Search Results (87)

Invasive candidiasis, predominantly driven by multidrug-resistant Candida species and intractable biofilms, represents an escalating global health crisis with mortality rates rivaling major infectious diseases. The clinical efficacy of conventional antifungal agents—azoles, polyenes, and echinocandins—is severely compromised by poor tissue penetration, dose-limiting systemic toxicity, and the rapid evolution of complex resistance mechanisms. Here, we review the two-decade structural evolution of nanotechnological interventions designed to overcome these pharmacological and biological barriers. We systematically analyze advanced nanosystems, including lipid-based formulations, natural polymers, and biogenic metallic nanostructures, highlighting their capacity to penetrate the dense extracellular polymeric substance (EPS), combat potential fungal ‘nano-resistance’, and significantly reduce metabolically dormant persister cell populations. The literature search was performed using the electronic databases PubMed, Scopus, Web of Science, and Google Scholar. Publications indexed between 2015 and 2025 were primarily considered, while seminal studies published before 2015 were included when necessary to provide historical context and foundational knowledge. We place specific emphasis on next-generation biomimetic and exosome-inspired nanocarriers, which significantly reduce systemic host toxicity while maximizing targeted antifungal efficacy. In this context, the synergistic integration of smart nanocarriers to actively disassemble fungal resistance networks, such as the target of rapamycin (TOR) signaling pathway and sphingolipid biosynthesis. Finally, we outline a strategic roadmap to bridge the translational “Valley of Death”. By prioritizing manufacturing standardization, comprehensive long-term biosecurity profiling, and rationally designed biomimetic platforms, we propose an alternative way to outpace the evolutionary adaptations of fungal pathogenesis and translate these innovations into the clinic. Full article

Cross-state air pollution can degrade air quality in regions surrounding urban areas. However, assessing health impacts and economic costs requires quantifying annual pollutant transport. This type of annual assessment poses significant technical challenges, including the need to differentiate between external and local pollution, which have different spatial distributions; the large number of required air quality simulations; and the extensive post-processing of results. The Mexico City Metropolitan Area is located within the most polluted airshed in the country and exports large quantities of atmospheric pollutants to neighboring airsheds; however, until now, the annual magnitude of the impact on the population and its associated costs had not been quantified. This paper presents the estimation of potentially avoidable premature mortality and the annual economic cost associated with importing PM_2.5 from the Mexico City Metropolitan Area into the metropolitan areas of Toluca and Cuernavaca. These estimates are based on 8640 simulations of air quality using the Hysplit 5.3.0 model, corresponding to each hour of 360 days in one year. Geoprocessing tools specifically designed in ArcGIS 10.4 were used to automate the calculations of PM_2.5 mass exchange, and the premature mortality and health costs were calculated using the BenMap-CE 1.5.0.4 program. Results indicate that the export of PM_2.5 from the Mexico City Metropolitan Area in 2018 may have resulted in 19,473 potentially avoidable premature deaths in the two recipient metropolitan areas. This impact could represent an annual economic cost of $12,197 million for the Toluca Valley Metropolitan Area and $4140 million for the Cuernavaca Metropolitan Area. Full article

Although the European Union positions the bioeconomy at the core of its sustainability transition and the European Green Deal, the cross-country distribution of bioeconomy value-added associated with mission-oriented public R&D support remains highly uneven. This paper investigates how national researcher capacity (as a proxy of absorptive capacity) shapes the macroeconomic effectiveness of bioeconomy-oriented public R&D support, and how societal climate-oriented environmental concern acts as a direct structural driver of bioeconomy value-added. Using a panel dataset of 27 EU Member States from 2008 to 2020, the study constructs an original bioeconomy-specific measure of government budget appropriations for R&D (GBARD) and estimates two-way fixed-effects models with Driscoll–Kraay standard errors to account for cross-sectional dependence. The findings reveal a clear capacity-dependent conditional moderation effect: public R&D support is significantly associated with higher bioeconomy value-added only when a critical mass of researcher capacity is present. Sectoral disaggregation demonstrates that business enterprise researcher capacity acts as the primary transmission channel linking public funds to the market, whereas higher-education capacity shows no statistically significant short-to-medium-term moderating effect, consistent with the academic research commercialisation time lags documented in the literature. Additionally, societal climate-oriented environmental concern is positively associated with bioeconomy value-added in the baseline models, consistent with its role as a demand-side factor fostering receptive conditions for bio-based transitions. The study concludes that increasing mission-oriented R&D funding alone is likely insufficient; to successfully cross the “valley of death,” public R&D should be accompanied by complementary policies that build private-sector absorptive capacity and cultivate green market demand. Full article

Amid the restructuring of the global knowledge economy, the structural imbalance of “high input, low commercialization” and the “valley of death” trap have emerged as core bottlenecks restricting the high-quality development of regional innovation. This study aims to explore the collaborative pathway connecting knowledge production to value creation by constructing a ternary Innovation–Platform–Commercialization (IPC) system, which covers front-end research and development (R&D), mid-end integration, and back-end commercialization. Based on China’s provincial panel data from 2013 to 2023, this paper comprehensively employs the coupling coordination model, spatial disparity analysis, and machine learning methods to quantitatively evaluate the coordinated evolutionary pattern of the system and deconstruct its core driving factors. The results indicate the following: First, the overall coordination of the IPC system has steadily improved, yet it exhibits significant spatial agglomeration and local lock-in risks. Second, the underlying cause of spatial disequilibrium has evolved from an absolute scale gap to cross-regional structural fractures. Third, the current core constraint on system development is no longer front-end R&D investment but rather high-value technology trading barriers and the insufficient empowerment of intermediary networks. Finally, the driving effects of traditional elements such as R&D funds and platform scale significantly diminish or even stagnate after crossing specific thresholds, whereas agile organizational structures exhibit superior potential for coordination empowerment. This research breaks through the limitations of traditional unidirectional linear transfer models, confirming that the constraint logic of regional coordination has substantially shifted from “insufficient macro-resource investment” to “micro-organizational operational friction.” Consequently, it provides a theoretical and decision-making basis for local governments to implement precise governance tailored to regional endowments. Full article

The increase in older adults and active lifestyles has made chondral and osteochondral lesions common in the population, making them one of the central challenges in orthopedics. Although hydrogel-based regenerative medicine offers an encouraging therapeutic option for these lesions, important obstacles still prevent these therapies from reaching the clinic. In view of these factors, we adopted a risk-based approach for this review, in line with the current legislative requirements in clinical translation and clinical trials. We identified the factors that could undermine patient safety or lead to poor outcomes. Then, we outlined solutions to remedy these problems that integrate hydrogel technology, clinical/pharmaceutical/surgical protocols, and post-operative follow-up. Upcoming studies should give priority to the development of hydrogel scaffolds modified to mimic cartilage’s mechanical and physicochemical properties, together with patient-specific features. Other crucial characteristics are host-tissue integration, long-lasting cartilage tissue regeneration, and a positive outcome. In parallel, to scale complex and costly innovations, efforts should focus on a harmonized, simplified legislative landscape, optimized standards, and established follow-up protocols. Getting through this “valley of death” between research and innovation is strategic for reaching the clinics and the largest number of patients. Full article

Feral donkeys (Equus asinus) are well adapted to arid ecosystems and are found in large populations in the deserts of Australia and the Americas. We assessed resource selection and seasonal home range size of female donkeys in southern California between 2020 and 2022 based on telemetry data. We also examined whether dyads with greater encounter rates were more likely to test positive for asinine herpesvirus 5 (AHV-5) and/or Streptococcus equi zooepidemicus (SEZ). Donkey home ranges were non-significantly larger in the cool/wet season (November through March; mean 318.37 ± sd 417.65 km²) than in the hot/dry season (April through October; mean 159.35 ± 212.43 km²). Donkeys selected flatter areas closer to water year-round but selected greater herbaceous cover during the cool/wet season and lower heat loads during the hot/dry season. Individuals testing positive for SEZ selected lower elevations during the wet season and closer distances to water during the dry season; donkeys testing positive for AHV-5 selected areas farther from water during the wet season and steeper slopes during the dry season. The dyad encounter rate was unrelated to presence of either disease. Our results contribute to the understanding of donkey ecology, allowing feral populations to be better controlled by specific and focused management. Full article

This study quantifies the spatiotemporal evolution of non-communicable disease (NCD) mortality risk associated with temperature extremes in the Metropolitan Area of the Valley of Mexico (MAVM) from 2000 to 2019. Using a Bayesian risk assessment framework, we analyzed 747,131 deaths to evaluate the impact of extreme temperature indices (Tn90p, Tn10p, TNn, Tx90p, Tx10p, TXx, DTR) across demographic and geographic dimensions. Results reveal a significant intensification of mortality risk, particularly for circulatory and metabolic diseases after 2005 and 2014. Risk expansion analysis identified 16 cases of robust relative risk (RR) intensification, predominantly among elderly populations. Females and males aged 65+ with metabolic diseases exhibited the highest thermal vulnerability. Our analysis further indicates a systematic shift in mortality risk toward higher nocturnal temperatures and reduced diurnal variability, suggesting a transition from cold-related stress to persistent nighttime heat exposure. Spatial Bayesian modeling shows a progressive homogenization of environmental risk across the metropolitan area, with high-risk thermal profiles expanding from the urban core toward peripheral municipalities, reducing the extent of previously lower-risk zones. Notably, the number of municipalities in the highest risk category for females aged 65+ with metabolic diseases increased by 550%, while for males of the same age, the expansion reached 163%. These findings indicate that vulnerability in megacities is a dynamic process driven by nocturnal warming and thermal instability. They highlight the urgent need to integrate climate-sensitive planning strategies—such as the identification and preservation of climatic refuge zones—into urban development policies, alongside continuous monitoring of temperature-related health risks. Full article

Evaluating innovation and optimising its role in the inventions is fundamental for applied research, that requires planning the use of available resources. Traditional assessment approaches often miss to capture how innovation stagnates between the ideation and prototyping phases (the Valley of Death), and to learn how innovation emerges from intermediate-steps contributed by individuals. This paper focuses on tracing innovation as an approach enabling mapping of pathways of intermediate-steps and opportunities for valorising unplanned outcomes. We adopt a qualitative case study to explore how innovation pathways can be conceptualised through technological readiness levels. The operational settings of an EU-funded project defined the boundaries of the study. A network analysis explored relationships among themes that emerged from respondents involved in the activities, following an inductive approach to derive themes from data. Findings indicate that intermediate innovation steps, including failures, are viewed as cumulative contributions to novelty. Their documentation is seen as an investment for unlocking latent value embedded in distributed knowledge. Within this scope, we outline a blockchain-based knowledge graph as a proof-of-concept for tracing cumulative contributions, identifying breakthroughs leading to technological maturity and supporting generation of hypothesis grounded on experimental trials. As a result, we suggest that paths recombining prior knowledge into novelty encode latent value that can be interpreted as a function of the network topology, and propose a conceptual framework for analysing value by means of information theory metrics applicable to innovation graphs. Full article

We analysed data collected at the Innsbruck Alpenzoo (Tyrol, Austria) over 33 years (1988–2020). We examined data from 4542 wild birds of 137 species that were rescued in the increasingly urbanised and densely populated Inn Valley around Innsbruck and examined the outcome of hospital treatment (survival or death); for a subgroup of 3440 birds, we examined the length of stay at the zoo. The birds were divided into nine different groups, and the reasons for admission were divided into nine categories to analyse how the reasons for admission and membership of a bird group influences rehabilitation success and the duration of care required. Orphaned birds, birds that had become entangled in man-made structures, and birds with unknown reasons for admission had the best survival rates (60%), while birds with physical injuries, victims of collisions, and attacks by cats had the lowest survival rates (37%). Survival rates were highest among areal insectivores (66%) and waterbirds (62%), and lowest among small songbirds (45%) and woodpeckers (<39%), which suffered disproportionately from the consequences of window collisions. The overall survival rate of hospitalised birds (51%) was higher, and the duration of care required (median 11 days) was especially shorter at Innsbruck Alpenzoo than at most other rehabilitation centres. We attribute this mainly to the professional care and varied, group-specific diet provided to the patients, which we describe in detail. We also discuss the problems and limitations of wild bird care for zoo staff in addition to their daily tasks. Thereby, it became apparent that the retirement of experienced bird carers at the beginning of the study period and the subsequent steady changeover of staff members had a negative impact on success rates. Full article

Background/Objectives: Although the binarism between type I and II endometrial cancer was dismissed and substituted with molecular classification, histopathological features remain of paramount importance. Hence, analysing survival outcomes according to histological type, our aim is to clarify whether the morphological features of the tumour retain prognostic relevance in the context of advanced disease. Methods: This is a retrospective analysis led within the Thames Valley Cancer Alliance Network. Results: We include 148 FIGO 2009 stage III–IV patients affected by endometrioid endometrial cancer (EEC) G1, G2, and G3, carcinosarcoma (CS), serous carcinoma (SC), and clear cell carcinoma (CCC) of the uterus. Five year overall survival (OS) is distinct among the histological groups (p-value < 0.001), being 73.3% for G2 endometrioid, 49.2% for G3 endometrioid, 8.3% for CS, and 28.4% for SC. The divergence was marked also for 5 year progression-free survival (PFS) (p-value < 0.001) as follows: for G2 endometrioid, was 76.4%; for G3 endometrioid, 52.7%; and for carcinosarcoma, 5.9%. PFS after 18 months for serous carcinoma was 5.7%. The multivariate analysis found G3 endometrioid (HR 2.91, 95% CI 1.20–7.11, p-value 0.018), carcinosarcoma (HR 12.15, 95% CI 5.07–29.11, p-value < 0.001), and serous carcinoma (HR 4.84, 95% CI 2.16–10.83, p-value < 0.001) as independent predictors of poor survival, as well as cervical invasion (HR 1.83, 95% CI 1.10–3.05, p-value 0.020) as the only histopathological feature confirmed. Regarding progression-free only carcinosarcoma (HR 14.91, 95% CI 5.28–41.11) and serous carcinoma (HR 17.68, 95% CI 6.41–48.75) were associated with an increased risk of recurrence. Conclusions: Our findings testify that, beyond the disease stage, histological subtype remains a major determinant of survival outcome. Cervical involvement is associated with a more aggressive disease, possibly correlated to death beyond relapse. Prospective trials involving advanced stage endometrial cancer, stratified by histological subtype and integrated with the molecular classification, are required. Full article

Many green technology innovations developed by academic institutions struggle to cross the “Valley of Death” (VoD), failing to achieve commercialization. Boundary-spanning green technology search (BGTS), as an inter-organizational mechanism facilitating the interaction of green technology knowledge between firms and external stakeholders, can bridge the gap between green scientific research and the commercialization of green products. Drawing on the resource orchestration theory and recombinant search theory, this study empirically analyzed data from 313 Chinese manufacturing enterprises to explore the pathway through which BGTS promotes green product development performance (GPDP) and examines the chain mediating role of knowledge coupling and green technology commercialization capability (GTCC), as well as the moderating role of digital technology adoption and product complexity. The findings reveal that the relationship between BGTS and GPDP is sequentially mediated first by knowledge coupling and then by GTCC. Digital technology adoption positively moderates the BGTS-GPDP relationship. Product complexity moderates the BGTS-GPDP relationship in an inverted U-shape. This study elucidates the micro-mechanism underlying the commercialization of green technologies, providing both theoretical insights and practical guidance for the green and high-quality transformation of manufacturing enterprises. Full article

This study adopts the 5W2H management tool to investigate the opportunities and challenges of enzymatic biodiesel production from residual oils. The methodological approach enables a structured evaluation of technical, economic, environmental, and governance aspects, clarifying critical conditions for feasibility and scalability. To illustrate this framework, the research applies it to the Brazilian biofuel sector, focusing on the valorization of Distillers Corn Oil (DCO), a by-product of corn ethanol production not intended for human consumption. Results show that enzymatic conversion of DCO can reduce feedstock costs by more than 50% and energy demand by up to 86.8% compared with conventional chemical processes. Nevertheless, the scalability of this technology faces critical barriers, such as enzyme costs, reaction times, and regulatory uncertainties. The study concluded that public–private partnerships and targeted policies, such as those under Brazil’s National Biodiesel Program (PNPB), are essential to overcoming these challenges and bridging the “valley of death” toward commercialization. By combining technical, economic, and governance perspectives, the study demonstrates that DCO-based enzymatic biodiesel has the potential to reinforce Brazil’s role in the global biofuels market while promoting a circular and sustainable energy transition. Full article

This study presents a comprehensive latitudinal analysis of air particulate matter (PM) across an 1400 km pollution corridor spanning Chile’s central-southern zone. We systematically analyzed PM_2.5 and PM₁₀ concentrations across eight major urban centers (2014–2015), providing crucial pre-Paris Agreement baseline data for South America’s most extensive air quality monitoring network. Our analysis reveals significant pollution gradients, with Coyhaique ranking one of the world’s most severely polluted cities (95th percentile globally, WHO database) and demonstrating an extreme 86% fine particulate matter ratio that far exceeds international urban standards. Residential wood combustion (RWC) demonstrates systematic correlations with fine PM concentrations (R² > 0.96), suggesting RWC is the dominant pollution driver across multiple climate zones. The documented pollution patterns represent a concerning continental-scale environmental pattern, with 4900–6500 annual premature deaths directly attributable to PM_2.5 exposure-one of the highest per-capita pollution mortality rates in South America. This work provides a methodological framework applicable to mountain-valley pollution systems globally while addressing critical knowledge gaps in regional air quality science. The evidence indicates the need for urgent implementation of comprehensive wood combustion control strategies and positions this research as essential baseline documentation for both national air quality policy and international climate change assessment frameworks. Full article

Hybrid Renewable Energy Systems are pivotal for the sustainable energy transition, yet their design and operation present complex optimization challenges due to diverse components, stochastic resources, and multifaceted objectives. This systematic review formalizes the HRES optimization problem space and identifies critical research gaps. Employing the PRISMA 2020 guidelines, it comprehensively analyzes the literature (2015–2025) from Scopus, IEEE Xplore, and Web of Science, focusing on architectures, mathematical formulations, objectives, and solution methodologies. The results reveal a decisive shift from single-objective to multi-objective optimization (MOO), increasingly incorporating environmental and emerging social criteria alongside traditional economic and technical goals. Metaheuristic algorithms (e.g., NSGA-II, MOPSO) and AI techniques dominate solution strategies, though challenges persist in scalability, uncertainty management, and real-time control. The integration of hydrogen storage, vehicle-to-grid (V2G) technology, and multi-vector energy systems expands system boundaries. Key gaps include the lack of holistic frameworks co-optimizing techno-economic, environmental, social, and resilience objectives; disconnect between long-term planning and short-term operation; computational limitations for large-scale or real-time applications; explainability of AI-based controllers; high-fidelity degradation modeling for emerging technologies; and bridging the “valley of death” between simulation and bankable deployment. Future research must prioritize interdisciplinary collaboration, standardized social/resilience metrics, scalable and trustworthy AI, and validation frameworks to unlock HRESs’ potential. Full article

Rift Valley Fever Virus (RVFV) is an arbovirus that predominantly affects sheep, goats, and cattle, causing epizootics in livestock and epidemics in humans. Infection in pregnant livestock leads to high abortion rates and neonatal mortality. In humans, RVFV usually causes a self-limiting febrile illness, but severe forms can develop, such as hepatitis, hemorrhage, encephalitis, and death. In addition, the association between RVFV infection during pregnancy and miscarriages or stillbirths has been documented. RVFV is transmitted by a range of mosquito species, and, due to the diffusion of these insects, the virus has spread in several world regions, making possible the risk of a public health emergency. Nevertheless, research remains limited and cellular pathology is still poorly characterized. This work aimed to fill some knowledge gaps on the comprehension of RVFV pathogenesis. For this purpose, transmission electron microscopy (TEM) was used to analyze cellular modifications associated with RVFV morphogenesis in four human cell lines (HuH-7, LAN-5, A549, and HTR-8/SVneo) derived from liver, brain, lung, and placenta. Our results showed that all four cell lines are permissive to RVFV infection and highlighted differences in the cytopathogenesis associated with the cell type. These findings could have important implications in understanding disease mechanisms and developing antiviral strategies. Full article