Search Results (549)

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

We prospectively evaluated whether cytotoxic T-lymphocyte (CTL) activation and T-cell receptor (TCR) Vβ clonality predict treatment-free remission (TFR) after tyrosine kinase inhibitor (TKI) cessation in chronic-phase chronic myeloid leukemia (CML). Forty-five patients with sustained deep molecular response (DMR) were enrolled (On-TKI, n = 38; Off-TKI, n = 7) and underwent one-year immuno-monitoring from consent. The primary endpoint was 12-month TFR, defined as retention of MR4. Overall, 32/45 patients (71%) maintained TFR at 12 months. Longer TKI exposure and stable DMR were associated with TFR; notably, patients fulfilling “≥7 years of TKI plus ≥1 year of DMR” and exhibiting CTL activation features—CD8 > CD4, memory > effector, and/or highly activated CTL clones on TCR Vβ repertoire—showed the highest likelihood of durable TFR. By contrast, NK cells, effector Tregs, and G-/M-MDSCs did not discriminate TFR status in this cohort. Although antigen specificity against CML stem cells was not directly tested, the memory-dominant CTL phenotype is consistent with immune control after antigen reduction. These findings suggest that a simple, clinically accessible strategy based on flow cytometric CTL profiling and TCR Vβ clonality may help inform TKI discontinuation decisions in CML. External validation is warranted to confirm transportability and refine clinical thresholds. Full article

Estrogen suppress food intake, and soy isoflavones exhibit estrogen-like activities. However, the specific isoflavone components responsible for appetite regulation and their underlying neuroendocrine mechanisms remain unclear. We investigated whether the major soy isoflavones daidzein and genistein differentially influence feeding behavior and hypothalamic appetite-regulating neuropeptides in female rats. Ovariectomized (OVX) and sham-operated female rats were fed a control diet or diets supplemented with daidzein or genistein (150 mg/kg diet) for one or two weeks under ad libitum conditions. A separate OVX group received subcutaneous estradiol. Hypothalamic expression of orexigenic and anorexigenic neuropeptides was quantified during the dark (active) and light (inactive) phases. Daidzein, but not genistein, significantly reduced food intake, body weight gain, and body fat in both OVX and intact females, whereas estradiol decreased these parameters only in OVX rats. Among all hypothalamic neuropeptides examined, urocortin was the only gene that responded to dietary daidzein, showing a significant increase exclusively during the light phase of Week 1. Neither NPY nor CRH expression was altered by daidzein. The temporal pattern of urocortin induction closely paralleled the reduction in food intake, suggesting a potential mechanistic link. Daidzein exerts a female-specific anorectic effect that cannot be explained solely by estrogenic activity. The selective upregulation of hypothalamic urocortin during the light phase represents a novel neuroendocrine response to dietary daidzein and may contribute to its suppression of food intake. These findings provide new insight into the sex-specific metabolic actions of dietary isoflavones. Full article

The treatment landscape for endometrial carcinoma (EC) is undergoing a paradigm shift from traditional histopathological dualism to precision medicine grounded in the Cancer Genome Atlas (TCGA) molecular classification. The “No Specific Molecular Profile” (NSMP) subgroup, the largest molecular cohort, has emerged as a particularly promising target for endocrine-based strategies. While endocrine therapy (ET) has been a mainstay for over 60 years due to its favorable safety profile, its efficacy as monotherapy remains modest. This review provides a comprehensive overview of current endocrine strategies, including traditional agents like progestins and aromatase inhibitors, and focuses on novel combination therapies designed to overcome resistance. Recent clinical trials have demonstrated that integrating molecularly targeted agents, such as CDK4/6 and mTOR inhibitors, significantly improves clinical outcomes. Specifically, patients with TP53 wild-type status and CTNNB1 mutations exhibit exceptional responses to these combinations. Furthermore, we discuss the potential of next-generation selective estrogen receptor degraders (SERDs) and the importance of refining patient selection through robust predictive biomarkers. Driven by molecular insights, endocrine therapy is transitioning from a secondary palliative option into a definitive cornerstone of precision oncology, offering a personalized and effective treatment for patients with advanced or recurrent endometrial carcinoma. Full article

Developing children’s number sense is an important aspect of early mathematical education and has been the focus of multiple studies targeting the kindergarten stage. We investigated the impact of reading mathematical stories on the number sense of kindergarten children. A small-scale intervention study was conducted with 46 kindergarten children aged 5–7 years. The study employed a non-equivalent quasi-experimental design involving comparison and intervention groups. The intervention involved eight mathematical stories presented in interactive reading environments during their class storytime. Therefore, both the books and the interactive reading style were considered core components of the intervention in this study. A pretest, posttest, and delayed test measured the children’s number sense, and the resulting data was analysed with ANCOVA. The results showed the intervention to have a promising effect on their number sense: the experimental group significantly outperformed the control group on both the posttest and delayed test. We consider it important that teachers be encouraged to make the maximum use of kindergarten storytelling sessions to further children’s early mathematical understanding. With acknowledgement of the limited sample size and its implications for the statistical generalisability of the findings, this study should be regarded as an exploratory investigation that can inform and encourage future large-scale research. In addition, the findings offer meaningful pedagogical implications that may support teachers and curriculum designers in early childhood education and provide valuable insights into the potential effects of reading mathematical stories interactively with children in kindergarten in authentic classroom contexts. Full article

Background: Corisin, a microbiota-derived proapoptotic peptide, has emerged as a key mediator of epithelial injury, inflammation, and acute exacerbation in fibrotic lung disease. Although acute corisin inhibition prevents exacerbations in experimental models, its therapeutic impact on established pulmonary fibrosis remains unclear. This study evaluated the short-term efficacy of corisin neutralization in advanced transforming growth factor-β1 (TGF-β1)-driven lung fibrosis. Methods: Male TGF-β1 transgenic mice with established fibrosis were allocated to computed tomography-matched groups and treated intraperitoneally with an anti-corisin monoclonal antibody (clone 21A) or control IgG every two days for one week. Bronchoalveolar lavage fluid (BALF) analysis, histopathology, assessment of apoptosis, Ashcroft scoring, and lung hydroxyproline quantification were performed on day 8. Results: Anti-corisin treatment significantly reduced BALF inflammatory cell counts, including macrophages and lymphocytes. Histological analyses demonstrated decreased alveolar epithelial apoptosis, reduced collagen deposition, and significantly lower Ashcroft fibrosis scores. Lung hydroxyproline content was also markedly decreased, indicating attenuation of extracellular matrix accumulation. Conclusions: Short-term neutralization of microbiota-derived corisin rapidly alleviates inflammation, epithelial injury, and fibrotic remodeling in advanced TGF-β1-induced pulmonary fibrosis. These findings identify corisin as an upstream driver of ongoing fibrogenesis and support its potential as a therapeutic target in progressive fibrotic lung disease. Full article

Endocervical adenocarcinoma is now classified within an etiologic framework based on the presence or absence of high-risk human papillomavirus (HPV) infection. Gastric-type endocervical adenocarcinoma (GAS) is the prototypical HPV-independent subtype, accounting for up to 25% of endocervical adenocarcinomas and showing a particularly high frequency in East Asia. GAS is typically diagnosed at a more advanced stage than usual-type HPV-associated endocervical adenocarcinoma (UEA); exhibits deep stromal and parametrial invasion, lymphovascular space invasion, and a strong propensity for ovarian and peritoneal metastasis; and is associated with markedly worse survival, even in stage I disease. Radiological evaluation is challenging because of diffuse infiltrative growth, prominent mucin production, and frequent underestimation of extra-cervical spread. Histologically, GAS shows gastric-type (pyloric) differentiation, ranging from minimal deviation adenocarcinoma to poorly differentiated forms, and often overlaps with precursor lesions such as atypical lobular endocervical glandular hyperplasia and gastric-type adenocarcinoma in situ. Immunophenotypically, GAS is typically p16-negative, ER/PR-negative, and frequently exhibits mutant-type p53 and expression of gastric markers including MUC6, HIK1083, and claudin 18.2. Recent next-generation sequencing and multi-omics studies have revealed recurrent alterations in TP53, CDKN2A, STK11, KRAS, ARID1A, KMT2D, and homologous recombination-related genes, together with the activation of PI3K/AKT, WNT/β-catenin, TGF-β, and EMT pathways and characteristic metabolic reprogramming. GAS is highly resistant to conventional chemotherapy and radiotherapy, and its current management follows guidelines for squamous and usual-type adenocarcinoma. Emerging data support precision-medicine approaches targeting HER2/HER3, PD-1/PD-L1, and claudin 18.2, and suggest a role for PARP inhibition and other genotype-directed therapies in selected subsets. Given its aggressive biology and rising relative incidence in the HPV-vaccination era, GAS represents a critical unmet need in gynecologic oncology. Future progress hinges on developing reliable diagnostic biomarkers, refining imaging protocols, and validating targeted therapies through international clinical trials. Full article

Hepatitis B virus (HBV) remains a major global health threat because covalently closed circular DNA (cccDNA) persists in hepatocytes and limits the efficacy of current antiviral therapies. Effective HBV research and drug screening require culture models that recapitulate the complete viral life cycle and allow for quantitative monitoring of replication. In this study, an 11-amino acid luminescent reporter, HiBiT, was inserted at multiple sites within the preS1 region of a genotype D HBV genome, and the C terminus of preS1 was identified as optimal for maintaining robust replication. We then established HepG2-B4 cells stably replicating HiBiT-HBV with HiBiT at the preS1 C terminus. Extracellular HiBiT activity and supernatant levels of HBV-DNA, HBsAg, and HBcAg increased continuously until day 42 and were reduced by nucleos(t)ide analog treatment, and cccDNA was confirmed by Southern blot analysis. Supernatants from HepG2-B4 cells infected naïve HepG2-NTCP cells and primary human hepatocytes, as shown by extracellular HiBiT activity. Transcriptome analysis revealed distinct gene expression changes in HepG2-B4 cells compared with parental HepG2 cells. These findings indicate that the HepG2-B4 system provides a rapid, quantitative, and scalable platform for HBV replication and infection studies and is suitable for mechanistic investigations and high-throughput antiviral screening. Full article

Anti-GQ1b antibody syndrome (AGABS) unifies triad-defined Miller Fisher syndrome (MFS), Bickerstaff brainstem encephalitis (BBE), and the ophthalmoplegic variant of Guillain–Barré syndrome (GBS-O) under a post-infectious immune mechanism centered on IgG to disialosyl gangliosides. The spectrum also encompasses triad-minus phenotypes—acute ophthalmoparesis without ataxia, acute vestibular syndrome, optic involvement, and acute sensory-ataxic neuropathy. A molecular-mimicry model with complement-mediated nodal/paranodal dysfunction explains severe early deficits despite bland limb nerve conduction studies (NCSs), the cranial/proprioceptive predilection, and generally favorable treatment responsiveness to immunotherapy. In practice, a serology-first strategy, complemented by targeted electrophysiology—blink and H-reflex testing, and, where feasible, paired SEP–ABR showing a literature-supported dissociation (normal ABR with impaired median-nerve cortical SEPs), which, in our series, was documented in one illustrative BBE case—and by structured neuro-otologic examination, mitigates the “normal-NCS trap” and enables timely treatment. Intravenous immunoglobulin (IVIg) is first-line; plasma exchange (PLEX) is an alternative in severe or IVIg-ineligible cases; and intravenous methylprednisolone (IVMP) may be added selectively for central/optic-weighted phenotypes without routine oral taper. We consolidate actionable diagnostic and therapeutic steps and examine them in an institutional series of 16 consecutive seropositive patients (2015–2025): all were anti-GQ1b-positive with frequent GT1a co-reactivity; most reported an antecedent infection—typically upper respiratory, less often gastrointestinal—within the two weeks before onset; limb NCSs were often nondiagnostic whereas reflex/evoked-potential studies were informative; two required intubation in addition to IVIg; outcomes were generally favorable with early immunotherapy. The practical message: order anti-GQ1b at first contact, pair targeted electrophysiology with neuro-otology, and treat early to exploit reversible nodal/paranodal dysfunction. Full article

Objectives: This pilot study examined telerehabilitation, which has emerged as a crucial modality in light of recent global challenges such as the COVID-19 pandemic. We examined the effectiveness of a mobile health telerehabilitation intervention developed for older adults with frailty. Methods: Six participants received a telerehabilitation intervention (Rehab Studio) that included exercise training videos. The participants were aged ≥65 years, had no history of dementia or psychiatric disorders, and had mild-to-moderate care needs. For 1 month, the participants received 1 h live online rehabilitation sessions with real-time communication with rehabilitation specialists (physical therapists and occupational therapists: PTs/OTs). The quality of life (QoL) (EuroQol 5 dimensions 5-level [EQ-5D-5L] questionnaire) and self-rated health scores were recorded before and after the intervention, and the data were analyzed using paired t-tests to determine whether the service was effective. Results: Significant differences were found in the total EQ-5D-5L and self-rated health scores (p < 0.05). The mean EQ-5D-5L score increased from 0.63 ± 0.13 before the intervention to 0.77 ± 0.14 after the intervention (p = 0.010), while the mean self-rated health score increased from 66.0 ± 18.0 to 83.3 ± 10.3, respectively (p = 0.019). Conclusions: This study revealed that the mobile health telerehabilitation intervention is safe and can improve QoL for older adults with frailty. However, the effectiveness of the intervention needs to be further investigated in patients with poor performance in daily living activities. Telerehabilitation could help to reduce the burden of nursing care in aging societies with declining birthrates. However, given the extremely small sample size (N = 6), these p-values should be interpreted with considerable caution. Statistical significance in such a small sample does not provide strong evidence for population-level effects, and our findings should be regarded as hypothesis-generating rather than confirmatory. Full article

Late bedtimes and insufficient sleep duration among children and adolescents have been consistently associated with daytime sleepiness, irritability, and poorer academic performance. To mitigate these adverse consequences of insufficient sleep, it is essential to provide children, students, teachers, and parents with not only knowledge about sleep improvement but also practical tools that facilitate behavioral change. This review synthesizes existing evidence from studies that have addressed this issue by evaluating students’ individual sleep behaviors using checklists of sleep-promoting practices. Drawing on practical examples from school-based interventions, the review highlights the effectiveness of sleep education programs for children and adolescents. These programs aim to bridge the gap between sleep-related knowledge and actual behavioral change by targeting daily sleep habits. Typically, such programs consist of a single 50 min educational session focusing on the importance of sleep and strategies for improvement, followed by a two-week self-help period during which students actively practice and monitor specific target behaviors. Overall, the findings indicate that sleep education programs incorporating self-help components not only enhance sleep-related knowledge but also promote healthier sleep behaviors and improve sleep patterns. Moreover, these programs effectively reduce daytime sleepiness and irritability among children and adolescents, thereby contributing to a healthier and more adaptive school life. Full article

Background/Objectives: Recent advances in large language models (LLMs) have enabled the multimodal interpretation of medical images, but their agreement in ophthalmology issues remains underexplored. This study evaluated the ability of ChatGPT-4o, a multimodal LLM, to classify idiopathic epiretinal membrane (ERM) using optical coherence tomography (OCT) based on the Govetto classification. Methods: This retrospective study included 250 eyes of 250 patients with idiopathic ERM who visited Uonuma Kikan Hospital between June 2015 and April 2025. Horizontal B-scan OCT images were independently classified into four stages by two masked ophthalmologists; cases with disagreement were excluded. ChatGPT-4o was prompted to identify ocular diseases and classify ERM stage. Agreement between ChatGPT-4o and ophthalmologists was evaluated using weighted Cohen’s κ, and logistic regression identified factors associated with disagreement. Results: Among 272 eligible eyes, 250 were analyzed (Stage 1: 87; Stage 2: 76; Stage 3: 63; Stage 4: 24). ChatGPT-4o identified the presence of ERM in 26.4% of cases on the first prompt. The perfect agreement rate for Govetto staging was 46.0%, with a weighted κ of 0.513 (95% CI: 0.420–0.605; p < 0.001), indicating moderate agreement. Disagreement was significantly associated with the presence of ectopic inner foveal layer (EIFL) (OR = 0.528, 95% CI: 0.312–0.893; p = 0.017). Conclusions: ChatGPT-4o showed moderate agreement with ophthalmologists in Govetto classification of idiopathic ERM using OCT images. Although its agreement was limited, the model demonstrated partial ability to recognize retinal structures, providing insight into the current capabilities and limitations of multimodal large language models in ophthalmic image interpretation. Full article

Functional steel surfaces engineered through tailored micro-nano structures are increasingly vital for various applications such as high-performance aerospace components, energy conversion systems and defense equipment. Femtosecond laser filament processing is a recently proposed remote fabrication technique, showing the capability of fabricating micro-nano structures on irregular and large-area surfaces without the need of tight focusing. Nevertheless, the mechanisms underlying the formation of filament-induced structures remain not fully understood. Here we systematically investigate the formation mechanisms of filament-induced micro-nano structures on stainless steel surfaces by processing stainless steel in three manners: point, line, and area. We clarify the decisive role of the unique core–reservoir energy distribution of the filament in the formation of filament-induced micro-nano structures, and reveal that ablation, molten metal flow, and metal vapor condensation jointly drive the structure evolution through a dynamic interplay of competition and coupling, giving rise to the sequential morphological transitions of surface structures, from laser-induced periodic surface structures to ripple-like, crater-like, honeycomb-like, and ultimately taro-leaf-like structures. Our work not only clarifies the mechanisms of femtosecond laser filament processed morphological structures on steels but also provides insights onto intelligent manufacturing and design of advanced functional steel materials. Full article

Background/Objectives: Mini-tablets have gained popularity as a pediatric dosage form owing to their high acceptability. Since 2022, the Showa University Hospital has prescribed acetylsalicylic acid (ASA) mini-tablets to pediatric patients with Kawasaki disease (KD). In this study, we investigated the real-world, at-home administration status of ASA mini-tablets in pediatric patients with KD. Methods: This retrospective study included 14 pediatric patients with KD on ASA mini-tablet therapy between November 2022 and October 2024. Medication administration completeness, mood changes during administration, administration patterns, beverages consumed, and swallowing-related events were analyzed. Associations between changes in the administration pattern or beverage consumption and swallowing events or mood changes were evaluated. Serious adverse events and coronary artery aneurysms were assessed using medical records. Results: Patients were prescribed ASA mini-tablets for a mean duration of 60.9 days. No serious adverse events or coronary aneurysms were observed. Among the 679 medication records, 5 swallowing-related events were identified. No mood changes following administration were observed in >90% of cases. The mood worsened to “Bad” once, with no further deterioration. The “All at once” administration pattern occurred in 64% of occasions across 12 patients (age: 9–79 months). Patients aged <3 years used medication-assisted jelly, whereas older patients mostly used water. Conclusions: ASA mini-tablets can be safely administered at home with minimal swallowing problems. Patients completed full doses irrespective of tablet number, age, administration pattern, or beverage, supporting ASA mini-tablets as an acceptable dosage form option for ASA in KD. Full article

The automation of quality control in agricultural food processing, particularly the detection of incomplete peeling in taro, constitutes a critical frontier for ensuring food safety and optimizing production efficiency in the Industry 4.0 era. However, this domain is fraught with significant technical challenges, primarily stemming from the inherent visual characteristics of residual peel: extremely minute scales relative to the vegetable body, highly irregular morphological variations, and the dense occlusion of objects on industrial conveyor belts. To address these persistent impediments, this study introduces a comprehensive solution comprising a specialized dataset and a novel detection architecture. We established the Taro Peel Industrial Dataset (TPID), a rigorously annotated collection of 18,341 high-density instances reflecting real-world production conditions. Building upon this foundation, we propose MDB-YOLO, a lightweight, multi-dimensional bionic detection model evolved from the YOLOv8s architecture. The MDB-YOLO framework integrates a synergistic set of innovations designed to resolve specific detection bottlenecks. To mitigate the conflict between background texture interference and tiny target detection, we integrated the C2f_EMA module with a Wise-IoU (WIoU) loss function, a combination that significantly enhances feature response to low-contrast residues while reducing the penalty on low-quality anchor boxes through a dynamic non-monotonic focusing mechanism. To effectively manage irregular peel shapes, a dynamic feature processing chain was constructed utilizing DySample for morphology-aware upsampling, BiFPN_Concat2 for weighted multi-scale fusion, and ODConv2d for geometric preservation. Furthermore, to address the issue of missed detections caused by dense occlusion in industrial stacking scenarios, Soft-NMS was implemented to replace traditional greedy suppression mechanisms. Experimental validation demonstrates the superiority of the proposed framework. MDB-YOLO achieves a mean Average Precision (mAP50-95) of 69.7% and a Recall of 88.0%, significantly outperforming the baseline YOLOv8s and advanced transformer-based models like RT-DETR-L. Crucially, the model maintains high operational efficiency, achieving an inference speed of 1.1 ms on an NVIDIA A100 and reaching 27 FPS on an NVIDIA Jetson Xavier NX using INT8 quantization. These findings confirm that MDB-YOLO provides a robust, high-precision, and cost-effective solution for real-time quality control in agricultural food processing, marking a significant advancement in the application of computer vision to complex biological targets. Full article