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The Brazilian Health Reform Movement succeeded in enshrining health as a constitutional social right, resulting in the creation of the Unified Health System (Sistema Único de Saúde, or SUS), based on the principles of universality, comprehensive care, equity, and democratized participation of users and workers in system management. However, the SUS faces a process of privatization by private Social Health Organizations (Organizações Sociais de Saúde, or OSS). This article reports part of a study involving researchers, including public mental health service workers. The methodological strategy explored narratives related to episodes of care in workplaces. The results revealed what we termed the 'enterprise-mode,' impacting both workers and the care provided in services managed by OSS. SUS health care workers on the shop floor face the challenge of commercial privatizing forces acting against the foundational principles of democratic management inscribed in the Brazilian Psychiatric Reform law enacted in 2001. A relationship is imposed that corrodes interactions within the team and between the team and service users, attempting to silence those who defend the SUS. However, the narratives also reveal sparks of resistance and insubordination emerging in the daily lives of SUS shop floor workers that can strengthen resistance movements for social health rights.

Although ovarian cancer is the most lethal among gynecological cancers, access to massive BRCA testing is still limited. Its cost-effectiveness is still a topic of discussion in several countries. In Brazil, olaparib was recently incorporated into the public health system, access to BRCA testing is still limited. In this article, we aim to review the cost-effectiveness of offering BRCA testing to the at-risk population. A working group composed of 14 specialists in surgical oncology and cancer genetics was established to discuss the cost-effectiveness of population-based BRCA testing for ovarian cancer. The project was divided into five main areas, each with subtopics assigned among the 14 participants. They were: the existing clinical testing guidelines, the current healthcare infrastructure in the Brazilian public health system, cost-effectiveness analysis, challenges in implementing prophylactic surgeries, and family counseling and risk communication. A comprehensive literature review was conducted, followed by a series of meetings among the article's contributors to reach consensus on unresolved issues. These discussions aimed to build recommendations based on the best available scientific evidence. Using as a basis the current structure already existing within the Brazilian public health service (SUS [Sistema Único de Saude]), and based on the testing of the at-risk population chosen by our experts, we estimated savings. The net savings for a population of 100 000 women would range from BRL 7030.30 (US$1255.41) to BRL 1853.92 (US$331.05). And these costs could have an even greater impact when public service PARP inhibitors are incorporated. The working group of the Brazilian Society of Surgical Oncology understands that large-scale BRCA testing is cost-effective, especially when risk-reducing surgery is implemented. Other measures are important, such as training teams of non-specialists to recognize the population at risk, in addition to creating an entire line of care for patients with ovarian cancer in the SUS.

Epidemiology has been fundamental for analyzing health problems and supporting decision-making in healthcare systems and public health. However, traditional epidemiological methods, designed fundamentally to identify causal associations at the population level through aggregate data measures, present inherent limitations in capturing individual heterogeneity in response to specific exposures. This population-based approach hinders personalized prediction of outcomes in a particular individual whose risk factors may manifest differently from the group average, particularly when multiple contextual variables and unique biological profiles are involved. Advances in artificial intelligence have generated tools capable of integrating large volumes of information, identifying complex patterns in specific subgroups, and producing more personalized estimates, transitioning from a reactive approach based on population averages toward predictive models centered on individual trajectories. However, these developments do not replace the methodological foundations of epidemiology, as the identification of exposures, outcomes, and causal relationships continues to depend on the epidemiological conceptual framework. From this perspective, current tensions do not represent a disciplinary crisis, but rather a transition toward broader approaches that combine population-based analyses with advanced predictive tools. This integration is particularly relevant for large-scale healthcare institutions and national health systems, which require models capable of leveraging diverse data to improve understanding of health processes and support clinical and operational decisions. La epidemiología ha sido fundamental para el análisis de los problemas de salud y para la toma de decisiones en los sistemas sanitarios y la salud pública. No obstante, los métodos tradicionales de la epidemiología, diseñados fundamentalmente para identificar asociaciones causales a nivel poblacional mediante medidas de datos agrupados, presentan limitaciones inherentes para capturar la heterogeneidad individual en la respuesta ante exposiciones específicas. Esta aproximación poblacional dificulta la predicción personalizada del desenlace en un individuo particular, cuyos factores de riesgo pueden manifestarse de forma distinta al promedio grupal, particularmente cuando intervienen múltiples variables contextuales y perfiles biológicos únicos. Los avances en inteligencia artificial han generado herramientas capaces de integrar grandes volúmenes de información, identificar patrones complejos en subgrupos específicos y elaborar estimaciones más personalizadas, transicionando desde un enfoque reactivo basado en promedios poblacionales hacia modelos predictivos centrados en trayectorias individuales. Sin embargo, estos desarrollos no sustituyen los fundamentos metodológicos de la epidemiología, ya que la identificación de exposiciones, desenlaces y relaciones causales continúa dependiendo del marco conceptual epidemiológico. Bajo esta perspectiva, las tensiones actuales no representan una crisis disciplinaria, sino una transición hacia enfoques más amplios que combinan análisis poblacionales con herramientas predictivas avanzadas. Esta integración resulta especialmente relevante para instituciones de gran escala, como las de seguridad social, que requieren modelos capaces de aprovechar datos diversos para mejorar la comprensión de los procesos de salud y apoyar decisiones clínicas y operativas.

This study analyses how LGBTQ+ healthcare users and healthcare professionals navigate and reconfigure access to healthcare within Brazil's Sistema Único de Saúde (Unified Health System) in contexts shaped by institutional LGBTQ-phobia. The study employed a qualitative intervention-research design informed by cartography. Fieldwork was conducted in a family health clinic in northeastern Brazil and combined participant observation with semi-structured interviews with LGBTQ+ healthcare users and healthcare professionals. The analysis conceptualises access not as a linear process but as a set of negotiated pathways, mapped as five routes of access to healthcare: facilitated access; access 'by force'; unnoticed access; access through detours; and access through support networks. These routes reveal how access is continuously produced through relational practices, micropolitical negotiations and collective arrangements that both reproduce and disrupt institutional norms. The findings position agency as a central analytical axis, demonstrating how subjects and professionals actively invent alternative forms of care in response to institutional violence and exclusion.

Brazil's Unified Health System (Sistema Único de Saúde, SUS) represents one of the world's largest universal health systems and provides a unique real-world platform for integrating prevention, diagnosis, treatment, and survivorship across the cancer continuum. While One Health frameworks have traditionally focused on infectious diseases, environmental exposures, and planetary health, their application to surgical oncology and health-system innovation remains insufficiently explored. This article proposes that the SUS offers a valuable model for operationalizing One Health and population health principles in prostate cancer care by connecting environmental, social, biological, and healthcare system determinants across the patient journey. The recent incorporation of robot-assisted radical prostatectomy (RARP) into the SUS represents a critical milestone in this evolution. Beyond the adoption of an advanced surgical technology, this initiative illustrates the capacity of a universal health system to evaluate, implement, and monitor complex innovations while balancing effectiveness, equity, sustainability, and population-level impact. The Brazilian experience highlights the emergence of a learning health system in which real-world evidence, implementation science, surgical quality assessment, and health policy interact to guide innovation at the national scale. In this context, RARP serves as a case study of how technological advances can be integrated into publicly funded healthcare while generating evidence relevant to diverse populations and healthcare settings. By bridging concepts from Surgical Public Health, population health, health-systems science, implementation science, and One Health, the SUS provides a distinctive framework for understanding how surgical innovation can contribute to resilient and equitable cancer care. As translational oncology increasingly incorporates environmental, societal, and biological determinants of disease, Brazil offers important lessons on the governance, evaluation, and dissemination of high-complexity surgical technologies within universal health systems. The insights emerging from this experience may help inform future strategies to optimize prostate cancer care and strengthen health-system resilience globally.

Biodiversity offsetting aims to compensate for ecological losses from development through conservation and restoration. However, its long-term outcomes under repeated impact-offset cycles remain uncertain. Using a conceptual forest succession model, we evaluated how offset outcomes are affected by interactions among compensation scale, duration of protection, habitat conversion rate, and land availability constraints. Additionally, we considered that these outcomes may differ across biodiversity components, including habitat maturity associated with successional habitat-forming species and metapopulation dynamics of persistent colonizers and successional specialists. We showed that effective offsetting requires restoring areas larger than those impacted and maintaining protection over timescales aligned with ecological recovery, particularly where ongoing habitat conversion reshapes landscape structure. High rates of habitat conversion consistently reduced offsetting success, particularly for colonizing species reliant on habitat quality and long-term protection. Our results further showed that delayed ecological responses and cumulative impacts can undermine offsetting efforts that appear effective in the short term. Robust offset design must therefore explicitly account for temporal lags, dynamic landscape trajectories, adequate spatial compensation, and multiple biodiversity indicators to avoid the ecological fallacy that short-term restoration success equates to long-term biodiversity and ecosystem integrity. Optimización de la compensación de la biodiversidad para la sucesión de hábitats y la dinámica de colonización Resumen La compensación de la biodiversidad tiene como objetivo compensar las pérdidas ecológicas derivadas del desarrollo mediante la conservación y la restauración. Sin embargo, los resultados a largo plazo en el marco de ciclos repetidos de impacto y compensación siguen siendo inciertos. Utilizamos un modelo conceptual de sucesión forestal para evaluar cómo los resultados de la compensación se ven afectados por las interacciones entre la escala de compensación, la duración de la protección, la tasa de conversión del hábitat y las restricciones de disponibilidad de suelo. También consideramos que estos resultados pueden variar según los componentes de la biodiversidad, incluyendo la madurez del hábitat asociada a especies de sucesión formadoras de hábitat y la dinámica de metapoblaciones de colonizadores persistentes y especialistas de sucesión. Demostramos que una compensación efectiva requiere restaurar áreas más extensas que las afectadas y mantener la protección durante periodos de tiempo acordes con la recuperación ecológica, especialmente cuando la conversión continua del hábitat remodela la estructura del paisaje. Las altas tasas de conversión del hábitat redujeron de forma sistemática el éxito de la compensación, en particular para las especies colonizadoras que dependen de la calidad del hábitat y de una protección a largo plazo. Nuestros resultados demostraron además que las respuestas ecológicas retardadas y los impactos acumulativos pueden socavar los esfuerzos de compensación que parecen eficaces a corto plazo. Por lo tanto, un diseño sólido de las medidas de compensación debe tener en cuenta explícitamente los retrasos temporales, las trayectorias dinámicas del paisaje, una compensación espacial adecuada y múltiples indicadores de biodiversidad, a fin de evitar la falacia ecológica según la cual el éxito de la restauración a corto plazo equivale a la biodiversidad y la integridad de los ecosistemas a largo plazo.

Understanding how phenotypic plasticity arises in sensory traits is a key challenge in evolutionary and developmental biology. Eusocial insects offer a useful model for exploring it, because their castes perform distinct tasks and occupy different light environments. We examined morphological variation and scaling in the visual systems of female castes of Protopolybia sedula, a neotropical wasp with simultaneous polygyny. Although queens are larger than workers, both castes showed similar eye area, ommatidial diameter, and ommatidia number. However, queens showed greater variability in ommatidial diameter, while workers varied more in eye area and ommatidia number. Allometric patterns also diverged: queen eye area scaled hypoallometrically and ommatidial diameter hyperallometrically with body size, whereas workers displayed isometric scaling for both traits. Analysis of ommatidia size and number indicates workers allocate more resources to increasing ommatidia number, while queens emphasize enlarging ommatidia. These differences highlight distinct developmental and scaling strategies that generate caste-specific visual adaptations. Additional language abstract Compreender como a plasticidade fenotípica em características sensoriais surge é um desafio fundamental na biologia evolutiva e do desenvolvimento. Insetos eussociais oferecem um modelo útil para explorá-la, pois suas castas desempenham tarefas distintas e ocupam diferentes ambientes luminosos. Examinamos a variação morfológica e a escala nos sistemas visuais de castas femininas de Protopolybia sedula, uma vespa neotropical com poliginia simultânea. Embora as rainhas sejam maiores que as operárias, ambas as castas apresentaram área do olho, diâmetro dos omatídios e número de omatídios semelhantes. No entanto, as rainhas mostraram maior variabilidade no diâmetro dos omatídios, enquanto as operárias variaram mais na área do olho e no número de omatídios. Os padrões alométricos também divergiram: a área dos olhos das rainhas apresentou escala hipoalométrica e o diâmetro dos omatídios hiperalométrica com o tamanho do corpo, enquanto as operárias exibiram escala isométrica para ambas as características. A análise do tamanho e do número de omatídios indica que as operárias alocam mais recursos para aumentar o número de omatídios, enquanto as rainhas priorizam o aumento do tamanho dos omatídios. Essas diferenças destacam estratégias distintas de desenvolvimento e escalonamento que geram adaptações visuais específicas para cada casta.

Hypertrophic cardiomyopathy (HCM) is an autosomal dominant myocardial disorder affecting 0·2% of the global population and a leading cause of sudden cardiac death in young individuals and athletes. Current guidelines recommend periodic clinical screening of first-degree relatives for early diagnosis and risk stratification. Genetic testing identifies at-risk individuals while exempting genotype-negative relatives from lifelong surveillance. However, it remains unavailable in Brazil's public health system (Sistema Único de Saúde, SUS). This study aimed to evaluate the cost-utility of genetic testing for HCM cascade screening in Brazil. A cost-utility analysis was conducted from the SUS perspective, using a hybrid decision tree and Markov model to project lifetime costs and health outcomes. Inputs were derived from literature and validated by a multidisciplinary expert panel. Genetic testing costs were micro-costed; other costs were obtained from Brazil's national reimbursement database (SIGTAP). Effectiveness was measured in quality-adjusted life-years (QALYs). Deterministic and probabilistic analyses assessed model robustness. Genetic testing was cost-effective (incremental cost-effectiveness ratio: US$1411 per QALY), yielding an incremental gain of 0·06 QALYs per relative at an additional cost of $87 per relative. Utility values had the greatest influence on cost-utility outcomes. In probabilistic analysis, genetic testing was cost-effective in 99·4% of simulations at the Brazilian willingness-to-pay threshold of $7421 per QALY. In the base-case hypothetical cohort of 1000 relatives (250 probands with four first-degree relatives each), 205 (20·5%) of 1000 relatives were exempted from lifelong surveillance, reducing screening visits by 18·6% per tested individual. Genetic testing is a cost-effective strategy for HCM cascade screening in Brazil's public health system. By exempting genotype-negative relatives from lifelong surveillance, it optimises resource allocation, reduces unnecessary follow-ups and psychological burden, and supports informed family planning. These findings provide an economic evidence base for integrating genetic testing into SUS clinical practice guidelines. Programa Nacional de Genômica e Saúde de Precisão (Genomas Brasil) of the Brazilian Ministry of Health and Conselho Nacional de Desenvolvimento Científico e Tecnológico.

The marketing of unproven stem cell-based interventions raises public health, ethical, and regulatory challenges. This article examines online marketing in Panama, identifies new businesses, and argues that lack of enforcement has contributed to their expansion. Urgent actions are needed to mitigate this market, protect patients, and generate evidence-based treatments.

Abandoned mines are among the main sources of long-term soil contamination, often leaving behind persistent concentrations of potentially toxic elements (PTE) that pose environmental and health risks. Ribeiro da Serra Sb-Au mine, in Portugal, active from 1858 to 1890, has left a significant environmental legacy. This study mapped the spatial distribution of mine processing residues, elemental characterisation distinguishing between anthropogenic and natural enrichment by determining soil sample concentrations of PTE, Hg mobility, and Total Organic Carbon (TOC) quantification. Multivariate analysis, spatial interpolation and comparison with Enrichment Factor were employed with the aim of understanding the distributions and sources of PTEs in the soils. Mercury is still present at the site, revealing high mobile (18.72 mg kg-1) and semi-mobile (3.58 mg kg-1) concentrations accumulated in waste piles, a remnant of Au amalgamation processes. High Hg concentrations (20.75 mg kg-1) pose significant environmental risks, even after more than a century, such as bioaccumulation potential and soil toxicity. Also, there are high concentrations of Pb (449.03 mg kg-1) in the waste piles from the Sb processing. This study highlights the critical importance of interpreting natural enrichment values of elements of Hg (EF = 267) and Pb (EF = 18) to discern pollution pathways resulting from mining and processing activities. Interpretation of natural enrichment values leads to a more accurate evaluation of environmental contamination and its sources. The Enrichment Factor shows that Sb (EF = 133) and Hg (EF = 267) are the elements that present extremely high enrichment (EF > 40).

This study aims to explore the feasibility of executing Skyline Queries-used to identify optimal data points based on multiple criteria-within compact data structures. While existing algorithms typically operate on plain or indexed datasets, this work investigates how such queries can be efficiently resolved using compact representations. We focus on implementing two Skyline Query variants, Constrained Skyline Query and Enumerating Skyline, within the k2-tree compact data structure. Our approach leverages the k2-tree's inherent indexing capabilities to evaluate these queries directly on compressed data, avoiding the need for decompression. The results demonstrate that the k2-tree structure effectively supports both types of Skyline Queries. Our experimental evaluation shows improved resource utilization compared to non-indexed methods, confirming that compact data structures can process these queries efficiently without data inflation. This article presents a comprehensive study of implementing skyline queries directly over compact data structures-specifically the k2-tree, supported by extensive experimental evaluation and a complete theoretical analysis of the proposed algorithms.

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The application of Big Data in healthcare enhances disease management by improving diagnostics and treatments, offering a foundation for positive impacts on the health of diverse populations. This paper aims to analyze the impact of Big Data on healthcare through a comprehensive review of scientific papers that explore its application in the management, diagnosis, and treatment of various diseases, assessing its benefits, challenges, and potential to revolutionize healthcare systems. The study compiled 63 papers from sources such as Web of Science, IEEE Xplore, Scopus, ScienceDirect, and ACM Digital Library, conducting an exhaustive systematic review of publications from 2018 to 2024 on the use of Big Data in healthcare. The findings indicate that prediction and decision-making are the most relevant criteria for evaluating the effectiveness of Big Data in healthcare. Additionally, it was observed that most research is published in journals ranked at the Q1 quartile level. Insights are provided on how Big Data criteria can optimize healthcare delivery, to guide evidence-based decision-making and healthcare system optimization.

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Many conservation challenges require negotiating trade-offs between the needs of different actors. Global frameworks such as the Kunming-Montreal Global Biodiversity Framework explicitly call for diverse participation and social equity in conservation decision-making. Achieving this requires integrating equity into both decisions and decision-making processes. Despite shifts toward strengthening social equity, practical guidance for incorporating equity into conservation decision-making processes remains limited. We argue that structured decision-making (SDM), an organized approach designed for complex decisions involving diverse actors, provides a useful framework for considering equity in conservation decision-making. We developed 10 strategies for improving social equity in conservation decision-making to strengthen both social and conservation outcomes. We systematically integrated equity's multiple dimensions throughout every SDM stage, making equity an inherent element in decision-making rather than an afterthought. For example, when clarifying the decision context, practitioners can create thorough stakeholder maps, ask diverse social groups how they want to be engaged, and design processes to facilitate their participation. At later stages, when assessing links between actions and outcomes, structured methods for information aggregation and tools to enable shared understanding support development of a shared vision and a path forward. By transforming general calls for inclusivity into specific, actionable strategies, we provide conservation practitioners, researchers, and decision makers practical guidance bridging the theory-to-practice gap. La toma de decisiones estructurada como marco para incorporar la equidad en las decisiones de conservación Resumen Muchos desafíos de conservación requieren negociar equilibrios entre las necesidades de los distintos actores. Los marcos globales, como el Marco Global de Biodiversidad de Kunming‐Montreal, abogan explícitamente por una participación diversa y la equidad en la toma de decisiones sobre conservación. Para lograrlo, es necesario integrar la equidad tanto en las decisiones como en los procesos de toma de decisiones. A pesar de los avances hacia el fortalecimiento de la equidad social, las orientaciones prácticas para incorporar la equidad en los procesos de toma de decisiones sobre conservación siguen siendo limitadas. Sostenemos que la toma de decisiones estructurada (TDE), un enfoque organizado diseñado para decisiones complejas que involucran a diversos actores, ofrece un marco útil para considerar la equidad en la toma de decisiones sobre conservación. Desarrollamos diez estrategias para mejorar la equidad en la toma de decisiones sobre conservación con el fin de fortalecer tanto los resultados sociales como los de conservación. Integramos sistemáticamente las múltiples dimensiones de la equidad en todas las etapas de la SDM, convirtiendo la equidad en un elemento inherente a la toma de decisiones en lugar de un elemento secundario. Por ejemplo, al aclarar el contexto de la decisión, los profesionales pueden crear mapas exhaustivos de las partes interesadas, preguntar a diversos grupos sociales cómo desean participar y diseñar procesos para facilitar su participación. En etapas posteriores, al evaluar los vínculos entre las acciones y los resultados, los métodos estructurados para la agregación de información y las herramientas que permiten un entendimiento compartido apoyan el desarrollo de una visión común y un camino a seguir. Al transformar los llamamientos generales a la inclusión en estrategias específicas y aplicables, brindamos a los profesionales de la conservación, a los investigadores y a los responsables de la toma de decisiones una guía práctica que acorta la brecha entre la teoría y la práctica.

To estimate the prevalence and neonatal mortality of isolated gastroschisis, assess temporal trends, identify risk factors for neonatal death, and describe its spatial distribution in a middle-income setting. This population-based study included all live births in São Paulo State, Brazil, from 2004 to 2017. Cases of isolated gastroschisis were identified from live birth and death certificates. Temporal trends in prevalence and neonatal mortality (0-27 days) were analyzed using Prais-Winsten regression to estimate annual percent change (APC). Maternal and neonatal factors associated with neonatal death were examined using Poisson and multivariate logistic regression. Spatial distribution across municipalities was described by quartiles according to maternal residence. Among 8,441,498 live births, 1664 cases of isolated gastroschisis were identified (prevalence: 1.97 per 10,000). Neonatal mortality rate associated with isolated gastroschisis was 0.35 per 10,000 live births, with a lethality rate of 17.7%. Prevalence (APC 3.0%; 95% CI: -1.3 to 7.5) and mortality (0.6%; -3.5 to 4.8) remained stable over time. Lower gestational age, fewer prenatal visits, and severe growth restriction were independently associated with higher risk of neonatal death. Spatial analysis showed heterogeneous distribution, with most municipalities reporting no cases and higher prevalence and mortality concentrated in few areas. In this middle-income setting, isolated gastroschisis showed stable but higher prevalence and neonatal mortality than in high-income countries. The heterogeneous spatial pattern suggests regional disparities in risk and outcomes, highlighting the need for targeted public health strategies and further research on gastroschisis epidemiology.

Hypervirulent Klebsiella pneumoniae (hvKp) is an emerging threat due to its capacity to cause severe community-acquired infections and its increasing convergence with multidrug resistance. However, functional assessment of hvKp virulence still relies largely on mammalian infection models, which are costly, ethically constrained, and poorly suited for scalable early-stage screening. Here, we establish a proof-of-concept cell-based biosensing framework using the social amoeba Dictyostelium discoideum to detect capsule-associated virulence phenotypes in the model hvKp strain SGH10. Using SGH10 and a scarless capsule-null ΔwcaJ mutant, we show that loss of capsule production strongly reduces mucoviscosity, zebrafish lethality, resistance to amoebal predation, inhibition of social development, and impairment of amoebal motility. These host behavioral responses were quantified through complementary readouts, including predation plaque expansion, multicellular development, fluorescence microscopy, live-cell tracking, and exploratory multivariate integration. Compared with SGH10, the ΔwcaJ mutant produced phenotypes resembling those of the avirulent control strain KpGe, supporting capsule production as a major driver of phagocytosis resistance and host-response disruption in this model. Rather than providing a broadly validated classifier for hvKp, our results define a calibrated experimental framework in which D. discoideum functions as a living phenotypic sensor for capsule-dependent virulence traits. This platform offers a low-cost, genetically tractable, and imaging-compatible system for dissecting hvKp host interactions and for guiding future validation of scalable virulence biosensing across larger and genetically diverse K. pneumoniae collections.

Arginine-specific gingipain B (RgpB), a key cysteine protease from Porphyromonas gingivalis, is associated with several systemic diseases. It is synthesized as a zymogen bound to a propeptide inhibitor that blocks its catalytic activity until activation in the extracellular environment. To identify inhibitory peptide variants with enhanced affinity, mutants of the propeptide inhibitory loop were designed. A total of 52 mutants were generated and, for each model, four independent molecular dynamics replicas were performed, followed by binding free energy calculations using MM/GBSA. Most variants exhibited more favorable binding affinities than the wild-type (WT) loop (-109.8 ± 4.9 kcal mol-1). Among them, V126K (-128.1 ± 5.6 kcal mol-1), E131D (-120.6 ± 8.2 kcal mol-1), and N132R (-135.8 ± 4.6 kcal mol-1) emerged as promising, with the first two showing statistically significant improvements using ANOVA followed by Tukey's post-hoc test (p = 0.001). Thermodynamic integration calculations were consistent with increased binding affinity for the selected variants. Thermodynamic integration calculations further confirmed a significant increase in the relative binding affinity for the selected variants compared to the wild type. These results provide a solid basis for future in vitro validation and establish an in silico framework to accelerate the rational design of propeptide-based inhibitors and the development of novel therapeutic approaches targeting RgpB.

The Venice Lagoon has experienced a long-term decline of salt marsh habitats due to sediment deficit, morphological deepening, increased hydrodynamic exposure, and human-induced alterations to lagoon processes. Identifying suitable locations for restoration is therefore a key challenge for lagoon management. This study applies a participatory GIS-based Multi-Criteria Decision Analysis (S-PMCA) to support the spatial prioritization of salt marsh restoration and rebuilding within the framework of the WaterLANDS and REST-COAST projects. The analysis combined stakeholder knowledge with spatially explicit environmental information. An initial set of criteria was reviewed through a pre-workshop survey involving 21 stakeholders and subsequently refined during a workshop attended by 43 participants. The final analysis incorporated six spatial criteria: distance from canals, wind fetch, proximity to existing salt marshes, historical salt marsh loss, seagrass protection, and water quality. Criteria were transformed into standardized suitability layers and weighted according to stakeholder preferences. Distance from canals received the highest average importance weight (21.4/100), whereas water quality received the lowest (13.8/100). Suitability maps were generated using an Ordered Weighted Averaging (OWA) approach and combined with a bathymetry-based proxy of restoration costs to perform a spatial cost-effectiveness assessment. Priority restoration areas were identified along lagoon margins and near the Malamocco-Marghera Canal, where wave attenuation potential, ecological connectivity, historical marsh presence, and favourable implementation conditions converge. By combining stakeholder preferences with morphodynamic conditions, ecological factors, and implementation costs, this study supports the identification of restoration areas that are both feasible and strategically relevant in the Venice Lagoon.