Search Results (3,437)

The increasing complexity of dendritic cell (DC)-derived exosome (DEX) immunotherapy demands structured monitoring protocols capable of translating molecular activity into actionable clinical outputs. This study proposes a standardized, multistage immunomonitoring framework designed to evaluate immune activation, cytokine polarization, and product integrity in DEX-based therapies. The protocol integrates open access methodologies—flow cytometry, cytometric bead array (CBA), and Western blotting—to assess CD69/CD25 activation, Th1/Th2/Th17 cytokine profiles, and vesicle identity across distinct checkpoints. These outputs are consolidated within the Structured Immunophenotypic Traceability Platform (STIP), which applies logic-based classifications (Type I–III) to support reproducible stratification of immune responses. Functional validation was performed through ex vivo co-culture models, enabling real-time interpretation of immune polarization, cytotoxic potential, and batch consistency. These outputs are supported by previous experimental validations published in Cancers and Biomedicines (2025), where PLPC and DC-derived vesicles demonstrated immunological consistency and a phenotypic stratification capacity. This approach provides a scalable monitoring structure that can support personalized treatment decisions, quality assurance workflows, and integration into regulatory documentation (e.g., CTD Module 5.3) for early-phase, non-pharmacodynamic immunotherapies. This conceptual protocol does not aim to demonstrate therapeutic efficacy but to provide a reproducible documentation framework for real-world immune monitoring and regulatory alignment in vesicle-based immunotherapy. Full article

Pancreatic ductal adenocarcinoma (PDAC) presents significant challenges in diagnosis, prevention, and treatment. Predictive biomarkers offer the potential to revolutionize clinical management, particularly in the preoperative setting, but their implementation requires careful consideration of ethical implications. This scoping review analyzes the ethical landscape of using immunohistochemistry (IHC) for molecular subtyping in PDAC, focusing on its utility, accessibility, and potential impact on patient care. We conducted a systematic literature search in the PubMed, Scopus and Google Scholar databases (2015–2025) using COVIDENCE, which identified 130 references. Of these, 79 were reviewed in a full-text format, and 9 ultimately met the inclusion criteria for our analysis. IHC offers several advantages as a companion diagnostic tool. It is relatively inexpensive, widely available in most pathology laboratories, and can be readily integrated into existing clinical workflows. This contrasts with more complex molecular subtyping methods, such as gene expression profiling, which can be costly, require specialized equipment and expertise, and may not be readily accessible in all clinical settings. Furthermore, accurate analysis of gene expression requires the localized targeting of individual cells; therefore, digesting the sample for bulk analysis would be less informative than using spatial localization techniques such as IHC. Because biomarker regulation can occur at the level of transcription or translation, protein-level assessment via IHC is often more accurate than mRNA analysis. Standardized IHC protocols for biomarker assessment are therefore essential for translating the molecular subtyping of PDAC into clinically actionable treatment strategies, especially for aggressive subtypes like basal-like tumors. This readily deployable IHC-based approach can optimize therapy selection, maximizing patient benefits and minimizing exposure to ineffective and potentially toxic treatments. This review critically analyzes the ethical dimensions of this method, grounded in the principles of autonomy, beneficence, non-maleficence, and justice. The review urges the medical community to fully utilize the potential of IHC-driven molecular subtyping to improve outcomes in PDAC, while ensuring equitable and responsible access to the benefits of precision oncology for all patients. Full article

Antibiotic resistance remains a pressing global health concern, necessitating the development of sustainable and innovative antimicrobial strategies. Plant-based nanomaterials, particularly those synthesized from agricultural byproducts, such as mango seeds, tomato skins, and orange peels, have emerged as promising candidates due to their potent antimicrobial activity and reduced likelihood of resistance development. These nanomaterials exert their effects through diverse mechanisms, including the generation of reactive oxygen species, the disruption of microbial membranes, and interference with critical cellular functions, such as DNA replication. Beyond their antimicrobial properties, recent studies have demonstrated their ability to modulate gut microbiota composition—promoting beneficial genera such as, Lactobacillus and Bifidobacterium, while inhibiting pathogenic species like Staphylococcus spp. This dual functionality positions them as attractive agents for prebiotic interventions and targeted dietary strategies. The convergence of plant-derived nanotechnology and personalized nutrition, guided by individual microbiota profiles, offers a novel paradigm for enhancing host health and preventing infection-related disorders. This review provides a comprehensive overview of the sustainable production of nanomaterials from agricultural and food industry waste, their antimicrobial and prebiotic applications, and their potential in regulating gut microbiota. Furthermore, we discuss emerging nanoenabled strategies to combat infectious diseases and highlight future directions for mechanistic studies, safety assessments, and clinical translation in pharmaceutical, nutraceutical, and functional food contexts. Full article

Background: The potential therapeutic role of fecal microbiota transplantation (FMT) in various diseases has been thoroughly studied over the last few decades. However, the majority of studies focus on the adult population, therefore, conclusions regarding the application of FMT in the pediatric population are much less clear. This systematic review aims to summarize the research conducted so far on the efficacy and safety of FMT in the pediatric population, assess the quality of the evidence of its effectiveness, and outline the most promising areas for future research. Methods: We performed a systematic literature search from the index date to 8 June 2024 on the Embase, PubMed, and Web of Science databases. One author screened the resulting 121 articles. Eventually, 35 eligible studies that reported FMT use in seven different diseases were identified. Results: All of the studies assessed FMT as a safe procedure without many serious adverse effects. The best-documented application, which is the only one recommended in official guidelines, is recurrent Clostridioides difficile infection. Other disease entities in which the use of FMT has been studied with good clinical effects are inflammatory bowel disease, allergic colitis, autism, Tourette syndrome, and colonization with multi-drug-resistant organisms. However, it should be noted that the majority of studies are cohort and case-control studies, without randomization, which translates into low evidence quality. In one randomized, controlled trial focusing on the effect of FMT on weight loss in obese individuals, a lack of effect was found. Conclusions: While FMT and subsequent iterations of gut microbiota-targeted interventions hold promising therapeutic potential for various disease entities in the pediatric population, the current evidence behind this conclusion is of low quality. Based on current studies, these methods appear to be both effective and safe. However, further randomized clinical trials are necessary, especially within the pediatric population, for which such studies remain scarce. Full article

(1) Background: Globally, lung cancer is the leading cause of cancer death, but immunotherapy has impressively improved the outcomes, generating longer progression-free survival and overall survival. Endocrine immune-related adverse events (irAEs) are mostly irreversible and need life-long hormonal substitution therapy. The evaluation of the quality of life of lung cancer patients experiencing endocrine toxicities during immune checkpoint inhibitor (ICI) treatment is relevant for both patients and healthcare providers. (2) Methods: This was a prospective cohort study of lung cancer patients treated with immune checkpoint inhibitors in a tertiary-level hospital in Romania from 1 December 2021 to 30 September 2024. Quality of life was assessed using versions of the EORTC QLQ-C30 and EORTC QLQ-LC-13 validated and translated into the Romanian language. We investigated several clinical variables to evaluate their impact on QoL. (3) Results: Fifty-nine lung cancer patients were evaluated for their QoL before ICI initiation and at the end of the study. Endocrine-irAEs occurred in 17 lung cancer patients (28.8%). Quality of life as assessed using the EORTC questionnaires was statistically significantly improved, even in patients experiencing endocrine-irAEs. (4) Conclusions: Our prospective cohort study succeeded in delivering the proof of concept of an increased QoL in lung cancer patients who had developed endocrine-irAEs under immunotherapy. Despite toxicities, especially rather frequent endocrine-irAEs, ICIs enabled durable disease control and symptom relief, improving the QoL of the overall trial population. As more lung cancer patients undergo immunotherapy in metastatic or early stages, we draw attention to this particular patient population with autoimmune endocrinopathies, as they will live longer and require life-long hormonal therapy. Full article

Transportation agencies face increasing challenges in identifying and prioritizing which infrastructure assets are most critical to maintain and protect, particularly amid aging networks, limited budgets, and growing threats from climate change and extreme events. However, existing prioritization approaches often lack consistency and fail to adequately incorporate diverse stakeholder perspectives. This study develops a systematic, stakeholder-informed method for ranking transportation assets based on their criticality to the overall transportation system. As a novel approach, we use the analytical hierarchy process (AHP) and present a case study of the applied approach. Six criteria were identified for ranking assets: annual average daily traffic (AADT), redundancy, freight output, roadway classification, Social Vulnerability Index (SoVI), and tourism. Stakeholder input was collected via an AHP-based survey using pairwise comparisons and translated into weighted rankings. Thirty complete responses (13.2% response rate) from experts (i.e., engineers, analysts, planners, etc.) were analyzed, with the resulting ranks from highest to lowest priority being AADT, redundancy, freight output, roadway classification, SoVI, and tourism. Stability analysis confirmed that rankings were consistent with a minimum of 15 responses. The resulting method provides a practical, replicable tool for agencies to perform statewide vulnerability/resiliency assessments ensuring that decision-making reflects a broad range of expert perspectives. Full article

This paper investigates the relationship between economic freedom and economic growth in Latin America and the Caribbean over the period 1997–2023, using data from 14 countries. To capture the multidimensional nature of economic freedom, two widely recognized indices—Heritage and Fraser—are incorporated into an extended Solow-type growth model. The empirical strategy relies on a dynamic panel data approach using the Arellano–Bond estimator, which allows for the control of unobserved heterogeneity, autocorrelation, and potential reverse causality. Robustness is assessed through alternative model specifications and in-sample forecasting using rolling-window techniques and Theil’s U-statistic. The results reveal a negative and statistically significant relationship between economic growth and the Heritage Index, while the Fraser Index shows a positive but generally non-significant effect. These findings highlight the methodological sensitivity of the economic freedom–growth nexus and suggest that context-specific institutional factors may shape how liberalization policies translate into development outcomes. The study contributes to the literature by jointly evaluating the impact of both indices in a unified dynamic framework, providing new evidence for a region marked by institutional heterogeneity and growth volatility. Full article

Glacial Lake Outburst Floods (GLOFs) have emerged as a critical threat to high-mountain communities and ecosystems, driven by accelerated glacier retreat and lake expansion under climate change. This review synthesizes advancements in remote sensing technologies and methodologies for GLOF monitoring, risk assessment, and mitigation. Through a Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA)-guided systematic literature review and bibliometric analysis of studies from 2010 to 2025, we evaluate the transformative role of remote sensing in overcoming traditional field-based limitations. Central to this review is the exploration of multi-sensor data fusion for high-resolution lake dynamics mapping, machine learning algorithms for predictive risk modelling, and hydrodynamic simulations for flood propagation analysis. This review underscores the importance of these technologies in improving GLOF risk assessments and supporting early warning systems, which are crucial for safeguarding vulnerable high-mountain communities. It addresses existing challenges, such as data integration and model calibration, and advocates for collaborative efforts between scientists, policymakers, and local stakeholders to translate technological advancements into effective mitigation strategies, ensuring the sustainability of these at-risk regions. Full article

Background/Objectives: The Visual Function and Corneal Health Status (V-FUCHS) questionnaire assesses vision-related quality of life in patients affected by Fuchs endothelial corneal dystrophy (FECD) through 15 items, which are divided into the “visual acuity (VA) Factor” and “glare Factor” domains. The purpose of this study was to translate and validate the Italian version of the V-FUCHS instrument. Methods: The original V-FUCHS questionnaire was translated into Italian using certified forward and backward translation methods and administered to patients with FECD undergoing a unilateral or bilateral Descemet membrane endothelial keratoplasty (DMEK) for FECD and healthy controls. Its test–retest reliability was assessed by administering the questionnaire twice, four weeks apart. Modified Krachmer grade, best-corrected visual acuity (BCVA) and central corneal thickness (CCT) were also measured. Results: A total of 74 participants, aged 45 to 83 years, were prospectively enrolled and divided into five subgroups: mild-to-moderate FECD (n = 18), advanced FECD (n = 15), unilateral DMEK (n = 9), bilateral DMEK (n = 12), and healthy controls (n = 20). Retest reliability confirmed the consistency and agreement of their responses (intraclass correlation coefficient > 0.90 for both factors). The Italian V-FUCHS effectively discriminated between different stages of FECD severity, with significant differences in VA and glare factor scores across all subgroups (p < 0.001). While both BCVA and CCT showed correlations with V-FUCHS scores, only the association between the VA factor and BCVA was statistically significant (p < 0.05), indicating that the VA factor meaningfully reflects patients’ measured VA. Conclusions: The proposed Italian version of the V-FUCHS questionnaire is a valid and reliable tool for assessing visual disability in patients with FECD before and after DMEK. This instrument may aid in optimizing endothelial keratoplasty timings and evaluating postoperative symptomatic improvements in FECD patients. Full article

The rapid pace of modern life has contributed to a significant decline in sleep quality, which has become an urgent global public health issue. Melatonin, an endogenous hormone that regulates circadian rhythms, is vital in maintaining normal sleep cycles. While oral melatonin supplementation is widely used, transdermal delivery systems present advantages that include the avoidance of first-pass metabolism effects and enhanced bioavailability. In this study, a novel melatonin transdermal delivery system was successfully developed using a thermosensitive poly(N-vinylcaprolactam) [p(NVCL)]-based carrier. The p(NVCL) polymer was synthesized through free radical polymerization and characterized for its structural properties and phase transition temperature, in alignment with skin surface conditions. Orthogonal optimization experiments identified 3% azone, 3% menthol, and 4% borneol as the optimal enhancer combination for enhanced transdermal absorption. The formulation demonstrated exceptional melatonin loading characteristics with high encapsulation efficiency and stable physicochemical properties, including an appropriate pH and optimal moisture content. Comprehensive in vivo evaluation using normal mouse models revealed significant sleep quality improvements, specifically a shortened sleep latency and extended non-rapid eye movement sleep duration, with elevated serum melatonin and serotonin levels. Safety assessments including histopathological examination, biochemical analysis, and 28-day continuous administration studies confirmed excellent biocompatibility with no adverse reactions or systemic toxicity. Near-infrared fluorescence imaging provided direct evidence of enhanced transdermal absorption and superior biodistribution compared to oral administration. These findings indicate that the p(NVCL)-based melatonin transdermal gel system offers a safe, effective and convenient non-prescription option for sleep regulation, with promising potential for clinical translation as a consumer sleep aid. Full article

Background: High in-domain accuracy in healthcare machine learning (ML) models does not guarantee reliable clinical performance, especially when training and validation protocols are insufficiently robust. This paper presents a standardized framework for training and validating ML models intended for classifying medical conditions, emphasizing the need for clinically relevant evaluation metrics and external validation. Methods: We apply this framework to a case study in knee osteoarthritis grading, demonstrating how overfitting, data leakage, and inadequate validation can lead to deceptively high accuracy that fails to translate into clinical reliability. In addition to conventional metrics, we introduce composite clinical measures that better capture real-world utility. Results: Our findings show that models with strong in-domain performance may underperform on external datasets, and that composite metrics provide a more nuanced assessment of clinical applicability. Conclusions: Standardized training and validation protocols, together with clinically oriented evaluation, are essential for developing ML models that are both statistically robust and clinically reliable across a range of medical classification tasks. Full article

Background: The timely detection of cognitive decline in highly educated adults is challenging due to their resilient cognitive abilities and the limited sensitivity of neuropsychological tests for this group. Therefore, evaluating subjective facets such as subjective cognitive decline (SCD) becomes imperative, potentially enabling the early identification of cognitive decline. Objective: Our primary objective was to identify effective methods, both objective and subjective, for the early detection of cognitive decline in highly educated older adults. A secondary objective was to translate and validate a Hebrew adaptation of the SCD questionnaire. Methods: Initially (T0), the study included 28 highly educated participants (mean age = 72.6, SD = 4.54; mean education 17.6, SD = 3.41). By the final evaluation (T7), 20 participants remained. Annual assessments involved objective neuropsychological tests and self-report questionnaires evaluating depression, anxiety, and SCD with changes analyzed over time using repeated measures ANOVA. Results: Significant declines were observed in the following objective neuropsychological tests: Rey–Osterrieth Complex Figure Test (ROCFT) copy, F(3,57) = 9.05, p < 0.001, ηp2 = 0.32, and Rey Auditory Verbal Learning Test (RAVLT) trial six, F(1,19) = 7.32, p < 0.05, ηp2 = 0.28, which is consistent with previous findings. The Hebrew SCD questionnaire demonstrated high reliability and validity and was highly correlated with cognitive decline. Conclusions: The ROCFT copy and the Hebrew SCD questionnaire can serve as valuable indicators for the early detection of cognitive decline in highly educated older adults. Full article

The transition toward sustainability in the construction industry requires integrated tools that align with circular economy principles. This study introduces the Interactive Stakeholder Journey Map in Construction (ISJMC), an innovative visual and systemic tool that supports waste management and circularity throughout the life cycle of construction assets. Although the sector is economically significant, it remains one of the main contributors to environmental degradation due to high resource consumption and low waste recovery rates. Developed according to EN 15643-3:2012, a European standard that provides a framework for assessing the social sustainability of construction works, focusing on aspects such as accessibility, health, and comfort and grounded in the Design Thinking methodology, ISJMC enables mapping stakeholder interactions, touchpoints, and responsibilities across all life cycle stages, including initiative, design, procurement, construction, use, and end of life. A systematic literature review and collaborative workshops guided the tool’s development and validation. The application in a real case involving a medium-sized Brazilian construction company helped identify significant pain points and opportunities for implementing circular practices. The results demonstrate that ISJMC (i) facilitates a systemic and visual understanding of material and information flows, (ii) promotes transparent mapping of resource value to support better decision-making, and (iii) encourages the identification of circularity opportunities while fostering collaboration among stakeholders. The tool revealed critical challenges related to waste generation and management. It supported co-creating sustainable strategies, including improved material selection, lean construction practices, and stronger supplier engagement. By translating complex standards into accessible visual formats, ISJMC contributes to the academic field, supports practical applications, and offers a foundation for expanding circular approaches in construction projects. Full article

Nipah virus (NiV) is a highly pathogenic paramyxovirus characterized by zoonotic infection, high mortality, and a lack of effective treatment, posing a serious threat to global public health security. Currently, it still lacks specific treatments or approved vaccines, and is listed as a potential pandemic threat pathogen by the World Health Organization. This paper systematically reviews the core progress and challenges of NiV investigation, with a focus on the development of animal models, vaccine development strategies, treatment strategy, and bottlenecks in translational medicine. Additionally, we discuss the strengths and limitations of existing animal models, including ferrets, hamsters, mice, and non-human primates (NHPs), and assess advances in vaccine platforms such as viral vectors, subunit vaccines, and mRNA-based vaccine candidates. The paper critically reviews the challenges facing translational research, conservation correlates, and outbreak preparedness, while also providing future research directions for pandemic preparedness and public health security strategies. Full article

Snakebite is a significant global public health challenge, and the limited application of antivenom has driven the exploration of novel therapies. Combination therapy using small-molecule drugs targeting phospholipases A₂ (PLA2) and metalloproteinases (SVMP) in venom shows great potential. Although Rhamnetin and RXP03 exhibit notable anti-phospholipase and anti-metalloproteinase activities, respectively, their antiophidic potential remains poorly explored. This study aims to evaluate the inhibitory effects of Rhamnetin and RXP03 on snake venom toxicity. Methodologically, we conducted in vitro enzymatic assays to quantify PLA₂/SVMP inhibition, murine models of envenomation (subcutaneous/intramuscular venom injection) to assess local tissue damage and systemic toxicity, and histopathological/biochemical analyses. In vitro experiments demonstrated that Rhamnetin effectively inhibited PLA₂ activity while RXP03 showed potent suppression of SVMP activity, with their combination significantly reducing venom-induced hemorrhagic activity. In murine models, the combined therapy markedly alleviated venom-triggered muscle toxicity and ameliorated oxidative stress. Furthermore, the combination enhanced motor performance and survival rate in mice, improved serum biochemical parameters, corrected coagulation disorders, and attenuated pathological damage in liver, kidney, heart, and lung tissues. This research demonstrates that dual-targeted therapy against metalloproteinases and phospholipases in snake venom can effectively prevent a series of injuries caused by snake venom. Collectively, the combined application of Rhamnetin and RXP03 exhibits significant inhibitory effects on a variety of venom-induced toxicities, providing pharmacological evidence for the development of antivenom therapies. However, the efficacy validation in this study was limited to murine models, and there is a discrepancy with clinical needs for delayed treatment in real-world envenomation scenarios. Despite these limitations, the findings provide robust preclinical evidence supporting the Rhamnetin–RXP03 combination therapy as a cost-effective, broad-spectrum antivenom strategy. Future studies are required to optimize dosing regimens and evaluate clinical translatability. Full article