Search Results (204,988)

The interaction between humans and birds plays an important role in shaping the sustainability of tropical rainforest ecosystems, particularly through bird vocalizations that function as bioacoustic indicators of ecological conditions while simultaneously embedding socio-cultural meanings within local communities. This study aims to (1) classify types and categories of bird sounds as perceived by rural communities, and (2) assess the role of bird vocalizations as cultural symbols supporting community-based conservation practices. The study was conducted across six islands and eight villages in North Maluku, Eastern Indonesia, using a qualitative approach based on semi-structured interviews and community workshops. A total of 435 respondents, all of whom were farmers residing along forest margins, participated in the study. The results documented 51 bird species belonging to 26 families, whose vocalizations were interpreted and classified by local communities into three acoustic categories: 21 species with loud calls (41.18%), 12 species with melodious calls (23.53%), and 18 species with sad calls (35.29%). Melodious vocalizations were commonly associated with values of beauty, calmness, and social harmony, whereas loud calls were predominantly interpreted as warnings, signals of alertness, or indicators of environmental change. These findings demonstrate that bird sounds serve not merely as ecological cues, but as culturally embedded symbols that guide daily activities, moral values, and conservation ethics within rural communities. By documenting the cultural significance of bird vocalizations across a clearly defined geographic context, this study provides an empirical basis for culturally informed conservation strategies aimed at protecting bird species subject to high levels of cultural use and ecological pressure. Full article

Central nervous system disorders drive disability, yet many neuroactive candidates fail because the brain is a hard compartment to dose. Plant-derived molecules spanning polyphenols, alkaloids, terpenoids, and cannabinoids are attractive because their pleiotropic actions can engage oxidative stress, neuroinflammation, and circuit dysfunction. In practice, the blood–brain barrier (BBB) restricts most native phytochemicals through tight-junction selectivity, rapid metabolism, low solubility, and transporter-mediated efflux. Key gaps include poor standardization of exposure metrics, limited human-relevant BBB models, and few head-to-head studies that compare delivery platforms on the same payload and outcome. This review tackles the mismatch between mechanistic promise and reliable brain exposure that stalls translation. The objectives are to link phytochemical liabilities to enabling strategies in nanomedicine, alternative routes, and transporter-targeted prodrugs, and to propose decision-grade endpoints for translation. We synthesize evidence on BBB transport logic, nanocarrier families, targeting ligands, intranasal delivery, focused ultrasound-mediated opening, and prodrug approaches that hijack influx transporters, while foregrounding safety and chemistry, manufacturing, and controls (CMC) constraints. Here we highlight that effective neurotherapeutics emerge when chemistry, carrier, route, and measurement are co-designed rather than optimized in isolation. This framework can guide platform selection, de-risk first in-human studies, and sharpen trial endpoints. More broadly, it offers a transferable playbook for barrier-limited drug development across neurology, psychiatry, and oncology. Full article

Terminal lakes in arid regions face severe degradation due to the dual pressures of climate change and anthropogenic water consumption. Traditional single-threshold methods for defining ecological water requirements often fail to balance ecosystem stability with water scarcity. To address this, this study constructs a comprehensive framework coupling “Morphometric Stability–Ecological Security Reliability–Resource Use Efficiency” to delineate the suitable ecological interval for Ebinur Lake, the largest saltwater lake in Xinjiang. Using multi-source remote sensing data (Landsat, Sentinel, ICESat, CryoSat), we reconstruct the long-term hydrological dynamics from 2001 to 2023. Results indicate a significant shrinking trend in the lake area, driven primarily by reduced inflow. We jointly consider the lake morphometric breakpoint, the ecological security baseline, and the lower bound of ecosystem service water use efficiency (ESWUE) to determine a minimum suitable ecological area of 500 km²; the regulation upper limit is set at 740 km² based on the marginal peak of ESWUE. However, monitoring data reveal that the lake falls below the minimum 500 km² baseline in approximately 40% of months, highlighting a severe ecological deficit risk. Furthermore, ESWUE analysis shows a peak in April (10 CNY/m³), suggesting that, under current climate conditions, a “Spring Surplus and Autumn Deficit” regulation strategy—advancing the replenishment window to the spring windy season—can maximize dust suppression benefits at a lower evaporative cost. This study provides a theoretical basis and methodological paradigm that will contribute to the sustainable management of shrinking terminal lakes globally. Full article

Since software development is in constant evolution, it presents new facets and emerging topics. For example, the integration of qualitative data analysis through Grounded Theory establishes a new approach to categorizing this discipline, allowing it to align with these new contributions. The present work applies an original Glaserian Systematic Mapping Study (GSMS) to explore new ways of categorizing software development using Grounded Theory (GT) and GT elements. The study provides insights from the perspective of human beings, including their trust and doubts, and their attitudes towards work teams. The categorization covers many aspects of software development. One of these relates to Agile development, which has been defined in two pairs: Agile/Non-Agile and Agile/Plan-driven. Although this may seem obvious, this categorization had not been defined in this way before. Data, in all its diversity, accompanies the software development process throughout its entire lifecycle. Another finding of the present work is the concept of bridges, which correspond to the diverse interrelationships within software development. Grounded Theory in the context of software development has enabled the creation of various types of bridges. These bridges could be established between individuals within the same development team, between different areas of software development, or between developers and their tools and artifacts, among others. These findings can be highly diverse and can help software engineers unlock their potential and explore various options in software development. Full article

Background/Objectives: Although copper nanoparticles (Cu-NPs) are increasingly explored as food and feed additives, there is still limited evidence on how the commonly consumed dietary fibre matrix modulates their effects on the gut microbiota. This study evaluated whether different dietary fibres (cellulose, pectin, inulin, psyllium) modulate Cu-NP–driven changes in caecal microbiota activity, composition, and bile acid metabolism in rats in a multifactorial design accounting for fibre type, copper dose, and copper form. Methods: Wistar male rats (n = 10 per group, 10 groups) were fed semi-purified diets for 6 weeks. Cu-NPs were provided at 6.5 or 13 mg Cu/kg diet and combined with cellulose (control fibre) or with pectin, inulin, or psyllium. Caecal digesta parameters, microbial enzyme activities, short-chain fatty acids (SCFAs), bile acids, and 16S rRNA sequencing were used to assess microbial diversity. Results: Final body weight did not differ among groups, whereas feed intake decreased most consistently with inulin and psyllium. Inulin and psyllium increased caecal digesta and tissue mass, while pectin increased caecal ammonia. Higher Cu-NPs dose reduced several microbial enzyme activities and lowered major SCFAs across most treatments; pectin most strongly preserved/enhanced glycosidase activities and was associated with increased SCFA levels vs. control, with a 32% rise in acetate, a 47% rise in propionate, and a 61% rise in butyrate. Fibre type dominated bile acid outcomes: psyllium reduced total bile acids by 11.8% vs. control, while inulin increased muricholic acids by 216% vs. control. Microbiota alpha and beta diversity separated primarily by fibre type, with distinct clustering particularly in pectin-fed groups. Across comparisons, Mucispirillum was consistently reduced in fibre-supplemented groups vs. cellulose, alongside recurrent changes in selected genera; functional profiling highlighted shared shifts in carbohydrate, fermentation, transport, and stress-response features under Cu-NPs exposure. Conclusions: The gastrointestinal and microbiota responses to Cu-NPs are strongly fibre-dependent; thus, Cu-NP safety and functionality should be evaluated together with the accompanying dietary fibre matrix, not as a standalone exposure. Implications for humans remain indirect and require confirmation in human-relevant models and clinical settings. Full article

Burkholderia pseudomallei is a saprophytic environmental bacterium and the causative agent of melioidosis, a serious opportunistic infection in tropical regions, including northern Australia. Infection occurs following environmental exposure via percutaneous inoculation, ingestion, or inhalation; however, the environmental reservoirs and transmission pathways responsible for human disease remain poorly defined. Groundwater has been implicated as a potential source of infection, but the factors influencing the persistence and mobility of B. pseudomallei in surface waters in North Queensland are not well understood. Water samples were collected from a groundwater-connected seasonal creek in Townsville, North Queensland, over a 12-month period encompassing wet and dry seasons. Samples were cultured on Ashdown agar and confirmed as B. pseudomallei by qPCR. Multi-locus sequence typing (MLST) was performed using targeted allele sequencing on the Oxford Nanopore MinION platform. Eighteen of 59 water samples were culture-positive for B. pseudomallei. Detection occurred exclusively in turbid, flowing water following ≥30 mm of rainfall and was observed in both wet and dry seasons. MLST of 48 isolates identified 18 sequence types, including 12 novel types. Six sequence types matched previously reported Townsville clinical isolates. These findings indicate that groundwater from a connected urban creek may function as a mobile reservoir for clinically relevant B. pseudomallei strains under specific hydrological and climatic conditions, highlighting rainfall-driven processes as key drivers of environmental exposure risk. Full article

Retinitis pigmentosa (RP) comprises a heterogeneous group of inherited retinal dystrophies characterized by the progressive degeneration of photoreceptors, leading to night blindness and gradual loss of peripheral vision. RP is characterized by a substantial genetic heterogeneity, with more than 85 genes implicated across autosomal dominant, autosomal recessive, and X-linked inheritance patterns. Recent studies have identified mutations in the ARL3 gene as a causative factor in both syndromic and non-syndromic forms of RP, including autosomal dominant and recessive cases. ARL3 encodes a small GTPase that plays a crucial role in intracellular trafficking, particularly within photoreceptors. This process is critical for maintaining ciliary function and phototransduction. Here, we investigate the pathogenic mechanisms of the ARL3 c.199G>C (p.Asp67His) variant identified in individuals from a four-generation family. We show that mutant ARL3 disrupts normal protein expression and affects ciliogenesis. Clinically affected individuals showed a non-syndromic retinal degenerative RP phenotype, with marked intrafamilial heterogeneity, ranging from extensive retinal atrophy to the absence of clinical manifestation, independent of age. This report highlights the incomplete penetrance and variable expressivity associated with the ARL3 variant and emphasizes the value of combining molecular diagnostics with functional validation to expedite molecular diagnosis. Full article

Background/Objectives: Non-small cell lung cancer (NSCLC) is the most frequent type of lung cancer, and its main treatments include chemotherapy with genotoxic drugs and immunotherapy. Central to the cellular response to genotoxic stress is the DNA damage response (DDR) network, regulated by key kinases such as ataxia-telangiectasia mutated and Rad3-related (ATR). Herein, we tested the hypothesis that inhibition of ATR enhances the cytotoxicity of genotoxic agents and the antitumor immune response. Methods: DDR-related parameters and redox status, expressed as GSH/GSSG ratio, and apurinic/apyrimidinic lesions, were evaluated in human (A549, H1299) and murine (LLC) NSCLC cell lines after co-exposure to ATR inhibitor (AZD6738) and ultraviolet C (UVC) irradiation or cisplatin. Using a syngeneic LLC model, treatments of AZD6738 alone or in combination with cisplatin and/or anti-programmed cell death 1 antibody (anti-PD1) were examined. Results: In all cell lines, combined treatment with AZD6738 and cisplatin or UVC irradiation markedly decreased cell viability, DNA repair efficiency, and GSH/GSSG ratios; increased drug-induced DNA damage; and augmented apurinic/apyrimidinic lesions. In vivo, following treatment with AZD6738 and cisplatin, flow cytometry analysis performed in tumor cells revealed an increased infiltration of CD3⁺ and CD8⁺ T cells, with the triple combination of AZD6738, cisplatin, and anti-PD1 achieving the strongest antitumor effect. The CD3⁺CD4⁻CD8⁻ double-negative (DN) T cell population in tumor samples also emerged as a contributing factor in this context. Conclusions: These results demonstrate that ATR blockade concurrently enhances the efficacy of genotoxic agents and immune checkpoint inhibitors, thus paving the way for combination therapies in NSCLC. Full article

Background: CGRP contributes to cerebrovascular regulation, mainly based on experimental and translational data; human evidence remains limited. Gepants, including atogepant, are effective migraine preventives and achieve partial penetration across the blood–brain barrier. However, their neurologic and cerebrovascular safety in heterogeneous patient populations remains incompletely characterized. Objective: To describe acute neurologic events observed during atogepant therapy, provide contextual information regarding their baseline occurrence, and explore potential mechanisms by which CGRP receptor blockade may influence neurovascular resilience. Methods: We report five adults treated with atogepant (30–60 mg/day) who developed acute neurologic symptoms prompting emergency hospital admission. All patients underwent comprehensive diagnostic assessment including neuroimaging, vascular studies, cardiac evaluation, and laboratory testing. To provide context, a retrospective comparison cohort of migraine patients not treated with gepants during a similar period was analyzed. Baseline characteristics were summarized, and event occurrence was compared using Fisher’s exact test. Results: Among 575 individuals treated with atogepant, five experienced acute neurologic events, including one cerebellar infarction and several transient focal syndromes without structural correlates. No cerebrovascular events requiring hospitalization were identified in the non-gepant cohort (n = 610). In an unadjusted analysis, this difference was statistically significant (p = 0.027). The events were clinically heterogeneous, and several lacked radiologic confirmation of ischemia. Conventional vascular risk factors were present in some patients. Conclusions: These findings do not imply causality but raise the possibility that CGRP receptor blockade may reduce cerebrovascular adaptability in susceptible individuals. Clinicians should remain vigilant for ischemia or microvascular dysfunction when patients receiving atogepant present with acute vertigo, diplopia, ptosis, or hemisensory symptoms—even when CT and CTA are normal—and obtain timely MRI and vascular assessment. The absence of comparable events in a retrospective non-gepant cohort provides contextual information but does not permit inference regarding increased risk due to potential confounding and unmeasured factors. The findings are exploratory and hypothesis-generating, underscoring the need for prospective controlled studies to clarify the cerebrovascular safety of CGRP receptor antagonists in routine clinical practice. Full article

Sustainable regional competitiveness is widely recognized as a cornerstone for fostering economic growth, social well-being, and environmental sustainability at the local level. Building upon our previous research, in which we extensively examined the ten factors shaping regional competitiveness, this study continues the investigation by focusing on the same nine factors while replacing environmental considerations with civil protection, utilizing updated literature spanning 2020 to 2025. The study’s time frame was from March 2025 to November 2025. A literature review methodology was adopted, emphasizing critical evaluation rather than a systematic review. Recent studies published within the last five years were analyzed, with particular attention to these ten recognized factors: (1) economy, (2) labor market, (3) poverty and social inclusion, (4) healthcare, (5) educational infrastructure, (6) environmental considerations, (7) transportation infrastructure, (8) science and technology, (9) high-tech industries, and (10) innovation. The key findings of the study emphasize the distinct yet interconnected role of each factor in shaping regional competitiveness. Economic development remains foundational, closely linked with education, causes of death, and sustainability, highlighting that a strong economy alone is insufficient. Labor market dynamics, including youth employment and skills development, are crucial for translating potential into growth, while addressing poverty and social exclusion requires coordinated social and economic policies. Public health indicator reflect societal challenges and helps identify areas where targeted interventions can enhance well-being and productivity. Education strengthens human capital, supports innovation and high-tech industries, and promotes social inclusion, creating the foundation for sustainable regional growth. Environmental issues shape the risks that civil protection must manage, while effective environmental protection reduces the need for emergency response. Transportation infrastructure connects economic activity, Research & Development (R&D), Information and Communication Technologies (ICT) deployment, and innovation, enhancing regional integration. Science and technology, particularly ICT, drive productivity and competitiveness, while human capital plays a central role in the development of high-tech industries, supporting innovation and economic diversification. Finally, innovation underpins the capacity of regions to adapt and maintain a long-term competitive advantage. Overall, this research demonstrates that by retaining the same nine core factors and replacing environmental considerations with civil protection, it is possible to gain new insights into regional competitiveness. Full article

Three-dimensional (3D) organoid and co-culture models have emerged as transformative tools for studying human endometrial function, implantation, and placental development, overcoming key limitations of animal and two-dimensional in vitro systems. This review synthesises available information of recent advances in endometrial epithelial organoids (EEOs), trophoblast organoids (TBOs), and increasingly complex co-culture platforms incorporating stromal, vascular, and trophoblast compartments to model epithelial–stromal crosstalk, decidualisation, angiogenesis, and embryo implantation. Emerging developments include assembloid systems, synthetic and semi-synthetic extracellular matrices, and microfluidic organ-on-a-chip technologies that enable long-term culture, hormonal responsiveness, and patient-specific modelling. These approaches have recapitulated key features of the mid-secretory endometrium, placental villous architecture, trophoblast differentiation, and early implantation events while revealing disease-associated dysfunctions in conditions such as endometriosis, adenomyosis, polycystic ovarian syndrome, and endometrial cancer. Despite significant progress, current models remain limited by incomplete cellular diversity, polarity constraints, and challenges in fully modelling immune and vascular interactions. Collectively, emerging 3D organoid and co-culture systems provide physiologically relevant platforms to interrogate human reproductive biology, elucidate mechanisms underlying implantation failure and placental disease, and support the development of personalised therapeutic strategies to improve reproductive outcomes. Full article

The rise of shared e-bike systems presents a promising solution for sustainable urban mobility, yet their operational efficiency is often hampered by unpredictable user demands. This challenge directly impacts the achievement of SDG 11 by creating service inconsistencies that can deter users. To address this, we propose a data-driven methodology for optimizing resource allocation in shared e-bike systems. Based on large-scale trip data from Ningbo, China, our analysis reveals significant spatiotemporal demand regularities at a fine-grained, cell-based level, including pronounced commuting peaks and clear spatial heterogeneity between high- and low-demand zones. Building upon these findings, we implement a SARIMAX model to generate accurate, hourly, day-ahead demand forecasts that incorporate key contextual information. Our results indicate that the SARIMAX model provides substantial improvements in predictive accuracy while offering superior interpretability and practical computational efficiency. The resulting forecasts enable data-informed decision-making for critical operations such as fleet rebalancing, battery swapping, and parking zone management. This study provides a robust and routine transparent tool for shared mobility operators, demonstrating how industrial engineering principles and statistical modeling can directly enhance the sustainability and user experience of urban transportation systems. Full article

Background: Suicidality continues to rise, while mental health services face obstacles of access, availability, and affordability. Digital peer support (DPS) may help bridge these gaps and facilitate early identification of suicidal ideation (SI). Objective: This study examined (1) the effectiveness of a hybrid solution combining a proprietary AI-based SI detection with real-time human moderation within DPS, (2) distribution of SI, (3) active SI referral, (4) linguistic differences in SI, (5) sentiment changes among users, and (6) the effects of peer SI disclosure. Methods: We retrospectively analyzed 169,181 live-chat transcripts encompassing 449,946 user visits (January–December 2024) from a DPS provider, Supportiv. Passive and active SI were identified using a hybrid AI and human moderator solution with post hoc LLM verification. Sentiment analysis and ANCOVA compared changes in sentiment across three propensity-matched user groups: passive SI users, non-SI users exposed to peer SI, and non-SI users not exposed to SI. Results: SI occurred in 3.19% of live chats. The AI model identified SI faster than humans (in 77.52% passive and 81.26% active cases), with 90.3% agreement. Moderators followed up 71.3 s after AI alerts and referred 5472 active SI users (1.21%) to crisis care. All users significantly benefited from DPS, with reductions up to 29.3% in depression, 26.8% in loneliness, 25.3% in despair, and 22.3% in helplessness, with optimism increasing up to 40.4%. Conclusions: AI-integrated, human-moderated DPS offers scalable and effective support for high-risk populations. The proprietary SI detection AI model accurately detects suicidality, allowing for human-moderated DPS to improve the mental well-being of users with and without SI, and maintains peer safety. Full article

The Church of St. Francis in Pula, Croatia, is a well-preserved example of Franciscan gothic sacral architecture from the late 13th century. As preaching was highly valued by the Franciscan order as a way of communicating with the faithful, the study is focused on determining whether speech intelligibility in the church would have been adequate for successful communication between priests and their audience. The archaeoacoustic analysis of the church was performed in four stages: (1) in situ acoustic measurements in the present state, (2) development and calibration of the model of the present state based on measurement results, (3) development of the two models of the presumed historical state based on the calibrated model and historical data, and (4) prediction of acoustic conditions in the present and the historical states in terms of reverberation time T₃₀ and of speech intelligibility in terms of speech transmission index STI. The factors considered in the study were (1) acoustics of the church, (2) profile of the audience (friars and the faithful), (3) layout of the audience areas (choir area in the front of the nave for the friars, back area of the nave for the faithful), (4) positions of the speech sources (altar for addressing the friars, pulpit for addressing the faithful), (5) occupancy (unoccupied and fully occupied church), (6) language used in liturgical ceremonies (Latin and native language), and (7) language proficiency of the audience (native speakers, users of a second language). The results show that (1) fair speech intelligibility (STI ≥ 0.45 for the faithful as native speakers, STI ≥ 0.50 for friars as non-native speakers of Latin) can be achieved for 50% of the audience in the choir area and for the entire audience in the back area in favourable conditions (fully occupied church, audience addressed from dedicated speaker positions), (2) the position of the pulpit (close to the audience and considerably elevated above it) is more favourable than the position of the altar (remote, barely elevated above the audience), and (3) in unoccupied conditions, fair speech intelligibility can still be achieved in at least 50% of the back audience area with the faithful gathered close to the pulpit, while it is not possible for the front audience area addressed from the altar. The summary conclusion is that the church of St. Francis in its presumed historical layout(s) would fulfil its primary function in a limited capacity. Fair speech intelligibility would likely have been sufficient for the audience to follow liturgical ceremonies conducted in the church, but not without difficulty. Full article

Corn is a critically important agricultural crop, with different parts consumed at specific growth stages—notably, fresh corn and corn grain. The field residue behaviors of clothianidin and phoxim in fresh corn and corn grain were investigated by using a QuEChERS technique combined with UPLC-MS/MS, and the dietary exposure risks of the insecticides were evaluated. Field trials were conducted under the recommended application conditions (2250 g active ingredient per hectare of 2% clothianidin and phoxim granules, applied once) at 12 agricultural regions across China under various climatic conditions to study the residue levels of pesticides. The samples were collected at harvest of fresh corn and corn grain, separately. The results indicated that the residues of the phoxim remained stable in all samples stored at −20 °C for 6 months (180 days). At harvest, the concentrations of clothianidin in fresh corn ranged from <0.01 to 0.027 mg/kg (below the MRL of 0.1mg/kg established by Japan); the concentrations of phoxim in fresh corn were all below 0.01 mg/kg (below the Chinese MRL of 0.1mg/kg). In corn grain, clothianidin residues ranged from <0.01 to 0.018 mg/kg (below the Chinese MRL of 0.02mg/kg), while phoxim residues were below 0.01mg/kg (below the Chinese MRL of 0.1mg/kg). Dietary risk assessment based on Chinese pesticide registration status and the per capita dietary structure of Chinese residents showed that the national estimated daily intake (NEDI) of clothianidin for the general population was 0.49 mg, accounting for 7.8% of the adult acceptable daily intake (ADI), while NEDI of phoxim for the general population was 0.048 mg, accounting for 19.2% of adult ADI. The results suggest that the associated health risks are acceptable for the general population. On the basis of these findings, it is recommended to establish an MRL for clothianidin in fresh corn in China at 0.1 mg/kg. This study provided basic data on the use and safety of clothianidin and phoxim in fresh corn and corn grain to help the Chinese government formulate a maximum residue level for clothianidin in fresh corn. Full article