Search Results (351)

Background: Pain is a complex phenomenon characterized by unpleasant experiences with profound heterogeneity influenced by biological, psychological, and social factors. According to the National Health Interview Survey, 50.2 million U.S. adults (20.5%) experience pain on most days, with the annual cost of prescription medication for pain reaching approximately USD 17.8 billion. Theranostic pain nanomedicine therefore emerges as an attractive analgesic strategy with the potential for increased efficacy, reduced side-effects, and treatment personalization. Theranostic nanomedicine combines drug delivery and diagnostic features, allowing for real-time monitoring of analgesic efficacy in vivo using molecular imaging. However, clinical translation of these nanomedicines are challenging due to complex manufacturing methodologies, lack of standardized quality control, and potentially high costs. Quality by Design (QbD) can navigate these challenges and lead to the development of an optimal pain nanomedicine. Our lab previously reported a macrophage-targeted perfluorocarbon nanoemulsion (PFC NE) that demonstrated analgesic efficacy across multiple rodent pain models in both sexes. Here, we report PFC-free, biphasic nanoemulsions formulated with a biocompatible and non-immunogenic plant-based coconut oil loaded with a COX-2 inhibitor and a clinical-grade, indocyanine green (ICG) near-infrared fluorescent (NIRF) dye for parenteral theranostic analgesic nanomedicine. Methods: Critical process parameters and material attributes were identified through the FMECA (Failure, Modes, Effects, and Criticality Analysis) method and optimized using a 3 × 2 full-factorial design of experiments. We investigated the impact of the oil-to-surfactant ratio (w/w) with three different surfactant systems on the colloidal properties of NE. Small-scale (100 mL) batches were manufactured using sonication and microfluidization, and the final formulation was scaled up to 500 mL with microfluidization. The colloidal stability of NE was assessed using dynamic light scattering (DLS) and drug quantification was conducted through reverse-phase HPLC. An in vitro drug release study was conducted using the dialysis bag method, accompanied by HPLC quantification. The formulation was further evaluated for cell viability, cellular uptake, and COX-2 inhibition in the RAW 264.7 macrophage cell line. Results: Nanoemulsion droplet size increased with a higher oil-to-surfactant ratio (w/w) but was no significant impact by the type of surfactant system used. Thermal cycling and serum stability studies confirmed NE colloidal stability upon exposure to high and low temperatures and biological fluids. We also demonstrated the necessity of a solubilizer for long-term fluorescence stability of ICG. The nanoemulsion showed no cellular toxicity and effectively inhibited PGE2 in activated macrophages. Conclusions: To our knowledge, this is the first instance of a celecoxib-loaded theranostic platform developed using a plant-derived hydrocarbon oil, applying the QbD approach that demonstrated COX-2 inhibition. Full article

Natural carbonate stones such as limestones and marbles are widely used in heritage and contemporary architecture, yet their durability is increasingly threatened by wildfire-related thermal stress. Since water transport plays a key role in stone deterioration, understanding how high temperatures affect hydric behavior is critical for conservation. This study investigates thirteen Portuguese carbonate lithotypes (including marbles, limestones, a travertine, and a breccia) exposed to temperatures of 300 °C and 600 °C. Capillary absorption and open porosity were measured, alongside Leeb hardness (HL) and ultrasonic pulse velocity (UPV), to evaluate their predictive capacity for post-fire moisture behavior. Results show that thermal exposure increases porosity and capillary uptake while reducing mechanical cohesion. Strong correlations between UPV and hydric parameters across temperature ranges highlight its reliability as a non-invasive diagnostic tool. HL performed well in compact stones but was less consistent in porous or heterogeneous lithologies. The findings support the use of NDT tests, like UPV and HL, for rapid post-fire assessments and emphasize the need for lithology-specific conservation strategies. Full article

Background and Objectives: Metabolic tumor volume (MTV) and inflammation-based indices have recently gained attention as potential prognostic markers of diffuse large B-cell lymphoma (DLBCL). We aimed to evaluate the prognostic significance of metabolic and systemic inflammatory parameters in predicting treatment response, relapse, and overall survival (OS) in patients with DLBCL. Materials and Methods: This retrospective cohort study included 70 patients with DLBCL. Clinical characteristics, laboratory values, and metabolic parameters, including maximum standardized uptake value (SUVmax^liver and SUVmax), heterogeneity indices HI1 and HI2, and MTV were analyzed. Survival outcomes were assessed using Kaplan–Meier and log-rank tests. Receiver operating characteristic analyses helped evaluate the diagnostic performance of the selected biomarkers in predicting relapse and mortality. Univariate and multivariate logistic regression analyses were conducted to identify the independent predictors. Results: The mean OS and mean relapse-free survival (RFS) were 71.6 ± 7.4 and 38.7 ± 2.9 months, respectively. SUVmax^liver ≤ 22 and HI2 > 62.3 were associated with a significantly shorter OS. High lactate dehydrogenase (LDH) levels and HI2 > 87.9 were significantly associated with a reduced RFS. LDH, SUVmax^liver, and HI2 had a significant predictive value for relapse. SUVmax^liver and HI2 levels were also predictive of mortality; SUVmax^liver ≤ 22 and HI2 > 62.3 independently predicted mortality, while HI2 > 87.9 independently predicted relapse. MTV was not significantly associated with survival. Conclusions: Metabolic tumor burden and inflammation-based markers, particularly SUVmax^liver and HI2, are significant prognostic indicators of DLBCL and may enhance risk stratification and aid in identifying patients with an increased risk of relapse or mortality, potentially guiding personalized therapy. Full article

Chemically demethoxylated and Ca-cross-linked orange-peel waste was engineered as a biosorbent for Mn(II) removal from water. A three-factor Box–Behnken design (biosorbent dose 3–10 g L⁻¹, initial Mn²⁺ 100–300 mg L⁻¹, contact time 3–8 h; pH 5.5 ± 0.1, 25 °C) required only 16 runs to locate the optimum (10 g L⁻¹, 100 mg L⁻¹, 8 h), at which the material removed 94.8% ± 0.3% manganese removal under the optimized conditions (10 g L⁻¹, 100 mg L⁻¹, 8 h, pH 5.5) of dissolved manganese and reached a Langmuir capacity of 29.7 mg g⁻¹. Equilibrium data fitted the Freundlich (R² = 0.968) and Sips (R² = 0.969) models best, indicating a heterogeneous surface, whereas kinetic screening confirmed equilibrium within 6 h. FTIR and SEM–EDX verified abundant surface –COO⁻/–OH groups and showed Mn deposits that partially replaced residual Ca, supporting an ion-exchange component in the uptake mechanism. A preliminary cost analysis (<USD 10 kg⁻¹) and > 90% regeneration efficiency over three cycles highlight the economic and environmental promise of this modified agro-waste for polishing Mn-laden effluents. Full article

Classical epidemic models treat vaccine uptake as an exogenous parameter, yet real-world coverage emerges from strategic choices made by individuals facing uncertain risks. During the last two decades, vaccination games, which combine epidemic dynamics with game theory, behavioural economics, and network science, have become a very important tool for analysing this problem. Here, we synthesise more than 80 theoretical, computational, and empirical studies to clarify how population structure, psychological perception, pathogen complexity, and policy incentives interact to determine vaccination equilibria and epidemic outcomes. Papers are organised along five methodological axes: (i) population topology (well-mixed, static and evolving networks, multilayer systems); (ii) decision heuristics (risk assessment, imitation, prospect theory, memory); (iii) additional processes (information diffusion, non-pharmacological interventions, treatment, quarantine); (iv) policy levers (subsidies, penalties, mandates, communication); and (v) pathogen complexity (multi-strain, zoonotic reservoirs). Common findings across these studies are that voluntary vaccination is almost always sub-optimal; feedback between incidence and behaviour can generate oscillatory outbreaks; local network correlations amplify free-riding but enable cost-effective targeted mandates; psychological distortions such as probability weighting and omission bias materially shift equilibria; and mixed interventions (e.g., quarantine + vaccination) create dual dilemmas that may offset one another. Moreover, empirical work surveys, laboratory games, and field data confirm peer influence and prosocial motives, yet comprehensive model validation remains rare. Bridging the gap between stylised theory and operational policy will require data-driven calibration, scalable multilayer solvers, and explicit modelling of economic and psychological heterogeneity. This review offers a structured roadmap for future research on adaptive vaccination strategies in an increasingly connected and information-rich world. Full article

Stream metabolism is traditionally defined as the combined metabolism of all aerobic organisms in a stream. Its component processes of oxygenic photosynthesis and aerobic respiration create and consume dissolved oxygen (DO) and therefore can be measured using time series of DO concentration, solar radiation, and water temperature, in conjunction with a model of DO dynamics that includes photosynthesis, respiration, and oxygen exchange with the atmosphere. A complication is that stream communities typically exhibit pronounced longitudinal heterogeneity in habitat type (e.g., shaded versus unshaded reaches) and species composition and abundance. The influence of a given stream reach and associated community on DO concentration propagates downstream with the current, gradually being replaced, over a transition zone, by the influence of the next downstream reach. Knowing the approximate length of this transition zone is important when estimating stream metabolism with one-station DO monitoring, since it indicates which stream reach and associated community the metabolism estimates apply to. We propose new methods for estimating the transition-zone length and for estimating the proportions of DO at a given location in a stream reach that entered the reach from upstream, from photosynthesis within the reach, and from atmospheric uptake within the reach. We also propose methods for estimating the residence-time distribution of DO present at a given stream location, and the corresponding distribution of upstream distances at which the DO entered the stream. Both distributions are approximately exponential. Thus, habitat immediately upstream of the sonde has the greatest influence on metabolism estimates with one-station monitoring, and it is therefore important to place the sonde so this habitat is representative of the study reach. Full article

Well-differentiated neuroendocrine neoplasms (NENs) are characterized by hyperexpression on the cell membrane of somatostatin receptors (SSTRs). The demonstration of SSTRs, mainly the subtype 2 (SSTR2), is the prerequisite for diagnostic and therapeutic strategies with radiolabeled somatostatin analogs (SSAs). SSTRs can be routinely demonstrated in vivo by SSA-positron emission tomography/computed tomography (SSA-PET/CT) and in vitro by immunohistochemistry (IHC). This systematic review and meta-analysis aimed to gather evidence from the available literature on the correlation between the in vivo PET/CT and in vitro IHC SSTR expression in NEN patients. A systematic review and meta-analysis were conducted following the preferred reporting items for systematic reviews and meta-analyses (PRISMA) 2020 guidelines. A comprehensive literature search was performed in PubMed/MEDLINE and Cochrane Library, selecting studies correlating SSTR expression in NENs via IHC and SSA-PET/CT. Data extraction, quality assessment, and statistical analysis were performed. Eleven studies met the inclusion criteria for systematic review (345 patients). Of these, eight studies (299 patients) provided sufficient quantitative data for meta-analysis. The pooled concordance between SSA-PET/CT and IHC was 76% (95% CI: 67.7–84.2), indicating a good correlation between in vivo and in vitro SSTR2 expression. Heterogeneity among studies was moderate (I² = 65%), reflecting different patient cohorts and methodologies regarding both SSA-PET/CT and IHC. No significant publication bias was detected. Our results confirmed good agreement between in vivo tumor uptake with SSA-PET/CT and in vitro SSTR2 expression with IHC, highlighting the potential of using IHC for clinical decision-making in NEN patients when SSA-PET/CT is not available. Full article

Background/Objectives: Radiolabeled biomolecules specifically targeting overexpressed structures on tumor cells hold great potential for prostate cancer (PCa) imaging and therapy. Due to heterogeneous target expression, single radiopharmaceuticals may not detect or treat all lesions, while simultaneously applying two or more radiotracers potentially improves staging, stratification, and therapy of cancer patients. This study explores a dual-tracer SPECT approach using [¹¹¹In]In-RM2 (targeting the gastrin-releasing peptide receptor, GRPR) and [^99mTc]Tc-PSMA-I&S (targeting the prostate-specific membrane antigen, PSMA) as a proof of concept. To mimic heterogeneous tumor lesions in the same individual, we aimed to establish a dual xenograft mouse model for preclinical evaluation. Methods: CHO-K1 cells underwent lentiviral transduction for human GRPR or human PSMA overexpression. Six-to-eight-week-old female immunodeficient mice (NOD SCID) were subsequently inoculated with transduced CHO-K1 cells in both flanks, enabling a dual xenograft with similar target density and growth of both xenografts. Respective dual-isotope imaging and γ-counting protocols were established. Target expression was analyzed ex vivo by Western blotting. Results: In vitro studies showed similar target-specific binding and internalization of [¹¹¹In]In-RM2 and [^99mTc]Tc-PSMA-I&S in transduced CHO-K1 cells compared to reference lines PC-3 and LNCaP. However, in vivo imaging showed negligible tumor uptake in xenografts of the transduced cell lines. Ex vivo analysis indicated a loss of the respective biomarkers in the xenografts. Conclusions: Although the technical feasibility of a dual-tracer SPECT imaging approach using ¹¹¹In and ^99mTc has been demonstrated, the potential of [^99mTc]Tc-PSMA-I&S and [¹¹¹In]In-RM2 in a dual-tracer cocktail to improve PCa diagnosis could not be verified. The animal model, and in particular the transduced cell lines developed exclusively for this project, proved to be unsuitable for this purpose. The in/ex vivo experiments indicated that results from an in vitro model may not necessarily be successfully transferred to an in vivo setting. To assess the potential of this dual-tracer concept to improve PCa diagnosis, optimized in vivo models are needed. Nevertheless, our strategies address key challenges in dual-tracer applications, aiming to optimize future SPECT imaging approaches. Full article

Dynamic oxygen uptake (VO₂) reflects moment-to-moment changes in oxygen consumption during exercise and underpins training design, performance enhancement, and clinical decision-making. We tackled two key obstacles—the limited fusion of heterogeneous sensor data and inadequate modeling of long-range temporal patterns—by integrating wearable accelerometer and heart-rate streams with a convolutional neural network–LSTM (CNN-LSTM) architecture and optional attention modules. Physiological signals and VO₂ were recorded from 21 adults through resting assessment and cardiopulmonary exercise testing. The results showed that pairing accelerometer with heart-rate inputs improves prediction compared with considering the heart rate alone. The baseline CNN-LSTM reached R² = 0.946, outperforming a plain LSTM (R² = 0.926) thanks to stronger local spatio-temporal feature extraction. Introducing a spatial attention mechanism raised accuracy further (R² = 0.962), whereas temporal attention reduced it (R² = 0.930), indicating that attention success depends on how well the attended features align with exercise dynamics. Stacking both attentions (spatio-temporal) yielded R² = 0.960, slightly below the value for spatial attention alone, implying that added complexity does not guarantee better performance. Across all models, prediction errors grew during high-intensity bouts, highlighting a bottleneck in capturing non-linear physiological responses under heavy load. These findings inform architecture selection for wearable metabolic monitoring and clarify when attention mechanisms add value. Full article

Against the backdrop of global climate change, enhancing farmers’ adaptive capacity to reduce crop production risks has emerged as a critical concern for governments and researchers worldwide. Drawing on social capital theory, this study develops a four-dimensional measurement framework comprising social networks, social trust, social norms, and social participation, utilizing survey data from 1772 households in the Yellow River Basin. We employ factor analysis to construct comprehensive social capital scores and apply ordered Probit models to examine how social capital influences farmers’ climate adaptation behaviors, with particular attention to the moderating roles of agricultural extension interaction and digital literacy. Key findings include: (1) Adoption patterns: Climate adaptation behavior adoption remains low (60%), with technical adaptation measures showing particularly poor uptake (13%); (2) Direct effects: Social capital significantly promotes adaptation behaviors, with social trust (p < 0.01), networks (p < 0.01), and participation (p < 0.05) demonstrating positive effects, while social norms show no significant impact; (3) Heterogeneous effects: Impact mechanisms differ by crop type, with grain producers relying more heavily on social networks (+, p < 0.01) and cash crop producers depending more on social trust (+, p < 0.01); (4) Moderating mechanisms: Agricultural extension interaction exhibits scale-dependent effects, negatively moderating the relationship for large-scale farmers (p < 0.05) while showing no significant effects for smaller operations; digital literacy consistently demonstrates negative moderation, whereby higher literacy levels weaken social capital’s promotional effects (p < 0.01). Policy recommendations: Effective climate adaptation strategies should integrate strengthened rural social organization development, differentiated agricultural extension systems tailored to farm characteristics, and enhanced rural digital infrastructure investment. Full article

The aim of this study was to examine the genetic characteristics that could be associated with the virulence characteristics of Escherichia coli collected from clinical samples. A collection of 100 non-repetitive E. coli isolates was analyzed. All isolates were typed by MLST. String production, biofilm formation and serum resistance were examined for all isolates. Twenty E. coli isolates were completely sequenced Illumina platform. The results showed that the majority of E. coli isolates (87%) produced significant levels of biofilm, while none of the isolates were positive for string test and resistance to serum. Additionally, the presence of CRISPR/Cas systems (type I-E or I-F) was found in 18% of the isolates. Analysis of WGS data found that all sequenced isolates harbored a variety of virulence genes that could be implicated in adherence, invasion, iron uptake. Also, WGS data confirmed the presence of a wide variety of resistance genes, including ESBL- and carbapenemase-encoding genes. In conclusion, an important percentage (87%) of the E. coli isolates had a significant ability to form biofilm. Biofilms, due to their heterogeneous nature and ability to make microorganisms tolerant to multiple antimicrobials, complicate treatment strategies. Thus, in combination with the presence of multidrug resistance, expression of virulence factors could challenge antimicrobial therapy of infections caused by such bacteria. Full article

With the increasing accumulation of plastic residues in agricultural ecosystems, microplastics (MPs) have emerged as a novel and pervasive environmental risk factor threatening sustainable agriculture. Compared to aquatic systems, our understanding of MP dynamics in agricultural soils—particularly their transport mechanisms, bioavailability, plant uptake pathways, and ecological impacts—remains limited. These knowledge gaps impede accurate risk assessment and hinder the development of effective mitigation strategies. This review critically synthesises current knowledge in the study of MPs within soil–plant systems. It examines how MPs influence soil physicochemical properties, plant physiological processes, toxicological responses, and rhizosphere interactions. It further explores the transport dynamics of MPs in soil–plant systems and recent advances in analytical techniques for their detection and quantification. The role of plant functional traits in mediating species-specific responses to MP exposure is also discussed. In addition, the review evaluates the ecological relevance of laboratory-based findings under realistic agricultural conditions, highlighting the methodological limitations imposed by pollution heterogeneity, complex exposure scenarios, and detection technologies. It also examines existing policy responses at both regional and global levels aimed at addressing MP pollution in agriculture. To address these challenges, we propose future research directions that include the integration of multi-method detection protocols, long-term and multi-site field experiments, the development of advanced risk modelling frameworks, and the establishment of threshold values for MP residues in edible crops. Additionally, we highlight the need for future policies to regulate the full life cycle of agricultural plastics, monitor soil MP residues, and integrate MP risks into food safety assessments. This review provides both theoretical insights and practical strategies for understanding and mitigating MP pollution in agroecosystems, supporting the transition toward more sustainable, resilient, and environmentally sound agricultural practices. Full article

Breast cancer remains a leading cause of cancer-related morbidity and mortality among women worldwide. Its treatment is complicated by molecular heterogeneity and the frequent development of multidrug resistance (MDR). Conventional drug delivery approaches are often limited by poor aqueous solubility, rapid systemic clearance, non-specific biodistribution, and off-target toxicity. This review will critically explore the possibility of surfactant-based drug delivery systems (DDSs) in addressing the constraints of standard breast cancer treatments. It focuses on the mechanisms by which surfactants promote solubility, facilitate cellular uptake, and overcome drug resistance, while also analyzing current therapeutic success and future directions. A thorough review of preclinical and clinical investigations was undertaken, focusing on important surfactant-based DDSs such as polymeric micelles, nanoemulsions, liposomes, and self-emulsifying systems (SEDDSs). Mechanistic insights into surfactant functions, such as membrane permeabilization and efflux pump inhibition, were studied alongside delivery systems incorporating ligands and co-loaded medicines. Pluronic^® micelles, TPGS-based systems, biosurfactant-stabilized nanoparticles, and lipid-based carrier surfactant platforms improve medication solubility, stability, and delivery. Genexol^® are examples of formulations demonstrating effective use and FDA translational potential. These systems now incorporate stimuli-responsive release mechanisms—such as pH, temperature, redox, immuno- and photodynamic treatment—artificial intelligence treatment design, and tailored treatment advancement, and responsive tailoring. Surfactant-enabled DDSs can improve breast cancer care. Innovative approaches for personalized oncology treatment are countered by the enduring challenges of toxicity, regulatory hurdles, and diminished scalability. Full article

Systemic cancer progression culminating in metastatic disease is implicitly dependent on tumour cell interactions with the vascular system. Indeed, different facets of the micro- and macro-vasculature can be regarded as rate-limiting ‘vascular checkpoints’ in the process of cancer dissemination. The underlying complex communication networks drive tumour neovascularization, angiogenesis, immunoregulation, activation of the coagulation system, angiocrine interactions, and non-angiogenic vascular responses across multiple cancer types. Yet, each cancer may represent a unique vascular interaction scenario raising a prospect of targeted modulation of blood and lymphatic vessels for therapeutic purposes, beyond the traditional notion of tumour anti-angiogenesis. While the emphasis of studies aiming to understand this circuitry has traditionally been on soluble, or ‘mono-molecular’ mediators, the rise of the particulate secretome encompassing heterogeneous subpopulations of extracellular vesicles (EVs; including exosomes) and particles (EPs) brings another dimension into the tumour–vascular communication web during the process of metastasis. EVs and EPs are nanosized cellular fragments, the unique nature of which lies in their ability to encapsulate, protect and deliver to target cells a range of bioactive molecular entities (proteins, RNA, DNA) assembled in ways that enable them to exert a wide spectrum of biological activities. EVs and EPs penetrate through biological barriers and are capable of intracellular uptake. Their emerging vascular functions in metastatic or infiltrative cancers are exemplified by their roles in pre-metastatic niche formation, thrombosis, vasectasia or angiocrine regulation of cancer stem cells. Here, we survey some of the related evidence supporting the biological, diagnostic and interventional significance of EVs/EPs (EVPs) in disseminated neoplastic disease. Full article

Background: Silicone breast implants have been linked to autoimmune/inflammatory syndrome induced by adjuvants (ASIA). This study evaluates the role of ^99mTc-HYNIC-TOC somatostatin receptor scintigraphy in assessing somatostatin-mediated inflammation and the impact of explantation on inflammatory activity. Methods: Fifty patients with silicone breast implants and symptoms suggestive of ASIA were evaluated. Pre- and postexplantation imaging was performed using ^99mTc-HYNIC-TOC scintigraphy. Matthews correlation coefficients quantified associations between clinical symptoms and imaging findings, and autoantibody profiles were analysed. Results: Scintigraphy identified a significant uptake in organs associated with autoimmune symptoms, particularly joints and salivary glands. Strong correlations were found between imaging findings and symptoms, including knee pain (MCC = 0.81) and sicca syndrome (MCC = 0.96). Explantation resolved abnormal uptake in the surgical bed, though variable uptake persisted in other organs, reflecting systemic inflammatory heterogeneity. Autoantibody analysis revealed positivity in 66% of patients, with antinuclear antibodies being most frequent (30%). Conclusions: ^99mTc-HYNIC-TOC scintigraphy effectively evaluates organ-specific inflammation in ASIA. Explantation reduces localized inflammation but does not consistently address systemic autoimmune responses. Larger prospective studies are needed to validate these findings and improve management strategies for ASIA. Full article