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Background and Objectives: Knee osteoarthritis (OA) is a leading cause of pain and disability, with radiographic severity influenced by age, biomechanical alignment, and structural joint features. Data describing the association between common radiographic parameters and OA severity in Eastern European clinical populations
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Background and Objectives: Knee osteoarthritis (OA) is a leading cause of pain and disability, with radiographic severity influenced by age, biomechanical alignment, and structural joint features. Data describing the association between common radiographic parameters and OA severity in Eastern European clinical populations remain limited. This study aimed to evaluate the associations between radiographic OA severity and coronal alignment, patellar height, and chondrocalcinosis in a Romanian clinical cohort. Materials and Methods: This single-center cross-sectional study included adult patients undergoing knee radiography for knee-related symptoms and/or functional assessment at a rehabilitation hospital between 2023 and 2025. Radiographs were obtained in the supine, non-weight-bearing position and included anteroposterior and lateral views. OA severity was graded using the Kellgren–Lawrence (KL) classification. Coronal alignment was assessed using the femorotibial angle, patellar height using the Insall–Salvati ratio (ISR), and chondrocalcinosis was recorded as present or absent. Associations between radiographic parameters and KL grade were analyzed using non-parametric statistics. Receiver operating characteristic (ROC) analyses were performed for exploratory assessment of limited separation between distributions. Results: Moderate to severe OA (KL ≥ 3) was present in 49% of patients. KL grade showed a moderate positive correlation with age (r = 0.50, p < 0.001) and differed significantly across coronal alignment categories (p < 0.001). Varus/valgus and pathological alignment classifications demonstrated moderate sensitivity (0.69–0.85) and variable specificity (0.52–0.85) for higher KL grades. ROC analyses of continuous alignment and ISR measures yielded area under the curve values ranging from approximately 0.65 to 0.68, indicating limited separation between distributions. Radiographically detected chondrocalcinosis was present in 5.3% of patients and showed no significant association with OA severity, and neither did patellar height. Conclusions: In this single-center Romanian clinical cohort, radiographic OA severity was associated with coronal plane alignment but not with patellar height or chondrocalcinosis. Alignment measures demonstrated limited discriminative ability and should be interpreted as complementary rather than diagnostic indicators of OA severity. These findings provide descriptive radiographic data from an Eastern European clinical population and highlight the need for longitudinal and population-based studies incorporating mechanical axis assessment and functional outcomes.
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Background: Intervertebral motion is a fundamental aspect of spinal biomechanics, crucial for understanding lumbar spine function, pain mechanisms, and surgical outcomes. Various methods exist for measuring and interpreting it, each with its own advantages, limitations, and specific applications. However, a comprehensive and standard
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Background: Intervertebral motion is a fundamental aspect of spinal biomechanics, crucial for understanding lumbar spine function, pain mechanisms, and surgical outcomes. Various methods exist for measuring and interpreting it, each with its own advantages, limitations, and specific applications. However, a comprehensive and standard taxonomy of study types for the measurement and interpretation of in vivo intervertebral motion in the lumbar spine is lacking. Objectives: This review aimed to systematically identify, characterise, and categorise the diverse study types deposited in the literature. Eligibility criteria: Only studies in English and of lumbar spine intervertebral motion in living subjects were considered, and only those that employed objective measurement of motion sequences were included. Sources of evidence: A comprehensive literature search was performed in PubMed, CINAHL, and SCOPUS for articles published between January 2000 and October 2025. Charting methods: After removal of duplicates, all studies were subjected to Title and abstract screening, followed by full-text screening of potentially eligible studies. Data selected were charted into tables under the headings: author, year, country, purpose, technology, participants, measurement, interpretation, radiation dosage, and significance of findings. Results: Forty-nine studies were abstracted and are described under 11 study types. These formed a taxonomy constituting the following six categories: normal biomechanical mechanisms, pathological and injury mechanisms, direct kinematic measurement, spinal stabilisation, dynamic radiography, and clinical markers. The resulting taxonomy will serve as a resource for researchers, clinicians, and policymakers by facilitating a more coherent understanding of the field and promoting standardisation in research design and reporting.
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We study the properties of a plasma sheath containing cold positive ions, secondary electrons, and primary electrons with a Cairns distribution (a non-thermal velocity distribution). We derive the generalized Bohm criterion and Bohm speed, the new floating potential at the wall, and the
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We study the properties of a plasma sheath containing cold positive ions, secondary electrons, and primary electrons with a Cairns distribution (a non-thermal velocity distribution). We derive the generalized Bohm criterion and Bohm speed, the new floating potential at the wall, and the new critical secondary electron emission coefficient. We show that these properties of the plasma sheath depend significantly on the α-parameter in the non-thermal α-distribution, and so they are generally different from those of the plasma sheath if the primary electrons were assumed to be a Maxwellian distribution.
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Background/Objectives: Despite the publication of several systematic reviews on adolescent health literacy, comprehensive evaluations of the relationship between health literacy and health-related behaviors are still limited. This systematic review sought to synthesize and critically appraise the available evidence on associations between health literacy
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Background/Objectives: Despite the publication of several systematic reviews on adolescent health literacy, comprehensive evaluations of the relationship between health literacy and health-related behaviors are still limited. This systematic review sought to synthesize and critically appraise the available evidence on associations between health literacy and health behaviors among adolescents. Methods. A systematic search of three databases (Scopus, PubMed, and PsycINFO) was conducted in accordance with PRISMA guidelines. Thirty-seven eligible cross-sectional studies were selected for qualitative synthesis. Methodological quality was evaluated using the Newcastle–Ottawa Scale adapted for cross-sectional studies. Results: The 37 included studies encompassed 71,558 adolescents (mean age range 11.0–17.0 years) and were conducted primarily in Europe (n = 22), with additional studies from the USA (n = 5), Asia (n = 8), and cross-cultural settings (n = 2). Across studies, 11 HL instruments were used (including two eHealth literacy measures), most commonly the Health Literacy for School-aged Children scale (n = 14). Physical activity (n = 22), nutrition-related indicators (n = 26), and smoking/alcohol/drug outcomes (n = 16) were assessed using heterogeneous operationalisations. Overall, higher HL was more often associated with healthier behavioral profiles, with more consistent patterns for nutrition-related outcomes. Findings for physical activity and substance use were more heterogeneous and, in some cases, varied depending on the HL measurement approach (subjective vs. objective) and the behavioral reference period. Conclusions: Current evidence indicates that higher health literacy in adolescents is generally associated with more favorable health behaviors, particularly regarding nutrition-related indicators. However, study heterogeneity and the predominance of cross-sectional designs limit comparability and causal inference. Future research should prioritize standardized measurement tools and longitudinal designs to clarify directionality and underlying mechanisms.
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Objectives: This study aimed to investigate the cost of hospitalization and length of stay (LOS) associated with dental infections and their impact on healthcare resources. Materials and Methods: Web of Science, Medline via Ovid, and Google Scholar were searched for articles published from
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Objectives: This study aimed to investigate the cost of hospitalization and length of stay (LOS) associated with dental infections and their impact on healthcare resources. Materials and Methods: Web of Science, Medline via Ovid, and Google Scholar were searched for articles published from 2013 to 2023 using relevant MeSH terms. A descriptive summary was produced to describe study characteristics, and selected studies were analyzed to evaluate financial implications and hospitalization outcomes. Results: After removing duplicates, 125 articles were screened, with 25 read in full and 9 excluded. Sixteen retrospective studies were included, encompassing 156,487 patients. Hospital length of stay ranged from 1.15 to 10 days, and hospitalization costs ranged from AUD 2402 to USD 47,836.60. Variability in outcomes appeared to be influenced by infection severity, healthcare infrastructure, and geographic setting. Conclusions: Dental infections impose a substantial and variable burden on healthcare systems. These findings emphasize the need for timely intervention, preventive strategies, and standardized management protocols to reduce clinical complications and financial strain on healthcare services.
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This article investigates the widespread occurrence of wave-like behavior in biological systems and reflects on the importance of reaction–diffusion frameworks to explain fast information transfer. Focusing on the classical Fisher–Kolmogorov equation, it demonstrates how the combination of nonlinear reaction dynamics and diffusion gives
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This article investigates the widespread occurrence of wave-like behavior in biological systems and reflects on the importance of reaction–diffusion frameworks to explain fast information transfer. Focusing on the classical Fisher–Kolmogorov equation, it demonstrates how the combination of nonlinear reaction dynamics and diffusion gives rise to stable traveling wavefronts that propagate at a constant speed while preserving their shape. We adopt a number of approaches (some novel) in dealing with the analyses, namely the symmetry method, soliton approach (algebraic) and Painlevé analysis, among others.
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Tb3+-doped CaF2 single crystals are attractive materials for green photonic applications due to their low phonon energy, high optical transparency, and efficient Tb3+ emission. In this work, CaF2 single crystals doped with different TbF3 concentrations (1, 5,
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Tb3+-doped CaF2 single crystals are attractive materials for green photonic applications due to their low phonon energy, high optical transparency, and efficient Tb3+ emission. In this work, CaF2 single crystals doped with different TbF3 concentrations (1, 5, and 10 mol%) were grown and systematically investigated in order to clarify the concentration-dependent spectroscopic behavior of Tb3+ ions in a fluorite host. Optical absorption spectroscopy, Judd–Ofelt analysis, steady-state and time-resolved photoluminescence, colorimetric evaluation, and emission cross-section and gain calculations were employed. Judd–Ofelt intensity parameters typical of fluoride hosts were obtained, enabling the calculation of radiative transition probabilities and lifetimes. The emission spectra are dominated by intense green luminescence from the 5D4 → 7F5 transition, while the absence of 5D3 emission is attributed to efficient cross-relaxation processes. Fluorescence lifetimes in the millisecond range show slight changes with Tb3+ concentration. Quantum efficiency increases from low to intermediate concentrations and tends to saturate at higher doping levels. CIE 1931 chromaticity coordinates confirm stable green emission, while emission cross-sections and gain parameters reveal a highest value for orange emission of 10 mol% TbF3-doped CaF2 crystal. These results indicate that CaF2:Tb3+ single crystals are promising materials for photonic applications.
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Brucellosis diagnosis remains challenging in resource-limited endemic settings. This retrospective case–control study evaluated the diagnostic utility of mean platelet volume (MPV) and hematological inflammatory ratios in brucellosis. Fifty patients with confirmed brucellosis and 50 age-matched healthy controls were included at a university hospital
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Brucellosis diagnosis remains challenging in resource-limited endemic settings. This retrospective case–control study evaluated the diagnostic utility of mean platelet volume (MPV) and hematological inflammatory ratios in brucellosis. Fifty patients with confirmed brucellosis and 50 age-matched healthy controls were included at a university hospital in Turkey (2015–2018). Complete blood count parameters, hematological ratios (neutrophil-to-lymphocyte ratio [NLR], platelet-to-lymphocyte ratio [PLR], lymphocyte-to-monocyte ratio [LMR]), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) were measured at diagnosis. Receiver operating characteristic (ROC) curve analysis evaluated diagnostic performance; multivariate logistic regression developed a combined model. Brucellosis patients showed significantly lower MPV (8.04 ± 0.95 vs. 8.56 ± 0.69 fL, p = 0.002), higher platelet counts (305.0 ± 116.0 vs. 246.0 ± 55.2 × 103/μL, p = 0.002), lower NLR (median: 1.69 vs. 2.07, p = 0.013), and higher LMR (median: 5.28 vs. 4.12, p = 0.008). ESR demonstrated the best individual diagnostic performance (area under the curve [AUC] = 0.842). The combined model (MPV + ESR + CRP) achieved superior performance (AUC = 0.891, sensitivity 84%, specificity 86%). Limitations include the single-center retrospective design, lack of internal validation, and comparison with healthy controls only. Notably, healthy controls were deliberately selected to establish baseline hematological profiles associated with brucellosis rather than to differentiate it from other infections. Brucellosis presents a unique hematological profile with decreased MPV and altered inflammatory ratios. The combined model offers a potentially cost-effective screening approach for endemic settings, pending external validation.
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Traditional villages embody tangible repositories of historical, cultural, and geographical heritage, and their sustainable and authentic development poses a global challenge. By applying complex adaptive system (CAS) theory via a bottom–up approach, we analyze traditional settlements using China’s Zheshui village as a representative
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Traditional villages embody tangible repositories of historical, cultural, and geographical heritage, and their sustainable and authentic development poses a global challenge. By applying complex adaptive system (CAS) theory via a bottom–up approach, we analyze traditional settlements using China’s Zheshui village as a representative case. Road networks and spatial configurations were examined through image analysis (ImageJ 1.54 p, Depthmap+ Beta 1.0), integrating space syntax, box-counting dimension, and point-density analysis to decode hierarchical point-line-plane structures. Key findings reveal that building units self-similarly aggregate into courtyards under landmark constraints, with courtyards further coalescing into villages. Road systems function as adaptive agents that facilitate nodal information flow while exhibiting fluidity and diversity. The village emerges as a macro-scale complex system from the building-unit level, displaying cross-scale self-similarity, yet intrinsic diversity in architecture and roads underlies its core complexity. BTM topic modeling of tourist sentiment—identifying tourists as novel adaptive agents—predictively guides strategies for enhanced cultural dissemination and public infrastructure. By establishing a CAS-driven internal generative mechanism, this work offers a novel methodological framework for authentic conservation and sustainable development.
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Granulocyte colony-stimulating factor (G-CSF) has been suggested as a supplementary approach for endometrial preparation in IVF. Clinical results continue to be inconsistent. This narrative review synthesises molecular and clinical information to elucidate the function of G-CSF in modifying endometrial receptivity and to identify
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Granulocyte colony-stimulating factor (G-CSF) has been suggested as a supplementary approach for endometrial preparation in IVF. Clinical results continue to be inconsistent. This narrative review synthesises molecular and clinical information to elucidate the function of G-CSF in modifying endometrial receptivity and to identify patient categories most likely to benefit. A thorough assessment was conducted on published research on G-CSF administration in women with treatment-resistant thin endometrium, recurrent implantation failure, and unselected IVF populations. The research demonstrates that G-CSF has phenotype-dependent effects. Improvements in pregnancy and live birth rates are inconsistent and seem dependent on the reversibility of underlying tissue disease; nevertheless, G-CSF reliably increases endometrial thickness in instances of thin endometrium and may restore eligibility for transfer. G-CSF improves implantation and early pregnancy outcomes in repeated implantation failure patients without modifying endometrial morphology, indicating a functional mechanism linked to immune-stromal synchronisation rather than structural expansion. In contrast, randomised controlled studies show no therapeutic benefit in unselected IVF groups. Discrepancies in research outcomes may mostly be attributed to variations in patient phenotype, initial endometrial function, and the therapy setting. Thus, G-CSF should be considered a specific approach for endometrial conditioning rather than just a supplementary component of IVF.
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by
Gavino Faa, Eleonora Lai, Pina Ziranu, Andrea Pretta, Ekta Tiwari, Mariele Dessì, Cinzia Solinas, Giorgio Saba, Francesco Loi, Claudia Codipietro, Simona Graziano, Laura Ottelio, Massimo Dessena, Ferdinando Coghe, Jasjit S. Suri, Luca Saba and Mario Scartozzi
ER-low breast cancer (1–9% ER expression) represents a biologically and clinically distinct entity at the interface between ER-positive and ER-negative disease. Although traditionally managed as hormone receptor-positive, mounting evidence indicates that ER-low tumors share molecular signatures, aggressive behavior, and chemotherapeutic responsiveness with triple-negative
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ER-low breast cancer (1–9% ER expression) represents a biologically and clinically distinct entity at the interface between ER-positive and ER-negative disease. Although traditionally managed as hormone receptor-positive, mounting evidence indicates that ER-low tumors share molecular signatures, aggressive behavior, and chemotherapeutic responsiveness with triple-negative breast cancer. Accurate ER assessment is hindered by methodological variability and interpretative challenges, leading to potential misclassification and suboptimal treatment choices. While the benefit of endocrine therapy remains uncertain, ER-low tumors consistently show sensitivity to chemotherapy and promising responses to neoadjuvant chemo-immunotherapy, paralleling outcomes observed in triple-negative breast cancer cohorts. Emerging artificial intelligence tools, including digital pathology and multimodal deep learning, may enhance ER quantification, reduce observer variability, and enable more precise patient stratification. This review synthesizes current pathological and clinical insights into ER-low breast cancer and highlights evolving therapeutic strategies, with a forward-looking perspective on AI-driven approaches to optimize personalized treatment for this challenging subtype.
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As large language models (LLMs) are increasingly used as digital respondents and generative agents in computational social science, prior work has primarily focused on the fidelity of their expressed opinions, often overlooking a fundamental question: the behavioral stability of outputs across repeated runs
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As large language models (LLMs) are increasingly used as digital respondents and generative agents in computational social science, prior work has primarily focused on the fidelity of their expressed opinions, often overlooking a fundamental question: the behavioral stability of outputs across repeated runs of the same model when the persona specification and task conditions remain unchanged. This paper proposes a behavioral stability evaluation framework for role-playing tasks, using the Political Compass questionnaire as the testbed. The questionnaire maps responses onto a two-dimensional coordinate system defined by an economic axis and a social axis, enabling political orientations to be directly quantified and compared in a continuous space. To ground the simulation in realistic user behaviors, we construct personas from publicly available social media texts and stratify them based on Political Signal Clarity. Across three LLMs, we compare repeated questionnaire completions under different decoding temperatures and prompting strategies. We characterize it along two complementary dimensions: dispersion of the resulting two-dimensional coordinates across runs, measured by an Overall Stability Score (OSS), and dispersion of per-item choices across runs, quantified by response entropy. We further use linear mixed-effects models to account for persona-level heterogeneity and to estimate the effects of key factors on stability. Our results show that coordinate drift and item-level dispersion do not always move in tandem. Increasing temperature typically amplifies variability, although models differ in their sensitivity. Contrary to its success in reasoning tasks, Chain-of-Thought (CoT) prompting failed to enhance stability in this value-laden context. Instead, it frequently amplified coordinate drift by introducing stochasticity into intermediate reasoning steps. Results show that LLMs exhibit greater behavioral stability when role-playing personas with clearer political signals. These findings suggest that stability should be treated as a pre-study benchmark before deploying LLM-based role-playing simulations, and that key generation settings and stability statistics should be reported alongside substantive conclusions.
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The aquaculture industry is growing rapidly. It is the fastest growing food industry in the world, with production expanding 16-fold between 1985 and 2018, according to the Food and Agriculture Organization FAO. The industry operates in an environment of high uncertainty, as the
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The aquaculture industry is growing rapidly. It is the fastest growing food industry in the world, with production expanding 16-fold between 1985 and 2018, according to the Food and Agriculture Organization FAO. The industry operates in an environment of high uncertainty, as the management of biological and environmental risks is critical. The aim of this research is to identify machine learning (ML) algorithms applied to quantify risks, categorize applications by sector, and evaluate data linkage to the extent that they feed into formal risk management protocols. A systematic review was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. This search was conducted in Scopus and Science Direct for publications up to January 2026. Initially, 134 records were identified, of which 38 studies were ultimately included in the analysis. The results showed that artificial intelligence (AI) and ML offer new predictive capabilities. Integrating Internet of Things (IoT) sensors, AI methods and ML algorithms improve risk mitigation. However, there is a significant disconnection between algorithmic predictions and operational action. Only 3 of 38 studies demonstrated integration with standardized risk management frameworks (e.g., ISO31000). The study concludes that while AI tools provide predictive efficiency, interdisciplinary frameworks are required to filter predictions through economic and ethical criteria. Strengthening this connection will bring the use of AI as a tool for proactive and standardized risk mitigation.
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Salt stress is a major environmental constraint affecting plant growth and productivity. Crop wild relatives provide valuable genetic resources for stress tolerance, yet transcriptomic information for forest-derived wild species remains limited. In this study, we analyzed transcriptional responses of V. hirsuta,
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Salt stress is a major environmental constraint affecting plant growth and productivity. Crop wild relatives provide valuable genetic resources for stress tolerance, yet transcriptomic information for forest-derived wild species remains limited. In this study, we analyzed transcriptional responses of V. hirsuta, a crop wild relative (CWR) of legumes, after seven days of salt stress using de novo transcriptome sequencing. Seedlings were exposed to salt stress, and differentially expressed genes (DEGs) were identified between control (Vh_S0) and salt-treated (Vh_S7) plants using an FDR-adjusted threshold (q < 0.05). Gene Ontology and KEGG enrichment analyses revealed that salt-responsive DEGs were mainly involved in regulatory signaling, metabolic adjustment, redox-related processes, and macromolecular organization. Up- and down-regulated DEGs showed distinct yet overlapping enrichment patterns, indicating complex transcriptional reprogramming under salt stress. Transcription factor analysis identified bHLH, MYB, bZIP, NAC, and WRKY families as major regulators, with many families containing both up- and down-regulated members. Notably, genes associated with Na+/K+ homeostasis were consistently up-regulated and validated by qRT-PCR. These results suggest that continuous seven days salt stress adaptation in V. hirsuta involves coordinated regulation of signaling pathways, transcriptional networks, and transporter-mediated ion homeostasis, providing a valuable transcriptomic resource for crop wild relatives.
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Background: Facial asymmetry affecting the mandibular contour may significantly impact facial harmony even in patients with stable occlusion. Although orthognathic surgery remains the standard for skeletal correction, it carries substantial morbidity. In selected cases, contour-focused approaches can achieve meaningful esthetic improvement with reduced
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Background: Facial asymmetry affecting the mandibular contour may significantly impact facial harmony even in patients with stable occlusion. Although orthognathic surgery remains the standard for skeletal correction, it carries substantial morbidity. In selected cases, contour-focused approaches can achieve meaningful esthetic improvement with reduced surgical burden. Objective: To describe the virtual surgical planning (VSP) workflow and clinical outcome of a unilateral Wing osteotomy for mandibular contour asymmetry. Case presentation: A 24-year-old woman presented with left-sided mandibular contour deficiency and facial asymmetry, despite stable Class I occlusion and preserved function. VSP with contralateral mirroring guided the design of the osteotomy and fabrication of a stereolithographic model and patient-specific cutting guide. Surgery was performed through a tunnelized mandibular approach using a 702 bur and reciprocating saw. Fixation was achieved with pre-bent 2.0 plates adapted to the 3D model, and Bio-Oss Collagen was interposed within the osteotomy gap. Occlusion and mental nerve function were preserved. Results: Postoperatively, the patient demonstrated improved facial symmetry, uneventful healing, preserved long-term neurosensory function, and high esthetic satisfaction. Conclusions: Unilateral Wing osteotomy guided by VSP and patient-specific instrumentation is a predictable, minimally invasive alternative to bimaxillary orthognathic surgery with genioplasty in selected patients presenting contour-focused asymmetry and stable occlusion. This case highlights a rare, underreported application of the technique.
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Background: The tumor microenvironment (TME) is a dynamic ecosystem that critically shapes tumor progression, immune escape, and therapeutic responses. Hedyotis diffusa Willd (HDW) has long been used in East Asian medicine for conditions associated with inflammation and malignancy, yet its immunological and microenvironmental
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Background: The tumor microenvironment (TME) is a dynamic ecosystem that critically shapes tumor progression, immune escape, and therapeutic responses. Hedyotis diffusa Willd (HDW) has long been used in East Asian medicine for conditions associated with inflammation and malignancy, yet its immunological and microenvironmental mechanisms have not been systematically synthesized. Methods: A scoping review of preclinical studies (2016–2025) was conducted following the Arksey-O’Malley framework and PRISMA-ScR guidance to systematically map experimental evidence on the antitumor, immune-related, and TME-associated effects of HDW. To complement and interpret these heterogeneous experimental findings at a systems level, a network pharmacology analysis was performed to identify bioactive compounds, predict their putative protein targets, and assess their convergence on immune- and microenvironment-related signaling networks through protein-protein interaction and pathway enrichment analyses. Results: Fifty-nine studies met eligibility criteria, encompassing in vitro and in vivo models across diverse cancer types. Experimental evidence from preclinical models showed that HDW extracts and bioactive fractions consistently suppressed proliferation, induced apoptosis and ferroptosis, inhibited epithelial-mesenchymal transition (EMT) and angiogenesis, and enhanced cytotoxic lymphocyte activity, while attenuating tumor-associated inflammation. In parallel, in silico network analysis identified 94 intersecting immune- and TME-related targets and revealed a densely connected interaction network centered on PI3K-Akt, STAT3, EGFR, and SRC. Enrichment analyses highlighted receptor tyrosine kinase signaling, inflammatory pathways, metabolic regulation, and focal adhesion as dominant functional themes. Conclusions: HDW acts as a multi-target botanical agent that integrates direct cytotoxicity with immune activation and TME remodeling. Network-in-formed interpretation indicates that the modulation of PI3K-Akt-STAT3 signaling is a common mechanistic axis linking experimental observations.
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Advances in multimodal therapy for high-risk neuroblastomas (NBs) have plateaued, prompting therapeutic initiatives to harness the immune system. NBs, however, are immunologically “cold” and a significant challenge to immunotherapy. Here, in a Jurkat lymphocyte cytotoxicity model, we describe an antigen-independent, cell-mediated mechanism for
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Advances in multimodal therapy for high-risk neuroblastomas (NBs) have plateaued, prompting therapeutic initiatives to harness the immune system. NBs, however, are immunologically “cold” and a significant challenge to immunotherapy. Here, in a Jurkat lymphocyte cytotoxicity model, we describe an antigen-independent, cell-mediated mechanism for eliminating NB cells, first detected in PMA-activated low pcDNA-SH-SY5Y and high TrkAIII-SH-SY5Y TrkAIII-expressing cells, which are resistant to Jurkat elimination under normal conditions. Characterization of this mechanism through live cell imaging, adhesion assays, RT-PCR, Western blotting and indirect IF, employing a variety of inhibitors, indicates that it initiates with PMA-induced NB cell CCL2 expression. This results in CCL2 promotion of Jurkat CCR2b expression, CCL2/CCR2b-mediated Jurkat LFA-1 activation and the formation of cytotoxic lipid-raft LFA1/ICAM-1 immune synapses, through which Jurkat m-TRAIL combines with PMA-enhanced NB cell DR5/TRAIL-R2 expression to induce NB cell apoptosis. This mechanism is enhanced by the NB-associated oncoprotein TrkAIII through Shp/Src-regulated c-FLIP sequester and is PD-L1/PD-1-independent and resistant to osteoprotegerin. It eliminates both non-MYCN-amplified (SH-SY5Y and SK-N-SH) and MYCN-amplified (SMS-KCNR) NB cells that exhibit PMA-inducible CCL2 expression but not MYCN-amplified NB cells (IMR-32 and NB-1) that exhibit CCL2 repression, and is offset by reciprocal NB cell-induced Fas-mediated Jurkat cell apoptosis. These findings form a solid foundation for further pre-clinical development aimed at identifying clinically relevant physiological immune cell equivalents and alternative PKC activators, with the ultimate goal of translating this mechanism into an effective immune-therapeutic approach for the treatment of high-risk non-immunogenic NBs, especially NBs that exhibit CCL2 and TrkAIII expression.
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Multiple myeloma (MM) is a plasma cell neoplasm. Studies of chemokines in MM pathogenesis have primarily focused on CCR1 ligands such as CCL3 (MIP-1α), CXCL12 and its receptor CXCR4, as well as CXCR2 and CXCR3 ligands. However, the roles of the remaining 30
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Multiple myeloma (MM) is a plasma cell neoplasm. Studies of chemokines in MM pathogenesis have primarily focused on CCR1 ligands such as CCL3 (MIP-1α), CXCL12 and its receptor CXCR4, as well as CXCR2 and CXCR3 ligands. However, the roles of the remaining 30 chemokines have been investigated much less frequently. This review compiles current knowledge on the significance of lesser-known chemokines in MM tumor processes, including CXCL13, CCR2 ligands (CCL2 [MCP-1], CCL7 [MCP-3]), CCL4, CCL5 (RANTES), CCL17, CCL20, CCL27, CCL28, and CX3CL1 (fractalkine). It describes their impact on bone destruction, bone marrow angiogenesis, chemoresistance, and the recruitment of cells into the MM niche, such as macrophages, myeloid-derived suppressor cells, and cytotoxic lymphocytes, along with their effects on mesenchymal stromal cells. A bioinformatic analysis highlights the significance of these chemokines in MM, and the possibility of targeting them in MM therapy is also considered.
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Salmonella remains a leading cause of foodborne illness worldwide, with poultry products representing a major source of human exposure, underscoring the need for rapid and reliable detection methods. Although qPCR offers sensitive and timely pathogen detection, assay performance is highly dependent on sample
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Salmonella remains a leading cause of foodborne illness worldwide, with poultry products representing a major source of human exposure, underscoring the need for rapid and reliable detection methods. Although qPCR offers sensitive and timely pathogen detection, assay performance is highly dependent on sample preparation efficiency and nucleic acid purity, particularly in complex food matrices. In this study, we systematically optimized the sample preparation workflow of a SYBR Green based qPCR assay for enrichment-free detection of Salmonella enterica in poultry. Multiple lysis chemistries, incubation times, DNA extraction methods, centrifugation strategies, inoculum sources, and magnetic nanoparticle (MNP) assisted workflows were evaluated using phosphate-buffered saline and chicken rinsate matrices. Among the conditions tested, lysis with 20 µL Proteinase K and 400 µL PrepMan™ for 20 min produced the lowest and most consistent Cq values. Although Promega Wizard® produced slightly lower mean Cq values than PrepMan™, statistical analysis showed no significant differences between extraction methods or centrifugation protocols, indicating comparable overall performance. Broth-derived inocula yielded earlier and more reproducible Cq values than colony-derived preparations. In contrast, inclusion of MNP processing resulted in higher Cq values in both matrices compared to the non-MNP workflow. Overall, these findings demonstrate that optimized lysis, extraction, and centrifugation workflows enhances the consistency and analytical reliability of direct qPCR detection of Salmonella in poultry matrices, supporting laboratory-based rapid detection applications.
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Background/Objectives: International guidelines—including the 2017 Japanese Circulation Society—recommend antibiotic prophylaxis before invasive dental procedures only for patients with clearly defined cardiac conditions at increased risk of infective endocarditis (IE), primarily Class I or IIa. However, IE prevention is not systematically incorporated into Japanese
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Background/Objectives: International guidelines—including the 2017 Japanese Circulation Society—recommend antibiotic prophylaxis before invasive dental procedures only for patients with clearly defined cardiac conditions at increased risk of infective endocarditis (IE), primarily Class I or IIa. However, IE prevention is not systematically incorporated into Japanese dental education, and dentists’ understanding of these indications remains unclear. We assessed dentists’ knowledge of guideline-based cardiac and procedural indications for prophylaxis, as well as their clinical practices regarding timing, duration, and antibiotic selection. Methods: A self-administered questionnaire was mailed to 3109 members of the Hyogo Dental Association. The survey evaluated recognition of Class I and IIa cardiac indications, dental procedures requiring prophylaxis, and self-reported prophylactic practices. Respondents were grouped by years of practice (≤20 vs. ≥21 years). Results: Overall, 367 dentists responded (11.8%). Correct identification of Class I indications was high for prosthetic valves (83.4%) and previous IE (93.7%) but low for complex congenital heart disease (55.5%) and post-shunt surgery (52.0%). Recognition of Class IIa indications was limited (36.4–51.1%). Awareness of procedural indications was high for tooth extraction (92.9%) and periodontal surgery (84.3%) but low for subgingival scaling (47.6%) and root canal treatment (36.7%). Only 60.5% of dentists correctly understood that prophylaxis is indicated for a Class I/IIa cardiac condition and an invasive dental procedure. Furthermore, 32.5% of dentists administered antibiotics within 1 h before treatment, and single-dose regimens were uncommon (14.7%). Multi-day regimens were frequently used. Amoxicillin was the most commonly selected antibiotic (40.8%). No major differences were observed between the groups. Conclusions: Although dentists demonstrated good awareness of major procedural indications, substantial gaps remain in recognizing Class I and IIa cardiac indications and in adhering to guideline-recommended timing and duration. Targeted education and improved collaboration between medical and dental professionals are needed to promote evidence-based IE prevention and reduce unnecessary antibiotic use.
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The decarbonization of shipping and the transformation towards digitally assisted or automated ship operation require new methods to analyze, predict, and optimize energy demand during maneuvering. The SimPleShip-SigMa sub-project of Hochschule Wismar developed and validated a comprehensive simulation-based framework combining real-time capable fast-time
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The decarbonization of shipping and the transformation towards digitally assisted or automated ship operation require new methods to analyze, predict, and optimize energy demand during maneuvering. The SimPleShip-SigMa sub-project of Hochschule Wismar developed and validated a comprehensive simulation-based framework combining real-time capable fast-time simulation of ship motion, detailed thermodynamic engine modeling, and hybrid data exchange via Functional Mock-up Units (FMU/FMI). The approach enables consistent coupling between navigation-related and machinery-related simulations and supports energy-optimized decision-making on the bridge. Operational relevance and validation of use cases were supported through collaboration with Carnival Maritime GmbH, providing practical feedback on large passenger-ship operations. The study presents the architecture of the simulation environment, the implementation of energy- and emission-prediction models, and the result of validation runs and simulator-based trials. The developed method was applied to a virtual cruise-ship scenario representing a confined coastal environment similar to the Geiranger Fjord. The work builds upon earlier research on simulation-augmented maneuvering and extends it toward a modular digital-twin concept linking hydrodynamic and thermodynamic models. The paper concludes with an outlook on applying the system for crew training, on-board support, and gradual automation of sustainable ship operations.
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Introduction: Chronic wounds affect approximately six million people in the United States. Despite established multidisciplinary wound care protocols, patient adherence to follow-up care remains suboptimal. We aimed to understand the impact of social drivers of health on patient decision-making for improving wound care
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Introduction: Chronic wounds affect approximately six million people in the United States. Despite established multidisciplinary wound care protocols, patient adherence to follow-up care remains suboptimal. We aimed to understand the impact of social drivers of health on patient decision-making for improving wound care follow-up adherence. Methods: We conducted a retrospective review of all hospitalized patients who consulted in-house wound care staff at a tertiary care center between August 2017 and June 2020, regardless of primary admission diagnosis. Referred patients received standardized care from a multidisciplinary team at an outpatient wound care facility. Primary endpoints were pre-discharge scheduling and follow-up rates. Follow-up efficacy was assessed through 90-day hospital readmission rates. Results: Of 444 patients, 205 (46.2%) were readmitted or expired within 90 days. Adjusted analysis identified lack of follow-up care reception as an independent predictor of hospital readmission (hazard ratio 2.39; 95% CI, 1.45–3.89; p < 0.001). Among 156 (35.1%) patients who scheduled follow-up, 110 (70.5%) adhered to their appointment. Patients not scheduling follow-up were older (median age 79 vs. 70 years, p < 0.001), longer hospital stays (median 9 vs. 6 days, p < 0.0001), and more frequently discharged to skilled nursing facilities (47.6% vs. 26.3%, p < 0.0001). Among scheduled patients, skilled nursing home residents demonstrated lower follow-up adherence (OR 0.3; 95% CI, 0.14–0.65; p < 0.01). Conclusions: Pre-hospital discharge communication for scheduling follow ups serves as a critical intervention point in patient decision-making for wound follow-up. Considering the limitations of a retrospective single-center study, we find that pre-discharge education about follow-up scheduling for high-risk groups, including patients ≥ 80 years and skilled nursing facility residents, may improve follow-up adherence and reduce readmissions.
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The efficient removal of toxic dyes from wastewater remains a major environmental challenge. In this study, we report a green and facile one-pot synthesis of zinc oxide nanowires (ZnO-NWs) using lemon verbena leaf extract as a sustainable capping and stabilizing agent. The extract
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The efficient removal of toxic dyes from wastewater remains a major environmental challenge. In this study, we report a green and facile one-pot synthesis of zinc oxide nanowires (ZnO-NWs) using lemon verbena leaf extract as a sustainable capping and stabilizing agent. The extract played a vital role in directing the 1D growth of the wurtzite hexagonal structure. Characterization confirmed a band gap of 3.12 eV and the characteristic Zn-O stretching at 375 cm−1. Photocatalytic activity tests using 20 mg of biosynthesized ZnO-NWs demonstrated excellent degradation performance. A rate constant of 0.0067 min−1 was achieved, with 99.95% degradation of Basic Fuchsin under natural sunlight for 3 h. Active species analysis highlighted the crucial roles of hydroxyl radicals (OH), holes (h+), and superoxide radicals (O2•−) radicals. Notably, the addition of 10 mM H2O2 produced a powerful synergistic effect, reducing the degradation time from 3 h to only 7 min and increasing the reaction rate by approximately 25-fold. These findings highlight the potential of biosynthesized ZnO-NWs as highly efficient, rapid, and sustainable photocatalysts for environmental remediation.
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The rapid development of renewable energy requires the support of large-scale energy storage technologies to maintain system balance. Salt cavern compressed air energy storage (CAES) is regarded as one of the key technological pathways for large-scale energy storage. In such systems, the wellbore
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The rapid development of renewable energy requires the support of large-scale energy storage technologies to maintain system balance. Salt cavern compressed air energy storage (CAES) is regarded as one of the key technological pathways for large-scale energy storage. In such systems, the wellbore serves as a critical structure connecting surface facilities and the underground salt cavern, while the cement sheath—formed between the casing and formation during well cementing—acts as the primary barrier ensuring the overall sealing integrity of the wellbore. Through cyclic loading–unloading tests on cement slurries under different temperatures, this study yields the following main conclusions: (1) Increasing temperature aggravates the accumulation of fatigue damage in cement specimens. Taking cumulative plastic strain as an example, it rises from 0.45% to 0.99% as the temperature increases from 25 °C to 115 °C. (2) Elevated temperature promotes greater irreversible energy dissipation under fixed cyclic stress limits. When the temperature rises from 25 °C to 115 °C, the dissipated energy density increases from 0.0033 mJ/m3 to 0.0046 mJ/m3, and its proportion relative to the input energy also increases from 5.52% to 7.13%. (3) Temperature rise leads to notable deterioration of the internal pore structure. At 115 °C, the NMR T2 distribution peak shifts rightward by 0.49 ms, the total pore volume increases by 150.53 mm3, and the corresponding permeability rises by 1.398 × 10−3 μm2. (4) Elevated temperature (up to 115 °C) weakens material performance through a dual mechanism: it accelerates dehydration of the cementitious system, reducing interparticle bond strength, while also promoting plastic slip. It is recommended to optimize the cement slurry formulation (e.g., by incorporating thermal stabilizers) to enhance its long-term sealing performance under service conditions.
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George Austin, Jesse Jones, Abigail Stevens, Elaine Zhang, Taylor Thompson, Michael Gomez, Geoffrey Vrla, Youngbin Oh, Jean-Philippe Marelli, Carl M. Jones, Brian Staskawicz and Myeong-Je Cho
Genetic engineering tools have the potential to rapidly and precisely improve the genome of slow-to-breed cacao. We previously developed an efficient protocol for transforming cacao using cotyledonary explants derived from secondary somatic embryos via Agrobacterium tumefaciens. In this study, we demonstrate that
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Genetic engineering tools have the potential to rapidly and precisely improve the genome of slow-to-breed cacao. We previously developed an efficient protocol for transforming cacao using cotyledonary explants derived from secondary somatic embryos via Agrobacterium tumefaciens. In this study, we demonstrate that our transformation protocol is successful in elite cultivars, INIAPG-038 and Matina 1-6, producing fertile seeds with stable visual marker inheritance regardless of whether the transgenic plants were used as the pollen or ovule donor. Three vectors were used in the transformations, each containing genes for enhanced yellow fluorescent protein (eyfp) and neomycin phosphotransferase II (nptII). Three transgenic INIAPG-038 events and one transgenic Matina 1-6 event were used to evaluate seed fertility and the stability of transgene inheritance in cacao seeds and plants. The T1 progeny of these four transgenic events were analyzed for YFP expression and transgene presence. YFP expression segregated at a 1:1 ratio in all events when the transgenic plants were crossed with non-transgenic plants, while a 3:1 segregation was observed when transgenic events were crossed with each other. The transgenic plants exhibited a normal phenotype compared to non-transgenic control plants, producing seeds with a 97% germination rate.
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While culture is recognized as a foundational informal institution, quantifying its causal impact on corporate outcomes remains a challenge. This study focuses on place-based social culture, specifically using a firm’s local Intangible Cultural Heritage (ICH) as the core cultural variable. We aim to
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While culture is recognized as a foundational informal institution, quantifying its causal impact on corporate outcomes remains a challenge. This study focuses on place-based social culture, specifically using a firm’s local Intangible Cultural Heritage (ICH) as the core cultural variable. We aim to identify its causal effect on firm performance (measured by ROA) and contrast it with another pivotal cultural force—the Spirit of the Long March. Leveraging the Double Machine Learning (DML) method, we find that ICH exerts a significant positive effect on ROA, with the estimated coefficient ranging from 0.0018 to 0.0020 (p < 0.01). In contrast, the effect of the Spirit of the Long March is statistically insignificant. Cross-validation using multiple machine learning algorithms confirms the robustness of our findings. Heterogeneity analysis reveals that the effect of ICH is more pronounced in state-owned enterprises and firms with older CEOs. Mechanism analysis further uncovers that ICH enhances performance primarily by fostering financial conservatism, specifically through a reduction in corporate leverage. Our study provides robust causal evidence on how place-based traditional culture shapes corporate financial policies and underscores the economic value of preserving intangible cultural assets.
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