Search Results (9,042)

The integration of nanotechnology into drug repurposing strategies is redefining the development landscape for diagnostic, therapeutic, and theranostic agents. In radiopharmacy, nanoplatforms are increasingly being explored to enhance or extend the use of existing radiopharmaceuticals, complementing earlier applications in other biomedical fields. Many of these nanoplatforms evolve into multifunctional systems by incorporating additional imaging modalities (e.g., MRI, fluorescence) or non-radioactive therapies (e.g., photodynamic therapy, chemotherapy). These hybrid constructs often emerge from the reformulation, repositioning, or revival of previously approved or abandoned compounds, generating entities with novel pharmacological, pharmacokinetic, and biodistribution profiles. However, their translational potential faces significant regulatory hurdles. Existing frameworks—typically designed for single-modality drugs or devices—struggle to accommodate the combined complexity of nanoengineering, radioactive components, and integrated functionalities. This review examines how these systems challenge current norms in classification, safety assessment, preclinical modeling, and regulatory coordination. It also addresses emerging concerns around digital adjuncts such as AI-assisted dosimetry and software-based therapy planning. Finally, the article outlines international initiatives aimed at closing regulatory gaps and provides future directions for building harmonized, risk-adapted frameworks that support innovation while ensuring safety and efficacy. Full article

Post-exertional malaise (PEM) is a defining symptom of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), yet its molecular underpinnings remain elusive. This study investigated the temporal–longitudinal DNA methylation changes associated with PEM using a structured two-day maximum repeated effort cardiopulmonary exercise testing (CPET) protocol involving pre- and two post-exercise blood samplings from five ME/CFS patients. Cardiopulmonary measurements revealed complex heterogeneous profiles among the patients compared to typical healthy controls, and VO₂ peak indicated all patients had poor normative fitness. The switch to anaerobic metabolism occurred at a lower workload in some patients on Day Two of the test. Reduced Representation Bisulphite Sequencing followed by analysis with Differential Methylation Analysis Package-version 2 (DMAP2) identified differentially methylated fragments (DMFs) present in the DNA genomes of all five ME/CFS patients through the exercise test compared with ‘before exercise’. With further filtering for >10% methylation differences, there were early DMFs (0–24 h after first exercise test) and late DMFs between (24–48 h after the second exercise test), as well as DMFs that changed gradually (between 0 and 48 h). Of these, 98% were ME/CFS-specific, compared with the two healthy controls accompanying the longitudinal study. Principal component analysis illustrated the three distinct clusters at the 0 h, 24 h, and 48 h timepoints, but with heterogeneity among the patients within the clusters, highlighting dynamic methylation responses to exertion in individual patients. There were 24 ME/CFS-specific DMFs at gene promoter fragments that revealed distinct patterns of temporal methylation across the timepoints. Functional enrichment of ME-specific DMFs revealed pathways involved in endothelial function, morphogenesis, inflammation, and immune regulation. These findings uncovered temporally dynamic epigenetic changes in stress/immune functions in ME/CFS during PEM and suggest molecular signatures with potential for diagnosis and of mechanistic significance. Full article

Accurate normalization of target gene expression in qRT-PCR experiments requires the development of stable and efficient housekeeping reference genes, particularly for tissue-specific genes in a given organ. Phyllanthus emblica L., an economically important cash tree, has been applied as medical or functional fruit for years in Asian countries due to its fruit that contains rich and diverse active compounds. Developing housekeeping reference genes is critical to investigate the physiological and molecular regulation of fruit development and ripening for P. emblica genetic improvement in breeding practice. Here, based on the expressional stabilities and efficiencies, expression profiles of 13 candidate genes at various fruit development stages were compared between two accessions using expression levels and multiple statistical methods, including BestKeeper, NormFinder, geNorm, ΔCt, and RefFinder. The validation test was conducted through qRT-PCR analysis of two fruit tissue-specific genes, PeGASA and PeMLP, across the different fruit development stages, combined with the comparison of gene expression consistency between qRT-PCR and transcriptomic data. These analyses identified PeACT and PeUBQ6, two regulators of tissue development and ripening, to be the most suitable housekeeping reference genes. Thus, we recommended PeACT and PeUBQ6 can serve as housekeeping reference genes for conducting qRT-PCR analysis in P. emblica fruit, helpful for investigating gene expression related to fruit development and ripening using the qRT-PCR technique. Full article

The growing use of bibliometric methods in literature reviews has intensified concerns about methodological transparency and consistency. This study compares English-language reviews authored by China-affiliated and non-China-affiliated researchers between 2015 and 2024. Through bibliometric content analysis and co-word network mapping, it evaluates the following: (1) the use and purposes of bibliometric software; (2) the clarity of methodological reporting, including software versions, threshold settings, data preprocessing, and database selection; (3) the extent to which limitations are acknowledged and recommendations proposed; and (4) the dominant conceptual themes shaping research practices. The analysis covers 50 highly cited reviews (25 per group) and 4000 additional papers for thematic mapping. Findings show both convergence and divergence: while tools such as VOSviewer, CiteSpace, Gephi, and Bibliometrix are widely adopted, non-China-affiliated studies exhibit greater transparency and reflexivity, whereas China-affiliated research often emphasizes output metrics and underreports methodological challenges. These contrasts reflect broader epistemological norms and research cultures. This study underscores the need for unified reporting standards and contributes to meta-research by offering practical guidance to improve the transparency, comparability, and rigor of bibliometric-supported literature reviews. Full article

This study explores the interplay between environmental justice and energy democracy in the context of forest-based energy conflicts in Türkiye, focusing on the case of the Akbelen Forest. It draws on qualitative data from community-based actions and legal documents to examine how local communities engage in collective action against extractivist energy policies that threaten their ecological and social environments. The findings reveal a complex web of multilayered injustices, including procedural, distributional, and recognitional dimensions, experienced by the affected populations. In this regard, the Akbelen case demonstrates how these different dimensions intersect and constitute a framework of “multiple justice”. The central argument of this study, developed primarily through our visualised network graph, is that the Akbelen case demonstrates the limitations of current environmental governance frameworks in accommodating community-based ecological values and rights. This analysis demonstrates how energy democracy can function as both a normative and strategic instrument for rethinking participatory planning and forest governance. The present paper contributes to ongoing debates in the fields of political ecology and environmental governance by situating grassroots mobilisation within a broader discussion of just energy transitions. The study also emphasises the necessity of inclusive, multi-actor governance models that prioritise democratic participation, ecological integrity, and intergenerational equity. Full article

We investigate a numerical method for approximating stochastic Caputo fractional differential equations driven by multiplicative noise. The nonlinear functions f and g are assumed to satisfy the global Lipschitz conditions as well as the linear growth conditions. The noise is approximated by a piecewise constant function, yielding a regularized stochastic fractional differential equation. We prove that the error between the exact solution and the solution of the regularized equation converges in the $L^2((0,T)\times \mathrm{\Omega })$ norm with an order of $O(\Delta t^{\alpha -1/2})$, where $\alpha \in (1/2,1]$ is the order of the Caputo fractional derivative, and $\Delta t$ is the time step size. Numerical experiments are provided to confirm that the simulation results are consistent with the theoretical convergence order. Full article

This study presents a gradient-informed proxy initialization framework designed to improve training efficiency and predictive performance in deep learning models for time-series forecasting. The method extends the Laor Initialization approach by introducing backward gradient norm clustering as a selection criterion for input-layer weights, evaluated through a lightweight, architecture-agnostic proxy model. Only the numerical input layer adopts the selected initialization, while internal components retain standard schemes such as Xavier, Kaiming, or Orthogonal, maintaining compatibility and reducing overhead. The framework is evaluated on a real-world financial forecasting task: identifying high-risk equities from the Thai Market Surveillance Measure List, a domain characterized by label imbalance, non-stationarity, and limited data volume. Experiments across five architectures, including Transformer, ConvTran, and MMAGRU-FCN, show that the proposed strategy improves convergence speed and classification accuracy, particularly in deeper and hybrid models. Results in recurrent-based models are competitive but less pronounced. These findings support the method’s practical utility and generalizability for forecasting tasks under real-world constraints. Full article

Background: Cancer-related pain is a common and distressing symptom among patients with cancer. Although acupuncture is widely used and supported by growing evidence, its real-world use and related patient attitudes remain underexplored in South Korea. This study aimed to investigate patterns of acupuncture use and identify factors influencing its use among Korean cancer patients experiencing pain. Methods: A cross-sectional survey was conducted from October 2023 to May 2024 at six Korean medicine hospitals. A total of 201 cancer patients with pain completed a questionnaire assessing acupuncture use, pain severity and interference, and beliefs using a modified version of the ABCAM (Attitudes and Beliefs about Complementary and Alternative Medicine) instrument. Treatment concerns, logistical barriers, and social norms were analyzed. Results: Of the 201 participants, 80.6% reported using acupuncture for cancer-related pain. Pain severity was the only significant predictor of acupuncture use (OR = 1.53, 95% CI: 1.10–2.12, p = 0.01). Acupuncture users reported fewer concerns about safety and side effects, fewer logistical barriers, and stronger encouragement from family, healthcare providers, and peers. Conclusions: This is the first study to explore real-world use of acupuncture for cancer pain in South Korea. Greater pain severity, perceived safety, ease of access, and social support were associated with higher acupuncture use. These findings suggest that improved patient education and integration of acupuncture into cancer care may enhance pain management for Korean patients. Full article

Background: This study aims to establish standardized reference values for myocardial T1 and T2 relaxation times in a clinically and imaging-defined real-world patient cohort, evaluating their variability in relation to age, sex, and comorbidities. By identifying key physiological and pathological influences, this investigation seeks to enhance CMR-based myocardial mapping for improved differentiation between normal and pathological myocardial conditions. Methods: This retrospective observational study analyzed T1 and T2 relaxation times using CMR at 1.5 Tesla in a cohort of 491 subjects. T1 and T2 times were measured using MOLLI and GRASE sequences, and statistical analyses assessed intra- and interindividual variations, including the influence of age, sex, and comorbidities, to establish reference values and improve myocardial tissue characterization. Results: T1 and T2 relaxation times were analyzed in 291 and 200 participants, respectively. The mean global T1 time was 1004.7 ± 49.8 ms, with no significant differences between age groups (p = 0.81) or sexes (p = 0.58). However, atrial fibrillation (AF) and mitral regurgitation (MR) were associated with significantly prolonged T1 times (p < 0.05). The mean global T2 time was 67.4 ± 8.6 ms, with age-related prolongation (p < 0.05), but no sex differences (p = 0.46). Comorbidities did not significantly influence T2 times, except for NYHA Class III–IV patients, who exhibited prolonged T2 values (p < 0.05). Conclusions: Standardized T1 and T2 reference values are essential to improve diagnostic accuracy and risk stratification in CMR-based myocardial tissue characterization. Future research should focus on multicenter validation, AI-driven analysis, and the development of age- and comorbidity-adjusted normative databases to enhance individualized cardiovascular care. Full article

Additive manufacturing offers new perspectives for creating complex geometries with improved design features at lower cost and with reduced manufacturing time. It may even become possible to print a micro-turbojet engine in one single print, but then unconventional geometrical constraints on compressor and turbine designs are inevitable. If a radial machine were printed through additive manufacturing as a standalone component, the most logical print direction would be from the radial outlet/inlet to the axial inlet/outlet to ease the process and limit the supports, with limited additional constraints compared to traditional manufacturing methods. If the rotor comprising a radial compressor and turbine needs to be printed in one single print, one of the components will be printed in a direction that is not favorable. In the present work, the radial turbine is considered to be printed in the unfavorable direction, namely, from the axial outlet to the radial inlet. These geometrical constraints orient the geometry towards a mixed-flow configuration with a trailing-edge cutback. Such design features reduce the available design space for improvement and will clearly have an unfavorable impact on performance. Therefore, a multi-disciplinary gradient-based adjoint optimization of the mixed-flow turbine is performed, striving to limit the adverse impact on total-to-total efficiency while respecting the mass flow rate and power matching with the upstream compressor. The structural constraint limits the p-Norm von Mises stress to a maximum threshold based on the material yield strength at the operating temperature. The results show that a satisfactory compromise can be found between manufacturability constraints, material limits and aerodynamic performance. Full article

Examples from urban infrastructure in the United States show that high-level policy reports focused on investment neglect performance improvement, as well as changes in society and technology. A study methodology using systems approaches, institutional analysis, and examples from US situations was used to probe causes and remedies of this policy shortcoming. A conceptual systems model of services and the Maslow hierarchy of needs identified essential services spanning water, energy, transit, and streets management. Drinking water services have greater clarity and were selected to assess actor roles, responsibilities, and actions. The institutional analysis and development framework was used to organize the actors, settings, norms, incentives, rules, and action arenas. Data from the drinking water sector indicated that infrastructure policy reports mix issues and obscure significant impacts on specific sectors. They assume a static view and do not consider transformations in social contracts, alternative technologies, and service delivery methods. Without policy reform, public trust in government services will diminish, but political and administrative realities constrain rational and comprehensive approaches. The drinking water social contract is unlikely to change, but partnerships can incentivize reforms like performance assessment and agency accreditation. Development of a road map for urban infrastructure policy reform will require research by task forces of leading-edge practitioners within categorical arenas like drinking water, electric power, transit, and public works. Full article

This paper examines the sexual and reproductive health (SRH) knowledge, experiences, service access, and unmet needs of Rohingya adolescent refugee girls living in the camps of Cox’s Bazar, Bangladesh. The refugee population in these camps is approximately 1.3 million, with more than half under the age of 18 and girls representing over one quarter of the total. Given the growing proportion of adolescent girls, SRH knowledge and service provision are critical both for the refugee community and for Bangladesh’s broader sustainable development goals. Drawing on direct accounts from adolescent girls and insights from community-based key informants, this research explores levels of SRH awareness, willingness to seek care, encounters with sexual violence, understanding of sexually transmitted diseases, and reproductive health priorities. It also identifies barriers to service delivery faced by healthcare and humanitarian providers. The findings highlight how cultural norms, social constraints, and religious beliefs intersect with structural barriers—including lack of education, financial dependence, gender-based violence, and the need for parental or spousal consent—to restrict access to SRH services. Despite these challenges, some participants reported successfully receiving reproductive health care. This paper calls for coordinated action from the government, humanitarian agencies, and social service organisations to improve both the availability and accessibility of SRH services for adolescent refugee girls. Strategies should include enhanced outreach, culturally responsive engagement, and sustained follow-up care to promote safety, dignity, and well-being within the camps. Full article

This study focuses on firefighters’ relationship with different types of change in their profession and what barriers and facilitators might contribute to how they respond. Informed by the Force Field analysis of change, interviews were conducted to better understand what specific barriers and facilitators contribute to their views on types of change and the level of influence they carried. Twenty-five interviews were conducted with firefighters from a variety of backgrounds, including different ages, genders, ranks, and experience levels for both career and volunteer firefighters. Thematic analysis identified different responses to four common rationales that helped to explain the acceptance or dismissal of changes. These were as follows: (1) openness or apprehension towards change; (2) the results of a cost–benefit analysis that considered financial and manpower limits, perceived legitimacy of the problem, and efficacy of the solution; (3) reference to past experiences with changes that had failed or succeeded; and (4) trusted messengers that respected the chain of command were preferred. These themes are applicable across multiple types of changes, including technological and cultural adaptation. However, they also reveal challenges that may emerge due to friction with firefighters’ professional identities and traditional masculine norms. The patterns identified here can help to inform future efforts to implement changes and to anticipate likely points of friction or motivation that can be leveraged. Full article

The harsh, cold, and dry winters in northern China necessitate burying wine grapevines (Vitis vinifera) for winter protection. In this study, we screened for stably expressed reference genes in wine grapes (V. vinifera) under low-temperature stress at 4 °C (chilling) and −15 °C (freezing). A cold-resistant line “Hanniang 1301” and its cold-sensitive parent ‘Cabernet Sauvignon’ were treated at 4 °C and −15 °C for varying durations. Nineteen candidate reference genes were selected for qPCR analysis. Gene stability under chilling and freezing stress was evaluated using the following five algorithms: Delta CT (ΔCt), geNorm, NormFinder, BestKeeper, and RefFinder. The optimal reference genes under chilling (4 °C) and freezing (−15 °C) conditions were pairs with dual-reference combinations. However, the genes selected differed between chilling and sub-freezing temperatures. For chilling stress (4 °C), EF1α-1 and EF1α-2 were the most stable. Meanwhile, for freezing stress (−15 °C), GAPDH and Actin were optimal. We identified suitable reference genes for gene expression studies in wine grapes under low-temperature stress; this establishes a theoretical foundation for optimizing reference gene selection in plants under other abiotic stresses. Full article

The new generation of Eurocode standards has prompted enquiries regarding the major distinctions from the current version, particularly in relation to the application of the N2 method. A substantial change has been made to the definition of elastic spectra. The new spectra are defined through a series of fixed, probabilistically determined points, yet they remain rooted in a probabilistic approach. Three building types—multi-storey reinforced concrete (RC) frames, steel moment frames, and steel braced frames—were analysed in accordance with ground accelerations of 1, 2, and 3 m/s², as well as across five soil types (A–E). Variations in target displacements between soil types, particularly A, B, and D, are notable in the results. For accelerations of 2 and 3 m/s², steel structures demonstrate consistent displacements, whereas RC frames exhibit values that are up to 20% higher, particularly on soils C and E. For soils A and B, the distribution of inter-storey drift remains consistent. Nevertheless, in the case of 1 m/s², the utilisation of next-generation spectra results in an average 46% decrease in inter-storey drifts. The significance of adapting design methods to the updated Eurocode provisions is underscored by these findings, which emphasise the substantial influence of soil type on building response and safety performance, particularly under increased seismic demands. Full article