This paper examines the effects of fiscal, political, and administrative dimensions of Colombian decentralization on the performance of municipal governments in providing water supply and sewerage services between 2008 and 2019. It also assesses the influence of municipal size and geographic location on service provision. To address these questions, panel data models were estimated, applying the Hausman and Taylor estimator, which corrects for endogeneity and accounts for time-invariant regressors such as geographic characteristics. The findings reveal that national transfers, municipal tax collection and royalties have a positive effect on urban water supply coverage, while own-source revenues significantly contribute to rural water supply as well as urban and rural sewerage coverage. Political competition does not appear to be a relevant factor, whereas administrative capacity yields mixed results. Furthermore, urban areas in the Caribbean region and rural areas in the Andean region display relative lags in service provision. Proximity to large or medium-sized cities exerts a negative influence on coverage. These results, which are robust for small municipalities—representing 95% of the sample—underscore the differentiated effects of decentralization, with urban areas experiencing greater advances than rural ones. The study argues that policies aimed at closing these gaps require inter-municipal coordination and flexible provision schemes tailored to rural and lagging communities.

This cross-sectional study aims to demonstrate the impact of China's 2015 review and approval reform on the delays in market entry for novel geriatric drugs, as well as the capability of domestic innovation in developing geriatric drugs. We analyzed the novel geriatric drugs approved by the US Food and Drug Administration (FDA) between 2005 and 2024 to assess the drug lags in China by using the EU and Japan as comparators. During this period, the FDA approved a total of 183 novel drugs targeting geriatric diseases, of which 109 were also approved by the NMPA. Post-reform, China's absolute approval lag decreased significantly, with median relative lag narrowing from 53.9 to 29.9 months. However, China's lag remained longer than the EU and Japan, driven by submission delays. Domestic innovative drug approvals surged post-reform, yet oncology dominated, overshadowing high-burden conditions like neurological disorders, cardiovascular disease, and respiratory diseases. Expedited programs reduced development duration (conditional approval: 49.4 vs. regular 70.9 months), but review times lagged behind the FDA (16.1 vs. 11.1 months). This study also discusses the considerations of China's regulatory agency regarding current issues in geriatric drug development and future regulatory plans. Future regulatory efforts in China should focus on promoting patient-centric approaches, optimizing trial designs (including clinical pharmacology modeling and artificial intelligence), and incorporating real-world evidence to address the unique needs of older adults. These measures will be crucial in ensuring equitable access to innovative therapies and mitigating the impact of the "silver tsunami" on health outcomes for China's rapidly aging population.

The phenomenon of “pan-entertainment” is predicated on the value principle of entertainment supremacy. The integration of entertainment elements into all facets of society has been precipitated by several factors, including the operation of commercial capital, the trend of individual atomization, and the coupling of various ideological trends. This phenomenon has resulted in the entertainment industry adopting a more significant role in society, extending beyond its traditional function to encompass a broader value concept and lifestyle. Consequently, it has become a primary driver in shaping the ideological qualities, values, and future social behavior patterns of adolescents. However, the relative lag of the pan-entertainment carriers, the secularization of the content, and the sentimentality of the form have precipitated a crisis in the leading power, regulatory power, and cohesion of patriotic education for young people. This has also resulted in a diminished capacity of patriotic education to permeate the mainstream ideological recognition and spiritual and cultural life of young people. The mainstream influence of patriotic education can be reshaped from aspects such as the creation of a positive environment, the optimization of supply content, and the innovation of narrative methods, with a view to comprehensively cultivating the patriotic awareness of young people.

Drawing on panel data from 31 Chinese provinces over the period 2010–2023, this study constructs evaluation indices for green finance and high-quality economic development. The entropy weight method, coupling coordination degree model, and Dagum Gini coefficient are employed to examine the spatiotemporal synergies and regional disparities between the two systems. Findings reveal that, although both system indices exhibit growth in overall development levels, a marked pattern of “relative lag in high-quality economic development” has emerged since 2018. With respect to coordination status, national coupling coordination fluctuates and remains suboptimal, characterised by “high coupling but low coordination”; by 2023, the system had regressed to a state of “severe disequilibrium”. Spatially, a fundamental shift occurred after 2018, yielding a new pattern of differentiation: western and northeastern regions overtaking others, an inverted U-shaped decline in the east, and subsidence in the central region. Although the overall Gini coefficient has narrowed significantly, inter-regional disparities now constitute the predominant source of spatial imbalance, with their contribution rising to 65.38%. Economic development level, industrial structure optimisation, and government intervention emerge as the principal positive drivers of coordination. The analysis concludes that structural lag and pronounced spatial heterogeneity persist in the synergy between the two domains; policy priorities should therefore shift from “developing green finance” to “empowering high-quality development”, complemented by differentiated inter-regional coordination strategies.

ABSTRACT With the vigorous development of the electric vehicle (EV) industry, the demand for charging has surged. However, the relative lag in the construction of charging infrastructure has led to a series of problems for drivers, such as difficulty in finding available charging stations and long waiting times for charging. To address this, this paper proposes an EV charging guidance framework based on an Informer network and Multi‐Agent Reinforcement Learning (MARL), aiming at achieving efficient EV charging guidance. First, this paper regards charging stations as independent agents, integrating information from vehicles, charging stations, and traffic, transforming the multi‐objective optimization problem of EV charging guidance into a multi‐agent reinforcement learning task. Then, an Actor‐Critic algorithm combined with the Informer is designed, utilizing the Informer in the Critic network to model the interactions between different charging stations, thereby reducing the complexity of policy learning and enhancing coordination among agents. Subsequently, after calculating the advantage function for the agents, the Actor network is updated to improve learning efficiency. The proposed algorithm was simulated and validated in two different EV charging scenarios. The simulation results show that compared with several state‐of‐the‐art methods, our algorithm achieved the best results in multi‐objective optimization, demonstrating its superiority and practicality of our proposed algorithm.

BackgroundA pronounced disparity exists in the accessibility of orphan drugs between China and developed countries, such as the United States. Identifying and analyzing the critical determinants that contribute to this gap is essential for enhancing the availability of orphan drugs and promoting equitable access for patients.MethodsWe included all new orphan drugs approved by the US Food and Drug Administration (FDA) between 2013 and 2023 and collected their approval information in China and the United States. Major factors of interest included accelerated review pathway, locations where pivotal clinical trials were conducted, therapeutic category, and other factors affecting the delay in drug launch. They were analyzed using multinomial logistic regression, analysis of covariance, and the Mann-Whitney U test.ResultsThe FDA approved a total of 242 new orphan drugs between 2013 and 2023. Among these, 119 (49.2%) of these drugs had been approved in China as of 1 January 2025, with a median lag time of 1,004 days (2.75 years). Among them, 47 drugs (41.2%) were included in the China’s List of Rare Diseases. Multinomial logistic regression analysis revealed that the conduct of pivotal trials supporting FDA approval in mainland China was associated with whether such drugs were launched in China (odds ratio = 10.53, 95% confidence interval 3.67–40.79; P < 0.001). Furthermore, the Mann-Whitney U test indicated that such characteristics as the inclusion of indications in China’s List of Rare Diseases, the granting of breakthrough therapy designation by the National Medical Products Administration (NMPA), and the inclusion of pivotal clinical trials in mainland China were all associated with the shortening of drug lag time.DiscussionOur findings suggest that orphan drug approval delays in China have improved significantly, but still face significant challenges. China’s involvement in the global collaborative development of drugs not only helps shorten the relative lag time for drugs to obtain approval in China but also avoids repeated trials and significantly improves R&D efficiency. We recommend that pharmaceutical companies include Chinese patients in the drug development stage so that they can enjoy cutting-edge innovative therapies more quickly.

Path to Health Equity and Improved Outcomes through Inclusive Sex and Gender Data Collection in Genomic Testing.

Metastasis constitutes the principal factor leading to the unfavourable prognosis of osteosarcoma patients. Hypoxia, as the inherent microenvironment of osteosarcoma, can upregulate HIF-1α via multiple pathways, thereby facilitating osteosarcoma proliferation and metastasis. Our previous research indicated that the inwardly rectifying potassium channel subfamily J member 2 (KCNJ2) inhibits the degradation of HIF-1α in osteosarcoma. Concurrently, HIF-1α upregulates the expression of KCNJ2 through a positive feedback regulatory mechanism. This positive regulatory mechanism significantly promotes the proliferation and metastasis of osteosarcoma. Therefore, the development of a KCNJ2-targeted therapeutic strategy capable of disrupting this reciprocal regulatory loop represents a crucial intervention for impeding osteosarcoma progression. The CRISPR/Cas9 targeted gene editing technology has garnered extensive attention in the field of tumour treatment due to its high efficiency and low off-target rate. Nevertheless, the relative lag of the delivery systems has restricted its application. The extracellular vesicles (EVs) secreted by bone marrow mesenchymal stem cells (BMSCs) have a natural targeting specificity for osteosarcoma and possess superior biocompatibility, making them ideal carriers for in vivo delivery. However, it is essential to confirm whether the CRISPR/Cas9 system mediated by EVs can accurately function intracellularly. Hence, we developed a fluorescence-based Cas9 editing efficiency reporter system. When CRISPR/Cas9 system induces double-strand breaks at specific target sites and results in frameshift mutations, osteosarcoma cells will stably express GFP. This system enables the transformation of gene editing events into quantifiable fluorescence signals. Furthermore, we engineered radiolabelled EVs derived from BMSCs to deliver the CRISPR/Cas9 system targeting KCNJ2. Using this reporter system, we confirmed their efficient gene-editing capabilities in vitro. Additionally, leveraging their radiolabelling properties, we validated their targeted distribution in vivo. Subsequent investigations revealed that our constructed 124I@EVs-Cas9 effectively suppresses the proliferation and metastasis of osteosarcoma by targeting the inhibition of KCNJ2 expression and promoting HIF-1α ubiquitin-dependent degradation (as depicted in Graphical Abstract).

In this era of media convergence with rapid technological development, broadcasting practitioners are faced with the problem of how to use new technologies to enhance news dissemination and turn dilemmas into opportunities. This study uses media convergence theory and Chinese broadcasting theory to conduct a collective case study of positive examples of barrier-breaking, analyzing different presenters and their programs. It analyses the impact of changes in how audiences receive information, the relative lag in the speed of communication, the limitations of the form of communication, and the decline in the influence of communication on the communication of broadcasters and presenters. It puts forward positive suggestions in terms of guiding public opinion, strengthening one's influence, adapting to the form of communication, and transforming the language style. This will inform the career development of radio and television industry practitioners in the era of media convergence.

In this era of media convergence with rapid technological development, broadcasting practitioners are faced with the problem of how to use new technologies to enhance news dissemination and turn dilemmas into opportunities. This study uses media convergence theory and Chinese broadcasting theory to conduct a collective case study of positive examples of barrier-breaking, analyzing different presenters and their programs. It analyses the impact of changes in how audiences receive information, the relative lag in the speed of communication, the limitations of the form of communication, and the decline in the influence of communication on the communication of broadcasters and presenters. It puts forward positive suggestions in terms of guiding public opinion, strengthening one's influence, adapting to the form of communication, and transforming the language style. This will inform the career development of radio and television industry practitioners in the era of media convergence.

In this era of media convergence with rapid technological development, broadcasting practitioners are faced with the problem of how to use new technologies to enhance news dissemination and turn dilemmas into opportunities. This study uses media convergence theory and Chinese broadcasting theory to conduct a collective case study of positive examples of barrier-breaking, analyzing different presenters and their programs. It analyses the impact of changes in how audiences receive information, the relative lag in the speed of communication, the limitations of the form of communication, and the decline in the influence of communication on the communication of broadcasters and presenters. It puts forward positive suggestions in terms of guiding public opinion, strengthening one's influence, adapting to the form of communication, and transforming the language style. This will inform the career development of radio and television industry practitioners in the era of media convergence.

In this era of media convergence with rapid technological development, broadcasting practitioners are faced with the problem of how to use new technologies to enhance news dissemination and turn dilemmas into opportunities. This study uses media convergence theory and Chinese broadcasting theory to conduct a collective case study of positive examples of barrier-breaking, analyzing different presenters and their programs. It analyses the impact of changes in how audiences receive information, the relative lag in the speed of communication, the limitations of the form of communication, and the decline in the influence of communication on the communication of broadcasters and presenters. It puts forward positive suggestions in terms of guiding public opinion, strengthening one's influence, adapting to the form of communication, and transforming the language style. This will inform the career development of radio and television industry practitioners in the era of media convergence.

BackgroundImmune checkpoint inhibitors (ICIs) have revolutionised antitumour therapy. However, regional differences in ICI labels, including the impact of the review process and supporting trial evidence, remain unclear.MethodsWe conducted a serial...

As the demand for high-frequency and high-power electronic devices has increased, gallium nitride (GaN), particularly in the context of high-electron mobility transistors (HEMTs), has attracted considerable attention. However, the ‘self-heating effect’ of GaN HEMTs represents a significant limitation regarding both performance and reliability. Diamond, renowned for its exceptional thermal conductivity, represents an optimal material for thermal management in HEMTs. This paper proposes a novel method for directly depositing diamond films onto N-polar GaN (NP-GaN) epitaxial layers. This eliminates the complexities of the traditional diamond growth process and the need for temporary substrate steps. Given the relative lag in the development of N-polar material growth technologies, which are marked by surface roughness issues, and the recognition that the thermal boundary resistance (TBRGaN/diamond) represents a critical factor constraining efficient heat transfer, our study has introduced a series of optimizations to enhance the quality of the diamond nucleation layer while ensuring that the integrity of the GaN buffer layer remains intact. Moreover, chemical mechanical polishing (CMP) technology was employed to effectively reduce the surface roughness of the NP-GaN base, thereby providing a more favorable foundation for diamond growth. The optimization trends observed in the thermal performance test results are encouraging. Integrating diamond films onto highly smooth NP-GaN epitaxial layers demonstrates a reduction in TBRGaN/diamond compared to that of diamond layers deposited onto NP-GaN with higher surface roughness that had undergone no prior process treatment.

Exposure to air pollution is a major health problem worldwide. This study aimed to investigate the effect of the level of air pollutants and meteorological parameters with their related lag time on the transmission and severity of coronavirus disease 19 (COVID-19) using machine learning (ML) techniques in Shiraz, Iran. Study Design: An ecological study. In this ecological research, three main ML techniques, including decision trees, random forest, and extreme gradient boosting (XGBoost), have been applied to correlate meteorological parameters and air pollutants with infection transmission, hospitalization, and death due to COVID-19 from 1 October 2020 to 1 March 2022. These parameters and pollutants included particulate matter (PM2), sulfur dioxide (SO2 ), nitrogen dioxide (NO2 ), nitric oxide (NO), ozone (O3 ), carbon monoxide (CO), temperature (T), relative humidity (RH), dew point (DP), air pressure (AP), and wind speed (WS). Based on the three ML techniques, NO2 (lag 5 day), CO (lag 4), and T (lag 25) were the most important environmental features affecting the spread of COVID-19 infection. In addition, the most important features contributing to hospitalization due to COVID-19 included RH (lag 28), T (lag 11), and O3 (lag 10). After adjusting for the number of infections, the most important features affecting the number of deaths caused by COVID-19 were NO2 (lag 20), O3 (lag 22), and NO (lag 23). Our findings suggested that epidemics caused by COVID-19 and (possibly) similarly viral transmitted infections, including flu, air pollutants, and meteorological parameters, can be used to predict their burden on the community and health system. In addition, meteorological and air quality data should be included in preventive measures.

The pharmaceutical industry is vital for healthcare advancement through innovative medications, improving lives. A substantial challenge is "Drug lag," hindering patient access and increasing disease adjusted life years burdens. We aim to examine drug lag for Iran Food and Drug Administration (IFDA) approved drugs versus US Food & Drug Administration (FDA), European Medicines Agency (EMA), and Pharmaceuticals and Medical Devices Agency (PMDA) over 2001 to 2021. We reviewed new molecular entities within this period, using descriptive statistics in Excel 2019. Drug lag is assessed from relative and absolute perspectives, considering approval gaps and annual rates. Among 710 FDA-approved drugs, 410 received EMA approval, 344 from PMDA, and 148 from IFDA. For 148 IFDA and FDA-approved drugs, the maximum drug lag was 237 months. The mean relative drug lag was 65.18 ± 61.56 months. Compared to EMA (112 drugs), the maximum lag was 257 months, with a mean relative lag of 70.29 ± 53.67 months. With PMDA (127 drugs), the maximum lag was 253 months, with a mean relative lag of 38.23 ± 60.57 months. Iran faces significant drug lag compared to developed countries' regulatory bodies, limiting patient access to innovative treatments. Addressing this issue is crucial for timely drug access, reducing disease burdens. Further research and policy interventions are needed to mitigate drug lag's impact on Iran healthcare landscape.

As the digital landscape continues to evolve, cyber warfare has emerged as a prominent domain of warfare, with superpower nations actively demonstrating their capabilities in the cyberspace. This study posits that African countries exhibit a relative lag in research and development of cyber warfare capabilities, as evidenced by the absence of African nations in the National Cyber Power Index released by the Belfer Centre for Science and International Affairs in 2022. To address this knowledge gap, this paper presents a comprehensive bibliometric analysis of cyber warfare research and development within the African continent. The analysis aims to illuminate research productivity, performance, science mapping, and key contributors at both national and institutional levels. It seeks to uncover thematic trends, pinpoint key research areas, and identify research connections within the African context. This research evaluates the African continent's research participation and development in the cyber and/or information warfare domain over the past 23 years. The analysis encompasses scholarly articles and conference proceedings published between 2000 and 2023, utilizing Scopus as the primary data source. Preliminary findings suggest that cyber warfare research in Africa is concentrated in a limited number of countries, with South Africa emerging as the leading contributor. A comparative analysis further reveals that developed countries generally outpace African nations in cyber warfare research and development, corroborating the rankings presented in the National Cyber Power Index (NCPI) and Global Cybersecurity Index (GCI).

In recent years, there has been significant focus on China's new drug lag, but relevant research is limited. This study explores the reasons for drug lag by assessing the impact of reforms in China's drug review system, particularly focusing on the influence of clinical development strategies. This study selected drugs first launched in the United States between 2017 and 2022, examining absolute and relative lag between China and the first-launch country (including submission and review lag). These delays with drugs approved in the European Union and Japan during the same period were compared with uncover the roots of delays in China, further identifying potential factors that could reduce these delays. The results indicate that the National Medical Products Administration (NMPA) has a longer relative lag compared with the European Medicines Agency (EMA) and the Pharmaceuticals and Medical Devices Agency (PMDA). The submission lag time of the NMPA significantly surpasses that of the EMA and PMDA, whereas the review lag time of the NMPA exceeds that of the PMDA but falls short of the EMA. Focusing on clinical trial strategies, bridging trials and multiregional clinical trials (MRCTs) are typically required by the NMPA in East Asia, resulting in longer clinical delay time. Whereas the EMA and PMDA primarily require international MRCTs in Europe and America, with a clinical delay of < 5 months. It is evident that there is a significant gap in clinical trial durations between China and other countries. Further optimization of clinical trial management is necessary to address the lag for new drugs in China.

In this study, an in-depth discussion was conducted on the current teaching situation of physical training courses in higher education, and a series of problems, such as the irrationality of curriculum design, the lack of site construction, the low overall quality of teachers’ team, the relative lag of teaching means and the singleness of teaching evaluation methods, were found. To solve the problems above, by combining the development trend of higher education in China and the characteristics of physical education, a series of development strategies and suggestions were proposed, including improving the curriculum, strengthening the construction of venues, improving the level of teachers, enriching teaching methods, and establishing a scientific evaluation system, aiming to improve the quality of physical training courses in higher education in an all-round way.

Seed amplification assays have been implemented in Parkinson’s disease to reveal disease-specific misfolded alpha-synuclein aggregates in biospecimens. While the assays’ qualitative dichotomous seeding response is valuable to stratify and enrich cohorts for alpha-synuclein pathology in general, more quantitative parameters that are associated with clinical dynamics of disease progression and that might potentially serve as exploratory outcome measures in clinical trials targeting alpha-synuclein would add important information. To evaluate whether the seeding kinetic parameters time required to reach the seeding threshold (LAG phase), the peak of fluorescence response (Imax), and the area under the curve (AUC) are associated with clinical trajectories, we analyzed LAG, Imax, and AUC in relation to the development of cognitive decline in a longitudinal cohort of 199 people with Parkinson’s disease with positive CSF alpha-synuclein seeding status. Patients were stratified into tertiles based on their individual CSF alpha-synuclein seeding kinetic properties. The effect of the kinetic parameters on longitudinal development of cognitive impairment defined by MoCA ≤25 was analyzed by Cox-Regression. Patients with a higher number of positive seeding replicates and tertile groups of shorter LAG, higher Imax, and higher AUC showed a higher prevalence of and a shorter duration until cognitive impairment longitudinally (3, 6, and 3 years earlier with p ≤ 0.001, respectively). Results remained similar in separate subgroup analyses of patients with and without GBA mutation. We conclude that a more prominent alpha-synuclein seeding kinetic profile translates into a more rapid development of cognitive decline.