Search Results (909)

The skin microbiota plays a key role in maintaining cutaneous homeostasis; however, microbial differences among physiological skin types within healthy individuals remain unclear. In this study, we investigated the association between skin microbiota diversity and four skin types (normal, oily, dry, and combination) in healthy young women (n = 43), with samples collected from the nasal region. Skin moisture and sebum levels were quantitatively measured, and microbiota profiles were analyzed using 16S rRNA gene amplicon sequencing targeting the V3–V4 regions. Normal skin exhibited higher alpha diversity, including Chao1 richness and Faith’s phylogenetic diversity, compared with other skin types (median Chao1 values were higher in normal skin than in other groups). Correlation analyses showed that skin moisture was positively associated with microbial richness (ρ = 0.397, p = 0.008), whereas sebum levels were negatively associated with phylogenetic diversity (ρ = −0.455, p = 0.002). Beta diversity analysis revealed that normal skin harbored a distinct microbial community structure. In addition, several bacterial genera were enriched in normal skin, whereas Enterobacterales were observed to be more abundant in non-normal skin types. These findings suggest that skin biophysical properties are associated with microbial community structure and diversity within healthy individuals, although the functional implications of these differences remain to be elucidated. Full article

Models are described for calculating the crack initiation times for Alloy 600 and Type 304 SS in PWR and BWR primary coolant circuits, respectively. In PWRs, initiation is defined in terms of the grain boundary oxidation concept of Scott and Le Calvar, whereas in BWRs, cracks are envisioned to nucleate from corrosion pits. In contrast, in BWRs, we envision cracks to nucleate from corrosion pits, with the difference in the two systems being primarily due to electrochemical factors. Thus, in BWR primary coolant and the absence of hydrogen water chemistry (HWC), the oxidizing conditions due to the radiolytic production of H₂O₂ cause the ECP to be significantly more positive than the critical pitting potential. Accordingly, the nucleation and growth of pits due to passivity breakdown and the establishment of differential aeration between the pit nucleus’s internal and external environments, which results in growth of pits to the critical size necessary to satisfy the Kondo criteria for transition of a pit into a crack, is judged to be a realistic scenario. Contrariwise, in PWR primary coolant, the ECP is so negative [≈−1.0 V_she] due to the large amount of pressurizing H₂ present in the circuit [20–60 cm³(STP)/kg H₂O] that the nucleation and growth of pits is not possible. However, Totsuka and Smialowska found that MA Alloy 600 suffers hydrogen-induced cracking (HIC) at an ECP < −0.85 V_she, demonstrating that, in service with a high hydrogen concentration, brittle fractures will occur. The initiation sites were not identified. The crack initiation models for Alloy 600 in PWRs and Type 304 SS in BWRs reproduce the effects of the following independent variables: applied stress, temperature, cold work, grain boundary segregations, water chemistry, pH, and electrochemical potential. The origins of the observed scatter in experimentally measured crack initiation times are discussed, and the challenges of developing a more general crack initiation model (GCIM) are identified. From a mathematical viewpoint, the most significant challenge arises from the nested distributions involving the many parameters and expressions within the GCIM that are either distributed because of an imprecise definition or because some experimentally determined input parameters are experimentally scattered. Additionally, the evolution of semi-elliptical surface cracks resulting from the electrochemical crack length (ECL) being shorter than the classical mechanical crack length (MCL) must be incorporated if the GCIM is to find utility in the water-cooled nuclear power industry where semi-elliptical surface cracks are normally observed. Full article

Background/Objectives: Malnutrition and undernutrition are critical health concerns associated with increased mortality and costs. Although these are distinct clinical concepts, they are often used interchangeably in clinical practice and are inconsistent with the diagnostic frameworks. This diagnostic ambiguity may obscure true patient profiles. This study aimed to clarify the real-world diagnostic patterns of malnutrition and undernutrition and identify associated drug prescription trends using a patient estimation database in Japan. Methods: We analyzed the AHI partners database of 2024. Patients were identified using the International Statistical Classification of Diseases and Related Health Problems, 10th Revision, code E46. Sex differences were analyzed and stratified according to age group: older adults (≥65 years) and younger adults (15–39 years). Odds ratios (ORs) were used to identify associated drugs. Results: Of 96,673,453 patients, 216,652 were diagnosed with malnutrition and 77,100 with undernutrition. In both categories, older adults accounted for more than half of the patients. Notably, distinct diagnostic labeling patterns were observed by sex. Malnutrition predominated in women (58.8%), whereas undernutrition was more prevalent in men (70.6%). This male predominance of undernutrition was reversed in younger adults, where women showed higher proportions in both categories. Prescription analysis identified 31 drugs frequently prescribed to the study population. Enteral elemental formulas had the highest OR (89.7). Some psychotropic drugs were frequently prescribed to women. Conclusions: Diagnostic patterns varied by sex and age, potentially reflecting distinct practices in diagnostic labeling. These findings highlight the need for standardized frameworks to ensure consistent assessments and effective nutritional interventions. Full article

To compare the genetic causes, prevalence, and clinical characteristics of syndromic and non-syndromic familial exudative vitreoretinopathy (FEVR). A total of 281 patients with FEVR who underwent clinical and genetic evaluation at five ophthalmological institutions in Japan between 2010 and 2023 were included. Whole-exome sequencing, Sanger sequencing, or karyotype analysis was performed using blood samples from probands and available family members. Clinical characteristics of FEVR probands were assessed according to the presence or absence of systemic abnormalities. Among the 281 FEVR probands, 42 (15%) had syndromic FEVR and 239 (85%) had non-syndromic FEVR. Syndromic FEVR was more frequently diagnosed during infancy (95% vs. 57%, p < 0.0001) and occurred more often in sporadic cases (69% vs. 50%, p = 0.028). Variants in Norrin/β-catenin signaling genes were less common in syndromic FEVR (29% vs. 54%, p = 0.0026), whereas symmetrical retinal severity was more frequently observed (67% vs. 39%, p = 0.001). Sex distribution did not differ between groups. Pathogenic variants were identified in 71% of syndromic cases, most commonly in KIF11, NDP, CTNNB1, DOCK6, TSPAN12, and LRP5. Syndromic FEVR exhibits distinct and heterogeneous genetic and clinical features compared with non-syndromic FEVR. Genotype–phenotype characterization may enable earlier diagnosis. Full article

Vaporized free chlorine, primarily present as hypochlorous acid (HOCl), is increasingly used for indoor microbial control; however, virus-dependent susceptibility and its molecular determinants remain unclear. We evaluated virucidal effects under controlled indoor conditions (0–9 ppb) against echovirus 30 (E30), influenza A/H1N1, and human adenovirus type 3 (HAdV3). Infectious titers were quantified by TCID₅₀ assays. Computational fluid dynamics (CFD) simulations and gas-sensor measurements assessed spatial dispersion, and structural analyses examined oxidation-sensitive amino acid residues. Significant reductions in infectivity were observed for E30 (99.0%, p = 0.00727) and influenza A/H1N1 (99.9%, p = 0.000597), whereas no significant reduction was detected for HAdV3 (p = 0.142). Analyses including all data points without outlier exclusion confirmed the robustness of these findings. CFD indicated uniform dispersion, although spatial heterogeneity within the indoor environment cannot be excluded. These findings suggest that viral susceptibility to vaporized HOCl is associated with residue-level composition and structural context; however, this relationship should be interpreted as correlative rather than causal. Moreover, integration of molecular and structural analyses provides a plausible mechanistic framework, although direct biochemical validation remains necessary. Structural analyses showed lower proportions of oxidation-sensitive residues in adenoviral proteins compared with influenza A hemagglutinin (OR = 0.34–0.40, adjusted p < 0.001) and the E30 VP1 intermediate. Residues were clustered in surface-exposed functional domains in susceptible viruses. Full article

Many female athletes experience menstrual cycle issues. We investigated clary sage (Salvia sclarea L.) essential oil inhalation’s effect on dysmenorrhea-related symptoms, antioxidant capacity, and salivary hormone levels in female collegiate athletes. This randomized crossover trial included 20 female collegiate athletes (mean age: 20.2 ± 1.2 years). The participants were randomly assigned to one of two conditions: clary sage essential oil (intervention) or water (control) inhalation. Each condition lasted for one menstrual cycle, with inhalation administered at bedtime for 60 min using a diffuser. Dysmenorrhea-related symptoms and their impact on athletic performance were assessed using a visual analog scale. Biochemical analyses included salivary antioxidant capacity and cortisol, estradiol, and progesterone level measurements. Data from 12 participants who completed the study were analyzed. Compared with water inhalation, clary sage essential oil inhalation significantly reduced menstrual pain, sleep disturbances, irritability, and anxiety (all p < 0.05). The impact of dysmenorrhea-related symptoms on performance and total symptom scores was also significantly lower in the intervention condition than in the control condition (both p < 0.05). Additionally, salivary antioxidant capacity was significantly higher following clary sage essential oil inhalation than after water inhalation (p < 0.05). However, no significant differences were observed in the salivary cortisol, estradiol, or progesterone levels between the intervention and control conditions. Clary sage essential oil inhalation may be an effective nonpharmacological approach for alleviating dysmenorrhea-related symptoms and enhancing antioxidant capacity in female collegiate athletes. The results highlight its potential as a noninvasive and easy-to-use daily method for managing menstrual symptoms. Full article

Background/Objectives: Near-infrared photoimmunotherapy (NIR-PIT) provides tumor-selective cytotoxicity with minimal collateral tissue damage and has emerged as a novel treatment option for recurrent head and neck squamous cell carcinoma (HNSCC). However, biomarkers that predict treatment response to NIR-PIT remain poorly defined. Therefore, this study aimed to exploratorily determine whether baseline nutritional and inflammatory composite biomarkers are associated with complete response to NIR-PIT in patients with recurrent HNSCC. Methods: Fifteen non-surgical candidates with recurrent HNSCC underwent NIR-PIT between January 2022 and December 2025. Baseline composite nutritional indices and inflammatory markers, including the systemic inflammation response index (SIRI), were assessed before and 4–8 weeks post-treatment. Tumor response was evaluated according to RECIST version 1.1. Exploratory comparisons between complete response (CR) and non-CR groups were performed using Wilcoxon rank-sum tests with effect size estimation. Results: Five of 15 patients achieved CR (33.3%). Baseline SIRI was significantly lower in the CR group than in the non-CR group (median 70.7 vs. 120.2; p = 0.03), with a large effect size (r = 0.55). In contrast, baseline composite nutritional indices and other inflammatory markers showed no significant association with treatment response. Nutritional status remained stable after NIR-PIT, as reflected by preserved nutritional index values. SIRI tended to increase post-treatment in patients who achieved CR. Conclusions: NIR-PIT achieved encouraging local tumor responses in recurrent HNSCC while preserving early nutritional status. Baseline SIRI may represent a potential inflammation-based correlate of CR, reflecting the balance between systemic inflammation and host immune status, and warrants validation in larger prospective cohorts. Full article

Mechanochromism is a phenomenon in which mechanical stimuli change the optical properties of a material, such as its color and emission properties. Various materials exhibiting this behavior have been intensively studied. Mechanochromic materials that exploit liquid crystals have been previously reported. Using liquid crystals, properties different from those of conventional materials, such as anisotropic response and multicolored luminescence due to intermediate aggregation phase stabilization, can be expected. Recently, we reported the preparation and evaluation of the optical properties of liquid-crystalline mechanochromic dyes with cholesterol terminals. The dyes formed gels in some solvents, changed their emission color, and exhibited a friable response without reaching a crystalline state. In addition, film-forming properties, processability, and responsiveness were improved in thin films mixed with polymers. However, the mechanical and thermal stabilities of the gels were low. In this study, a compound similar to the polymerizable unit was synthesized to produce tougher gels. In addition, triblock polymers with a mechanoresponsive dye in the hard segment were synthesized. The xerogel film prepared from the monomer showed an irreversible blue shift in photoluminescent color by mechanical grinding and also exhibited linearly polarized photoluminescence by uniaxial grinding due to force-induced alignment. On the other hand, the xerogel film prepared from the triblock copolymer showed a blue shift in photoluminescent color that can approximately revert to the initial state by thermal annealing, though it showed no anisotropy by uniaxial grinding, indicating that polymerization partially preserves mechanical responsiveness. Full article

Glioblastoma (GBM) is an aggressive human malignancy. Recent advances in GBM research have highlighted innovative therapeutic approaches, including the use of small molecules that eliminate GBM in mouse models. However, there are few reports on the restoration of lost neuronal functions in patients. Considering that GBM contains GBM-initiating cells (GICs) with characteristics of both cancer and neural stem cells, we investigated whether GICs could be redirected toward non-tumorigenic neurons to support the preservation of neural function in the brain with GBM. We demonstrated that the neuronal differentiation inducer Isoxazole 9 (ISX9) effectively induced GICs to differentiate into neurons, accompanied by significant changes in their gene expression profiles. The sequential application of ISX9 and the DHODH inhibitor brequinar (BRQ), which successfully eradicated undifferentiated GICs, not only promoted neuronal differentiation but also inhibited GIC tumorigenesis in the mouse brain, leading to prolonged survival and preservation of motor function in tumor-bearing mice. Furthermore, pathological analysis revealed that this combination not only reduced the size of GIC brain tumors but also facilitated the formation of synapse-like structural contacts between GIC-derived cells and host mouse neurons, suggesting remodeling of the tumor–neural interface within the tumor-developed area. Collectively, these findings suggest that the modulation of tumorigenic GIC differentiation may represent a strategy to preserve neural circuit integrity within the tumor-bearing brain. 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

The engineering of theranostic nanoparticles, which integrate diagnostics and therapy in a single administration, enables targeted drug delivery and disease visualization. In cancer theranostics, gadolinium-based nanoparticles are valuable tools for noninvasive magnetic resonance imaging (MRI) and provide high-resolution images of the tumor. When MRI is combined with other imaging modalities, complementary therapeutic information is obtained for more accurate identification of tumor characteristics and precise guidance of anticancer drug delivery. Among the many possible modalities combined with MRI, photoacoustic imaging (PAI) is a candidate that enables sensitive in vivo detection of tumors. We have already succeeded in synthesizing biocompatible gelatin-coated gadolinium oxide nanoparticles with a controlled size by adjusting the timing of gelatin addition, which were a highly efficient contrast agent for MR and PA dual imaging. Herein, we conjugated a clinically used anticancer drug (doxorubicin, DOX) to size-defined and biocompatible gadolinium oxide nanoparticles which are novel theranostic probes. Succinylated gelatin enabled the electrostatic conjugation of DOX with gadolinium oxide nanoparticles, and the release of DOX was controlled through the enzymatic degradation of gelatin by matrix metalloproteinases-2 and -9 (MMP-2 and MMP-9), which are highly expressed in cancer cells. The released DOX efficiently inhibited the growth of HeLa cells in vitro and the growth of the inoculated tumor tissues in vivo. The dual-modality MRI and PAI capabilities provide anatomical information that assists in the localization and targeting of theranostic probes. 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

This study aimed to establish fabrication methods for two types of functional microcapsules (MCs) and to verify their fundamental performance in cementitious materials. The alkaline-supplying and CO₂-absorbing MCs were evaluated independently. It was hypothesized that alkaline-supplying MCs could suppress carbonation while limiting strength loss to ≤20%, whereas CO₂-absorbing MCs could increase long-term CO₂ uptake by ≥30% relative to plain mortar. The alkaline-supplying MCs reduced the 24-week carbonation depth by approximately 35%, with a ~20% reduction in compressive strength at a 5% addition level. In contrast, CO₂-absorbing MCs resulted in a ~30% strength reduction at 5% addition but increased CO₂ uptake by 1.4 times that of plain mortar over 140 d. In conclusion, the results demonstrate that MCs can effectively impart carbonation-resistance or CO₂-absorption functionality; however, a clear trade-off exists between functional enhancement and mechanical degradation due to capsule stiffness and density limitations. Because the two types of MCs rely on different mechanisms, they were tested in separate mortar systems. As this study focused on MC fabrication and fundamental functional verification, future work should optimize shell design, density control, and amine selection to balance structural performance with durability enhancement and CO₂-sequestration capability. Full article

Cancer cachexia is a multifactorial metabolic syndrome that profoundly impairs treatment tolerance and prognosis; however, how tumor-intrinsic transcriptional programs contribute to cachexia induction and shape responses to chemotherapeutic stress remains poorly understood. In this study, we analyzed a paired human duodenal neuroendocrine carcinoma cell-line model consisting of the non-cachexia-inducing parental line TCC-NECT-2 and its cachexia-inducing derivative AkuNEC. Bulk RNA sequencing was performed under baseline conditions and after doxorubicin treatment (10 μM, 24 h), and transcriptomic differences were assessed using log2 fold-change–based analyses to characterize baseline reprogramming, drug-induced responses, and differential stress adaptation. Despite comparable morphology and similar levels of doxorubicin-induced acute cytotoxicity, AkuNEC cells exhibited extensive baseline transcriptional reprogramming relative to TCC-NECT-2, including coordinated upregulation of inflammatory, secretory, and metabolic regulators previously implicated in cancer cachexia, together with suppression of structural and homeostatic programs. Following doxorubicin exposure, AkuNEC cells showed a distinct transcriptional response characterized by selective reorganization of proliferation-, metabolism-, and stress-related pathways, indicating enhanced transcriptional plasticity rather than uniform stress suppression. Differential response analyses further revealed preferential induction of genes involved in cell cycle control, DNA replication, and metabolic adaptation in AkuNEC under chemotherapeutic stress. These findings indicate that cachexia-inducing capacity is embedded within tumor-intrinsic transcriptional states and is amplified by stress-induced plasticity, supporting a network-level model of cancer cachexia that links systemic host effects with tumor adaptation to therapy. The TCC-NECT-2/AkuNEC model provides a tractable framework for dissecting these tumor-intrinsic mechanisms and their relevance to cachexia-associated cancer biology. Full article