Search Results (744)

Women have been historically underrepresented in every step of scientific enquiry and, therefore, the knowledge of female bodies is lacking. Now the tide is turning to bring focus on the role of sex and gender in human health and disease. The increasing demands by publishers, funders, and policymakers to pay attention to both sex and gender are commendable. Nevertheless, the premise of the definitions of sex, framed as biological attributes of an individual, contrasting with gender, which is defined through the sociocultural roles, identities, and power structures, carries all pitfalls of the nature–nurture divide, undermining that they are deeply intertwined and interact continuously across the lifespan, shaping physiology and behavior. Current scientific studies rarely disentangle the two for etiological purposes, for their respective contributions to health outcomes. Despite this, there is a push to use both terms appropriately in research and society. This invariably results in the oversimplification of complex processes of sex/gender intertwining, leading to incomplete or misleading causal inferences. Here, I make a case for retiring the sex/gender etiological split in the scientific and public discourse and embracing sex/gender intertwining, rather than minimizing it. This will then enable researchers to focus on how they interact with other variables to produce phenotypes, bringing scientific clarity. Full article

The rapid tourism development in the Municipality of Athens significantly impacts both the local economy and the daily lives of its residents. This study investigates the Social Carrying Capacity (SCC) of Athens by exploring the perceptions, experiences, and attitudes of local citizens and professionals towards the tourism phenomenon. A primary quantitative study was conducted between July and October 2024, utilising a structured online questionnaire based on a stratified random sampling method across the Municipal Communities of Athens, yielding 787 valid responses. The findings reveal a dichotomy in public perception: while the majority recognises the positive economic contributions of tourism—particularly in the catering and hospitality sectors—significant concerns are raised regarding negative socio-environmental impacts. The most severe consequence identified is the surge in housing costs and rent prices, predominantly driven by short-term rentals, followed by increased pressure on public infrastructure, cleanliness, and traffic congestion. Despite these challenges, a considerable portion of the respondents maintains a generally tolerant attitude towards visitors and believes there is still a margin for further tourism growth. The study concludes that to ensure sustainable urban tourism, policymakers must implement targeted strategies, including the regulation of short-term rentals and substantial investments in public infrastructure, thereby balancing economic benefits with residents’ quality of life. Full article

Achieving the simultaneous improvement of environmental quality and export quality represents a critical breakthrough for countries pursuing high-quality economic development. Based on panel data for 67 countries over the period 1995–2020, this study investigates the impact of environmental regulation on export sophistication within the context of globalized production. First, this paper constructs an index of export sophistication from a global perspective and employs a Panel Smooth Transition Regression model to preliminarily identify a single-threshold effect of environmental regulation on export sophistication. On this basis, a baseline regression model incorporating the quadratic term of environmental regulation is established, and a series of robustness checks and heterogeneity analyses are conducted. The results indicate that, in both developed and developing countries, environmental regulation exhibits a significant “U-shaped” effect on export sophistication, although notable country heterogeneity exists. Compared with developed countries, developing countries display a higher turning point and stronger policy effects, suggesting that their micro-level agents possess greater tolerance for environmental regulation and that marginal changes in regulatory intensity exert a more pronounced influence on export sophistication. Furthermore, inspired by the theory of ecological fallacy, this study does not confine itself to the conventional dichotomy between developed and developing countries. Instead, it classifies countries according to their levels of export sophistication and conducts quantile regression analysis accordingly. The findings reveal that the impact of environmental regulation becomes increasingly significant and stable as the level of export sophistication rises. Only when technological capability reaches a certain threshold can environmental regulation exert a positive incentive effect; when technological levels are too low, they are insufficient to support the upward trend of the “U-shaped” relationship. Full article

Rapid urbanization and complex topography complicate Urban Heat Island (UHI) spatio-temporal dynamics. Traditional models and coarse-resolution imagery often fail to capture fine-scale, spatially non-stationary seasonal driving mechanisms. This study investigates the multi-dimensional drivers of surface thermal dynamics in Kunming, a typical low-latitude plateau city, using seasonal median LST composite (2018–2025). Integrating eXtreme Gradient Boosting (XGBoost) with eXplainable Artificial Intelligence (XAI) models decoupled the nonlinear impacts of these drivers. Results reveal a seasonal thermal dichotomy: Summer exhibits the most intense UHI effect with extreme peak temperatures, while Spring presents an anomaly where natural and vegetated Local Climate Zones (LCZs) show pronounced warming. SHapley Additive exPlanations (SHAP) analysis identified a seasonal rotation: anthropogenic and structural factors dominate Summer and Autumn warming, whereas natural and topographic regulators govern Spring and Winter. GeoShapley deconstruction demonstrated strong spatial non-stationarity. Building-density warming is amplified in poorly ventilated urban cores, and fragmented vegetation’s cooling is offset by anthropogenic heat during peak summer. This study provides new insights into the seasonal drivers of urban thermal environments in plateau cities. Full article

Resolving the dichotomy between wide detection ranges and low mechanical hysteresis remains a critical challenge in flexible electronics, largely governed by the intrinsic viscoelastic creep of polymeric dielectrics. Drawing inspiration from the distinctive load-bearing mechanisms of traditional Chinese Sparrow Brace architecture, we report a mechanically optimized tilted micro-architecture designed to enhance structural resilience. Unlike conventional soft elastomeric pillars that easily succumb to mechanical failure, this BOPS-based tilted geometry provides excellent load-bearing capacity, effectively preventing premature failure. Finite element analysis (FEA) confirms that this tilted geometry forces a fundamental shift from conventional bulk compression to structural bending. Because this bending-dominated architecture drives rapid elastic recovery, it significantly mitigates the severe effects of the polymer’s viscoelastic creep under the tested loading conditions, achieving reliable signal reversibility with low hysteresis. We fabricated this specific architecture via programmable femtosecond laser direct writing (FsLDW) on biaxially oriented polystyrene (BOPS) films, harnessing the material’s entropy-driven self-growth kinetics. By merging this localized growth mechanism with the architectural design, we effectively bypassed the complexities of traditional molding, achieving mask-free, in situ growth of large-scale, highly uniform dielectric micro-arrays. The resulting sensor delivers a remarkably broad working range (up to ~2.28 MPa) coupled with a negligible recovery error (~1.3%), an agile dynamic response (~70/80 ms), and consistent operational durability. Ultimately, this work combines architecture-inspired structural design with advanced femtosecond laser surface microengineering, providing a conceptually novel and scalable pathway for next-generation flexible sensing. Full article

While there has been a recent focus on reforming kindergarten curricula to emphasize a play-based learning (PBL) approach, a lingering dichotomy remains between play-based learning and pedagogical instruction aimed at academic preparation. Early music education is a critical component of the current policy emphasis on arts education and PBL, yet there is scarce research on play-based pedagogy in music education, particularly regarding children’s engagement and the applied instructional models. This study investigates how instructional practices affect children’s behavioral and emotional engagement in musical play. Data were collected at two Hong Kong kindergartens (K1–K3) using classroom observations and the Engagement Check II (ECII) tool. Thematic content analysis revealed three instructional approaches: teacher-directed routines with minimal aspects of play, guided play within structured musical contexts, and open-ended, child-initiated musical play. Analysis of the ECII data revealed high levels of behavioral engagement, with guided-play contexts yielding higher levels of behavioral and emotional engagement compared to highly teacher-directed instructional approaches. Differences in engagement levels during musical play were revealed to be correlated with age. This study highlights the need for culturally responsive music teacher training, supportive school culture, and aligned curriculum and policy implementation. Full article

We study the long-time behavior of nonlinear stochastic evolution equations in a separable Hilbert space driven by a Q-Wiener process. The linear part of the equation is generated by a strongly continuous semigroup with an exponential dichotomy, which provides fixed rates of decay and growth. The nonlinear drift and diffusion terms are globally Lipschitz and become small as time tends to infinity. Our main result shows that under these conditions, the mean-square Lyapunov exponents of the nonlinear system coincide with those of the linear part. In other words, nonlinear stochastic perturbations that decay in time do not change the main growth or decay rates of solutions in the mean-square sense. This result provides simple and verifiable criteria ensuring that the long-time Lyapunov behavior of the nonlinear stochastic equation is fully determined by the linear semigroup, even in the presence of time-dependent stochastic perturbations. Full article

Dickkopf-1 (DKK1) is a 266-amino-acid secreted glycoprotein originally identified as a high-affinity antagonist of the canonical Wnt/β-catenin signaling pathway and has emerged as a complex regulator in oncology. While historically considered as a tumor suppressor due to its ability to abrogate Wnt-driven proliferation, recent discoveries highlight a paradoxical pro-oncogenic role across various malignancies. The molecular mechanisms by which DKK1 promotes tumor progression, metastasis, and immune evasion are driven by its interaction with cell-surface receptors, specifically LRP5/6 and CKAP4. The DKK1-CKAP4 axis independently activates PI3K/AKT signaling, facilitating epithelial–mesenchymal transition (EMT), chemoresistance, and the formation of osteolytic bone lesions. Furthermore, DKK1 serves as a critical orchestrator of the tumor microenvironment (TME) by driving comprehensive immune reprogramming. It mediates the recruitment of myeloid-derived suppressor cells (MDSCs) and inactivates cytotoxic CD8⁺ T cells and natural killer (NK) cells, thereby fostering an immunosuppressive tumor microenvironment and resistance to checkpoint inhibitors. Interestingly, cancer-associated fibroblasts (CAFs) are a primary source of DKK1 in the stroma, where they facilitate immune evasion. Clinically, elevated circulating DKK1 levels correlate with advanced disease stages, increased metastatic potential, and poor overall survival in solid and hematological tumors. When used in combination with established biomarkers, serum DKK1 levels demonstrate significant utility for early detection and therapeutic monitoring. Given its intricate impact on malignancy, DKK1 has become a promising therapeutic target, with ongoing clinical trials investigating neutralizing antibodies such as DKN-01 to disrupt its oncogenic and immunosuppressive signaling. Understanding the context-dependent nature of DKK1 signaling remains essential for refining its application as both a biomarker and a component of emerging precision immunotherapy strategies. By prioritizing the literature from the last decade, this review characterizes DKK1 as a key mediator of tumor progression and immune reprogramming, while assessing its clinical potential as a biomarker and therapeutic target. Full article

This study presents a comprehensive and systematic integrative review of Neighborhood-Level Energy Hubs (NLEHs) as pivotal enablers of sustainable and resilient urban energy systems. In response to accelerating climate pressures, rapid urbanization, and the decentralization of energy production, NLEHs are conceptualized as multi-carrier platforms that enable coordinated energy generation, storage, conversion, and exchange at the neighborhood scale. Utilizing a PRISMA-informed methodology to synthesize 125 core studies, the review systematically evaluates recent advances across five interconnected dimensions: conceptual foundations, system typologies, energy flow architectures, urban integration, and optimization paradigms. Unlike conventional reviews, this study explicitly bridges the critical gap between techno-economic optimization and socio-environmental priorities. A key novelty is the proposed mathematical integration of energy justice and Social Life Cycle Assessment (S-LCA) directly into optimization algorithms (e.g., MILP and MPC) as dynamic constraints and penalty terms. Particular emphasis is placed on participatory governance models, lifecycle sustainability metrics, and digitalization tools such as AI-driven energy management systems and urban digital twins. The analysis further reveals critical research gaps, highlighting a stark geographic dichotomy between high-tech, market-driven NLEHs in the Global North and resilience-oriented hybrid microgrids in the Global South, alongside the lack of adaptive regulatory frameworks. By proposing a unified Cyber–Physical–Social perspective, this study provides actionable insights for planners, policymakers, and researchers to support the development of scalable, inclusive, and context-sensitive NLEH implementations. Ultimately, the paper contributes to redefining neighborhood-scale energy systems as not only efficient and low-carbon infrastructures, but also as socially equitable, globally scalable, and institutionally adaptive components of future smart cities. Full article

In the context of behavioral finance, detecting credit card fraud remains a critical challenge, particularly when dealing with highly imbalanced datasets and ambiguous transaction patterns. This complexity highlights the limitations of traditional fraud detection models, which rely on a rigid binary distinction between “fraudulent” and “legitimate” transactions. Such a perspective restricts analysts’ ability to capture the nuanced and uncertain nature of fraudulent behavior, underscoring the need for a more flexible and practical approach. Accordingly, this study draws on Derrida’s deconstructive philosophy of binary oppositions to challenge the dominant dichotomy underlying conventional detection systems. This perspective provides a theoretical foundation for rethinking fraud detection by operationalizing deconstructive principles through the integration of fuzzy rules and machine learning architectures. The proposed approach is designed to address uncertainty, class imbalance, and semantic instability in financial transaction data. By combining fuzzy logic with deep learning, the framework deconstructs the rigid binary classification of transactions, enabling interpretation along a spectrum of legitimacy rather than as mutually exclusive categories. Deep learning techniques identify complex, nonlinear patterns that reveal overlaps between fraudulent and legitimate behaviors, while fuzzy membership functions model uncertainty and capture borderline cases that cannot be effectively handled by binary classification. Full article

The progression of chronic bone diseases is intricately linked to dysregulated macrophage polarisation. However, a comprehensive understanding of the complex interplay between macrophage polarisation and metabolic reprogramming in the context of bone disorders remains elusive. Thus, this review conducted a systematic search of major databases, including PubMed, using combinations of keywords such as “macrophage polarisation,” “immunometabolism,” “metabolic reprogramming,” and “chronic bone diseases” (including “osteoporosis,” “osteoarthritis,” and “periodontitis”). Inclusion criteria prioritised original research published within the last five years to capture recent advances. Diverging from previous reviews constrained by the classical M1/M2 dichotomy, this article aims to delineate the heterogeneity and functional plasticity of macrophages within the bone microenvironment, emphasising metabolic reprogramming as a central mechanism driving the dynamic behaviour of macrophages across various skeletal pathologies. Furthermore, this review highlights the pivotal roles of specific metabolites—such as succinate, itaconate, and citrate—within the osseous microenvironment, underscoring their influence on macrophage phenotypic transitions and the regulation of bone metabolic homeostasis. Finally, this article envisages innovative therapeutic strategies targeting the “metabolism–immunity axis,” encompassing the design of nano-delivery systems to modulate macrophage metabolism, the utilisation of engineered extracellular vesicles, the development of immunometabolism-modulating biomaterials, and the exploration of naturally occurring bioactive molecules. Based on these findings, the present work proposes the “metabolism–immunity–skeleton” axis as a theoretical framework, thereby establishing a robust foundation for the development of precision metabolic immunotherapy tailored to a spectrum of chronic bone diseases. Full article

Port cities represent an interdependent system in which port and urban activities overlap and develop. While ports serve as the gateway for the city, expanding market reach and attracting investments, cities provide the necessary labor and services required for the operation of the ports. However, the mutual relationship between ports and cities is threatened by conflicts such as urban sprawl, which leads to friction by taking the space needed for storing containers at ports. Similarly, ports generate high noise and air pollution, threatening the quality of life in urban centers. Therefore, implementing best practices to manage the port–city dichotomy is essential to ensure the coexistence of the port and city. This study re-examined the port–city relationship in the framework of urban planning to guide redevelopment decisions within the Piraeus city port in Greece. Data were collected through a mixed-methods approach involving secondary research and roundtable discussions. The findings showed that a key design parameter of the Piraeus city port is the development and exploitation of the city’s relationship with water, from a functional, spatial, and aesthetic point of view. Furthermore, a guide was developed to facilitate the redevelopment of the city port and improve decision-making. The recommendations also emphasize the integration of the port city into a global economic forum and highlight its dynamism, ensuring mutual benefits for the city and port. Full article

This article examines the assumed dichotomy between the Black church and the juke joint within African American cultural discourse. Often portrayed as moral opposites—one sacred and the other secular—this study argues that such a binary reflects a Eurocentric interpretive framework rather than the actual historical realities of Black communal life. Through cultural and historical analysis, the article asserts that both institutions originated from similar conditions of racial exclusion and served as complementary spaces that nurtured African American identity, resilience, and community connections. Using the film Sinners as a key cultural text, the study explores how contemporary media narratives complicate rigid distinctions between sacred and secular Black spaces, identities, music, and spirituality. The character Sammie illustrates the permeability between these spaces, embodying a cultural logic where spiritual refuge and expressive release coexist. The analysis places this view within the African philosophical concept of Ubuntu, which emphasizes relational identity and the inseparability and oneness of the Black community. Drawing on the scholarship of James H. Cone, the article also shows that spirituals and blues share roots in African diasporic musical traditions. These traditions demonstrate the deep interconnection between religious and secular forms of Black expression. Ultimately, the study concludes that the Black church and the juke joint should be understood not as opposing institutions but as interconnected cultural spaces that collectively sustain African American spiritual, social, and artistic life. Full article

Background: The chemokine CCL5 exhibits a complex role in cancer immunotherapy, yet its dual immunomodulatory functions in non-small cell lung cancer (NSCLC) remain poorly understood. Methods and Results: Based on a newly analyzed clinical cohort of 33 advanced NSCLC patients receiving anti-PD-1 therapy combined with platinum-based chemotherapy, we found that elevated baseline peripheral blood CCL5 levels significantly predicted shorter overall survival (27.6 months vs. not reached, HR = 2.779, p = 0.038) and a higher incidence of immune-related pneumonitis (p = 0.0072). These clinical observations were supported by the re-analysis of a previously published single-cell RNA sequencing (scRNA-seq) dataset (n = 8), which indicated that high CCL5 expression in peripheral blood T/NK cells was associated with a lower major pathological response (p = 0.029). To explore the underlying mechanisms, we conducted detailed analyses using a large, publicly available tumor scRNA-seq dataset (GSE243013, n = 234). These analyses revealed that high intratumoral CCL5 simultaneously promoted the recruitment of both immune effector cells (CD8⁺ T cells, NK cells) and immunosuppressive populations (Tregs, MDSCs). This paradoxical immune landscape correlated with elevated immune checkpoint expression and significantly higher TIDE scores (1.47 vs. 0.83, p < 0.001). CellChat and SCENIC network analyses identified intensified T cell–myeloid communication and key transcription factors (e.g., FOXP3, EOMES) mediating this dichotomy. Conclusions: This hypothesis-generating study raises the possibility that CCL5 orchestrates paradoxical immune responses and may serve as a biomarker in NSCLC. Further validation in larger prospective, independent cohorts is required. Full article

Background: Depressive symptoms have been linked to systemic inflammation, yet estimates in population-representative data vary by symptom severity and analytic specifications. We quantified the association between depressive symptom severity and high-sensitivity C-reactive protein (hs-CRP) in U.S. adults using design-based inference. Methods: We analysed pooled NHANES 2015–2018 data for adults aged ≥ 20 years (unweighted n = 9164; complete-case adjusted models n = 8173). Depressive symptom severity was categorised using the Patient Health Questionnaire-9 (PHQ-9) with 0–4 as the reference group and a pre-specified primary contrast of 10–14 versus 0–4. Outcomes were (i) continuous hs-CRP modelled on the log scale, reported as geometric mean ratios (GMR), and (ii) elevated inflammation defined as hs-CRP > 3 mg/L, modelled using a log-link to obtain prevalence ratios (PR). Models incorporated NHANES complex sampling and adjusted for a pre-specified core covariate set (age, sex, race/ethnicity, education, poverty-income ratio, and smoking). Sensitivity analyses excluded hs-CRP > 10 mg/L and added BMI. Results: After adjustment, the geometric mean hs-CRP was 1.43 mg/L (95% CI 1.21–1.70) for PHQ-9 0–4 and 1.63 mg/L (95% CI 1.29–2.08) for PHQ-9 10–14. For the primary contrast (10–14 vs. 0–4), the adjusted GMR was 1.14 (0.96–1.35) and the PR was 1.15 (0.95–1.39). Using a clinically relevant dichotomy (PHQ-9 ≥ 10 vs. <10), depressive symptoms were associated with higher hs-CRP (GMR 1.24 (1.07–1.43)) and a higher prevalence of hs-CRP > 3 mg/L (PR 1.19 (1.01–1.39)). Associations were strongest for PHQ-9 15–19 (GMR 1.62 (1.20–2.19); PR 1.49 (1.15–1.92)). In sensitivity analyses for the primary contrast, GMR estimates ranged from 1.01 to 1.14 and PR estimates ranged from 1.05 to 1.15, with attenuation towards the null after excluding hs-CRP > 10 mg/L and after additional adjustment for BMI. Conclusions: Higher depressive symptom severity was associated with higher hs-CRP and a higher prevalence of low-grade systemic inflammation in U.S. adults, with the clearest elevations observed among those with moderately severe symptoms. For the pre-specified moderate-symptom contrast, point estimates were modest and sensitive to handling of high hs-CRP values and adiposity-related adjustment. Full article