Search Results (6,398)

Background/Objectives: Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of various malignancies, but their use is frequently accompanied by immune-related adverse events, among which immune-mediated colitis (IMC) represents one of the most common and clinically significant gastrointestinal toxicities. IMC may lead to treatment interruption, increased morbidity, and compromised quality of life. This review aims to provide a comprehensive overview of the pathophysiology, risk factors, diagnosis, management, and emerging therapeutic strategies with particular emphasis on the role of the gut microbiota and fecal microbiota transplantation (FMT). Methods: This review integrates current international guidelines, meta-analyses, clinical trials, and recent translational studies addressing IMC. The available evidence on immunological mechanisms, predictive biomarkers, clinical presentation, diagnostic algorithms, and treatment options was critically synthesized to outline a structured and multidisciplinary management approach. Results: IMC is driven by dysregulated immune activation, cytokine release, and alterations in gut microbiota. Incidence and severity vary according to ICI class, combination regimens, tumor type, and patient-related factors. Diagnosis requires exclusion of infectious causes, laboratory assessment, and endoscopic and histologic evaluation with CTCAE-based severity grading. Corticosteroids remain the cornerstone of first-line therapy, while infliximab and vedolizumab are effective in steroid-refractory cases. Emerging therapies, including JAK inhibitors and FMT, have shown promising results in refractory disease. Conclusions: IMC is a complex and potentially severe complication of ICI therapy that necessitates early recognition, accurate grading, and individualized, multidisciplinary management. Severity-guided treatment, timely escalation to biologics, and careful balancing of immunosuppression with antitumor efficacy are essential for optimal outcomes. Future research should focus on biomarker validation, microbiome-targeted therapies, and prospective trials to refine therapeutic algorithms and define the optimal role and timing of FMT in clinical practice. Full article

Background: The effectiveness of prostate-specific antigen (PSA)-based early detection of prostate cancer remains controversial and implementation-dependent. Screening policy changes have substantially altered PSA testing behavior in the United States, yet longitudinal evidence from non-organized European settings is limited. We assessed 12-year changes in awareness and utilization of PSA-based early detection and identified subgroups requiring targeted counseling. Methods: Two cross-sectional survey waves were conducted in 2009 (Study Phase 1) and 2021 (Study Phase 2) among men recruited via general practitioner practices in urban and rural regions of Germany. The survey was developed and reported according to the Consensus-Based Checklist for Reporting of Survey Studies (CROSS). Identical questionnaires were used across phases. Endpoints were awareness of PSA-based early detection and prior PSA testing. Univariable and multivariable logistic regression evaluated independent associations with sociodemographic and behavioral factors. To assess sensitivity to compositional differences between survey waves, post-stratified weighted analyses re-aligning Study Phase 2 to the Study Phase 1 distribution of age category, educational attainment, and smoking status were conducted. Results: The analytic cohort comprised 890 men (Study Phase 1, n = 755; Study Phase 2, n = 135). Compared with Study Phase 1, Study Phase 2 participants more frequently were non-smokers (63.0% vs. 48.5%, p < 0.001) and had a university degree (38.5% vs. 30.5%, p = 0.002). In primary multivariable analyses, higher educational attainment (OR 1.71, 95% CI 1.24–2.36) and paternity (OR 1.94, 95% CI 1.25–3.01) were independently associated with greater awareness, whereas increasing age (OR 1.39, 95% CI 1.29–1.50) and higher educational attainment (OR 1.63, 95% CI 1.19–2.24) were independently associated with utilization. Study phase was not independently associated with either endpoint in primary models. In post-stratified sensitivity analyses, study phase was positively associated with utilization, indicating sensitivity of temporal contrasts to population composition. Conclusions: In primary multivariable analyses, we did not detect statistically significant temporal differences in awareness or utilization of PSA-based early detection within this German non-organized setting. The emergence of a study phase effect in weighted sensitivity analyses suggests that apparent time trends may be influenced by compositional differences between survey waves. Persistent social gradients, particularly related to educational attainment, underscore the importance of targeted, evidence-based counseling in opportunistic early detection systems. Larger, prospectively designed studies are needed to distinguish true temporal change from sampling-related effects. Full article

Rapid urbanization and increasing traffic volumes necessitate effective road safety measures, particularly in metropolitan areas. Enhancing road safety is a fundamental pillar of social sustainability as it directly reduces the socio-economic burden of traffic accidents and promotes resilient urban environments. This article analyzes the impact of infrastructural traffic-calming devices on road safety parameters using a GIS-based method. This study provides a quantitative tool for monitoring and measuring the effectiveness of sustainable transport infrastructure. The study examines six different types of devices across 44 locations within the GZM Metropolis, Poland, utilizing official police data (Accident and Collision Records System—SEWIK) from a period of two years before and two years after implementation. The primary parameters analyzed include the frequency of incidents, the severity of injuries, and the structure of accident types. The results demonstrate a substantial positive association following the interventions, with an average 41.33% reduction in road incidents across all tested devices. Specifically, speed bumps proved most effective, reducing incidents by over 66%. However, the analysis revealed a critical anomaly: While pedestrian refuge islands decreased the overall number of minor injuries, they correlated with an increase in the number of severe injuries, suggesting a need for careful consideration. Furthermore, the study confirms a positive shift in the structure of incidents, notably a substantial decrease in rear-end and side-impact collisions. The findings offer practical evidence for evidence-based urban policies, contributing to the development of safe, inclusive, and sustainable transport systems in line with global sustainability goals. Full article

Despite consensus in the mathematics education literature regarding the mutually dependent components of math proficiency, as well as the importance of their development, most elementary-aged students in the United States demonstrate a lack of proficiency in math according to national assessment data. Whole number knowledge, which includes skills in computation and word-problem solving, is understood to be a critical foundation for the development of later math skills. This study used a multiple-baseline experimental design to evaluate the impacts of an evidence-based mathematics intervention, Accelerating Mathematics Performance with Practice Strategies (AMPPS), on third- through fifth-grade students’ skills with complex computation, as well as on their word-problem-solving performance. Furthermore, we evaluated effects on students’ math self-concept. Five students identified to have difficulties in math received AMPPS in a one-on-one, in-person format. The results of the study were mixed. For example, when using visual analyses as our primary analytic method, these analyses did not show robust intervention effects on students’ computation skills but did show at least some improvement for most students’ word-problem-solving skills. Additionally, supplemental analyses comparing student growth to national and school-based norms suggested that all participants seemed to benefit from the intervention, but these analyses were not intended to examine experimental causality. Despite study limitations and a lower than optimal number of AMPPS sessions (dosage) provided to students, the present study offers several directions for future research, as well as possible implications for practitioners regarding intervention selection, intensity, and evaluation. The findings will also be discussed in the context of conducting systematic replication studies, which are essential for understanding the generality of a given phenomenon (e.g., an effect of a school-based intervention) across a wide range of situations and conditions. Full article

Background: Surface electromyography (sEMG) of periocular muscles is a non-invasive technique used to assess eyelid dynamics and facial neuromuscular function, with applications in ophthalmology, neurology, and rehabilitation. Despite its clinical and research potential, substantial methodological variability—particularly in electrode placement, acquisition parameters, and signal processing—has limited reproducibility and hindered broader clinical translation. A comprehensive synthesis of existing methodologies was therefore needed to support future standardization. Objectives: The review aimed to systematically map current periocular sEMG methodologies, identify sources of methodological heterogeneity, organize findings into structured methodological domains, and develop a conceptual framework along with a minimum reporting set to promote transparency, reproducibility, and comparability across studies. Eligibility Criteria: Studies were eligible if they investigated surface electromyography of periocular muscles and reported methodological details related to electrode placement, signal acquisition, processing, or analysis. Randomized controlled trials, observational studies, and pilot investigations were included. No restrictions were placed on publication year. Sources of Evidence: Comprehensive searches were conducted in PubMed, Embase, and Web of Science from database inception through November 2025. Grey literature sources were also examined to enhance coverage and reduce publication bias. Charting Methods: Two reviewers independently screened records and extracted data. Extracted information was organized into predefined methodological domains. A thematic synthesis approach was used to identify recurring methodological patterns, and findings were integrated into a structured conceptual framework. Results: Sixteen studies published between 2002 and 2025 met the inclusion criteria, encompassing randomized trials, observational studies, and pilot investigations. Considerable heterogeneity was identified across studies in electrode characteristics, placement strategies, reference configurations, sampling frequencies, and normalization procedures. Three recurring methodological domains emerged: instrumentation and acquisition, analytical and normalization approaches, and clinical or experimental applications. Based on these domains, the authors developed a conceptual methodological framework and proposed a minimum reporting set intended to improve methodologyical transparency and support reproducibility and multicenter comparability. Conclusions: Periocular sEMG represents a promising yet methodologically fragmented field. This scoping review provides the first comprehensive synthesis of periocular sEMG practices and establishes an evidence-based platform for standardized acquisition, processing, and reporting. Adoption of the proposed framework may strengthen reproducibility, facilitate multicenter collaboration, and accelerate integration into clinical and research settings. Full article

Background/Objectives: HPV vaccination is highly effective in preventing HPV-related cancers when administered before viral exposure. However, vaccination practices for patients already diagnosed with gynaecological cancers remain poorly characterized. Understanding clinicians’ perspectives and barriers is essential for optimizing preventive strategies in oncologic care. Methods: We conducted an international, web-based survey among members of the European Society of Gynaecological Oncology (ESGO) and the European Network of Young Gynaecological Oncologists (ENYGO). The questionnaire explored clinicians’ attitudes, practices, and perceived obstacles regarding HPV vaccination in patients with gynaecological cancer or pre-invasive disease across multiple clinical scenarios and age groups. Results: A total of 149 respondents from 33 countries completed the survey. Most clinicians supported HPV vaccination for patients treated for cervical precancer (78–82% for patients under 45 years), and even for invasive cervical cancer (57–62%). Recommendations varied by patients’ age, cancer type, and treatment status. For endometrial and ovarian cancer, endorsement ranged from 16% to 53%, depending on patient age. Timing of vaccination was a point of divergence: some clinicians favoured vaccination immediately after treatment for CIN2+, while others recommended delaying vaccination depending on HPV test results. Reported barriers discouraging HPV vaccination recommendations included misinformation (69.8%), lack of patient education materials (52.3%), and time constraints (48.3%), alongside economic factors and uncertainty about efficacy in oncologic settings. Conclusions: The survey shows that HPV vaccination is often recommended beyond evidence-supported indications. Randomized trials have not demonstrated a reduction in CIN2+ recurrence with adjuvant vaccination, and no evidence supports vaccination in women with invasive gynaecological cancers. These findings reveal a gap between clinical practice and available evidence, highlighting the need for clearer, evidence-based guidance. Full article

The UK faces an urgent challenge to simultaneously accelerate housing delivery and reduce whole-life carbon emissions, yet robust empirical evidence on the carbon performance of modular steel housing remains limited. This study aims to quantify the carbon impacts of a modular light-gauge steel frame social housing dwelling in the UK and to benchmark its performance against contemporary low-carbon construction typologies. A cradle-to-grave life cycle assessment was conducted using primary project data from a real modular housing development, with embodied carbon modelled in One Click LCA and operational energy assessed through SAP 10.2-verified datasets. The results indicate a total whole-life carbon footprint of 91.3 tCO₂e over a 50-year period, with embodied emissions (A1–A3) accounting for 38.2% and operational energy and water use contributing 48.1%. The normalised embodied carbon intensity of 366 kgCO₂e/m² (A1–A5) is comparable to recent high-performing cross-laminated timber buildings, demonstrating that optimised modular steel systems can allow for low-carbon outcomes typically associated with bio-based construction. Sensitivity analysis shows that low-carbon foundation concrete, bio-based insulation, and steel optimisation can reduce upfront emissions by approximately 8–10%. Dynamic energy simulations were also used to assess how different design choices influence operational carbon emissions. This study provides transparent, real-project evidence of the whole-life carbon performance of UK modular light-gauge steel frame housing and identifies practical design strategies for further decarbonisation. The findings support informed decision-making for policymakers, designers, and housing providers seeking scalable, low-carbon residential solutions. Full article

Background: Aquaculture, a vital component of global food security, faces sustainability challenges due to intensive farming practices, including water pollution, disease outbreaks, and antibiotic overuse. Probiotics, prebiotics, and synbiotics have emerged as eco-friendly alternatives to antibiotics. However, research results remain heterogeneous across aquatic species and intervention strategies. Methods: Following PRISMA 2020, we searched two databases (up to January 2026) for in vivo trials. Two reviewers screened and extracted data, and 177 eligible studies were ultimately included, covering single-/multi-strain probiotics (SSP/MSP), live/inactivated microbial preparations, and diverse synbiotic formulations. Results: Among 177 studies, Bacillus spp. were the most widely reported and effective probiotic strains. MSP and synbiotics exhibited superior efficacy in boosting aquatic animal growth performance and disease resistance over SSP in 68% of the included trials. Probiotics act through the competitive exclusion of pathogens, immune modulation, and enhanced digestive enzyme activity; prebiotics selectively stimulate beneficial gut microbiota, improving nutrient absorption and immune function through metabolites such as short-chain fatty acids; synbiotics combine the advantages of both, exerting synergistic effects. Furthermore, as water additives or fermented feed ingredients, probiotics reduce nitrogenous waste and organic pollutants, contributing to bioremediation. Conclusions: All three additives are effective. Standardized application protocols and long-term trials are needed for sustainable aquaculture. This review provides a unified evidence-based foundation for the rational use of these additives in aquaculture. Full article

Background: Malignant pleural effusion (MPE) represents a frequent and clinically challenging manifestation of advanced malignancy, particularly in metastatic non-small cell lung cancer (NSCLC). Its management requires integration of diagnostic imaging, symptom-directed therapeutic strategies, and, increasingly, molecular profiling technologies. Recent advancements in this field based on liquid medium (so-called liquid biopsy) have achieved a significant increase in sensitivity, enhancing our ability to investigate biofluids and suggesting their potential integration into standard diagnostic practices, far beyond the canonical plasma biopsies. Fluid obtained from MPE after cytological sample centrifugation is rich in cell-free DNA and less susceptible to nucleic acid degradation during processing, improving overall diagnostic accuracy. Methods: This narrative review summarizes current evidence on the clinical management of malignant pleural effusions in patients with metastatic NSCLC, integrating imaging, procedural management, and molecular profiling from a multidisciplinary tumor board perspective. The primary objective was to synthesize contemporary knowledge with particular attention to the feasibility, reliability, and reproducibility of pleural fluid-based molecular testing. Results: MPE poses diagnostic and therapeutic challenges for all members of the multidisciplinary tumor board, traditionally associated with an adverse prognosis. However, recent advances in cytopathology, histopathology, and liquid-based techniques demonstrate that MPE could be an important source of prognostic or predictive information. At the same time, optimal patient management requires careful integration of imaging findings and procedural strategies (such as pleurodesis or indwelling pleural catheters) with individualized systemic therapy selection. Cell-free DNA in pleural effusions is a promising field of exploration and study, potentially suitable for future guideline implementation, after validation in adequately powered studies, contributing to improving patient management, particularly useful in fragile subsets. Conclusions: The management of MPE in advanced NSCLC is evolving toward a multidisciplinary, precision-oriented model that integrates clinical evaluation, imaging, procedural interventions, and molecular testing. Liquid biopsy technology has gained enough analytical robustness and clinical feasibility to be a useful tool in routine analysis. Biofluid-based molecular testing may have outstanding potential, contributing to improving patient management, avoiding repetitive procedures, and optimizing the overall efficiency and cost-effectiveness of diagnostic practices. Moreover, collaborative projects among different specialties help in consolidating trust in the tumor board decision-making process. Full article

Background/Objectives: Breast cancer awareness is essential for early detection and timely help-seeking among women and represents a key component of multidisciplinary breast cancer prevention. The Breast Cancer Awareness Measure (Breast-CAM) is widely used to assess awareness of breast cancer symptoms, risk factors, and screening behaviors. Its measurement quality across populations has not yet been comprehensively evaluated. As Breast-CAM is a population-reported measurement instrument, evaluation using a standardized framework for measurement properties is required. This systematic review and meta-analysis aimed to assess the psychometric properties of the Breast-CAM across diverse populations and cultural adaptations, in accordance with COSMIN (COnsensus-based Standards for the selection of health Measurement INstruments) methodological standards. Methods: Major bibliographic databases and trial registries were systematically searched for peer-reviewed English-language studies published between 2010 and 2025 that evaluated at least one psychometric property of the Breast-CAM in adult women. Methodological quality was assessed using the COSMIN Risk of Bias checklist. Measurement properties were evaluated according to COSMIN criteria, and the certainty of evidence was graded using a modified GRADE approach. Meta-analysis was performed when data were sufficiently comparable. Results: Seventeen studies met the inclusion criteria for narrative synthesis, of which eleven were included in a meta-analysis, representing fourteen cultural adaptations of the instrument. A descriptive random-effects meta-analysis of reported Cronbach’s α yielded a pooled estimate of 0.89 (95% confidence interval 0.85–0.92). This value should be interpreted cautiously, as structural validity was frequently insufficient across cultural adaptations, limiting interpretation of internal consistency according to COSMIN guidance. Other measurement properties, including reliability and measurement error, were frequently inadequately assessed or unreported. The certainty of evidence ranged from very low to moderate. Conclusions: Content validity was generally rated as sufficient, although certainty of evidence was low. Despite the high pooled α estimate, the reliability of Breast-CAM cannot be firmly established because structural validity was frequently insufficient across cultural adaptations. In accordance with the COSMIN ceiling rule, internal consistency was not considered sufficient in the absence of adequate structural validity. Key measurement properties, including test–retest reliability, measurement error, and responsiveness, were rarely evaluated. Further high-quality psychometric studies, particularly in culturally diverse populations, are needed to address these gaps and support appropriate use of the instrument in research and public health practice. Full article

Background: This study examines the competitive dynamics of the artisanal wooden furniture industry in Misantla, Veracruz, Mexico, a predominantly informal productive system characterized by family-managed production units and strong territorial embeddedness. Methods: A mixed-methods research design was employed. Quantitative data were collected from 187 family-managed production units (86 woodworking units and 101 workshops) using a structured questionnaire based on five-level Likert scales assessing external efficiency, collective efficiency, and innovation. Statistical analyses included descriptive measures and chi-square tests to examine associations between competitiveness and collective strategies, while qualitative validation and thematic interpretation based on expert assessments were used to contextualize sectoral practices and structural constraints. Results: The findings indicate a low overall competitiveness score (1.92/5), associated with informal practices, limited technical training, and weak supply chain integration. Despite these constraints, the sector maintains a strong cultural identity and contributes to its local economy. Conclusions: Artisanal supply chains can achieve functional levels of logistics performance through internal coordination dynamics. Strengthening collaboration mechanisms is a viable strategy for improving logistics performance in artisanal manufacturing systems in emerging economies. These findings provide empirical evidence to support the design of collaborative strategies that integrate traditional craftsmanship with modern supply chain practices in artisanal micro-industries. Full article

Assessing and optimizing regional ecological networks is critical for mitigating fragmentation-driven ecological risks and informing evidence-based territorial spatial planning in China. In this study, we developed a comprehensive evaluation framework integrating ecosystem services, ecological sensitivity, and landscape connectivity to identify ecological sources in Anyang City, China. We then extracted ecological corridors and nodes using circuit theory and constructed the city’s ecological network. Notably, we applied complex network theory combined with topological robustness analysis for optimization to enhance network stability. The analysis identified 43 ecological sources (820.72 km²; 11.16% of the region), predominantly distributed in western Anyang. A total of 82 corridors (460.35 km), 62 pinch points, and 120 barrier points were mapped—primarily in the west, revealing critical connectivity deficits. Network optimization through the addition of 10 strategic corridors significantly enhanced structural balance and functionality, with average degree, closeness centrality, clustering coefficient, eigenvector centrality, and graph density increasing by 5.55–12.19%, and their standard deviations decreasing by an average of 19.32%. Global efficiency (+8.74%), the largest connected component ratio (+0.73%), and node/edge recovery robustness (+17.44%/+18.08%) also improved markedly, confirming greater connectivity and resilience. Our methodology comprehensively integrates ecosystem functional services, disturbance resistance, and spatial structural stability, providing a practical reference for the construction and optimization of regional ecological networks in mountainous–plain transition zones of China. Full article

Crocus sativus L. (saffron), a sterile geophyte of the Iridaceae family, has been traditionally used in culinary and medicinal practices and is currently gaining attention as a source of pharmacologically active metabolites. The main bioactive compounds (BACs) of saffron, crocin, crocetin, picrocrocin, and safranal, are associated with a wide range of biological activities, including anti-inflammatory, antioxidant, immunomodulatory, antimicrobial, antiproliferative, and antidiabetic properties, among others. This review aims to comprehensively and critically summarize the preclinical and clinical evidence for saffron-derived BACs in the context of the most prevalent non-communicable diseases. A literature search of the main scientific databases was conducted to identify peer-reviewed articles on neurodegenerative disorders, cancer, cardiovascular diseases, and diabetes mellitus, with additional topics on ethnopharmacology, phytochemistry, safety, and toxicity. The mechanistic findings include anti-inflammatory, immunomodulatory, antioxidant, antiproliferative, and neuroprotective effects, mediated by activation of the Nrf2 pathway and inhibition of NF-κB. Eligibility criteria were applied, excluding publications focused primarily on food, cosmetics, or technological applications, to prioritize mechanistic and therapeutic endpoints. The findings suggest that BACs from saffron extracts have promising disease-modifying properties and symptom-relieving actions, especially in the case of neurologic disorders, mild cognitive impairment, and some models of metabolic and oncological diseases. Nevertheless, the current variability in study design, dosage, standardization of plant extracts, and sample size limits a conclusive clinical application. More carefully designed studies with a representative number of cases and well-defined plant preparations are needed to validate efficacy, establish structure-activity relationships, and define the prevention and therapeutic potential of saffron in evidence-based pharmacotherapy. Full article

Regarding the precipitation behavior of Cu particles in steel, conventional studies have primarily focused on isothermal precipitation, which has limitations in characterizing precipitation kinetics under variable temperature conditions. For this purpose, in the present study, the Fe-3%Si-Cu alloy was selected as a model system to systematically investigate the regulation of Cu particle precipitation behavior and associated strengthening effects in a ferrite matrix during continuous heating—a process path that better aligns with practical conditions. The results indicate that, during the continuous heating process, an increase in the heating rate from 10 °C/h to 600 °C/h leads to a significant rise in the peak temperature, from 490.2 °C to 609.7 °C, while the time required to reach the peak temperature decreases substantially, from approximately 9.1 h to 19.6 min. Through TEM microstructure analysis and characterization, it is evident that rapid heating at 500 °C/h significantly promotes the high-density nucleation of B2 and 9R-Cu metastable phases while effectively suppressing particle coarsening. This results in a finely dispersed nano-Cu precipitate phase with an average particle size of 8.21 nm and a number density of 30.35 × 10¹⁰ cm⁻². Under the rapid heating condition of 500 °C/h, the precipitation strengthening contribution of Cu particles reaches 501.86 MPa, significantly higher than the 451.02 MPa observed under the slow heating condition of 50 °C/h. This study, from the perspective of the coupling effect between thermodynamics (driven by undercooling) and kinetics (governed by diffusion), elucidates the kinetic behavior of Cu particle precipitation during continuous heating. It provides a novel fundamental and strengthening theory in the field of ferrite metallurgy for copper-enriched electrical steels and related engineering steels, offering significant insights for further understanding the role of copper in ferrite-based steels. Full article

Peer review is the cornerstone of scholarly publishing and, in medicine, the ultimate guarantor of the reliability of clinical evidence that informs guidelines, therapeutic strategies, and patient care. However, the current peer review system is increasingly strained by bias, abuse, and reviewer overload. Favoritism toward prominent authors, editorial “nepotism,” coercive citation practices, superficial evaluations, and even documented cases of idea theft from confidential manuscripts undermine the trustworthiness of the scientific literature upon which clinical decisions depend. In this paper, we argue that artificial intelligence (AI) and large language models (LLMs) offer a transformative opportunity to strengthen the integrity and efficiency of medical peer review. AI-driven tools can perform rapid consistency checks, detect statistical errors or plagiarism, and enforce compliance with ethical and methodological standards across thousands of manuscripts. Early implementations of AI-guided review platforms, plagiarism detectors, and citation-anomaly algorithms demonstrate that machine assistance can make reviews more thorough, objective, and reproducible. At the same time, we acknowledge the limitations of AI, including hallucinations, a lack of human judgment, and risks to confidentiality if misused. To address these concerns, we propose a hybrid model in which AI handles routine screening and technical tasks under strict safeguards, while human experts retain final responsibility for scientific evaluation. This human–AI partnership may represent an essential step toward improving the quality, fairness, and reliability of the clinical evidence base. Full article