Search Results (9,150)

Oncomodulin (OCM) is the most abundant Ca²⁺ buffering protein found in mature outer hair cells (OHCs). Cadherin 23 (CDH23) is a crucial component of the tip-links in hair cell stereocilia. The absence or dysfunction of these two proteins contributes to the early onset of age-related hearing loss (AHL). In this study, we investigated the effects of the Cdh23^753G→A mutation on OHC function using new Ocm-knockout (KO) mouse models (Ocm^tm1a/tm1a) with or without the Cdh23^753G→A mutation. Despite having the same genetic background, Ocm-KO mice carrying the Cdh23^753G→A mutation displayed a notable decline in OHC function across all measured frequencies as early as three months of age. In contrast, Ocm-KO mice without the Cdh23^753G→A mutation did not exhibit comparable hearing loss until they reached twelve months of age. Additionally, we examined the role of OCM in preserving OHC function under ototoxic stress induced by HPβCD (2-hydroxypropyl-β-cyclodextrin). The distortion product otoacoustic emission data show that the administration of HPβCD resulted in a more pronounced decline in OHC function in Ocm-KO mice compared to wild-type (WT) mice. Time-lapse recording also shows that HPβCD treatment led to greater structural deterioration and more rapid rupture events in OHCs from Ocm-KO mice than in those from WT mice. These findings suggest that the Cdh23^753G→A mutation, rather than other potential strain-specific genetic factors associated with AHL, significantly exacerbates the early onset of AHL phenotypes in Ocm-KO mice. Furthermore, our data indicates that the OCM protein in OHCs enhances their ability to withstand ototoxic stimuli. Full article

Urban agglomerations have become the dominant spatial platform of urbanization, regional coordination, and economic transformation in China. Yet whether the expansion of agglomeration scale at the urban-agglomeration level alleviates or intensifies energy use remains insufficiently understood. Extending the scale of analysis from individual cities to integrated urban agglomerations, this study investigates 64 cities in four major Chinese urban agglomerations, including Beijing–Tianjin–Hebei, the Yangtze River Delta, the Pearl River Delta, and Chengdu–Chongqing, over the period 2006–2023. Using panel data models, this study examines the impact of the scale agglomeration within urban agglomeration on urban energy intensity. The results show that the overall agglomeration scale generated by urban agglomeration formation significantly suppresses energy intensity while indicating a robust energy-saving effect: every 10% increase in agglomeration scale is associated with a decline of approximately 0.0893 million tons of standard coal per CNY 100 million of GDP. This finding remains stable after addressing endogeneity concerns and performing a series of robustness checks. Mechanism analyses further suggest that this effect operates primarily through talent agglomeration, technological progress, and public transportation expansion. In addition, the energy-saving effect is more pronounced in smaller cities, cities with lower administrative rank, cities with weaker factor mobility, and cities characterized by poorer air quality but stronger public environmental attention. These findings contribute to the literature on urban agglomeration and green development by showing that the agglomeration scale within urban agglomerations can generate inclusive energy-efficiency gains, especially for relatively disadvantaged cities, thereby offering important implications for spatial governance and low-carbon transition in rapidly urbanizing economies. Full article

Background: H1-antihistamines are widely used for allergic and upper respiratory conditions; however, several agents included in this class have been associated with cardiac electrophysiological adverse effects, including QT interval prolongation and torsades de pointes (TdP). These effects are largely exposure-dependent and mechanistically linked to inhibition of cardiac ion channels. Chlorpheniramine maleate (CPM), a first-generation H1-antihistamine, has been implicated in arrhythmic events primarily under conditions of increased systemic exposure, prompting interest in whether alternative routes of administration may lower cardiac risk. Methods: This narrative review integrates mechanistic, preclinical, clinical, pharmacokinetic, and regulatory evidence. Information was extracted from PubMed, Google Scholar, and Scielo using search terms such as cardiotoxicity, chlorpheniramine, QT prolongation, intranasal administration, and cardiac arrhythmias, with no language restriction. Results: Comparative pharmacokinetic evidence shows that, on a dose-normalized basis, intranasal and oral chlorpheniramine exhibit comparable bioavailability; however, in a clinical context, intranasal doses (1.12–2.24 mg) are lower than oral daily doses (4–12 mg/day), resulting in a lower systemic exposure (Cmax and AUC) with intranasal administration. Available pharmacovigilance or epidemiological data have not specifically evaluated intranasal chlorpheniramine, and the number of dedicated safety trials remains limited. Conclusions: Preclinical, in vitro, mechanistic studies suggest that intranasal administration of chlorpheniramine should confer superior cardiac safety compared to the oral route. However, clinical data from human studies directly comparing the cardiac safety of intranasal chlorpheniramine versus systemic chlorpheniramine is extremely limited. More data from clinical trials, case–control studies, and regulatory databases are needed to validate these theoretical claims. Full article

This study examines administrative staff perceptions of selected AI-related dimensions and their association with sustainable administrative performance at the University of Hail. Specifically, it focuses on expert systems, automated machine learning, and ease of use as perceived dimensions of AI-related administrative support. Methodology: A quantitative cross-sectional survey design was employed. Data were collected using a structured Likert-scale questionnaire administered to a purposive sample of 230 administrative staff members. Descriptive statistics and regression analysis were used to assess the perceived level of AI-related support and its association with sustainable administrative performance. Results: The overall perceived level of AI-related support was moderate, indicating partial integration of AI-related practices in administrative work. Expert systems, automated machine learning, and ease of use each showed a positive and statistically significant association with sustainable administrative performance. Expert systems showed the strongest standardized association. Collectively, the three dimensions explained a substantial proportion of the variance in sustainable administrative performance. Limitations: The study is limited by its cross-sectional design, reliance on self-reported questionnaire data, and focus on a single university using purposive sampling, which restricts causal interpretation and generalizability. The findings also reflect perceptions rather than objectively verified implementation data. Full article

Background: Effective sick-day management, including ketosis home management aimed at preventing diabetic ketoacidosis (DKA), is essential for families living with a child/adolescent with type 1 diabetes (T1D). Methods: Adolescents living with T1D and caregivers of younger children living with T1D were invited to participate in an interview consisting of five parts: (I) demographic data, (II) subjective self-ratings on competence in ketosis home management, (III) objective assessment of competence in ketosis home management using a standardized clinical case scenario consisting of 10 management steps, in which participants were asked to describe the actions they would take to prevent DKA, and (IV) practical demonstrations to objectively assess skills in (IVa) urine dipstick self-testing and (IVb) insulin administration, (V) household availability of (Va) urine dipsticks and (Vb) insulin cartridges. Results: (I) We enrolled 61 adolescents and 79 caregivers. (II) Competence in ketosis home management was subjectively self-rated as good to very good. (III) Adolescents reported 4 (median; Q25/Q75 3/5) and caregivers 5 (4/5) of 10 management steps. Never self-testing ketone levels was reported by 33% of adolescents and 11% of caregivers. (IVa) At least one handling error occurred in 100% of adolescents’ and in 98% of caregivers’ practical demonstrations of urine dipstick self-testing and in (IVb) 98% of adolescents’ and 98% of caregivers’ insulin administrations. (Va) Altogether urine dipsticks were available in 43% of households, whereas (Vb) insulin cartridges were available in 78% of households. Conclusions: Our results demonstrate a mismatch between challenges in ketosis home management and high subjective self-ratings. Full article

Hydrogen refueling stations (HRSs) are a critical enabling infrastructure for fuel cell electric vehicles (FCEVs), yet their deployment in dense metropolitan areas often faces a dual challenge: limited travel-time accessibility for users and low public acceptance driven by perceived safety risks. This study develops an integrated, city-scale framework to quantify HRS accessibility and resident acceptance and to identify expansion priorities for Seoul, South Korea. We combine (i) an online perception survey of 1000 adult residents (October 2024) capturing environmental awareness, perceived safety, siting preferences, and willingness-to-travel distance; (ii) spatial demand data on FCEV registrations by administrative dong (n = 2443 vehicles, 2022); and (iii) network-based travel-time analysis using the Seoul road network and the current HRS supply (n = 10, 2024). Accessibility is evaluated under three travel-time thresholds (10, 15, and 20 min), with service-area delineation and demand-weighted underserved-area diagnosis. Candidate expansion sites are generated and screened using operational and regulatory constraints (e.g., site area and proximity to protected facilities), followed by a p-median location-allocation optimization to select five additional sites that minimize demand-weighted travel impedance. Results indicate that, under the 20 min threshold (7.7 km at an average operating speed of 23.1 km/h), 50 of 425 dongs (11.8%) and 244 of 2443 FCEVs (10.0%) are outside the baseline service coverage. After adding five sites (total n = 15), underserved dongs decrease to 5 (1.2%) and underserved FCEVs to 26 (1.1%) for the 20 min threshold, with consistent improvements across shorter thresholds. Survey responses further reveal that only 12.5% of respondents perceive HRSs as safe, while 46.5% report a maximum willingness-to-travel distance of up to 5 km, underscoring the need for both accessibility enhancement and risk-aware communication. The proposed workflow offers a transparent, reproducible approach to support equitable and risk-informed HRS planning by jointly considering network accessibility, demand distribution, and social acceptance, thereby contributing to sustainable urban mobility, low-carbon transport transition, and socially acceptable hydrogen infrastructure deployment. Beyond local accessibility improvement, the study is framed in the broader context of sustainability, as equitable and socially acceptable hydrogen refueling infrastructure can support low-carbon urban transport transitions and more resilient metropolitan energy-mobility systems. Full article

This narrative review examines the clinical application of tiletamine–zolazepam (TZ) in exotic pet and wildlife anesthesia, addressing the complexities inherent in managing a broad taxonomic spectrum with diverse physiological profiles and temperaments. As a fixed-dose combination, TZ is a cornerstone of multimodal protocols designed to achieve balanced anesthesia. Its lyophilized formulation permits reconstitution with various sedative solutions, facilitating low-volume administration, a critical requirement for the immobilization of wildlife and small exotic patients. Given the significant variability in species-specific responses and environmental influences, selecting and adapting appropriate TZ-based protocols remain a challenge for practitioners. By synthesizing heterogeneous data into expert-validated guidance, this review provides specialized and general veterinarians with practical considerations for the judicious use of TZ. Emphasis is placed on integrating TZ within multimodal protocols to mitigate arousal risks, ensure consistent immobilization, and facilitate rapid recovery. This approach seeks to optimize anesthetic outcomes and promote animal welfare across these physiologically diverse populations. Full article

The COVID-19 pandemic intensified communication challenges for community college leaders navigating prolonged uncertainty and organizational disruption. This qualitative study examines how community college administrators described and interpreted their communication practices during the pandemic. Guided by the Elaboration Likelihood Model (ELM), this study explores how leaders made sense of message design, audience responsiveness, and trust under conditions of information overload and emotional strain. Semi-structured interviews were conducted with twelve administrators from community colleges across the United States, including presidents, vice presidents, and senior-level directors. Data were analyzed using reflexive thematic analysis. Five themes emerged: communication breakdowns between employee groups; tailored messaging for specific constituencies; preferences for in-person and interactive communication; trust-building through transparency; and reliance on collaborative communication structures. Participants described communication as an ongoing relational and organizational practice rather than a one-time transmission of information. Administrators reported adapting strategies by combining repetition, audience-specific framing, interactive formats, and structural supports to manage uncertainty and sustain institutional trust. Findings are not intended to be generalizable but provide contextually grounded insight into leadership communication during an extended crisis. This study contributes to scholarship on higher education leadership and crisis communication by illustrating how persuasion, sensemaking, and relational cues intersected in administrators’ communication practices. Full article

Background/Objectives: Dietary antioxidants are frequently utilized by breast cancer (BC) patients to mitigate treatment-related toxicities and enhance quality of life. However, their clinical efficacy remains highly controversial due to conflicting epidemiological and clinical data. This review aims to critically evaluate the molecular mechanisms, clinical outcomes, and translational challenges of antioxidant supplementation in BC management. Methods: A comprehensive evaluation of current literature—encompassing observational cohorts, randomized controlled trials, and mechanistic in vitro/in vivo models—was conducted. The analysis focused on the pharmacological interactions of diverse bioactive compounds (polyphenols, vitamins, carotenoids) with BC progression and standard antineoplastic regimens. Results: Current evidence demonstrates a paradoxical, double-edged role of antioxidants in oncology. While specific interventions (e.g., Coenzyme Q10, melatonin) effectively ameliorate treatment-induced toxicities without compromising therapeutic efficacy, the concurrent administration of antioxidants during cytotoxic chemotherapy can inadvertently neutralize essential reactive oxygen species (ROS), correlating with increased disease recurrence and mortality. Furthermore, clinical translation is severely hindered by the intrinsic hydrophobicity of natural compounds, the lack of whole-food matrix standardization, and dose-dependent hepatotoxicity. Emerging targeted delivery systems, such as lipid nanoformulations, show significant potential in overcoming these pharmacokinetic barriers. Conclusions: The therapeutic viability of antioxidant supplementation in BC is not universal; it is heavily dictated by intrinsic tumor biology, specific treatment modalities, and chronopharmacology. These findings underscore a critical biological imperative to transition from generalized dietary guidelines toward a rigorous paradigm of precision nutritional oncology, strictly avoiding concurrent antioxidant supplementation during active oxidative therapies. Full article

Corporate risk prediction is a central problem in financial analysis and corporate risk management. This study proposes a functional approach in which firms are represented through multivariate financial trajectories constructed from retrospective windows of accounting indicators, over which a similarity measure is defined and incorporated into a k-nearest neighbors classifier. The target variable is derived from administrative records, combining reporting discontinuity and firm administrative status as a proxy for financial distress. The empirical application is conducted using data from firms in the tourism sector in Colombia and is evaluated through stratified cross-validation. The results show that the trajectory-based representation captures gradual patterns of financial deterioration and improves the performance of k-NN relative to its static variable counterpart. In addition, the approach enhances interpretability by enabling the identification of historically comparable firms and the analysis of the financial dimensions that explain their similarity. Overall, the model provides a complementary perspective for corporate risk analysis based on the comparison of financial trajectories. Full article

This study reconceptualises marginality in China’s inter-provincial border regions as a dynamic, scale-sensitive spatial relationship rather than a static condition of underdevelopment. Using the Hubei–Henan–Anhui border area as a case study, we quantitatively assess marginality across three dimensions—production, livelihood, and ecology—based on panel data from 61 counties for 2000, 2010, and 2021. The entropy-weighted TOPSIS method is used to calculate comprehensive development indices, and geographic detector models identify key driving factors. The results show that production marginality is persistently shaped by economic level and industrial structure. Livelihood marginality exhibits a clear temporal shift: dominant drivers move from healthcare security to cultural amenities and finally to transport accessibility. Ecological marginality remains primarily determined by natural endowments such as habitat quality and ecosystem services. Theoretically, the study advances marginality analysis by integrating spatial, temporal and dimensional perspectives. Practically, it offers a diagnostic framework to support differentiated, cross-administrative governance strategies that can transform peripheral border regions into cooperative hubs. Full article

Weather is an essential part of life that affects livelihoods such as agriculture, aviation, etc. Existing systems for weather prediction use deep learning frameworks such as Recurrent Neural Networks and Long Short-term Memory. These models, however, suffer from vanishing gradients that affect the accuracy of the prediction. Using the Deep Belief Networks, we developed a model to address this. Historical weather data is obtained from the Philippine Atmospheric, Geophysical and Astronomical Services Administration for model training. The ground-level sensor data was used to normalize the inputs for the model. The resulting multiclass accuracy is 80%. A larger dataset is recommended for better performance. Full article

Accurate air quality forecasting requires the effective integration of heterogeneous data sources that vary in spatial coverage, temporal resolution, and sensing reliability. This paper presents a unified spatio-temporal data processing framework designed to support multi-source air quality forecasting by jointly leveraging regulatory monitoring stations of the Central Pollution Control Board (CPCB) as reference-grade anchors and community-driven Internet of Things (IoT) sensing platforms for spatial densification. The proposed end-to-end workflow addresses key challenges associated with heterogeneity, data quality, and interoperability through systematic schema harmonization, multi-stage data cleaning, and robust missing data imputation using a Robocentric Iterated Extended Kalman Filter (RIEKF). The processed data are temporally aligned to a uniform sampling grid and enriched with spatial descriptors, including geospatial coordinates, administrative boundaries, and proximity-based emission features. These enriched observations are subsequently fused into a unified spatio-temporal representation that captures both spatial dependencies and temporal dynamics across the sensor network. Dynamic graphs constructed from this representation are processed using a Mobility-Aware Peripheral-Enhanced Graph Neural Network to forecast pollutant concentrations and generate categorical air quality indices. The framework is evaluated using regression metrics reported as RMSE/MAE in µg/m³ and MAPE in %, together with standard AQI classification metrics, demonstrating its effectiveness in improving predictive accuracy and robustness for real-world air quality forecasting applications. Full article

Background: Population-level evidence on delivery of neuro-oncology care is essential for evaluating access, equity, and quality of treatment pathways. However, real-world data describing how patients with central nervous system (CNS) tumors, especially with glioblastoma, are managed across healthcare systems remain limited. This study aimed to characterize treatment pathways using linked registry and administrative data within a regional care network. Methods: All adult CNS tumors diagnosed between 2016 and 2020 were identified in the Veneto Cancer Registry. Tumor grading was derived using a validated text-mining algorithm, and surgical, radiotherapy, and systemic treatments were captured through linkage with regional healthcare utilization databases. Patterns of care were evaluated by tumor subtype, grade, and diagnostic pathway. Results: Among 1634 histologically confirmed tumors, glioblastoma represented the largest group. Surgical intervention was widely implemented, with high resection rates in glioblastoma and meningioma. Combined chemoradiotherapy constituted the primary adjuvant approach for glioblastoma and high-grade diffuse gliomas, whereas management of lower-grade tumors showed greater variability. Approximately one-third of patients received no oncologic therapy, primarily associated with older age or diagnostic uncertainty. Analysis of recurrent glioblastoma showed heterogeneous systemic treatment use, reflecting evolving therapeutic practice. Conclusions: Linking population-based registry and administrative data provides actionable insight into real-world delivery of neuro-oncology care, in particular for glioblastoma patients. This approach enables monitoring of treatment variability, identification of potential access gaps, and evaluation of system-level performance, supporting data-driven planning of multidisciplinary services and future quality improvement initiatives. Full article

Deaths caused by or connected to exposure to Brazilian prisons are widely acknowledged as frequent and preventable, yet official data fails to capture their scale, causes, and circumstances. To circumvent what official administrative datasets miss, this article examines an original dataset of 1077 criminal case files from 27 Brazilian state courts involving individuals who died between 2017 and 2021 after having been incarcerated. Drawing on the systematic document review of these cases, we analyze sociodemographic characteristics, health information, causes of death, and judicial responses, distinguishing between deaths occurring in custody (“internal”) and after release (“external”). Our findings reveal pervasive omissions in basic demographic and medical information, extensive use of ill-defined causes of death, and a striking absence of investigation in most cases, including deaths under direct state custody. We identify instances of obfuscation and judicial inaction that, together with the absence of reliable administrative data, are likely to sustain institutional ignorance and normalize preventable deaths. This study advances debates on incarceration and health, state accountability, and proposes the concept of prison lethality: the capacity of carceral spaces to increase people’s exposure to health risks and harms, combined with the epistemic practices that shed light on or obfuscate this capacity. Full article