Search Results (905)

Indoor positioning remains a recurrent and significant challenge in research. Unlike outdoor environments, where the Global Positioning System (GPS) provides reliable location information, indoor scenarios lack direct line-of-sight to satellites or cellular towers, rendering GPS inoperative and requiring alternative positioning techniques. Despite numerous approaches, indoor contexts with resource limitations, energy constraints, or physical restrictions continue to suffer from unreliable localization. Many existing methods employ a fixed number of reference anchors, which sets a hard balance between localization accuracy and energy consumption, forcing designers to choose between precise location data and battery life. As a response to this challenge, this paper proposes an energy-aware indoor positioning strategy based on Mobile Ad Hoc Networks (MANETs). The core principle is a self-adaptive control loop that continuously monitors the network’s positioning accuracy. Based on this real-time feedback, the system dynamically adjusts the number of active anchors, increasing them only when accuracy degrades and reducing them to save energy once stability is achieved. The method dynamically estimates relative coordinates by analyzing node encounters and contact durations, from which relative distances are inferred. Generalized Multidimensional Scaling (GMDS) is applied to construct a relative spatial map of the network, which is then transformed into absolute coordinates using reference nodes, known as anchors. The proposal is evaluated in a realistic simulated indoor MANET, assessing positioning accuracy, adaptation dynamics, anchor sensitivity, and energy usage. Results show that the adaptive mechanism achieves higher accuracy than fixed-anchor configurations in most cases, while significantly reducing the average number of required anchors and their associated energy footprint. This makes it suitable for infrastructure-poor, resource-constrained indoor environments where both accuracy and energy efficiency are critical. Full article

Next-generation cancer immunotherapy increasingly combines tumor-targeting antibodies or antibody–drug conjugates (ADCs) with immune effector cells to enhance therapeutic precision. However, many existing approaches rely on genetic modification or complex manufacturing, limiting their clinical scalability and rapid deployment. To address this issue, we developed an antibody capture protein (ACP)-based surface engineering platform that enables the rapid, reversible, and non-genetic functionalization of NK cells with therapeutic antibodies or ADCs. This approach uses a DMPE-PEG-lipid conjugate to anchor thiolated protein A (ACP) to the NK cell membrane via hydrophobic insertion, thereby stably and selectively binding to the Fc region of IgG molecules. Using this strategy, we developed ACP-modified NK cells (AC-NKs) that can selectively capture therapeutic antibodies (trastuzumab (TZ), trastuzumab-emtansine (T-DM1), and sacituzumab (SZ)) pre-bound to each target antigen on tumor cells and induce antigen-specific cytotoxic responses. The resulting AC-NKs exhibited enhanced tumor recognition and cytotoxicity against HER2-positive and Trop-2-positive cancer cells in vitro. Compared with conventional combination therapies, AC-NKs enhanced immune activation, as demonstrated by effective delivery of cytotoxic agents, enhanced cancer cell engagement, and upregulation of CD107a expression. Notably, the system supports multiple antigen targeting and tunable antibody loading, enabling adaptation to tumor heterogeneity and resistant phenotypes. This platform might also provide a simple, scalable, and safe method for rapidly developing programmable immune cell therapies without genetic modification. Its versatility supports multi-antigen targeting and broad applicability across NK and T cell therapies, offering a promising path toward personalized, off-the-shelf chemoimmunotherapy. Full article

The controlled incorporation of halogens into carbon materials remains a challenge, particularly under mild and scalable conditions. In this work, we investigate the fixation of iodine on high-surface-area graphite (HSAG-100) using green solvents and moderate temperatures. Commercial HSAG was treated with iodine in aqueous and in organic media, with and without promoters, and characterized by XPS, LEIS, N₂ physisorption, TGA/TPD, and XRD. The results reveal that iodine contents up to ~0.6 at% can be achieved, with incorporation strongly influenced by solvent and reaction time. XPS and LEIS confirmed the presence of C–I bonds, while BET analysis showed only moderate decreases in surface area and unchanged mesopore size distribution. Thermogravimetric and TPD analyses demonstrated the high thermal stability of C–I species, and XRD patterns ruled out intercalation between graphene layers. Collectively, these findings demonstrate that iodine can be covalently anchored to HSAG under mild conditions, preserving the graphitic structure and generating stable edge functionalities, thus opening a route for the design of halogen-doped carbons for catalytic and electrochemical applications. Full article

Generational approaches to climate engagement among older adults remain limited. This study examines the evolution of eco-anxiety, environmental activism, and pro-environmental behavior from a life course perspective, focusing on older adults in Spain. A nationwide CATI survey of 3000 residents aged 18 and older was conducted, employing validated multidimensional scales for eco-anxiety, environmental activism, and pro-environmental behavior, each rescaled to a 0–10 range. Data were analyzed using descriptive statistics, analyses of variance, and hierarchical regression models to estimate linear and quadratic age effects beyond sex, education, and subjective social class. Results show that (1) eco-anxiety follows an inverted-U pattern, peaking at ages 45–49 and declining significantly after 60; (2) environmental activism remains high until the late sixties, while everyday pro-environmental behaviors sharply decline after retirement; and (3) eco-anxiety and environmental action in older adults are partially decoupled, reflecting the role of supportive personal and contextual factors beyond emotional concern. The findings challenge prevailing stereotypes of passive older adults by demonstrating that older age can constitute a significant period of climate engagement. Despite a slight decline in climate concern following retirement, the willingness to take action remains notably resilient. Older adults maintain consistent involvement in environmental volunteering and activism, often motivated by a desire to leave a lasting legacy and shaped by personal experiences of past crises and collective struggles. However, pro-environmental behaviors show a marked decrease in older adults, not due to diminished interest but likely as a result of structural constraints such as declining health, limited income, and inadequate housing conditions. This study suggests that, in the context of liquid modernity marked by rapid change and uncertainty, older adults may serve as societal anchors—preserving narratives, emotional bonds, and civic networks. Through policies that address structural barriers, this anchor role can be supported, empowering older adults to improve their well-being and strengthening community resilience in the face of climate change. Full article

Background and Objectives: Laryngeal cancer imposes a disproportionate burden on speech, airway protection and long-term quality of life. Contemporary population-based data for Central and Eastern Europe remain scarce, and the post-pandemic trajectory is uncertain. Materials and Methods: We performed a nationwide, retrospective ecological time-series study using Romanian mortality registers and hospital-discharge files for 2017–2023. Crude and age-standardised mortality rates (ASMRs) were calculated, county-level indirect standardisation and spatial autocorrelation assessed and joinpoint regression quantified temporal trends. Forecasts to 2040 combined Holt–Winters/ARIMA models with Elliott-wave heuristics anchored to Fibonacci retracements. Results: In 2023, 798 laryngeal cancer deaths yielded a crude mortality of 3.65/100,000 (95% CI 3.41–3.91). Male mortality (7.07/100,000) exceeded female mortality 18-fold. Rural residents experienced a higher rate than urban counterparts (4.26 vs. 3.04/100,000), a difference unchanged after indirect age standardisation. National ASMR fell by 3.7% annually (p < 0.01), yet five counties formed a high-risk corridor (standardised mortality ratios 1.59–1.82); Moran’s I = 0.27 (p < 0.01) indicated significant spatial clustering. Pandemic-era surgical throughput collapsed by 48%, generating a backlog projected to persist beyond 2030. Ensemble forecasting anticipates a doubling of discharges and mortality between 2034 and 2037 unless smoking prevalence falls by ≥30% and radon exposure is curtailed. Conclusions: Although overall laryngeal cancer mortality in Romania is declining, the pace lags behind Western Europe and is threatened by geographic inequities and pandemic-related care delays. Aggressive tobacco control, radon-remediation policies and expansion of surgical and radiotherapeutic capacity are required to avert a forecasted surge in the next decade. Full article

Adenosine triphosphate (ATP) is readily released into the extracellular space as an autocrine and paracrine purinergic signaling molecule. We originally reported a genetically encoded, fluorescent protein-based Förster Resonance Energy Transfer (FRET) biosensor that can detect micromolar levels of extracellular ATP. Through mutagenesis of the ATP binding site and optimization of cell-surface display, here we report the development of a second-generation biosensor called ECATS2 with greater than three-fold higher affinity for extracellular ATP. We found that the tether length between the FRET biosensor and the cell surface anchor is critical to optimization of its performance. Furthermore, we demonstrate that the improved sensor can detect extracellular ATP release upon hypoosmotic stress in cultured astrocytes. This new sensor contributes an improved tool for the ratiometric detection of extracellular ATP dynamics and purinergic signaling. Full article

Digital transformation has re-engineered tourism marketing and how destination branding competes for tourist attention, yet scholarship offers little systematic quantification of these changes. Drawing on 160 peer-reviewed studies published between 1990 and 2025, we combine grounded-theory thematic synthesis with a random-effect meta-analysis of 60 datasets to trace branding performance across five technological eras (pre-Internet and brochure era: to mid-1990s; Web 1.0: 1995–2004; Web 2.0: 2004–2013; mobile first: 2013–2020; AI-XR: 2020–2025). Results reveal three structural shifts: (i) dialogic engagement replaces one-way promotion, (ii) credibility migrates to user-generated content, and (iii) artificial intelligence–driven personalisation reconfigures relevance, while mobile and virtual reality marketing extend immersion. Meta-analytic estimates show the strongest gains for engagement intentions (g = 0.57), followed by brand awareness (g = 0.46) and image (g = 0.41). Other equity dimensions (attitudes, loyalty, perceived quality) also improved on average, but to a lesser degree. Visual, UGC-rich, and influencer posts on highly interactive platforms consistently outperform brochure-style content, while robustness checks (fail-safe N, funnel symmetry, leave-one-out) confirm stability. We conclude that digital tools amplify, rather than replace, co-creation, credibility, and context. By fusing historical narrative with statistical certainty, the study delivers a data-anchored roadmap for destination marketers, researchers, and policymakers preparing for the AI-mediated decade ahead. Full article

The study begins with the questions “Where was Paradise?” and “How was the Garden cultivated?”, and the relationship between different modes of interpretation. It compares the biblical data (Gen. 2) with patristic testimonies (John Chrysostom, Ambrose, Ephrem, Gregory of Nyssa, John of Damascus) and symbolic readings (Philo, Cyprian, Hippolytus), in order to assess whether the plurality of meanings generates confusion or coherence. Situated within the divergent approaches of these patristic authors—especially concerning literal and figurative aspects—I aim to outline an integral theological reading of the Eden tradition and of the aforementioned questions. The methods used in this research are comparative biblical and patristic exegesis, structured through a four-step framework: (1) retaining the literal sense when the text provides anchors (rivers, orientation); (2) shifting from description to vocation in the moral-liturgical sense (“to work”/“to keep”); (3) accepting the ineffable (2 Cor. 12) as a boundary; (4) articulating an ontology of paradisiacal matter. The findings of this study are as follows: Eden is an earthly reality, but one with transfigured materiality; “work” is an inner activity (obedience, contemplation) without toil; and the diversity of interpretations proves to be complementary: the literal anchors the “where/what”, while the spiritual illuminates the “why/how”, together avoiding both inert geography and ungrounded symbolism. Full article

The Public Opinion Survey of Human Attributes–Stuttering (POSHA–S) Database, intermittently updated, at the time of this report, contains 25,739 respondents from 45 countries with responses in 28 languages, representing 11 world regions. Among public and selected population samples, more than 600 self-identified stutterers are included. The Microsoft Excel database file features more than 150 columns of POSHA–S results. Some data, such as state/province and country of respondents, primary job or occupation, languages known, race, and religion, are included as text. Other demographic items and all attitude items are numerical data. The POSHA–S has check boxes or scales of 1–5 for other demographic variables and general ratings that compare stuttering to four other “anchor” attributes (intelligence, left-handedness, obesity, and mental illness). All subsequent stuttering attitude items are scored on a scale of 1–3, reflecting “no”, “not sure”, and “yes”, respectively. All scaled ratings are converted to a uniform −100 to +100 scale, with some item ratings inverted so that, uniformly, higher ratings reflect more positive attitudes and lower ratings reflect more negative attitudes. All respondents are classified according to population, a category within population, region or continent, country, language, and other distinctive features. Full article

Endothelial hyperpermeability is a hallmark of diverse inflammatory and vascular pathologies, including sepsis, acute respiratory distress syndrome (ARDS), ischemia–reperfusion injury, and atherosclerosis. Traditionally considered a passive return to baseline following stimulus withdrawal, barrier recovery is now recognized as an active, endothelial-driven process. Earlier work identified individual components of this restorative phase, such as cyclic adenosine monophosphate (cAMP)/exchange protein directly activated by cAMP 1 (Epac1) signaling, Rap1/Rac1 activation, vasodilator-stimulated phosphoprotein (VASP) phosphorylation, and targeted cytoskeletal remodeling, as well as kinase pathways involving PKA, PKG, and Src. However, these were often regarded as discrete events lacking a unifying framework. Recent integrative analyses, combining mechanistic insights from multiple groups, reveal that nitric oxide (NO) generated early during hyperpermeability can initiate a delayed cAMP/Epac1 cascade. This axis coordinates Rap1/Rac1-mediated cortical actin polymerization, VASP-driven junctional anchoring, retro-translocation of endothelial nitric oxide synthase (eNOS) to caveolar domains, PP2A-dependent suppression of actomyosin tension, and Krüppel-like factor 2 (KLF2)-driven transcriptional programs that sustain endothelial quiescence. Together, these pathways form a temporally orchestrated, multi-tiered “inactivation” program capable of restoring barrier integrity even in the continued presence of inflammatory stimuli. This conceptual shift reframes NO from solely a barrier-disruptive mediator to the initiating trigger of a coordinated, pro-resolution mechanism. The unified framework integrates cytoskeletal dynamics, junctional reassembly, focal adhesion turnover, and redox/transcriptional control, providing multiple potential intervention points. Therapeutically, Epac1 activation, Rap1/Rac1 enhancement, RhoA/ROCK inhibition, PP2A activation, and KLF2 induction represent strategies to accelerate endothelial sealing in acute microvascular syndromes. Moreover, applying these mechanisms to arterial endothelium could limit low-density lipoprotein (LDL) entry and foam cell formation, offering a novel adjunctive approach for atherosclerosis prevention. In this review, we will discuss both the current understanding of endothelial hyperpermeability mechanisms and the emerging pathways of its active inactivation, integrating molecular, structural, and translational perspectives. Full article

Background/Objectives: The aim was to provide a comprehensive, systematic review on the Lateral Extra-articular Tenodesis (LET) methods used in anterior cruciate ligament (ACL) reconstruction in the light of recent data. Methods: To identify all of the essential studies that reported relevant data concerning primary outcomes: indications for surgery, surgical technique, graft type, fixation method, and tibial fixation location, an extensive search of the major and significant electronic databases (PubMed, Cochrane Central, ScienceDirect, Web of Science, Embase) was performed by three independent authors. A systematic investigation was conducted in November 2023, with no limits regarding the year of publication. After the database search, three independent reviewers screened all the papers, which followed strictly the inclusion and exclusion criteria, identifying a title, abstract, and full text concerning LET, surgical technique, femoral attachment, tibial attachment, graft type, fixation method, knee angle during fixation, and graft tension at fixation in ACL reconstruction. A systematic review of the collected literature was carried out according to the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Study quality was assessed using the Cochrane Risk of Bias Tool. Results: Of the 35 papers reviewed, seven surgical techniques of LET differing in the way the procedure was performed were separated. The majority of papers were from Italy (n = 11), USA (n = 3), France (n = 3), and Canada (n = 3). The number of total participants across all studies was 6253. The majority of studies (17 papers) used the Lemaire modified procedure, and 10 papers used the MacIntosh technique modified by the Coker–Arnold approach. Most of the papers mentioned fixation location on the lateral distal part of the femur including six articles referring directly to lateral femoral epicondyle. Most authors (25 papers) defined tibial attachment as Gerdy’s tubercle. The most common graft was the iliotibial band and fixation method was sutures. The types of fixation in the surgical techniques of the collected papers were Sutures, Staples, Anchor, Interference screw, K-wire, Bioabsorbable Screw and Titanium Screw with a serrated polyethylene washer. Conclusions: Despite variability in technique, the Lemaire-modified procedure emerged as the preferred approach for Lateral Extra-articular Tenodesis, suggesting a general consensus around its reliability and reproducibility in clinical practice. The frequent use of the iliotibial band as graft material reflects its accessibility and suitability for reinforcing anterolateral stability. Similarly, the consistent use of sutures and fixation at Gerdy’s tubercle may indicate a favorable balance between technical ease and biomechanical strength. The variability in femoral fixation points—either at the lateral femoral condyle or epicondyle—highlights the ongoing debate or surgeon preference, underscoring the need for further comparative studies to establish optimal fixation strategy. Collectively, these patterns may help guide surgical decision-making, particularly when tailoring procedures to individual patient anatomy or surgical expertise. Full article

Siamese network trackers are a prominent paradigm in visual object tracking due to efficient similarity learning. However, most Siamese trackers are restricted to the bounding box tracking format, which often fails to accurately describe the appearance of non-rigid targets with complex deformations. Additionally, since the bounding box frequently includes excessive background pixels, trackers are sensitive to similar distractors. To address these issues, we propose a novel segmentation-assisted model that learns binary mask representations of targets. This model is generic and can be seamlessly integrated into various Siamese frameworks, enabling pixel-wise segmentation tracking instead of the suboptimal bounding box tracking. Specifically, our model features two core components: (i) a multi-stage precise mask representation module composed of cascaded U-Net decoders, designed to predict segmentation masks of targets, and (ii) a saliency localization head based on the Euclidean model, which extracts spatial position constraints to boost the decoder’s discriminative capability. Extensive experiments on five tracking benchmarks demonstrate that our method effectively improves the performance of both anchor-based and anchor-free Siamese trackers. Notably, on GOT-10k, our method increases the AO scores of the baseline trackers SiamRPN++ (anchor-based) and SiamBAN (anchor-free) by 5.2% and 7.5%, respectively while maintaining speeds exceeding 60 FPS. Full article

Rhodopsin, the prototypical Class A G protein-coupled receptor (GPCR) and visual pigment of rod photoreceptors, has long served as a structural and mechanistic model for GPCR biology. Mutations in rhodopsin are the leading cause of autosomal dominant retinitis pigmentosa (adRP), making this receptor a critical therapeutic target. In this review, we summarize the chemical, structural, and biophysical features of small-molecule modulators of this receptor, spanning both classical retinoid analogs and emerging non-retinoid scaffolds. These ligands reveal recurrent binding modes within the orthosteric chromophore pocket as well as peripheral allosteric and bitopic sites, where they mediate folding, rescue trafficking, photocycle modulation, and mutant stabilization. We organize ligand performance into a three-tier framework linking binding affinity, cellular rescue potency, and stability gains. Chemotypes in tier 2, which show sub-micromolar to low-micromolar activity with broad mutant coverage, emerge as promising candidates for optimization into next-generation scaffolds. Across scaffolds, a recurring minimal pharmacophore is evident by a contiguous hydrophobic π-surface anchored in the β-ionone region, coupled with a strategically oriented polar handle that modulates the Lys296/Glu113 microenvironment, offering tractable design vectors for non-retinoid chemotypes. Beyond the chromophore binding pocket, we highlight opportunities to exploit extracellular loop epitopes, cytoplasmic microswitch clefts, dimer/membrane interfaces, and ion co-binding sites to engineer safer, state-biased control with fewer photochemical liabilities. By integrating rhodopsin photobiophysics with environment-aware, multi-state medicinal chemistry, and by addressing current translational challenges in drug delivery, this review outlines a rational framework for advancing rhodopsin-targeted therapeutics toward clinically credible interventions for RP and related retinal degenerations. Full article

A common misconception is that behavioral economics rejects microeconomics. This entry explains how behavioral economics, despite challenging core assumptions of rationality, remains fundamentally aligned with the structure of microeconomics. Anchored in the insight that rational market outcomes can emerge even when individual behavior is non-rational, it revisits the explanatory role of constraints in economic theory. Rather than displacing microeconomics, behavioral economics extends it by incorporating bounded rationality while preserving key structural principles. Central to this integration is Say’s law, the macro-level notion that production generates income and thus the capacity for demand. This connection makes microeconomic constraints reflect deeper macroeconomic principles. Even when market behavior is distorted by correlated cognitive biases and their associated positive feedback dynamics—such as herding or bubbles—the fundamental identity that supply generates the income necessary for demand remains intact, provided that adjustments occur over the long run. The analysis also considers how behavioral deviations affect aggregate outcomes. Ultimately, this entry shows that behavioral economics is not a departure from microeconomics but its natural extension: by embedding bounded rationality within the framework of economic constraints, it preserves the structural coherence of microeconomics while adding psychological depth. Full article

Childhood cancer treatments, including chemotherapy, radiation therapy, and combined modalities, pose significant risks to auditory function due to their ototoxic effects. Cisplatin, a chemotherapeutic agent commonly used in pediatric oncology, causes dose-dependent irreversible sensorineural hearing loss by damaging the inner ear structures, primarily through the generation of reactive oxygen species and the activation of apoptotic pathways. Radiation therapy exacerbates these effects, contributing to both sensorineural and conductive hearing loss via mechanisms such as vascular injury, inflammation, and fibrosis. The severity of hearing loss is influenced by the treatment timing, the cumulative dose, patient age, genetics, and concurrent therapies. The damaging effects of chemotherapy and radiation extend beyond the cochlea, involving the surrounding temporal bone as well as multiple levels of the auditory pathway. While pediatric patients may be candidates for bone-anchored hearing devices or cochlear implants, the need for serial imaging and the potential for implant-related MRI artifacts can complicate the timing of hearing rehabilitation. Moreover, the impact on the subcortical and cortical auditory structures may further influence the rehabilitation outcomes. This scoping review lays the foundation for future clinical and research efforts focused on the development of comprehensive pediatric guidelines for hearing preservation, monitoring, and rehabilitation, while also fostering multidisciplinary collaboration. Full article