Search Results (131)

Rare actinobacteria are promising sources of specialized metabolites, yet genome mining still prioritizes genomes encoding many biosynthetic gene clusters (BGCs) rather than clusters that are distant from characterized chemistry. Here, we describe the isolation of a novel Jiangella strain reported from a marine, animal-associated plastisphere and place its biosynthetic repertoire in the context of the whole genus, providing a genome-based prioritization of candidate biosynthetic targets. Digital DNA-DNA hybridization (57.8%) and OrthoANIu (94.65%) values against its closest relative, J. alba DSM 45237ᵀ, support its assignment as a candidate novel species, although formal species description will require additional phenotypic and chemotaxonomic characterization. antiSMASH predicted twelve BGCs, within the range observed across the genus (7–13), of which only one matched a characterized pathway, and the Biosynthetic Novelty Index of the genome was 865.3, the fourth highest among the twelve genomes analyzed. Across these genomes, 124 BGCs grouped into 70 gene cluster families, 74% of them strain-specific. Two families without any characterized representative, a lasso-peptide family and a RiPP recognition element-containing family, were instead conserved across a subclade, down to nearly identical precursor peptides. No antimicrobial activity was detected under the conditions tested. Genus-wide comparison therefore identifies conserved yet uncharacterized families as rational priorities that cluster counts alone would miss. Full article

Localized phytochemical formulations may provide complementary strategies for controlling mucosal colonization by Streptococcus agalactiae and Streptococcus pyogenes, but computational prioritization requires orthogonal biological validation. This study integrated molecular docking against the redox-sensing transcriptional repressor Rex of S. agalactiae and a protein tyrosine phosphatase target of S. pyogenes (SP-PTP) with in vitro broth microdilution, biofilm, target-bridging, and epithelial-tolerance experiments. Isoflavone showed the most favorable natural-compound interaction with Rex (ΔG = −8.3 kcal/mol), whereas secoisolariciresinol diglucoside (SDG) led the natural-ligand ranking for SP-PTP (ΔG = −5.2 kcal/mol). The complete formulation produced MIC50 values of 0.031% and 0.063% v/v against S. agalactiae and S. pyogenes, respectively; inhibited biofilm formation by 89.2% and 80.1%; and preserved >92% epithelial viability at 1× MIC. Among the three natural candidates with complete matched broth data, target-normalized docking and composite MIC50/MIC90/MBC50 ranks were perfectly concordant in both species; pooled species-stratified Spearman analysis yielded ρ = 1.000 (exact p = 0.0556; n = 6). In contrast, the extended panel including antibacterial comparators showed negligible concordance (ρ = 0.081; p = 0.7826; n = 14). Principal component analysis assigned 74.8% of variance to an in vitro potency axis and 24.6% to a largely orthogonal docking axis. Thus, the experiments confirmed the target-specific ordering of the natural candidates but did not support extrapolation of docking rank across mechanistically heterogeneous antibacterial classes. Intracellular target inhibition, genetic causality, and component synergy remain unestablished. Full article

Background: Previous studies have examined bioactive constituents of Prunus dulcis oil, Pinus sylvestris essential oil, and related phytochemical matrices separately; however, their combined chemical profile, comparator-context molecular-docking landscape, and comparative cellular response in melanoma and non-malignant fibroblast models remain insufficiently characterized. Methods: The analyzed study samples were profiled by GC/MS and GC/FID-based fatty-acid methyl ester analysis. An archived molecular-docking dataset was used to summarize structurally plausible interactions of six formulation-associated markers with eight melanoma-relevant or melanoma-adjacent targets and to present representative three-dimensional complexes. Because complete protocol metadata and co-crystallized-ligand redocking records were unavailable, the computational findings were interpreted descriptively. Neutral-red uptake assays assessed the 24 h viability of B16F10 melanoma cells and MRC-5 fibroblasts after exposure to each oil, the dual-oil formulation, or cisplatin. Four-parameter logistic models provided estimated IC₅₀ values, and exact two-sided permutation tests were used for Spearman rank analyses. Results: The dual-oil formulation yielded estimated IC₅₀ values of 1.42% v/v in B16F10 cells and 4.85% v/v in MRC-5 cells, corresponding to an apparent selectivity index of 3.41. The complete eight-concentration series was non-monotonic and showed no significant rank association (B16F10: ρs = −0.4286, exact p = 0.2992; MRC-5: ρs = −0.3810, exact p = 0.3599). In a post hoc analysis of the descending branch (≥0.37% v/v), the association was perfect in B16F10 cells (ρs = −1.0000, exact p = 0.0167) but did not reach significance in MRC-5 cells (ρs = −0.9000, exact p = 0.0833). The docking matrix identified target-dependent numerical prioritization patterns; however, small score differences were not interpreted as evidence of stronger binding or cellular target engagement. Conclusions: The findings define an exploratory chemical–computational–cellular framework and a preliminary formulation-level viability phenotype. They do not establish synergy, apoptosis, pathway modulation, therapeutic efficacy, or clinical safety. Independent multi-batch chemical confirmation, a fully documented and redocking-validated computational protocol, expanded melanoma and normal-skin cell panels, orthogonal functional assays, longer exposure periods, mechanistic validation, and subsequent in vivo studies are required. Full article

Background: The EU Health Technology Assessment Regulation (EU-HTA R), effective January 2025, mandates Joint Clinical Assessments (JCAs) to harmonize HTA across Member States. However, its implementation raises fundamental questions about methodological coherence, institutional capacity, and epistemological alignment. Objectives: This manuscript (1) systematically assesses whether the stated strategic and operational objectives of the EU-HTA R are achievable under current implementation conditions; (2) examines the implications for EU institutional legitimacy if these objectives are not met; and (3) proposes an epistemological framework as a prerequisite for developing a coherent joint HTA methodology. Methods: We conducted a critical policy analysis of the EU-HTA R, its implementing guidance documents, and published templates, supplemented by a comparative review of Member State HTA methodologies and their underlying philosophical foundations. Results: The analysis reveals that the EU-HTA R is unlikely to achieve its strategic goals under current conditions. Key findings include: guidance documents of substandard methodological quality; a restricted assessment scope that excludes scientific judgement and contextualization; insufficient resources and additional workload for national HTA bodies without reducing existing obligations; unresolved epistemological divergences among Member States spanning Bayesian vs. frequentist approaches, Fisher vs. Neyman–Pearson frameworks, and utilitarian vs. deontological ethical foundations; and procedural shortcomings in stakeholder consultation and expert involvement. These shortcomings risk undermining the epistemic authority and legitimacy of EU institutions. Conclusions: Prior epistemological and normative alignment across Member States is a prerequisite for any robust shared HTA methodology. Revisions to the EU-HTA R and comprehensive updates of guidance documents are necessary, with concrete safeguards—including independent peer review, identified authorship, and adequate resourcing—to ensure substantive rather than merely nominal implementation. A phased roadmap is proposed: establishing clear objectives, aligning epistemological foundations, developing institutional structures, and creating operationally consistent guidance. Full article

The present study addressed a timely and important issue in cognitive and media psychology about the relationship between media multitasking and cognition. This study examined attention control, working memory, convergent associative thinking, and fluid reasoning, examining multiple functions within the same analytical framework and moving beyond the narrow focus on single cognitive domains that characterizes much prior research. The main aim was to deepen the understanding of the associations of media multitasking with these core domains of human cognition. A total of 214 healthy young adults (18–30 years) completed the Short Media Multitasking Questionnaire, Raven’s Progressive Matrices, the Digit Span Test, the Trail-Making Test, and the Remote Associates Task. Multivariate general linear models and subsequent regression analyses were performed while controlling for age and gender. The results did not reveal a significant overall association between media multitasking and the combined cognitive outcomes. At the univariate level, higher media multitasking scores were associated with lower performance on the Remote Associates Task, although the observed effect size was small. Given the cross-sectional design and reliance on self-reported media multitasking, longitudinal studies employing objective measures of media multitasking use are needed to clarify the robustness and directionality of these associations. Full article

The increasing environmental impacts of conventional agriculture have intensified the search for farming approaches capable of balancing food production, resource efficiency, and ecosystem protection. In this context, multiple sustainability-oriented approaches have emerged, including organic agriculture, integrated production, sustainable agriculture, and regenerative agriculture. This study develops a comparative framework based on a structured literature review covering the period January 2000–March 2026 to assess these approaches from both practice-based and governance perspectives. The analysis examines key environmental management dimensions, alongside governance-related aspects. The results reveal substantial convergence across approaches regarding core environmental practices, including cover cropping, crop diversification, reduced tillage, and input optimisation. However, important differences emerge in system integration, governance structures, and sustainability objectives. Efficiency-oriented approaches mainly prioritise productivity and resource optimisation, whereas regenerative and organic approaches place stronger emphasis on ecosystem restoration and soil health. The study highlights the limitations of current sustainability assessment frameworks and emphasises the need for integrated, outcome-based approaches capable of capturing both environmental impacts and regenerative benefits across agricultural systems. Full article

The erythrocyte sedimentation rate (ESR) is a routine marker of inflammation in human medicine, and it is influenced by erythrocyte features and the level of some plasma proteins. The Westergren method is the reference technique in humans; however, this manual technique has been scarcely used in animals and has not been validated. An automated veterinary in-clinic device (MINI-PET) is able to measure ESR on EDTA-blood tubes. This study aimed to evaluate the comparability of ESR values measured with two tests in cats and dogs admitted to a veterinary clinic and in anemic individuals. Analytical comparability and decision limits were calculated in both species and clinical groups. Comparisons were also made between the two species. The two ESR methods had different decision limits in the investigated population of dogs and cats, and a method-specific interpretation of their results is suggested. Healthy cats had significantly higher values than healthy dogs using both the Westergren and MINI-PET methods. By both methods, anemic individuals had higher ESR values than the matched subgroups with erythrogram values within the reference range, probably due to concurrent inflammation in most anemic animals studied. In general, ESR measures should be evaluated in conjunction with erythrogram values. Full article

The sustainable management of chemical fumigants in intensive horticulture represents one of the most complex challenges in European agricultural policy, requiring the integration of agronomic knowledge, regulatory frameworks, economic viability, and stakeholder perspectives. This study proposes and tests a multi-phase consultation methodology designed to bridge the gap between individual expert knowledge and collective, evidence-based consensus, moving from qualitative field-based elicitation to structured multidisciplinary engagement and incorporating both scientific data and practical experience. A total of 72 experts were involved across two phases. In phase 1, in-depth face-to-face interviews (n = 18) captured field-level knowledge on integrated pest management strategies, risk perception, and decision-making criteria, including the economic sustainability of production systems, a dimension prioritized in the European Commission’s Vision for Agriculture and Food. Phase 2 consisted of a one-day multistakeholder event (n = 54)—bringing together researchers, regulators, industry representatives, and farmers—to confront qualitative findings with experimental data on operator safety, groundwater protection, and consumer residues. This deliberate transition from individual perception to informed, shared consensus represents the methodological core of the approach and its most distinctive contribution. The phase 1 results showed that the majority of experts considered chemical fumigants currently indispensable, while recognizing complementary strategies—particularly solarization and natural substances—as valuable supporting tools. The phase 2 experimental data confirmed operator exposure below regulatory thresholds, no groundwater contamination under professional application conditions, and the absence of detectable residues in treated crops. The results demonstrate that this structured consultation can generate actionable knowledge for integrated nematode and soil-borne disease management, with a methodology replicable across other complex regulatory and agronomic contexts within the European framework. Full article

This paper summarizes an analysis of the Joint Clinical Assessment (JCA) subgroup’s recommendations for systematic literature reviews (SLRs). While the JCA offers clear guidance on study classification, exclusion criteria reporting, and PRISMA diagram use, several of its recommendations diverge from established best practices in evidence-based medicine (EBM). A comparison with recognized guidelines, such as those from Cochrane and EUnetHTA, reveals that the JCA guidance may lack reliability, comprehensiveness, and reproducibility. Aligning JCA recommendations with gold standards in SLR methodology would address these shortcomings and enhance methodological rigor. Full article

Four years after the European Regulation on Health Technology Assessment (EU HTAR) came into force and a little over a year after the implementation phase of the Regulation started, with the publication of the first Joint Clinical Assessment (JCA) report imminent, it is good timing to take a step back and revisit what has been achieved and look at what the main challenges on the way forward are [...] Full article

Seabed studies are a valuable tool in the investigation of active continental margins, both in volcanic and sedimentary settings. Being an example of a slope-confined sedimentary basin, the “Ammontatura” slope basin has been discussed using multibeam bathymetry and seismo-stratigraphic data matched with previously available cores. Being a significant tectonically controlled slope bounded by the Capri-Sorrento regional fault, the southern slope of the Sorrento Peninsula has been explored employing a dense network of bathymetric profiles. The data have shown the underwater extension of the mainland drainage system, comprising a dense network of submarine gullies, reflecting the onshore drainage system. The northern Ischia debris avalanche deposits have been studied through seismo-stratigraphic data, previously unpublished, whose geologic evolution has been placed within the Quaternary stratigraphic framework of Ischia. This research revealed how several geological events, such as the tectonic phases, the emplacement of erosional and depositional domains, the volcanic eruptions, and the reworking of volcanic deposits, interacted in controlling the sedimentary structure of slope basins. In the Ammontatura slope basin, the tectonic setting has probably controlled its emplacement along a NE–SW trending regional fault, resulting from the submarine prolongation of the Sarno-Sebeto normal fault, while intense reworking of volcaniclastic deposits acted as the main control factor in slope settings. Full article

Indirect treatment comparisons (ITCs) are essential in the context of joint clinical assessments (JCAs) under Regulation (European Union [EU]) 2021/2282, bridging evidence gaps where head-to-head data are lacking and enabling assessment across diverse national patient, intervention, comparator, and outcome (PICO) requirements. This paper critically reviews the EU Health Technology Assessment Coordination Group’s (HTACG) guidelines on direct and indirect comparisons, with particular focus on ITCs. While the guidelines promote transparency and rigorous evaluation of assumptions, they adopt a restrictive stance on assumption violations, the use of unanchored comparisons, and population-adjusted methods such as matching-adjusted indirect comparisons (MAIC) and simulated treatment comparisons (STC). The guidance shows limited support for Bayesian methods and undervalues meta-regression in favor of subgroup analyses. Operational implications for health technology developers (HTDs) are substantial, including new requirements for dual systematic reviews, multiple network structures, and shifted null hypothesis testing. Moreover, the guidelines effectively dissuade the use of non-randomized comparisons in rare or rapidly evolving indications and may inadvertently hinder access to effective treatments. Emerging practices such as external control arms (ECA) or target trial emulation are underdeveloped. Notably, there is no indication that the guidelines are grounded in systematic methodological validation studies. As JCAs evolve, greater methodological flexibility, empirical grounding, and clear operational guidance will be essential. Refining the guidelines along these principles would enhance their practical utility, mitigate intrinsic assessment variability, support consistent assessments across Member States (MS), and ultimately improve patient access to innovative therapies. Full article