Search Results (281)

Background/Objectives: Tablet development requires simultaneous optimization of multiple quality attributes under limited experimental budgets, yet formulation–property relationships are highly nonlinear in mixture systems. To support pre-formulation decision-making prior to extensive tablet prototyping, this study proposes an AI framework that organizes formulation and process data together with raw-material property records into a reusable database, and enriches conventional composition/process features with physically motivated mixture descriptors derived from raw-material properties and formulation/process settings. Methods: Mixture-level scalar descriptors are constructed by composition-weighted aggregation of material properties, and particle size distribution (PSD) is incorporated via a compact set of summary statistics computed from composition-weighted mixture PSDs. Three feature sets are compared: (i) Materials + Processes (MP), (ii) MP with scalar Descriptors (MPD), and (iii) MPD with PSD summaries (MPDD). Five target properties are modeled: hardness, disintegration time, flow function, cohesion, and thickness. We train and evaluate Random Forest, Extra Trees Regressor, Lasso, Partial Least Squares, Support Vector Regression, and a multi-branch neural network that processes the three feature blocks separately and concatenates them for prediction. For interpolation assessment, repeated Train/Dev/Test splitting (5:3:2) across multiple random seeds is used, and the effect of feature augmentation is quantified by paired RMSE improvements with bootstrap confidence intervals and paired Wilcoxon signed-rank tests. To assess robustness under practical formulation updates, rolling-origin time-series splits are employed and Applicability Domain indicators are computed to characterize out-of-distribution coverage. Results: Across interpolation evaluations, mixture-descriptor augmentation (MPD/MPDD) improves hardness and disintegration time in most settings, whereas gains for flow function are smaller and cohesion/thickness show mixed effects under limited sample sizes. Conclusions: Under extrapolation-oriented evaluation, the descriptors can improve hardness but may degrade disintegration-time prediction under covariate shift, emphasizing the need for careful descriptor selection and dimensionality control when deploying pre-formulation predictors. Full article

This study proposes a new deep learning-based approach for detecting pitting corrosion on stainless-steel sheet pile surfaces in drainage channels. Conventional ultrasonic thickness measurement methods cannot detect microscopic pitting corrosion that occurs before measurable thickness reduction. The research develops an automated detection system using visible images captured with smartphone cameras and U-net semantic segmentation. Two stainless steel grades (SUS410 and SUS430) were exposed for 5 years to a brackish water environment and analyzed. The deep learning approach achieved F1-scores of 0.831 (SUS410) and 0.808 (SUS430), outperforming binary thresholding methods (F1-scores: 0.407 and 0.329, respectively). Data augmentation improved performance by 1–3 percentage points. The method enabled non-destructive, quantitative assessment of early-stage corrosion using readily available equipment, providing a practical tool for infrastructure maintenance and long-term durability evaluation. Full article

Background: Continuity of care for rheumatoid arthritis patients within regional networks enables stable long-term clinical data collection, despite chronic rheumatologist shortages in Japan. We determined 5-year drug survival and discontinuation reasons for eight biological disease-modifying antirheumatic drugs (bDMARDs) using a regional multicenter registry. Methods: We retrospectively analyzed 1182 patients initiating their first (naïve, n = 784) or subsequent (switch, n = 398) bDMARD between May 2001 and August 2022 across five institutions. The primary endpoint (5-year drug survival) and secondary endpoints (discontinuation risk factors and cumulative incidence of reasons) were evaluated using Kaplan–Meier curves, Cox proportional hazards, and Fine & Gray models. Results: Baseline characteristics varied significantly among bDMARDs. Five-year drug survival in the naïve cohort ranged from tocilizumab (50.8%) to golimumab (22.6%); in the switch cohort, from abatacept (42.6%) to infliximab (10.0%). In multivariable Cox analysis of naïve patients, male sex (hazard ratio [HR] = 1.49, 95% confidence interval [CI] = 1.09–2.02), lower baseline 28-joint Disease Activity Score with erythrocyte sedimentation rate (DAS28-ESR) (HR = 0.90, 95% CI = 0.82–0.99), and absence of methotrexate co-therapy (HR = 0.73, 95% CI = 0.55–0.97) predicted discontinuation. The lower baseline DAS28-ESR association potentially reflects successful courses toward intentional cessation following remission. Discontinuations were attributed to inadequate response (27.1%), non-adverse events (25.3%), and adverse events (17.3%). Conclusions: Tocilizumab and abatacept demonstrated the highest retention rates in biologic-naïve and switch cohorts, respectively. Early, individualized drug selection and dose optimization are crucial to maximizing long-term bDMARD effectiveness before switching. Full article

Ciprofloxacin (CIP) is an antibiotic that is widely used in humans and animals. However, the compound has been detected in animal-derived products and the environment due to its extensive use, causing serious concern for public health and environmental safety. The issue raises the urgent need to develop innovative techniques to monitor CIP. Therefore, this study aims to develop a simple and sensitive CIP sensor called the boron-doped diamond nanoparticle-modified screen-printed electrode (BDD NPs/SPE) and the nickel oxide nanoparticle-modified BDD NPs/SPE (NiO NPs/BDD NPs/SPE). NiO NPs were synthesized via green synthesis using Spatholobus littoralis Hassk. root extract as the reducing agent. The formation and characteristics of NiO NPs were then confirmed through a UV-Vis spectrophotometer, XRD, PSA, FT-IR, and XPS. The successful modification of SPE was confirmed through SEM-EDX, followed by measurements using square-wave voltammetry. The results showed that the modified SPE could detect CIP over a concentration range of 0.1–100 µM and produced a low detection limit of 0.109 µM for BDD NPs/SPE and 0.054 µM for NiO NPs/BDD NPs/SPE. The proposed method was successfully applied to the determination of CIP in commercial tablets, milk, and human urine, with a satisfactory % recovery from 95 to 100%. The current study successfully developed a simple yet highly sensitive sensor that enabled robust, reliable, and efficient detection of CIP, showing its strong potential for practical applications. Full article

Epigenetic clocks have successfully estimated biological age by identifying CpG sites whose DNA methylation levels correlate with chronological age. However, these statistical models provide limited mechanistic insight into the biological underpinnings of ageing. While they capture the “pace” of ageing, they fail to quantify the “resilience” of biological systems—the capacity to recover, reorganize, and maintain homeostasis under stress. To overcome this limitation, we introduce EpiAge-R (Epigenetic Age with Resilience), a mechanistic framework that shifts the focus from passive correlation to active recovery potential. The EpiAge-R framework integrates multilayered biological information—including long-read methylation sequencing, chromatin context, histone modification balance, 3D genome topology, and mitochondrial dynamics—into a unified Resilience Index. By distinguishing between degenerative methylation drift (damage) and adaptive repair processes (resilience), EpiAge-R aligns with nonlinear multi-omics ageing trajectories. This framework provides a quantitative foundation for next-generation biomarkers and precision longevity interventions, aiming to define optimal health rather than statistical normality. Full article

A 2D model of an InGaAs/InAlAs single-photon avalanche photodiode has been developed. The influence of the active area structure in the multiplication region on the diode’s operating parameters has been studied. It was found that changing the diameter of the structure’s active region leads to a change in the dark current in the linear part of the current–voltage curve and a change in the breakdown voltage. Reducing the diameter of the active region from 25 $\mathsf{\mu }$m to 10 $\mathsf{\mu }$m allowed decreasing the dark current in the linear mode by about 10 dB. It has been shown that the quality of the SPAD device can be assessed by knowing the avalanche breakdown voltage and the overall current–voltage curve plot if we consider structures with the same multiplication region thickness and different remaining layers. The higher the breakdown voltage, the better the structure’s quality due to smaller local increases in the field strength. Following this statement, we conclude that for further use in single-photon detectors, it is reasonable to pick specific SPADs from a batch on the sole basis of their current–voltage curves. Full article

Urban public green spaces are widely recognized for having positive effects on mental health, yet existing research shows imbalances in subjects and methodologies. Most studies examine healthy adults and self-reported indicators, giving limited attention to vulnerable populations; this may have led to a gap in evidence regarding “who is represented and who is overlooked.” This study systematically reviewed 235 empirical papers published in 2004–2024 following PRISMA 2020 to examine epistemic equity. The Equity Bias Framework was applied to operationalize epistemic equity by assessing imbalances in study design, psychometric measures, and population sampling. Results showed that the cross-sectional design, self-report, and community-dwelling adults combination accounted for the largest share (n = 99, 27.8%), whereas only 9 combinations in total (2.5%) involved clinical populations. The experimental design × self-report × university student patterns (n = 14, 3.9%) outnumber all experimental studies involving age-disadvantaged or clinical groups (n = 4, 1.1%). These patterns indicate that existing research evidence is shaped more by feasibility and accessibility than by representativeness and clinical relevance, raising concerns about epistemic equity. By introducing the Equity Bias Framework, this study provides a lens on current evidence and direction for research and policy promoting methodological diversity and sample inclusivity. Full article

We present the case of a 27-year-old woman diagnosed with Löffler’s endomyocarditis complicated by intraventricular thrombus and cerebral infarction. She was treated with prednisolone and anticoagulation therapy; however, tapering of corticosteroids resulted in recurrence of intraventricular thrombosis. Given disease relapse after medication withdrawal, lifelong anticoagulation was indicated. At 29 years of age, she sought pregnancy counseling. Conception was permitted after stabilization of prednisolone dosage, with a planned switch from a vitamin K antagonist to therapeutic-dose unfractionated heparin during pregnancy. Following disease stabilization, she conceived via artificial insemination. Serial echocardiography at 22 and 34 weeks of gestation demonstrated preserved cardiac function without thrombus recurrence. She delivered a healthy infant by emergency cesarean section at 39 weeks of gestation due to fetal distress. No thrombus recurrence was observed postpartum, and she remained clinically stable during 13 months of follow-up. This represents the case of a successful pregnancy in a woman with a history of recurrent intraventricular thrombosis due to Löffler’s endomyocarditis, highlighting the importance of early diagnosis, sustained immunosuppression, individualized anticoagulation, and multidisciplinary preconception planning. Full article

Seasonal fluctuations in the chemical composition of fine particulate matter (PM_2.5) are known to influence its toxicological properties; however, their integrated biological effects remain incompletely understood. In this study, PM_2.5 was continuously collected over two consecutive years at a single urban site in Japan and classified by season. The samples were comprehensively characterized for ionic species, metals, carbonaceous fractions, and polycyclic aromatic hydrocarbons (PAHs), and their pulmonary effects were evaluated in vivo following intratracheal administration in mice. Seasonal PM_2.5 exhibited pronounced compositional differences, with higher levels of secondary inorganic aerosol components in summer and enrichment of PAHs and mineral-associated components in winter. These seasonal differences translated into distinct biological responses. Reactive oxygen species (ROS) production (1.6–2.7-fold increase) and bronchoalveolar lavage (BAL) neutrophil infiltration were strongly associated with PAH-rich PM_2.5, whereas interleukin-1α (IL-1α) showed robust positive correlations with mineral components, including K⁺, Ca²⁺, and Mg²⁺, which were predominantly enriched in winter PM_2.5. In contrast, secondary inorganic aerosol species displayed a limited capacity to induce IL-1α. Compared with summer samples, winter PM_2.5 induced significantly higher levels of ROS production and IL-1α (approximately 1.5–2.6-fold increase). Using TLR2- and TLR4-deficient mice, we further demonstrated that PM_2.5-induced increases in BAL cell counts, ROS, IL-6, and TNF-α were partially attenuated in TLR4 knockout mice, indicating a contributory but not exclusive role for TLR4 signaling in PM_2.5-driven pulmonary inflammation. Collectively, these findings demonstrate that seasonal variations in PM_2.5 composition, not particle mass alone, critically shape oxidative stress and innate immune responses in the lungs. In particular, winter PM_2.5 enriched in mineral-associated components preferentially activates IL-1α-mediated alarmin pathways, underscoring the importance of the particle composition in determining seasonal air pollution toxicity. Full article

In this study, we investigated the electrochemical reduction of carbon dioxide (CO₂) using a phosphorus-doped polycrystalline diamond (PDD) electrode and compared it with a conventional boron-doped diamond (BDD) electrode. In the reduction reaction of CO₂ in a 0.5 M KCl aqueous solution, the PDD electrode showed high selectivity for formic acid production over a wide potential range. This tendency was particularly evident at potentials below −1.8 V (vs. RHE). Moreover, at more negative potentials of −2.4 V and −2.6 V, formic acid remained the dominant product, while hydrogen evolution was the main reaction on the BDD electrode at the negative potentials. Similarly, in electrochemical reduction using an 0.1 M KClO₄ aqueous solution, carbon monoxide was confirmed to be a major product, and hydrogen generation was effectively suppressed in a more negative potential range. In other words, PDD is a promising electrode material that can efficiently convert CO₂ into valuable chemicals while suppressing hydrogen evolution, even in negative potential regions. Full article

Biomimetic scaffolds are required in tissue engineering to provide structural support as well as promote cell adhesion, proliferation, and differentiation. Fibrous scaffolds composed of micro- and nanofibers replicate the architecture of the native extracellular matrix. Electrospinning is widely used for fabricating nanofibers; however, constructing fibrous scaffolds that integrate multiple fiber scales into a single structure is difficult. We addressed this issue by developing a fiber-spinning device using two pairs of counter-facing syringes that simultaneously produce micro- and nanofibers under different processing conditions. Poly(ε-caprolactone) solutions are ejected through needle-type nozzles via centrifugal force, and fiber diameter is controlled by adjusting the polymer concentration and nozzle diameter. We fabricated scaffolds with the proposed device, which exhibited a random three-dimensional fibrous network in which microfibers and nanofibers were homogeneously integrated. C2C12 myoblasts cultured on the composite scaffolds strongly adhered to the fibrous network, remained viable, and extended along the fibers to form multinucleated cells within the structure. The developed system produced composite micro/nanofiber scaffolds with tunable morphology and biocompatibility, providing a platform for fibrous tissue engineering applications. Full article

Background: Recent trials, including JCOG0802/WJOG4607L and CALGB140503, have confirmed the oncological adequacy of segmentectomy for early-stage non-small-cell lung cancer (NSCLC). This shift emphasizes the preservation of pulmonary function and minimal invasiveness. Robot-assisted thoracic surgery (RATS) offers enhanced anatomical precision and potentially improves segmentectomy outcomes. Methods: We reviewed the current evidence comparing sublobar resection and lobectomy for early-stage NSCLC, focusing on RATS segmentectomy. Clinical trials, perioperative and long-term outcomes, technical innovations, and patient selection criteria were analyzed. Comparative data among RATS, video-assisted thoracoscopic surgery (VATS), and open approaches were synthesized, including the emerging roles of AI and 3D imaging. Results: Segmentectomy yields survival outcomes equivalent or superior to lobectomy for stage IA peripheral NSCLC ≤2 cm, with better pulmonary function despite higher locoregional recurrence. RATS enhances visualization, dexterity, and ergonomics, thereby enabling precise dissection and lymph node assessment. Compared to VATS and open surgery, RATS shows lower conversion rates, reduced pain, and comparable oncological control. Innovations, such as indocyanine green imaging, 3D modeling, and AI-guided navigation, support margin accuracy and personalized care. Conclusions: Segmentectomy has redefined the surgical standards for early-stage NSCLC. RATS maximizes the minimally invasive benefits by combining oncological safety and functional preservation. Its technical precision facilitates complex resections and integration with digital planning tools to advance personalized thoracic surgery. RATS represents the next evolution of minimally invasive thoracic surgery, redefining the balance between oncological safety and functional preservation in early-stage NSCLC. Full article

In malignant-type gastric cancer, peritoneal dissemination is the most frequent metastatic process and is an inoperable condition for which effective treatment is lacking. Our research has revealed that galectin-4 plays an important role in the peritoneal metastasis of gastric cancer cells. Based on this, we hypothesized that inhibiting galectin-4 could suppress peritoneal metastasis. The inhibitory activity towards galectin-4 binding was evaluated using an enzyme-linked immunosorbent assay, while the suppressive effect on gastric cancer cell proliferation was assessed using an adenosine triphosphate-based cell viability assay. Direct binding to galectin-4 was examined by surface plasmon resonance analysis. Chemically synthesized fucoidan analogs exhibited significant suppressive activity against the proliferation of gastric cancer cells, partly via a galectin-4-mediated pathway. Among the 13 fucoidan analogs tested, analog 10, whose sugar chains composed of repeating 2,3-O-sulfated α(1,4)-linked L-fucose, showed significant inhibitory activity against galectin-4 binding and cell proliferation. 14, the cholestanol-conjugated analog 10, exhibited a pronounced increase in inhibitory activity, consistent with potential multimerization. Molecular docking and site-directed mutagenesis studies revealed that Arginine-45 in galectin-4 is important for binding to fucoidan analogs. In conclusion, fucoidan analogs with a strong affinity for galectin-4 are promising candidates for inhibiting the peritoneal metastasis of galectin-4-positive gastric cancer cells. Full article

Histamine sensing that uses enzymatic reactions is the most common form of testing due to its selectivity for histamine. However, enzymes are difficult to store for long periods of time, and the inactivation of enzymes decreases the reliability of the results. In this study, we developed a novel, quick, and easily operated histamine sensing technique that takes advantage of the histamine redox reaction and does not require enzyme-based processes. Because the redox potential of histamine is relatively high, we used a boron-doped diamond (BDD) electrode that has a wide potential window. At pH 8.4, which is between the acidity constant of histamine and the isoelectric point of histidine, it was found that an oxygen-terminated BDD surface successfully detected histamine, both selectively and exclusively. Measurements of the sensor’s responses to extracts from fish meat samples that contained histamine at various concentrations revealed that the sensor responds linearly to the histamine concentration, thus allowing it to be used as a calibration curve. The sensor was used to measure histamine in another fish meat sample treated as an unknown sample, and the response was fitted to the calibration curve to perform an inverse estimation. When estimated in this way, the histamine concentration matched the certified value within the range of error. A more detailed examination showed that the sensor response was little affected by the histidine concentration in the sample. The detection limit was 20.9 ppm, and the linear response range was 0–150 ppm. This confirms that this sensing method can be used to measure standard histamine concentrations. Full article