MAE = 9.57°, SD 1.64°), while Model1 offered faster throughput (18.3 FPS vs. 2.9 FPS). Two-stage pedicle detection using VPR-based linear regression provides clinically acceptable angle estimation accuracy in lumbar oblique radiography. Automated angle verification enables real-time positioning feedback during imaging, post-imaging image quality documentation in PACS, and retrospective auditing of facility positioning protocols. These comprehensive implementations are expected to standardize lumbar oblique radiography. Full article

Background/Objectives: The PHOTON trial established the efficacy of aflibercept 8 mg using fixed-interval dosing in treatment-naïve patients; however, real-world evidence regarding pro re nata (PRN) regimens in switch cases remains limited. This pilot study evaluated the short-term efficacy and safety of switching to aflibercept 8 mg with PRN dosing in eyes with DME. Methods: This retrospective study included 20 eyes from 12 patients with DME who switched to aflibercept 8 mg and were followed for 6 months. Patients received initial induction doses (1–3 injections based on predetermined anatomical and functional criteria) followed by PRN dosing based on clinical findings. Primary outcomes were changes in best-corrected visual acuity (BCVA) and central retinal thickness (CRT). Treatment intervals and injection frequency were also analyzed. Results: Mean logMAR BCVA was maintained from baseline (0.242 ± 0.252) throughout the follow-up period: 0.164 ± 0.218 at 1 month, 0.138 ± 0.241 at 2 months, 0.145 ± 0.204 at 3 months, 0.143 ± 0.181 at 4 months, 0.149 ± 0.166 at 5 months, and 0.180 ± 0.224 at 6 months. No statistically significant changes in BCVA from baseline were observed at any time point. Mean CRT decreased from baseline (369.6 ± 138.3 μm) at all follow-up time points: 251.5 ± 82.1 μm at 1 month, 269.1 ± 104.5 μm at 2 months, 255.8 ± 67.8 μm at 3 months, 275.2 ± 76.6 μm at 4 months, 301.4 ± 81.2 μm at 5 months, and 302.7 ± 86.8 μm at 6 months. Statistically significant reductions in CRT were observed at 1 through 4 months (1 month: p = 0.000010; 2 months: p = 0.000243; 3 months: p = 0.000035; 4 months: p = 0.000597), whereas the reductions at 5 months (p = 0.0317) and 6 months (p = 0.0424) were not statistically significant. The mean number of injections over 6 months was 1.45 ± 1.05 (median 1; range 1–4), with 70% of eyes achieving treatment intervals ≥ 4 months. Five eyes (25%) required only the switching dose with no additional treatment during follow-up. No intraocular inflammation or retinal vasculitis was observed. Conclusions: Switching to aflibercept 8 mg with PRN dosing provided sustained anatomical improvement and maintained visual acuity in DME, with one quarter of the cases maintaining these outcomes with only a single additional injection. These real-world findings from a pilot study suggest that the PRN approach appears feasible and effective in real-world practice, offering a practical treatment option that may help reduce treatment burden while maintaining disease control. Full article

Background: The COVID-19 pandemic has underscored the critical importance of supply chain resilience. However, little is known about firms’ willingness to implement logistics and supply chain resilience strategies (SCRESTs), and how this willingness varies across contexts. This study investigates the willingness of Japanese manufacturing firms to implement SCRESTs and examines how the pandemic has influenced this willingness. Methods: Using survey data from 549 Japanese manufacturing firms collected from March to April 2022, we employed binary choice models and the average treatment effect on the treated (ATET) analysis to examine the factors influencing the willingness to implement SCRESTs before and during/after the pandemic. Results: Firms demonstrated significantly higher willingness to implement SCRESTs during/after the pandemic compared with before. Company size, industry sector, logistics strategy, implementation obstacles, and past SCREST implementation significantly influenced willingness across both periods. The ATET analysis confirmed that past SCREST implementation positively affects future willingness. Conclusions: The pandemic served as a catalyst for enhanced supply chain resilience awareness among Japanese manufacturers. Sector-specific interventions addressing both informational and structural barriers are essential to sustain and strengthen the willingness to implement SCRESTs, particularly in strategically important sectors where financial incentives alone may prove insufficient. Full article

Leucine-rich repeat-containing 8A (LRRC8A; also known as SWELL1), the essential subunit of volume-regulated anion channels (VRACs), is amplified in multiple malignancies and has been implicated in tumor progression and therapeutic resistance. Three-dimensional (3D) cancer spheroids have been well-established as in vitro models that recapitulate characteristics of tumor stemness and intrinsic drug resistance. In the present study, spheroid formation in human breast cancer cell lines, YMB-1 and MDA-MB-468, conferred resistance to multiple anticancer drugs, including doxorubicin (DOX), gemcitabine (GEM), and 5-fluorouracil (5-FU), thereby mimicking the characteristic properties of breast cancer stem-like cells. LRRC8A expression was upregulated in 3D spheroids compared with adherent 2D monolayers, and its pharmacological inhibition induced membrane hyperpolarization accompanied by intracellular Cl⁻ accumulation. Inhibition of LRRC8A significantly sensitized spheroids to DOX, GEM, and 5-FU. Spheroid formation increased the expression of multidrug resistance-related protein 3 (MRP3) and the drug-metabolizing enzyme cytochrome P450 3A4 (CYP3A4), whereas LRRC8A inhibition suppressed their expression. The transcriptional upregulation of MRP3 and CYP3A4 was mediated through the NRF2–CEBPB/D transcriptional axis. Collectively, these findings suggest that LRRC8A inhibition may represent a therapeutic strategy to overcome chemoresistance by repressing MRP3 and/or CYP3A4 expression in breast cancer stem cells. Full article

Groundwater used for drinking in settlements located near decommissioned uranium mining facilities may contain elevated naturally occurring radioactive materials, posing long-term public-health concerns. The purpose of this study was to evaluate the radiological quality of groundwater used for drinking in the Saumalkol settlement by applying gross alpha–beta screening and isotope-specific analysis of ²²⁶Ra and ²²⁸Ra to identify the main contributors to groundwater radioactivity and estimate the associated radiation dose from water consumption. Groundwater samples were analyzed using gross alpha–beta screening and isotope-specific determination of ²²⁶Ra and ²²⁸Ra by radiochemical separation and low-background counting, and ingestion doses were estimated using international dose coefficients. Gross alpha activity averaged 2.26 ± 0.96 Bq/L, with most samples exceeding the WHO screening value of 0.5 Bq/L, while gross beta activity averaged 0.65 ± 0.17 Bq/L. Mean activity concentrations of ²²⁶Ra and ²²⁸Ra were 0.17 ± 0.03 Bq/L and 1.47 ± 0.9 Bq/L, respectively, with significantly higher ²²⁸Ra in deep boreholes and a systematic predominance of ²²⁸Ra over ²²⁶Ra (p < 0.05), indicating a thorium-controlled geochemical signature in fractured crystalline aquifers. The estimated annual committed effective ingestion dose from radium isotopes was 0.46 mSv, exceeding the reference level of 0.1 mSv for drinking-water exposure. These findings demonstrate that groundwater radioactivity in Saumalkol is dominated by radium from the thorium series and highlight the need for sustained radionuclide-specific monitoring and targeted water management strategies in uranium-affected regions. Full article

High-fat diets (HFDs) containing dietary fats with different fatty acid (FA) compositions alter gut microbiota composition in a fat-source-dependent manner. Immunoglobulin A (IgA) and unabsorbed lipids in the distal gut are potential regulators of the gut microbiota. However, their roles in mediating gut microbiota alterations induced by dietary fats with different FA compositions remain unclear. This study aims to examine the associations of these two factors with fat-source-dependent gut microbiota alterations. BALB/c mice were fed a normal diet, a high-lard diet, a high-olive oil diet, or a high-soybean oil diet for 27 weeks. Fecal samples were collected to assess microbiota composition, the IgA coating index (ICI)—which quantifies the extent of IgA coating on gut microbiota—and fecal fatty acid concentrations. At the phylum level, the concentration of fecal total long-chain fatty acids (LCFAs) was positively correlated with the relative abundance (RA) of Bacillota and negatively correlated with that of Bacteroidota. In addition, a trend toward a positive association between the RA and the ICI was observed for Bacillota but not for Bacteroidota. At the genus level, the RAs of 12 taxa were positively correlated with fecal LCFA concentrations, whereas those of 6 taxa were negatively correlated. Although the RAs of most taxa appeared to be influenced by unabsorbed lipids and additional factors, only four Bacillota genera exhibited a positive correlation between the RA and the ICI. Our observations suggest that IgA coating of the gut microbiota may have a minimal association with fat-source-specific alterations in gut microbiota composition during HFD intake. Full article