Search Results (468)

Background and Objectives: In early-stage HER2-positive breast cancer, ado-trastuzumab emtansine (T-DM1) has been adopted as the preferred adjuvant approach for patients left with residual invasive disease despite neoadjuvant therapy. The influence of different neoadjuvant regimens on subsequent outcomes in real-world settings remains uncertain. Materials and Methods: From 2019 to 2025, 102 patients treated with adjuvant T-DM1 following surgery after neoadjuvant chemotherapy were retrospectively assessed. Neoadjuvant regimens included doxorubicin plus cyclophosphamide followed by trastuzumab-paclitaxel, doxorubicin plus cyclophosphamide with pertuzumab–trastuzumab–docetaxel, or docetaxel–carboplatin–trastuzumab–pertuzumab. Clinical features, treatment response, survival, and toxicity were evaluated. Results: The mean age of the cohort was 49.7 years, and the majority of patients (80.4%) were aged 40 years or older. Hormone receptor positivity was 82.0%, and invasive ductal carcinoma accounted for 97.1% of cases. Regional responses included 39.2% with axillary pCR despite residual breast lesions, and 5.9% with breast pCR accompanied by axillary disease. Kaplan–Meier analysis demonstrated disease-free survival rates of 100%, 95.2%, and 92.2% at 1, 3, and 5 years, respectively. Adverse events were predominantly grade 1–2, while grade 3–4 toxicities occurred in under 5% of the cohort. Baseline characteristics varied across regimens, reflecting real-world treatment preferences, but survival outcomes remained comparable. Conclusions: Adjuvant T-DM1 was associated with high survival rates and manageable toxicity across different neoadjuvant regimens, underscoring its consistent benefit in routine clinical practice. Full article

Background: Autism Spectrum Disorder (ASD) affects ~1 in 36 children and is increasingly studied as a candidate for non-invasive neuromodulation. Two of the most widely applied modalities are quantitative EEG (QEEG)-guided repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS), both targeting the dorsolateral prefrontal cortex (DLPFC). While both have shown promise, questions remain regarding their relative clinical profiles and scalability. Objective: To conduct a within-cohort reanalysis of QEEG-guided rTMS outcomes in paediatric ASD and to contextualise these findings alongside published reports of home-supervised tDCS. Methods: Individual participant data (n = 56, ages 6–17) from a prospective rTMS cohort were reanalysed, focusing on the Social Responsiveness Scale (SRS-2), Autism Diagnostic Observation Schedule (ADOS-2), Aberrant Behavior Checklist (ABC), Repetitive Behavior Scale–Revised (RBS-R), and QEEG biomarkers. Findings were then situated within a narrative synthesis of published paediatric tDCS trials, which consistently report caregiver-supervised feasibility but did not provide raw, baseline-adjusted data suitable for reanalysis. Results: rTMS was associated with large within-cohort improvements (Hedges’ g ≈ 1.0–1.6), including an 11-point reduction in SRS-2 T-scores, a 12-point reduction in ABC totals, and robust QEEG normalisation (β/γ suppression, α enhancement). Published tDCS studies report moderate, clinically meaningful improvements in social communication, executive functioning, and regulation (Cohen’s d ≈ 0.4–0.6), with excellent adherence and no serious adverse events. Conclusions: rTMS produced robust behavioural and neurophysiological improvements within its cohort, while published tDCS trials demonstrate moderate, feasible benefits in home settings. Because of incomplete baseline data and protocol differences, no direct statistical comparison was possible. These findings suggest complementary roles: rTMS as a high-intensity clinic-based intervention, and tDCS as a scalable, family-centred option. A stepped-care framework that combines both modalities should be considered hypothesis-generating only and requires validation in harmonised, randomised controlled trials. Full article

Smart manufacturing demands adaptive, scalable, and human-centric solutions for predictive maintenance. This paper introduces the concept of Agentic AI, a paradigm that extends beyond traditional multi-agent systems and collaborative AI by emphasizing agency: the ability of AI entities to act autonomously, coordinate proactively, and remain accountable under human oversight. Through federated learning, edge computing, and distributed intelligence, the proposed framework enables intentional, goal-oriented monitoring agents to form self-organizing predictive maintenance ecosystems. Validated in a ceramic manufacturing facility, the system achieved 94% predictive accuracy, a 67% reduction in false positives, and a 43% decrease in unplanned downtime. Economic analysis confirmed financial viability with a 1.6-year payback period and a €447,300 NPV over five years. The framework also embeds explainable AI and trust calibration mechanisms, ensuring transparency and safe human–machine collaboration. These results demonstrate that Agentic AI provides both conceptual and practical pathways for transitioning from reactive monitoring to resilient, autonomous, and human-centered industrial intelligence. Full article

Genetic information, whether inside or outside the nucleus, is exposed to a variety of harmful physico-chemical factors. Although DNA damage repair systems have been extensively studied, little information about post-repair and non-genomic DNA damage metabolism is available in the literature. Adenosine deaminase (ADA) is an abundant enzyme found on both sides of the cell membrane that regulates the concentration of adenine derivatives. In this article, it has been shown that 7,8-dihydro-8-oxo-2′-deoxyadenosine (^OXOdAdo) and (5′R/S) 5′,8-cyclo-2′-deoxyadenosine ((5′R/S)cdAdo) are suitable substrates for ADA. For this purpose, theoretical Density Functional Tight Binding and RP-HPLC analyses were applied. The products of ADA activity, i.e., ^OXOdIno (7,8-dihydro-8-oxo-2′-deoxyinosine) and (5′R/S) cdIno ((5′R/S) 8-cyclo-2′-deoxyinosine), were identified and confirmed by high-resolution mass spectroscopy. Although the (5′R) and (5′S)cdAdo enzymatic deamination processes are much slower (34% and 32% after 168 h, respectively) than the process observed for dAdo, 5′,8-cyclo-2′-deoxyinosine should be considered when monitoring cyclopurine levels in physiological fluids. The same should be considered in the case of ^OXOdAdo, which is completely converted to ^OXOdIno within one minute and may therefore be less visible than ^OXOdGuo during mass spectroscopy analysis. Both these observations are important, given the abundance of 2′-deoxyadenosine on both sides of the cell membrane and its potential conversion into ^OXOdAdo and (5′R/S)cdAdo. They may also explain why the observed level of ^OXOdAdo is much lower than that of ^OXOdGuo in cells and physiological fluids, even though their difference in ionisation potential is only 0.25 eV. Future studies are needed to further investigate the metabolism of DNA damage and to identify the enzymes involved in nucleic acid biochemistry. Full article

Preimplantation genetic testing for monogenic disorders (PGT-M) is a powerful tool for identifying genetic disorders prior to gestation. For hemoglobinopathies like thalassemias and sickle cell disease, PGT-M offers a preventative strategy to ensure that only embryos deemed genetically healthy are transferred. A comprehensive review of 22 original articles explores and summarizes the existing evidence on PGT-M techniques in hemoglobinopathies. The review focuses on key aspects such as accuracy, benefits, and drawbacks related to various hemoglobinopathies. Given the limited quantity of DNA obtained from an embryo biopsy, whole genome amplification (WGA) is a critical step for amplifying the sample. One of the available methods of WGA, multiple displacement amplification (MDA) is one of the most widely adopted method with acceptable allele drop-out (ADO) rates for hemoglobinopathies compared with traditional methods. Dealing with ADO constitutes a primary technical obstacle in PGT-M. The failure to amplify one allele in single-cell analysis is a major factor limiting the overall diagnostic accuracy of the procedure. To mitigate this issue, PCR-based and next-generation sequencing (NGS)-based approaches are employed. These methods incorporate linkage analysis with genetic markers such as short tandem repeats (STRs) or single-nucleotide polymorphisms (SNPs) to reduce the risk of incorrect interpretations from ADO and enhance the proportion of conclusive results. A future direction for PGT-M that involves the development of non-invasive methods (niPGT) will be included and discussed. Full article

Oroxylum indicum is a traditional food in Asia rich in flavonoids and health-related effects. However, research into the use of O. indicum as a functional food ingredient is overlooked. This review synthesized literature from 2010 to 2025 using the PRISMA framework, bibliometric mapping, and the Antecedents–Decisions–Outcomes (ADO) model. In total, 185 articles were included, covering in vitro, in vivo, in silico, and limited human investigations. Bibliometric analysis shows a growing global interest, with recent focuses on molecular docking, cancer, and conservation. Phytochemical investigations consistently report key flavonoids, including baicalein, baicalin, oroxylin A, chrysin, oroxin A, and oroxin B. Studies have linked these compounds to different health benefits, including antioxidants, cardiovascular, and neurological protection. Application of the ADO framework organized research into motives, methods, and outcomes, and highlighted scientifically validated ethnomedicinal uses, such as diabetes and liver protection. Meanwhile, gaps, including obesity-related studies, long-term safety, and clinical trials, remain. More importantly, although young fruits are locally consumed as vegetables or beverages, translation into functional foods is limited by bitterness, lack of standardized preparations, and insufficient dose–response data at dietary intakes. This review discusses the bioactive potential of O. indicum and outlines research priorities for its development in functional food. Full article

This paper introduces cognitive adaptivity as a novel framework for addressing human factors in cybersecurity during the Industry 5.0–6.0 transition, with a focus on hard-to-abate industries where digital transformation intersects sustainability constraints. While the integration of IoT, automation, digital twins, and artificial intelligence expands industrial efficiency, it simultaneously exposes organizations to increasingly sophisticated social engineering and AI-powered attack vectors. Traditional resilience-based models, centered on recovery to baseline, prove insufficient in these dynamic socio-technical ecosystems. We propose cognitive adaptivity as an advancement beyond resilience and antifragility, defined by three interrelated dimensions: learning, anticipation, and human–AI co-evolution. Through an in-depth case study of the ceramic value chain, this research develops a conceptual model demonstrating how organizations can embed trust calibration, behavioral evolution, sustainability integration, and systemic antifragility into their cybersecurity strategies. The findings highlight that effective protection in Industry 6.0 environments requires continuous behavioral adaptation and collaborative intelligence rather than static controls. This study contributes to cybersecurity literature by positioning cognitive adaptivity as a socio-technical capability that redefines the human–AI interface in industrial security. Practically, it shows how organizations in hard-to-abate sectors can align cybersecurity governance with sustainability imperatives and regulatory frameworks such as the CSRD, turning security from a compliance burden into a strategic enabler of resilience, competitiveness, and responsible digital transformation. Full article

This study advances toward establishing the theoretical foundations of Industry 6.0 by developing a comprehensive framework that integrates artificial intelligence (AI), decentralized control systems, and cyber–physical production environments for intelligent, sustainable, and adaptive manufacturing. The research employs a tri-modal methodology (deductive, inductive, and abductive reasoning) to construct a theoretical architecture grounded in five interdependent constructs: advanced technology integration, decentralized organizational structures, mass customization and sustainability strategies, cultural transformation, and innovation enhancement. Unlike prior conceptualizations of Industry 6.0, the proposed framework explicitly emphasizes the cyclical feedback between innovation and organizational design, as well as the role of cultural transformation as a binding element across technological, organizational, and strategic domains. The resulting framework demonstrates that AI-driven decentralized control systems constitute the cornerstone of Industry 6.0, enabling autonomous real-time decision-making, predictive zero-defect manufacturing, and strategic organizational agility through distributed intelligent control architectures. This work contributes foundational theory and actionable guidance for transitioning from centralized control paradigms to AI-driven distributed intelligent manufacturing control systems, establishing a conceptual foundation for the emerging Industry 6.0 paradigm. Full article

This paper reviews the current research landscape on Personal Saving Behavior, focusing on its antecedents and outcomes. Using bibliographic analysis of publication trends—highlighting productive authors, journals, countries, and keywords—the literature is synthesized. A framework-based systematic review is conducted to understand factors influencing saving behavior and its effects, employing the TCM framework to analyze theory, context, and methods across selected studies. Additionally, the ADO framework is used to discuss antecedents, decisions, and outcomes related to personal saving behavior. The review consolidates 112 articles from 2000 to 2025, grouping unique antecedents into nine categories. It also examines how specific antecedents positively or negatively impact saving decisions and outcomes. Finally, using the TCM and ADO frameworks, the study identifies research gaps and discusses future directions, especially from the perspectives of behavioral economics and critical incidents. Full article

This study analyzes the spectral properties of word-initial and intervocalic ejectives in Wolaytta, an Omotic language of southern Ethiopia. Using tokens embedded in three vowel contexts, we examined mean burst intensity, spectral moments, and vowel perturbation following ejection. Results show that ejectives adjacent to high front vowels were produced with greater intensity, supporting the hypothesis that increased oral cavity tenseness correlates with acoustic energy. Centroid and standard deviation differentiate place of articulation, while skewness and kurtosis distinguish singleton from geminate ejectives. Post-ejective vowel pitch and spectral tilt varied systematically with the ejectives’ place of articulation, indicating creaky phonation induced by ejection. Overall, the findings enhance our understanding of factors impacting acoustic features of ejectives. Full article

This study investigates how AI-driven innovations are reshaping manufacturing value chains through the transition from Industry 4.0 to Industry 6.0, particularly in resource-intensive sectors such as ceramics. Addressing a gap in the literature, the research situates the evolution of manufacturing within the broader context of digital transformation, sustainability, and regulatory demands. A mixed-methods approach was employed, combining semi-structured interviews with key industry stakeholders and an extensive review of secondary data, to develop an Industry 6.0 model tailored to the ceramics industry. The findings demonstrate that artificial intelligence, digital twins, and cognitive automation significantly enhance predictive maintenance, real-time supply chain optimization, and regulatory compliance, notably with the Corporate Sustainability Reporting Directive (CSRD). These technological advancements also facilitate circular economy practices and cognitive logistics, thereby fostering greater transparency and sustainability in B2B manufacturing networks. The study concludes that integrating AI-driven automation and cognitive logistics into digital ecosystems and supply chain management serves as a strategic enabler of operational resilience, regulatory alignment, and long-term competitiveness. While the industry-specific focus may limit generalizability, the study underscores the need for further research in diverse manufacturing sectors and longitudinal analyses to fully assess the long-term impact of AI-enabled Industry 6.0 frameworks. Full article

The European Union (EU) is fundamentally transforming sustainability governance by developing dual approaches that extend far beyond traditional environmental policy. This study explores how EU institutions integrate strategic sustainability, which embeds environmental goals within economic security and geopolitical frameworks, with systemic sustainability, which emphasizes circularity, stakeholder engagement, and long-term resilience. Using hermeneutic methodology, the research analyzes key policy documents including the European Green Deal, Circular Economy Action Plan, and Carbon Border Adjustment Mechanism to reveal how sustainability narratives align with strategic autonomy and economic resilience. The findings demonstrate that sustainability governance now operates as a multi-dimensional paradigm balancing sovereignty, competitiveness, and inclusiveness. The study introduces the Neo-Sovereign Strategic Management (NSSM) framework, conceptualizing sustainability as a strategic field where economic security, geopolitical influence, and environmental objectives converge. This dual strategic–systemic approach represents a paradigm shift from standalone environmental goals toward integrated governance that positions sustainability as both economic driver and geopolitical asset. The research contributes to the sustainability governance literature by providing actionable insights for policymakers navigating the complex intersection of environmental objectives, economic security, and strategic autonomy in contemporary EU governance. Unlike existing models such as multi-level governance or resilience theory, the frameworks conceptualize sustainability as a strategic field where sovereignty, competitiveness, and legitimacy converge. Full article

We report the mode of interaction of copper(II) ions with tyrosine (Tyr, L) in binary and ternary systems with Ado, AMP, ADP, and ATP (L’) as second ligands in an aqueous solution. The composition and overall stability constants of the complexes formed were determined using the potentiometric method. The coordination sites were identified through spectroscopic (VIS, EPR, IR) methods, as well as DFT and computational–molecular modeling. In the binary Cu(II)/Tyr system, the main reaction centers of the ligand molecule involved in the interactions with copper(II) ions are nitrogen (-NH₂ group), as well as oxygen atoms (-COO⁻ group), as confirmed, for example, by comparing the mode of coordination in the CuH₂(Tyr)₂ species and the [CuH₂(Tyr)₂(H₂O)] × 1.5H₂O solid complex obtained. In the ternary Cu(II)/L/L’ systems, MLHxL’ and mixed MLL’ protonated complexes are formed. Only in the ATP system were no MLL’(OH)_x hydroxocomplexes found. An increase in the number of phosphate groups in ADP and ATP molecules has no effect on their participation in the coordination in ternary species, and these ligands interact just like in binary species (i.e., in ADP, both α- and β-phosphate groups, and in ATP, only the γ-phosphate group). It was observed that the introduction of a second ligand into the Cu(II)/Tyr system did not change, over the entire pH range studied, the tyrosine coordination mode. Full article

Background: Dental caries arise from polymicrobial biofilms and require interventions that address both local virulence and systemic burden. Methods: A curated set of 124 neem-derived phytochemicals was screened against Streptococcus mutans glucansucrase (3AIC) and Staphylococcus aureus DNA gyrase B (3U2D) using harmonized AutoDock Vina parameters. Ligand standardization and receptor preparation followed conventional protocols. Results: The most favorable docking scores reached −10.7 kcal·mol⁻¹ for 3AIC and −8.9 kcal·mol⁻¹ for 3U2D. Redocking produced pose RMSD values of 1.52 Å (3AIC) and 0.96 Å (3U2D). Per-receptor ADMET profiles for the six top-ranked compounds indicated median logP values of 4.93 (3AIC) and 4.52 (3U2D), median TPSA values of 80.3 and 62.9 Ų, median rotatable bonds of 2.5 and 1.0, and median QED values of 0.41 and 0.76, respectively. Conclusions: An integrated, dual-target screen prioritized neem constituents with plausible local anti-cariogenic activity and physicochemical features compatible with systemic disposition. These in silico findings motivate targeted experimental validation. Full article

This study focused on the development and characterization of polyvinyl alcohol (PVA)- and konjac glucomannan (KGM)-based composite films enriched with natural bioactive additives. A PK (PVA/KGM) matrix with the optimum tensile strength was selected, and five film formulations were prepared by incorporating Aronia melanocarpa extract (AME), red dragon fruit extract (DFE), and thyme essential oil (TEO). TEO was also introduced via a Pickering emulsion (PE) technique. The total phenolic content (TPC) and free radical scavenging activity (FRSA) of extracts and films were determined, where AME exhibited the highest antioxidant activity (TPC: 243 mg GAE/g; FRSA: 81.7%). The additive-free PK film displayed limited antioxidant activity (18%), while antioxidant capacity significantly improved with extract and EO incorporation. The PK-A film (AME-added) demonstrated the highest tensile strength and lowest water vapor permeability, supported by increased local crystallinity detected in XRD. Color analysis indicated dominant red-violet tones in AME films and greenish-yellow tones in DFE films. FTIR confirmed that no new chemical bonds were formed between active compounds and the polymer matrix. DSC thermograms revealed consistent melting peaks (~150 °C) for all films, while Tg varied from 37 to 73 °C depending on additive type, reflecting plasticization effects of extracts and the counterbalancing effect of essential oil. The most hydrophobic (76.8°) and opaque sample was PK-ADO, prepared via the PE technique. Overall, natural extracts improved the structural, thermal, barrier, and antioxidant properties of PK films. Full article