Search Results (6,520)

Background: Owing to significant clinical heterogeneity, the achievement of accurate survival forecasting for individuals with colorectal cancer and peritoneal metastasis continues to be a complex undertaking. We aimed to transcend traditional prognostic limitations by evaluating machine learning boosting models against standard regression-based methods in terms of estimating overall survival (OS). Methods: Utilizing a multi-institutional registry of 150 patients diagnosed with synchronous peritoneal metastasis of colorectal cancer, we integrated 124 clinicopathological variables to refine our predictive models. Beyond standard preprocessing—including standardization and median imputation—we rigorously compared XGBoost and LightGBM against Ridge, Lasso, and linear regression via five-fold cross-validation. To specifically address right-censoring, an XGBoost Cox model was implemented and validated using Harrell’s C-index, with SHAP and LIME providing essential model interpretability. Results: Boosting models consistently outperformed linear alternatives, which struggled with high error rates and negative R2 values. Specifically, XGBoost achieved an MAE of 475 ± 60 and an RMSE of 585 ± 88. The XGBoost Cox model reached a C-index of 0.64 ± 0.06. SHAP analysis highlighted inflammatory markers and peritoneal disease extent as the most influential prognostic drivers. Conclusions: While boosting models offer a clear accuracy advantage over linear methods, their prognostic power remains moderate. These findings underscore the potential of ensemble learning in oncology, yet mandate external validation before these tools can be integrated into clinical decision-making. Full article

Aerosols are a major transmission route for seasonal influenza infections. Titanium dioxide (TiO₂) photocatalyst has broad-spectrum antiviral activity, including in vitro influenza virus inactivation; however, whether the TiO₂ photocatalyst can effectively inactivate airborne influenza A viruses in vivo under conditions that mimic natural aerosol transmission remains unclear. Here, we evaluated in vivo inactivation of airborne H1N1 seasonal influenza virus by a photocatalyst-equipped air purifier using a mouse model. Influenza virus WSN strain aerosols were sprayed in a 60 L acrylic box with a nebulizer, circulated through a photocatalyst-equipped air purifier, exposed to BALB/c mice for 40 min after circulation, and subsequently collected with an air sampler. Thirty minutes of TiO₂ photocatalyst treatment reduced influenza virus infectivity by 99.97%, and significantly lowered lung viral titer in mice on day 3 post-infection. Over 14 days post-infection, mice showed no >10% weight loss, 100% survival, and disease progression to the PBS (−) aerosol group. This suggests that the photocatalyst-equipped air purifier may reduce H1N1 seasonal influenza onset, preventing viral spread. Full article

Backgrounds and Aim: Pancreatic cancer is frequently diagnosed at advanced stages, highlighting the need for biomarkers that are capable of detecting early-stage disease in asymptomatic individuals. Recently, apolipoprotein A2 isoforms (ApoA2-ATQ/AT) have been reported as a new blood biomarker for pancreatic cancer. We recently developed diagnostic models based on 100 highly expressed serum microRNAs (miRNAs) combined with CA19-9; these models achieved high accuracy in terms of distinguishing individuals with pancreatic cancer from healthy individuals. This study aimed to compare the diagnostic performance of these miRNA-based models with that of the ApoA2-ATQ/AT biomarker. Methods: Comprehensive sequencing of serum miRNAs was conducted using samples from 120 pancreatic cancer patients recruited across 14 hospitals, along with 93 healthy controls without cancer. Serum CA19-9 levels, miRNA index values, miRNA+CA19-9 index values, and ApoA2 index values were assessed. miRNA-based indices were derived from classification models built on an automated machine-learning platform. Results: The miRNA model (AUC 0.94; 95% CI 0.91–0.97) and the miRNA+CA19-9 model (AUC 0.99; 95% CI 0.98–1.00) outperformed ApoA2 (AUC 0.89; 95% CI 0.84–0.93) in terms of distinguishing individuals with pancreatic cancer from healthy controls across all stages. In early-stage disease (stages 0–I and 0–II), both miRNA-based models also demonstrated superior performance. Strong negative correlations were observed between the ApoA2 index and both the miRNA model index (r = −0.62) and the miRNA+CA19-9 index (r = −0.63). Conclusions: These findings suggest that miRNA-based diagnostic models, particularly when combined with CA19-9, could serve as powerful tools for the early detection of pancreatic cancer. Full article

High-precision and reliable self-localization is essential for autonomous navigation systems. However, in urban canyons (urban environments with clusters of high-rise buildings), Global Navigation Satellite Systems (GNSS) suffer from severe multipath and Non-Line-of-Sight (NLOS) signal reception. This causes a theoretically unbounded positive bias in pseudorange measurements, significantly degrading positioning integrity. To address this challenge, this study proposes a novel GNSS/Inertial Measurement Unit (IMU) tightly coupled integrated navigation system using factor graph optimization (FGO) integrated with machine learning-based NLOS detection. To train the NLOS detection model, we utilized a dual-polarized antenna to label signals based on the strength difference between RHCP and LHCP components, achieving a detection accuracy of 0.89. A random forest classifier identifies NLOS signals, and based on its classification labels, the variance of the corresponding GNSS pseudorange factors within the FGO framework is dynamically inflated. This effectively mitigates the impact of outliers while preserving the graph topology. Experimental evaluations in dense urban environments demonstrated that the proposed method improves horizontal positioning accuracy by 84.8% compared to conventional standalone GNSS positioning. The dynamic integration of machine learning-based signal classification and tightly coupled FGO provides an extremely robust positioning solution, proven to meet the stringent reliability requirements demanded of autonomous systems even under severe signal obscuration. Full article

Renal organic anion transporters 1 (OAT1) and 3 (OAT3) mediate the excretion of endogenous metabolites and xenobiotics. Flavonoids interact significantly with these transporters, but the structural determinants—especially regarding in vivo phase II metabolism—remain unclear. This review integrates recent cryogenic electron microscopy (cryo-EM) structural biology and transporter kinetics to delineate the molecular basis of flavonoid–OAT interactions. We highlight phase II metabolites as key in vivo effectors. Structurally, OAT1 strictly favors compact, planar anionic scaffolds, whereas OAT3 accommodates bulkier, conjugated forms. Crucially, flavonoids exert a “double-edged” toxicological effect: high-affinity OAT inhibition risks herb–drug interactions, yet competitively limits the tubular uptake of nephrotoxins. Furthermore, disease states and post-translational regulation reshape these interactions. By bridging structural insights with biomarker-guided pharmacokinetics, we propose a mechanistic framework to improve the precise safety assessment of flavonoid-containing therapeutics. Full article

Background/Objectives: Diagnosing anterior cruciate ligament (ACL) insufficiency, particularly partial tears, remains challenging with standard static imaging. This study introduces a novel conceptual approach: assessing the dynamic kinematics of the infrapatellar fat pad (IPFP) as an indirect marker of ACL deficiency. Methods: In this biomechanical proof-of-concept study, dynamic ultrasound tracked IPFP kinematics in eight cadaveric knees evaluated in intact (Control), Sham, and Torn ACL states during passive flexion. The primary endpoints were (i) the absolute anteroposterior position at 90° (y₂ − y₁) and (ii) the posterior displacement during the 60–90° flexion arc (ΔY 60–90°). Results: ACL deficiency significantly altered deep-flexion IPFP kinematics. For ΔY 60–90°, the Torn ACL group demonstrated a substantial loss of posterior excursion compared to the Control group (Mean ± SD: −0.25 ± 1.03 vs. 2.88 ± 1.29 mm; Welch’s p < 0.001; Hedges’ g = 2.54, 95% CI: 1.18 to 3.89) and the Sham group (3.46 ± 1.63 mm; p < 0.001; g = −2.57, 95% CI: −3.90 to −1.25). Consequently, for y₂ − y₁ at 90°, the Torn ACL group remained abnormally anterior versus Control (p = 0.003; g = −1.97) and Sham (p < 0.001; g = −1.82). Conclusions: ACL deficiency induces a distinct reduction in posterior IPFP displacement. While these massive effect sizes establish a strong biomechanical rationale, this study serves as a foundational proof-of-concept. Large-scale in vivo clinical trials are strictly required to validate its diagnostic utility before clinical implementation. Full article

Background/Objectives: Vision-language models (VLMs) such as GPT (Generative Pre-Trained Transformer) have shown potential for medical image interpretation; however, challenges remain in generating reliable radiological findings in clinical practice, as exemplified by dental pathologies. This study proposes a Self-correction Loop with Structured Output (SLSO) framework as an integrated processing methodology to enhance the accuracy and reliability of AI-generated findings for jaw cysts in dental panoramic radiographs. Methods: Dental panoramic radiographs with jaw cysts were used to implement a 10-step integrated processing framework incorporating image analysis, structured data generation, tooth number extraction, consistency checking, and iterative regeneration. The framework functioned as an external validation mechanism for GPT outputs. Performance was compared against the conventional Chain-of-Thought (CoT) method across seven evaluation items: transparency, internal structure, borders, root resorption, tooth displacement, relationships with other structures, and tooth number. Results: The SLSO framework improved output accuracy for multiple items compared to the CoT method, with the most notable improvements observed in tooth number identification, tooth displacement detection, and root resorption assessment. In successful cases, consistently structured outputs were achieved after up to five regenerations. The framework enforced explicit negative finding descriptions and suppressed hallucinations, although accurate identification of extensive lesions spanning multiple teeth remained limited. Conclusions: This investigation established the feasibility of the proposed integrated processing methodology and provided a foundation for future validation studies with larger, more diverse datasets. Full article

Commercially available wearable health devices (WHDs) carry the potential to decentralize healthcare systems. These devices can empower individuals with health knowledge by offering a low-cost and accessible way to monitor physical activity, sedentary behavior, cardiac health, and sleep. However, a lack of standardization in design, health, and safety regulations means that consumer-grade WHDs on the market vary in efficacy to affect positive behavior change in users, as user compliance alone does not indicate whether these devices actually influence wellbeing outcomes long term. We use a grounded theory analysis of the experiences of seven long-term informed users of the same wearable, the Oura Ring, to propose a substantive theory describing the tacit challenges that these users face in order to truly benefit from their device even after extended use. We provide recommendations as to how designers of wearable devices can facilitate the user’s journey to surpass these obstacles. Full article

The growing accessibility of small satellite technologies and international cooperation frameworks has enabled many emerging countries to initiate space development activities; however, the mechanisms through which they build and advance satellite development capabilities remain insufficiently theorized, as existing models such as the Space Technology Ladder capture only high-level milestones. To address this gap, this study proposes the Satellite Technology Ladder (SaTL), a structured 16-level framework integrating satellite development methods and satellite size as indicators of technological maturity. We conducted a comprehensive longitudinal analysis of all satellite projects initiated since 1990 across 16 emerging countries, coding each project according to the SaTL scheme and evaluating national trajectories over time. The analysis reveals four distinct developmental trajectories: (1) prolonged dependence on foreign procurement, (2) gradual capability enhancement through externally supported development, (3) expansion of domestic industrial ecosystems following initial collaboration, and (4) independent development from the outset based on pre-existing technological foundations. These findings demonstrate that technological advancement depends not only on technology introduction but also on absorptive capacity, institutional learning, and broader industrial structures. SaTL thus offers a theoretically grounded and empirically validated tool for assessing capability formation and informing policy strategies in emerging spacefaring nations. Full article

Naked mole-rats are extremely long-lived rodents with a lifespan of up to 40 years, during which cellular and tissue aging is rarely observed. In this study, we analyzed the extracellular matrix (ECM) of naked mole-rat skin at the molecular level to elucidate the molecules involved in anti-aging and their localization. Raman spectroscopy and Fourier transform infrared spectroscopy were applied to investigate the hierarchical structure of the ECM, showing that, whereas the epidermis of aged mice had thinned, the epidermis of naked mole-rats became thickened and hyaluronic acid (HA) was distributed under the basement membrane. Furthermore, naked mole-rat skin had a regular skin texture and flexibility, allowing the maintenance of a youthful appearance. Hyaluronic acid in naked mole-rats characteristically exists as clusters (chain HA) in skin tissue, where it is thought to permit moisture retention and maintain elasticity, contributing to the skin’s youthful appearance. These results suggested that not only the density of ECM but also its spatial distribution and topographic properties are important for skin anti-aging. Our findings may contribute to the elucidation of skin disease pathology, the development of therapeutic gel scaffolds, and the control of aging. Full article

Horses develop spontaneous tumors, typically in old age. Although local tumor control can be achieved using conventional therapies, systemic therapies are required to treat recurrent and/or metastatic tumors. Immune checkpoint inhibitors, such as anti-PD-L1 antibodies, have been approved for the treatment of various tumor types in humans; however, little is known about the immunosuppressive roles of the PD-1/PD-L1 pathway in horses, and the therapeutic potential of these inhibitors remains to be elucidated. Previously, we reported that the rat monoclonal anti-PD-L1 antibody 6C11-3A11 cross-reacts with horse PD-L1 to block the PD-1/PD-L1 interaction. To further develop antibodies for therapeutic purposes, their immunogenicity must be reduced to maximize efficacy and safety. To this end, we designed an equinized (equine-ized) anti-PD-L1 antibody, Eq6C11, using the complementarity-determining regions of 6C11-3A11. Eq6C11 had antigen-binding properties comparable to those of 6C11-3A11 and inhibited equine PD-L1 binding to PD-1 in a recombinant protein-based assay. Treatment with Eq6C11 significantly increased IFN-γ and IL-2 production in equine peripheral blood mononuclear cell cultures, suggesting its stimulatory activity on T-cell activation. Although further studies are needed to clarify its immunogenicity and clinical activity, these results encourage further development of Eq6C11 as a candidate immune checkpoint inhibitor for cancer immunotherapy in horses. Full article

Cosmetic dermatology has largely focused on topical applications targeting the stratum corneum. However, emerging evidence suggests that visible aging is a systemic readout of internal “organ clocks” and molecular dysregulation across the epidermis and dermis. This review proposes an “inside–out strategy” that seeks to re-conceptualize aesthetic vitality as a measurable indicator of systemic physiological resilience. The author describes theoretically proposed organ–skin axes, including the role of molecular signaling of kidney-derived klotho (KL1 fragment) via FGFR1-α–klotho complexes and muscle-derived irisin through the AMPK/PGC-1-α pathway in modulating skin homeostasis. Drawing on recent breakthroughs in non-human primate models (2023–2025), this synthesis explores the potential of systemic interventions—including nicotinamide adenine dinucleotide (NAD+) precursors (sirtuin 1 SIRT1 activators), senolytics (targeting BCL-2/p16), and glucagon-like peptide-1 (GLP-1) receptor agonists—as candidates to potentially synchronize these internal clocks. Furthermore, the review identifies direct regenerative interventions, such as retinoids (RAR/RXR signaling), chemical peels (HIF-1-α induction), exosomes (miR-21/29 delivery), and poly-L-lactic acid PLLA (mechanotransduction via YAP/TAZ), positioning them as potential physical and chemical epigenetic modulators that may support the restoration of cellular transcriptional fidelity. This article proposes a new paradigm for regenerative aesthetics that focuses on restoring the youthful phenotype by optimizing systemic molecular crosstalk and epigenetic transcriptional fidelity. Full article

Despite their significance as forensic targets, alkyl nitrites, classified as illegal drugs, have received little attention in forensic analysis due to their high volatility and chemical instability. Here, we present a high-performance analytical approach using a pulsed dc soft plasma ionization-quadrupole mass spectrometry (pulsed dc SPI-MS) system, uniquely designed to operate using ambient air as the discharge gas. In this system, the modulation of the duty ratio functions as a “structural probe” to identify reactive isomers. Unlike conventional dielectric barrier discharge (DBD) sources that typically operate at atmospheric pressure, our SPI system utilizes a controlled pressure regime of several kPa, where the nitrogen in the ambient air effectively functions as a third-body gas to suppress excessive internal energy. The control of the duty ratio in our pulsed dc SPI source allowed for the successful manipulation of ion–molecule reaction pathways for highly reactive analytes. By optimizing several parameters, including duty ratio and discharge pressure, we achieved a unique ionization regime where the molecular-related ion [2 M − 3 H]⁺ was predominantly detected as the base peak with minimal fragmentation. Notably, by reducing the duty ratio from 50% to 5%, both the target ion occupancy and signal intensity were significantly enhanced, achieving a limit of detection (LOD) as low as 0.16 parts per million by volume (ppmv). This sensitivity is several orders of magnitude higher than previously reported thresholds, enabling rapid identification of C4–C6 alkyl nitrite isomers. This method transforms the duty ratio into a powerful diagnostic tool for identifying reactive intermediates, providing a practical and efficient approach for the onsite identification of illegal alkyl nitrites in forensic and security fields. Full article

Human papillomavirus (HPV) can cause cervical cancer. Global viral eradication relies on specific criteria, including a single host species and effective vaccines, a feat successfully achieved with smallpox and rinderpest. Although measles is also a candidate for elimination, its progress has been hindered by vaccine hesitancy based on misinformation about vaccine safety. Similarly, HPV is an ideal candidate for eradication due to its strict human infectivity and the proven vaccine efficacy in reducing cancer rates and establishing herd immunity. We highlighted the growing global consensus on single-dose HPV vaccination to improve feasibility and compliance with comparable effectiveness and safety to three-dose vaccination. Supporting this, we demonstrated that mice receiving a single HPV vaccine produced anti-HPV antibodies without a prolonged pro-inflammatory cytokine profile. On the other hand, in Japan, a nine-year suspension of proactive government recommendations occurred due to alleged adverse events termed “HPV vaccination-associated neuro-immunopathic syndrome (HANS),” drastically reducing vaccination rates, despite rigorous international studies have confirmed the vaccine’s safety. Critical scientific evaluation demonstrated that HANS failed to meet the criteria for autoimmune diseases (Witebsky’s postulates); no evidence has been presented that HANS is a novel autoimmune disease. The claim of molecular mimicry between HPV L1 and human proteins was based solely on flawed computational analyses. Furthermore, the hypothesis implicating a pathogenic role for aluminum adjuvants was unsupported by experimental evidence; HANS animal models were flawed methodologically and unreproducible experimentally. In summary, we believe that implementing worldwide HPV vaccination strategies, including gender-neutral and single-dose programs, as well as denouncing pseudoscientific claims hold the potential to eliminate high-risk HPV types globally. Full article

Gastric-type lesions in the duodenum, including pyloric gland adenoma and gastric foveolar metaplasia, have been increasingly recognized for their unique histogenesis and potential link through the metaplasia–neoplasia sequence. However, the coexistence of neoplastic and non-neoplastic gastric-type lesions within the same histological section has not been previously reported. Here, we present a case of a 73-year-old Japanese woman who underwent endoscopic submucosal dissection for a 34 × 20 mm elevated lesion in the duodenal bulb. Based on the preoperative biopsy results, pyloric gland adenoma was diagnosed; however, histopathological examination of the resected specimen revealed a far more complex picture. The main lesion consisted of two contiguous components: a hyperplastic polyp with gastric foveolar-type phenotype (Lesion I) and a pyloric gland adenoma mixed with gastric foveolar-type hyperplastic polyp (Lesion II). Importantly, the transitional zone between these components demonstrated histological continuity, with areas showing admixture of hyperplastic and adenomatous features within the same microscopic field. A separate hyperplastic polyp with gastric foveolar-type phenotype (Lesion III) was also identified, separated from Lesions I and II by intervening normal duodenal mucosa. All lesions shared a gastric-type mucin phenotype (MUC5AC-positive, CD10-negative), and extensive Brunner’s gland hyperplasia was observed throughout the specimen. This case provides compelling morphological evidence for a histogenetic link between non-neoplastic gastric-type hyperplasia and pyloric gland adenoma, supporting the concept of a metaplasia–neoplasia sequence in the duodenum. Furthermore, the presence of an additional separate lesion with the same phenotype suggests a field change in the development of gastric-type lesions. Full article