Search Results (23,802)

Histone deacetylases (HDACs) 1–3 are key regulators of gene expression and represent important therapeutic targets in cancer, neurodegenerative, and immune disorders. Many potent class I HDAC inhibitors display slow- and tight-binding kinetics, which profoundly influence their efficacy and pharmacodynamics. In particular, their dissociation rate (off-kinetic) is critical, since prolonged target engagement greatly influences drug efficacy in vivo. However, the off-kinetics of HDAC inhibitors are often overlooked in the early stages of drug development. Here, we investigated the dissociation kinetics of tucidinostat, trapoxin A, and TNG260 in comparison to the pan-HDAC inhibitor vorinostat. Using biochemical 100-fold jump dilution assays, NanoBRET assays, and cellular washout experiments, we characterized the dissociation of these compounds from purified proteins and in a cellular context. Tucidinostat showed moderately slow off-kinetics, while the clinical candidate TNG260 demonstrated pronounced tight-binding properties. Trapoxin A displayed remarkable discrepancies between assays, as it showed fast dissociation kinetics in the biochemical assay, but tight-binding properties in a cellular setting. These findings not only address the previously unexplored dissociation kinetics of two clinically relevant inhibitors, but also underscore the importance of comprehensive kinetic profiling of novel HDAC inhibitors in cellular models. Full article

The smart city concept has become a dominant framework for contemporary urban governance, largely driven by advances in digital technologies and data-driven decision-making. However, the prevailing technocratic orientation of smart city development risks marginalising the sociopolitical dimensions of urban governance, particularly citizen and stakeholder participation. Although smart governance frameworks increasingly recognise participation as a normative principle, limited empirical attention has been paid to the participation motivators that drive engagement among different urban stakeholder groups. This study addresses this gap by analysing the key motivators influencing stakeholder participation in urban development within a smart city context. Building on established behavioural and participation theories, the article develops an Urban Participation Motivator Model comprising four core motivators: social pressure, emotional trigger, rational motivation, and reward for participation. The model is empirically tested using quantitative survey data from 620 respondents representing four stakeholder groups in Riga, Latvia: municipal residents, municipal employees, municipal politicians, and real estate developers. Data are analysed using descriptive statistics and non-parametric methods, including the Kruskal–Wallis test. The results reveal statistically significant differences in the perceived importance of participation motivators across stakeholder groups. Emotional triggers and social pressure emerge as the most influential motivators overall, while rational motivation is particularly salient for professional stakeholders. Reward for participation plays a weaker but differentiated role, being most relevant for municipal employees. These findings highlight the need for differentiated motivator-sensitive urban communication and participation strategies to enhance inclusiveness, democratic legitimacy, and long-term engagement in smart city development. Full article

The retrofit of existing residential buildings plays a critical role in reducing energy consumption and carbon emissions in the building sector. However, previous retrofit evaluations often fail to account for the age-related thermal and lighting requirements of residents in aging residential buildings, thereby overlooking the substantial behavioral heterogeneity that shapes retrofit effectiveness. This study evaluates the comprehensive performance of different building envelope retrofit strategies, considering occupants’ thermal and visual comfort, from the perspectives of energy efficiency, economic feasibility, and environmental sustainability. First, age-specific differences in occupancy patterns, thermal preferences, and lighting requirements between elderly and non-elderly comparison group occupants were systematically extracted from the literature. Then, a typical high-rise residential building was modeled in EnergyPlus to serve as the reference building, within which the differentiated occupant behavior models were implemented, and the pre-retrofit condition was defined as the baseline scenario. Next, six commonly applied exterior wall insulation materials and different glass configurations and window frames were parameterized and evaluated under varying insulation thicknesses and remaining building service life scenarios. Finally, the energy-saving performance, economic benefits, and carbon reduction potential of envelope retrofit measures were quantitatively assessed across three primary functional zones (bedroom, living room, and study), using area-normalized indicators. The results indicate that, in the retrofit of existing residential buildings, bedrooms and study rooms exhibit greater retrofit benefits than living rooms, primarily due to longer occupancy durations and higher heating demand. In terms of retrofit strategies, exterior wall insulation consistently outperforms window retrofitting in energy-saving potential, with energy-saving rates of approximately 3.2–4.3% depending on functional zone, material type, and insulation thickness. Among the evaluated materials, vitrified microbead insulation performs best overall in terms of energy, economic, and carbon benefits at 40–60 mm thickness. These findings support occupant-informed, low-carbon retrofit decision-making for existing residential buildings. Full article

Background/Objectives: Sizeable between- and within-country inequalities in childhood immunization impair progress towards the goals set by the global Immunization Agenda 2030 (IA2030) of achieving universal coverage of all persons with essential life-saving vaccines. Monitoring global trends in immunization inequalities helps to identify population subgroups that are less likely to benefit from vaccines and provides evidence for tracking progress on regional and global goals and informing equity-oriented interventions. This paper assesses the state of within-country inequality in childhood immunization across low- and middle-income study countries. Methods: Using data from household health surveys, the analysis quantifies within-country inequality across up to 92 countries, areas and territories, for nine childhood immunization indicators (seven coverage indicators and two indicators of non-receipt of vaccines) by five dimensions of inequality (child sex, mother’s age, mother’s education, household economic status and place of residence). Absolute and relative summary measures of inequality (difference, ratio, slope index of inequality, relative index of inequality and population attributable risk) were calculated to assess the latest situation of inequality (i.e., using the most recent survey from 2014 to 2023) and change over time (i.e., comparisons with data from 2004 to 2013). Results: The latest situation of inequality revealed overall low or no inequality by child sex, mother’s age and place of residence, with more pronounced inequality related to mother’s education and household economic status. The median differences between the most and least educated subgroups ranged between 9 and 14 percentage points for immunization coverage indicators, and between 6 and 9 percentage points for non-receipt of vaccines indicators. The extent of inequality in childhood immunization tended to remain about the same as the previous decade, with modest reductions in absolute economic-related and place of residence inequality in DTP3 immunization, as well as place of residence inequality in full immunization (declining by 3.25, 2.42, and 2.16 percentage points over 10 years, respectively). Distinct patterns of economic-related inequality were evident across country income groups, with low-income countries reporting larger inequality than lower- and upper-middle-income countries; there was substantial variation at the country level. Conclusions: Economic- and education-related inequalities in childhood immunization within low- and middle-income countries have persisted over the past decade. Full article

Urban pedestrianization has become a widely adopted strategy to promote sustainable mobility, improve urban livability, and enhance the quality of public space. Despite its potential benefits, pedestrianization interventions often generate heterogeneous perceptions among different user groups, which may influence their long-term acceptance. This study analyzes citizen perceptions of an urban pedestrianization intervention implemented in the city of Loja, Ecuador, considering residents, business owners or employees, and pedestrians or visitors. A structured survey was conducted, and the collected data were analyzed using exploratory analytical techniques, including rescaled single-item indices, user segmentation, and Spearman correlation analysis to identify patterns and relationships among variables. The results reveal significant associations between socio-demographic characteristics, user type, and acceptance of permanent pedestrianization, as well as differentiated patterns of urban experience. These findings provide empirical evidence to support decision-making in urban mobility policies and contribute to the academic discussion on pedestrianization in intermediate Latin American cities. Full article

Background/Objectives: Healthy food incentive programs (HFIP), such as fruit and vegetable voucher incentives, can supplement other nutrition assistance programs to support food and nutrition security. However, little is known about the prevalence of HFIP, particularly at the municipal level. This study examines the prevalence of HFIP in a nationally representative sample of U.S. municipalities and the association between the availability of HFIP and municipal characteristics. Methods: Using data from the CDC’s 2021 National Survey of Community-Based Policy and Environmental Supports for Healthy and Active Living (n = 1982 municipalities), a weighted bivariate analysis and multivariable logistic regression analysis were conducted to estimate the prevalence of HFIP overall and by municipal characteristics, and to assess the relationship between municipal characteristics and HFIP. Results: Only 7.8% of municipalities reported offering HFIP in 2021. The odds of having an HFIP were higher in municipalities with a food policy council (aOR 2.8; 95%CI: 1.9, 3.9) compared to those without. Larger communities (size ≥ 50,000 reported 24.6%) and those with a higher prevalence of residents living in poverty were also more likely to offer HFIP. Conclusions: Few municipalities reported offering HFIP. Results suggested that engaging institutions and individuals (e.g., via food access coalitions) may be strategies that could support municipalities initiating and implementing HFIP to improve diet quality and reduce chronic disease risk. Full article

Background and Objectives. Mother-to-child transmission (MTCT) or vertical transmission of human immunodeficiency virus (HIV) is largely preventable in settings where prevention of MTCT (PVT) strategies are consistently implemented. Romania represents a particular epidemiological context, as individuals from the historical pediatric HIV cohort have now reached reproductive age. This study assessed current PVT outcomes in northeastern Romania and explored the remaining circumstances in which transmission still occurs. Materials and Methods. We performed a retrospective observational analysis at the Regional HIV/AIDS Center of Iași (“Sfânta Parascheva” Clinical Hospital of Infectious Diseases), including all pregnant women living with HIV and their HIV-exposed infants followed between 2023 and 2025. Maternal data comprised age, place of residence, origin from the Romanian pediatric cohort, antiretroviral therapy (ART) adherence, and HIV RNA viral load in the third trimester. Obstetric characteristics, delivery mode, neonatal antiretroviral prophylaxis, and infant HIV RNA PCR results during follow-up up to 18–24 months were also evaluated. Results. A total of 61 HIV-positive pregnant women and 53 HIV-exposed infants were included. Viral suppression during pregnancy was documented in 59 women (96.7%), while two cases of detectable viremia in late pregnancy were linked to poor ART adherence. All women delivered by elective cesarean section, and all infants received neonatal antiretroviral prophylaxis, with Raltegravir added in selected higher-risk situations. Overall, MTCT was 3.8% (2/53). No transmission events were recorded in 2023 or 2024; both cases occurred in 2025 (15.4% of infants born that year) and exclusively in the context of maternal viremia. Women originating from the historical pediatric HIV cohort accounted for 31.1% (19/61) of pregnancies, and no transmission was observed among their infants. Conclusions. In northeastern Romania, PVT programs remain highly effective when maternal viral suppression is achieved. Residual transmission was confined to situations of maternal viremia driven by ART non-adherence, highlighting the continued importance of adherence support during pregnancy. Full article

Industrial heritage in resource-depleted mining towns faces the dual challenge of physical decay and social severance. To achieve sustainable urban revitalization, adaptive reuse strategies must align with local collective memory and emerging experiential consumption trends. Adopting a Scene Theory perspective, this study constructs a multi-level analytical framework using Meitanba Town (Hunan, China) and its power plant as a case study. A mixed-methods approach was employed, combining semantic network analysis of 1582 online user comments with 61 offline questionnaires distributed to local residents to quantitatively diagnose current scene elements, functions, and features. The quantitative results reveal a significant imbalance: while “Functional Media” achieved the highest comprehensive score (10.0) due to strong historical recognition, “Diverse Groups” scored the lowest (3.4), indicating a lack of social inclusivity. Specifically, residents expressed the highest demand for sports facilities (31.2%) and cultural spaces (23.7%), identifying the main workshop (26.4%) and chimney as core carriers of industrial identity. Responding to these findings, the paper proposes three targeted strategies: (1) Activate: creating open-access recreation scenes to satisfy urgent sports demands; (2) Link: constructing immersive cultural scenes to narrate the “coal–electricity–life” history; and (3) Enhance: developing industry-powered commercial scenes to avoid homogenization. This study enriches the localized application of Scene Theory and provides a data-driven, context-adjustable analytical and strategic model that can inform the sustainable renewal of mining towns globally, with its specific implementation requiring adaptation to local social, economic, and cultural characteristics. Full article

This study presents a comparative analysis of residential segregation among the three largest foreign-born populations residing in Spain: Moroccans, Romanians, and Colombians. Using data from Spain’s Population and Housing Census (INE), the research analyzed the segregation index across 34 urban areas in medium-sized cities. Three urban areas in Catalonia were selected for the intraurban case studies, and Pearson correlation coefficients were calculated for 60 sociodemographic variables. The objectives were to identify indicators that helped diagnose potential segregation contexts and to explore residential patterns by country of origin. The study was grounded in a central premise: the foreign-born population cannot be treated as a homogeneous group, as aggregation conceals group-specific inequalities and differentiated spatial configurations. The findings showed that segregation occurred. Moroccans exhibited the highest levels of segregation, which was associated with socioeconomic vulnerability and also a marked residential preference for central urban areas. Colombians displayed lower levels of segregation and greater territorial dispersion, pointing to broader residential access. Romanians presented intermediate and heterogeneous patterns, which combined localized concentrations with peripheral settlement. The results highlighted how intraurban differentiation emerged from interactions between different migrant profiles, housing opportunity structures, and urban morphology, providing an empirical basis on which to design targeted urban policies. Full article

Understanding the socio-demographic drivers of residential energy-saving behavior is critical for designing effective energy policies and technologies. This study applies a Multiple Indicators, Multiple Causes (MIMIC) model to examine how individual characteristics are associated with two latent constructs: energy concern and smart-home interest and usage. Using survey data collected from urban residents in Guangdong Province (N = 261), structural equation modeling was employed to assess both measurement and structural components of the model. The results show that income is positively associated with both energy concern and smart-home interest and usage, whereas being a bill payer is negatively related to both. Gender also plays a role, with females reporting higher energy concern. Other factors, such as age, education, and time spent at home, did not show significant effects. The model showed acceptable global fit indices; however, the reliability and convergent validity of the latent constructs were limited. Accordingly, the findings should be interpreted as exploratory associations observed within this sample and may serve as a basis for future research on segmentation in similar urban contexts. Full article

Background/Objectives: Wound healing is a complex biological process involving coordinated interactions among inflammatory cells, growth factors, extracellular matrix components, and resident tissue cells. Despite significant advances in experimental research, translation of these findings into clinical practice remains limited, partly due to the lack of reproducible and ethically accessible human wound models. Pilonidal disease, a chronic inflammatory condition of the sacrococcygeal region, is frequently treated by surgical excision with healing by secondary intention. The resulting open wound provides a unique opportunity to study the natural progression of human tissue repair. Methods: This narrative review examines current knowledge on wound-healing physiology, commonly used experimental wound models, and clinical studies related to pilonidal disease. Evidence from experimental, translational, and clinical literature was evaluated to explore the potential of open pilonidal excision wounds as a standardized human model for wound-healing research. Results: Following open excision, healing typically occurs within 4–10 weeks through the classical phases of inflammation, proliferation, and tissue remodeling. During this period, the wound remains externally accessible, allowing repeated clinical observation and serial collection of tissue samples, wound fluid, and exudate. This accessibility facilitates investigation of key biological processes, including angiogenesis, fibroblast proliferation, epithelial migration, cytokine signaling, and extracellular matrix remodeling. Compared with in vitro systems and animal models, the open pilonidal wound offers direct insight into human wound biology under clinically relevant conditions. Conclusions: Open pilonidal excision wounds constitute a reproducible and ethically feasible in vivo human model for translational wound-healing research. This model may support biomarker discovery and contribute to the development of new therapeutic strategies for impaired healing and chronic wounds. Full article

This cross-sectional study included 112 community-dwelling older adults aged ≥ 60 years residing in Tha Sala District, Nakhon Si Thammarat Province, Thailand, recruited using a community-based quota sampling approach. Locomotive syndrome (LS) was assessed using the two-step test and classified according to the Japanese Orthopaedic Association criteria. Physical activity was evaluated using the Thai version of the Global Physical Activity Questionnaire across work-related, transportation-related, and recreational domains. Frailty and cognitive status were assessed using the Thai version of the FRAIL questionnaire and the Montreal Cognitive Assessment, respectively. Binary logistic regression analysis was used to examine associations. The prevalence of LS was 74.1%, with 37.5%, 33.0%, and 3.6% in participants classified as having LS stages 1, 2, and 3, respectively. Transportation-related physical activity was significantly associated with lower odds of LS. Frailty and mild cognitive impairment frequently coexisted with LS but were not independently associated with LS after adjustment for age and sex. Transportation-related physical activity emerged as a key protective factor, highlighting the importance of habitual mobility in daily life. Our findings suggest that LS overlaps with, but is not identical to, frailty and cognitive decline in relatively robust community settings. Early screening and mobility-related physical activity may be crucial in preventing functional decline in rapidly aging societies. Full article

The Air-front Smart City (ASC) concept is proposed to address the stagnation of industries in developed countries and stimulate economic growth in developing countries while maintaining a higher quality of life for people and contributing to decarbonization and overall United Nations SDGs in an existing study. However, no studies have been conducted to assess ASC policies. Therefore, this study integrates the integrated accessibility index into the quality of life (QOL) and quality of business (QOB) evaluation models to assess the startup ecosystem in Aichi, Singapore, and Munich within the ASC concept. The study uses survey data conducted in Aichi to estimate monetary values of QOL and QOB component indicators, calculates the integrated accessibility indices, and estimates QOL and QOB. Furthermore, the study sets scenarios to assess the impacts of living and business urban policies in Aichi. Additionally, the study using Aichi parameters compares the startup ecosystem in Singapore and Munich. The result shows that the key drivers of startup attraction are corporate tax rate, economic growth, and safety; enhancing these indicators directly increases startups’ QOB, business partners, and residents’ QOL. It was found that QOB in Singapore is comparatively higher, whereas QOL is higher in Aichi. Full article

Ocular diseases pose significant therapeutic challenges due to the eye’s intricate anatomy and efficient physiological clearance mechanisms, which result in the rapid elimination of topically administered drugs and an overall bioavailability of less than 5%. Anterior segment disorders—including keratitis, glaucoma, and dry eye syndrome—account for the majority of ophthalmic conditions and are primarily managed with pharmacological agents. However, due to extremely low drug bioavailability and poor patient compliance, their therapeutic outcomes often result in a decreased disease control rate or require early surgical interventions. Nebulized drug delivery, particularly employing advanced vibrating mesh technology, has emerged as a promising strategy to overcome these limitations. By converting liquid formulations into a uniform aerosol of micron-sized (1–10 μm) droplets, this approach achieves extensive and consistent coverage of the ocular surface, increases the absorption contact area, prolongs drug residence time, and ultimately enhances drug bioavailability. Preliminary clinical evidence indicates that nebulized therapies outperform traditional eye drops by achieving higher drug concentrations in the aqueous humor and demonstrating superior pharmacodynamic profiles and patient tolerability—particularly in conditions such as dry eye syndrome and glaucoma. This review presents a comprehensive overview of the mechanistic principles, technological advancements, and translational applications of nebulization-based ocular drug delivery systems. We place special emphasis on the integration of next-generation platforms that incorporate microelectromechanical systems (MEMS) and intelligent sensing technologies, enabling precision medicine approaches tailored to individual ocular pathophysiological characteristics. By bridging biomedical engineering and clinical ophthalmology, these innovations not only optimize existing therapeutic regimens but also pave the way for non-invasive delivery of complex biologics and gene therapies—potentially reshaping the landscape of anterior segment drug delivery. Full article

The use of animals in biomedical research and university teaching remains socially sensitive, shaped by ethical concerns, regulations, and public expectations. While animal models are still essential for basic and translational research, society increasingly demands transparency, strong welfare protections, and the development of alternative methods. This study investigated Spanish university students’ attitudes toward the use of animals in basic research, translational research, and educational settings, and examined their acceptance of different species for addressing human health problems. It also assessed how sociodemographic variables, personality traits, empathy, and anthropomorphism relate to these views. The sample included 653 students, predominantly women, heterosexual, and urban residents. Most participants supported the use of animals in research, whereas opinions regarding teaching uses were more divided. Attitudes toward the use of laboratory animals consistently differed by gender and field of study, with men and students in science-related disciplines showing higher acceptance. Of the psychological variables assessed, only anthropomorphism showed moderate negative correlations with support for the use of laboratory animals across all contexts. Species strongly influenced attitudes: companion animals generated the most opposition, primates and livestock elicited mixed responses, and rodents, invertebrates, and aquatic species received the highest support. Overall, students generally accept animal use but vary substantially by species, gender, and academic background. Full article