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Search Results (239)

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22 pages, 5082 KB  
Article
A Two-Stage Deep Learning Framework for AI-Driven Phishing Email Detection Based on Persuasion Principles
by Peter Tooher and Harjinder Singh Lallie
Computers 2025, 14(12), 523; https://doi.org/10.3390/computers14120523 - 1 Dec 2025
Viewed by 618
Abstract
AI-generated phishing emails present a growing cybersecurity threat, exploiting human psychology with high-quality, context-aware language. This paper introduces a novel two-stage detection framework that combines deep learning with psychological analysis to address this challenge. A new dataset containing 2995 GPT-o1-generated phishing emails, each [...] Read more.
AI-generated phishing emails present a growing cybersecurity threat, exploiting human psychology with high-quality, context-aware language. This paper introduces a novel two-stage detection framework that combines deep learning with psychological analysis to address this challenge. A new dataset containing 2995 GPT-o1-generated phishing emails, each labelled with Cialdini’s six persuasion principles, is created across five organisational sectors—forming one of the largest and most behaviourally annotated corpora in the field. The first stage employs a fine-tuned DistilBERT model to predict the presence of persuasion principles in each email. These confidence scores then feed into a lightweight dense neural network at the second stage for final binary classification. This interpretable design balances performance with insight into attacker strategies. The full system achieves 94% accuracy and 98% AUC, outperforming comparable methods while offering a clearer explanation of model decisions. Analysis shows that principles like authority, scarcity, and social proof are highly indicative of phishing, while reciprocation and likeability occur more often in legitimate emails. This research contributes an interpretable, psychology-informed framework for phishing detection, alongside a unique dataset for future study. Results demonstrate the value of behavioural cues in identifying sophisticated phishing attacks and suggest broader applications in detecting malicious AI-generated content. Full article
(This article belongs to the Section AI-Driven Innovations)
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11 pages, 439 KB  
Article
Kinship as Evidence: Genealogy, Law, and the Politics of Recognition
by Oluwaseyi B. Ayeni, Oluwajuwon M. Omigbodun and Oluwakemi T. Onibalusi
Genealogy 2025, 9(4), 138; https://doi.org/10.3390/genealogy9040138 - 1 Dec 2025
Viewed by 238
Abstract
Genealogy has shifted from the private domain of family history to a central mechanism in law and governance. This article examines how genealogical claims are used as evidence in three critical domains: citizenship, inheritance, and indigenous recognition. Using a comparative socio-legal approach, the [...] Read more.
Genealogy has shifted from the private domain of family history to a central mechanism in law and governance. This article examines how genealogical claims are used as evidence in three critical domains: citizenship, inheritance, and indigenous recognition. Using a comparative socio-legal approach, the study analyses statutes, case law, and interdisciplinary scholarship to reveal both convergences and divergences in evidentiary practice. Across legal systems, descent remains decisive in allocating rights and recognition, yet the hierarchy of proof varies. Civil law states privilege documentary records, common law courts increasingly rely on DNA testing, and indigenous forums continue to give authority to oral genealogies. The rapid growth of genetic genealogy databases adds new complexity. While these technologies expand opportunities for verification, they also create ethical challenges concerning privacy, consent, and the extension of genealogical data into surveillance. To address these dynamics, the article develops an evidence regime framework that treats genealogy as criteria of proof, media of proof, institutional gatekeepers, and social consequences. The findings highlight genealogy’s dual character: it enables claims to rights yet also reproduces exclusion when evidentiary hierarchies are imposed. The article argues for pluralist standards that respect documentary, genetic, and oral genealogies, offering a pathway toward more inclusive and just legal recognition. Full article
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23 pages, 330 KB  
Article
Intergenerational Transfers in a Tractable Overlapping- Generations Setting
by James Feigenbaum, T. Scott Findley and Sepideh Raei
Mathematics 2025, 13(23), 3769; https://doi.org/10.3390/math13233769 - 24 Nov 2025
Viewed by 310
Abstract
Motivated by the Generation-Skipping Transfer Tax (GSTT) in the United States, we examine how varying estate tax rates by the heir’s age affects welfare. Methodologically, we introduce a parsimonious constant elasticity of substitution (CES) bequest utility that is markedly more tractable than the [...] Read more.
Motivated by the Generation-Skipping Transfer Tax (GSTT) in the United States, we examine how varying estate tax rates by the heir’s age affects welfare. Methodologically, we introduce a parsimonious constant elasticity of substitution (CES) bequest utility that is markedly more tractable than the altruistic specifications commonly used in the literature, delivering closed-form optimal rules and transparent parameterization. Using this new framework, we provide a proof of concept showing how transfers from older to younger generations can enhance equilibrium welfare in a dynamically efficient economy à la Samuelson (1975). We embed the tractable bequest utility in a two-period overlapping-generations model with age-dependent estate tax schedules. Numerical exercises—parameterized to the fact that estate tax revenue is small relative to labor income taxation—indicate that lowering the tax rate on bequests to younger heirs (grandchildren) relative to older heirs (adult children) raises the present value of lifetime resources and overall welfare, effectively reversing the logic of the current GSTT. The findings highlight a practical avenue for implementing a “reverse social security” transfer from old to young that can improve welfare in dynamically efficient economies. Full article
(This article belongs to the Special Issue Advances in Theoretical and Empirical Economic Modeling)
54 pages, 11655 KB  
Article
Comparative Assessment of Finnish University Campus Transformation Using New European Bauhaus–Inspired Sustainability Indicators
by Elżbieta Komarzyńska-Świeściak, Magdalena Anna Strauchmann and Aleksandra Urszula Tądel
Sustainability 2025, 17(22), 10425; https://doi.org/10.3390/su172210425 - 20 Nov 2025
Viewed by 578
Abstract
University campuses are key testbeds for circular and climate-resilient transformation. This study evaluates how redevelopment strategies at eight Finnish campuses align with long-term environmental and social goals using indicators derived from the New European Bauhaus (NEB) framework. A mapping and qualitative synthesis of [...] Read more.
University campuses are key testbeds for circular and climate-resilient transformation. This study evaluates how redevelopment strategies at eight Finnish campuses align with long-term environmental and social goals using indicators derived from the New European Bauhaus (NEB) framework. A mapping and qualitative synthesis of 97 peer-reviewed publications (2015–2024) was combined with a comparative analysis of sustainability strategies, carbon-neutrality roadmaps, and campus development strategies (2010–2024). Indicators were formulated based on campus-specific challenges and NEB core values—sustainability, inclusion, and esthetics—and operationalized across five areas: blue-green infrastructure, low-emission mobility, student housing, carbon reduction and renewables, and cultural heritage/community integration. Results show strong commitments to energy efficiency, mobility, and biodiversity. However, socio-spatial dimensions—student housing, participatory inclusion, and place identity—are weak or externalized. Reporting practices are uneven, and metrics are not standardized, limiting comparability across institutions. We argue that SDG-based monitoring should be complemented by NEB’s place-sensitive criteria to bridge strategy–implementation gaps and to future-proof campus redevelopment. An illustrative conceptual case for Helsinki’s Viikki campus demonstrates how the indicators can be integrated into design scenarios. Policy recommendations highlight how integrating NEB’s place-sensitive criteria with ESG/SDG frameworks can strengthen the strategic and spatial coherence of campus transformations. Full article
(This article belongs to the Special Issue Sustainability in Cities and Campuses)
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23 pages, 1348 KB  
Article
Integrating Territorial Intelligence and Behavioral Insights in Urban Residential Decision-Making: Evidence from a Mixed-Methods Study in Casablanca, Morocco
by Zakaria Belabbes, Siham Ikhmim and Atman Dkhissi
Sustainability 2025, 17(22), 10391; https://doi.org/10.3390/su172210391 - 20 Nov 2025
Viewed by 481
Abstract
Understanding why households choose particular urban neighborhoods requires bridging traditional rational-choice explanations with emerging evidence on cognitive, social, and informational influences. This study investigates how territorial intelligence (TI)—defined as the availability and use of spatial data, planning information, and participatory knowledge platforms—interacts with [...] Read more.
Understanding why households choose particular urban neighborhoods requires bridging traditional rational-choice explanations with emerging evidence on cognitive, social, and informational influences. This study investigates how territorial intelligence (TI)—defined as the availability and use of spatial data, planning information, and participatory knowledge platforms—interacts with behavioral factors to shape residential relocation decisions. Employing an explanatory sequential mixed-methods design, we surveyed 356 recent movers in Casablanca, Morocco, and conducted 20 follow-up semi-structured interviews. Quantitative analysis shows that each additional consulted data source increased the odds of selecting a central, transit-rich location by 45 %, while prior awareness of development plans raised those odds by 60 %, controlling for income, tenure, affordability, dwelling attributes, and socio-demographics. Data use also predicted higher post-move satisfaction, particularly when individual housing preferences aligned with chosen locations. Qualitative findings reveal that residents view territorial data as a tool for “future-proofing” but also experience information overload, leading some to revert to heuristics or social advice. The interplay of rational cost–benefit logic, bounded cognitive processing, and TI-mediated knowledge underscores the need for planning strategies that combine economic fundamentals with behaviorally informed data provision. By integrating micro-level decision evidence with the territorial intelligence framework, the study offers practical guidance for urban planners aiming to nudge residential choices toward more sustainable, policy-consistent outcomes. Full article
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35 pages, 961 KB  
Article
Society and Mining: Reimagining Legitimacy in Times of Crisis—The Case of Panama
by Chafika Eddine
Mining 2025, 5(4), 72; https://doi.org/10.3390/mining5040072 - 6 Nov 2025
Viewed by 880
Abstract
This study examines Panama’s 2023 mining restrictions to illuminate persistent legitimacy crises in extractive governance. Employing a qualitative case study, it draws on 25 semi-structured interviews with government officials, industry representatives, Indigenous leaders, local communities, mining critics and other civil society actors, alongside [...] Read more.
This study examines Panama’s 2023 mining restrictions to illuminate persistent legitimacy crises in extractive governance. Employing a qualitative case study, it draws on 25 semi-structured interviews with government officials, industry representatives, Indigenous leaders, local communities, mining critics and other civil society actors, alongside policy and document analysis. Findings suggest that legitimacy reconstruction relies on four interdependent conditions: procedural justice, institutional trust, epistemic legitimacy, and relational governance. Stakeholders consistently emphasized transparency, capacity building, and inclusive engagement as essential for future mining activity, underscoring that technical standards alone are insufficient without credible institutions. Building on—but extending beyond—frameworks such as Social License to Operate (SLO) and Free, Prior and Informed Consent (FPIC), this paper offers Social Legitimacy for Mining (SLM) as a provisional, co-produced framework. Developed through literature synthesis and refined by diverse stakeholder perspectives, SLM is applied in Panama as an illustrative proof of concept that may inform further research and practice, while recognizing the need for additional adaptation across jurisdictions. Full article
(This article belongs to the Special Issue Envisioning the Future of Mining, 2nd Edition)
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23 pages, 333 KB  
Article
Examining the Impact of the Nationality and Borders Act 2022 on Refugee Women
by Nora Honkala
Laws 2025, 14(6), 82; https://doi.org/10.3390/laws14060082 - 27 Oct 2025
Viewed by 1390
Abstract
The Nationality and Borders Act 2022 was enacted despite significant opposition from refugee charity and legal sectors. It is without question that the Act changes the domestic landscape of the refugee status determination system and has the potential to also negatively influence refugee [...] Read more.
The Nationality and Borders Act 2022 was enacted despite significant opposition from refugee charity and legal sectors. It is without question that the Act changes the domestic landscape of the refugee status determination system and has the potential to also negatively influence refugee status determinations in other jurisdictions. There are several sections of the Act that are particularly problematic for women’s claims of asylum. The Act reverses well-established international and regional human rights and refugee law principles and standards. The reversal, in some cases, of decades of jurisprudence on the interpretation of the Refugee Convention poses a concern for the integrity of the law and administrative justice. While the Act imposes barriers for all claimants, it disproportionately affects some of the most complex cases, including refugee women fleeing gender-based persecution. Of the various changes brought about by the Act, this article focuses on three that are particularly relevant to women asylum seekers: first, the regressive way in which membership of a particular social group has been framed; second, the heightened standard of proof now required; and third, the associated evidential burdens in relation to trauma and disclosure. Ultimately, these changes are likely to have a disproportionate and discriminatory impact on women seeking asylum, particularly those fleeing gender-based persecution. Full article
19 pages, 349 KB  
Article
AI-Enabled ESG Compliance Audit for Stakeholders
by Eid M. Alotaibi and Abdulaziz M. Alwathnani
Sustainability 2025, 17(21), 9513; https://doi.org/10.3390/su17219513 - 25 Oct 2025
Cited by 1 | Viewed by 1437
Abstract
Environmental, social, and governance (ESG) disclosures face credibility risks due to Scope 2 Greenhouse Gas (GHG) reports lacking standardized compliance checks, raising concerns about their reliability. This study therefore develops and evaluates an AI-enabled artefact for ESG compliance auditing. This artefact applies natural [...] Read more.
Environmental, social, and governance (ESG) disclosures face credibility risks due to Scope 2 Greenhouse Gas (GHG) reports lacking standardized compliance checks, raising concerns about their reliability. This study therefore develops and evaluates an AI-enabled artefact for ESG compliance auditing. This artefact applies natural language processing (NLP) to extract reported values, implements rule-based checks grounded in the GHG Protocol, and produces transparent output. A design science research (DSR) approach guided the design, demonstration, and evaluation of the artefact, which was applied to sustainability reports from five technology companies. The results revealed that it replicates auditor judgments and reduces workload by over ninety percent in the sample. These findings serve as a proof-of-concept for automation in ESG compliance auditing. The theoretical contributions include extending the literature on AI in ESG auditing by reframing its role from producing interpretive scores to enabling transparent compliance verification. This study also demonstrates how DSR can help produce artefacts that embed rule-based logic into ESG assurance with rigor and practical relevance. The practical contributions include highlighting how a lightweight tool can enable auditors, regulators, boards, and investors to screen disclosures and benchmark credibility without sacrificing professional judgment. Full article
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48 pages, 15781 KB  
Article
Autonomous AI Agents for Multi-Platform Social Media Marketing: A Simultaneous Deployment Study
by Joongho Ahn and Moonsoo Kim
Electronics 2025, 14(21), 4161; https://doi.org/10.3390/electronics14214161 - 24 Oct 2025
Viewed by 3431
Abstract
This exploratory proof-of-concept study investigated the simultaneous deployment of autonomous, persona-driven Artificial Intelligence (AI) agents across multiple social media platforms using the ElizaOS framework. We developed three platform-specific agents with seven-layer character architectures and deployed them on Twitter/X, Discord, and Telegram for 18 [...] Read more.
This exploratory proof-of-concept study investigated the simultaneous deployment of autonomous, persona-driven Artificial Intelligence (AI) agents across multiple social media platforms using the ElizaOS framework. We developed three platform-specific agents with seven-layer character architectures and deployed them on Twitter/X, Discord, and Telegram for 18 days. The system processed 5389 interactions while gathering feedback from 28 volunteer participants. Addressing three research questions, we found that: (1) automation effectiveness was platform-dependent, with direct support platforms (Telegram, Discord) rated more useful than broadcast-oriented Twitter/X; (2) character design impact depended primarily on platform-persona alignment rather than architectural sophistication; and (3) technical performance showed platform-specific patterns, with median storage times ranging from 9.0 milliseconds (Twitter/X) to 61.5 milliseconds (Telegram) and high variability across all platforms. A notable finding was what we term the “Discord Paradox”—high quality ratings (4.05/5) but lowest preference (8.7%), suggesting platform familiarity and accessibility influence adoption more than agent quality. While the deployment demonstrated technical feasibility and revealed distinct user dynamics across platforms, the findings indicate that platform-specific optimization may be more effective than universal approaches. This exploratory study advances understanding of multi-platform agent deployment for marketing automation, identifying behavioral patterns and platform-specific dynamics that offer testable hypotheses for future systematic research. Full article
(This article belongs to the Special Issue AI Applications of Multi-Agent Systems)
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46 pages, 16421 KB  
Article
An Adaptive Urban Project for Coastal Territories: The Lazio Coast as a Laboratory of Resilience and Ecological Transition
by Carmela Mariano, Alessandra De Cesaris, Carlo Valorani, Mattia Martin Azzella, Marsia Marino, Maria Racioppi, Chiara Filicetti and Federico Ianiri
Sustainability 2025, 17(21), 9388; https://doi.org/10.3390/su17219388 - 22 Oct 2025
Viewed by 1051
Abstract
Within the ongoing scientific and disciplinary debate on the interplay between climate change and land-use governance, this paper highlights the critical role of urban planning and design in shaping environmental regeneration strategies for coastal urban areas vulnerable to flooding phenomena. These flood events—driven [...] Read more.
Within the ongoing scientific and disciplinary debate on the interplay between climate change and land-use governance, this paper highlights the critical role of urban planning and design in shaping environmental regeneration strategies for coastal urban areas vulnerable to flooding phenomena. These flood events—driven by the combined effects of sea-level rise (SLR) and riverine flood—represent one of the key challenges facing the “global risk society” given their increasing impact on urban areas and the tangible economic, social, and environmental damages they produce. In this context, this paper presents selected outcomes from the findings of the research project “Climate-proof planning and regeneration strategies for adaptation to sea-level rise. Experimentation and innovation in local urban planning in at-risk areas of the Lazio region”, conducted at Sapienza University of Rome. The project focuses on research and experimental planning in coastal areas of Lazio identified as being at risk of SLR-related flooding by 2100. It aims to define theoretical–methodological and operational references for urban regeneration with an ecosystemic approach within the framework of so-called climate-proof planning. This study examines three macro-areas, further subdivided into seven distinct sites, categorized by their prevailing urban functions. For each site, following a preliminary assessment of flood-prone zones, tailored design actions are proposed. These actions are framed within three overarching of urban resilience strategies, developed in previous research by the authors: “defence”, “adaptation”, and “relocation”. Full article
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34 pages, 5206 KB  
Article
Enhancing Transparency and Trust in Higher Education Institutions via Blockchain: A Conceptual Model Utilizing the Ethereum Consortium Approach
by Yerlan Kistaubayev, Francisco Liébana-Cabanillas, Aijaz A. Shaikh, Galimkair Mutanov, Olga Ussatova and Ainura Shinbayeva
Sustainability 2025, 17(20), 9350; https://doi.org/10.3390/su17209350 - 21 Oct 2025
Viewed by 811
Abstract
It has been recognized that Blockchain technology contributes to environmentally sustainable development goals (SDGs). It has emerged as a disruptive innovation capable of transforming various economic and social sectors significantly. This conceptual paper is driven by the need to explore how blockchain, specifically [...] Read more.
It has been recognized that Blockchain technology contributes to environmentally sustainable development goals (SDGs). It has emerged as a disruptive innovation capable of transforming various economic and social sectors significantly. This conceptual paper is driven by the need to explore how blockchain, specifically a consortium-based Ethereum architecture, can be integrated into higher education institutions to ensure data sovereignty, integrity, and verifiability while adhering to legal and ethical standards such as GDPR. We propose a multi-layered blockchain-based model for Kazakhstan’s Unified Platform of Higher Education (UPHE). This model employs hybrid on-chain/off-chain data storage, smart contract automation, and a Proof-of-Authority consensus mechanism to address system limitations, including data centralization and inadequate verification of academic credentials. Empirical simulations using Blockscout and Ethereum-compatible tools demonstrate the model’s feasibility and performance. This paper contributes to the growing discussion on educational blockchain applications by presenting a scalable, secure, and transparent architecture that aligns with institutional governance and Environmental, Social, and Governance (ESG) principles. It also supports the objectives of UN SDG 4 (i.e., Quality education) by fostering trust, transparency, and equitable access to verifiable educational credentials. Full article
(This article belongs to the Special Issue Emerging Technologies Implementation in Sustainable Management)
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20 pages, 7890 KB  
Article
One Bloom Is Not Like the Other—Distinct Environmental Drivers Result in Domoic Acid Events in Monterey Bay, California
by Aubrey Trapp, Andrew Baker, Kendra Hayashi and Raphael M. Kudela
Toxins 2025, 17(10), 511; https://doi.org/10.3390/toxins17100511 - 17 Oct 2025
Viewed by 755
Abstract
Domoic acid (DA), produced by Pseudo-nitzschia diatoms, is the one of the major toxin threats from harmful algal blooms (HABs) on the west coast of the United States. DA events vary in magnitude, timing, and duration, and elucidating drivers for individual events is [...] Read more.
Domoic acid (DA), produced by Pseudo-nitzschia diatoms, is the one of the major toxin threats from harmful algal blooms (HABs) on the west coast of the United States. DA events vary in magnitude, timing, and duration, and elucidating drivers for individual events is a persistent challenge. Monterey Bay experiences near-annual DA events and hosts long-term HAB monitoring at the Santa Cruz Municipal Wharf (SCW). Here we characterize two toxin events, occurring in May 2023 and March 2024. The events were similar in magnitude and duration, but an exploration of physical, biological, and chemical dynamics revealed distinct environmental drivers. These differences resulted in a significant deviation in cellular DA (cDA) within the same species of Pseudo-nitzschia. In addition, opportunistic solid-phase adsorption toxin tracking (SPATT) was used for environmental metabolomics. The novel application of SPATT revealed 159 metabolites that were strongly correlated with DA in both events and produced a spectral match to a new marine natural product using Global Natural Products Social Molecular Networking (GNPS). This work takes a multivariable approach to understanding toxin drivers and lends proof of concept for the integration of environmental metabolomics in HAB monitoring. Full article
(This article belongs to the Special Issue Ecology and Evolution of Harmful Algal Blooms)
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22 pages, 760 KB  
Article
The Effect of Materialism on Impulsive Buying: The Mediating Role of the Diderot Effect
by Rana Şen Doğan
Behav. Sci. 2025, 15(10), 1403; https://doi.org/10.3390/bs15101403 - 16 Oct 2025
Viewed by 1746
Abstract
Materialism is recognized as an important determinant of consumer behavior. However, studies exploring how materialism influences impulsive buying through the Diderot effect in digital contexts remain scarce. This study analyzes data from 416 adult consumers in Türkiye using Structural Equation Modeling (SEM). Four [...] Read more.
Materialism is recognized as an important determinant of consumer behavior. However, studies exploring how materialism influences impulsive buying through the Diderot effect in digital contexts remain scarce. This study analyzes data from 416 adult consumers in Türkiye using Structural Equation Modeling (SEM). Four hypotheses were tested: (i) materialism increases the Diderot effect, (ii) the Diderot effect strengthens impulsive buying, (iii) materialism directly influences impulsive buying, and (iv) materialism indirectly affects impulsive buying through the Diderot effect. The findings support all four hypotheses. Materialism significantly increases both the Diderot effect and impulsive buying in online environments. The Diderot effect partially mediates this relationship and acts as an independent predictor of impulsive tendencies. The study also points out that digital stimuli such as recommendation systems, fast payment options, and social proof may reinforce this mechanism, highlighting the importance of understanding consumer behavior in digital settings. Overall, the results underline that materialistic desires, when combined with the completion motive of the Diderot effect, strongly shape impulsive tendencies. Beyond advancing theory, the study emphasizes that marketing strategies should go beyond promoting higher consumption and instead foster conscious and sustainable shopping practices. This approach not only supports consumer well-being, but also contributes to building ethical and sustainable markets. Full article
(This article belongs to the Section Behavioral Economics)
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27 pages, 19715 KB  
Article
Applying Computational Engineering Modeling to Analyze the Social Impact of Conflict and Violent Events
by Felix Schwebel, Sebastian Meynen and Manuel García-Herranz
Entropy 2025, 27(10), 1003; https://doi.org/10.3390/e27101003 - 26 Sep 2025
Viewed by 875
Abstract
Understanding the societal impacts of armed conflict remains challenging due to limitations in current models, which often apply fixed-radius buffers or composite indices that obscure critical dynamics. These approaches struggle to account for indirect effects, cumulative damage, and context-specific vulnerabilities, especially the question [...] Read more.
Understanding the societal impacts of armed conflict remains challenging due to limitations in current models, which often apply fixed-radius buffers or composite indices that obscure critical dynamics. These approaches struggle to account for indirect effects, cumulative damage, and context-specific vulnerabilities, especially the question of why similar events produce vastly different outcomes across regions. We introduce a novel computational framework that applies principles from engineering and material science to conflict analysis. Communities are modeled as elastic plates, “social fabrics”, whose physical properties (thickness, elasticity, coupling) are derived from spatial socioeconomic indicators. Conflict events are treated as external forces that deform this fabric, enabling the simulation of how repeated shocks propagate and accumulate. Using a custom Python-based finite element analysis implementation, we demonstrate how heterogeneous data sources can be integrated into a unified, interpretable model. Validation tests confirm theoretical behaviors, while a proof-of-concept application to Nigeria (2018) reveals emergent patterns of spillover, nonlinear accumulation, and context-sensitive impacts. This framework offers a rigorous method to distinguish structural vulnerability from external shocks and provides a tool for understanding how conflict interacts with local conditions, bridging physical modeling and social science to better capture the multifaceted nature of conflict impacts. Full article
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33 pages, 8009 KB  
Article
Retargeting Gram-Positive-Only Adarotene-Derived Antibacterials to Broad-Spectrum Antibiotics
by Salvatore Princiotto, Luigi Cutarella, Alessandra Fortuna, Marta Mellini, Bruno Casciaro, Maria Rosa Loffredo, Alvaro G. Temprano, Floriana Cappiello, Livia Leoni, Maria Luisa Mangoni, Mattia Mori, Loana Musso, Francesca Sacchi, Cecilia Pinna, Giordano Rampioni, Sabrina Dallavalle and Claudio Pisano
Antibiotics 2025, 14(9), 956; https://doi.org/10.3390/antibiotics14090956 - 21 Sep 2025
Viewed by 844
Abstract
Background: Bacterial resistance to antibiotics continues to rise globally, posing a significant public health challenge and incurring substantial social and economic burdens. In response, the World Health Organization (WHO) has published a list of priority pathogens for which effective treatment options are [...] Read more.
Background: Bacterial resistance to antibiotics continues to rise globally, posing a significant public health challenge and incurring substantial social and economic burdens. In response, the World Health Organization (WHO) has published a list of priority pathogens for which effective treatment options are critically limited. Several antibiotics are categorized as Gram-positive-only (GPO) agents due to their lack of activity against Gram-negative species. Although these compounds often target conserved bacterial processes, their limited spectrum is largely attributed to poor penetration of the Gram-negative outer membrane (OM). Results: In this study, we designed and synthesized a series of adarotene-derived compounds to evaluate the impact of introducing positively charged groups on their interaction with the Gram-negative OM. One of the newly synthesized derivatives, SPL 207, displayed minimum inhibitory concentration (MIC) values ranging from 8 to 64 µM against a panel of Gram-positive and Gram-negative bacteria. The ability of SPL207 to disrupt outer and inner membrane permeability was evaluated using fluorescence assays and confocal microscopy, revealing that the compound compromises membrane integrity across all tested Gram-negative bacteria. Strong synergistic activity was observed in combination with colistin against three P. aeruginosa colistin-resistant strains. Atomistic details of membrane interference were elucidated by molecular dynamics (MD) simulations, with SPL207 clearly acting as a membrane destabilizer by enhancing Ca2+ ions diffusion and lipids destabilization. Conclusions: Although the observed MIC values remain above clinically acceptable thresholds, these findings provide a promising proof of concept. The further structural optimization of adarotene derivatives may yield novel broad-spectrum agents with improved antimicrobial potency against MDR pathogens. Full article
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