Search Results (9,125)

Background/Objectives: Multidrug-resistant (MDR) Escherichia coli resistant to third-generation cephalosporins are a growing One Health concern, but data on extraintestinal pathogenic E. coli (ExPEC) from wildlife in North Africa remain scarce. We aimed to characterize ESBL/AmpC-producing ExPEC from captive wild mammals in Tunisia and to situate these isolates in a global genomic context. Methods: In 2018, 30 fecal samples from 14 captive wild mammals in a private farm were screened on cefotaxime agar. Four cefotaxime-resistant E. coli isolates were recovered from a llama, lion, hyena, and tiger. Antimicrobial susceptibility testing and Illumina whole-genome sequencing were combined with in silico typing, resistome and virulome profiling, plasmid and mobile element analysis, human pathogenicity prediction and core-genome MLST-based minimum-spanning trees. Results: All isolates were MDR but remained susceptible to carbapenems, colistin and tigecycline. Two ST162/B1 isolates from the llama and tiger carried bla_CMY-2, whereas two ST69/D isolates from the lion and hyena harbored bla_CTX-M-15 and qnrS1. Genomes encoded 61–68 antimicrobial resistance genes and 114–131 virulence-associated genes, together with IncF-, IncI1- and IncY-type plasmids and IS26-rich insertion sequence profiles. Mating-out assays yielded cefotaxime-resistant transconjugants, supporting plasmid transferability of bla_CMY-2 or bla_CTX-M-15. PathogenFinder predicted a ≥0.93 probability of human pathogenicity for all isolates. cgMLST-based trees showed that Tunisian ST69 and ST162 clustered within internationally disseminated lineages containing human, animal and food isolates, rather than forming wildlife-restricted branches. Conclusions: Captive wild mammals in Tunisia can harbor high-risk ExPEC lineages combining ESBL/AmpC production, multidrug resistance and extensive virulence and mobility gene repertoires. These findings highlight captive wildlife as potential reservoirs and sentinels of clinically relevant E. coli and underscore the need for integrated WGS-based One Health surveillance at the human–animal–environment interface in North Africa. Full article

This study investigated the epidemiology, antimicrobial resistance, and transmission risks of β-lactamase, cefotaxime-hydrolyzing, Munich (bla_CTX-M)-positive Escherichia coli (CTX-M-EC) in large-scale pig farms in Jiangxi Province (China). In total, 278 samples (manure, wastewater, drinking water, and flies) were collected. CTX-M-EC strains were isolated and analyzed using antimicrobial susceptibility testing, resistance gene profiling, multilocus sequence typing, and genetic environment analysis with gene transfer assessed by transduction experiments. Twenty-seven CTX-M-EC strains (9.71%) were isolated, all exhibiting multi-drug resistance with 100% resistance to cefotaxime, ciprofloxacin, and tetracycline, and >90% resistance to ceftazidime, florfenicol, and trimethoprim-sulfamethoxazole. Four bla_CTX-M subtypes were identified. bla_CTX-M-55 was the predominant subtype (70.37%) and was distributed across diverse sequence types and serotypes. Each strain harbored multiple antibiotic resistance genes, plasmids, and virulence genes. Mobile elements such as ISEcp1 and IS26 were detected surrounding the bla_CTX-M gene, and 96.29% of strains successfully transferred the bla_CTX-M gene via transduction. Clones highly homologous to pig manure strains were detected in flies and sewage, suggesting that this resistance gene can spread between animals, the environment, and vectors. These findings highlight the high transmission risk of bla_CTX-M and underscore the need for rational antibiotic use, waste management, and vector control within a One Health framework. Full article

General pustular psoriasis (GPP) is a rare, potentially life-threatening neutrophilic dermatosis. Pediatric cases are uncommon and often misdiagnosed due to overlapping clinical and histopathological features with other pustular dermatoses. We present a case of an 11-year-old boy, initially diagnosed with Sneddon–Wilkinson syndrome, who presented with disseminated pustular eruptions, with no response to antibiotics, dapsone, and glucocorticosteroids. In histopathology, we observed subcorneal neutrophilic pustules. Due to atypical features and poor treatment response, the patient underwent genetic testing, which revealed a homozygous IL36RN gene c.338C>T (p.Ser113Leu) pathogenic variant, which enabled a definitive diagnosis of GPP. Treatment with acitretin led to clinical improvement. Pediatric GPP poses diagnostic and treatment challenges. Genetic testing for IL36RN pathogenic variants may aid in the diagnosis, especially in atypical cases. The presence of the biallelic IL36RN pathogenic variant supports the diagnosis of DITRA (Deficiency of the IL-36 Receptor Antagonist, ORPHA:404546)—a monogenic autoinflammatory form of GPP. Full article

Extracellular vesicles (EVs) can disseminate replication-competent viral genomes complexed with selected host proteins, enabling stealth cell-to-cell transfer within lipid membrane-enclosed bubbles. In addition to complementing free-virion spread, EV-associated genomes can be protected from neutralizing antibodies and persist under conditions in which classical virion production decreases. Here, we propose a route-resolved framework in which interconnected cellular secretory pathways, including endoplasmic reticulum (ER) remodeling, multivesicular body (MVB) biogenesis, secretory autophagy, and plasma-membrane budding, jointly generate EV heterogeneity and create discrete opportunities for the capture, protection, and export of infectious cargo. We highlight reticulon-3 (RTN3), an ER-shaping protein, as an upstream regulator that can couple infection-induced ER microdomains to endosomal docking and to autophagy-linked trafficking decisions that bias intermediates toward secretion rather than degradation. Supporting this view, transmission electron microscopy of dengue virus-infected cells reveals extensive vesicular remodeling, including irregular MVBs adjacent to the plasma membrane and autophagosome-like double-membrane structures, consistent with altered vesicular routing following RTN3 perturbation. Collectively, these route-resolved, spatially organized spatio-organelle changes support a pathomechanistic model in which RTN3-mediated ER remodeling reshapes ER-endosome-autophagy trafficking interfaces, creating regulated decision points that can be leveraged to stratify infectious EV subsets (with infectivity-linked single-vesicle and quantitative proteomics approaches) and to inform host-directed strategies that curb non-lytic viral dissemination. Full article

Triple-negative breast cancer (TNBC) is one of the most aggressive and clinically challenging subtypes of breast cancer, defined by the absence of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 expression. The lack of actionable molecular targets contributes to limited therapeutic options, frequent recurrence, and a high propensity for distant metastasis. Metastatic dissemination remains the principal cause of mortality in patients with TNBC and is driven by complex molecular mechanisms involving multiple interconnected signaling networks. This review summarizes current knowledge of the molecular mechanisms underlying metastatic progression in TNBC, with particular emphasis on signaling pathways that regulate tumor invasion, migration, and colonization of distant organs. We discuss the roles of key pathways, including PI3K/Akt, TGF-β, Wnt/β-catenin, NF-κB, and Rho/ROCK signaling, in the regulation of epithelial–mesenchymal transition, cytoskeletal remodeling, cancer stem cell phenotypes, and tumor–microenvironment interactions. A deeper understanding of these signaling networks may facilitate the identification of novel therapeutic targets and support the development of more effective strategies to limit metastatic disease in TNBC. Full article

Background/Objectives: High-grade serous ovarian carcinoma (HGSOC) is associated with high relapse rates despite aggressive multimodal treatment. BRCA mutations, present in a substantial subset of patients, confer homologous recombination deficiency and increased sensitivity to platinum-based chemotherapy. This study evaluated the association between BRCA mutation status and clinical outcomes, focusing on dissemination patterns, treatment allocation, perioperative parameters, and progression-free survival (PFS). Methods: This prospective single-center cohort included 133 consecutive patients with newly diagnosed HGSOC treated between January 2020 and December 2025. Primary treatment strategy (primary debulking surgery [PDS] or neoadjuvant chemotherapy [NACT]) was determined by multidisciplinary assessment. BRCA testing was performed using tumor tissue or germline analysis. Patients were followed for 24 months. PFS was analyzed using Kaplan–Meier estimates and Cox regression models. Results: Pathogenic BRCA mutations were identified in 39.1% of patients. BRCA-mutated tumors demonstrated significantly lower rates of peritoneal carcinomatosis (50% vs. 77.77%, p = 0.001) and were more frequently managed with PDS (59.6% vs. 41.8%, p = 0.048). Perioperative outcomes were comparable between groups. Disease progression occurred less frequently in BRCA-mutated patients (32.69% vs. 51.85%, p = 0.017). In univariate analysis, BRCA mutation was associated with a 48% reduction in progression risk (HR 0.52, 95% CI 0.27–0.99, p = 0.048). After adjustment for age, FIGO stage, and residual disease, BRCA mutation was not independently associated with progression (HR 0.57, p = 0.124), although a protective trend was observed, while residual disease remained a significant predictor. Conclusions: In this prospective cohort, BRCA mutation status was associated with distinct dissemination patterns and a significant reduction in progression risk in HGSOC. Although residual disease remained the strongest independent prognostic factor after multivariable adjustment, a trend toward improved PFS observed among BRCA-mutated patients supports the role of homologous recombination deficiency as a meaningful modifier of disease trajectory. These findings reinforce the clinical relevance of molecular stratification in the contemporary management of HGSOC. Full article

Background: Irrigation with swine wastewater may increase the dissemination risk of antibiotic resistance genes (ARGs) in the rhizosphere and alter root exudate composition. However, the relationship between root exudates and ARG dynamics under swine wastewater irrigation remains poorly understood. This study therefore aimed to clarify how root exudates are connected with ARG dynamics under swine wastewater irrigation. Methods: To address this, untargeted metabolomics and metagenomic sequencing were combined to characterize rhizosphere ARG composition, microbial community structure, and root exudate profiles in different soybean cultivars under swine wastewater irrigation. Results: The results showed that irrigation water source and soybean cultivar were associated with variation in soil ARG composition and changes in plant root metabolic profiles. Under wastewater irrigation, the relative abundances of secondary metabolites in root exudates were generally elevated, particularly those of organic nitrogen compounds and organic oxygenated compounds. Cultivar-related variation remained evident in rhizosphere microbial communities and ARG profiles, and differences in exudate composition among cultivars became smaller. Irrigation water source and soybean cultivar were associated with changes in ARG dynamics. This association was mainly linked to variation in rhizosphere microbial community structure rather than direct effects of root exudates on ARGs. Xanthine and 3-isobutylpentanedioic acid, identified as key root exudates, increased under wastewater irrigation and were related to variation in the potential ARG host genus SCGC-AG-212-J23 and the related ARGs. In contrast, 5-methylheptan-3-one decreased under wastewater irrigation and was correlated with variation in SCGC-AG-212-J23, Gp6-AA40, and the related ARGs. Conclusions: Swine wastewater irrigation and soybean cultivar altered root metabolism, which were linked to variation in rhizosphere microbial communities. These changes may have collectively contributed to shifts in rhizosphere ARGs. This could provide a basis for understanding the ecological relationships among root exudates, microorganisms, and ARGs under swine wastewater irrigation. Full article

Tumor-associated macrophages (TAMs) are among the most abundant immune cell populations in breast cancer and have emerged as central regulators of tumor progression, metastatic dissemination, immune evasion, and therapeutic resistance. While TAMs were historically described using a simplified M1/M2 polarization framework, accumulating evidence indicates that TAMs in breast cancer comprise a continuum of phenotypic and functional states shaped by ontogeny (tissue-resident vs monocyte-derived), spatial localization (including hypoxic, perivascular, and invasive niches), tumor-intrinsic programs, and therapy-induced selective pressures. In breast cancer, mechanistic studies integrating lineage tracing, intravital imaging, single-cell and spatial profiling, and clinical analyses have established that TAMs actively coordinate rate-limiting steps of the metastatic cascade. These include promotion of angiogenesis and vascular permeability, orchestration of tumor cell invasion and TMEM-mediated intravasation, facilitation of metastatic seeding and niche formation, and suppression of anti-tumor immunity. TAMs also critically influence therapeutic response by modulating chemotherapy efficacy and limiting the activity of immune checkpoint blockade. Therapeutic strategies targeting TAMs in breast cancer have evolved from depletion approaches (CSF1/CSF1R blockade) to inhibition of monocyte recruitment (CCL2/CCR2 axis), functional reprogramming (CD40 agonism, PI3Kγ inhibition), and macrophage-directed checkpoint modulation (CD47–SIRPα axis). Early clinical studies demonstrate clear pharmacodynamic activity but highlight the need for context-specific and combination-based approaches. This review focuses on TAM biology in breast cancer progression and metastasis, synthesizing key mechanistic and translational evidence and proposing a framework in which spatially and functionally defined macrophage states act as rate-limiting regulators of dissemination and therapy response. We further outline principles for rational TAM-targeting strategies that integrate tumor stage, metastatic niche, and treatment context. Full article

The detailed mechanism and sequence by which tick-borne flaviviruses (TBFVs), such as Langat virus (LGTV), infect and disseminate in arthropod hosts remain undefined. To begin characterizing these processes, we used artificial membrane feeding chambers to feed adult Ixodes scapularis ticks with blood containing LGTV. At 24, 48, 72, and 96 hours (h) after attachment, we removed and dissected the partially fed ticks to obtain the midgut and salivary glands. Histology confirmed infection in cells of the digestive epithelium lineage; infection was noted in midgut generative cells and the more differentiated functional digestive cells over the course of feeding. The viral envelope (E) protein, nonstructural protein 3 (NS3), and double-stranded RNA (dsRNA) were readily detected in these cells by 48 h after infection. Parallel analysis indicated that cells in salivary gland acini were also infected by 48 h, where virus target cells appeared to be the granular cells in acini types II and III. Thus, both salivary glands and midgut showed direct evidence of infection by 48 h. Although viral staining was not observed at 24 h, when organs were removed at 24 h and individually cultured ex vivo, the virus was detected. Taken together, our results provide evidence of LGTV infection in both the salivary glands and midgut within the first 24 h of a blood meal. The findings should prompt a reevaluation of the systemic dissemination of TBFV in infected ticks. Full article

Senecavirus A (SVA) has rapidly emerged as a globally distributed swine pathogen, with clinical signs mimicking vesicular diseases such as Foot-and-Mouth Disease, posing challenges for timely detection and control. Here, we analyzed 329 complete SVA genomes spanning multiple continents to provide a comprehensive view of its evolutionary dynamics, recombination patterns, haplotype diversity, and global dissemination. Phylogenetic analyses revealed two major lineages: Lineage 1, consisting mainly of early strains from the United States before 2007, and Lineage 2, which emerged post-2007 and subsequently spread across the Americas and East Asia. Recombination was confined to Lineage 2 and concentrated in nonstructural regions, particularly 2C, highlighting intra-lineage genetic exchange as a driver of recent diversification. Haplotype analysis of the 3AB gene identified 170 distinct haplotypes, revealing a star-like network structure consistent with rapid population expansion from a central ancestral variant, while secondary branches reflect ongoing regional diversification. Despite this high genetic variation, genome-wide dN/dS ratios remained below one, and purifying selection was strongest in the N-terminal domains of structural and nonstructural proteins, indicating functional constraints that maintain viral fitness. Time-scaled phylogenetic reconstruction and Bayesian Skyline analysis revealed rapid lineage diversification and a marked increase in effective population size in the early 2010s. Phylogeographic inference further identified repeated introductions from the Americas into East Asia, likely facilitated by swine trade and other anthropogenic factors. Collectively, SVA evolution is driven by frequent mutation and intra-lineage recombination yet constrained by pervasive purifying selection, generating extensive genetic diversity while maintaining functional integrity, with implications for genomic surveillance and targeted control. Full article

Hospital wastewater represents a critical hotspot for the dissemination of antibiotic resistance genes (ARGs), serving both as an environmental reservoir and a transmission pathway for multidrug-resistant bacteria into receiving ecosystems. The intense antibiotic selective pressure within healthcare facilities promotes the emergence, persistence and amplification of resistant strains, posing substantial risks to public health and environmental integrity. This study aimed to characterize Escherichia coli (E. coli) isolates recovered from hospital wastewater effluents in multiple cities across Gabon, with emphasis on bacterial loads, antimicrobial resistance patterns and associated genetic determinants. Wastewater samples were aseptically collected from sewer outlets of eleven healthcare facilities distributed across five provinces over a 12-week period, structured into two six-week sampling campaigns to capture temporal variability. A total of 158 bacterial isolates were obtained, among which 49 were confirmed as E. coli. Mean concentrations of presumptive E. coli ranged from 7.1 × 10³ to 1.49 × 10⁹ CFU/mL, indicating substantial microbial contamination of hospital effluents. Antimicrobial susceptibility testing using the Kirby–Bauer disk diffusion method against 19 antibiotics revealed that all isolates exhibited multidrug-resistant phenotypes. Resistance rates were particularly high to β-lactams and third-generation cephalosporins, reaching 90–100% in most facilities, reflecting strong selective pressure and widespread circulation of resistance mechanisms in urban aquatic environments. In contrast, carbapenems and amikacin remained comparatively effective, with resistance levels below 40%, suggesting partial preservation of last-resort therapeutic options. The values of the Multiple Antibiotic Resistance Index (MARI) ranged from 0.21 to 0.84, indicating selection pressure on different classes of antibiotics. Phylogenetic analysis showed a predominance of phylogroup A, traditionally considered commensal but increasingly associated with the spread of resistance. Groups B2, D/E and F proved to be the most resistant. These groups showed marked resistance to first-line antibiotics. The blaCTX-M-1 was the most prevalent resistance determinant (66.6%), occurring twice as frequently as blaSHV (33.3%), a finding that confirms the significant circulation of extended-spectrum β-lactamase-producing E. coli. Overall, these findings highlight hospital wastewater as a major reservoir and dissemination source of multidrug-resistant E. coli, underscoring the urgent need for improved wastewater treatment, strengthened antimicrobial stewardship and integrated One Health-based surveillance strategies. Full article

Social media engagement drives both individual behavior and content dissemination, yet traditional analytics often reduce interactions to simple counts, obscuring the complex structures underlying user activity. In the highly competitive digital landscape, understanding how users interact with content is crucial for businesses aiming to optimize social media campaigns and maximize return on investment (ROI). Traditional engagement metrics, such as likes and shares, fail to capture the underlying structure and dynamics of user behavior. This study investigates the latent patterns of engagement by combining topological data analysis (TDA) with behavioral clustering across 100,000 posts on multiple platforms. Using persistent homology and k-nearest neighbour graphs, we reveal a primary bifurcation between Active (validation-focused) and Passive (consumption/propagation) users, nested four-strain substructures, and over 650 significant $H_1$ loops indicating recurring feedback cycles. Active users exhibit strong cluster cohesion and high engagement rates, while Passive users contribute broadly to content diffusion with slightly higher loop counts, highlighting distinct functional roles in social media dynamics. These findings provide a principled framework for targeting content, reinforcing feedback loops, and leveraging hub posts to amplify engagement. By linking topological structure to behavioral patterns, this work advances both the theoretical understanding of digital interaction and the practical design of more effective social media campaigns. Full article

The CSDU-CSSI DAYS 25—II International Conference on “Challenges and Perspectives in Urban Water Management Systems”—was held on the 18th and 19th of November 2025 in Trieste (Italy), hosted by Università degli Studi di Trieste and jointly organized by Centro Studi Idraulica Urbana (CSDU) and Centro Studi Sistemi Idrici (CSSI), which are two Italian non-profit private societies engaged in urban water scientific research and dissemination [...] Full article

Introduction: Breast cancer-related lymphedema (BCRL) affects quality of life (QoL) and increases healthcare costs. Resistance training (RT) is proposed as a preventive strategy, although its safety and effectiveness remain uncertain. Objective: To evaluate the effectiveness and safety of RT in preventing BCRL in women at risk. Methods: MEDLINE, Embase, CENTRAL, PEDro, and LILACS databases were searched from their inception to January 2025, along with the gray literature, trial registries, and preprints. Risk of bias was assessed using RoB 2, and certainty of the evidence (CoE) was assessed using GRADE. Primary outcomes were the occurrence of lymphedema and overall QoL; secondary outcomes included pain, upper limb function, range of motion (ROM), grip strength, and adverse events. Results: Eight RCTs (n = 1131) were included. The effects of RT on lymphedema and arm volume are very uncertain (very low CoE). For QoL, pain, ROM, and grip strength, the findings were inconsistent and uncertain (low to very low CoE). Adverse events were mild and transient, with no serious complications. Conclusion: RT is probably safe in women at risk of developing BCRL. Its preventive effectiveness is highly uncertain. Well-designed RCTs with standardized diagnostic criteria, patient-centered outcomes, and long-term follow-up are needed to establish their role in BCRL prevention with greater certainty. Ethics and dissemination: This study did not require ethical approval. The results will be disseminated through publications in peer-reviewed journals and academic presentations. Registration: PROSPERO (CRD42023455720). Full article

This article presents the design and development of an interactive architecture oriented toward the management of traditional vallenato, a musical genre recognized as an Intangible Cultural Heritage of Humanity by UNESCO. Architecture combines the principles of contextual awareness and the use of massive open online courses (MOOCs) to face the current challenges of preservation, dissemination, and teaching of this cultural expression, threatened by commercialization and the loss of its traditional roots. Through a modular structure, adaptive technological tools are integrated to capture, process, and use contextual information, personalizing learning experiences and strengthening the link between communities and their cultural heritage. The proposal consists of several functional layers, including context management, user profiles, educational resources, and a persistence unit, each designed to ensure the interoperability and sustainability of cultural data. In addition, the capacity of architecture to be used in other cultural contexts is highlighted, expanding its impact on different artistic manifestations and heritages worldwide. This article includes a comparative analysis with other existing models, highlighting the advantages of this solution in terms of customization and adaptability. Finally, opportunities for improvement and expansion are explored, as well as the pending challenges in the implementation of this technological tool in educational and cultural environments. Full article