Search Results (9,134)

Background/Objectives: Pancreatic adenocarcinoma remains one of the most lethal malignancies, largely due to aggressive biological behavior and limited available insight into biomarker-based prognostic stratification. The aim of our research was to investigate the role of macrophage migration inhibitory factors (MIFs), interleukin-8 (IL-8/CXCL8), and stem cell factors (SCFs) in pancreatic adenocarcinoma. Methods: In this single-center study, sixty hospitalized patients diagnosed with pancreatic adenocarcinoma were prospectively enrolled, and a cross-sectional analysis of baseline cytokine levels was performed. Serum MIF, IL-8/CXCL8, and SCF were assessed in a single analytical run using Luminex xMAP technology. Results: Elevated MIF and IL-8/CXCL8 levels characterized an inflammatory phenotype, associated with leukocytosis, neutrophilia, increased fibrinogen levels, and unequal prevalence of new-onset diabetes. Higher MIF levels were further associated with larger tumor dimension, while IL-8/CXCL8 was associated with increased bilirubin level and recent weight loss (p < 0.05). In contrast, increased SCF predicted a dissemination phenotype as defined by metastasis occurrence (65.4% vs. 28.6%, p = 0.012). SCF demonstrated significant discriminatory ability for metastasis (AUC 0.712, p = 0.013) and remained significantly associated in multivariable analysis. Conclusions: MIF and IL-8/CXCL8 primarily reflect inflammation-driven processes, whereas SCF identifies a dissemination-dominant phenotype, suggesting distinct biological pathways underlying disease progression in pancreatic cancer. Full article

Background: High infectious disease burden and uncontrolled antibiotic usage across human, animal, and environmental contaminants make antimicrobial resistance (AMR) a growing public health problem in Africa. Mobile genetic elements (MGEs) such plasmids, transposons, integrons, conjugative elements, and phages help spread AMR via horizontal gene transfer (HGT) across human, animal, food, and environmental sources. Despite growing evidence for antibiotic resistance genes (ARGs), Africa lacks a one-health-focused synthesis of mobile genetic element-mediated AMR. Objective: This systematic review and meta-analysis aimed to consolidate information on MGEs and ARGs in AMR dissemination throughout Africa’s one health interface. Methods: The literature was searched using PubMed, Scopus, and ScienceDirect. Observational. molecular epidemiology, whole genome sequencing (WGS), and metagenomic investigations of MGE-associated AMR in Africa were eligible. The study selection, data extraction, and quality assessment were performed by two independent reviewer and quality was graded using ROBVIS 2 utilizing Rayyan software. Narrative synthesis, random-effect meta-analysis, subgroup analysis, and meta-regression were utilized. Results: A total of 109 studies were included, with 91 studies contributing to the meta-analysis. MGEs reported were plasmids (71.7%) and integrons (54.8%). ARGs carried by MGEs were blaCTMX-M-15 (78.6%), Sul2 (69.6%), blaTEM (59.1%), and tetA (49.9%). Horizontal gene transfer was seen in 259 instances; however, transmission was unclear. In 442 observations, transmission pathways across human, animal, and environmental interfaces showed AMR prevalence of 75.1% in human, 98.0% in human–animal, and 61.3% in one health interface. Whole-genome sequencing was the most frequently used method for detecting MGEsThe pooled pathogen and AMR prevalence rates were 73.3% (95% CI: 60.5–83.7%) and 94% (95% CI: 85–98%), with significant heterogeneity (I² = 97.8% and 97.4%, respectively). The prevalence of Escherichia coli was 93% and Salmonella enterica 85% in subgroup analysis. Fluoroquinolones, aminoglycosides, and beta-lactams were prevalent in humans (89.7%) and human–animal interactions (98.0%) according to AMR Class. Conclusions: Horizontal gene transfer has propagated MGE-mediated antimicrobial resistance across human, animal, and environmental interfaces in Africa. To combat AMR in Africa, coordinated, genomics-informed One Health surveillance and antibiotic stewardship are needed. Due to variability and publication bias, these data should be considered cautiously. Pooled data may only show descriptive patterns, and not necessarily precise continent-wide prevalence estimates. Full article

The contemporary media landscape has sustained a substantial transformation with the rise of AI-driven algorithmic platforms that enable activist organizations to produce and disseminate their own forms of political communication and campaigns. This study examines the YouTube channel of Code Pink, a prominent U.S.-based anti-war and social justice organization, to explore how activist media practices intersect with contemporary forms of journalism. Over a one-month period, video transcripts from the organization’s YouTube channel were analyzed using NVivo 15, employing a hybrid qualitative approach that combined inductive and deductive coding. Deductive codes were informed by sustained observation of the channel over one year (short and long videos on YouTube, TikTok, and X), supplemented by engagement with relevant news coverage, while inductive coding followed grounded theory principles, allowing themes to emerge directly from the transcripts. Large Language Models (LLMs) were employed as exploratory analytic tools to support AI-assisted qualitative analysis, complementing manual coding processes. The analysis focuses on how Code Pink frames political events and U.S. foreign policy through confrontational interviews, protest documentation, and the dissemination of commentary to online audiences. Findings suggest that the organization’s video content operates simultaneously as political activism, protest performance, and quasi-journalistic reporting. Activists frequently adopt journalistic techniques—including interviewing political figures, providing on-the-ground commentary, and framing narratives around public accountability—while also advancing explicit ideological positions that challenge dominant media narratives. The study highlights how platform-based activist media blurs the boundaries between journalism, advocacy, and political performance, contributing to the construction of alternative public narratives in the digital age. Full article

Archaeological sites present critical issues related to fragmented documentation systems, the difficulty of integrating stratigraphic analyses with three-dimensional survey data, and the lack of digital tools capable of connecting scientific documentation, conservation needs, and public dissemination. This study proposes an integrated digital workflow for the archaeological park of Aeclanum, in which reality-based multi-scale survey data are transformed into an HBIM model structured through stratigraphic interpretation, material analysis, and semantically organised information. The resulting three-dimensional dataset supports the subsequent Scan-to-BIM process, ensuring consistency between the digital representation and the existing remains. Within this framework, the HBIM model is conceived not only as a geometric representation of the current state, but also as an information environment incorporating data on construction techniques, materials, and decay conditions, thus providing a basis for conservation-oriented assessment and future intervention priorities. At the same time, the model supports digital reconstruction hypotheses consistent with archaeological evidence, later developed within an immersive environment that allows visitors to compare the present condition of the site with its reconstructed historical configuration. The workflow highlights the potential of HBIM as an interface between survey, knowledge organisation, conservation support, and digital enhancement. Full article

Bioplastics are increasingly expected to function not only as alternatives to fossil-derived plastics but also as components of circular plastic systems. However, currently bioplastics remain limited by cost, feedstock availability, achievable biomass content, and end-of-life compatibility. This review examines these limitations by organizing recent technological and policy trends in bioplastics, with particular attention to Japan’s social and industrial infrastructure. On this basis, we discuss a systems-level framework for circular plastics that integrates regionally underutilized non-edible biomass, decentralized production concepts, and the emerging possibility of cell-plastics based on unicellular green algae. We argue that the practical dissemination of biomass plastics requires not only material development but also compatibility with molding processes, recycling and biodegradation pathways, and regional collection and treatment systems. In this context, cell-plastics derived from Chlamydomonas reinhardtii are positioned as an emerging technological platform for direct biomass utilization and interfacial material design, although their large-scale implementation remains limited by current cultivation and manufacturing constraints. We propose that circular biomass-plastics systems in Japan should be developed as regionally adapted production frameworks with clearly defined end-of-life pathways, rather than as simple substitutes for petroleum-derived plastics. Full article

As China’s first World Heritage Mixed Property site, Mount Tai enjoys international renown, with its historic buildings serving both as the central carriers of its cultural heritage and as significant tourism resources. Existing studies have predominantly emphasized the form, scale, and construction techniques of individual buildings or architectural complexes, while less attention has been given to the overall spatial pattern shaped by the interplay of natural and social environments and to the mechanisms underlying its formation. Taking the administrative area of Tai’an City as the study extent, this research selects 451 officially protected historic buildings, classified by period and type, and employs GIS-based spatial analysis and statistical methods to examine their spatiotemporal distribution patterns and influencing factors. The results indicate the following. (1) The temporal distribution exhibits an И-shaped fluctuation pattern, with ancient architecture and ancient sites together accounting for nearly 60% of the total and constituting the core resource categories. This distribution curve is shaped jointly by preservation conditions, social stability, and heritage designation preferences. (2) The spatial distribution displays a pronounced clustering pattern, with the kernel density core shifting over forty kilometers from southwest to northeast, generating an evolutionary trajectory from Dawen River basin agglomeration to Mount Tai mountain belt agglomeration. (3) The overall pattern is associated with both natural and anthropogenic factors. During the early stages, natural conditions such as hydrology and topography provided foundational constraints, whereas in later periods, human factors, including fengshan ritual culture, religious activities, economic development, and institutional governance, exhibit increasingly apparent associations with the distribution pattern. Based on these findings, this study proposes a strategic spatial framework comprising one cultural pilgrimage ring and four thematic corridors, which translates the spatial analytical results into planning implications for the regional integration of historic building resources, and discusses differentiated conservation strategies, thereby providing an analytical foundation and a reference pathway for the dissemination of Mount Tai culture and the sustainable development of heritage tourism. Full article

The evolution and spatial dissemination of SARS-CoV-2 Omicron subvariants have been characterized by rapid lineage replacement and complex transmission dynamics influenced by regional connectivity. This study presents a comprehensive discrete phylogeographic analysis of 90,136 SARS-CoV-2 sequences collected in Poland from 2022 to 2024 to reconstruct the dispersal dynamics of major Omicron lineages, including BA.1, BA.2, BA.5, CH.1, XBB.1, and JN.1. Utilizing Bayesian statistical frameworks, we identified significant viral transitions between the 16 Polish voivodeships and established variant-specific dominance windows ranging from 2 to 4 months. Our findings reveal a highly dynamic epidemic landscape with shifting regional epicenters. The initial BA.1 wave was primarily driven by the Mazovian voivodeship, accounting for 36.1% of outward migration events. This pattern shifted dramatically with the rise in BA.2, which was centered in the industrial Silesian region in the south-west, a densely populated area with strong economic ties to neighboring countries, potentially reflecting a different introduction or transmission dynamic. Furthermore, the epidemic landscape continued to reconfigure during the BA.5 wave, marked by the emergence of new transmission hubs in eastern border regions such as Lublin. Subsequent lineages exhibited distinct geographic signatures: BA.5 spread broadly along the Baltic-central corridor, CH.1 was centered in the north-east, XBB.1 re-emerged in the west-central region of Greater Poland, and JN.1 was driven overwhelmingly by Lesser Poland. These transitions highlight that regional transmission hubs are transient and influenced by local factors such as population density, cross-border mobility, and socio-economic connectivity. This study underscores the critical value of dense genomic surveillance in identifying evolving dispersal routes to inform adaptive, region-specific public health interventions. Full article

Background/Objectives: Freshwater microalgae–bacteria consortia are increasingly utilized in wastewater treatment and biomass production. However, bacteria associated with the algal phycosphere may act as environmental reservoirs of multidrug-resistant (MDR) phenotypes and antibiotic resistance genes (ARGs), including resistance to last-resort antibiotics such as colistin. Methods: An axenic culture of the freshwater microalga Pectinodesmus pectinatus was established using a NaClO-based cleaning protocol. Three phycosphere-associated bacterial strains (Chryseobacterium sp., Pseudomonas monteilii, and Stenotrophomonas pavanii) were isolated and identified by 16S rRNA gene analysis. Antimicrobial susceptibility testing was performed using broth microdilution against 16 antibiotics. Whole-genome sequencing of the most resistant isolate, S. pavanii, was conducted using Oxford Nanopore technology, followed by genome annotation and in silico resistome analysis using CARD, AMRFinderPlus, and ResFinder. Results: Among the three isolates, S. pavanii exhibited the broadest resistance profile, including high minimum inhibitory concentrations (MICs) to multiple β-lactams and colistin (MIC ≥ 16 μg/mL). No plasmid-borne mcr genes were detected. Instead, the genome encoded multiple chromosomal determinants potentially associated with polymyxin non-susceptibility, including lipid A and lipopolysaccharide modification pathways (e.g., arn genes and eptA), outer-membrane maintenance and LPS transport systems, multidrug efflux pumps, and regulatory elements. Integration of genomic and phenotypic data suggested that the observed colistin non-susceptibility may be associated with intrinsic chromosomal determinants inferred from whole-genome analysis. Conclusions: This study demonstrates that the P. pectinatus phycosphere can harbor multidrug-resistant (MDR) bacteria, including strains exhibiting colistin non-susceptibility potentially associated with a repertoire of intrinsic chromosomal resistance mechanisms inferred from genomic analysis. Therefore, freshwater microalgae-based systems should be considered potential environmental reservoirs contributing to the dissemination of antimicrobial resistance. Full article

Longmeizi 龍眉子 was an inheritor of the Southern Lineage of Daoism 道教南宗 under Weng Baoguang 翁葆光. By tracing the historical documentation of Longmeizi’s Daoist lineage, it becomes evident that the narrative details were continuously enriched through textual accumulation. By tracing and analyzing the formative history of documents related to Longmeizi’s Daoist lineage, it is evident that in the process of forming this Daoist lineage, lineage identity 宗派認同 was continuously solidified and even “labeled 標籤化” within these layered texts. The transmission genealogy between patriarchs across generations gradually became clear, definite, and verifiable. After Longmeizi compiled the Jinye Huandan Yinzheng Tu 金液還丹印證圖 (Illustrations of the Return of the Liquified Gold to the Cinnabar Field) from the Jiading period (1208–1224) of the Southern Song Dynasty to the beginning of the Yuan Dynasty, this book was initially transmitted within the Daoist lineage: Longmeizi → Bai Yuchan 白玉蟾 → Wang Jinchan 王金蟾. By the end of the Yuan Dynasty, a literatus named Yuanyangzi Lin Jing 元阳子林静 from Wuxing 吴兴 had also read this book. During the Ming and Qing dynasties, the mode of transmission for the Jinye Huandan Yinzheng Tu shifted from being primarily transmitted orally within Daoist circles to being primarily disseminated through the printing and circulation of books. This led to the emergence of many different versions and commentaries of the Jinye Huandan Yinzheng Tu. Through the compilation and printing of book series, the Jinye Huandan Yinzheng Tu gained broad circulation during the Ming and Qing dynasties. Its annotators, publishers, and readers spanned various identities and social classes, while its geographic reach extended to the Central Plains (Zhongyuan 中原), Southwest China, and Jiangnan regions. By examining the textual circulation history of the Jinye Huandan Yinzheng Tu, it can be observed that the development of the book printing industry during the Ming and Qing periods, particularly the flourishing of series publications, facilitated a shift in the primary mode of transmission for Daoist texts and even in the nature of the texts themselves. On the other hand, the case study of the Jinye huandan yinzheng tu is an example that illustrates the diversity and richness in the methods of Daoist cultural transmission and their development during the Ming and Qing dynasties. Full article

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