Search Results (4,698)

Background/Objectives: Immunisation coverage gaps in Central and Eastern Europe (CEE) are commonly attributed to barriers of access. This study measured how the professionals who deliver immunisation services weigh competing barriers, whether their assessments differ when the referent is their own country rather than the CEE region as a whole, and how they rank candidate interventions on expected impact and near-term feasibility. Methods: Sixty-two professionals working in twelve countries and at the European level (47 based in CEE, 39 of them in Romania) completed a cross-sectional structured survey around a multi-stakeholder meeting in Bucharest (14 May 2026). Respondents rated 15 barriers twice, for their own country and for the CEE region; rated 16 interventions for the expected impact and 12–24-month feasibility; force-ranked their selections; and assigned the lead responsibility for five system functions. Results: Digital misinformation was the highest-rated barrier in every subgroup and at both geographic levels. The assessments differed by geographic referent: within respondents, trust and information barriers were rated more severe for their own country and access barriers more severe for the region (d_z = 0.52), a pattern attenuated but retained after standardising within each level; the same regional object was also described differently by respondents inside and outside CEE (d = 1.02). Across the 16 intervention-level means, the expected impact and feasibility were only weakly and imprecisely associated (r = 0.21, 95% CI −0.32 to 0.64), although, within respondents, the two were modestly correlated (r = 0.33). Continuing professional education for primary care ranked first on expected impact and led the forced-choice ranking in every subgroup. The lead responsibility was the clearest for professional training and least settled for equity monitoring. Conclusions: Barriers were assessed differently depending on whether the referent was the respondent’s own country or the region as a whole. These are professionals’ perceptions, not measured outcomes: access may rank low partly because the panel does not face it personally, and the findings do not place cost and structural determinants second. Regional strategies built on assumptions about neighbouring systems may misallocate attention, and the equity agenda this panel endorses rests on a monitoring function no actor owns. Full article

Background/Objectives: Chronic spontaneous urticaria (CSU) is a mast-cell-driven disease with autoimmune mechanisms and an incompletely clarified aetiology, in which a substantial proportion of patients remain symptomatic despite second-generation H1-antihistamines; until recently, omalizumab was effectively the only targeted option, leaving a considerable non-responder fraction. Between February 2024 and September 2025 the landscape changed: dupilumab (anti-IL-4Rα) and the first oral Bruton tyrosine kinase (BTK) inhibitor, remibrutinib, were approved for CSU; omalizumab biosimilars reached the market; the higher-affinity anti-IgE antibody ligelizumab was discontinued; and the investigational anti-KIT antibody barzolvolimab advanced to phase 3—creating new therapeutic opportunities for non-responders while leaving the choice among these second-line options unresolved by current guidelines. We provide a critical synthesis and propose an evidence-graded process for agent selection, together with a proposed repositioning of the available agents, taking the 2022 EAACI/GA²LEN/EuroGuiDerm/APAAACI guideline as the acknowledged reference. Methods: Critical narrative review with a structured but non-systematic search (PubMed, ClinicalTrials.gov) and a pre-specified evidence hierarchy (guideline to expert opinion); each clinical claim is annotated by its level of evidence. Results: Four agents are appraised in turn—omalizumab (anti-IgE, first-line), dupilumab (anti-IL-4Rα), remibrutinib (oral BTK inhibitor, small-molecule comparator) and barzolvolimab (anti-KIT, investigational). Current evidence appears to support omalizumab as first-line, with mechanism-guided second-line choices conditioned on endotype, comorbidity, prior biologic exposure and safety. Conclusions: The complexity of CSU and the incomplete response to currently available therapies support a patient-tailored approach to treatment selection. Full article

1-deoxy-D-xylulose-5-phosphate synthase (DXS) is the first key enzyme in the methylerythritol phosphate (MEP) pathway of plant terpenoid biosynthesis, and it plays a vital role in Eucommia ulmoides terpenoid biosynthesis. In this study, bioinformatics methods were used to comprehensively identify and analyze the expression pattern of the EuDXS gene family, aiming to provide a basis for further functional study of EuDXS genes. A total of four EuDXS gene family members were identified and named EuDXS1 to EuDXS4. The encoded proteins contained 625 to 713 amino acid residues, with molecular weight ranging from 67.98 kDa to 76.61 kDa. The theoretical isoelectric points varied from 6.79 to 8.69, aliphatic index was between 85.29 and 91.29. In silico subcellular localization prediction revealed that all EuDXS proteins were localized in chloroplasts. EuDXS gene members were categorized into three subfamilies, which were unevenly distributed on three chromosomes. The promoters of EuDXS genes contained various cis-acting elements related to stress response, phytohormone signaling, light response and growth regulation. Expression pattern analysis showed that EuDXS genes exhibited tissue-specific expression: EuDXS1 was highly expressed in stem, leaf and fruit, EuDXS2 was predominantly expressed in fruit. EuDXS1 and EuDXS2 exhibited high expression levels at the early developmental stage of fruits and leaves. In addition, EuDXS genes responded to salt and drought stress in varying degrees. Transient expression in tobacco revealed that EuDXS1 and EuDXS2 could increase carotenoid and total chlorophyll content. This study will provide important genetic resources for further exploration of EuDXS gene function and germplasm innovation in E. ulmoides. Full article

Early-stage selection of pile foundation systems is associated with considerable uncertainty due to limited site information and the need to consider multiple geotechnical, structural, and construction-related factors simultaneously. This study proposes a rule-based decision-support framework, named GeoSupport Decision Platform (GSDP), for transparent and systematic evaluation of pile foundation alternatives across varying engineering conditions. A multicriteria scoring procedure is introduced into the proposed framework to evaluate the recommended pile alternative for the application. The implemented procedure combines compatibility scores and weighting coefficients based on engineering judgement and related to soil type, groundwater conditions, frost depth, load level, vibration/noise restrictions, and site accessibility. The ranked pile alternative list, closely linked to the suitability scores, is an outcome of the framework. The applicability of the GSDP framework is illustrated through two case studies based on construction sites in Kokshetau and Astana, Kazakhstan, representing different geotechnical and construction conditions. For the Kokshetau construction site, the GSDP framework recommends driven piles with a suitability score of 0.975 as the most suitable foundation alternative, followed by bored piles and micropiles, with suitability scores of 0.905 and 0.845, respectively. In contrast, for the Astana case, bored/CFA piles are ranked first with a suitability score of 0.970, followed by micropiles (0.825) and driven piles (0.775). In both cases, the highest-ranked pile alternative corresponds to the pile foundation system adopted at the respective construction site. The results show that the framework generates transparent, interpretable recommendations through a weighted scoring procedure and provides brief explanations that align with the engineering solution chosen for the case study. The contrasting rankings, which demonstrate the ability of the framework to respond to site-specific conditions rather than systematically favoring a single pile type, indicate the GSDP’s practical engineering significance for the preliminary selection of pile foundations when site investigation data are limited. Full article

ESG has profoundly influenced asset pricing and resource allocation in capital markets. However, existing research largely focuses on the economic consequences of absolute ESG levels, with limited attention paid to how the gap between corporate ESG performance and aspiration levels—the ESG performance aspiration gap—is related to the behavior of information intermediaries in the capital market. Using a sample of A-share non-financial listed companies on the Shenzhen Stock Exchange from 2013 to 2024, this paper empirically examines the relation between the ESG performance aspiration gap and institutional investors’ site visits and its potential underlying channel. The findings are as follows. First, the ESG performance aspiration gap is positively correlated with institutional investors’ site visits. This conclusion remains robust after a series of robustness tests. Second, the mechanism analysis is consistent with information asymmetry serving as a potential channel linking the ESG performance aspiration gap and institutional investors’ site visits. Third, the moderating effect analysis shows that both marketization level and analyst coverage negatively moderate the positive relation between the ESG performance aspiration gap and institutional investors’ site visits. This paper extends the research boundaries of the economic consequences of ESG and institutional investors’ information search behavior, providing a new theoretical explanation for how the capital market responds to the dynamic changes in corporate ESG performance. It also offers policy implications for improving the ESG information disclosure system and enhancing the information efficiency of the capital market. Full article

Background: Serial serum tumor-marker testing is widely used in clinical practice, but its relationship to concurrent imaging response and survival in advanced gastric cancer (AGC) remains uncertain. We evaluated five serum tumor markers—carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 19-9, CA72-4, CA125, and tissue polypeptide antigen (TPA)—in patients receiving first-line palliative systemic therapy. Methods: We retrospectively analyzed 140 patients with unresectable locally advanced or metastatic gastric adenocarcinoma treated between 2021 and 2024. Results: Baseline positivity rates for the individual markers ranged from 43.6% to 73.6%, and at least one marker was elevated in 90.0% of patients. Baseline CA125 positivity was associated with a lower objective response rate compared to CA125 negativity (29.7% vs. 55.3%). Among the 117 patients with complete serial measurements of all five markers, decreases in CEA, CA72-4, CA125, and TPA were more frequent in responders than in nonresponders. Individual marker decreases showed limited discriminatory performance, whereas multi-marker thresholds showed complementary operating characteristics: a decrease in ≥2 markers had a sensitivity of 89.7%, while decreases in all five markers had a specificity of 93.2%. Patients with ≥3 elevated baseline markers had shorter median overall survival than those with <3 elevated markers (8.0 vs. 18.8 months; HR, 2.269; p < 0.001). Conclusions: Multi-marker assessment may provide complementary information at the time of radiological response assessment, but these exploratory findings require prospective and external validation before clinical use. Full article

Maritime Education and Training (MET) is undergoing rapid digital transformation, yet adoption of adaptive learning technologies (ALT) remains uneven, constrained by the Standards of Training, Certification and Watchkeeping (STCW) regime and by human and organizational barriers. A persistent question in the technology-acceptance literature is how individual acceptance becomes organizational readiness in safety-critical, regulated settings. This study models the translation from educator attitudes to perceived institutional readiness through the mediating role of perceived usefulness. Partial least squares structural equation modeling was applied to survey data from 104 maritime educators. The model explained 42.8% of the variance in perceived institutional readiness and 34.8% in perceived usefulness. Educator attitudes significantly predicted perceived institutional readiness (β = 0.298), and the relationship was partially mediated by perceived usefulness (indirect β = 0.202, 95% CI 0.12 to 0.35): educators must first be convinced of an ALT’s practical value before judging their institution ready to adopt it. A hypothesized moderation by professional experience was not supported and is reported as exploratory. Because predictor and outcome were self-reported by the same respondents, the outcome is interpreted as perceived readiness rather than a verified organizational state. The study contributes a validated model of the individual-to-organizational translation mechanism in MET and guidance for MET leaders integrating ALT under STCW. Full article

How much a college education pays off varies widely from one student to the next, and that variation matters for admissions, financial aid, and mobility policy. Most estimates, however, report a single average return and treat each institution as an isolated row in a table, ignoring how schools relate to one another and how outcomes are distributed across demographic groups. We present FairEdu-GCT (Graph-Enhanced Causal Transformer), a framework that couples a heterogeneous graph encoder with a Transformer sequence model and an explicit fairness penalty. Institutions, geographic regions, and academic disciplines form a typed graph whose edges record graduate flows, spatial proximity, and disciplinary overlap. A Relational Graph Attention Network (R-GAT) turns this structure into institutional ecosystem embeddings that carry peer effects, regional labor-market signals, and the spread of institutional prestige, none of which survives in tabular representations. A Transformer then encodes each student’s educational history and merges it with the institutional embedding through a cross-modal attention bridge, and a counterfactual decoding head returns the full conditional earnings distribution under alternative institutional choices rather than a single point estimate. Because students are not randomly assigned to schools, we make no claim of strict causal identification; we treat CATE and PEHE strictly as estimation-quality diagnostics for a confounding-adjusted contrast, not as evidence of a proven causal effect. We instead adjust for observed confounders through a doubly robust objective and add an equalized opportunity regularizer so that accuracy does not come at the expense of protected subgroups. On linked U.S. College Scorecard, IPEDS, and NLSY97 data (6256 institutions drawn from 7312 Title IV schools; 161,043 person-institution-year records from 8984 respondents followed for ten years), FairEdu-GCT lowers RMSE by 16.2% and Precision in Estimation of Heterogeneous Effects (PEHE) by 25.1% against the strongest baseline (Causal Forest, DragonNet, TARNet, and TabTransformer), and shrinks the demographic parity gap by 46.5%. All gains are reported with 95% confidence intervals and effect sizes over ten seeds, and an extended fairness audit (calibration, predictive parity, and subgroup robustness) confirms the improvement is not confined to the two metrics we optimize. Ablations attribute a 9.0% RMSE reduction to the R-GAT encoder alone. A group-conditional SHAP analysis further shows that graph-derived proximity to regional technology clusters is an unusually strong predictor for first-generation minority students, a signal that tabular features cannot recover and one we read as a within-model association rather than a policy lever. Full article

Background: Automated assessment of relational competencies by large language models (LLMs) is gaining traction in medical education, yet its empirical reliability remains poorly documented. Methods: We evaluated ATENA, a GPT-3.5-Turbo virtual-patient simulator deployed at the Faculty of Medicine of Nice (France), in two sequential components. First, 21 university hospital professors rated seven dimensions of realism on 7-point Likert scales. Second, across 129 student simulations of a single diagnostic disclosure scenario, expert human scores based on the empathic communication coding system (ECCS) were compared with ATENA’s automated scores using agreement metrics, Bland–Altman analysis, confusion matrix, and qualitative subcorpus analysis. Results: Realism was rated high on six of seven dimensions. Evaluative agreement was poor (ICC = 0.146), with a systematic overscoring bias (+0.80 points) and wide limits of agreement [−1.57; +3.16]. Three bias patterns emerged—score compression (76% of scores within 4.2–4.3), overscoring of weak performance, and underscoring of exemplary performance—indicating that ATENA responds to formal markers of empathy present in nearly every transcript. Conclusions: In this first-generation version of ATENA, the system distinguishes stronger from weaker interviews without being able to place them at the level assigned by expert human raters. These patterns preclude any certificatory use and support a critical, formative-only deployment grounded in instructor algorithmic literacy. The audit protocol applies to any LLM evaluator scored against human coding on a validated instrument. Full article

Background/Objectives: visceral leishmaniasis (VL) remains an important zoonotic disease in endemic Mediterranean regions, where children represent one of the populations at highest risk of developing symptomatic infection. Although pentavalent antimonials have historically been considered first-line therapy for VL, their use in Italy has become increasingly limited because of restricted availability, safety concerns, and the widespread adoption of liposomal amphotericin B (L-AmB). Methods: this multicentre retrospective observational study evaluated the contemporary management of paediatric VL in three tertiary referral centres in Catania, Southern Italy, between January 2016 and December 2025. Results: 19 children were included, with a mean age of 4.13 years. The most common clinical manifestations were prolonged fever, pancytopenia, and hepatosplenomegaly. Three different L-AmB regimens were identified, with the 10 mg/kg/day for two consecutive days schedule representing the most frequently adopted protocol. L-AmB was well tolerated; three patients (15.8%) experienced disease relapse during follow-up, all of whom responded successfully to additional L-AmB treatment, resulting in an overall clinical cure rate of 100%. Notably, no patient received pentavalent antimonials, reflecting their complete replacement in routine clinical practice. Conclusions: these findings provide real-world evidence that L-AmB has effectively become the contemporary first-line treatment and standard of care for paediatric VL in an endemic Mediterranean setting, highlighting the discrepancy between historical therapeutic paradigms and current clinical practice. Full article

Background: Abdominal pain is one of the most common complaints in community pharmacy, yet how individuals define it, which symptoms they associate with it, and how they manage it through self-care remains poorly characterized. Objective: This study aimed to investigate individual perceptions, definitions, and self-care behaviors related to abdominal pain among adults attending Italian community pharmacies and to explore healthcare-seeking behaviors and needs. Methods: A cross-sectional observational survey was conducted among adults attending community pharmacies across Italy. Eligible participants were aged ≥18 years and provided consent for data processing; individuals with cognitive or language barriers were excluded. Thirty-three SIFAC clinical pharmacists administered an expert-reviewed 18-item digital questionnaire (October–December 2025), covering pain perception, healthcare needs, and self-care behaviors. Data were analyzed descriptively. Results: 406 pharmacy customers were enrolled (66.7% female; mean age 44.3 years). Over 93% reported at least one episode in the previous 12 months. The term was applied heterogeneously across localizations, symptom profiles, and attributed causes. The pharmacist was the preferred professional for mild-to-moderate episodes (29.9%) and high-intensity episodes without alarm signs (40.2%). Conversely, the physician was most frequently consulted for high-intensity episodes with alarm signs (53.4%) and first-time episodes (16.1%). Self-medication was reported by 89.4%, with probiotics and intestinal flora products (57.4%), antispasmodics (43.8%), and antacids and gastric acid suppressants (32.5%) most commonly used. Despite this, 55.3% expressed insecurity about autonomous management. Conclusions: The findings indicate that community pharmacists represent an important point of contact in the initial management of abdominal pain among pharmacy customers. The heterogeneous symptom profiles, widespread use of self-medication, and uncertainty reported by many respondents about autonomous management support the potential value of structured symptom assessment, personalized counselling, and clear guidance on when medical evaluation is warranted. Full article

This paper examines the seismic vulnerability of historical buildings located in Lugoj City Center, an urban area of the Banat region in Western Romania, known for repeated earthquakes and rich architectural heritage. This research responds to the need for fast and practical means to help with the prioritization of risk mitigation and rehabilitation of historical cities, where detailed structural data are often limited. In light of the analysis of current European empirical, analytical, and hybrid techniques of seismic vulnerability assessment, this paper proposes a simplified empirical technique based on a systematic vulnerability index form. The suggested assessment comprises 42 indicators grouped in four weighted categories: structural aspects, architectural–artistic value, urban importance, and socio-economic importance. It is applied to 17 selected historical buildings of Lugoj City Center, including civil, religious, cultural, and infrastructural buildings. The assessment produced an average vulnerability index of 89.57, with 11 buildings classified as D1, 5 as D2, and 1 as D3, and an expected damage state under the VIII EMS-98 scenario. Thus, this study highlights the importance of combining seismic safety with heritage conservation and offers a flexible framework for urban-scale assessments, intervention planning, and preservation strategies in Lugoj and similar historic centers. This preliminary study represents the first phase of broader research addressing material degradation, monitoring, structural improvement, and socio-economic loss. Full article

Population-level evidence on gambling-related risk remains limited in Central Asia, and no validated bilingual screening instrument has been available in Kazakhstan. This study evaluated the psychometric performance of the bilingual Kazakh–Russian Problem Gambling Severity Index (PGSI) and examined the distribution and correlates of PGSI-defined gambling severity in a multi-regional sample. A total of 1015 adults aged 18–60 years were recruited across all 17 regions and three cities of republican significance. Among the 474 respondents who directly completed all nine PGSI items, internal consistency was good (Cronbach’s α = 0.846), and the first principal component accounted for 45.9% of the variance. Of these respondents, 275 (58.0%) met the conventional PGSI ≥ 8 screening threshold. The same 275 respondents constituted 27.1% of the overall survey sample (N = 1015). These percentages reflect different analytic denominators and are interpreted as sample-specific rather than as estimates of national prevalence. Item-level patterns indicated that elevated scores predominantly reflected cumulative moderate-frequency endorsements across multiple domains. In adjusted analyses, gambling expenditure and frequency showed the strongest associations with PGSI ≥ 8 status. Continuous-score analyses yielded a broadly consistent pattern, indicating that the principal behavioral associations were not solely attributable to dichotomization at the screening threshold. These findings provide initial psychometric evidence for the bilingual PGSI in Kazakhstan and support continued psychometric investigation before its use in epidemiological research or population-level screening. Full article

This study investigates how environmentally sustainable and socially responsible entrepreneurship is perceived and prioritized within the Albanian business community and explores the factors that may further support it. Based on 200 structured surveys of business representatives (each responding on behalf of a different Albanian company), this study examines how IT support and sustainability orientation affect the perceived importance and current implementation of sustainability practices. These practices include environmental practices such as waste and water management, economic aspects such as responsible growth and stakeholder collaboration, and social responsibility initiatives related to employee development, inclusion, and community engagement. The study also investigates how perceived reporting limitations affect perceived economic and circular-economy opportunities in Albanian firms. To examine the underlying structure of these dimensions, a Principal Component Analysis (PCA) was first conducted on the listwise-complete subset of the sample (n = 152), followed by a Confirmatory Factor Analysis (CFA) and Structural Equation Modeling (SEM) on the full sample (n = 200). The analysis identified six latent factors, including Ecological, Social, and Economic Sustainability, Ecological, Social, and Economic Sustainability, IT Support for Sustainability, Limitations in Sustainability Reporting, Circular Economy Activities and Opportunities, Economic Opportunities and Benefits of Sustainability Reporting (KMO = 0.903; Bartlett’s χ²(1378) = 6746.19, p < 0.001) with excellent internal consistency (Cronbach’s α = 0.813–0.946). SEM revealed that IT support for Sustainability (β = 0.42) and Ecological–Social–Economic Sustainability Orientation (β = 0.47) together account for 56% of the variance in the perceived importance of sustainability implementation drivers, while perceived reporting limitations are negatively associated with both perceived economic opportunities and circular economy activities. Overall, the findings suggest that Albanian businesses are increasingly aware of the importance of sustainable entrepreneurship and recognize the potential of the circular economy and sustainability reporting. However, realizing this potential may depend on enhancing internal capabilities, particularly IT support and strategic orientation, while simultaneously improving the institutional environment so that sustainability can become a mainstream notion. Full article

Histone acetylation, catalyzed by histone acetyltransferases (HATs) and reversed by histone deacetylases (HDACs), is a central epigenetic mechanism that regulates gene expression in eukaryotes. Identifying and characterizing these enzymes has rapidly advanced our understanding of this dynamic modification. In phytopathogenic fungi, HATs and HDACs modulate several cellular processes, including development, pathogenicity, and secondary metabolism. The filamentous fungus Fusarium graminearum causes Fusarium head blight, a destructive disease that reduces wheat yield and contaminates grain with the trichothecene mycotoxin deoxynivalenol (DON). Consequently, elucidating the regulatory networks that control fungal development, host colonization, and mycotoxin biosynthesis is essential for effective disease management. This review collates current knowledge on acetylation homeostasis in phytopathogenic fungi, with particular emphasis on F. graminearum, and evaluates evidence supporting a model wherein acetylation acts as a conditional regulatory hub rather than a universal transcriptional switch. Drawing on gene-deletion mutant analyses, large-scale acetylome profiling, and comparative genomics across multiple fungal species, we first cataloged the major HAT families—GNAT, MYST, CBP/p300, and TAF1—and HDAC families—Rpd3, Hos2, Hda1, and Sir2—and summarized the lysine acetylation and deacetylation sites they target, including H2BK11, H2BK16, H3K9, H3K14, H3K18, H3K23, H3K27, and H3K56. We then examine how acetylation homeostasis, defined as the dynamic balance between acetylation and deacetylation, regulates fungal morphogenesis, pathogenicity, and DON biosynthesis in F. graminearum, highlighting the functional interplay between HAT and HDAC complexes—exemplified by Gcn5 and Hos2 (Hdf1)—and their integration with cAMP–PKA and MAPK signaling cascades. We further analyzed how acetylation-dependent regulation intersected with proteasome-mediated protein stability, non-histone acetylation, and crosstalk with histone ubiquitination and methylation and assessed how acetylation responds to host-derived metabolites and microbial competitors, thereby extending its regulatory influence beyond canonical histone marks. Finally, comparative analyses across Magnaporthe oryzae, Aspergillus species, Botrytis cinerea, and Ustilago maydis reveal both conserved and species-specific roles of acetylation in pathogenicity. We conclude by advancing a refined conceptual model wherein acetylation operates not as a universal transcriptional on/off switch but as a conditional regulatory hub and is site-, locus-, and stage-specific and signal-responsive. Future studies that combine ChIP-seq, CUT&Tag, and multi-omics approaches will further clarify the direct molecular targets of HATs and HDACs and define their stage-specific activities during host colonization, thereby enabling the design of precise, pathogen-specific interventions. This framework offers new perspectives for developing targeted strategies to manage fungal diseases and reduce mycotoxin contamination. Full article